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Compounds for Inhibiting, Arresting and Possibly Reversing Non-Enzymatic Glycation in Skin
j333-2 — Non-enzymatic glycation and cross-linking (Maillard reaction) are well known processes which accelerate the aging of key biological molecules. For example, non-enzymatic glycation of macromolecules such as proteins and certain phospholipids (e.g., phosphatidylethanolamine and phosphatidylserine) appears to play an important role in the evolution of diabetic complications. Moreover, glycation is involved in aging of structural proteins such as collagen and elastin. The first two intermedi...
Method for Inhibiting, Arresting and Possibly Reversing Non-Enzymatic Glycation
j333-1 — Non-enzymatic glycation and cross-linking (Maillard reaction) are well known processes which accelerate the aging of key biological molecules. For example, non-enzymatic glycation of macromolecules such as proteins and certain phospholipids (e.g., phosphatidylethanolamine and phosphatidylserine) appears to play an important role in the evolution of diabetic complications. Moreover, glycation is involved in aging of structural proteins such as collagen andelastin and in food spoilage. The f...
Equal Channel Angular Extrusion for Consolidation of Polymer Resins
j533 — Ultra high molecular weight polyethylene (UHMWPE) is the material of choice for artificial joints and other bearings because of its toughness, low friction, and exceptional abrasion resistance. The present invention provides an angular extrusion (AE) method for creating monolithic polymers with high entanglement density and can be applied to polymeric materials such as UHMWPE. AE of polymers has commercial potential as a method of forming an improved bearing surface in many applications wh...
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Sudden Acceleration Motor Vehicle Shutdown Device
j689 — The drive motors used in electric vehicles have torque curves unlike those in internal combustion engines. Electric drive motors can produce enough torque to overpower conventional vehicle braking systems. Therefore an electrical malfunction could cause unintended acceleration that pressing the brake pedal could not overcome. Dartmouth researchers have invented a safety device – Sudden Acceleration Motor Vehicle Shutdown Device using a hydraulic brake pressure detector to address this pro...
j549 — Microwave imaging for biomedical applications, especially for early diagnosis of breast cancer, has attracted increasing interest in last several decades. This fact is due to the high contrast between the dielectric properties of the normal and malignant breast tissues at microwave frequencies, ranging from high megahertz to low gigahertz. The available range of dielectric properties for different soft tissue can provide important functional information about tissue health. Nonetheless, one ...
Diagnosing, Prognosticating and Treating Collagenase-1 (Matrix Metalloproteinase-1) Related Diseases
j173 — Degradation of the extracellular matrix is part of the pathological process associated with many diseases: e.g., joint destruction in arthritis, invasion and metastasis in cancer, bone dissolution in periodontitis, and plaque rupture in athererosclerosis. Most of this connective tissue degradation is accomplished by a family of enzymes called the Matrix Metalloproteinases, or MMPs, a family of enzymes that, collectively, degrade most matrix components. A sub-family of MMPs is the interstitia...
Enhancer of Luminol-mediated Chemiluminescence
j38 — The NADPH oxidase of phagocytic leukocytes generates superoxide anion, a toxic oxygen radical important to bacteriostatic and paracitocidal inflammatory responses. Ongoing studies of the oxidase, the components that comprise it, and the signaling pathways leading to its activation are of interest to basic and clinical research, and to clinical diagnoses. At present, the most sensitive method for measuring rates of superoxide production in leukocytes is luminol-mediated chemiluminescence. ...
Synthesizing Novel Furanosteroids
j373 — The furanosteroids are a class of pentacyclic fungal metabolites that share in common a furan ring bridging positions 4 and 6 of the steroid skeleton. Members of this class are known for their powerful anti-inflammatory and antibiotic properties as well as their ability to selectively block certain intracellular signaling pathways, in particular those associated with cell growth and development. Accordingly, furanosteroids such as viridin and wortmannin have potential as therapeutic agents f...
