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Scientist
1689
Sensing the levels of protein-based biomarkers in biological samples is crucial for diagnosis of various diseases including cancer. Optical biosensors offer sensitivity and cost-effectiveness; however, current commercially available devices fail to provide sufficient selectivity and signal to noise...

Sensing the levels of protein-based biomarkers in biological samples is crucial for diagnosis of various diseases including cancer. Optical biosensors offer sensitivity and cost-effectiveness; however, current commercially available devices fail to provide sufficient selectivity and signal to noise ratios for protein targets.

The technology presents an approach for obtaining sensitive and widely applicable method for detecting and labeling a wide range of proteins in their native environment. It is based on the modification of thiazole orange with one or several protein binders. The result is a series of fluorescent molecular sensors customized to detect various proteins in bio-fluids and living cells with excellent signal-to-noise ratios.

Selective even towards isoforms of the same protein, several such biosensors are now developed against key biomarkers of different cancers, such as Glutathione S-Transferases (GST), His-tag and more. Together, they represent a novel class of highly sensitive fluorescent protein sensors that can pave the way for accurate, high-throughput medical diagnostics and live cell imaging.

Applications


·         Detection of proteins in biological samples for medical diagnostics

·         Fluorescent detection of His-tag or GST labeled proteins for imaging in living cells

·         Differentiating between protein isoforms


Advantages


·         High S/N - signal to noise ratio

·         High selectivity – enables to detect even different isoforms of the same target

·         Compatible with biological samples and living cells


Technology's Essence


Asymmetrical cyanine dyes constitute a unique class of fluorescent molecular sensors whose activation does not involve FRET, ICT, or PET processes. Instead, their fluorescence emission is turned on upon restriction of their torsional motion. Upon binding to DNA or peptide aptamers, this torsional motion leads to an enhanced fluorescence signal.

The present inention, developed by Dr. David Marguleis and his team, is based on TO derivatives linked to a specific "protein binder" – a molecule that selectively binds a desired target protein. The result is a highly selective series of sensors, able to detect their target biomarkers at nanomolar concentrations, with excellent S/N (signal-to-noise) ratios. With simple structural modifications, these sensors can be adjusted to distinct even between different isoforms of the same target, highlighting their strong selectivity.

Most importantly, sensing is compatible with diverse types of biological media including serum, blood, urine, saliva and other body fluids samples, rendering them especially suitable for medical applications.

Currently, the team is developing TO-sensors for GST, MMPs, PSA, Estrogen receptor, Fibronectin , Fgf and PDGF - known biomarkers of different cancers, b-amyloid - a known biomarker of Alzheimer's disease, Caspases, HDAC and His-tag. Such sensor for His-tag may be used as a powerfull research tool, to circumvent the limitations of common labeling methods, in living cells. 

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  • Prof. David Margulies
1549
A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one...

A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one or more ErbB ligands correlates with decreased patient survival. The currently approved drugs for the treatment of cancers driven by the ErbB family target the receptors rather than the ligands, and they include either monoclonal anti-receptor antibodies, or tyrosine kinase inhibitors (TKIs). Because of resistance and moderate clinical efficacies of anti-receptor antibodies and TKIs it is worthwhile considering alternative strategies. The present technology combines several antibodies, capable of blocking ErbB ligands, with chemotherapy.

Applications


  • Treatment of cancers that possess the ErbB receptors (e.g. colorectal, liver, bladder, and head and neck tumors)

Advantages


  • Effective blockade of the tumorigenic action of ErbB-specific ligands
  • The combination protocol may enhance the sensitivity to chemotherapy

Technology's Essence


In the outlined technology, monoclonal antibodies were generated against two ligands, namely TGF-? and heparin-binding EGF-like growth factor. Combining the two antibodies with a chemotherapeutic drug enhanced the ability of chemotherapy to inhibit pancreatic tumors in mice. Therefore, this technology offers a general cancer therapeutic strategy that entails profiling the repertoire of growth factors secreted by a tumor, and combining with chemotherapy several antibodies capable of blocking autocrine ligands, in a way that sensitizes tumors to cytotoxicity and delays onset of chemoresistance.

