For patients with AML, identification of their specific subtype and genetic background is crucial for predicting their outlook and decision of treatment. Therefore, understanding the molecular characteristics of specific subtypes of AML can lead to novel therapeutics and improve patient survival. The...
For patients with AML, identification of their specific subtype and genetic background is crucial for predicting their outlook and decision of treatment. Therefore, understanding the molecular characteristics of specific subtypes of AML can lead to novel therapeutics and improve patient survival. The present invention relates to a unique vulnerability of AML subtypes, in which specific chromosome abnormalities result in the dependence of the cancer cells on the activity of native RUNX1. Selective inhibition of RUNX1 under these genetic backgrounds results in killing of the cancer cells. Thus, the methods described in this innovation may lead to the development of novel AML therapeutics.
Specificity targets a signaling vulnerability which is unique to AML and does not occur in healthy cells.
Critical impact the inhibition of RUNX1 in addicted cells induces irreversible killing of the cancer cells by apoptosis rather than just inhibiting their proliferation.
Targeting RUNX1 in the addicted AML subtypes can potentially improve patient survival and also be used as a therapy for patients which developed secondary resistance in response to conventional chemotherapy.
The RUNX1 transcription factor is a frequent target of various chromosomal translocations. The t(8;21) and inv(16) AML subtypes create oncoproteins which interfere with RUNX1 activity in a dominant-negative manner. While RUNX1 is frequently inactivated in other forms of AML, an active RUNX1 allele is maintained in both t(8;21) and inv(16) AML patients, underscoring the medical significance of native RUNX1 in A-E and C-S mediated leukemogenesis. Knockdown (KD) of RUNX1 in cell culture models for A-E and C-S showed that these cells are physiologically dependent on RUNX1 activity for their survival and inhibition of RUNX1 in these cells leads to apoptotic cell death. This apoptosis is triggered by decreased expression of key mitosis-regulatory gene. Therefore, AML subtypes associated with an altered RUNX1 activity or expression are addicted to native RUNX1 for their survival. Targeting RUNX1 in these patients is expected to activate apoptosis and compromise leukemogenesis. Thus, the genetic addiction described in the current innovation can be used for the development of novel targeted therapies for AML.
CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical...
CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical importance in patients with chronic obstructive pulmonary disease (COPD), trauma, burn wounds, sepsis, or in patients requiring ventilation. The infections are currently treated with antibiotics, which rapidly become inefficient as resistant bacteria strains arise. The present technology suggests a novel therapeutic approach for the prevention and treatment of bacterial lung infection in susceptible populations, especially CF patients
Alternative treatment for bacterial lung infections.
A prophylaxis for patients susceptible to bacterial lung infections
A novel therapeutic approach to prevent or cure bacterial lung infection.
The new therapy is based on reinforcement of the physiological innate immunity rather than on antibiotics.
The new therapy can be easily administered, via inhalation.
FTY720, a SPH analog, is already in clinical use for treating multiple sclerosis.
Sphingosine (SPH), a natural bactericidal agent which acts as a part of the human innate immune system in the skin, was found to be an effective treatment and prophylaxis for bacterial lung infections in cystic fibrosis (CF) mice. The new technology is based on the discovery that both CF human patients and CF mice display reduced rates of SPH in the airways. Moreover, normalizing SPH levels by inhalation prevents or cures the infections in CF mice, thus rendering SPH and its analogs a potent therapeutic agent for CF patients, an alternative to antibiotics.
Dysregulation of the immune system is the underlying cause of potentially fatal conditions such as sepsis and severe allergic reactions. Adequate therapies are currently absent or lacking. There is therefore an unmet medical need for therapies that would target the underlying causative immune pathways...
Dysregulation of the immune system is the underlying cause of potentially fatal conditions such as sepsis and severe allergic reactions. Adequate therapies are currently absent or lacking. There is therefore an unmet medical need for therapies that would target the underlying causative immune pathways. Anti-microbial peptides (AMPs) possess promising anti-inflammatory activities, however, are commonly toxic. In a series of newly synthesized peptides, the outlined invention provides a method to modify naturally occurring AMPs to possess both potent therapeutic anti-inflammatory activity and minimal toxicity in-vitro and in-vivo. The resulting series of peptides were shown to remarkably inhibit severe allergic reaction as well.
