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Technology Name
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Scientist
1647
Novel algorithms developed at the Weizmann Institute of Science for Content-Based Image Retrieval (CBIR) can enhance search engines by crowd-sourcing and improved clustering.Discovering visual categories among collection of images is a long standing challenge in computer vision, which limits images-...

Novel algorithms developed at the Weizmann Institute of Science for Content-Based Image Retrieval (CBIR) can enhance search engines by crowd-sourcing and improved clustering.
Discovering visual categories among collection of images is a long standing challenge in computer vision, which limits images-based search engines. Existing approaches are searching for a common cluster model. They are focused on identifying shared visual properties (such as a shared object) and subsequently grouping the images into meaningful clusters based upon these shared properties. Such methods are likely to fail once encountering a highly variable set of images or a fairly limited number of images per category.
Researchers form Prof. Michal Irani lab suggest a novel approach based on ‘similarity by composition’. This technology detects statistically significant regions which co-occur across images, which reveals strong and meaningful affinities, even if they appear only in few images. The outcome is a reliable cluster in which each image has high affinity to many images in the cluster, and weak affinity to images outside the cluster.

Applications


  • Images search engines - can be applied for collaborative search between users.
  • Detecting abnormalities in medical imaging.
  • Quality assurance in the fields of agriculture, food, pharmaceutical industry etc.
  • Security industry- from counting people up to identifying suspicious acts.
  • Computer games and brain machine interface.

Advantages


• Can be applied to very few images, as well as benchmark datasets, and yields state-of-the-art results.
• Handles large diversity in appearance.
• The search is not a global search, it requires no semantic query, tagging or pre-existing knowledge.
• The multi-images collaboration significantly speeds up the process, reducing the number of random samples and iterations.
• Set of images are obtained in time which is nearly linear in the size of the image collection.


Technology's Essence


In “clustering by composition”, a good cluster is referred as one in which each image can be easily composed using statistically significant pieces from other images in the cluster while is difficult to compose from images outside the cluster. Multiple images exploit their ‘wisdom of crowds’ to further improve the process. Using a collaborative randomized search algorithm images can be composed from each other simultaneously and efficiently. This enables each image to direct the other images where to search for similar regions within the image collection. The resulted sets of images affinities are sparse yet meaningful and reliable.

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  • Prof. Michal Irani
1554
We present a novel approach resulting in efficient and robust wireless energy transfer in the mid-range. Applications of wireless energy transfer are already in use and are continuously being developed. The main limit of wireless energy transfer techniques is that both the transmitter and transformer...

We present a novel approach resulting in efficient and robust wireless energy transfer in the mid-range. Applications of wireless energy transfer are already in use and are continuously being developed. The main limit of wireless energy transfer techniques is that both the transmitter and transformer need to be of the same resonance. In addition, this technique is very susceptible to noise which limits efficiency. The present invention provides a technique for a robust and efficient mid-range wireless power transfer between two coils. This technique can transfer the energy between the coils without being sensitive to any resonant constrains, noise and other interferences that exist in the neighborhood of the coils

Applications


  • Simultaneous energy transfer to several electrical gadgets.

Advantages


  • Efficient
  • Not sensitive to electrical interference.
  • No need for an exact resonance match between transmitter and transformer.

Technology's Essence


The efficiency and robustness of this technology is achieved by adapting the process of rapid adiabatic passage (RAP) for a coherently driven two state atom to the field of wireless energy transfer. In other words, the resonance of the transmitter is tuned adiabatically to scan a resonant frequency range, thus arriving at a dynamic solution to the electrical transfer problem.

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  • Prof. Yaron Silberberg
1621
Novel treatment for angiogenesis-related diseases.Angiogenesis — the growth of new blood vessels from pre-existing vasculature — has an essential role in development, reproduction and repair. Pathological angiogenesis is a common theme in a broad range of diseases such as cancer, autoimmune diseases,...