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  • Prof. Yosef Yarden
1783
Aluminum and magnesium alloys are gaining more recognition for light-weight materials applications. In spite of this, such alloys have not been used for critical mechanical applications mainly due to their inferior mechanical properties compared to other engineering materials such as steel. Hence, many...

Aluminum and magnesium alloys are gaining more recognition for light-weight materials applications. In spite of this, such alloys have not been used for critical mechanical applications mainly due to their inferior mechanical properties compared to other engineering materials such as steel. Hence, many researchers have attempted to reinforce these alloys and obtain light-weight materials with excellent mechanical properties. The reinforcement process of the alloy can be achieved by introducing another material to form metal matrix composites. Different studies show that such composites exhibit improved properties, such as increased yield strength and tensile strength, enhanced stiffness, improved thermochemical properties, etc. However, the introduction of nanomaterials into the metal matrix is rather difficult due to the harsh manufacturing conditions employed for processing the metal composites.

The group of Prof. Reshef Tenne has developed state-of-the-art aluminum- and magnesium-based metal matrix composites, comprising small amounts of inorganic nanomaterials, such as nanotubes and spherical nanoparticles. The new nanocomposites exhibit much superior mechanical properties compared to the pristine alloy.

 

Table 1: Mechanical properties of different alloys reinforced with nanoparticles versus their neat form

Metal

Alloy

Neat UTS, MPa

Neat elongation

Added Nanoparticles

improvement UTS, %

improvement elongation, %

Aluminum

AA6061

170

0.28

0.2wt.% INT

21%

68%

AA6061

170

0.28

0.2wt.% IF

16%

39%

AA356

175

0.09

0.02wt.% INT

9%

44%

Magnesium

AZ31

135

0.14

0.2wt.% INT

54%

85%

AZ61

130

0.10

0.2wt.% INT

45%

96%

Applications


·         Automotive, transportation, and aerospace industries

·         Jet engine technologies

·         Electronics

·         Medical technologies


Advantages


·         Light-weight metal alloys

·         Excellent mechanical properties

·         Straight-forward fabrication technique


Technology's Essence


Aluminum and magnesium alloys were combined with small amounts (up to 0.5 wt.%) of either tungsten disulfide nanotubes (WS2 INT) or inorganic fullerene-like tungsten disulfide nanoparticles (WS2 IF) to form metal matrix composites (MMC) using a melt-stirring reactor operated at high temperatures (Al MMCs: 250-750?C; Mg MMCs: 400-720?C). These nano-structures exhibit unique mechanical properties, which make their usage as a metal reinforcement very promising. The nanoparticles showed quite a remarkable stability at these elevated processing temperatures and were found to be uniformly distributed. Despite the small amounts of added nanostructures, their addition led to remarkable improvements in the mechanical properties of the alloys. Surprisingly, both the tensile strength of the alloys and their elongation were improved by approximately 10-50% and 40-100% (and consequently the fracture toughness was significantly increased), respectively. Depending on the nano-structure type and concentration, the hardness, yielding strength, ultimate tensile strength, and ductility were significantly improved. For example, the yielding strength, ultimate tensile strength (UTS), and ductility of AA6061/0.2wt.% WS2 INT MMCs were improved by 15%, 21% and 68%, respectively. Representative mechanical properties of different aluminum and magnesium alloys reinforced with nanoparticles versus their neat form are shown in Table 1. Stress-strain curves of AA6061 aluminum alloy reinforced with different nanoparticle loading are presented in Figure 1. Physical considerations suggest that the main mechanism responsible for the reinforcement effect lies in the mismatch between the thermal expansion coefficients of the metal and the nano-structures.

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  • Prof. Tenne Reshef
1736
Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production. Improvement in the...

Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production.

Improvement in the metabolic pathway related to carbon fixation would have great value in increasing crop yields, synthesizing high value compounds in algae, and developing means in removing CO2 from the atmosphere to combat climate change.