Novel Therapy for sepsis and severe allergic reactions
Very potent anti-inflammatory and anti-allergenic agents
Targeted against the underlying cause of both indications, which is an improper and uncontrolled immune response
Diversity elucidating the parameters that control efficiency and toxicity allows to modify the basic formula to optimally fit different systems
With natural AMPs properties in mind, Prof. Shai and his team characterized the key modifications that underline anti-inflammatory activity and toxicity. A series of peptides with variable degrees of hydrophobicity, length, charge, position of charge and amino acid chirality were tested for their LPS neutralizing activity. It was found that ~20mer peptides under the formula Kn(AL)mKn (wherein n et each occurrence is independently 0-2, and m is 6-9) demonstrate anti-inflammatory activities at nanomolar concentrations as evident by inhibition of TNF? secretion from macrophages, following LPS induction. Furthermore, a single dose of an exemplary peptide was able to inhibit septic shock in mice induced by purified LPS or by whole heat-killed E.coli. In contrast to previous attempts, which focused on increasing hydrophobicity, the core of the present invention is the designation of an optimal hydrophobicity that is necessary for high activity and low toxicity. Additional important features for LPS neutralizing were found to be ?-helical structure and strong oligomerization ability. Surprisingly, the present peptides were shown to contain highly potent anti-allergenic activity as well. In-vitro inhibition of Fc?RI-mediated degranulation was recapitulated in-vivo
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.
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.
MTCH2 as a novel target for the treatment of obesity.Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-...
MTCH2 as a novel target for the treatment of obesity. Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes and certain types of cancer, some of the leading causes of preventable death. Physicians and patients alike consider the weight-loss efficacy of the current therapeutics to be unsatisfactory. Therefore, there is an unmet need for innovative options that are at once safe and efficacious, and allow the patient to maintain weight loss. The present invention describes the identification of Mitochondrial Carrier Homolog 2 (MTCH2) as a novel player in muscle metabolism and the therapeutic potential of inhibiting MTCH2 for the treatment of diet-induced obesity and diabetes.
A fresh approach for targeting weight-related disorders
Direct effect on metabolism instead of indirect mechanisms of current therapeutics which target appetite modulation.
Protection from diet-induced obesity can be used as a prevention treatment for people with a tendency for weight gain.
MTCH2 functions as a receptor-like protein for the pro-apoptotic BID protein in the mitochondria. MTCH2 was identified as one of six new gene loci associated with Body Mass Index (BMI) and obesity in humans suggesting that MTCH2 may also play a role in metabolism. MTCH2 was recently shown by the Grosss lab to also function as a repressor of mitochondria oxidative phosphorylation (OXPHOS) in the hematopoietic system. Deletion of MTCH2 in skeletal muscle increases mitochondrial OXPHOS and mass, and increases capacity for endurance exercise. In addition, loss of MTCH2 increases mitochondria and glycolytic flux in muscles as measured by monitoring pyruvate and lactate levels. MTCH2 knockout mice are protected from diet-induced obesity, hyperinsulinemia, and are more prone to weight loss upon caloric restriction. Therefore, the association of MTCH2 with mitochondrial function offers a potential novel target for muscle metabolism modulation in the fight against metabolic disorders such as obesity and diabetes.
A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combinationBreast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect...
A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combination Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect women at a younger age. Unfortunately TNBC cannot be treated with the common receptor targeted therapies since it does not express these targets, the estrogen, progesterone and Her2/neu receptors. Therefor systemic treatment options are currently limited to cytotoxic chemotherapy. The lack of effective targeted therapies, resistance to chemotherapy, and early metastatic spread have contributed to the poor prognoses and outcomes associated with TNBC. The current technology offers a novel therapeutic strategy for TNBC. The application of two novel, noncompetitive antibodies against EGFR, achieves a robust degradation EGFR resulting in tumor inhibition.
Novel and unique antibody targeted therapy for TNBC.
The novel anti EGFR antibodies can cooperate synergistically with the currently marketed EGFR antibodies.
