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Stuff 'n Stuff

Sci-Tech News & Olds

( April 2014 )






Molecular Music ( See also : J. STERNHEIMER : Protein Music )

A. RABINOVICH : Plasmatron Carburetor

Z. ZHONG : Graphene Infrared Lens

Glassesoff Vision Training App

D. DEUTSCH : Speech-Music

V. SCHAUBERGER : The Energy Evolution ( Translated & Edited by Callum Coates )

A. PERBELLINI / C. VENTURA : Epigenetic Reprograming

A ALPEREN : Power Extraction From pressure

D. CRAIK : Conotoxin Analgesic


B. SHARMA, et al. : Plastic to Diesel Fuel ( See also : ZADGAONKAR ... CHERRY ... CORTRIGHT ... ITO .. McNAMARA )

Z. LIU, et al. : Organo-Iridium Catalysts vs Cancer



Back Issues : January ... February ... March ...




Molecular Music

( See also : Joel STERNHEIMER : Protein Music )

www.oursounduniverse.com
Susan Alexjander

WATER
-- Molecular water frequencies also correspond to 'some kind of an F# chord. Again, Dr. Deamer provided me with the wave numbers of water which are:

1600 converted to hertz = 698 F/F#
2100 converted to hertz = 918 A#
3500 converted to hertz = 134.58 C#
   
SCHUMANN RESONANCE
   
'Octavise' the Schumann frequencies into our hearing range, six of the seven tones are F#s, A#s and C#s. The seventh is a D#
    
F# - creates an unusual oscillating effect between the two cavities of the brain, especially when generated by the tuned resonant cavity of a quartz crystal bowl. It has a frequency of 5.8 kHz (5800 Hz)
   
F# References:

a. 360 is often referred to as Spherical Consciousness i.e. expanded awareness.
b. 11.11 = F/F# an opening gateway for mind expansion.'
c. speed of light = 363.83 F# (186,282.3959Hz)
d. Gematria of Consciousness = 175 (F/F#)
e. Gematria of Zero Point Field = 174 (F/F#)
d. Gematrias of hate + love = 88
good + evil = 89
yin + yan = 88....all octaves of F/F#.   
   

http://algoart.com/music.htm
Genetic Music From DNA and Protein

The music on this page was composed algorithmically with Algorithmic Arts software from the raw genetic data that is available as free downloads on the internet .
Currently there are 3 CD albums available, with more to follow. On this page, you can either audition or download the full tracks as free .mp3 files.

http://www.aber.ac.uk/~phiwww/pm/

ProteinMusic
 
ProteinMusic is a Java program converting DNA sequences into music. The original idea for this project came from R. D. King here at the University of Wales, Aberystwyth and C. G Angus from the Shamen (King, R.D. & Angus, C.G. (1996)). They developed a program written in C on an Apple Mac together with a MIDI connection to a synthesizer in 1996. This program here is a complete re-write of the original program in Java.

http://ndbserver.rutgers.edu/atlas/music/musical_atlas.html
ATLAS: The Musical Atlas

The Nucleic Acid Database has been developing different musical algorithms to provide a unique look into the structure of DNA.

http://www.botany.hawaii.edu/faculty/bridg...nflections/mp3/
Music from DNA by John Dunn and K. W. Bridges

http://www.helenwhitehead.com/Dissert/genetic17.htm

You wouldn't think there was music in me. But beautiful and strange music has been developed from the sequence of nucleotides in my DNA.
Using special software John Dunn selected and/or developed synthesizer sounds to be used to create music by translating the individual DNA codons, the strings of guanine, adenine, cytosine and thymine, into the proteins they form, taking account of "start" and "stop" signals.

The amino acids of each protein sequence plus chemical properties of the amino acids and the bases themselves were interpreted as pitches, pan positions, transpose values, tempi, tone, colors and so on. The realization of the piece was developed manually, until the piece was right.

http://www.dnamusic.com/articles/music_and_metamusic.htm

Hidden right there in plain sight is one of the most profound truths of our existence. From ancient Hindu mystics to modern quantum physicists the collective wisdom of humankind has repeatedly discovered that the universe is an immense energy field vibrating on a score of frequencies. No matter how we separate the individual notes, they all play together to create a single harmonious song.[2]

The Bible, so central to the beliefs of many Western cultures, tells us that "In the beginning was the Word." Yet many Eastern and aboriginal cultures maintain that the world was not spoken, but, rather, SUNG into existence. For a growing number of scientists, their research into the impacts of music on the brain and consciousness now favors the influence of song over speech. In fact, quantum string theory describes our bodies, all physical matter, and even the Earth itself, as cosmic instruments staying in tune with a larger universal orchestra.

http://www.artic.edu/~pgena/genexs.html
http://www.artic.edu/~pgena/DNAmus.html
Peter Dena: DNA music for Genesis

The physio-musical conversion of DNA sequences occurs via a series of formulae that were worked out in a manner based on physical properties of DNA and musical parameters. Once the sequences are converted by my custom algorithms they are played by the DNA Mixer, which reads linearly much like the ribosomes—organelles that read codons for amino acid conversion—traverse the mRNA, mixing multiple sequences simultaneously just like in our cells.

From the onset I believed that a musical reading of DNA ought to be rendered literally. As the sequences represent life of many sorts, I am reluctant to tamper with the “score.” The DNA mixer can realize sequences as digital sound and/or print them out in musical notation. Ideally, performances of the gene sequences should be executed live from the computer as in an installation, where the ribosome simulations can be positioned spontaneously before playing. Red Blood Cells is a mix of five genes that are present in human blood: alpha and beta globin, heme synthetase, transaldolase, and glucose 6 phosphate. These are realized simultaneously, just as they are produced in the body. The piece was premiered in November, 1995 at the XI Colloquium on Musical Informatics at the University of Bologna. In May, 1996 it was aired over Icelandic National Radio during a series on American Electronic Music, and in August of the same year it was presented in Hong Kong at the 1996 International Computer Music Conference.

http://www.nslij-genetics.org/dnamusic/
DNA Music

DNA and music?? What is the connection? And why is it included in a page on correlation structure of DNA sequences? Because: the correlation stucture "1/f spectra" have been found in both musical signals and DNA sequences.

Prof. Susumu Ohno (of Beckman Research Institute of the City of Hope, who died on January 13, 2000, at the age of 71) proposed years ago that the repetition process governs both the musical composition and the DNA sequence construction . see this paper by Ohno in Immunogenetics (1986) titled: "The all pervasive principle of repetitious recurrence governs not only coding sequence construction but also human endeavor in musical composition".

When DNA sequences are converted to music, it sounds musical!

Models with duplication and mutation operations, such as the "expansion-modification model" are able to generate sequences with 1/f spectra.

http://whozoo.org/mac/Music/
http://whozoo.org/mac/Music/samples.htm
Human protein sequences from the Gene Project Reports at Texas Wesleyan University

Note: all of the sequences from the links immediately above are simple linear readouts of the amino acid sequences of the proteins indicated. However some sense of the protein's higher order structure emerges from the alternation between the higher-pitched polar amino acids and the lower-pitched nonpolar amino acids.

http://www.molecularmusic.com/

Welcome to the World of Molecular Music -- The site for music derived from the molecules of life.

Created by award-winning biochemist and musician Dr. Linda Long, Molecular Music provides a pioneering link between the seemingly disparate worlds of music and biological science. It involves the generation of music from three-dimensional biological molecules called proteins. Dr. Linda Long has developed it as tool for teaching molecular modelling of complex protein structures, and to generate music from herbs, medicinal plants and the human body for relaxation and therapeutic purposes.

Molecular Music is computer generated music that creates a gateway into understanding life, allowing us to perceive nature in her many forms through sound. Music is not limited by words or logic and so may communicate with us on deeper levels, freeing us to directly experience the essence of all living matter and giving us an insight into the voice of nature.

Music of the Body

Music of the Body is a CD of music derived from protein hormones found in the human body. Its soothing and uplifting properties make it ideal for use by health professionals and alternative medicine practitioners to accompany their therapeutic work (e.g. massage therapy with essential oils, reiki and music therapy), and by individuals to enhance meditation, mind-body visualization techniques, and bodywork e.g. yoga. It may also be used to promote relaxation in health clubs, health clinics, spas and beauty salons, and induce calm in clinical settings such as hospitals and dentists.

Computer generated note sequences, derived from protein hormones found in the human body, have been arranged by Dr. Linda Long to create complex 'multi-dimensional' musical pieces which contain sequences describing both the secondary and tertiary features of the individual hormones.

Thyrotropin .. Thyroid hormone .. Parathyroid hormone ..  Guanylin .. Somatostatin ..  Growth hormone .. Progesterone receptor protein ..Chorionic gonadotropin .. Follitropin ..

Crystals

Crystals arise in accordance with laws of symmetry, so they have very simple orders which can be interpreted harmonically. These properties are already expressed in the atomic structure of the crystal. There are 32 crystal classes, covering all existing specimens. Crystal symmetry is classed in terms of rotation and mirroring. For rotational symmetry, the only possible values are 360’, 180’, 120’, 90' and 60', which corresponds to the fractional series 1/1, 1/2, 1/3, 1/4, 1/6 (where 1/1 = 360'), and can in turn be interpreted harmonically (c, c’, g’, c”, g”).

At the beginning of the 20th century, the German mineralogist Victor Goldschmidt discovered a mathematical formula to classify how crystals form surfaces. His table corresponds exactly to the Pythagorean Lambdoma right up to the number 4 (or 1/4) – this is particularly interesting because he was not familiar with the Lambdoma.

Listen to mp3 clips of music derived from herbs, medicinal plants and the human body. Visit our online education section with a preview version of Molecular Music's first interactive exhibit currently showing at Bristol.


http://algoart.com/music.htm
Dunn & Clark: Life Music (1998)

A collaboration with biologist Dr. Mary Anne Clark, produced from the primary and secondary structure of protein sequences, using BioSon software (built on KAM), and EMu Proteus (Clark) and Morphius (Dunn) synths. In each piece, pitch is determined by amino acid identity and instrumentation is chosen according to protein folding pattern, with different instruments representing regions of alpha-helix, beta-strands and turns. An article detailing this work has been published in Leonardo On Line. The title is: Life Music: The Sonification of Proteins : Beta-globin , Calmodulin, Gamma Lens Crystallin, Alcohol Dehydrogenase, Lysozyme C, Spidroin, Collagen.) Life Music


http://sourceforge.net/projects/proteinmusic/
http://sourceforge.net/projects/proteinmusic/files/latest/download
Website : http://www.aber.ac.uk/~phiwww/pm/
ProteinMusic

ProteinMusic is a Java program converting DNA sequences into music. The original idea for this project came from R. D. King at the University of Wales, Aberystwyth and C. G Angus from the Shamen (King, R.D. & Angus, C.G. (1996)).

http://brenthugh.com/audio/
Music of the genome 1-9
8:17 ( 2.92 Mb )


http://algoart.com/
ArtWonk4

ArtWonk4 produces music, visuals and wordplay based on generative algorithms you interactively create by connecting modules (graphical objects representing functions and processes) in real time, adjusting the parameters as you go, in a drag & drop environment especially designed to be fast to learn, fast to use.

Source material can be anything at all: Fractals, DNA, EEGs, EKGs, stock quotes, you name it. Built in data extraction reads data from virtually any source, and an extensive DNA editor opens mountains of public domain genetic sequences to explore.

ArtWonk v4.2 was released in September, 2010, but the algorithms and generative processes in ArtWonk have been in development for over 20 years, since the first release of MusicBox for MSDOS in 1986. It represents the ongoing life work of pioneer music and graphics developer John Dunn. This makes ArtWonk vast, deep, and comprehensive; but it is easy and playful to use because it is always running, always live, and you get instant feedback on every change you make.