The present technology is an engineered E. coli with a carbon fixation pathway. The unique innovation can be used to efficiently screen the activity of RuBisCO, the most abundant carbon fixing enzyme on earth, which is further applicable to improving biomass production in different photosynthetic organisms such as plants and algae.

Applications


·      Powerful platform for screening and improving various enzymes in the carbon fixation process.

·      Unique metabolic pathway for use in Synthetic Biology applications.

·      Possible Carbon Credits for developing improved means of carbon fixation.


Advantages


·      E. coli is fast growing and easily manipulated by various genetic tools.

·      Novel source of biomass production.

·      Potentially low cost R&D system.


Technology's Essence


The technology functions by the recombinant insertion of two enzymes from the Calvin-Benson-Bassham (CBB) into E. coli, kinase prk and the carboxylating enzyme RuBisCO. With further modifications, the engineered E. coli’s metabolism was divided into two subsections. First a carbon fixing metabolism that can incorporate inorganic CO2 into sugar production, the second subsection consumes organic pyruvate to produce energy to drive the aforementioned carbon fixing cycle. Subsequently the technology is overall carbon neutral, but is an inexpensive and fast platform for screening improvements in the CBB carbon fixation pathway.

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  • Prof. Ron Milo
1786
Perovskites are a class of crystalline materials with a common complex chemical structure. Lead-halide hybrid organic-inorganic perovskites have recently emerged as highly efficient optoelectronic materials. Such materials are being intensively investigated and developed for photovoltaics,...

Perovskites are a class of crystalline materials with a common complex chemical structure. Lead-halide hybrid organic-inorganic perovskites have recently emerged as highly efficient optoelectronic materials. Such materials are being intensively investigated and developed for photovoltaics, photodetection, light-emitting diodes, and laser devices. Solar cells containing hybrid organic-inorganic perovskites have achieved over 20% certified efficiency.

Perovskites are most commonly synthesized by combining a metal salt (for example, a lead-based salt such as lead iodide) with an organic halide salt in a single step, by spin-coating from a solution of both salts, by co-evaporation, or by a two-step method of forming the metal salt film and subsequently exposing it to the organic halide. The existing fabrication methods suffer from high toxicity, complexity and high energy input.

We present a new method for the preparation of halide perovskites on a substrate for optoelectronic devices and solar cells, including tandem cells that produce higher voltages.

Applications


·      Solar cells

·      Other optoelectronic devices (e.g., photodetectors, light-emitting diodes, lasers)


Advantages


·      Reduced toxicity

·      Simple and straight-forward fabrication method

·      Excellent morphology control of the perovskites


Technology's Essence


Perovskites are crystalline materials with the formula ABX3, in which A and B are cations and X represents an anion. In hybrid organic–inorganic perovskites (HOIPs), A is an organic cation, B is a metal cation, and X is a halide anion.

The synthesis of HOIPs usually involves the use of toxic metal salts (for example, lead iodide or lead acetate) and organic solvents (such as dimethylformamide). Additionally, the combination of a metal salt with several organic solvents, such as dimethylsulfoxide, increases the toxicity of the solution in use.

The new fabrication method utilizes a metal or a metal alloy and an organic halide salt. In the first step, a layer comprising one of the components is deposited on a substrate. Then, the deposited layer is treated with a solution or a vapor of the second component to form a halide HOIP on a solid surface. This method provides a direct conversion of an elemental metal or a metal alloy to a halide perovskite or a perovskite related material. The main advantage of the presented method is the reduced toxicity of the solution used in the process. Additionally, the metals (mainly lead) are much less toxic in terms of manufacturing than the salts of the same metals.

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  • Prof. David Cahen
1798
The rising demand for exclusive visual impact in many applications, along with escalating regulatory requirements drive the development of new, environmentally benign, pearlescent materials. Guanine, a common naturally mineralized material, is being used in a variety of products in industries, such as...

