gebhart/patrepeval huggingface dataset:
Recognition of Superpotent Sweetener Ligands by a Library of Monoclonal Antibodies (1997)

Monoclonal antibodies (mAb) made to the superpotent guanidino sweet tasting ligand, N-(p-cyanophenyl)-N'-(diphenylmethyl)-guanidineacetic acid were examined for their molecular recognition specificities using 14 different sweetener analogues in a competitive radioimmunoassay. The effects of variations in pH on ligand binding was also examined by radioimmunoassay. Photoaffinity labelling of the binding site was accomplished using a radiolabelled azido-derivative of the parent ligand, and L-chain or H-chain labelling was easily identified in several different mAb. For two of the mAb examined in this study (NC6.8 and NC10.14), the analogue binding studies are in agreement with the known Fab-ligand crystal structures. Monoclonal antibodies to this family of sweet tasting compounds may be useful probes for the study of sweet taste chemistry and identification of novel sweet taste ligands from combinatorial chemical libraries.
Flowing liquid sample jet for resonance Raman and ultrafast optical spectroscopy (2003)

A wire-guided, gravity-driven jet apparatus is described that produces optically stable thin films of liquids flowing at rates suitable for high repetition rate spectroscopy. Unlike conventional free-flowing jets, the design works well for low viscosity solvents including water and aqueous solutions of proteins. The construction of the wire guide, jet nozzle, and flow system is described. A stable water film whose thickness can be varied from 6 to 100 μm is demonstrated that has been employed in resonance Raman and femtosecond transient absorption experiments.
Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis (2011)

The major cellular event in the development and progression of liver fibrosis is the activation of hepatic stellate cells (HSCs). Activated HSCs proliferate and produce excess collagen, leading to accumulation of scar matrix and fibrotic liver. As such, the induction of activated HSC death has been proposed as a means to achieve resolution of liver fibrosis. Here we demonstrate that cannabidiol (CBD), a major non-psychoactive component of the plant Cannabis sativa, induces apoptosis in activated HSCs through a cannabinoid receptor-independent mechanism. CBD elicits an endoplasmic reticulum (ER) stress response, characterized by changes in ER morphology and the initiation of RNA-dependent protein kinase-like ER kinase-, activating transcription factor-6-, and inositol-requiring ER-to-nucleus signal kinase-1 (IRE1)-mediated signaling cascades. Furthermore, CBD induces downstream activation of the pro-apoptotic IRE1/ASK1/c-Jun N-terminal kinase pathway, leading to HSC death. Importantly, we show that this mechanism of CBD-induced ER stress-mediated apoptosis is specific to activated HSCs, as it occurs in activated human and rat HSC lines, and in primary in vivo-activated mouse HSCs, but not in quiescent HSCs or primary hepatocytes from rat. Finally, we provide evidence that the elevated basal level of ER stress in activated HSCs has a role in their susceptibility to the pro-apoptotic effect of CBD. We propose that CBD, by selectively inducing death of activated HSCs, represents a potential therapeutic agent for the treatment of liver fibrosis.
Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. (1993)

Allelic loss studies have been instrumental in identifying tumor suppressor gene loci in a variety of cancers. In this study we analyzed prostate cancer specimens from 52 patients for allelic loss using 8 polymorphic probes for the short arm of chromosome 8. Overall, 32 of 51 (63%) informative tumors showed loss of at least one locus on chromosome 8p. The most frequently deleted region is observed at chromosome 8p22-8p21.2. Loss of one allele is identified in 14 of 23 (61%) tumors at D8S163, in 15 of 32 (47%) tumors at lipoprotein lipase, and in 20 of 29 (69%) tumors at MSR, all on 8p22. Loss of one allele is identified in 16 of 27 (59%) tumors at D8S220 at 8p21.3-8p21.2. In addition to frequent loss of one allele at the MSR locus, one metastatic prostate cancer sample demonstrated homozygous deletion of MSR sequences. Loci telomeric and centromeric to this region are largely retained. A chromosome 8p deletion map is constructed and defines the smallest region of overlap to a 14-cM interval at 8p22 between D8S163 and lipoprotein lipase, flanking the MSR locus. Evidence of chromosome 8q multiplication at locus D8S39 was detected in 5 of 32 (16%) tumors, all of which demonstrated loss with at least one probe on chromosome 8p. This study extends the previous finding of frequent loss of chromosome 8p in prostate cancer by defining a common region of loss of heterozygosity at 8p22 and a homozygous deletion of the MSR locus contained within this region. This is the first homozygous deletion identified in the genome of a human prostate cancer and the highest rate of loss yet reported on chromosome 8p in cancer. These results strongly suggest the presence of a tumor suppressor gene in this region which is frequently inactivated in prostate cancer.
TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists (2006)