Genetic Music From DNA and Protein
-- The sound pieces on this page were all composed using algorithmic music software developed by me (John Dunn) over the past 25+ years. Except where otherwise noted, the music is also by me, although often with help from and in collaboration with others, for both the music and the algorithms and software features that made the music what it is. Most tracks are based on DNA and protein genetic data sequences that are freely available on the Internet. Two excellent sources of genetic sequences are the Swiss Protein Data Bank and the NIH GenBank.


http://www.dnamusic.com/articles/music_and_metamusic.htm
Music and Metamusic—A Universal Bridge
by
Barbara Bullard and Matthew Joyce


YouTube : Professor Barbara Bullard - Metamusic :
http://www.youtube.com/watch?v=n_cXL7jr2-c&feature=mfu_in_order&list=UL
http://www.youtube.com/watch?v=4FtRcp6leJU
http://www.youtube.com/watch?v=LGlP0jFiAW8
http://www.youtube.com/watch?v=tRnXUs6aDj0
http://www.youtube.com/watch?v=i0wMTC3i2uU

http://www.petergena.com/genexs.html
http://www.petergena.com/DNAmus.html
Peter Gena DNA Music for Genesis
   
Red Blood Cells (1995), digitally synthesized DNA sequences --
The physio-musical conversion of DNA sequences occurs via a series of formulae that were worked out in a manner based on physical properties of DNA and musical parameters. Once the sequences are converted by my custom algorithms they are played by the DNA Mixer, which reads linearly much like the ribosomes—organelles that read codons for amino acid conversion—traverse the mRNA, mixing multiple sequences simultaneously just like in our cells.

From the onset I believed that a musical reading of DNA ought to be rendered literally. As the sequences represent life of many sorts, I am reluctant to tamper with the “score.” The DNA mixer can realize sequences as digital sound and/or print them out in musical notation. Ideally, performances of the gene sequences should be executed live from the computer as in an installation, where the ribosome simulations can be positioned spontaneously before playing. Red Blood Cells is a mix of five genes that are present in human blood: alpha and beta globin, heme synthetase, transaldolase, and glucose 6 phosphate. These are realized simultaneously, just as they are produced in the body...

Collagen and Bass Clarinet (1997), bass clarinet and five DNA sequences --
Collagen is the main structural protein found in animal connective tissue (it forms gelatin when boiled). Collagen and Bass Clarinet, was commissioned by Italian clarinetist Frederico Paci. He premiered it at the Aspekte Musik Festival in Salzburg, Austria in 1997. The six parts (the bass clarinet plus five computer tracks) are generated from two collagen DNA sequences (three copies of each). Thus, one of the six was outputted as musical notation (properly transposed) for the bass clarinet, and the remaining five "channels" were realized and played electronically by a DNA mixer, programmed by the composer in MAX/MSP.

Prolation Collagen (2005) --
for disklavier uses the same DNA sequence, but is set as a prolation canon for five voices, where each subsequent voice augments the note values progressively to simulate different meters.

Immunoglobulin (2005, revised '06), interactive installation --
Upon the major overhaul of the DNA programs during a residency in Bellagio, my subsequent goal was to implement a sonic mapping of the human immunoglobulin system. Our immune system is made up of multiple random generators that continually produce billions of unique DNA sequences that are put on call to fight off invading diseases. Each immune gene consists of one of three fixed lead sequences (Gamma, Kappa and Lambda), stitched at the head of a variable region, or randomly generated string. The programming effort requires an algorithm that initiates lead sequences and generates the variable regions until an end codon is encountered.


GB2350469
A method of producing audibly discernible sounds 

Inventor(s): Helen LONG

Means for producing an audibly discernable representation of a three dimensional structure such as a biological structure comprises a preliminary analysis of the structure to determine three dimensional positional coordinate data, processing this data to filter out large scale and small scale variations into successive sets of data, combining this data into a single sequence and generating audible sounds therefrom relating to the positional coordinate data. The biological structure represented are proteins whereby the CA carbon atoms of the amino acids of the proteins are analysed by x-ray crystallography to produce the data sets for generating the audible sounds.

The present invention relates generally to a method for producing audibly discernible sounds, and particularly to a method in which the sounds are representative of complex structures.

In the representation of complex structures occupying three-dimensional space it has been conventional either to use stylised models of the structures, themselves occupying the three-dimensional space, or to represent the structures in two-dimensions with an appropriate representational convention by which the information concerning the third dimension is conveyed.

Each of these representational techniques has inherent drawbacks. Threedimensional models, although they can be produced accurately, are not readily transportable nor are is they indefinitely extendable, so that, for example, a highly complex structure may be limited to a representation of only a portion under immediate examination. Although two-dimensional representations are more readily portable, and can also be converted into a form suitable for display on a screen such as a computer screen, the necessity for a drawing convention to represent the third dimension results in a degree of imprecision and uncertainty in the accuracy of the representation. The present invention proposes a complete departure from conventional representational techniques by proposing to provide an audibly discernible representation of spatial information.

The present invention finds particular (but not exclusive) application in the 2 representation of naturally-occurring structures such as biological structures, especially proteins. Structure, pattern and form are inherent in naturally-occurring biological material, and these features may be drawn upon to provide parameters for audibly discernible representations. In the representation of spatial information in audible form the audible information may approximate to, or be considered as, music. Culture and musical tradition has resulted in the evolution of music consisting of references and structures often not consciously appreciated by the listener but nevertheless having an effect on the physiological perception of the music. Recent developments in digital computing have made available to musicians further means by which musical composition may be developed, and it is not unknown for a digital computer to be used as a compositional tool for developing new structures in music. This new type of - music is sometimes called algorithmic, and such music, developed with computer process rules, may combine tonal and structural relationships which it would be difficult to calculate by traditional means.

The audible representation of biological structures such as proteins may, therefore, result in sounds which may be musical in their form. Proteins are biological macro molecules which are the fundamental building blocks in all life forms. Proteins are composed of a plurality of sub units, amino acids, which are arranged according to the individual amino acid properties to form a three dimensional molecule. It is recognised that music is defined by the intervals between notes rather than the absolute pitches of the notes and, correspondingly, proteins may be considered as being defined more by their overall patterns than by their absolute or primary sequences. Proteins structures, may be considered to comprise four mains elements or levels of complexity, namely'a I w..

3 primary structure which is the linear order in which the amino acid sub units occur. A secondary and a tertiary structure determined by the properties of these amino acids which give rise to structural features referred to by biologists as loops, turns, alpha helices and beta strands or beta sheets depending on the spatial arrangements of the sub units in the linear sequence. Quaternary structures are recognisable as the quaternary structure is the broadest structural level concerned with the'arrangement of individual protein "blocks" which fit together to form the final protein molecule.

At the primary level, alpha helices are uniform coil-like structures in which the 10 functional groups or R-groups of the amino acid project outward from the helix axis.

On the other hand secondary structures known as beta strands fold back and forth with individual amino acid R-groups projecting from the folded chain on alternate sides. Different beta strands may be aligned with one another, adjacent strands forming weak bonds which connect them into what are called beta-sheets. Also at the secondary/tertiary level regions of the molecule referred to as "tums' follow a difFerent directional path and are commonly found connecting two regions of an alpha helix or beta strands. These are structures spanning both the secondary and tertiary level in that the folding patterns of the secondary structures are combined to produce the overall tertiary structure of a protein. Information concerning the relationship of these features is usually considered at a visual level and represented visually. The present invention provides an alternative means of representation allowing other senses to be involved.

According to one aspect of the present invention, therefore, a method of producing an 4 audibly discernible representation of a three dimensional sti-ucture comprises the steps of:

generating numerical information concerning the spatial position of identifiable components of the structure from analysis of the structure, converting the numerical information into a derived digital signal by forming moving averages of the numerical information, subjecting the derived digital signal to a conversion from the three- dimensional value to produce a signal having a scalar value representing at least one of the properties of a audibly discernible sound, and generating a sound having that or those properties.

At a fundamental level it may be considered that each positional coordinate representing the presence of a feature or structural element of the structure may be allocated a unique discernible sound. It is of course important that the same sound is repeatably produced by the same feature, but it is not essential that only one feature produce that sound.applied to the representation of a naturally occurring structure, such as a protein the analysis may be performed by x-ray crystallography to determine the relative locations of the amino acids of which the protein is composed. In its application to other stru ctures, however, different analysis techniques may be used on order to generate the raw positional data and, of course, the coordinate. information may represent the positions of other significant elements in the structure. In an engineering structure, for example, the positional coordinates may represent the nodes in a load-bearing assembly and/or the stresses applied to elements of a structure during operation or when performing its function. For example, the stresses exerted on an element of a building may be represented by pitch, variation of which represents increases in the stress so that dynamic variation of the stress pattern can be represented audibly which enables a plurality of different signals to be perceived simultaneously even in a structure in which, with a traditional visual representation, certain 5 components may be masked or covered by others and therefore not visible.

In the representation of structures such, as proteins the resultant data of the x-ray crystallography analysis may comprise a set of positional coordinates representing the relative positions of at least some of the atoms of the amino acids of the protein. In particular the positional coordinate data may represent the three dimensional positions in space, with respect to a given frame of reference, of the CA carbon atoms of the amino acids of the protein.

Although individual unique sounds may be generated these sounds may not necessarily be represented-by individual musical notes, but could be other detectable sounds such as chords or discordant sounds.

In the performance of the method of the invention the said moving averages comprise at least a first moving average of the value of the positional coordinate data scanned over successive groups of carbon atoms to provide an approximate representation of the secondary structure of the amino acids in the protein.

Likewise, a second moving average of the values of the first moving average may be taken over a range of values thereof greater than the range used to form the first 6 moving average. This second moving average provides a further degree of "smoothing" to act effectively to filter out the smaller scale variations, without completely excluding larger scale variations.

Further sequences of digital signals may be derived from the said first and second moving averages, for example by determining the differences between the first moving average and the positional coordinate data, whereby to provide a digital data signal in which larger scale variations are not present and smaller scale variations are amplified.

The second further sequences of digital signals may be derived from the first and second moving averages by determining the differences between the first and second moving averages whereby, in effect, to act as a midfrequency filter on the data.

The method may include deriving a third further sequence of digital signals by normallsing the second moving average values about a selected origin to represent the large scale features of the positional coordinate data stream. This, effectively, acts as a low frequency filter to produce signal dependent on the large scale features.

The said first, second and third further sequences of digital signals may each be multiplied by a respective weighting factor and summed to produce a single sequence of averaged and processed three dimensional coordinate values which are then mapped onto a sequence of one-dimensional values. This may be achieved via a three dimensional wave form generated by spectral synthesis, using a fourier synthesis technique, or by other techniques which provide a repeatable mapping of a three- 7 dimensional point onto a one-dimensional point which can be interpreted as a musical parameter. A simple example might be to sum together the three coordinate values to get a single one-dimensional value.

The one-dimensional value may be pitch or volume and other means may be provided for varying the attack and decay of the sound in order to generate musical notes.

The present invention also comprehends a method of producing an audibly discernible representation of a three-dimensional structure in which the identification of the details of secondary structures in the positional coordinate data is obtained by means of a filter.

In another aspect of the invention a method of producing audibly recognisable sounds representing respective amino acids in a protein structure comprises the steps of subjecting the protein structure to an x-ray crystallography analysis to produce a series of raw data signals representing the three-dimensional positional coordinates of the CA carbon atoms of the amino acids of which the protein is composed; filtering the said raw data signals to generate a plurality of derived moving averages thereof whereby to filter out large and small scale variations respectively; generating from the derived moving averages a composite signal including weighted moving averages as components thereof, and generating from the said composite signal an audible signal in which each amino acid is represented by an identifiable musical note.

The present invention may be embodied in apparatus including visual display means by 8 which the raw data positional coordinate signals may be displayed graphically in synchronism with the audible output signals such that visual and aural correspondence is discernible.

The present invention also comprehends apparatus for producing an audibly discernible representation of a three-dimensional structure, comprising: means for analysing numerical information to generate representations of the position of identifiable components thereof, means for forming moving averages of the said numerical information, means for converting the moving averages of the numerical information into scalar values, and means for allocating pitch or volume values to the said scalar values to generate audible sounds related to the structure.

Various examples of the invention will now be more particularly described.

Example I - for the generation of musical notes representing the individual amino acids of a protein structure, each x, y and z positional coordinate of the CA carbon atom from each amino acid in an original protein sequence SO derived from x-ray crystallography analysis is processed twice, once to extract a first moving average SI, calculated by averaging the values of the sequence SO over a range of five amino acids, and then a second time to extract a second moving average S2 calculated by averaging the values of the moving average S I over a range of twenty five amino acids. The first moving average represents the secondary structure of the protein and the second 9 moving average represent the tertiary structure.