Novel treatment for angiogenesis-related diseases.Angiogenesis — the growth of new blood vessels from pre-existing vasculature — has an essential role in development, reproduction and repair. Pathological angiogenesis is a common theme in a broad range of diseases such as cancer, autoimmune diseases, age-related macular degeneration and atherosclerosis. The global market for angiogenesis stimulators and inhibitors is forecast to reach ~US $50 billion by the year 2015. Most of the currently marketed angiogenesis regulators, such as Avastin, typically display modest efficacy and therefore further highlight the great need for the development of novel therapeutics. The current technology presents a novel method to treat angiogenesis-related disorders by modulating apolipoprotein B (ApoB).

Applications


  • ApoB is a potential therapeutic target for the treatment of cancer and other non-neoplastic diseases.
  • ApoB levels may serve as a biomarker for cancer metastasis.

Advantages


  • The anti-angiogenic effect of LDL administration was demonstrated in vivo, in zebrafish models, as well as in vitro, in relevant human cells lines.
  • Regulation of ApoB levels may be applied to treat a broad range of angiogenesis-dependent diseases.
  • Detection of ApoB levels can be readily achieved by analysis of body fluids such as blood and plasma.

Technology's Essence


Using a high-throughput genetic screen for vascular defects in zebrafish, researchers at the Weizmann Institute of Science have identified a genetic mutation that leads to excessive angiogenesis. The mutated gene is responsible for the assembly of ApoB-containing lipoproteins such as LDL, otherwise known as the ‘bad’ cholesterol. The group has found that low levels of LDL promote the formation of new blood vessels by directly interacting with the VEGF pathway. The outlined technology offers methods to modulate the levels of ApoB in order to stimulate, or inhibit angiogenesis, dependent on the therapeutic strategy. For example, inhibition of angiogenesis by increasing ApoB levels may repress tumor growth and attenuate its metastatic potential. In another application of this technology, increased circulating levels of ApoB can serve as a biomarker for the overproduction of blood vessels, thus enabling early diagnosis of pathogenic states in angiogenesis-dependent diseases.

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  • Prof. Karina Yaniv
1585
Our scientific team has discovered a method to apply the Gabor Transform to signal processing and data compression. Compared to existing methods that are based on Fourier transform, the new method provides for up to 25% savings in content size for video, audio and images, without any loss in quality...

Our scientific team has discovered a method to apply the Gabor Transform to signal processing and data compression.

Compared to existing methods that are based on Fourier transform, the new method provides for up to 25% savings in content size for video, audio and images, without any loss in quality.

By embracing our method, content providers, ISPs and mobile carriers can achieve major savings in data storage and data transfer costs.

Applications


The method can be used in virtually all applications involving data storage, communication and signal processing. One of the main commercial application is for lossy data compression for video, audio and images. Those types of content constitute the bulk of today’s Internet traffic, and improved compression will generate substantial savings in storage and data transfer costs.

The method also applies to the storage, communication and processing of quantum information and may therefore be expected to have applications in quantum calculations, quantum communication and quantum information processing.


Advantages


Existing data compression methods are based on numerical implementations of the Fourier transform, known as FFT, DCT and similar.

Compared to these methods, Gabor transform method demonstrates a very significant advantage in terms of the size of compressed material.  

The method provides for up to 25% savings in data size, while keeping the same perceived quality of the content.


Technology's Essence


We have discovered the definitive solution to the problem of obtaining accuracy and stability in the Gabor transform.  We realized that there must be an exact informational equivalence between the Gabor transform and the discrete Fourier transform (DFT). The latter is known to provide an exact representation of functions that are band-limited with finite support.  Since the DFT implicitly assumes periodic boundary conditions, to obtain this exact equivalence one needs to modify the Gaussians in the Gabor transform to obey periodic boundary conditions. This leads to Gaussian flexibility with Fourier accuracy --- precisely what has been sought since 1946.

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  • Prof. David J. Tannor
1564
A new recyclable size-selective filtration device. Particle size, chemical purity and dispersion of nanoparticles crucially determine their optical, electronic and chemical properties. Size-selective separation technologies are becoming increasingly important for the development of nanoparticles with...