The rising demand for exclusive visual impact in many applications, along with escalating regulatory requirements drive the development of new, environmentally benign, pearlescent materials. Guanine, a common naturally mineralized material, is being used in a variety of products in industries, such as cosmetics, paints and jewelry due to its pearlescence effect. However, the industrial application of guanine crystals is limited since they are extracted from biological sources (mostly fish scales) with limited control over crystals dimensions, morphology and quantity for industrial applications. The main reasons impeding the use of synthetic guanine crystals are guanine insolubility in most solvents and the difficulty of obtaining crystals in the desired morphology. For these reasons, there is a thriving need for the development of a synthetic approach for the formation of well-defined anhydrous guanine crystals with tailor-made properties.

The new technology provides a novel synthetic method for the preparation of highly versatile pearlescent materials, based on guanine crystals, from aqueous solutions. The controllable size and shape of the resulting materials and the sustainability of the method make them suitable alternatives for the existing naturally occurring pearlescent pigments.

Applications


·      Cost-effective and environmentally-friendly approach

·      Control over crystals properties, including size and phase (anhydrous guanine and guanine monohydrate)

·      The same technology can be applied for the crystallization of other materials (purines and pteridines)


Advantages


·      Cosmetics and personal care products

·      Printing inks and decorative paints

·      Automotive paints.


Technology's Essence


Guanine is practically insoluble in neutral aqueous solutions. However, in aqueous acidic or basic solutions, where the molecules are ionized, guanine is much more soluble. The process involves dissolving guanine powder in either acidic or basic solutions, using HCl or NaOH, respectively, and then inducing crystallization by adjusting the pH of the solution. The crystal morphologies differ significantly when carrying out the crystallization in solutions adjusted to different pH regimes. Using pH induced crystallization, the interplay between the initial guanine concentration and the rate of pH change allow substantial control over the crystallization process and ultimately over the crystal size.

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  • Prof. Lia Addadi
1795
Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small,...

Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small, difficult-to-reach, spaces for medical and other applications. Multimode fibers are being explored as ultra-thin lensless replacements for the commonly used endoscopes. The difficulty with imaging or focusing light through a multimode fiber is phase randomization of light propagating through the fiber, which results in a complex speckle pattern at the fiber output. To overcome this obstacle, an access to both fiber ends is required for pre-calibration.

A novel endoscopic method that was developed by Prof. Silberberg at the Weizmann Institute of Science allows light focusing through a multimode fiber by approaching solely the proximal end and retrieving information about the distal end using non-linear optical feedback.

Applications


·         Clinical imaging of narrow cavities (blood vessels, respiratory system, joints, etc.)

·         Selective targeting and burning of fluorescent targets (imaging and treatment)  


Advantages


  • Ultra-thin (micro-meter scale) and flexible

  • Lensless endoscopy

  • High resolution and accuracy


Technology's Essence


We consider a two-photon lensless multimode fiber-based endoscope, where an ultrashort pulse is delivered to a fluorescently tagged sample through the fiber. The pulses excite two photon fluorescence (2PF) from a 2PF screen placed against the fiber distal end. The back-propagated 2PF that is collected by the same fiber is separated from the excitation light at the proximal end by a dichroic mirror (DM), and the Fourier-transformed image of the fiber facet is recorded by an EMCCD camera. It is then used as feedback for a wavefront-shaping optimization algorithm, controlling a spatial light modulator (SLM) at the proximal fiber end. The nature of the light propagation in the fiber allows for scanning and controlling the focus position at the fiber distal end.

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  • Prof. Yaron Silberberg
1722
Our technology provides a new type of oxidative cleavage reaction of organic compounds with highly selective product formation.Polyoxometalate (POM) catalysts have become well-known for their utility and diversity in specific reactions. Through the elucidation of POM catalytic pathways, greater...