A promising therapeutic scenario to treat TNBC.
Enhanced EGFR degradation and improved anti-tumor activity, in contrast to clinically approved anti-EGFR mAbs, which display no cooperative effects.
Lysosomal EGFR degradation pathway induced by epitope-distinct antibody mixture may potentially lead to improved therapeutic outcome, and reduced resistance.
Prof. Yosef Yarden and his team demonstrated that a combination of novel antibodies that target distinct regions on the human EGF receptor resulted in its robust and synergistic down-regulation, leading to pronounced tumor growth inhibition. Furthermore, the combined mAbs induced lysosomal degradation of EGFR, while avoiding the recycling route. Such irreversible mode of EGFR degradation may potentially increase response rate or delay the onset of patient resistance. Conversely, combining cetuximab and panitumumab, the mAbs routinely used to treat colorectal cancer patients, did not improve receptor degradation because they are both attracted to the same epitope on EGFR.
Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity. Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is...
Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity. Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is highly diffusive and buoyant. Currently, hydrogen is stored physically as a gas, requiring high-pressure tanks, or in liquid form at cryogenic temperatures, both methods require high energy input. Proposed chemical storage systems are based on relatively expensive materials, suffer from poor regeneration after hydrogen release and require elevated temperatures and pressures. The presented technology utilizes inexpensive and abundant organic compounds that generate hydrogen gas during a chemical transformation. Hydrogen release and the regeneration of the original compound are performed in mild conditions using the same catalyst. This system is a promising candidate to be the basis of compact and cost-effective chemical hydrogen storage platforms.
High potential hydrogen storage capacity (6.6 wt%)
Inexpensive and readily available hydrogen carriers (aminoalcohols)
Relatively mild release and regeneration conditions
Hydrogen-fueled systems, including fuel cells
High capacity hydrogen storage systems
The technology is based on aminoalcohols that are catalytically converted to cyclic dipeptides, while forming hydrogen gas, using a ruthenium pincer catalyst. Peptide hydrogenation, using the same catalyst, regenerates the aminoalcohol. The same method can be applied with diaminoalkanes and alcohols as well. The reaction requires a relatively low organic solvent volume, a catalytic amount of base (KOtBu) for the in situ generation of the active catalyst and mild reaction conditions in terms of hydrogen pressure (50 bar) and temperature (~100 oC). Repetitive cycles of the dehydrogenation-hydrogenation reactions can be performed without adding new catalyst, while maintaining high percentages of aminoalcohol conversion.
Lower collateral toxicities allow for greater flexibility in treatment dosage.
Enhanced patient survival rate.
More favorably considered as a line of therapy due to decreased side effects.
Utilization of well-characterized compounds alleviates safety and toxicity considerations.
ER stress, elicited by chemotherapeutic agents such as doxorubicin, 5FU, vincristine and bortezomib, or statins such simvastatin, triggers cell death at least in part through generation of leukotriene C4 (LTC4), which induces ROS accumulation, DNA damage and subsequent cell death. LTC4 can be produced by two parallel pathways. Cells of hematopoietic origin express C4 synthase (LTC4S) and secrete their LTC4 load, thereby affecting nearby tissues. In contrast, as discloses by the present invention, non-hematopoietic cells generate LTC4 by the enzyme MGST2 (an isoenzyme of LTC4S), and retain it to act internally leading to their demise. This difference is the basis for the present invention. Thus, LTC4 receptor antagonists (montelukast, pranlukast, etc.) will alleviate the toxicity of chemotherapy towards non-hematopoietic tissues and cells, but retaining the therapeutic effectiveness of chemotherapy on lymphocytic leukemia, lymphoma and myeloma patients. In conjuction, it was found that pranlukast attenuated cell death triggered by a broad range (0.5-4 µg/ml) of simvastatin (a statin) concentrations.
Preparation of Re-doped inorganic MoS2 nanoparticles with good sodium ion reversible intercalation properties, to be used as cathode material for next generation sodium ion batteries. Lithium ion batteries (LIB) are currently the leading energy storage solution used in many applications. But lithium is...