From these three digital data streams S 50, 51, 52 may be derived three further sequences as follows:

1 ' SO- 1 is calculated by subtracting the first moving average S 1 from the original three dimensional data SO. This has the effect of emphasising the small twists and turns of the protein and of masking the larger scale curves over the protein structure as a whole. This in effect acts as a high 6equency filter on the three-dimensional structure of the protein and highlights the spiral shape of the alpha helices. By subtracting the first moving average from the original data all the short-term fluctuations are maintained within the structure of the alpha helices without interference from larger scale changes. By mapping this to pitch variation an accurate sonic representation of the alpha helices is obtained. This mapping results in the generation of sequences of arpeggios when the alpha helices are traversed, and the same or a slightly varying note is is heard when the beta sheets are traversed. This latter results from the fact that a beta sheet contains few small-scale changes.

SI-2 is created by subtracting the second moving average from the first moving average. This has the effect of amplifying the medium sized turns of the protein whilst attenuating the higher frequency alpha helix turns and the lower frequency large scale curves. This process acts as a medium frequency filter on the three-dimensional structure.

Finally, S2-3 is derived by calculating the mean position of all the amino acids in the raw data SO to create a second moving average by subtracting this mean from each value of a coordinate for an amino acid in the moving average S2. The resulting sequence S2-3 is essentially identical to the sequence S2 but is normalised about a central zero origin point. This sequence represents the larger scale curves of the 5 original three-dimensional protein structure, effectively acting as a low frequency filter.

Weighting factors are then applied to each sequence and the weighted sequences summed to give a final sequence ST = a (SO-1) + b(S 1-2) + c (S2-3). The magnitude of the weighting factor a determines the proportion of the high frequency component of the protein in the final sequence ST whilst b and c determine the mid frequency and low frequency component.

The sequence ST is than mapped onto musical parameters such as pitch via a threedimensional waveform generated by three-dimensional spectral synthesis, thus creating is sequences of notes which express visual features in musical form. The waveform maps a three-dimensional coordinate value onto a one-dimensional value, that is the value of that point in the waveform. The three dimensional input values are a sequence of coordinate values ftom ST and the output is a sequence of one-dimensional values which are interpreted as notes in musical scales or dynamic levels (volume). This mapping may be achieved as follows. First a random number (ranging from 5 to 20 or more) of vectors are provided which reside in a 2-dimensional frequency-space (the frequency-space is the spectral analog to the final 2 dimensional landscape). Each vector has a randomly determined position in this frequency-space and has a randomly determined phase and magnitude associated with it (represented by a complex number).

11 For mathematical reasons, there must also exist for each vector a 'mirror' vector with the same vector location but having a complex number associated with it that is a complex conjugate of the original vector's complex number. Therefore there must always be an even number of these vectors.

Once these vectors with their associated complex numbers have been generated it is a simple process of fourier synthesis so that given a 2-dimensional coordinate in cartesian space, one can sum the contributions of each vector (at the cartesian coordinate) to end up with a scalar (1 -dimensional) value which can be interpreted as a height value. Details are given by D. Saupe. Since the resulting "landscape" is constructed from a combination of waves, for a small list of vectors it has the property that two points close to each other in 2-dimensions have similar resulting height values (i.e. mathematically speaking, the landscape is continuously differentiable everywhere.

is This process is extended to 3-dimensions by generating a list of 3dimensional vectors in frequency -space. When given a point in 3-dimensional cartesian space, these vectors can be summed using complex arithmetic to provide a 1 - dimensional scalar value. This allows a 3-dimensional coordinate (i.e. 3-dimensional position of a CA atom after the moving average process) to be turned into a 1 -dimensional scalar value.

In an analogous way to the 2-dimensional synthesis, two points close to each other in 3-dimensional cartesian-space will have close 1 -dimensional results ftom the mapping.

This means that close 3-dimensional positions will have close (audibly related) pitch, amplitude or other such musical value.

12 Whilst this invention may make use of a fourier synthesis technique, fourier synthesis by such is not new, and this invention includes the use of any other method of mapping a 3-dimensional point, for example derived from filters or moving averages of x-ray crystallography data to a 1dimensional point which can be interpreted in a musical fashion. A simple example might be simply to sum together the x, y, and z values of the 3-dimensional coordinate to get a single 1 -dimensional value. Another alternative in the specific case of proteins may be to use the coordinates of the second moving average as an "axis" and to calculate "angular" offsets of the original data from that axis. As the alpha helix twists around a sequence of angles averaging around 360' may 10 then be derived.

This output is then written to a NMI text file for conversion into music or a layer in a musical arrangement using known MIDI music software to produce complex multi timbral musical pieces containing melodies reflecting the large-scale tertiary structures 15 or small repetitive arpeggios expressing the structural nature of the alpha helices.

Example 2:
for the production of a musical representati-on of a protein. This follows the same basic method as described in relation to example I above, with the addition of tempo, rhythm and key changes derived from the x-ray crystallography coordinate 20 data.

In this example positions in the original data sequence are determined where the musical parameter changes are to take place corresponding to visual transmission points in the secondary structure of the protein, for example where an alpha helix, a 13 beta sheet, a loop or a turn begins or ends.

The secondary structure details are identified using a filter. This filter outputs secondary structure features from an input comprising the three-dimensional data.

Two filter techniques may be used in the identification of the secondary structures, namely:

Filter technique 1.
The three dimensional distance of each CA carbon atom is taken from the mean position of the CA carbon atoms of a particular section of the protein. The filter moves a vrindow containing data covering approximately 10 CA carbon atoms for different amino acids along a section of the crystallography data looking at the distance of each CA carbon atom from the mean value of all the carbon atoms in the current window. From these distances it is possible to determine the likelihood of the current window containing data from an alpha helix or a beta sheet. The termination points of these features may thus be identified.

Filter technique 2.
In this technique matched filters are used with parameters tuned to those found in protein alpha helices and beta strands and the like. For example, alpha helices will have an approximate pitch of 4.6 angstrom units, beta sheets will have an approximate pitch of 13.5 angstrom units.

Example 3.
This example may be embodied in a model giving participants the opportunity to create their own pieces of music from a range of onscreen three dimensional proteins. The three dimensional x-ray crystallography x, y, z coordinate data is used as the basis for an animated display of the progress of the generated music 14 along the physical structure of the proteins as displayed graphically on a computer screen. By choosing from a selection of moving average operations the user can see how the chosen proteins are converted into musical sounds. The weightings a, b, c of example 1 may be made available to the user for selection, and their combination by 5 the computer then results in a sequence of notes.

Each note, corresponding to a specific arnino acid in the display, is then sounded with the an-dno acid on the display, with the visual representation of the protein being highlighted simultaneously whereby to demonstrate and emphasise the correspondence 10 between the musical notes and the protein sequences.

Example 4:
a display booth or exhibition kiosk may be equipped with an interactive touch screen compute. system containing both the audio and visual components described in relation to examples 1 and 3. The screen may display graphics generated is using a graphics processor depicting a traverse through the biological material of a plant, animal, insect, fungal, bacteria, yeast or human Iandscape". The protein molecules are used to derive musical sounds identifying the proteins. This may also have an educational value in, enabling aural recognition of proteins.

Example 5.
Another educational application may be developed as a three dimensional tactile model of a protein containing a plurality of switches connected to a computer system whereby the display of an audio visual information device may be influenced. On touching a particular amino acid (that is operating the associated switch) the an-dno acid on the display screen would be highlighted and the corresponding note, chord or is other musical sound representing this amino acid generated for the user to hear.

The present invention thus expands and crosses the boundaries between science and art, enabling new approaches to understanding biological structure to be achieved as S well as the generation of music for educational or purely entertainment purposes. Use of this invention in protein homology modelling, where fast and easily recognisable differences in proteins of similar structure are required, may be developed as there is a currently unfulfilled demand for such a tool in this widely used research technique.

Protein-derived music may be of therapeutic interest in the treatment of conditions currently treated using music therapy. It is believed that such specialised music may offer a focused and precise application which optimises and hence is more cost efFective than, known music therapies utilising music derived from other sources.

Protein-derived music may be used to strengthen mind-body connections. Likewise, protein-derived music may be used for studying and modelling protein sequence data, complementing existing techniques which have wide application in drug design. Since alpha helices, beta strands and turns each have characteristic combinations of hydrophobic and hydrophilic amino acids, different structural categories of proteins, which combine these secondary elements in different ways, also have different musical characteristics. The sounds generated therefrorn may therefore be used effectively in the discrimination and demonstration of different protein types.

Protein music may also be used in sequence alignment and structural homology determination as structural homology may be heard when it might not easily be 16 perceived visually.



Alexander RABINOVICH, et al. :

Plasmatron Fuel Reformer


Science & Mechanics ( February 1970 )



http://connection.ebscohost.com/c/articles/2639544/plasmatron-device-can-cut-car-nox
Professional Engineering;12/08/99, Vol. 12 Issue 22, p50 ( December 1999 )

Plasmatron device can cut car NOx
 
by Diinah Greek
 
ABSTRACT -- Offers a look at the plasmatron device developed by Alexander Rabinovich and colleagues in the plasma technology division at the Massachusetts Institute of Technology. Ability to cut emissions of pollutants such as nitrogen oxides; Mechanism; Testing; Features.

http://worldwidescience.org/topicpages/p/plasmatron+fuel+reformer.html

Plasmatron-catalyst system 

A plasmatron-catalyst system. The system generates hydrogen-rich gas and comprises a plasmatron and at least one catalyst for receiving an output from the plasmatron to produce hydrogen-rich gas. In a preferred embodiment, the plasmatron receives as an input air, fuel and water/steam for use in the reforming process. The system increases the hydrogen yield and decreases the amount of carbon monoxide.

HYDROGEN GENERATION FROM PLASMATRON REFORMERS :
A PROMISING TECHNOLOGY FOR NOX ADSORBER REGENERATION AND OTHER AUTOMOTIVE APPLICATIONS 


Plasmatron reformers are being developed at MIT and ArvinMeritor [1]. In these reformers a special low power electrical discharge is used to promote partial oxidation conversion of hydrocarbon fuels into hydrogen and CO. The partial oxidation reaction of this very fuel rich mixture is difficult to initiate. The plasmatron provides continuous enhanced volume initiation. To minimize electrode erosion and electrical power requirements, a low current, high voltage discharge with wide area electrodes is used. The reformers operate at or slightly above atmospheric pressure. Plasmatron reformers provide the advantages of rapid startup and transient response; efficient conversion of the fuel to hydrogen rich gas; compact size; relaxation or elimination of reformer catalyst requirements; and capability to process difficult to reform fuels, such as diesel and bio-oils. These advantages facilitate use of onboard hydrogen-generation technology for diesel exhaust after-treatment. Plasma-enhanced reformer technology can provide substantial conversion even without the use of a catalyst. Recent progress includes a substantial decrease in electrical power consumption (to about 200 W), increased flow rate (above 1 g/s of diesel fuel corresponding to approximately 40 kW of chemical energy), soot suppression and improvements in other operational features.. Plasmatron reformer technology has been evaluated for regeneration of NOx adsorber after-treatment systems. At ArvinMeritor tests were performed on a dual-leg NOx adsorber system using a Cummins 8.3L diesel engine both in a test cell and on a vehicle. A NOx adsorber system was tested using the plasmatron reformer as a regenerator and without the reformer i.e., with straight diesel fuel based regeneration as the baseline case. The plasmatron reformer was shown to improve NOx regeneration significantly compared to the baseline diesel case. The net result of these initial tests was a significant decrease in fuel penalty, roughly 50% at moderate adsorber temperatures. This fuel penalty improvement is accompanied by a dramatic drop in slipped hydrocarbon emissions, which decreased by 90% or more. Significant advantages are demonstrated across a wide range of engine conditions and temperatures. The study also indicated the potential to regenerate NOx adsorbers at low temperatures where diesel fuel based regeneration is not effective, such as those typical of idle conditions. Two vehicles, a bus and a light duty truck, have been equipped for plasmatron reformer NOx adsorber regeneration tests.

Low current plasmatron fuel converter having enlarged volume discharges 

A novel apparatus and method is disclosed for a plasmatron fuel converter ("plasmatron") that efficiently uses electrical energy to produce hydrogen rich gas. The volume and shape of the plasma discharge is controlled by a fluid flow established in a plasma discharge volume. A plasmatron according to this invention produces a substantially large effective plasma discharge volume allowing for substantially greater volumetric efficiency in the initiation of chemical reactions within a volume of bulk fluid reactant flowing through the plasmatron.