Our technology provides a new type of oxidative cleavage reaction of organic compounds with highly selective product formation.
Polyoxometalate (POM) catalysts have become well-known for their utility and diversity in specific reactions. Through the elucidation of POM catalytic pathways, greater versatility has been achieved. This technology is one such application of a novel POM catalyst and is exploited to cleave carbon-carbon double bonds in alkenes (olefins) through an aerobic oxidation reaction. Oxidation reactions are of particular interest because they are difficult to achieve on an industrial scale while maintaining “green” chemistry practices. [1]

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[1] Green Chem., 2007, 9, 717-730

Applications


  • As a novel catalyst in industrial organic chemistry processes
  • Sold as a stand-alone catalyst for laboratory or individual use

Advantages


  • Environmentally friendly oxidation reaction
  • Easy catalyst regeneration

Technology's Essence


Our approach is motivated by societal considerations that demand environmentally benign and sustainable solutions for oxidative reactions. As such, we have developed a scheme to react NO2 with a transition-metal-substituted POM which yields a metal-nitro intermediate that is competent for forming the precursors for oxidation with molecular oxygen, O2, to have a final product of ketones and/or aldehydes, and regenerate the POM catalysts.[1]
This method has preference towards di/tri-substituted alkenes. High yields of ketones or aldehydes have been produced and the POM catalyst is regenerated without further oxidation to carboxylic acids, as is typical with other oxidative catalysts.
The selective cleavage of carbon-carbon double or triple bonds with metal-nitro or metal-nitrito compound has not been reported. This exciting new discovery could lead to a wide variety of organic reactions not previously possible, along with revolutionary green oxidative chemistry techniques.

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[1] J. Am. Chem. Soc., 2014, 136(31), pp10941-10948 

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  • Prof. Ronny Neumann
1690
Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts, phage infection of starter cultures for dairy processing remains the most common cause...

Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts, phage infection of starter cultures for dairy processing remains the most common cause of slow or incomplete fermentation and product downgrading. Standard anti-phage measures (sanitation, culture handling) fail to provide sufficient protection, exposing the production process to massive economic setbacks.
Extensive R&D efforts have led to the discovery of phage resistance systems, however many phages can circumvent these systems, and in addition not all LABs can accommodate them.
Therefore, there is a strong need for additional defense systems that could naturally protect LABs against phages.
The Sorek laboratory at the Weizmann Institute of Science has recently identified hundreds of novel functional toxin/antitoxin systems in bacterial genomes. These systems were discovered using analysis of data from millions of shotgun cloning experiments across 388 bacterial species. Acting as an abortive infection agent to prevent phage spread, some of these systems were already validated as conferring resistance against phage infection upon introduction to E.coli cells.
In another novel technology, researchers at Dr. Rotem Sorek’s lab identified a novel anti phage gene cassette, termed BREX (Bacteriophage Exclusion), which confers complete or partial resistance against phages spanning a wide phylogeny of phage types, including lytic and temperate ones.

Applications


  • Tools for conferring anti-phage traits to bacterial starters.

Advantages


  • Provides efficient phage-resistance features.
  • Robust: confers resistance to a broad range of phages, including both lytic and temperate ones.
  • General: the same defense system may be applied in various cultures, not confined to specific strains.
  • Novel systems, provides a fresh approach to the field of phage resistance 

Technology's Essence


Toxin/antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, are proposed to function in phage defense via abortive infection. The two genes, which reside on the same operon, code for small proteins where inhibition of the toxin is carried out through protein-protein interaction. Upon a specific signal (phage infection) the antitoxin degrades rapidly by one of the housekeeping bacterial proteases, resulting in either bacteriocidic (cell-killing) or bacteriostatic (growth-inhibiting) effects, thus protecting the colony against phage spread. The inventors took advantage of the concept that toxins could only be cloned when the neighboring antitoxin was present on the same clone to systematically reveal active TA pairs. Following extensive statistical and experimental validations, 8 novel families of TA pairs that are likely to play a role in phage defense were identified. By introducing these systems into new bacteria, the inventors showed that the toxin/antitoxin pairs could protect the engineered bacteria from phage infection.
BREX is a novel cassette of six genes that confers protection against a wide range of phages, including virulent and temperate ones. This cassette is composed of genes not typically found in other defense systems, and hence employs a novel mechanism of anti-phage protection. Scientists at the Sorek lab further uncovered the mode of action of this novel system. It was shown that the system is not an abortive infection system (i.e., does not lead to suicide of the infected cell), and that it allows phage adsorption but blocks phage replication in a DNA degradation independent manner.