Identification and Uses of Iron and other Divalent Cations Transporters
j164 — Iron deficiency afflicts over 3 billion people worldwide, and plants are the principal source of iron in most diets. In response to iron deficiency, all plants except the grasses induce Fe(III) chelate reductase activity, Fe(II) transport activity and proton release into the rhizosphere. Dartmouth researchers have identified an Arabidopsis mutant, frd3, that constitutively expresses all three of these iron deficiency responses. Therefore, it is tempting to speculate that FRD3 encodes a regul...
Metal Transport Genes Which Can Be Used for Toxic Metals Removal
j5 — Pollution of the environment is one of the major problems facing the modern world. Removal of toxic metals poses particularly difficult problems, as unlike organic pollutants they cannot be biodegraded. Currently the standard way of removal of toxic metals from contaminated areas is by excavation and subsequent burial of the soil at a hazardous waste site. Phytoremediation -- the rapidly developing technique of using plants to extract metals from soil - presents a much preferred alternative....
Inexpensive Process for Separation and Mass Production of Cellodextrins
j231 — Cellodextrins (-1,4-glucose oligomers) are of interest for investigating cellulase hydrolysis mechanisms and kinetics. In addition, cellodextrins have been used to investigate aspects of microbial cellulose utilization including regulation of cellulase synthesis, cell growth, and bioenergetics. Non-digested oligosaccharides including cellodextrins have been found to have health-improvement functions such as lowing cholesterol levels and prevention of diabetes and obesity. Currently, cellode...
Motion Sickness Prevention or Treatment
j217 — Motion sickness has been a long-standing problem for travelers, aviators and sailors. For some people, motion sickness symptoms can ruin a trip or even be disabling. Common remedies taken to prevent symptoms often have undesirable side effects. Researchers at Dartmouth have discovered that the anti-histamine chlorpheniramine is effective in the prevention of motion sickness. Our studies demonstrated that chlorpheniramine increased the amount of stressful motion that subjects could toler...
Environmentally Safe Method for Synthesizing Tirapazamine and It’s Derivatives
j201 — Dartmouth researchers have developed a new method of synthesis of 3-amino-1,2,4-benzotriazines. The method utilizes air-assisted coupling between nitrobenzene or its derivatives and guanidine salts in basic medium having no need for the presence of halogens in the aromatic ring. Hence the method produces no environmentally harmful halogen or heavy metal wastes that are inevitable in the case of classic nucleophilic aromatic substitutions. The parent 3-amino-1,2,4-benzotriazine is a prec...
Producing Thiono Derivatives Useful in Drug Synthesis
j146 — Thionation, the conversion of a carbonyl group to the corresponding thiocarbonyl group, is a standard method for the preparation of a variety of useful organosulfur derivatives, including thionoesters, thionolactones, thioamides, etc. To date, the best reagent for bringing about this transformation has been Lawesson's reagent (LR). However, LR has two drawbacks which limit its usefulness: it is expensive, and the large amount of reagent-derived byproducts which accompany its reactions can on...
Screening for Drug Resistance in Cancer Treatment
j615 — There is a great deal of interest in developing personalized therapy for cancer based on the knowledge that cancer is a heterogeneous group of diseases and that individual patient characteristics as well as individual tumor characteristics can affect the response of a patient to drug treatment. An example of such personalized therapy is the subtyping of breast tumor tissue for estrogen receptors before choosing what type of chemotherapy to administer, where the presence of these hormone rece...
Molecularly Imprinted Polymer Using TEOS and Vitamin D3
j599 — Cholecalciferol, or Vitamin D3, is a secosteroid hormone that plays an important role in the regulation of calcium absorption, bone mineralization, and bone mineral density. Vitamin D3 deficiencies can cause rickets and osteomalacia, and have been associated with cardiovascular disease, symptoms of depression, and cognitive deficits. These are common deficiencies for third-world and aged persons. Vitamin D3 is naturally synthesized by the upper epidermis as it is exposed to UVB radiation (29...