Vanilloid receptor type 1 (TRPV1) is a ligand-gated nonselective cation channel that is considered to be an important integrator of various pain stimuli such as endogenous lipids, capsaicin, heat, and low pH. In addition to expression in primary afferents, TRPV1 is also expressed in the CNS. To test the hypothesis that the CNS plays a differential role in the effect of TRPV1 antagonists in various types of pain, the analgesic effects of two TRPV1 antagonists with similar in vitro potency but different CNS penetration were compared in vivo. Oral administration of either A-784168 (1-[3-(trifluoromethyl)pyridin-2-yl]-N-[4-(trifluoromethylsulfonyl)phenyl]-1,2,3,6-tetrahydropyridine-4-carboxamide) (good CNS penetration) or A-795614 (N-1H-indazol-4-yl-N'-[(1R)-5-piperidin-1-yl-2,3-dihydro-1H-inden-1-yl]urea) (poor CNS penetration) blocked capsaicin-induced acute pain with the same potency. In complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, oral administration of either compound blocked thermal hyperalgesia with similar potency. Furthermore, intraplantar or intrathecal administration of A-784168 blocked CFA-induced thermal hyperalgesia, suggesting that both peripheral and CNS TRPV1 receptors may play a role in inflammatory thermal hyperalgesia. The effects of the two TRPV1 antagonists were further assessed in models presumably mediated by central sensitization, including CFA- and capsaicin-induced mechanical allodynia and osteoarthritic pain. In these models, the potency of the two compounds was similar after intrathecal administration. However, when administered orally, A-784168, with good CNS penetration, was much more potent than A-795614. Together, these results demonstrate that TRPV1 receptors in the CNS play an important role in pain mediated by central sensitization. In addition, these results demonstrate that significant CNS penetration is necessary for a TRPV1 antagonist to produce broad-spectrum analgesia.
Soft competitive adaptation: neural network learning algorithms based on fitting statistical mixtures (1991)

In this thesis, we consider learning algorithms for neural networks which are based on fitting a mixture probability density to a set of data.
We begin with an unsupervised algorithm which is an alternative to the classical winner-take-all competitive algorithms. Rather than updating only the parameters of the winner on each case, the parameters of all competitors are updated in proportion to their relative responsibility for the case. Use of such a competitive algorithm is shown to give better performance than the more traditional algorithms, with little additional cost.
We then consider a supervised modular architecture in which a number of simple networks compete to solve distinct pieces of a large task. A soft competitive mechanism is used to determine how much an expert learns on a case, based on how well the expert performs relative to the other expert networks. At the same time, a separate gating network learns to weight the output of each expert according to a prediction of its relative performance based on the input to the system. Experiments on a number of tasks illustrate that this architecture is capable of uncovering interesting task decompositions and of generalizing better than a single network with small training sets.
Finally, we consider learning algorithms in which we assume that the actual output of the network should fall into one of a small number of classes or clusters. The objective of learning is to make the variance of these classes as small as possible. In the classical decision-directed algorithm, we decide that an output belongs to the class it is closest to and minimize the squared distance between the output and the center (mean) of this closest class. In the version of this algorithm, we minimize the squared distance between the actual output and a weighted average of the means of all of the classes. The weighting factors are the relative probability that the output belongs to each class. This idea may also be used to model the weights of a network, to produce networks which generalize better from small training sets.
E7080, a Multi–Tyrosine Kinase Inhibitor, Suppresses the Progression of Malignant Pleural Mesothelioma with Different Proangiogenic Cytokine Production Profiles (2009)