A new recyclable size-selective filtration device.

Particle size, chemical purity and dispersion of nanoparticles crucially determine their optical, electronic and chemical properties. Size-selective separation technologies are becoming increasingly important for the development of nanoparticles with well-defined sizes, which have application in the fields of optoelectronic devices, biomedicine, materials, and catalysis.

Researchers at the Weizmann Institute have fabricated supramolecular ultrafiltration membranes that can be used for filtration and size-selective chromatography of nanoparticles. The membranes are composed of a self-assembled three-dimensional fibrous network that is held together by reversible non-covalent interactions.

The membranes are robust, easy to fabricate, and recyclable.

Applications


  • Size-selective separation of semiconductor and metal nanoparticles
  • Uniformity and monodispersity of nanoparticles in solution.
  • Size exclusion chromatography of nanoparticles in the sub-5-nm size regime.

Advantages


  • Efficient and inexpensive

  • Fast and easy fabrication

  • Recyclable

  • Self-assembled

  • Dual application regime: filtration and/or chromatography


Technology's Essence


The recyclable supramolecular membranes are formed from unique perylene derivatives that are large and flat aromatic molecules. These molecules are insoluble in water and form a 3-D network over a solid support, which can be used for the separation of nanoparticles.

The filters can be subsequently recycled from this mixture using an organic solvent (e.g. dichloromethane), which separates the membrane material from the water-soluble nanoparticles, and reused without loss of performance.

This material is hence highly attractive for application in the field of nanotechnology.

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  • Prof. Boris Rybtchinski
1629
A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.Nearly...

A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.
Nearly all methods analyze pathway activity in a global “atomistic” manner, based on an entire sample set, not attempting to characterize individual tumors. Other methods use detailed pathway activity mechanism information and other data that is unavailable in a vast majority of cancer datasets.
The new algorithm described here transforms gene-level information into pathway- level information, generating a compact and biologically relevant representation of each sample. This can be used as an effective prognostic and predictive tool that helps healthcare providers to find optimal treatment strategies for cancer patients. Furthermore, this method can be generically used for reducing the degrees of freedom in order to derive meaningful output from multi-dimensional data using limited knowns.

Applications


  • Personalized cancer treatment.
  • A tool for mining insight from large datasets with limited knowns.

Advantages


  • Provides personalized solutions.
  • Can be utilized for rare conditions with very limited known information.
  • Proved on real oncologic datasets.
  • A Generic unsupervised learning tool.

Technology's Essence


The algorithm analyzes NP pathways, one at a time, assigning a score DP(i) to each sample i and pathway P, which estimates the extent to which the behavior of pathway P deviates from normal, in sample i. To determine this pathway deregulation score the expression levels of those dP genes that belong to P using available databases are used. Each sample i is a point in this dP dimensional space; the entire set of samples forms a cloud of points, and the “principal curve” that captures the variation of this cloud is calculated. Then each sample is projected onto this curve. The pathway deregulation score is defined as the distance DP(i), measured along the curve, of the projection of sample i, from the projection of the normal samples.

 

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  • Prof. Eytan Domany
  • Prof. Eytan Domany
1593
The study of social behavior in groups of mice may have crucial implications for understanding the social aspects of different disorders.  To be executed correctly, group studies require the ability to track individual’s behavior within the group structure. The main challenge of current research tools...

The study of social behavior in groups of mice may have crucial implications for understanding the social aspects of different disorders. 
To be executed correctly, group studies require the ability to track individual’s behavior within the group structure. The main challenge of current research tools is to allow individuals identification while maintaining sufficient resolution for accurate tracking.
The present technology provides a system that utilizes fluorescent fur dyes to differentially mark and track individuals within a group. Using a sensitive color camera and a newly designed tracking algorithm, behavior of groups may be recorded and analyzed with high temporal and spatial resolution.   
The technology further offers a method for characterizing the group’s interactions using the maximum entropy model.