Preparation of Re-doped inorganic MoS2 nanoparticles with good sodium ion reversible intercalation properties, to be used as cathode material for next generation sodium ion batteries. Lithium ion batteries (LIB) are currently the leading energy storage solution used in many applications. But lithium is both toxic and limited in quantity (hence expensive) and cannot supply the growing demand for energy storage units as well as the need for cleaner and safer technologies. Sodium ion batteries (SIB) are attractive new generation batteries as they incorporate the much less toxic and much more abundant sodium ion. Our novel nanoparticles were shown to have competitive electrochemical performances with specific capacity of about 130 mAh/g at 2C and 74 mAh/g at high discharge rate of 20C.
Electrode material for sodium ion batteries
Possible applications in magnesium ion batteries
Competitive specific capacity
Improved electrical conductivity towards Na ions
The cathode material's reversible intercalation capacity plays a significant role in determining the total capacity of an energy cell. Intercalation requires entering of ions into the electrode material through diffusion channels. The faceted structure of inorganic nanoparticles (IF) induces intrinsic dislocations and stacking faults which serve as ion diffusion channels. Doping of the nanoparticles increases both conductivity, due to n-type doping of the Mo metal, and the number of structural defects (hence diffusion channels), resulting in total increased electrical conductivity. The synthetic procedure for producing Re-doped MoS2 nanoparticles is straightforward, based on known and published protocols.
L-DOPA is a high value compound used in the treatment of Parkinsons disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.Betalains are robust, flavorless, natural water soluble dyes,...
L-DOPA is a high value compound used in the treatment of Parkinsons disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts. Betalains are robust, flavorless, natural water soluble dyes, in the color ranges of both red-violet and yellow-orange. Currently there is no natural quality source for water soluble natural yellow dyes, with present natural yellow dyes being water insoluble. The present technology offers an alternative method that is simple, does not produce side-products, and is non-toxic with Tyrosine being the only feedstock. The technology produces L-DOPA and natural water soluble yellow and red Betalain dyes, both within yeast and in different plant species.
Production of L-DOPA for use in pharmaceuticals or dietary supplements.
Synthesis of water soluble yellow and red natural dyes for use as colorants, antioxidants, and food supplements.
Altering coloration of ornamental plants by inserting the metabolic pathway.
One-step reaction for L-DOPA synthesis from Tyrosine.
Non-toxic and non-hazardous synthesis.
Ecologically friendly - no waste management issues.
Multiple colors can be produced with yellow, red, or orange if pathways combined.
Flavorless - avoid influencing the taste of different products.
Flexibility in biosynthetic production - multiple possible host systems.
The present technology takes advantage of the Betalain biosynthetic pathway to selectively produce L-DOPA and natural Betalain dyes. A newly discovered, specific, cytochrome P450-CYP76AD6 begins the pathway, with the capacity to convert Tyrosine to L-DOPA. Then L-DOPA is converted to Betalamic acid via DOPA 4, 5-dioxygenase. With the Betalamic acid intermediate, the biosynthetic pathway diverges to make either Betaxanthins (yellow dyes) or Betacyanins (red dyes). In the production of yellow dyes an amine (e.g. amino acid) spontaneously reacts with Betalamic acid. In the case of red dyes, cycloDOPA (generated by the enzyme CYP76AD1 modifying Tyrosine and L-DOPA) and a Betalain-related glucosyltransferase react with Betalamic acid. Furthermore the two pathways can be done in parallel to produce an orange color.
Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets. The present...
Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets. The present discovery elucidates the pathway by which argininosuccinate synthase (ASS1) down-regulation confer cancer progression. It shows that decreased activity of ASS1 in cancers supports proliferation by linking excess aspartate to pyrimidines synthesis. Importantly, these studies highlight Citrin (a mitochondrial aspartate transporter) inhibition as a potential method to decrease aspartate levels and selectively target this metabolic pathway in ASS1 depleted cancers.
Targeted Treatment for ASS1 depleted cancers.
Targeted therapy, against a well defined pathway, increases the prospects for success.
Selective targeting cancer metabolic dependency minimizes the chances for healthy cells damage that lead to side effects.