These results strongly suggest broad-spectrum activity of E7080 against MPM with different proangiogenic cytokine production profiles in humans.
Generalized constrained energy minimization approach to subpixel target detection for multispectral imagery (2000)

Subpixel detection in multispectral imagery presents a challenging problem due to relatively low spatial and spectral resolution. We present a generalized constrained energy minimization (GCEM) approach to detecting targets in multispectral imagery at subpixel level. GCEM is a hybrid technique that combines a constrained energy minimization (CEM) method developed for hyperspectral image classification with a dimensionality expansion (DE) approach resulting from a generalized orthogonal subspace projection (GOSP) developed for multispectral image classification. DE enables us to generate additional bands from original multispectral images nonlinearly so that CEM can be used for subpixel detection to extract targets embedded in multispectral images. CEM has been successfully applied to hyperspectral target detection and image classification. Its applicability to multispectral imagery is yet to be investigated. A potential limitation of CEM on multispectral imagery is the effectiveness of interference elimination due to the lack of sufficient dimensionality. DE is introduced to mitigate this problem by expanding the original data dimensionality. Experiments show that the proposed GCEM detects targets more effectively than GOSP and CEM without dimensionality expansion.
Effect of ankle position and a plaster cast on intramuscular pressure in the human leg. (1994)

Intramuscular pressure was measured with transducer-tipped catheters that had been inserted into the anterior and deep posterior compartments of the leg in seven healthy adults. Intramuscular pressure increased three to sevenfold (depending on the position of the ankle) in both compartments after the application of a plaster cast from the proximal part of the thigh to the malleoli. While the cast was in place, the baseline intramuscular pressure was elevated by the inflation of a tourniquet, which was located on the proximal part of the thigh, to a pressure of sixty millimeters of mercury (8.00 kilopascals). The intramuscular pressure in both the anterior and the deep posterior compartments was found to be lowest when the ankle joint was between the neutral and the resting positions (between 0 and 37 degrees of flexion). After the cast was bivalved and the opening on each side was spread approximately one-half centimeter, there was a significant decrease in intramuscular pressure of 47 per cent in the anterior compartment and of 33 per cent in the deep posterior compartment (p < 0.05 for both).
Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge (1999)

HIV infection is accompanied by an early immune dysfunction limiting host control of virus and likely contributing to difficulties in achieving a successful vaccine against HIV. We report here that the HIV Tat protein is strongly immunosuppressive, both immediately after immunization of mice with soluble protein (sTat), and in seroconverting humans, and propose that Tat-induced suppression cripples immune surveillance to HIV infection. We show that macrophages are sensitive to sTat stimulation at concentrations 1,000-fold lower (500 pM) than T cells, and this stimulation is accompanied by the immunosuppressive induction of Fas ligand on the macrophage. T cell proliferative defects induced by sTat in vitro can be completely (at lower concentrations of sTat) or partially (at higher concentrations) reversed by antagonists to Fas/Fas ligand interaction. We further report a method to preserve immunogenicity while inactivating Tat immunosuppression through oxidation, which advances the use of oxidized Tat as a component of an anti-HIV vaccine. These observations define additional methods to study the immunosuppressive functions of sTat that now may be rapidly applied to primary isolates from individuals with differing clinical courses. Our findings have immediate relevance for vaccine development, by describing and supporting a strategy that includes inactivated sTat in a multicomponent, anti-HIV vaccine.
Vagus nerve stimulation in refractory epilepsy: SPECT activation study. (2000)