 

Applications


 


Advantages


  • High spatial and temporal resolution – enabled by sensitive color video tracking.
  • Enables high detailed analysis of individual behavior within the group.
  • Suitable for community study of groups - limited only by available fur dyes.
  • Compatible with long-term analysis.
  • Simple, cost effective.
  • Minimal suffering and improved animal welfare.

  • Technology's Essence


    The present technology takes advantage of the fact that mice are nocturnal (active at night) animals, to mark their fur with different fluorescent dyes. Under ultraviolet light, the mice can be accurately and automatically tracked, over a number of days. As the mice are allowed to move freely in an interesting arena for exploration containing ramps, nest boxes and barriers (Figure 1), their trajectory and behavior are recorded using a sensitive color camera.
    The system further includes an image processing module which analyses the recorded images, calculates a spatiotemporal model and the nature of social interactions between individuals.
    Combining detailed behavioral and genetic analysis ate the level of individuals, in association with group analysis, may enable the identification of genetic and neuronal correlates of complex social interactions. 

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    • Prof. Alon Chen
    1569
    Liposomes are vesicles formed by natural lipids commonly named phospholipids. Phospholipids contain the phosphocholine head group which has great impact on their characteristics. In general the use of natural lipids provides biocompatibility; liposomes are frequently used as drug delivery agents, and...

    Liposomes are vesicles formed by natural lipids commonly named phospholipids. Phospholipids contain the phosphocholine head group which has great impact on their characteristics. In general the use of natural lipids provides biocompatibility; liposomes are frequently used as drug delivery agents, and we now propose to use them for bio-lubrication purposes. Our phosphatidylcholine liposomes, which are in their more rigid gel phase, form close-packed boundary layers in a hydrated environment. This leads to a striking reduction of the friction coefficient at high pressures because the uniform close-packed arrangement of these liposomes creates a particularly robust layer. These characteristics make these liposomes excellent candidates for use as boundary lubricant materials.

    Applications


    Bio-lubricant materials for:

    • Medical applications such as reduction of skinsoreness from rubbing and suppression of plaque formation, and in biomedical devices including catheters
    • Cosmetic applications such as use in conditioners and shampoos
    • Friction reducers in synovial joints where osteoarthritis-related problems arise

    Advantages


    • Rapid and simple liposome preparation procedure
    • Strong decrease of friction coefficient at physiological pressures
    • Material robustness and stability

    Technology's Essence


    Our phosphatidylcholine liposomes spontaneously adsorb and self-assemble onto a solid surface in aqueous solution to form a robust boundary layer which provides extremely efficient lubrication at the interfaces. The lubrication occurs under pressures of up to 100 atmospheres or more. These characteristics are preserved up to the gel-to-liquid-crystalline phase transition temperature (Tm= 53ºC for the HSPC liposomes for example). The lipids head groups which are highly hydrated and exposed at the outer liposome surfaces provide these remarkable properties by virtue of the hydration lubrication mechanism.

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    • Prof. Jacob Klein
    1640
    Although early programs targeting MMPs (matrix metalloproteins) were largely unsuccessful due to adverse side effects, they remain a viable and highly desirable therapeutic target. The main obstacle in the attempts to target MMPs is the ability to selectively target individual family members. The...

    Although early programs targeting MMPs (matrix metalloproteins) were largely unsuccessful due to adverse side effects, they remain a viable and highly desirable therapeutic target. The main obstacle in the attempts to target MMPs is the ability to selectively target individual family members. The present invention provides highly selective targeted therapy against MMP-7, which is strongly associated with aspects of cancer development such as angiogenesis and metastasis.
    The innovative concept leading to this high selectivity is immunization with both a synthetic metal-protein mimicry molecule, previously developed by the present inventors, followed by the metalloenzyme itself (e.g. MMP-7). The resulting antibody exhibits exceptional degree of specificity towards MMP-7 over other MMPs.
    The present technology offers an opportunity to re-introduce improved MMP-targeting agents to the cancer therapeutics market, in particular aggressive cancers that face a major unmet medical need. 