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  • Prof. Rotem Sorek
1765
A new image reconstruction tool based on non-iterative phase information retrieval from a single diffraction pattern was developed by the group of Prof. Oron.  Lensless imaging techniques enable indirect high resolution observation of objects by measuring the intensity of their diffraction patterns....

A new image reconstruction tool based on non-iterative phase information retrieval from a single diffraction pattern was developed by the group of Prof. Oron. 
Lensless imaging techniques enable indirect high resolution observation of objects by measuring the intensity of their diffraction patterns. These techniques utilize radiation in the X-ray regime to image non-periodic objects in sizes that prohibit the use of larger wavelengths. However, retrieving the phase information of the diffraction pattern is not a trivial task, as current methods are divided based on a tradeoff between experimental complexity and computational reconstruction efficiency.
The method described here is suitable for use with existing lensless imaging techniques to provide direct, robust and efficient phase data while requiring reduced computational and experimental complexity. This method, demonstrated in a laboratory setup on 2D objects, is also applicable in 1D. It can be applied to various phase retrieval applications such as coherent diffractive imaging and ultrashort pulse reconstruction

Applications


  • Phase microscopy
  • Signal processing
  • Holography
  • X-ray imaging

Advantages


  • A Generic solution to the phase retrieval problem
  • Non-iterative approach
  • An efficient and noise robust tool

Technology's Essence


The method is based on the fact that the Fourier transform of the diffraction intensity measurement is the autocorrelation of the object. The autocorrelation and cross-correlations of two sufficiently separated objects are spatially distinct. Based on this, the method consists of three main steps: (a) The sum of the objects’ autocorrelations, as well as their cross-correlation, are reconstructed from the Fourier transform of the measured diffraction pattern. (b) The individual objects’ autocorrelations are reconstructed from their sum and the cross-correlation. (c) Using the two intensities and the interference cross term, double-blind Fourier holograph is applied to recover the phase by solving a set of linear equations.

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  • Prof. Dan Oron
1802
A new signal processing tool for the detection of pulses travelling through media with complex or unknown dispersion properties was developed by the group of Prof. Gal-Yam, originally for detecting radio bursts in astronomical observations. Pulses are applied in various fields such as oil & gas...

A new signal processing tool for the detection of pulses travelling through media with complex or unknown dispersion properties was developed by the group of Prof. Gal-Yam, originally for detecting radio bursts in astronomical observations.
Pulses are applied in various fields such as oil & gas exploration, detection (e.g. sonar, lidar and radar) and communication. When pulses pass through dispersive media, the arrival times at the detector of different frequency components may differ, and as a result the pulse may become degraded (e.g. transformed to a longer pulse with reduced intensity), even to the level of becoming indistinguishable in terms of signal to noise. This problem becomes even more challenging when detecting short pulses that travel through complex or unknown media.
The new method presented here provides a proven and efficient solution that can be applied for different scenarios where short pulses dispersed by complex media are used. 

Applications


  • Detection and surveying technologies- sonar, lidar, radar etc

Advantages


  • Efficient, requires limited computational resources
  • Generic, can be applied to various setups
  • Easily implementable into existing systems

Technology's Essence


The method includes obtaining an input array of cells, each indicating an intensity of a frequency component of the signal at a representative time. A fast dispersion measure transform (FDMT) is applied to concurrently sum the cells of the input array that lie along different dispersion curves, each curve defined by a known non-linear functional form and being uniquely characterized by a time coordinate and by a value of the dispersion measure. Application of FDMT includes initially generating a plurality of sub-arrays, each representing a frequency sub-band and iteratively combining pairs of adjacent sub-arrays in accordance with an addition rule until all of the initially generated plurality of sub-arrays are combined into an output array of the sums, in which a cell of the output array that is indicative of a transmitted pulse is identified.