Onboard Plasmatron Hydrogen Production for Improved Vehicles 

A plasmatron fuel reformer has been developed for onboard hydrogen generation for vehicular applications. These applications include hydrogen addition to spark-ignition internal combustion engines, NOx trap and diesel particulate filter (DPF) regeneration, and emissions reduction from spark ignition internal combustion engines First, a thermal plasmatron fuel reformer was developed. This plasmatron used an electric arc with relatively high power to reform fuels such as gasoline, diesel and biofuels at an oxygen to carbon ratio close to 1. The draw back of this device was that it has a high electric consumption and limited electrode lifetime due to the high temperature electric arc. A second generation plasmatron fuel reformer was developed. It used a low-current high-voltage electric discharge with a completely new electrode continuation. This design uses two cylindrical electrodes with a rotating discharge that produced low temperature volumetric cold plasma., The lifetime of the electrodes was no longer an issue and the device was tested on several fuels such as gasoline, diesel, and biofuels at different flow rates and different oxygen to carbon ratios. Hydrogen concentration and yields were measured for both the thermal and non-thermal plasmatron reformers for homogeneous (non-catalytic) and catalytic reforming of several fuels. The technology was licensed to an industrial auto part supplier (ArvinMeritor) and is being implemented for some of the applications listed above. The Plasmatron reformer has been successfully tested on a bus for NOx trap regeneration. The successful development of the plasmatron reformer and its implementation in commercial applications including transportation will bring several benefits to the nation. These benefits include the reduction of NOx emissions, improving engine efficiency and reducing the nation's oil consumption. The objective of this program has been to develop attractive applications of plasmatron fuel reformer technology for onboard applications in internal combustion engine vehicles using diesel, gasoline and biofuels. This included the reduction of NOx and particulate matter emissions from diesel engines using plasmatron reformer generated hydrogen-rich gas, conversion of ethanol and bio-oils into hydrogen rich gas, and the development of new concepts for the use of plasmatron fuel reformers for enablement of HCCI engines.

Onboard Plasmatron Generation of Hydrogen rich Gas for Diesel Engine Exhaust Aftertreatment and Other Applications 

Plasmatron reformers can provide attractive means for conversion of diesel fuel into hydrogen rich gas. The hydrogen rich gas can be used for improved NOx trap technology and other aftertreatment applications.

PATENTS

Alexander RABINOVICH : Plasmatron Fuel Reformer

LOW POWER COMPACT PLASMA FUEL CONVERTER
WO0114702

Plasmatron-internal combustion engine system
US5425332

Plasmatron-internal combustion engine system
US5437250

Apparatus and Method for NOx Reduction
US2007289291

Rapid response plasma fuel converter systems
US5887554

Integrated plasmatron-turbine system for the production and utilization of hydrogen-rich gas
US5852927

Homogeneous charge compression ignition control utilizing plasmatron fuel converter technology
US2004099226

PLASMATRON FUEL CONVERTER HAVING DECOUPLED AIR FLOW CONTROL
WO2004094795

WIDE DYNAMIC RANGE MULTISTAGE PLASMATRON REFORMER SYSTEM
WO2005094335

HYDROGEN AND CARBON MONOXIDE ENHANCED KNOCK RESISTANCE IN SPARK IGNITION GASOLINE ENGINES
WO2004111417



Zhaohui ZHONG , et al.

Graphene Infrared Lens


http://www.dailymail.co.uk/sciencetech/article-2584617/The-contact-lens-infrared-vision.html

19 March 2014
The contact lens that could let you see in the dark: Researchers reveal graphene 'supervision' sensor

By Mark Prigg

Researchers have unveiled plans for a smart contact lens that could give its wearer infrared 'night vision'.

The team say that by sandwiching graphene inside the lens they can build a sensor capable of capturing every from visible light to infrared.

They have already built a prototype smaller than a fingernail, and experts say it could one day be built into lenses for soldiers and others who need to see in the dark.

WHAT IS GRAPHENE?

Graphene is made of a single layer of carbon atoms that are bonded together in a repeating pattern of hexagons.

It is one million times thinner than paper, and Graphene’s flat honeycomb pattern grants it many unusual characteristics, including the status of strongest material in the world.

Zhaohui Zhong at the University of Michigan say their layered approach can lead to ultrathin sensors.

'We can make the entire design super-thin,' said Zhong, assistant professor of electrical and computer engineering.

'It can be stacked on a contact lens or integrated with a cell phone.'

The prototype device created by Zhong is already 'smaller than a pinky nail' and can be easily scaled down.

'If we integrate it with a contact lens or other wearable electronics, it expands your vision,' Zhong said.

'It provides you another way of interacting with your environment.'

It takes advantage of graphene's 'supersensor' properties.

The material shows a very strong effect when it’s struck by photons (light energy).

It turns into what is known as a 'hot carrier' - an effect that can be measured, processed, and turned into an image.
 
The team developed a way to sandwich the graphene to make it as sensitive as CMOS silicon imaging sensors in commercial digital cameras.

'Graphene is a promising candidate material for ultra-broadband photodetectors, as its absorption spectrum covers the entire ultraviolet to far-infrared range,' the team wrote in Nature.
The team are investigating using graphene to sandwich between two layers of a lens, rather like this Google prototype for a glucose monitoring lens for diabetics

'Here, we report an ultra-broadband photodetector design based on a graphene double-layer heterostructure.

'The detector is a phototransistor consisting of a pair of stacked graphene monolayers (top layer, gate; bottom layer, channel) separated by a thin tunnel barrier.

'Under optical illumination, photoexcited hot carriers generated in the top layer tunnel into the bottom layer, leading to a charge build-up on the gate and a strong photogating effect on the channel conductance.

'The devices demonstrated room-temperature photodetection from the visible to the mid-infrared range, with mid-infrared responsivity higher than 1 A W-1, as required by most applications'

US2012225296
UNIFORM MULTILAYER GRAPHENE BY CHEMICAL VAPOR DEPOSITION  

Inventor(s):     ZHONG ZHAOHUI [US]; LEE SEUNGHYUN [US]; LEE KYUNGHOON [US] +
Also published as:     WO2012031238 (A2)  WO2012031238 (A3)

A method of producing uniform multilayer graphene by chemical vapor deposition (CVD) is provided. The method is limited in size only by CVD reaction chamber size and is scalable to produce multilayer graphene films on a wafer scale that have the same number of layers of graphene throughout substantially the entire film. Uniform bilayer graphene may be produced using a method that does not require assembly of independently produced single layer graphene. The method includes a CVD process wherein a reaction gas is flowed in the chamber at a relatively low pressure compared to conventional processes and the temperature in the reaction chamber is thereafter decreased relatively slowly compared to conventional processes. One application for uniform multilayer graphene is transparent conductors. In processes that require multiple transfers of single layer graphene to achieve multilayer graphene structures, the disclosed method can reduce the number of process steps by at least half.

BACKGROUND OF THE INVENTION

[0003] Single and few-layer graphene has emerged as a promising material for novel applications in electronics due to certain advantageous optical and electrical properties and due to its potential for integrating bottom-up nanomaterial synthesis with top-down lithographic fabrication at a wafer size or macro scale. Its semi-metallic nature with high carrier mobility and low opacity also makes it a good candidate for use as transparent conductors for photovoltaic devices, touch panels, and displays, for example. Graphene structures also have high chemical resistance, low manufacturing costs, and, being atomically thin, are relatively flexible when compared to some other transparent conductor materials such as indium tin oxide (ITO). Bilayer graphene (BLG) in particular holds further promise for use in post-silicon electronics applications because a bandgap up to 250 meV can be induced in the material using an electric field, which is not possible with single or monolayer graphene (SLG), and because exciton binding energies in BLG are tunable by electric field- induced bandgap.

[0004] A monolayer or single layer graphene is a plane of carbon atoms bonded in a hexagonal array. Several methods have been used to synthesize graphene films including the reduction of graphene oxide, liquid exfoliation using organic solvents, and chemical vapor deposition (CVD). The CVD method has drawn much attention, as this method can yield high quality graphene films. Homogeneous single layer graphene has been synthesized on transition metal substrates, such as copper, that have low carbon solubility using low pressure CVD (LPCVD). But the sheet resistance of pristine or undoped SLG is on the order of 2000-6000[Omega]-too large to for use as a transparent conductor, for example. Stacking multiple individually produced layers of SLG and individually doping each layer is one method that has been used to achieve lower film resistance for graphene structures. But fabrication of a multi-sheet SLG stack can require a multitude of transfer processes, depending on the number of SLG sheets desired in the stack. This can lead to high processing time and cost, and a higher likelihood of defects in the films.

[0005] Bilayer graphene has been fabricated by initially producing two separate monolayers of graphene and subsequently using a sacrificial carrier to physically stack one of the separate monolayers on the other. BLG has also been fabricated via mechanical exfoliation of graphite to produce SLG that is subsequently stacked with another SLG, but the sheet size is limited to the square-micron range and such processes are not scalable to sizes large enough to be practical for use in many electronics applications. The synthesis of wafer scale uniform bilayer graphene product presents a tremendous challenge.

[0006] Graphene sheets having multiple layers of graphene with lower sheet resistance than SLG have been directly synthesized using an LPCVD method on other transition metals, such as nickel, that have relatively high carbon solubility and on copper using atmospheric pressure CVD (APCVD). Multiple layer graphene (MLG) structures produced by these methods typically have non-uniform thickness, with different numbers of graphene layers throughout the structure, and rough surfaces compared to LPCVD-grown SLG. Graphene sheet thickness variation can be problematic for use in electronics applications because it causes the sheet resistance and optical transmittance to vary among different areas of the sheet. Additionally, APCVD processes that are used to produce MLG can lead to higher numbers of defects compared to LPCVD SLG due to particulate deposition resulting from APCVD conditions.

SUMMARY OF THE INVENTION

[0007] In accordance with one embodiment, a method of directly synthesizing uniform multilayer graphene by chemical vapor deposition is provided.

[0008] In accordance with another embodiment, a method of producing multilayer graphene is provided. The method comprises the steps of: (a) placing a substrate having a metal surface in a reaction chamber of a furnace; (b) flowing H2 gas in the reaction chamber; (c) increasing the temperature in the reaction chamber to a desired level; (d) after the temperature in the reaction chamber reaches the desired level, ceasing flow of the H2 gas, and flowing reaction gas in the reaction chamber for a desired time; and (e) after the desired time, decreasing the temperature in the reaction chamber at a controlled rate.

[0009] In accordance with another embodiment, a method of producing multilayer graphene is provided. The method comprises the steps of: (a) placing a substrate having a metal surface in a reaction chamber of a furnace; (b) evacuating the reaction chamber; (c) purging the reaction chamber with a working gas; (d) flowing H2 gas in the reaction chamber; (e) increasing the temperature in the reaction chamber to a desired level; (f) after the temperature in the reaction chamber reaches the desired level, ceasing flow of the H2 gas so that the reaction chamber is free of H2 gas, and flowing reaction gas in the reaction chamber at a pressure in the reaction chamber of less than 0.5 Torr; and (g) thereafter decreasing the temperature in the reaction chamber at a rate of less than 100[deg.] C./min.

[0010] In accordance with another embodiment, a method of making a multilayer graphene film is provided. The method comprises the steps of: (a) synthesizing uniform multilayer graphene by chemical vapor deposition; (b) providing a uniform graphene sheet having at least one layer of graphene; and (c) stacking the uniform multilayer graphene of step (a) together with the uniform graphene sheet of step (b).

[0011] In accordance with another embodiment, a multilayer graphene film is provided. The film has interlayer uniformity and also has the same number of graphene layers throughout a major portion of the sheet...

Experimental Sample Preparation

[0093] A 25 [mu]m thick copper foil (99.8%, Alfa Aesar) was placed into an inner quartz tube reaction chamber inside a three-inch horizontal tube furnace of a commercial CVD system (First Nano EasyTube 3000). The system was purged with argon gas and evacuated to a pressure of about 0.1 Torr. The chamber was then heated to 1000[deg.] C. in an H2 (100 sccm) environment at a pressure of about 0.35 Torr. When a chamber temperature of 1000[deg.] C. was reached, 70 sccm of CH4 was flowed through the chamber for 15 minutes at a pressure of 0.45 Torr. The sample was then cooled slowly to room temperature with a feedback loop to control the cooling rate. The pressure was maintained at 0.5 Torr with 100 sccm of argon flowing. A time vs. temperature plot from the CVD growth process is shown in FIG. 5.