    Applications


    • Therapy for MMP-7 associated diseases
    • Diagnostic tool for MMP-7 associated diseases

    Advantages


    • Highly selective
    • Safe – avoids adverse effects that are associated with broad spectrum MMP inhibitors.
    • Efficient – targeting a physiological active conformation of the enzyme

    Technology's Essence


    The present technology is based on a previous invention that was developed in Prof. Sagi's lab, of synthetic metal-protein mimicry molecules that mimic the conserved structure of the metalloenzyme catalytic zinc-histidine complex within the active site of each MMP enzyme.
    These molecules were shown to be powerful immunogens in the generation of highly selective MMP antibodies since they recognize both electrical and structural determinants residing within the enzyme active site. The potential of this method to successfully generate MMP-targeting therapeutics was shown for MMP-9/2 inhibitory antibodies in mouse models of inflammatory bowel disease.
    Prof Sagi and her team now take this invention a step further to achieve even higher specificity. They show that immunizing with the mimicking molecules described above, followed by immunization with the metalloenzyme itself increases selectivity further.   
    Implemented for MMP-7-targeting, this approach yielded an antibody with a 5 fold lower Ki towards MMP-7 than towards other MMPs (e.g. MMp-2 and MMP-9).


     

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    • Prof. Irit Sagi
    • Prof. Irit Sagi
    1601
    A potent combination therapy against non-invasive breast cancer Breast cancer is the most common cancer in females. Among the different subtypes of breast cancer, ductal carcinoma in situ (DCIS) represents an intermediate step between normal breast tissue and invasive breast cancer. Currently, about 25...

    A potent combination therapy against non-invasive breast cancer

    Breast cancer is the most common cancer in females. Among the different subtypes of breast cancer, ductal carcinoma in situ (DCIS) represents an intermediate step between normal breast tissue and invasive breast cancer. Currently, about 25% of breast cancers that are diagnosed in the US are DCIS. DCIS is commonly treated by surgical intervention followed by adjuvant radiation therapy. However, a significant fraction of the DCIS lesions, which display HER2 gene amplification, are associated with increased relapse rate following surgery. Therefore, in cases of HER2-overexpressing DCIS a molecularly targeted therapy might be necessary for complete eradication of microscopic remnants following surgical tumor removal. The current technology presents an potential DCIS therapeutic strategy that collectively targets the functionally linked HER2 and Notch pathways.

     

    Applications


    • Combination therapy for DCIS patients following surgical tumor removal.
    • Classification of DCIS patients according to HER2 Notch activation patterns to identify patients with increased risk of relapse after surgery.
    • Diagnostic antibodies to NRG4 to screen for cancer cell subtypes that express/over-express NRG4.
    • NRG4 fusion conjugates, where NRG4 acts as a vehicle to direct the conjugate to cells specifically expressing the receptor ErbB4.

     


    Advantages


    • Targeted cancer therapies will give doctors a better way to tailor cancer treatment.
    • Targeted cancer therapies hold the promise of being more selective, thus harming fewer normal cells, reducing side effects, and improving the quality of life.
    • The proposed treatment strategy may prove beneficial in DCIS patients with poor prognosis.

     


    Technology's Essence


    The HER2/Neu oncogene, a member of the HER/ErbB signaling network, encodes a receptor-like tyrosine kinase, whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. Pre-invasive lesions, such as DCIS, overexpress HER2 at higher frequency than invasive ones. Another signal transduction pathway critical for breast cancer progression comprises Notch family receptors and their membrane-bound ligands. In the current technology, a team of researchers from the Weizmann Institute of Science uncovered that overexpression of HER2 in a novel experimental model of DCIS leads to transcriptional upregulation of Notch pathway components, resulting in enhanced tumor cell survival and proliferation. Combined treatment with HER2 and Notch pathway inhibitors resulted in decreased proliferative and tumorigenic potential. The current technology offers specific and combined targeting of HER2 and Notch pathways for DCIS treatment. This approach may also be tailored for DCIS patients with enhanced co-expression of HER2 and Notch.