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  • Prof. Avishay Gal-Yam
1733
The spatial distribution of proteins inside the cell is under tight regulation. This regulation is necessary to ensure proper functioning of the cell, and is of particular importance when extracellular stimulation is applied. Upon stimulation, many signaling proteins rapidly and dynamically change...

The spatial distribution of proteins inside the cell is under tight regulation. This regulation is necessary to ensure proper functioning of the cell, and is of particular importance when extracellular stimulation is applied. Upon stimulation, many signaling proteins rapidly and dynamically change their location. Today, there is a widely recognized need to identify novel sequences which regulates nuclear translocation.
Recently, Prof. Zeger and his team discovered a new level of regulation to stimulated transcription. They showed that ?-like importunes are central mediators of nuclear translocation of signaling proteins. Furthermore they identified the site of interaction and designed accordingly a peptide which was found to prevent nuclear translocation.
This technology presents peptides with the potential of treating inflammatory and immune disease by regulating (prevent or promote) the translocation of proteins into the nucleus.

Applications


  • Inflammation
  • Immune diseases

Advantages


  • Effective
  • Safe

Technology's Essence


The researchers found that ?-like importins play a key role in JNK and p38 translocation. They also found that the translocation of these MAPKs is mediated by the formation of either Imp3/Imp7/MAPK or Imp3/Imp9MAPK heterodimers. Most importantly, the researchers identified the site in p38 that mediate the interaction with Imp7 and Imp9 and showed that the important sequence lies within residues 20-30 of p38?. Subsequently they synthesized a 14 amino acid myristoylated peptide based on the sequence of residues 21-34 of p38?. When it was applied to HeLa cells prior to stimulation, it prevented the nuclear translocation and Imp7/9 interaction of the MAPKs. Since the peptides of this technology are able to specifically inhibit the nuclear activities of p38 (such as inflammatory activities) without modulating their cytoplasmic activities, these peptides may serve as a therapeutic agent for inflammatory and apoptosis related diseases without having side effect.

 

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  • Prof. Rony Seger
1704
Neuropathic Gaucher’s (nGD), is a rare but very severe manifestation of the disease, with a varying degree of involvement of the central nervous system, in addition to systemic symptoms. As of today, there is no cure for these severe conditions. The search for such cure is tremendously hindered by the...

Neuropathic Gaucher’s (nGD), is a rare but very severe manifestation of the disease, with a varying degree of involvement of the central nervous system, in addition to systemic symptoms. As of today, there is no cure for these severe conditions.
The search for such cure is tremendously hindered by the unmet need for a reliable biochemical biomarker for nGD.
The present invention identifies the glycoprotein non-metastatic B (GPNMB) as a potential powerful nGD biomarker for use in early diagnosis, determination of disease severity, as well as a straight forward readout in clinical and preclinical experiments.

Applications


Diagnosis and drug development for neuropathic GD

Advantages


Straight forward diagnostic tool – based on standard biochemical assays
Relatively simple clinical procedure – samples are collected from CSF and not brain
High sensitivity – for the diagnosis of disease severity
Compatible with preclinical experiments

Technology's Essence


Prof. Futerman and his team preformed a quantitative global proteomic analysis (using LC-MS/MS) of cerebrospinal fluid (CSF) samples from four patients with Type 3 GD, to identify mis-regulated proteins, compared with healthy subject.
Glycoprotein non-metastatic B (GPNMB), a protein that was previously associated with several lysosomal storage disorders, exhibited very high levels (a 42-fold increase) in the CSF of type 3 GD patients.  Two peptides were identified from GPNMB, both located in the non-cytosolic domain, suggesting that GPNMB is cleaved and secreted into the CSF from the brain. LC-MS/MS results were validated by ELISA and by western blot analysis in CSF and in human brain samples.
Several proof of principle experiments were conducted in order to prove the validity of using GPNMB as a biomarker for monitoring disease state and treatments efficacy in neuropathic GD in patients and mouse models:
GPNMB levels were shown to be correlated with the severity of type 3 Gaucher’s disease patients, as measured by lower IQ score and lower score in Purdue Pegboard test, assessing eye-hand coordination. In addition, using conduritol b epoxide (CBE)-injection based mouse model that simulate different severities and recovery periods, it was shown that GPNMB levels rapidly rise or decline to reliably reflect progress/remission states of the diseases.