[0094] Two different methods were used to transfer the produced uniform multilayer graphene from copper foil substrate to SiO2 substrates. The first method utilized thermal release tape (Nitto Denko) to transfer the graphene from the copper foil. The tape was applied to the copper surface and a force of 6.25 N/cm<2 >was applied to the copper/graphene/tape stack for 10 minutes using a EVG EV520IS wafer bonder. The opposite side of the substrate was exposed to O2 plasma for30 seconds to remove the graphene on that side. The substrate was etched away using an iron (III) nitrate (Sigma Aldrich) solution (0.05 g/ml) for 12 hours. A 4-inch silicon wafer with thermally grown SiO2 was precleaned with nP12 nanoPREP using plasma power of 500W for 40 seconds to modify the surface energy and produce a hydrophilic surface. The tape and graphene stack was transferred to the pre-cleaned SiO2 wafer and a force of 12.5N/cm<2 >was applied for 10 minutes. The substrate was then heated to 120[deg.] C. to overcome the adhesion of the thermal release tape. The tape was then peeled off and the adhesive residue was removed with warm acetone.

[0095] Polymethylmethacrylate (PMMA) film may be used in another method to transfer graphene. This method does not require a bonding tool but the edge portion of the graphene film may be rough due to uneven thickness of spin-coated PMMA at the edge. In this method, the growth side of the CVD graphene sample was coated with 950PMMA A6 (Microchem) resist and cured at 180[deg.] C. for 5 minutes. The other side of the substrate was exposed to O2 plasma for 30 seconds to remove the graphene on that side. The sample was then left in iron (III) nitrate (Sigma Aldrich) solution (0.05 g/ml) for at least 12 hours to completely dissolve away the copper layer. The sample was transferred onto a silicon substrate with a thermal oxide layer. The PMMA coating was removed with acetone and the substrate was rinsed several times. Raman spectroscopy as well as optical microscope were used to characterize the graphene films from all transfers, and electrical transport measurement was done with samples transferred by the PMMA method.

[0096] For the above-described electrical testing, graphene devices were fabricated according to the following process. After the multilayer graphene was transferred onto SiO2/Si substrate, Ti/Au (5 nm/100 nm) was deposited to form the source/drain electrodes. Bilayer graphene films were then patterned into 1 [mu]m*1 [mu]m, 1 [mu]m*2 [mu]m, and 2 [mu]m*2 [mu]m pieces using conventional lithography and oxygen plasma etching. After 40 nm of Al2O3 was deposited as the top gate dielectric by atomic layer deposition (ALD), top gates were patterned and the metals were evaporated (Ti/Au: 5 nm/100 nm). It is noted that the adhesion between metal electrodes and graphene was not perfect, as some metal peeled off. Gate leakage/breakdown at high field was also observed for some devices. These devices are regarded as fabrication defects, as described in conjunction with FIG. 4(a).



Glassesoff Vision Training App

http://www.dailymail.co.uk/sciencetech/article-2583746/The-app-let-throw-away-reading-glasses.html
18 March 2014

Could the 'eye training' app really let you throw away your reading glasses?

By Mark Prigg

A new app that claims to be able to improve people's eyesight by 'training' them with a series of exercises has become a hit.

Called GlassesOff, it uses a series of patterns to create 15 minutes exercises for users.

If done three times a week, its makers say it could mean they no longer need reading glasses after three months.

The app uses a series of games, puzzles and tests to improve a user's eyesight - if they can play for 15 minutes three times a week for three months.

HOW IT WORKS

GlassesOff uses a completely different approach that is exclusively aimed at teaching the visual system of the brain to better use its potential.

This allows the brain to compensate for blurred information captured by the eyes as we age.

The foundation for this technology is provided by the brain's ability to adapt, the app makers say.

The app uses patterns designed to strengthen  connections within circuits relevant to a task, such as recognizing letters when reading.

'Traditionally, near distance reading improvement solutions were limited to optical corrections such as glasses, contact lenses and refractive surgery,' said said Nimrod Madar, CEO of GlassesOff.
 
'However, human vision performance is in fact limited by two factors: the quality of an image captured by the eye and the image processing capability of the brain as it interprets such images.

'Our solution is designed to improve reading by enhancing the image processing function of the visual cortex, demonstrating the amazing potential of the human brain.

'We created this app because we wanted to empower people who experienced natural age-related changes in reading ability to take control of their vision and improve their quality of life.

'Our personalized app constantly adapts according to users’ progress, with the ultimate goal of freeing them from dependency on magnifying devices such as reading glasses.”

The GlassesOff app is free to download from the App Store and offer users access to a vision evaluation and the first segment of the GlassesOff program.

After Using the GlassesOff app for approximately two weeks, users will be given the option to subscribe to the full version, which includes additional advanced segments, for $59.99.

However, during the launch, subscriptions will be offered at a special price of just $9.99.

App claims exercise will improve eyesight

The app gives users regular tests to check their progress, giving them a 'brain speed' ranking as they improve

The researchers have also published several studies backing up the app's effectiveness.

In a study carried out at the University of California at Berkeley and published in Nature Scientific Reports, all subjects who completed the GlassesOff program were able to read standard newspaper font size without the use of reading glasses, while improving their 'Eye Age' by an average of 8.6 years.

A second study looks at the correlation between the fovea, which is part of the retina, and crowding, processing speed and vision sharpness.

The findings demonstrate that the GlassesOff technology may be applicable to improved performance of daily tasks, such as sports, reading, driving, and more.

'This study results reaffirm our product’s ability to help reading by improving visual processing speed.

'The results are encouraging and relevant for our planned launch of a series of pipeline products for mass market segments, including those designed to improve visual functions in sports and reading speed,' said Madar.

http://www.glassesoff.com/

Revolutionary science delivered directly to your iPhone

Human vision is limited by two main factors:

The quality of an image captured by the eyes.

The image processing capabilities of the brain as it interprets an image captured by the eyes.

GlassesOff scientists have developed a proprietary method for improving near vision sharpness, by improving the image processing function in the visual cortex of the brain.

eople can impact their vision by increasing the quality of images captured by their eye (e.g., wearing glasses, going through corrective eye surgery), or by enhancing their brain’s image processing abilities.

At some point, every person will suffer from the inevitable natural deterioration in near distance reading capabilities. This deficiency has typically been addressed by traditional products for improvement of reading capabilities, mainly magnification devices such as reading glasses or contact lenses that support reading.

GlassesOff scientists have developed a patented method for boosting the image processing function in the visual cortex of the brain, thereby improving a person’s near vision sharpness and reading capabilities.

Scientifically Proven Solution

Our technology is based on extensive scientific research and achievements that have been published in the leading scientific publications, such as Nature, Science, PNAS, Vision Research, Scientific Reports and others.

During the last two decades, scientists have demonstrated that contrast-driven neural responses are robustly affected by lateral propagations between neurons in the visual cortex. A positive effect of this interaction is called “collinear facilitation”, which amplifies weak and slow responses and their underlying mechanism of neuronal excitations. This function strengthens selective synapses to elevate weak stimuli above the noise, and is the foundation of GlassesOff technology.

Weaker and slower neuronal responses in the visual cortex, either as a consequence of blurred input from the eyes or abnormal development, result in degraded basic visual functions both in the spatial domain, e.g. contrast sensitivity, and the temporal domain, e.g. processing speed. These changes eventually affect high-level visual tasks, such as letter identification. GlassesOff scientists have shown that using neuronal plasticity retained in the adult brain, it is possible to increase collinear facilitation to compensate for spatial and temporal deficiencies.

Selected peer-reviewed scientific publications and scientific presentations:

http://uripolat.files.wordpress.com/2012/06/srep00278.pdf

Training the brain to overcome the effect of aging on the human eye

The effectiveness of the GlassesOff product was examined in a recent study conducted at the University of California at Berkeley and published in Nature’s Scientific Reports. This study clearly demonstrated the significant benefit of the GlassesOff training program for reading abilities and eye age. Moreover, cutting-edge optometric equipment allowed the scientists to unequivocally determine that the actual source of the observed benefits is solely in the brain and not in the optics of the eyes.

http://uripolat.files.wordpress.com/2011/05/2004-polat-pnas-amblyopia.pdf

Improving vision in adult amblyopia by perceptual learning

Perceptual training was applied to an adult visual system with abnormal development of the primary visual cortex of the brain leading to amblyopia (“lazy eye”). Training yielded significant benefits that transfer to higher visual tasks, resulting in a two-fold improvement in contrast sensitivity and in letter-recognition tasks in patients between 9 and 55 years old. This is the first evidence for a remarkable vision improvement following perceptual learning in a condition previously acknowledged as untreatable in adults.

http://uripolat.files.wordpress.com/2012/06/2009-practical_pl.pdf

Making perceptual learning practical to improve visual functions

Generalization, or transfer, of gains acquired on a trained task to other functions is crucial for both understanding the neural mechanisms and the practical values of the training. This study describes a perceptual learning method applied to amblyopia (“lazy eye”), myopia (near-sightedness) and presbyopia (age-related near vision decline). The gains were transferred to visual acuity, processing speed and reaction time. Thus, perceptual learning can become a practical method for improving visual functions in people with impaired or blurred vision.

http://uripolat.files.wordpress.com/2012/06/sterkin_yehezkel_polat_vr_2012.pdf

Learning to be fast: gain accuracy with speed

The effectiveness of perceptual learning on contrast detection in young adults was tested using behavioral and neurophysiological (Event-Related Potentials, ERPs) measurements. A remarkable improvement in all behavioral measurements, including sensitivity and reaction time, along with shorter latency and increased amplitude of an ERP marker of neuronal interactions within the visual cortex of the brain.  Thus, perceptual learning that strengthens inter-neuronal interaction results in a faster processing speed and higher contrast sensitivity.

http://www.glassesoff.com/wp-content/uploads/2013/05/ARVO_2013.pdf

Digital precise remote near vision sharpness evaluation on mobile devices

GlassesOff developed a tool for precise remote evaluation of near vision sharpness in order to accurately and remotely estimate reading abilities. Tested on 73 volunteers on iPhone 4, the application better predicts the functional reading acuity due to the brief stimuli presentation, as opposed to single letter detection used in golden standard reading chart measurements.

http://www.glassesoff.com/wp-content/uploads/2013/05/ARVO_2012.pdf

Perceptual training on mobile devices improves near visual functions

The resolution and quality of smart phone screens are much better than those of PC monitors, with an average pixel size several times smaller in Apple’s retina display than in PC screens. This enables one to achieve better contrast sensitivity by a factor of 2-3, thus providing more prospect for training near visual functions.

http://www.glassesoff.com/wp-content/uploads/2013/05/AAO_2012.pdf

Perceptual training on mobile devices for the aging human eye

Training with GlassesOff on mobile devices is an effective solution for improving near vision sharpness in presbyopia by enhancing image processing in the brain, with better contrast sensitivity compared to PC.

http://uripolat.files.wordpress.com/2011/05/2009-experreviews1.pdf

Neuroplasticity following perceptual learning for visual improvement

The aim of this review is to show that perceptual learning can be applied for practical purposes to improve visual functions of people with special needs. Prof. Polat predicts that perceptual learning methodology will be modified in the near future into complementary or standalone procedures to aid care providers in treating and improving a variety of visual functions that are not addressed by conventional treatment.



Diana DEUTSCH, et al.

Illusory Transformation  from Speech to Song


[ PDF ]

Repetition of a spoken phrase can be perceptually transformed to sound like song rather than speech...



Viktor SCHAUBERGER

The Energy Evolution

( Translated & Edited by Callum Coates )


[ PDF ]





Alberto PERBELLINI / Carlo VENTURA

Epigenetic Reprograming

Nonstem adult cells can be epigenetically reprogrammed backward to a state where they can become neural, cardiac, skeletal, muscle or insulin-producing cells:

Use of retinoic esters of hyaluronic acid for the differentiation of totipotent stem cells
US2006216820
      
The present the invention relates to a new use of retinoic of hyaluronic acid, that exhibit pre-differentiating activity on totipotent stem cells. The invention also relates to a process to differentiate said stem cells and to select molecules capable of modulating the pro-differentiating activity of those esters.