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    • Prof. Yosef Yarden
    1536
    Designer cellulosomes are synthetic multi-enzyme complexes that can degrade cellulosic biomass efficiently and economically. The goal of second generation biofuel production is to efficiently convert agricultural waste, algae and other cellulosic biomass into sugar monomers.   Cellulosic biomass...

    Designer cellulosomes are synthetic multi-enzyme complexes that can degrade cellulosic biomass efficiently and economically. The goal of second generation biofuel production is to efficiently convert agricultural waste, algae and other cellulosic biomass into sugar monomers.

     

    Cellulosic biomass pretreated (e.g. with acid) under ideal conditions, still requires very high enzyme doses to provide efficient bioconversion.

    The cost of enzymes and pretreatment is a major hurdle in the production of low-cost cellulosic biofuel, competitive with that of fossil fuels or ethanol produced from corn or sugarcane.

     

    The complex structure of cellulosic materials is built to resist bacterial hydrolytic enzymes. The cooperation of many types of carbohydrate-active enzymes is required for effective degradation. By designing synthetic cellulosomes, researchers at The Weizmann Institute enhance synergy between carbohydrate-active enzymes to achieve remarkable degradation rates. Their discoveries can lead to highly efficient conversion of cellulosic biomass, and thus have a major impact in the field of food production and sustainable energy.

    Applications


    • High-yield, cost-effective conversion of plant cell wall biomass into soluble sugars for the food industry and the production of biofuels and biochemicals.

    Advantages


    • Bio-engineered cellulosomes exhibit synergistic degradation activity of natural substrates compared to the combined action of the free wild-type enzymes.

    Technology's Essence


    The invention involves the conversion of enzymes (cellulases and xylanases) from the free mode to the cellulosmal mode by attachment using a recombinant dockerin molecule. The dockerin-bearing enzymes are incorporated into designer cellulosomes by interacting with a matching cohesion-containing chimeric scaffoldin (scaffoldin subunits contain the cohesin modules that incorporate the enzymes into the cellulosome complex via their resident dockerins). This approach has generated over two fold enhancement of synergistic hydrolysis on plant cell wall cellulosic biomass. These results create new possibilities for designing superior enzyme compositions for degradation of complex polysaccharides into simple soluble sugars.

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    • Prof. Edward A. Bayer
    1574
    Spinal cord injuries (SCI) patients are deprived from using their abdominal muscles in order to facilitate an efficient cough and clear their airways. Functional Electric Stimulation (FES) may provide the abdominal contraction that is required; however, in order for such a device to fully substitute...

    Spinal cord injuries (SCI) patients are deprived from using their abdominal muscles in order to facilitate an efficient cough and clear their airways. Functional Electric Stimulation (FES) may provide the abdominal contraction that is required; however, in order for such a device to fully substitute the help of a caregiver, it must be easily activated and precisely synchronized with the patient's intent to cough in order to replace the voluntary cough.
    The present inventors present a device, which integrates nasal air signals, in the form of active sniff, with triggering of FES at a precisely timed onset following glottis closure. Tetraplegic patients that used this system produced a cough that is comparable to a physiotherapist-assisted cough and reported a major improvement in quality of life.
    This device offers a fresh approach to cough assistance which combines superior comfort and efficiency, perfectly adjusted to the needs of spinal cord trauma.

    Applications


    • Self controlled – enables quality of life, independence, intimacy.
    • Simple, compacted and portable.
    • Enables "smart coughing" – a patient's needs or commands are used to modify parameters synchronizing the cough.
    • Nasal air sensors are considered less intrusive and more reliable, than currently used mouth air sensors.
    • Potentially low cost system.

