gebhart/patrepeval huggingface dataset:
Steerable Induction of the Thymosin β4/MRTF-A Pathway via AAV-Based Overexpression Induces Therapeutic Neovascularization (2017)

Viral vectors have been frequently used in a variety of preclinical animal models to deliver genetic constructs into tissues. Among the vectors used, adeno-associated viral vectors (AAVs) may be targeted to specific tissues, depending on the serotype used. Moreover, they show robust expression for prolonged periods of time and have a low immunogenic potential. Furthermore, AAVs, unlike other vector systems, only display a low rate of genomic integration. However, to ensure efficient transgene production, expression is typically driven by constitutively active promoters, such as the cytomegalovirus (CMV) promoter. Tetracyclin responsive promoters represent a promising alternative to unregulated promoters. The present study compares AAVs encoding either constitutively active CMV or tet-off promoter regions in the preclinical models of hindlimb and chronic myocardial ischemia. Therapeutically, mediators regulating vessel maturation, specifically thymosin beta 4 (Tβ4) and the downstream signaling molecule myocardin-related transcription factor A (MRTF-A) as well as the endothelial activator angiopoietin-2 (Ang2) were overexpressed via AAVs using both promotors. In the model of rabbit hindlimb ischemia, temporary (tet-off) expression of Tβ4 improved capillary density, collateralization, and perfusion in the ischemic hindlimb, with no detectable difference to constitutive Tβ4 overexpression. Similarly, constitutive overexpression of MRTF-A alone was able to improve capillarization, collateralization and perfusion. Temporary expression of Ang2 for 7 days further increased capillary density and pericyte coverage compared with MRTF-A alone, without further improving collateralization or perfusion. In the pig model of chronic myocardial ischemia constitutive expression of Tβ4 for 4 weeks induced capillary and collateral growth similarly to a pulsed expression (2 day expression per week for 3 weeks). Taken together these findings demonstrate for two models of preclinical interventions that temporary gene expression may lead to similar results as constitutive expression, highlighting the potential of controlled temporary gene expression for induction of vascular growth as a therapeutic approach.
Topiramate Produced Weight Loss Following Olanzapine-Induced Weight Gain in Schizophrenia (2002)

Article AbstractLetter to the EditorSir: Anticonvulsants are increasingly used as an augmentation strategy in schizophrenia. Topiramate, with the unique side effect of reducing appetite and weight, was found effective as a mild-to-moderate mood stabilizer. Topiramate was found to produce weight loss after clozapine induced weight gain in a schizophrenic patient. We report here the effect of topiramate in a patient with schizophrenia and olanzapine-induced weight gain.
Purification and partial characterization of a rat kidney aldehyde dehydrogenase that oxidizes retinal to retinoic acid (1993)

A NAD-dependent aldehyde dehydrogenase (EC 1.2.1.3) which catalyzes the oxidation of retinal to retinoic acid was purified to homogeneity from rat kidney by using Affi-Gel blue affinity chromatography and chromatofocusing, followed by Mono-Q anion-exchange chromatography. The apparent molecular weight of the native enzyme determined by size-exclusion fast protein liquid chromatography was 140,000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a subunit molecular weight of 53,000. The isoelectric point as measured by chromatofocusing was 8.5. The enzyme also catalyzed the oxidation of acetaldehyde, but showed much lower Km value for the retinal substrate. We suggest that aldehyde dehydrogenase found in the kidney may be a specific retinal dehydrogenase, involved in vitamin A metabolism.
Dynamic combinatorial chemistry: on the road to fulfilling the promise (2007)

Dynamic combinatorial chemistry makes use of reversible reactions between functionalised monomeric building blocks to generate a mixture of products (dimers or oligomers) under thermodynamic equilibrium. This system reorganises upon addition of a target so that species that bind to, and are therefore stabilised by the target, are favourably formed and are thus amplified. Since the mid-1990's, dynamic combinatorial chemistry has been successfully applied to the identification/selection of ion receptors, enzyme inhibitors, catalysts, materials and nucleic acid ligands. Although it is now established as a powerful tool with broad applications some intrinsic limitations appeared when working on systems of increasing complexity. We present here the most recent advances in the field of dynamic combinatorial chemistry that have been developed to overcome these limitations and explore new areas of application.
Artificial Fertilization among Yellowfin and Gulf Menhaden (Brevoortia) and Their Hybrid (1968)

Eggs of yellowfin menhaden, Brevoortia smithi, were artificially fertilized with sperm from yellowfin menhaden, Gulf menhaden (B. patronus), and naturally occurring hybrid menhaden, and reared through the larval yolksac stage at sea under controlled temperature and salinity. Hatching occurred after 38 hours at 21 C. The last larva died 7 days after hatching. Specimens of embryos and larvae were preserved during development and later photographed. Survival of the cross-fertilized eggs equalled that of the intraspecific fertilizations.
Carotid artery stenting: technical considerations. (2000)