Attila ALPEREN

POWER EXTRACTION FROM PRESSURE
   
PESWiki.com
Pure Energy Systems News
September 18, 2013

http://TurXotorDemo.com

2013 : TurXotor Demo

On October 24-27, the Turkish government will be holding a four-day Turkish Innovation Fair in Istanbul featuring the best Turkish technologies of the year, and that two of the Alperen Group technologies will be among the three on display.

On September 7, Attila Alperen told me that his Alperen™ Group's TurXotor® motor is poised to be among the top three featured at the event. He said that the Turkish government wants to create a large electric car industry in Turkey around this invention that will enable electric vehicles to never have to be plugged in, and to be able to operate with only a few batteries on board, because the power source is onboard, pulling energy from the environment somehow -- harnessing the wheelwork of nature, as Tesla coined it.

TurXotor® is a motor that works as a generator at the same time -- the only system like this in the world, as far as Mr. Alperen is aware. So the TurXotor® motor powers the wheels of the electric vehicle -- and produces electricity at the same time, both to replenish the source battery and provide extra for the other electrical needs of the vehicle such as lights, radio, heat, windows, etc.

The Alperen™ Group doesn't describe their technology as a "free energy" technology. They shy away from words like "overunity" as well. They depict it as merely an efficient regeneration of the used technology. But obviously, if they are propelling a vehicle down the road, they have to be harvesting energy from somewhere beside the battery, if they don't have to ever recharge the battery from an external source.

Attila said this will solve two problems presently associated with electric cars: range, and battery costs. The range will become unlimited, and the battery costs will be significantly reduced, because the vehicle will only need enough to serve as a buffer for acceleration input and deceleration harvesting of regenerative braking. They won't be needed for storage for duration travel. You'll be able to travel as far as you want without ever stopping for fuel or to recharge your batteries.

This will be the first time the TurXotor® will be publicly demonstrated. The event will enable interested parties worldwide to see the technology demonstrated as well as discuss licensing manufacturing of the technology. Normally, Attila is not very accommodating for people to come and see the technology demonstrated, so this will be a rare opportunity.

Attila said that at the event, the TurXotor® motor-generator will be demonstrated in isolation, showing its attributes of torque, electricity generation, and efficiency. It will also be open to inspection, not concealed in a "black box" of any kind.

Though such a technology has a myriad of applications, at present, the only application that is being licensed is for manufacturing the motor to fit electric vehicles, or trains, or ships.
 
WO2013048352
METHOD OF POWER EXTRACTION FROM PRESSURE

The method of invention consists of the extraction and utilization of potential energy as usable energy contained in pressurized liquid, air, and gas which is transferred via transfer lines such as pipes without losing the pressure values of inlet and outlet of the system.

DESCRIPTION

The method of invention consists of the extraction and utilization of potential energy as usable energy contained in pressurized liquid, air, and gas which is transferred via transfer lines such as pipes without losing the pressure values of inlet and outlet of the system.

Every pressurized liquid, air, and gas has a usable potential energy. In the current systems, the need for additional inlet pressure power increases at Inlet(3) in proportion to the amount of usable energy in the Turbine Shaft(5). Thanks to this invention this potential energy is converted into usable energy in the Turbine Shaft(5). Contrary to the current systems, during the utilization of this energy in the Turbine Shaft(5), the equality of Outlet(4) pressure power and Inlet(3) pressure power is preserved.

The sample system showing the operating principle of the invention consists of eight parts. These are; Turbine(l), Pressure Preservation Chamber(2), Inlet(3), Outlet(4), Turbine Shaft(5), alternators, generators, and loads (6) Pressure Preservation Chamber Spaces(7), and Pressure Direction Nozzle(8).

The operating principle of the invention is as follows: In order to generate mechanical energy, any or some of the pressurized liquid, air, and gas applied from Inlet(3) are directed to the Turbine(l) blades positioned in the Pressure Preservation Chamber(2) via Pressure Direction Nozzle(8). This mechanical energy generated in the Turbine(l) is transferred to the outside the system via the Turbine Shaft(5) and thus the generating of mechanical power necessary for any alternators, generators, and loads (6) is provided. The pressure power from Inlet(3), after applied to the Turbine(l) inside the Pressure Preservation Chamber(2) whose internal pressure is preserved and which is kept closed, is transferred to the outside of the system from the Outlet(4) without losing its (inlet's) own pressure power.

Since the turbine is positioned in the Pressure Preservation Chamber(2), the counter power applied to the Turbine(l) via the Turbine Shaft(5) by the alternators, generators, and loads (6) is not reflected back to the Inlet(3).

Therefore, while the pressure from Inlet(3) is transferred to the outside of the system without losing its pressure value at Outlet(4), the potential energy contained in this pressure power is extracted via the Turbine Shaft(5) as usable energy.

There are no Pressure Preservation Chamber(2) and spaces in the current available systems. As a result, the counter power of the alternators, generators, and loads (6) is reflected back to the Inlet(3) via the Turbine Shaft(5) and the Turbine(l). However, thanks to this invention, the counter power is not reflected back to the Inlet(3) since the Turbine(l,) is positioned in the Pressure Preservation Chamber Spaces(7).


Basinçtan güç ekstraksiyon (açiga çikartma) yöntemi.
TR201109533

Yüksek verimli türbin.
TR201107424



David CRAIK : Conotoxin Analgesic

http://www.smh.com.au/national/chronic-pain-relief-scientists-trial-nonaddictive-drug-from-snail-venom-20140317-34y5l.html
March 18, 2014

Chronic pain relief: Scientists trial non-addictive drug from snail venom

Lucy Carroll



Venom used to paralyse their prey: The carnivorous tropical marine cone snail.

A new drug extracted from snail venom could provide a breakthrough in treating severe chronic pain without the risk of addiction and dangerous side effects, researchers have found.

The venom - considered 100 times stronger than morphine - could lead to the development of a new class of oral drugs used to relieve nerve pain associated with injury, cancer, AIDS and other diseases.

''It's a very exciting discovery which has the potential to be a blueprint for other protein-based medication,'' David Craik, lead researcher and professor of biomolecular structure at the University of Queensland, said.

The prototype drug, which has been tested on rats, is taken from carnivorous tropical marine cone snails, which use their venom to paralyse their prey. The venom contains hundreds of peptides, or ''mini proteins'', known as conotoxins, which have a pain-killing effect.

''Snails have had 60 million years of evolution to fine-tune their venom, which contains some very powerful molecules,'' said Professor Craik, who will present his findings at an American Chemical Society meeting this week.

''If we can tap into that then it saves us having to do the hard work that evolution has already done for us,'' he said.

A preliminary study using tiny proteins from the venom ''appears to significantly reduce pain'' in lab rats, he said. ''Our digestive system is designed to break down proteins. What we've done is taken a protein and re-enginered it to make it stable enough to work orally.''

Only one conotoxin-derived drug, ziconotide, has been approved for human use but it must be injected into the spine.

PATENTS

Novel nucleic acid molecules
AU2006200422

Cyclised conotoxin peptides
AU6070599

A novel molecule
AU784222

CYCLISED ALPHA-CONOTOXIN PEPTIDES
US8354372

TYROSINE-RICH CONOPEPTIDES
US2010093620

Cyclised alpha-conotoxin peptides
CN101448516

CYCLISED CONOTOXIN PEPTIDES
ES2308847

CYSTINE KNOT MOLECULES
US2011244564

J-SUPERFAMILY CONOTOXIN PEPTIDES
US2011064668

NOVEL NUCLEIC ACID MOLECULES
AT482975
 


Brajendra SHARMA, et al.
Plastic to Diesel Fuel


( See also : ZADGAONKAR ... CHERRY ... CORTRIGHT ... ITO .. McNAMARA )

http://news.illinois.edu/news/14/0212bags_oil_BrajendraKumarSharma.html
http://www.sciencedaily.com/releases/2014/02/140212132853.htm

February 12, 2014

Plastic shopping bags make a fine diesel fuel

Used plastic shopping bags can be converted into petroleum products that serve a multitude of purposes.

by Diana Yates
 
Plastic shopping bags, an abundant source of litter on land and at sea, can be converted into diesel, natural gas and other useful petroleum products, researchers report. The conversion produces significantly more energy than it requires and results in transportation fuels -- diesel, for example -- that can be blended with existing ultra-low-sulfur diesels and biodiesels.

Used plastic shopping bags can be converted into petroleum products that serve a multitude of purposes. Plastic shopping bags, an abundant source of litter on land and at sea, can be converted into diesel, natural gas and other useful petroleum products, researchers report.

The conversion produces significantly more energy than it requires and results in transportation fuels -- diesel, for example -- that can be blended with existing ultra-low-sulfur diesels and biodiesels. Other products, such as natural gas, naphtha (a solvent), gasoline, waxes and lubricating oils such as engine oil and hydraulic oil also can be obtained from shopping bags.

A report of the new study appears in the journal Fuel Processing Technology.

There are other advantages to the approach, which involves heating the bags in an oxygen-free chamber, a process called pyrolysis, said Brajendra Kumar Sharma, a senior research scientist at the Illinois Sustainable Technology Center who led the research. The ISTC is a division of the Prairie Research Institute at the University of Illinois.

"You can get only 50 to 55 percent fuel from the distillation of petroleum crude oil," Sharma said. "But since this plastic is made from petroleum in the first place, we can recover almost 80 percent fuel from it through distillation."

Americans throw away about 100 billion plastic shopping bags each year, according to the Worldwatch Institute. The U.S. Environmental Protection Agency reports that only about 13 percent are recycled. The rest of the bags end up in landfills or escape to the wild, blowing across the landscape and entering waterways.

Plastic bags make up a sizeable portion of the plastic debris in giant ocean garbage patches that are killing wildlife and littering beaches. Plastic bags "have been detected as far north and south as the poles," the researchers wrote.

"Over a period of time, this material starts breaking into tiny pieces, and is ingested along with plankton by aquatic animals," Sharma said. Fish, birds, ocean mammals and other creatures have been found with a lot of plastic particles in their guts.

Whole shopping bags also threaten wildlife, Sharma said.

"Turtles, for example, think that the plastic grocery bags are jellyfish and they try to eat them," he said. Other creatures become entangled in the bags.

Previous studies have used pyrolysis to convert plastic bags into crude oil. Sharma's team took the research further, however, by fractionating the crude oil into different petroleum products and testing the diesel fractions to see if they complied with national standards for ultra-low-sulfur diesel and biodiesel fuels.

"A mixture of two distillate fractions, providing an equivalent of U.S. diesel #2, met all of the specifications" required of other diesel fuels in use today -- after addition of an antioxidant, Sharma said.

"This diesel mixture had an equivalent energy content, a higher cetane number (a measure of the combustion quality of diesel requiring compression ignition) and better lubricity than ultra-low-sulfur diesel," he said.

The researchers were able to blend up to 30 percent of their plastic-derived diesel into regular diesel, "and found no compatibility problems with biodiesel," Sharma said.

"It's perfect," he said. "We can just use it as a drop-in fuel in the ultra-low-sulfur diesel without the need for any changes."

Journal Reference:

Fuel Processing Technology, 2014; 122: 79
DOI: 10.1016/j.fuproc.2014.01.019

Brajendra K. Sharma, Bryan R. Moser, Karl E. Vermillion, Kenneth M. Doll, Nandakishore Rajagopalan : Production, characterization and fuel properties of alternative diesel fuel from pyrolysis of waste plastic grocery bags.



http://www.sciencedirect.com/science/article/pii/S0378382014000290?via=ihub
Fuel Processing Technology -- Volume 122, June 2014, Pages 79–90
http://dx.doi.org/10.1016/j.fuproc.2014.01.019

Production, characterization and fuel properties of alternative diesel fuel from pyrolysis of waste plastic grocery bags ?