Hydrothiolation of Unactivated Alkenes
j590 — Conventional methods for preparing sulfones proceed via Mitsunobu reaction of the corresponding alcohol followed by oxidation. However, the Mitsunobu reaction is an inherently non-atom economical process which produces stoichiometric amounts of hydrazine dicarboxylate and triphenylphosphine oxide by-products, of which the latter can sometimes be difficult to separate from the final product. Dartmouth scientists have now demonstrated that catalytic Ga(OTf)3 and trifluoroacetic acid (TFA)...
Non-Covalent Immobilization of Infectious Prion Protein
j583 — Prion diseases are fatal neurodegenerative illnesses that occur in genetic, sporadic and infectious forms. From a public health perspective, prion diseases are challenging to control because infectious prions are highly resistant to environmental degradation and can potentially be transmitted by several different routes. The critical molecular event in the pathogenesis of prion diseases is the misfolding of the host-encoded prion protein (PrPC) into an infectious isoform (PrPSc). Dartmo...
Co-Detection of microRNA and Proteins
j584 — Examination of formalin-fixed paraffin embedded (FFPE) tissues is the cornerstone for histological and molecular pathology diagnosis of solid tumors. High-throughput profiling experiments have linked altered expression of miRNAs to different types of cancer. Several methodologies have been applied to detect miRNAs in FFPE specimens. However, tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. In this respect, i...
Preventing Joint Destruction in Osteoarthritis
j574 — Osteoarthritis (OA) is the most common chronic disease of the joints, with no effective therapeutic treatments. It is considered a heterogeneous group of degenerative joint diseases associated with aging or mechanical stress, as seen in obesity. Since joint destruction outpaces repair of cartilage and joint tissues in OA, therapeutic strategies to block matrix metalloproteinase (MMP) degradation of collagen are attractive. However, the highly conserved structure of the MMP catalytic domain h...
microRNA Biomarkers for Human Breast and Lung Cancer
j520 — Lung cancer is the number one cause of cancer deaths in men, and lung and breast cancer combined are the leading causes of cancer deaths in women. Therefore, early detection and treatment of these cancers is of utmost importance in increasing survival. MicroRNAs (miRNAs) are an abundant class of short endogenous RNAs that act as post-transcriptional regulators of gene expression by base-pairing with their target mRNAs. Perturbed miRNA expression patterns have been reported in many human canc...
Prevention or Treatment of Immune-Relevant Disease by Modification of Microfloral Populations
j459 — Oral tolerance has been associated with the control of experimental autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), the animal model of human multiple sclerosis (MS). Oral antigens have been shown to suppress EAE, providing evidence that oral tolerance can be elicited in this demyelinating inflammatory condition. Dartmouth researchers have now shown that oral administration of a combination of antibiotics and exogenous commensal bacteria, such as such as B...
Screening and Compositions for Treating Bacterial Infections
j538 — Toxin and antitoxin (TA) systems are commonly found in prokaryotes. These systems function to allow the organisms to rapidly adjust rates of protein and DNA synthesis in order to respond to external stimuli and/or stress. Among these TA systems is the MazEF system, which includes the toxin MazF and the antitoxin MazE. The MazF toxin has been shown to cleave translated mRNAs and through this mechanism to block protein synthesis within prokaryotic cells. MazEF has been found to be an important...
BiTE Fusion Protein for Cancer Therapy
j546 — Activation of the immune system, especially effector T cells, can be harnessed as effective anti-tumor therapy. However, the number of tumor-specific T cells is low, so it can be difficult to activate sufficient numbers of T cells to alter tumor growth. Adoptive transfer of tumor-specific T cells into patients provides a means to treat cancer. Yet, isolation and expansion of large numbers of tumor-specific T cells that retain their antigen specificity and function can be a challenging task. ...
Identifying an Agent that Inhibits Candida Albicans-Mediated Host Cell Differentiation
j488 — The stratified squamous epithelium of wet mucosal surfaces of immunocompromised mammalian hosts may become heavily invaded by the opportunistic fungal pathogen, Candida albicans. A hallmark of pseudomembranous candidiasis or thrush is the presence of hyperkeratinization, which provides an environment that supports heavy growth of C. albicans. Dartmouth researchers have now found that C. albicans affects the expression of molecular markers of differentiation. Specifically, it has been de...