CAS is an effective treatment for carotid stenosis. With proper selection of patients and meticulous technique, complication rates compare favorably with those of CEA.
Autism Spectrum Disorders: Concurrent Clinical Disorders (2007)

Individuals with autism spectrum disorder are heterogeneous in clinical presentation, concurrent disorders, and developmental outcomes. This study characterized the clinical co-occurrences and potential subgroups in 160 children with autism spectrum disorders who presented to The Autism Center between 1999 and 2003. Medical and psychiatric co-occurrences included sleep disorders, epilepsy, food intolerance, gastrointestinal dysfunction, mood disorder, and aggressive and self-injurious behaviors. Sleep disorders were associated with gastrointestinal dysfunction (P < .05) and mood disorders (P < .01). Food intolerance was associated with gastrointestinal dysfunction (P = .001). Subjects with mood disorder tended to develop aggressive or self-injurious behaviors (P < .05). Developmental regression was not associated with increased co-occurrence of medical or psychiatric disorders. Medical co-occurrence did not present as a risk factor for psychiatric co-occurrence, and vice versa. These results showed a high prevalence of multiple medical and psychiatric co-occurrences. There may be common pathophysiologic mechanisms resulting in clinical subgroups of autism spectrum disorders. Recognition of the co-occurrence of concurrent disorders may provide insight into the therapeutic strategy.
Baring it all to software: Raw machines (1997)

The most radical of the architectures that appear in this issue are Raw processors-highly parallel architectures with hundreds of very simple processors coupled to a small portion of the on-chip memory. Each processor, or tile, also contains a small bank of configurable logic, allowing synthesis of complex operations directly in configurable hardware. Unlike the others, this architecture does not use a traditional instruction set architecture. Instead, programs are compiled directly onto the Raw hardware, with all units told explicitly what to do by the compiler. The compiler even schedules most of the intertile communication. The real limitation to this architecture is the efficacy of the compiler. The authors demonstrate impressive speedups for simple algorithms that lend themselves well to this architectural model, but whether this architecture will be effective for future workloads is an open question.
Enhanced Coupling of Subterahertz Radiation with Semiconductor Periodic Slot Arrays (2007)

In this work, a theoretical study of the coupling of TM polarized subterahertz (THz) radiation with periodic semiconductor rectangular slot arrays was conducted, using InSb as an example. Simulation results showed that the structure with 4-12 microm thickness provides over a 20-30-fold increase in the electric field at slot edges in a nanosize region ( approximately 500 nm). The enhancement of the THz electromagnetic field extends across the slots and reaches peak values at the edges due to discontinuity effects. Because of the strong local electromagnetic field enhancement, the structure can potentially be used for the development of novel biophotonic sensors, leading to improved detection sensitivity.
Country wise classification of human names (2006)

Person names in a country follow a particular statistical trend and names of a large set of individuals in a country are derived from a set of names having smaller cardinality. The frequency distribution of person names of different countries varies from each other. The intuitive ability of humans to guess the country of origin of a person from his name is based on these facts. It is possible to design a data mining approach for deciding the country of origin of a person from his name-using the first name and second name as the only independent parameters-and such a tool has wide range of applications. But this is an unexplored problem, complexity and lack of information about human names across different countries may be the reason. In this paper we try to tackle this problem with two data mining algorithms. Firstly, we try a k-nearest neighbor classification for first names and second names, followed by a rule based decision making. The algorithm is trained and tested on person names from nine countries. This method shows accuracy up to 73% for a set of ten countries. Secondly, we try an unsupervised method to improve the knowledge base of the system at runtime. This algorithm can effectively handle the scenarios of 1) a small training set. 2) Apriori probabilities of working set are unknown at training time. The method shows accuracy up to 64% for nine countries.
Interactions between the sorbitol pathway, non-enzymatic glycation, and diabetic vascular dysfunction (1996)

These observations suggest that vascular dysfunction induced by increased sorbitol pathway metabolism (caused by elevated glucose levels) and by products of non-enzymatic glycation (at normal glucose levels) is mediated by a common final pathway consistent with a scenario in which: increases superoxide production-->increases intracellular calcium levels-->increases nitric oxide synthesis-->increases blood flow and increases vascular permeability.
Transformation of 2,3,9,10-Tetraoxygenated Protoberberine Alkaloids into 2,3,10,11-Tetraxygenated Protoberberine Alkaloids (1985)