Brajendra K. Sharmaa, Bryan R. Moserb, Karl E. Vermillionb, Kenneth M. Dollb, Nandakishore Rajagopalana

Abstract

Pyrolysis of HDPE waste grocery bags followed by distillation resulted in a liquid hydrocarbon mixture with average structure consisting of saturated aliphatic paraffinic hydrogens (96.8%), aliphatic olefinic hydrogens (2.6%) and aromatic hydrogens (0.6%) that corresponded to the boiling range of conventional petroleum diesel fuel (#1 diesel 190–290 °C and #2 diesel 290–340 °C). Characterization of the liquid hydrocarbon mixture was accomplished with gas chromatography–mass spectroscopy, infrared and nuclear magnetic resonance spectroscopies, size exclusion chromatography, and simulated distillation. No oxygenated species such as carboxylic acids, aldehydes, ethers, ketones, or alcohols were detected. Comparison of the fuel properties to the petrodiesel fuel standards ASTM D975 and EN 590 revealed that the synthetic product was within all specifications after addition of antioxidants with the exception of density (802 kg/m3). Notably, the derived cetane number (73.4) and lubricity (198 µm, 60 °C, ASTM D6890) represented significant enhancements over those of conventional petroleum diesel fuel. Other fuel properties included a kinematic viscosity (40 °C) of 2.96 mm2/s, cloud point of 4.7 °C, flash point of 81.5 °C, and energy content of 46.16 MJ/kg. In summary, liquid hydrocarbons with appropriate boiling range produced from pyrolysis of waste plastic appear suitable as blend components for conventional petroleum diesel fuel.

1. Introduction

Plastic retail bags are ubiquitous in modern society because they represent a convenient means to transport purchased goods from the supermarket to the home. Plastic bags are plentiful, inexpensive to produce, sturdy yet low weight, and easy to store and transport. However, the same properties that make them commercially successful also contribute to their proliferation in the environment. Although they are recyclable, the U.S. EPA noted that only 13% of the approximately one trillion produced in 2009 were recycled in the U.S. [1]. The remainder were disposed of in landfills, released into the environment as litter, or used in secondary applications by end-users eventually ending in landfills. Plastic bags may take centuries to naturally decompose due to their stable chemical composition [2]. In addition to being a source of litter in urbanized areas, plastic bags exacerbate localized flooding by clogging municipal drainage systems and constitute a significant portion of floating anthropogenic marine debris [3], [4] and [5]. In fact, plastic bags contribute to the so-called Great Pacific Garbage Patch of floating refuse in the Pacific Ocean and have been detected as far north and south as the poles [3], [4] and [5]. Once in the environment, plastic bags are lethal to animals that ingest or become entangled in them [6], [7] and [8]. Because of these and other factors, various regional and national governments have banned or are contemplating bans or fees on plastic bags [9].

Standard plastic bags consist of thin polyethylene (PE) sheets produced commercially from polymerization of ethylene. PE is divided into categories based on density and molecular branching frequency. The two types most important to production of plastic bags are low-density PE (LDPE) and high-density PE (HDPE). HDPE is a copolymer with up to 1% 1-butene and is made historically with either Cr or Ziegler catalysts at 1–16 MPa at temperatures as low as 60 °C. More recently, single site catalysts such as metallocenes have been employed [10]. LDPE is produced at high temperatures (200–300 °C) and supercritical ethylene pressures (130–260 MPa) using peroxide-free radical initiators [10]. HDPE is a linear copolymer with a density range of 0.945–0.965 g/cm3 whereas LDPE is branched with densities ranging from 0.915 to 0.925 g/cm3[10]. Due to these differences in structure, the crystalline melting point, softening point and tensile strength of LDPE are considerably lower than the corresponding values for HDPE [10]. However, LDPE shows higher elongation at break and higher impact strength than does the more rigid HDPE [10]. It is also translucent rather than opaque due its lower crystallinity (55%) relative to HDPE (85–95%) [10]. HDPE is more commonly utilized for production of plastic bags due to its greater tensile strength coupled with its less energy-intensive production process. Pyrolysis is defined as the irreversible anaerobic thermochemical decomposition of material at elevated temperature (300 + °C). The principal benefit of pyrolysis is conversion of low energy density substrates into higher density liquid (bio-oil) and solid (biochar) fractions. A low-density volatile (syngas) fraction is also produced. Pyrolysis has been utilized for millennia to produce charcoal and coal. More recently, pyrolysis is used to produce charcoal, activated carbon, coke, carbon fiber, and methanol, among others. The distribution of products (bio-oil, biochar and syngas) is dependent on the type of pyrolysis, reaction conditions and feedstock. Pyrolysis is classified into four categories: slow, fast, flash, and gasification. Of these, fast and flash pyrolysis maximizes bio-oil production, slow pyrolysis augments the yield of biochar and gasification maximizes syngas production. With regard to production of liquid transportation fuels, fast or flash pyrolysis is employed to produce bio-oil [11], [12], [13] and [14]. The properties and composition of bio-oil such as high moisture and heteroatom content, presence of oxygenates such as organic acids, and broad distillation curve prevent its direct use as a transportation fuel; thus upgrading such as hydroprocessing and distillation is necessary [14], [15] and [16].

Fast or flash pyrolysis has been reported on biological materials such as wood [13], triglycerides [17], grasses [18], shrubs [19], corn cobs and stover [20], alfalfa [21], oilseed presscakes [22], and pig compost [23], among others. Examples of fast pyrolysis on non-biological feedstocks include scrap tires [24] and [25], sewage sludge [25], general municipal solid waste [26], waste electrical and electronic equipment [27], and various plastics [25], [28], [29], [30], [31], [32], [33], [34], [35] and [36]. The plastics include polystyrene [30], [31] and [32], poly(vinyl chloride) [30] and [31], polypropylene [31], [32], [33] and [34], PE terephthalate [32], acrylonitrile–butadiene–styrene [32], and PE [30], [31], [32], [35] and [36]. In some cases plastics were co-pyrolyzed with other materials such as waste motor oil [32]. With regard to fast pyrolysis of PE, pyrolysis of LDPE [30], HDPE [35] and [36] and various mixtures [31] and [32] was reported. In all PE studies, the properties of the resulting bio-oils were not reported, nor were the upgrading to fuel-grade hydrocarbons and subsequent fuel property determination.

The objective of our study was the production, characterization and evaluation of alternative diesel fuel from pyrolysis of HDPE waste grocery bags. Comparison of our pyrolyzed polyethylene hydrocarbons (PPEH) with conventional petroleum-derived ultra-low sulfur (< 15 ppm S) diesel (ULSD) fuel was a further objective, along with a comparison to petrodiesel standards such as ASTM D975 and EN 590 (Table 1). Blends of PPEH with ULSD and biodiesel were prepared and the resultant fuel properties measured. It is anticipated that these results will further understanding of the applicability and limitations of HDPE as a feedstock for the production of alternative diesel fuel.

Table 1. Fuel properties of pyrolyzed polyethylene hydrocarbons (PPEH) and ULSD along with a comparison to petrodiesel fuel standards.a

2. Materials and methods

2.1. Materials

Plastic HDPE grocery bags were collected from local retailers and represent the typical ones used in grocery stores. Summer grade ULSD was donated by a major petrochemical company. With the exception of conductivity and corrosion inhibitor additives, ULSD contained no performance-enhancing additives. Soybean oil methyl esters (SME) were donated by a BQ-9000 certified commercial producer. All other chemicals were obtained from Sigma-Aldrich Corp (St. Louis, MO). All materials were used as received.

2.2. Pyrolysis of HDPE to produce plastic crude oil

Thermochemical conversion of plastic grocery bags (HDPE) to oils were conducted using a pyrolysis batch reactor in triplicate. Pyrolysis was performed in a Be-h desktop plastic to oil system (E-N-Ergy, LLC, Mercer Island, WA) containing a 2 L reactor and oil collection system using approximately 500 g of plastic grocery bags each time. The pyrolysis reactor has two heating zones (upper and lower); the upper and lower temperatures were set to 420 and 440 °C, respectively. Once the reactor reached the set temperatures, a reaction time of 2 h was employed from that point on. Vapors produced as a result of pyrolysis were condensed over water as plastic crude oil (PCO). The upper oil layer was separated and weighed. The reactor lid was opened once the temperature was below 50 °C to remove the remaining residual solid material and weighed separately. The mass balance yields were calculated as the ratio of the corresponding product phase (liquid and solid) obtained in 12 batch experiments to the initial feedstock mass. Lastly, the gas-phase yields were calculated based on the resulting mass difference.

2.3. Distillation of plastic crude oil to yield diesel-range hydrocarbons

Distillation of PCO was performed in a Be-h desktop plastic to oil system. A known amount of PCO (1 L) was added to the Be-h reactor vessel. The oil collection tank was cleaned by removing the water and dried before starting distillation. For collecting the gasoline equivalent fraction (< 190 °C), the upper and lower temperatures were set to 175 and 190 °C, respectively. Once the liquid stopped dripping into the collection vessel, the gasoline equivalent fraction was removed, filtered, and weighed to provide yield. The upper zone temperature was then raised to 275 °C and lower zone to 290 °C to collect a #1 diesel equivalent fraction (190–290 °C). The # 2 diesel equivalent fraction (290–340 °C) was then collected by setting the upper zone temperature to 330 °C and lower zone to 340 °C. The material remaining in the reactor vessel was an atmospheric residue equivalent fraction (> 340 °C), which was removed using a siphon pump once the reactor temperature was below 50 °C. All fractions except the atmospheric residue equivalent (> 340 °C) were filtered through Whatman filter paper #4 to remove residual solid particles.

2.4. Chemical characterization of plastic oil fractions

2.4.1. Gas chromatography–mass spectroscopy (GC–MS)

2.4.2. Simulated distillation by GC–FID

2.4.3. Size exclusion chromatography (SEC) analysis

2.4.4. NMR and FT-IR spectroscopy

2.5. Fuel properties

2.6. Preparation of PPEH–petrodiesel blends

3. Results and discussion

3.1. Preparation and chemical composition of pyrolyzed plastics

The pyrolysis temperature range of 420–440 °C was chosen based on previous studies [34]. These temperatures resulted in decomposition reactions of HDPE to provide hydrocarbons of different chain lengths. Pyrolysis of waste plastic grocery bags at temperatures of 420–440 °C provided 74% yield of liquid product referred to as PCO, as shown in Fig. 1. Although not determined in the present paper, literature data suggested gaseous product obtained from pyrolysis of PE consisted primarily of ethane and ethene (C2, 52%) and C4 (32%) compounds [34]. The higher solid residue yield (17%) is likely due to the inorganic content and/or char content and/or unconverted HDPE. As the pyrolysis of PE has higher activation energy (280–320 kJ/mol) compared to polypropylene (190–220 kJ/mol), therefore, increasing the pyrolysis temperature to certain extent could result in increased amounts of the liquid fraction [34]. Also, this residue may have been the fraction boiling above 420 °C (analogous to the higher boiling vacuum gas oil fraction, VGO from petroleum distillation). Further thermal cracking of this product could have been achieved by increasing pyrolysis temperature and/or time, which we speculate would have resulted in higher yields of the desired PCO fraction. This residue along with the VGO fraction from PCO have potential to be used as lubricant basestocks, which upon further refining such as dewaxing/wax isomerization may yield API Group II/III lubricant base oils.

The PCO thus obtained after pyrolysis of waste plastic grocery bags was distilled into four fractions (< 190; 190–290; 290–340; and 340 + °C equivalent of motor gasoline (MG), diesel#1 (PPEH-L), diesel#2 (PPEH-H) and VGO respectively. The product yields are represented in Fig. 2. Similar results were obtained from SimDist analysis of PCOs with maximum coefficient of variation ranging from 0 to 7% (Table 2). In the absence of a catalyst, the major product is PPEH-L (41%). The product distribution can be changed with the use of zeolite catalysts such as ZSM-5, which will increase conversion to more low boiling products, such as MG and PPEH-L [34].

Fig. 2. Distillate fractions yield (%) on distillation.

Table 2. Distillate fraction yields (wt.%) of plastic crude oils (PCO) using simulated distillation (HTGC–FID).

Elemental analysis of waste plastic grocery bags and PCO fractions revealed less than 0.5% nitrogen content and less than 0.7% oxygen content (Table 3). As expected, waste plastic grocery bags have an empirical formula of CH2.1N0.005O0.007 quite similar to that of polyethylene (CH2). Higher carbon and hydrogen content and lower oxygen and nitrogen content resulted in a higher calculated HHV [37], [38] and [39] of 49–50 MJ/kg for most of the fractions, making these high energy liquid fuels

(Table 3). The calculated values were slightly higher than the actual determinations (Table 1)...