    Advantages


    • Intuitive and easy to learn and control for any computer user. 
    • Simultaneous use of different controllers to improve and diversify gaming applications. 
    • Non-invasive and safe device

    Technology's Essence


    Nasal air controller technology and FES are integrated using an Arduino microcontroller device. This is an open-source electronics prototyping platform based on flexible, easy-to-use hardware and software.
    The microcontroller receives analog inputs from pressure sensors and is programmed to trigger the FES. A command to cough from the patient may be two consecutive sniffs (nasal air signals). In addition, the system can potentially identify intent to cough using nasal air signals, without the need for a direct command.
    One of the most important parameters of the invention is that the FES will be given during glottis closure. The system continuously samples the nasal air signal and defines glottis closure as a plateau in the signal. A machine learning element determines a typical glottis closure duration for each patient, providing the FES within this frame.
    The FES is than given to the abdomen in order to facilitate coughing. The duration of the FES may be determined by a feedback which may be a value of emitted CO2, value of EMG, volume of sounds etc.
    Finally, the device may be further down-sized to enable mobility and suit outdoor use.

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    • Prof. Noam Sobel
    1646
    Dedicated and highly efficient EPR analysis of small volume samples in a range of few µl is now made simple with a novel device invented at the Weizmann Institute of Science. This device features a new ejection mechanism and a unique cold trap which enables collection of all time points in a RFQ series...

    Dedicated and highly efficient EPR analysis of small volume samples in a range of few µl is now made simple with a novel device invented at the Weizmann Institute of Science. This device features a new ejection mechanism and a unique cold trap which enables collection of all time points in a RFQ series in one continuous experiment.
    In order to design and develop inhibitors for therapeutic purposes, the reaction mechanisms of enzymes must be understood. For biological applications, a common methodology of addressing this need is combining Rapid Freeze Quench with Electron Paramagnetic Resonance (RFQ)-EPR, which allows the trapping and analysis of short lived intermediates in chemical reactions. However, commercial RFQ-EPR devices are limited for high field EPR applications due to the demand of large sample volumes for each time point.
    Prof. Goldfarb and her team built a new RFQ apparatus based on microfluidic flow and unique ejection and freezing systems, which can be used for collecting small volume samples in capillaries for high field EPR.

    Applications


    This technology, combined with the variety of W-band high resolution EPR technique (ENDOR, DEER and ESEEM) enables better mechanistic studies of enzymatic reactions, with an emphasis on structural transformations during the reaction, in an efficient and accurate way.


    Advantages


    • Collecting all RFQ time points in one continues experiment.
    • Produce small volume samples in the range of a few µl, and handles small capillaries, for high field ERP.
    • An improved dead time of ~5ms, relative to the commercial RFQs with a typical dead-time of 5–10 ms.
    • Ease-of-use and speed.

    Technology's Essence


    The innovative apparatus consists of two main parts: the microfluidic device and the freeze-quench setup. The microfluidic device comprises a mixer, which mixes the two reacting solutions, a flow path where the reaction occurs, and a sprinkler from which the solution is sprayed out of the device. Prof. Goldfarb and her colleagues improved the common mixing device by adding a fast stream of nitrogen gas which mixes with the ejected reaction solution, and sprays the frozen aerosol out in tiny drops at high speed.
    The innovative RFQ device was planned to have a cold solid surface on which the freezing happens rather than the traditional ejection into a cold liquid, in order to minimize the losses of the frozen solution. Moreover the plate rotates at a speed correlated to the flow speed of the solution, thus samples of different reaction times can freeze on a different radius. The frozen samples are then collected into quartz capillaries.

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    • Prof. Daniella Goldfarb
    1551
    A novel set of manganese, ruthenium and related borohydride complexes (Pincer-type) were developed as remarkably efficient and environmentally-benign catalysts for the synthesis of alcohols, amines, amides, imines and esters, which are the basic building blocks for the research, chemicals,...