Selective Inhibition of ACAT1 Activity in the Treatment of Alzheimer’s Disease
j483 — Acyl-CoA:Cholesterol Acyltransferase (ACAT) converts free cholesterol to cholesterol ester, and is one of the key enzymes in cellular cholesterol metabolism. Two ACAT genes have been identified which encode two different enzymes, ACAT1 and ACAT2. While both ACAT1 and ACAT2 are present in the liver and intestine, the cells containing either enzyme within these tissues are distinct, suggesting that ACAT1 and ACAT2 have separate functions. Dartmouth researchers have now found that ACAT1, b...
Caveolin 1-Reporter Protein Knock-In Mouse
j509 — Caveolin 1 (Cav1) is the gene product of the Cav1 locus. Cav1 is a phosphoprotein with a structural role in the formation of caveolae, organelles with a variety of assigned functions. Cav1 is involved in multiple signal transduction pathways, and is believed to be a tumor suppressor, as well as an angiogenesis inhibitor. Caveolae are involved in mechanical sensing, buffering of membrane tension in cells under stretch, as well as in inflammation and permeability. Loss of Cav1 results in sever...
Female Reproductive Tract and Anal Prophylaxes
j456 — HIV has multiple portals of entry through both the lower and upper female reproductive tract (FRT). Once deposited in the vagina, HIV, like sperm and radio-opaque dyes, moves rapidly from the vagina and ectocervix into the endocervix, uterus, and Fallopian tubes. Immune cells in the FRT are phenotypically and functionally distinct from blood cells in that they are hormonally controlled to support sperm migration, fertilization and implantation. Moreover, menstrual cycle-dependent variations ...
Pancreatic Cancer Treatment - Compositions and Methods
j530 — Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States. In spite of recent therapeutic advances, long-term survival in PDAC is often limited to patients who have had surgery in the early stage of the disease. The biological aggressiveness of PDAC is due, in part, to the tumor's resistance to chemotherapy and to its propensity to metastasize even when the primary tumor is small. PDAC is also characterized by a high frequency of mutations in th...
Inhibiting Growth of Cancer Stem Cells
j528 — Recent evidence indicates that cells within a tumor are heterogeneous and represent different stages of development. In certain types of cancer, a population of cells has been identified that are termed cancer stem cells, where a cancer stem cell is defined as a cell that has the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise a tumor. Dartmouth researchers have now found that testicular germ cell tumors (TGCT cells) are extremely responsive ...
Inhibiting the Interaction Between CFTR and CAL
j467 — CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is the target of mutations that cause cystic fibrosis (CF). The most common mutant CFTR allele in the Caucasian population is the deletion of phenylalanine at position 508 (ΔF508-CFTR). The ΔF508-CFTR mutation results in a CFTR protein capable of conducting chloride, but absent from the plasma membrane because of aberrant intracellular processing. While chemical chaperones have been developed to restore the folding of ΔF508-CFTR, CAL...
Decreasing Type III Deiodinase Activity to Modulate Adiposity and Blood Glucose Levels
j462 — Although thyroxine (tetraiodothyronine; T4) is the principal secretory product of the vertebrate thyroid, its essential metabolic and developmental effects are primarily mediated by 3,3,5-triiodothyronine (T3). Type III deiodinase (D3), an enzyme primarily found in fetal tissues, placenta, skin and brain as well as brown and white preadipocytes, functions exclusively as a 5-deiodindinase and catalyzes the conversion of T4 and T3 to inactive metabolites (rT3 and T2, respectively). Dartmo...
Diagnosing and Treating Community-Acquired Methicillin-Resistant Staphylococcus Aureus
j426 — Methicillin-resistant Staphylococcus aureus (MRSA) infections are the most common cause of nosocomial or hospital-acquired infections. However, the incidence of MRSA infections has substantially increased over the last five years in healthy individuals due to the worldwide emergence of a distinct form of MRSA infections known as community-acquired methicillin-resistant S. aureus (CA-MRSA). CA-MRSA strains appear to have evolved independently of hospital-acquired MRSA (HA-MRSA), causing a dif...
j437 — Many new drugs and diagnostic imaging agents often fail to work in vivo due to their limited bioavailability or poor pharmacodynamics in the body. This is especially true of many fluorescent chromophores and photoactive chromophores used in photodiagnostic imaging and photodynamic therapy of malignancies. Dartmouth researchers have now generated a new formulation for the solubilization and dispersion of a chromophore via peptide conjugation and stepwise polyethylene glycolation. Whether...