The boiling point distribution of PCO fractions was obtained using high temperature GC–FID. Table 2 shows that the method developed for boiling point distribution was repeatable with a CV of less than 7% for distribution of various fractions in PCO and was similar to actual distillation data. All PCOs contained a large percentage of fraction 2 (PPEH-L) followed by PPEH-H and MG. Around 98% of the PCO was distilled under 400 °C, which is a good range for producing various fuels such as naphtha,
gasoline, aviation fuel, diesel, and fuel oil. The boiling point distribution of PCO and its four fractions is shown in Fig. 3. As boiling point and MW distribution of PCO were similar to petroleum fractions and contained negligible heteroatom content, therefore, we speculate that these PCOs will be compatible with petroleum crude oil for refining in a conventional refinery. The compatibility is further depicted in 10–50% blends of PPEH in ULSD as shown in Fig. 4. As the PPEH content increased in ULSD, the boiling point distribution shifted towards the higher boiling range, although overall the mixture remained within the boiling range of diesel fuel...

Depicted in Table 7 and Table 8 are fuel properties of PPEH-L (Table 7) and PPEH-H (Table 8) blended with ULSD. For each sample, blends of 10 (P10), 20 (P20), 30 (P30), 40 (P40) and 50 (P50) vol.% in ULSD were investigated. With regard to cold flow properties, as the percentage of PPEH-L increased in blends with ULSD, values for CP, CFPP and PP became progressively lower due to the superior low temperature performance of PPEH-L relative to ULSD. In the case of PPEH-H, the opposite trend was elucidated in which cold flow properties (CP and PP) deteriorated as the concentration of PPEH-H in ULSD increased. CFPP of PPEH-H was not measured due to insufficient sample. Similarly, oxidative stability decreased as the percentage of PPEH increased in blends with ULSD. Comparison to the IP specification in EN 590 revealed that only the P10–30 blends of PPEH-H were above the minimum specification of 20 h. Results obtained from measurement of OT corroborated those obtained for IP: deterioration of stability as the concentration of PPEH increased in ULSD as indicated by progressively lower OTs.

Table 7. Fuel properties of pyrolyzed polyethylene hydrocarbons (PPEH-L) blended with ULSD.a

3.4. Influence of blending biodiesel with PPEH

...It was found that diesel obtained from pyrolysis of plastic is as compatible with biodiesel as ULSD due to quite similar hydrocarbon structures and chain length distribution of molecules.

4. Conclusions

Pyrolysis of HDPE waste plastic grocery bags followed by distillation resulted in a major liquid hydrocarbon product (PPEH-L) with average structure consisting primarily of saturated aliphatic paraffinic hydrogens (94.0%) and smaller amounts of aliphatic olefinic hydrogens (5.4%) and aromatic hydrogens (1.0%) that corresponded to the boiling range typical of conventional petroleum diesel fuel (190–290 °C). Negligible heteroatom-containing species were detected from elemental analysis. Also obtained was a heavier boiling fraction (290–340 °C) equivalent of diesel#2 from distillation of the crude pyrolysis product, PPEH-H, which also consisted of paraffinic protons (96.8%), olefinic protons (2.6%) and aromatic protons (0.6%). Based on the results obtained after determination of fuel properties and comparison to petrodiesel standards, the following conclusions were made regarding the applicability of these materials as alternative liquid transportation fuels:

1. PPEH-H is more appropriate as an alternative diesel fuel because it exhibited higher values for FP, IP, KV, DCN, HHV, density, and lubricity than PPEH-L.
2. PPEH-H, after addition of antioxidants, met all ASTM D975 and EN 590 fuel specifications with the exception of density in the case of EN 590.
3. PPEH-L did not meet EN 590 specifications for IP, KV, FP, and density due to its higher content of lower MW constituents.
4. A 1:1 mixture of PPEH-H and PPEH-L met all ASTM D975 and EN 590 specifications with the exception of density and IP in case of EN 590, therefore PPEH-L and PPEH-H distillates can be collected together to provide ~ 64% diesel equivalent fraction from pyrolysis of plastic grocery bags.
5. P10–P30 blends of PPEH-H with ULSD met all ASTM D975 specifications whereas only the P20–P30 blends met all EN 590 limits. P40 and P50 blends require antioxidants to meet the oxidative stability specification listed in EN 590.
6. P10 blend of PPEH-L with ULSD met all ASTM D975 specifications except lubricity, while none of the blends of PPEH-L with ULSD met EN 590 specifications primarily due to poor DCN, IP, FP, and KV.
7. Diesel obtained from pyrolysis of plastic is as compatible with biodiesel as ULSD due to similar hydrocarbon structures and chain length distribution of molecules.
8. Biodiesel blends with PPEH-H met the specifications for lubricity and KV, while PPEH-L blends satisfied the lubricity limits, but not KV limits. PPEH-L improved low temperature properties of SME biodiesel whereas PPEH-H had the opposite effect.

Based on these findings, PPEH-H and a mixture of PPEH-H/PPEH-L are suitable blend components for ULSD in the P10–P50 blend range so long as antioxidants are employed...



 Zhe Liu, et al.
 
 ZL-105 vs Cancer

 
http://www2.warwick.ac.uk/newsandevents/pressreleases/new_drug_raises/

New drug raises potential for cancer treatment revolution

A revolution in cancer treatment could soon be underway following a breakthrough that may lead to a dramatic improvement in cancer survival rates.

A new study at the University of Warwick, published today in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body’s natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.

Called ZL105, the drug is a compound based on the precious metal iridium. The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.

Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said “The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell ‘power-house’. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects”.

Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.

Study co-author Professor Peter J. Sadler said “Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments.”

“Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.

“In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by patients” argues Professor Sadler.

This research could also lead to substantial improvements in cancer survival rates. “Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells” said Dr Romero-Canelon.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201311161/abstract;jsessionid=487D95E3B88B65F3288F6BC1F5D4638E.f01t03
Angewandte Chemie International Edition, Vol. 53 Issue 13
DOI: 10.1002/anie.201311161
11 MAR 201

The Potent Oxidant Anticancer Activity of Organoiridium Catalysts

Dr. Zhe Liu, Dr. Isolda Romero-Canelón, Bushra Qamar, Jessica M. Hearn, Dr. Abraha Habtemariam, Dr. Nicolas P. E. Barry, Dr. Ana M. Pizarro, Dr. Guy J. Clarkson and Prof. Dr. Peter J. Sadler

Abstract

Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(?5-Cpxbiph)Ir(phpy)(Cl)] (1-Cl), which contains p-bonded biphenyltetramethylcyclopentadienyl (Cpxbiph) and C^N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(?5-Cpxbiph)Ir(phpy)(py)]+ (1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy.

NOVEL IRIDIUM/RHODIUM ANTI-CANCER COMPOUNDS
US2013065864

Inventor: HABTEMARIAM ABRAHA/LIU ZHE [GB] (+3)    

Also published as:     WO2011148124 / EP2575801 / CN102905705 / CA2797921 / AU2011257002

The present invention relates to novel iridium and/or rhodium containing complexes for use as a cytotoxic, such as an anti-cancer agent. There is also provided a method of preparing said compounds.

FIELD OF THE INVENTION

[0001] The present invention relates to novel iridium and/or rhodium containing complexes for use as cytotoxic, such as anti-cancer agents. There is also provided a method of preparing said compounds.

BACKGROUND OF THE INVENTION

[0002] A significant development of organometallic chemistry in recent years has been the increasing use of pentamethylcyclopentadienyl compounds. Not only are such compounds usually more soluble in organic solvents and more readily crystallized than their unsubstituted cyclopentadienyl analogs, but they are generally more stable as a result of the steric and electron-donation effects of the five methyl groups. This is particularly so for the ([eta]<5>-pentamethylcyclopentadienyl)iridium complexes, where the [eta]<5>-C5Me5 acts as an excellent ligand toward Ir(III) since it is displaced only with considerable difficulty.<1 >

[0003] Sheldrick's group in Germany has studied the biological activity of ([eta]<5>-pentamethyl cyclopentadienyl)iridium complexes with polypyridyl ligands. Their work focuses on the intercalative binding properties of polypyridyl (pp) ligands (pp=dpq, dppz and dppn) into DNA. Recently they have showed that [([eta]<5>-C5Me5)IrCl(dppz)](CF3SO3) and [([eta]<5>-C5Me5)Ir((NMe2)2CS)(dppn)](CF3SO3)2 possess in vitro cytotoxic activity towards MCF-7 and HT-29 cancer cell lines, while [([eta]<5>-C5Me5)Ir(phen)Cl](CF3SO3) and [([eta]<5>-C5Me5) Ir(en)Cl](CF3SO3) are inactive against MCF-7 (breast cancer).<2 >Furthermore they have studied the influence of polypyridyl ligands (pp=dpq, dppz and dppn) and monodentate ligands (L-Cl, (NH2)2CS, (NMe2)2CS) on DNA intercalation (see FIG. 1).<3 >They also found that the complexes [IrCl3(DMSO)(pp)] (pp=phen, dpq, dppz, dppn), (FIG. 1), are potent cytotoxic agents toward the human cell lines MCF-7 and HT-29 and their IC50 values are dependent on the size of the polypyridyl ligands.<4 >Their work on iridium and rhodium polypyridyl complexes of general formula [Me(hal)3(sol)(pp)], in which hal is a halogenide and sol is a solvent, is described in EP2072521.

[0004] DNA binding of the type [([eta]<5>-C5Me5)Ir(Aa)(dppz)](CF3SO3)n containing S-coordinated amino acids has been studied and X-ray structure of [([eta]<5>-C5Me5)Ir(9-EtG)(phen)](CF3SO3)2 has been reported.<5 >

[0005] The biological activity of three novel indium(III) complexes with 1,2-naphthoquinone-1-oximato ligand are also described.<6 >The complex [([eta]<5>-C5Me5)Ir (pyTz)Cl]<+ >containing the 2-(pyridine-2-yl)thiazole (pyTz) N,N-chelating ligand is reported to be inactive towards human ovarian cancer cell lines A2780 and A2780cisR (cisplatin-resistant)...

[0072] Examples of cancers which may be treated by the active compounds include, but are not limited to, a carcinoma, for example a carcinoma of the bladder, breast, colon (e.g. colorectal carcinomas such as colon adenocarcinoma and colon adenoma), kidney, epidermal, liver, lung, for example adenocarcinoma, small cell lung cancer and non-small cell lung carcinomas, oesophagus, gall bladder, ovary, pancreas e.g. exocrine pancreatic carcinoma, stomach, cervix, thyroid, prostate, or skin, for example squamous cell carcinoma; a hematopoietic tumour of lymphoid lineage, for example leukemia, acute lymphocytic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma, or Burkett's lymphoma; a hematopoietic tumor of myeloid lineage, for example acute and chronic myelogenous leukemias, myelodysplastic syndrome, or promyelocytic leukemia; thyroid follicular cancer; a tumour of mesenchymal origin, for example fibrosarcoma or habdomyosarcoma; a tumor of the central or peripheral nervous system, for example astrocytoma, neuroblastoma, glioma or schwannoma; melanoma; seminoma; teratocarcinoma; osteosarcoma; xenoderoma pigmentoum; keratoctanthoma; thyroid follicular cancer; or Kaposi's sarcoma.

[0073] Preferred cancers include leukaemia, CNS cancer, melanoma, prostrate cancer, colon cancer, breast cancer or any selection thereof.

Osmium (ii) arene azo anti-cancer complexes
CN103108880

http://onlinelibrary.wiley.com/doi/10.1002/anie.201311161/abstract;jsessionid=487D95E3B88B65F3288F6BC1F5D4638E.f01t03
Angewandte Chemie International Edition, Vol. 53 Issue 13
DOI: 10.1002/anie.201311161
11 MAR 2014

The Potent Oxidant Anticancer Activity of Organoiridium Catalysts†

Dr. Zhe Liu, Dr. Isolda Romero-Canelón, Bushra Qamar, Jessica M. Hearn, Dr. Abraha Habtemariam, Dr. Nicolas P. E. Barry, Dr. Ana M. Pizarro, Dr. Guy J. Clarkson and Prof. Dr. Peter J. Sadler

Abstract

Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(?5-Cpxbiph)Ir(phpy)(Cl)] (1-Cl), which contains p-bonded biphenyltetramethylcyclopentadienyl (Cpxbiph) and C^N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(?5-Cpxbiph)Ir(phpy)(py)]+ (1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy.




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