Cancer cells hijack and remodel existing metabolic pathways for their benefit in what is termed the Warburg effect. Researchers from Dr. Ayelet Erez's lab, at the Weizmann institute of Science, have delineated the metabolic benefit(s) conferred by loss of ASS1 to cancers. In agreement with previous experience, they found that ASS1 deficiency has an additional arginine- independent effect that is directly related to its substrate, aspartate. By focusing on the relevant physiological and pathological model systems, it was found that ASS1 deficiency-mediated increase in aspartate levels lead to excessive proliferation through pyrimidine synthesis. The link between the two is provided by CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, dihydroorotase complex) and the mTOR signaling pathway. Importantly, the present inventors have found that blocking Citrin, the mitochondrial aspartate transporter, rescues cell proliferation by reducing aspartate levels. Citrin may thus serve as a strong candidate for targeted therapy of ASS1 depleted cancers. Supporting this model, retrospective survival analysis of several cancers reveal that cancers with both decreased ASS1 expression and high Citrin levels have a trend for significantly worse prognosis.
Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases.Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes....
Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases. Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes. Hypertension and diabetes elicit fibrotic processes in the heart, placing a high percentage of the western world population at risk, yet the early identification of fibrotic development in high-risk patients is hindered by lack of adequate fibrosis imaging modalities. This in turn leads to increased morbidity and additional financial burden to health care services. The current standard method to assess myocardial fibrosis employs the usage of MRI coupled with intravenous infusion of Gadolinium contrast agent. However, this method suffers from considerable drawbacks including reduced sensitivity (that permits diagnosis only at advanced stages of disease), lengthy scan times and toxicity of the contrast agent, which excludes a significant subset of patient populations from diagnosis. Thus, the capacity to diagnose myocardial fibrosis in its early stages would allow successful therapeutic intervention, and may also create a platform for the non-invasive study of fibrotic development, thereby facilitating the design of targeted therapies. The current invention is comprised of a novel cardiovascular magnetic resonance method with enhanced sensitivity, without the need for contrast agent administration.
Detection of cardiac fibrosis due to various pathologies, including hypertension, diabetes and heart failure.
The method can be applied to detect fibrotic tissues in a broad range of disorders including cancer, renal fibrosis and pathologies related to skeletal muscles.
A platform for the clinical study of targeted therapies that may prevent or arrest fibrotic diseases.
Monitoring the efficacy of treatment tailored to target fibrotic tissue development.
The method relies on magnetization transfer to provide contrast, and therefore obviates the need for any extrinsic, toxic contrast agent such as Gadolinium.
Improved sensitivity over current contrast agent-based cardiac MRI methods.
The method can be readily applied to existing MRI clinical imaging systems.
A team of researchers at the Weizmann Institute has developed a novel approach for detection of myocardial fibrosis using magnetization transfer contrast (MCT) MRI cardiac imaging technology. The method was tested in vivo on animal models of heart failure and proved highly sensitive for detection of scar tissue formation and monitoring of fibrotic development. One prominent advantage of the present technology over current cardiac imaging modalities is that it eliminates the requirement for extrinsic contrast agents, thereby circumventing potential adverse toxic side effects.
Novel immunosupressive peptides, derived from the TM domain of the HIV protein gp41, with high selectivity towards distinct immune cell populations.Uncontrolled activity of immune cells is an underlying cause of both autoimmune and inflammatory diseases. One of the major challenges in the field is to...
Novel immunosupressive peptides, derived from the TM domain of the HIV protein gp41, with high selectivity towards distinct immune cell populations. Uncontrolled activity of immune cells is an underlying cause of both autoimmune and inflammatory diseases. One of the major challenges in the field is to develop therapeutics that would target specific populations of immune cells, in order to avoid immune-deficiencies that would leave patients exposed to infections. The present invention provides novel peptides, based on Immunosupressive regions within the TM domain of the HIV gp41 fusion protein. These peptides were shown to specifically and efficiently inhibit T-cells and TNF? secretion from inflammatory macrophages. Importantly, these peptides were shown to have particular inhibitory effects towards T cells that are activated in a multiple sclerosis model.