A b s t r a c t -2,3,10,11-Tetraoxygenated tetrahydroprotoberberine ( 6 ) were synthesized from the corresponding 2,3,9,10tetraoxygenated protoberberine alkaloids (1) through oxidative C8-CEa bond cleavage, photocyclization, and deoxygenation.Naturally occurring tetraoxygenated protoberberine alkaloids can be classified into two groups1 according to substitution patterns of oxygen functions in ring A and D. One is naturally abundant 2,3,9,10-tetraoxygenated protoberberines such as berberine ( l a ) and the other is 2,3,10,11-tetraoxygenated ones as exemplified by pseudoberberine ( 2 0 ) .Some of the latter type of alkaloids, pseudoberberine (201, 2,3,9,10-Tetraoxygenated P r o t o b e r b e r i n e 2,3,10,11-Tetr00~~genated P r o t o b e r b e r i n e R'O OR^ OR' pseudocoptisine (2~).etc. have recently isolated.
Recent progress in protein and peptide delivery by noninvasive routes. (1991)

Much progress has been made in the last 5 years toward delivery of protein and peptide drugs by noninvasive routes. The obstacles of instability, poor absorption, rapid metabolism, and nonlinear pharmacokinetics are great challenges for which some solutions are now emerging. Structural modifications of the protein by chemical or recombinant means have improved stability and minimized enzymatic cleavage in some cases. Protection of the protein or peptide drug via liposomes or polymers also offers a means for increasing stability and prolonging half-life. Novel permeation enhancers, which show minimal irritation to mucosal membranes, have become available and show promise for increasing absorption of proteins delivered by a number of noninvasive routes. There are examples in which several of these methods have been used concomitantly to achieve maximum effect; for instance, a bioadhesive microsphere formulation containing a novel permeation enhancer was used to maximize nasal delivery of insulin. Therefore, general methods exist whereby delivery by any noninvasive route may be improved. In some cases, choice of the best route of delivery for a particular drug makes the difference between success and failure. A comparison of the enzyme activity at the various sites of delivery is helpful and, fortuitously, the enkephalins, model peptides whose rate of cleavage and type of degradation products offer information about the type and activity of enzymes present, have been studied extensively. This work is reviewed for each delivery site as are the effects of coadministration of enzyme inhibitors. Permeation enhancers and examples for their use at each site of delivery are presented. The use of polymers for bioadhesion and for protection from metabolism at various sites is reviewed. Since systemic delivery of proteins via the pulmonary route is now receiving more attention, special emphasis is given to that work. Generally, the focus is on work published or presented since 1988, since publications prior to that date have already been thoroughly reviewed. The studies presented indicate that the problems of delivering protein and peptide drugs by noninvasive means can be minimized; although delivery by these routes still may not be bioequivalent to invasive methods, the convenience to the patient will, in some cases, outweigh the demand for complete bioequivalence.
P2X7 receptor activation induces inflammatory responses in salivary gland epithelium (2012)

Inflammation of the salivary gland is a well-documented aspect of salivary gland dysfunction that occurs in Sjogren's syndrome (SS), an autoimmune disease, and in γ-radiation-induced injury during treatment of head and neck cancers. Extracellular nucleotides have gained recognition as key modulators of inflammation through activation of cell surface ionotropic and metabotropic receptors, although the contribution of extracellular nucleotides to salivary gland inflammation is not well understood. In vitro studies using submandibular gland (SMG) cell aggregates isolated from wild-type C57BL/6 mice indicate that treatment with ATP or the high affinity P2X7R agonist 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) induces membrane blebbing and enhances caspase activity, responses that were absent in SMG cell aggregates isolated from mice lacking the P2X7R (P2X7R(-/-)). Additional studies with SMG cell aggregates indicate that activation of the P2X7R with ATP or BzATP stimulates the cleavage and release of α-fodrin, a cytoskeletal protein thought to act as an autoantigen in the development of SS. In vivo administration of BzATP to ligated SMG excretory ducts enhances immune cell infiltration into the gland and initiates apoptosis of salivary epithelial cells in wild-type, but not P2X7R(-/-), mice. These findings indicate that activation of the P2X7R contributes to salivary gland inflammation in vivo, suggesting that the P2X7R may represent a novel target for the treatment of salivary gland dysfunction.
In vitro antibacterial activity of concentrated polyethylene glycol 400 solutions (1983)

It was found that concentrated polyethylene glycol 400 (PEG 400) solutions have significant antibacterial activity against various pathogenic bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. This effect might be attributed to two effects: lowering of water activity and, superimposed on this, the specific action of PEG-400 molecules on bacterial cells. Phase-contrast microscopic observations of cells placed in contact with PEG 400 revealed clumping and morphological changes of bacterial cells. The larger changes in appearance were evidenced by the species which were more rapidly killed by PEG 400. The results obtained suggested that concentrated PEG 400 solutions may have a potential value in medicine as a topical antibacterial agent. The feasibility of this application is the subject of present investigation.
Thyroid hormone analogs. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart (1988)

Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction of mitochondrial 3-phosphoglycerate oxidoreductase, GPDH) were measured in rat liver and heart for these new analogues and for the 18 previously reported 3'-substituted 3,5-diiodo-L-thyronines. Analysis of the binding data using theoretical conformational and quantitative structure-affinity methods implies that the 3'-substituent recognition site on the thyroid hormone receptor is hydrophobic and limited in depth to the length of the natural iodo substituent, but has sufficient width to accommodate a phenyl or cyclohexyl group. Receptor binding is reduced by approximately 10-fold in 3'-acyl derivatives which form strong intramolecular acceptor hydrogen bonds with the adjacent 4'-hydroxyl. The compounds studied showed no differences in their relative affinities for heart and liver nuclei, suggesting that receptors in these tissues are similar. However, the relationships between thyromimetic activity (induction of GPDH) and nuclear binding showed some tissue differences. A high correlation between activity and binding is observed for full agonists in the heart, but an equally significant correlation for the liver data is only seen when 3'-substituent bulk (molar refractivity) is included in the analysis. These results suggest the possibility that differential tissue penetration or access to receptors may occur in vivo.
Early Chemokine Cascades in Murine Cardiac Grafts Regulate T Cell Recruitment and Progression of Acute Allograft Rejection (2001)

The identification of early inflammatory events after transplant in solid tissue organ grafts that may direct T cell recruitment and promote acute allograft rejection remain largely unknown. To better understand temporal aspects of early inflammatory events in vascularized organ grafts, we tested the intragraft expression of four different chemokines in heterotopically transplanted A/J (H-2(a)) and syngeneic heart grafts in C57BL/6 (H-2(b)) recipient mice from 1.5 to 48 h after transplant. Similar temporal expression patterns and equivalent levels of chemokine expression were observed in both syngeneic and allogeneic cardiac allografts during this time period. Expression of the neutrophil chemoattractant growth-related oncogene alpha (KC) was observed first and reached peak levels by 6 h after transplant and was followed by the monocyte/macrophage chemoattractant protein-1 (JE) and then macrophage inflammatory proteins 1beta and 1alpha. Administration of rabbit KC antiserum to allograft recipients within 30 min of cardiac transplantation attenuated downstream events including intra-allograft expression of the T cell chemoattractants IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma, cellular infiltration into the allograft, and graft rejection. Similarly, depletion of recipient neutrophils at the time of transplantation significantly extended allograft survival from day 8 to 10 in control-treated recipients up to day 21 after transplant. These results indicate the induction of highly organized cascades of neutrophil and macrophage chemoattractants in cardiac grafts and support the proposal that early inflammatory events are required for optimal recruitment of T cells into allografts during the progression of acute rejection of cardiac allografts.
Proton NMR aromatic spectrum of the operator binding domain of the .lambda. repressor: resonance assignment with application to structure and dynamics (1987)

The aromatic 1H NMR resonances of the operator binding domain of lambda repressor are completely assigned. Since the resonances of this 23-kilodalton domain are too broad for the application of two-dimensional strategies for sequence-specific assignment, an alternative approach has been used. Assignments are obtained by a combination of one- and two-dimensional NMR methods, by the study of genetically altered domains, and by the biosynthetic incorporation of deuterium labels. The resulting assignments provide sensitive markers for tertiary and quaternary structure. Nuclear Overhauser enhancements demonstrate that the major features of the crystal structure, including the dimer contacts, are retained in solution. The rates of aromatic ring rotation indicate that the globular domain is not rigid; significant barriers to ring rotation are observed only in the dimer contact.
Nonalcoholic fatty liver disease and the metabolic syndrome (2005)

In the last 15 years evidence has been accumulating suggesting that hepatic steatosis may be the starting point for a progressive liver disease. Nonalcoholic steatosis (nonalcoholic fatty liver disease, NAFLD) is now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma. Liver disease of other etiology, namely hepatitis C virus, may interact with NAFLD, although the underlying mechanism(s) have not been fully elucidated. Type 2 diabetes mellitus, obesity and dyslipidemia are the principal factors associated with NAFLD, which is now considered the hepatic expression of metabolic syndrome (MS). Several studies have dealt with the relationship of NAFLD and MS, the risk of liver disease associated with the classical features of MS, the importance of insulin resistance as the common soil of different diseases. We still need to clarify the mechanism(s) responsible for liver disease progression from pure fatty liver, to steatohepatitis and to cirrhosis, and the reason(s) why only a few NAFLD cases progress to terminal liver failure while others (the majority) will have a cardiovascular outcome. The epidemics of obesity and diabetes of Western countries is expected to produce a significant increase of metabolic liver disease in the next years. Prevention and intervention programs based on lifestyle are therefore mandatory to reduce the burden of metabolic liver disease.