Nicotinamide Riboside Kinases and Their Uses for Prodrug Development
j263 — Dartmouth scientists have discovered two human genes encoding nicotinamide riboside kinases that are highly specific for activation of a class of anti-cancer, anti-viral and immunosuppressive prodrugs related to tiazofurin. These genes and their encoded enzymes are useful for drug development and for identifying patients who may be susceptible to treatment with a prodrug related to tiazofurin. These findings are claimed in the published United States Patent Application Nos. 11/542,832, ...
Bioactive Small Molecules from Lactic Acid Bacteria for Prevention of HIV-1 in Adults and Infants
j448 — robiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit to the host. Probiotics most commonly include strains of lactic acid bacteria within the genera of Lactobacillus and Bifidobacteria. Ingestion of live probiotic bacteria has been associated with an improvement in intestinal and immune health when consumed on a regular basis. Dartmouth researchers have now developed culture and fractionation methods that yield small bioactive molecules...
j392 — Toxoplasma gondii is an obligate intracellular parasite capable of infecting most warm-blooded vertebrates and many nucleated cell types. Parasite transmission occurs orally through ingestion of tissue cysts or sporozoites from feline feces in contaminated soil, food, and water. Infection typically results in an asymptomatic primary infection that leads to a chronic latent infection affecting 30% of the world's population. Dartmouth researchers have now generated attenuated uracil auxot...
CD161 Ligand, PILAR, for Modulating Activation and Proliferation of T Cells
j396 — CD161 is a C-type lectin receptor initially associated with murine NK cells. Unlike murine lymphocytes, the expression of CD161 in human T cells identifies mostly memory lymphocytes and only a small proportion of invariant NK T cells. CD161 engagement in humans has been recently associated with the enhancement of IFN-γ and TNF-α production in the context of a T cell receptor (TCR) signal, while inducing the production of IL-12 by dendritic cells. The only previously identified ligand of CD16...
Inhibiting, Arresting, and Possibly Reversing Non-Enzymatic Glycation in Diabetic Patients
j333 — Non-enzymatic glycation and cross-linking (Maillard reaction) are well known processes that accelerate the aging of intracellular proteins and extracellular structural proteins such as collagen and elastin. Numerous studies indicate that non-enzymatic glycation appears to play an important role in the evolution of diabetic complications. Consequently, preventing, arresting or reversing this process in diabetics would of great significance. The first two intermediates formed in the Maill...
Determining Collateral Artery Development in Coronary Artery Disease
j380 — Coronary artery disease (CAD) is the most common cause of morbidity and mortality in industrialized societies. Collateral arteries function as "natural bypasses" effectively restoring the blood flow to compromised tissues and play an important physiologic role in promoting survival and protecting tissues from ischemic damage. Circulating monocytes have been suggested to play a role in the collateral formation. Abnormalities in monocyte function then may be one of the factors responsible for ...
Prognosis and Treatment of Breast Cancer
j307 — Spot 14, also known as thyroid hormone-responsive Spot 14 (THRSP) or S14, is a primarily nuclear protein that is abundant in tissues active in long chain fatty acid synthesis, including the lactating mammary gland. It has been shown that the S14 gene is located on chromosome 11q13 and is overexpressed in most breast cancers. Dartmouth researchers have now found that S14 is a marker for aggressive breast cancers. High-level S14 expression exhibits a strong positive correlation with tumor...