Selective therapy towards T cell mediated autoimmune diseases (e.g. multiple sclerosis)
Selective therapy towards TNF?-associated inflammatory disorders
Specific towards defined cell populations avoids general immune suppression
Significant efficiency towards MS-associated T-cell activation
The present invention takes advantage of the potent immune evasion mechanisms that are utilized as part of the HIV virus pathogenesis. Gp41, a component of the virus envelop, is a transmembrane glycoprotein that mediates viral entry into cells of the immune system. In addition to its role in mediating the actual fusion event, gp41 has been shown to contain immunosuppressive activities that are attributed to its N terminus. Using biochemical and biophysical approaches, Prof. Shai and his team from the Weizmann institute, reveal yet another immunosuppressive activity of gp41, exerted via its transmembrane domain. Importantly, this immunosupressive activity was shown to be specific for T cell activation (mediated through binding to CD3/TCR complex) and Toll-Like Receptor (TLR)-mediated activation of macrophages. The present inventors generated synthetic peptides that derive from the gp41 trasmembrane domain and demonstrated their suppressive activity in both in-vitro and in-vivo models. Significantly, T-cell activation was inhibited following activation with a peptide associated with the propagation of multiple sclerosis (MOG 35-55), proposing a specific inhibitory activity towards MS-generating mechanisms. Macrophages inhibition was shown to significantly compromise the secretion of pro-inflammatory factors, predominantly TNF?, following LTA (lipotechoic acid) activation.
Converting two low-energy photons into a single higher-energy photon is of significant importance in many fields. In medical imaging, photon up-conversion is used for imaging scattered specimens, while in photovoltaic devices it could be used to harvest photons with energies lower than the bandgap of...
Converting two low-energy photons into a single higher-energy photon is of significant importance in many fields. In medical imaging, photon up-conversion is used for imaging scattered specimens, while in photovoltaic devices it could be used to harvest photons with energies lower than the bandgap of the absorber. Currently available systems, based on rare-earth-doped dielectrics, and organic materials are limited in both tunability and absorption cross-section. In fact, no known up-conversion systems operate on photons in the 1000-1500 nm range. Stable inorganic nanocrystalline up-conversion systems designed at the Weizmann Institute of Science provide broad tunability of both the absorption edge and the luminescence color. These materials have the potential to be utilized in applications such as high-energy photon sources, photovoltaics and IR detection.
Easy to manufacture
Operation at room temperature
The new up-conversion systems are based on a novel design comprising a compound semiconductor nanocrystal, which incorporates two quantum dots with different bandgaps separated by a tunneling barrier. The expected up-conversion mechanism occurs by the sequential absorption of two photons. The first photon excites an electronhole pair by interband absorption in the lower-energy core, resulting in a confined hole and a relatively delocalized electron. The second absorbed photon leads to further excitation of the hole, allowing it to cross the barrier layer. This, in turn, is followed by radiative recombination with the delocalized electron.
A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses. The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt...
A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses.
The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt stimulations. This may allow TMS-EEG to be used as a diagnostic tool for various neurologic and psychiatric conditions.
However, large electric artifacts are induced in the EEG by the TMS, which are unrelated to brain activity and obscure crucial stages of the brain's response. These artifacts are orders of magnitude larger than the physiological brain activity, and persist from a few to hundreds of milliseconds. However, no generally accepted algorithm is available that can remove the artifacts without unintentionally and significally altering physiological information.
The software designed according to the model along with a friendly GUI is a powerful tool for the TMS-EEG field. The software has tested and proven to be effective on real datasets measured on psychiatric patients.
TMS triggered EEG diagnostics
Easy to use software with a GUI
Exposes the full EEG from the brain
The new software tool is based on the observation that, contrary to expectation, the decay of the electrode voltage after the TMS pulse is a power law in time rather than an exponential. A model based on two dimensional diffusion of the accumulated charge from the high electric fields of the TMS in the skin was built. This model reproduces the artifact precisely, including the many perplexing artifact shapes that are seen on the different electrodes. Artifact removal software based on this model exposes the full EEG from the brain, as validated by continuously reconstructing 50Hz signals that are the same magnitude as the brain signals.