    A novel set of manganese, ruthenium and related borohydride complexes (Pincer-type) were developed as remarkably efficient and environmentally-benign catalysts for the synthesis of alcohols, amines, amides, imines and esters, which are the basic building blocks for the research, chemicals, pharmaceutical and agrochemical industries. In addition, a catalytic carbon-carbon bond formation using non-activated aliphatic nitriles and carbonyl compounds was achieved with the manganese complex. These reactions are conducted under mild and neutral conditions, using low catalyst loading, require no hydrogen acceptors or oxidants, employ no corrosive or toxic reagents and generate no waste. Moreover, manganese is one of the most abundant transition metals on earth crust, making it appealing and biocompatible when considering a system for eventual scale-up and industrial use.

    In view of global concerns regarding economy, environment and sustainable energy resources, there is an urgent need for the discovery of new catalytic reactions. These newly developed catalysts address key problems of current traditional synthetic methodologies, both from the economic and the environmental aspects.

    Applications


    ·         Pharmaceuticals

    ·         Dyes

    ·         Cosmetics and fragrances

    ·         Fibers

    ·         Agrochemicals


    Advantages


    ·         Cost-effective in terms of reagents, reactions conditions (low temperature and pressure) and waste treatment (green reactions).

    ·         New synthetic pathways that were not possible before, such as the synthesis of amides and imines directly from alcohols and amines, esters synthesis from alcohols and methanol synthesis from CO2 and hydrogen.

    ·         Broad substrate scope.

    ·         Excellent yields.


    Technology's Essence


    Prof. David Milstein’s group has discovered a new mode of action for metal-ligand cooperation, involving aromatization–dearomatization of ligands. Pincer-type, pyridine-based complexes of Mn, Ir, Rh, Ru, Pd, Pt and acridine complexes of Ru have been shown to exhibit such cooperation, leading to facile activation of C-H, C-C, H-H, N-H, O-H bonds, and to novel, environmentally friendly reactions catalyzed by Mn and Ru.

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    • Prof. David Milstein
    1604
    Novel reporter gene for magnetic resonance imaging applications.The ability to image the duration and location of gene expression in vivo and noninvasively is imperative for the future of biology and clinical medicine. Magnetic Resonance Imaging (MRI) is a widely used noninvasive clinical diagnostic...

    Novel reporter gene for magnetic resonance imaging applications.The ability to image the duration and location of gene expression in vivo and noninvasively is imperative for the future of biology and clinical medicine. Magnetic Resonance Imaging (MRI) is a widely used noninvasive clinical diagnostic tool that offers views into deep tissues at exquisite spatial resolution. Recently, MRI has emerged as a valuable tool for monitoring the expression of genes by utilizing metal-complexed MRI agents to display transgene activity in vivo. However, administration of metal complexes into tissues and cells is challenging. Intra-cellular metalloproteins such as Ferritin have been utilized as endogenous MRI contrast agents, but offer relatively low sensitivity. The present technology provides a novel Ferritin-based transgene with enhanced MRI contrast.

     

    Applications


    • Non-invasive imaging of gene expression in transgenic mice models.
    • Monitoring target gene expression in pre-clinical studies.
    • Long-term cell labeling and tracking.
    • Visualization of cellular- and gene-based therapeutics.

    Advantages


    • Does not require delivery of exogenous substrate.
    • Enhanced MRI contrast over current Ferritin-based reporters.
    • Conversion to magnetite is achieved in physiological conditions and not by synthetic modification or by extreme heating. 

    Technology's Essence


    Ferritin, the main Iron storage intracellular protein, contains a paramagnetic ferryhydrate core, and thus was proposed as an endogenous MRI reporter gene. However, Ferritin provides relatively low sensitivity. One way to increase sensitivity of Ferritin is to convert the non-crystalline ferrihydrate in its core into crystal magnetite as has been done chemically, to form magneto-ferritin. The current method enhances the magnetic properties of Ferritin by engineering a Ferritin protein fused to a bacteria-derived peptide. This novel recombinant fusion protein facilitates conversion of ferrihydrate into crystal magnetite and by this induces MRI contrast. The new construct can serve for monitoring delivery and differentiation of cells in vivo in cellular based therapy. 

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    • Prof. Michal Neeman

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