Regulating RNA Translation via CD154 CA-Dinucleotide Repeat
j323 — The expression of CD154 (CD40 ligand), a member of the Tumor Necrosis Factor gene family, by activated T lymphocytes is critical in the development of humoral and cell-mediated immunity. CD154 blockade retards the development and progression of immune responses in an array of transplantation and autoimmune disease models ranging from Systemic Lupus Erythematosus to Rheumatoid Arthritis to Multiple Sclerosis. Overexpression of splice isoforms of polypyrimidine tract binding protein differenti...
Identifying Agents which Modulate GTPASE Activity Involved in Insulin-Stimulated GLUT4 Translocation
j306 — Insulin treatment of fat and muscle cells causes a rapid increase in glucose transport. The basis for this effect is an increase of glucose transporters of the GLUT4 type at the cell surface. This translocation of GLUT4 is achieved by modification of AS160 (Akt substrate of 160-kDa) which has a GTPase activating protein (GAP) domain for members of the Rab G protein family. AS160 is phosphorylated by the insulin-activated protein kinase Akt, Evidence indicates that phosphorylation of AS160 in...
Inhibiting Sonic Hedgehog Activity
j314 — Lung cancer is the most common cause of cancer in men and women in the United States. Lung cancer can be divided into two distinct classes, non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). While constitutive Hedgehog signaling has been demonstrated in SCLC, this class represents only 20% of all lung cancers. Dartmouth researchers have now found that the Hedgehog pathway is constitutively active in a subset of NSCLC. Moreover, it has been found that overexpress...
Regulatory T Cell Mediator Proteins
j269 — Regulatory T cells (Treg) play an important role in constant and inducible control of T cells responses in vitro and in vivo. Treg cell depletion results in the induction of autoimmune pathology and exacerbation of T cells responses to foreign and self-antigens, including heightened anti-tumor responses as well as ablation of transplantation tolerance and rapid graft rejection. Dartmouth researchers have now found a novel member of the PD-L1 family expressed by Treg cells. This novel pr...
Increasing Cardiac Mass and Performance
j305 — Congestive heart failure (CHF) is a chronic, degenerative condition that impairs the heart's ability to pump blood at normal filling pressures to adequately meet the energy requirements of the body. Multidrug treatment regimens that include diuretics, vasodilators and inotropic agents such as angiotensin-converting enzyme inhibitors, can slow the progression of CHF and reduce the number of acute episodes. However, treatment remains directed at symptoms and is most effective in the early stag...
Nucleic Acid Sequences Encoding Luciferase for Expression in Filamentous Fungi
j284 — Bioluminescence is the light produced in certain organisms as a result of luciferase-mediated oxidation reactions. The luciferase genes, e.g., the genes from luminous beetle and, in particular the luciferase from Photinus pyralis, are very useful luminescent reporter genes. Despite its utility as a reporter, native luciferase is not generally useful in many organisms, including the filamentous fungi, because of low expression levels. Dartmouth researchers in collaboration with their col...
Detecting Cardiac Collateral Formation
j279 — Coronary collateral circulation has been recognized as an alternative source of blood supply to an ischemic myocardial area. Collateral artery formation is associated with smaller infarcts, less ventricular aneurysm formation, improved ventricular function, fewer future cardiovascular events and improved survival. Dartmouth researchers have now found that there is a strong positive correlation between increases in the presence or formation of collateral arteries and N-terminal probrain ...
Preventing or Treating Variola Virus Infection
j334 — Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and causes smallpox. Although smallpox was eradicated in 1980, it remains a potential agent for bioterrorism. As a category A biological weapon, its potential to devastate populations is a concern. Moreover, despite the efficacy of a live vaccinia virus vaccine, the level of toxicity is deemed unacceptably high due in part to the fact that a live vaccine can be lethal to immunosuppressed individua...
Transgenic Non-Human Animal Model of Lung Tumorigenesis
j308 — Lung cancer is the leading cause of cancer mortality for men and women in United States. Key molecular changes, especially at early stages of carcinogenesis, represent potential pharmacological targets for lung cancer chemoprevention and therapy. Aberrant expression of cyclin E has been frequently observed in premalignant lung lesions, indicating that this is an early step in lung carcinogenesis. Overexpression of cyclin E also occurs in overt non-small cell lung cancers (NSCLCs) and has pro...