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  • Prof. Anthony H. Futerman
1780
A method based on Fast Neutron Resonance Transmission (FNRT) radiography that enables determining weight percentages of oil and water in thick, intact cores taken from subterranean or underwater geological formations. As part of geological exploitation to find oil and water, cores are extracted and...

A method based on Fast Neutron Resonance Transmission (FNRT) radiography that enables determining weight percentages of oil and water in thick, intact cores taken from subterranean or underwater geological formations. As part of geological exploitation to find oil and water, cores are extracted and tested to determine oil/water content.
This new method allows determining such content rapidly, in non- destructive, specific and quantities analysis of the cores.

Applications


  • Determining the identity and proportions of substances of oil and water content and their distribution in inspected cores

Advantages


  • A non-destructive method which enables to determine the fluid content along the entire length of an intact core or aggregate of cores within their protective sleeves.
  • More comprehensive information and considerable saving of analysis time compared to conventional sampling methods.
    Suitable for all types of rocks including tight-shale rocks.
  • This method enables to measure the weight fraction of oil and water in the core regardless of the core shape, thickness or distribution.
  • The fluid weight fractions in the samples are determined independently, thus the ratio of oil-to-rock weight-ratio is independent of the water content.
  • Due to high penetration of fast neutrons, the method is suitable for screening intact thick rock cores (10-15 cm), for which alternative probes, such as X-rays or slow neutrons suffer limited penetration.

Technology's Essence


In order to map the oil and water content and their distribution, an aggregate of intact cores within their protective sleeves is positioned on a moving conveyor belt and scanned by a broad- energy, fast- neutron beam. The neutrons are detected by a spectroscopic fast neutron imaging detector. The map of neutron-transmission spectra in each pixel provides information of oil/water content and distribution in such cores. 

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  • Prof. Amos Breskin
1750
Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases...

Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.
Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases, with an exceptionally high potency. Although not as lethal as nerve agents, organophosphate insecticides can be harmful in large or prolonged doses. The standard therapy has limited efficacy, carry risks of serious adverse effects and have relatively short shelf life in field conditions.
Bioscavengers represent a preferred to rapidly detoxify organophosphates in the blood, before they had the chance to reach its physiological targets and cause damage, but usually require the use of very high doses.
The present invention provides genetically modified phosphotriesterase (PTE) variants, which serve as catalytic bioscavengers for V-type nerve agents, with exceptional detoxification activity at low doses, and improved stability.

Applications


  • Prophylactic or post exposure treatment for nerve gases attack, in particular V-type agents
  • Treatment for pesticides poisoning

Advantages


  • High catalytic activity – allow high efficacy at low doses
  • Reduced effective doses allows to reduce adverse effects
  • High stability increasing shelf life
  • Compatible with both prophylaxis and post exposure
  • Compatible for both surface decontamination and administration to patients

Technology's Essence


Researchers at Prof. Tawfik lab use directed evolution to drive protein mutagenesis towards desired traits. Appling this approach, using the actual threat agents, the present inventors generated recombinant phosphotriesterase (PTE) variants with improved catalytic efficiencies towards V-type nerve agent hydrolysis. Serving as catalytic bioscavengers, these recombinant PTE variants hydrolyze organophosphates without being consumed and thus can be applied at low doses (catalytic efficiency (kcat/KM) greater than 3.106 M-1min-1).
Importantly, PTE is efficient both as a prophylactic agent that may be given several hours prior to exposure as a preventive measure, and as post exposure antidote, even days after in a single or multiple-doses.
It is compatible with both decontamination of surfaces and detoxification administrated to a patient by standard routes such as orally or injectables.
Finally, some PTE variants show superior stability properties, retaining at least 50% of their catalytic activity at 50?C, indicating extended shelf life. This may be especially critical in field conditions, where the risk for nerve agent exposure is high.

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  • Prof. Dan S. Tawfik

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