Our findings are consistent with the hypothesis that acute VNS reduces seizure onset or propagation through inhibition of the thalamic relay center. Differences with limited H2(15)O PET data may be associated with temporal effects caused by a stimulation-induced local hemodynamic response and need further investigation. SPECT allows study of cerebral physiopathologic effects of vagus nerve electrostimulation in complex partial epilepsy.
Pathological tremors: Deterministic chaos or nonlinear stochastic oscillators? (2000)

Pathological tremors exhibit a nonlinear oscillation that is not strictly periodic. We investigate whether the deviation from periodicity is due to nonlinear deterministic chaotic dynamics or due to nonlinear stochastic dynamics. To do so, we apply various methods from linear and nonlinear time series analysis to tremor time series. The results of the different methods suggest that the considered types of pathological tremors represent nonlinear stochastic second order processes. Finally, we evaluate whether two earlier proposed features capturing nonlinear effects in the time series allow for a discrimination between two pathological forms of tremor for a much larger sample of time series than previously investigated. (c) 2000 American Institute of Physics.
Evidence for a Locus Regulating Total Serum IgE Levels Mapping to Chromosome 5 (1994)

Genetics studies of total serum IgE levels were performed since high IgE levels correlate with clinical expression of allergy and asthma. Families ascertained through a parent with asthma were genotyped for markers on 5q where there are multiple candidate genes that may influence the control of IgE and inflammation. Evidence for linkage of the IgE phenotype to 5q was obtained by both sib-pair and lod score analysis with evidence for recessive inheritance of high IgE levels from segregation analysis. These findings represent a major step in mapping genes important in the regulation of allergic responses and the pathogenesis of asthma.
Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency? (1999)

PURPOSE: The current investigators have shown that androgen treatment suppresses inflammation and stimulates the function of lacrimal glands in mouse models of Sjögren's syndrome. Recently, others have hypothesized that androgen insufficiency induces an autoimmune process in lacrimal tissue, leading to inflammation, a Sjögren's syndrome-like pathology, and aqueous tear deficiency. The purpose of the present study was to test this hypothesis. METHODS: Lacrimal glands were obtained from adult testicular feminized (Tfm) and control mice; castrated rats, guinea pigs, and rabbits; and castrated rats without anterior or whole pituitary glands and were processed for histology and image analysis. Tear volumes were measured in mice, in patients taking antiandrogen medications, and in age-matched human control subjects. RESULTS: Tfm mice, which are completely resistant to classical androgen action, did not have increased lymphocyte infiltration in their lacrimal glands or decreased tear volumes. No inflammation was evident in lacrimal tissues of male or female rats, guinea pigs, or rabbits 12 to 31 days after castration, no inflammation existed in rat lacrimal glands 15 to 31 days after orchiectomy and pituitary removal, and no aqueous tear deficiency was apparent in patients receiving antiandrogen therapy. CONCLUSIONS: Androgen deficiency may promote the progression of Sjögren's syndrome and its associated lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. However, androgen insufficiency alone does not cause lacrimal gland inflammation, a Sjögren's syndrome-like pathology in lacrimal tissue, or aqueous tear deficiency in nonautoimmune animals and humans.
UDEL/SMU at TREC 2009 Entity Track (2009)

We report our methods and experiment results from the collaborative participation of the InfoLab group from University of Delaware and the school of Information Systems from Singapore Management University in the TREC 2009 Entity track. Our general goal is to study how we may apply language modeling approaches and natural language processing techniques to the task. Specifically, we proposed to find supporting information based on segment retrieval, to extract entities using Stanford NER tagger, and to rank entities based on a previously proposed probabilistic framework for expert finding.
Somniloquy: augmenting network interfaces to reduce PC energy usage (2009)

Reducing the energy consumption of PCs is becoming increasingly important with rising energy costs and environmental concerns. Sleep states such as S3 (suspend to RAM) save energy, but are often not appropriate because ongoing networking tasks, such as accepting remote desktop logins or performing background file transfers, must be supported. In this paper we present Somniloquy, an architecture that augments network interfaces to allow PCs in S3 to be responsive to network traffic. We show that many applications, such as remote desktop and VoIP, can be supported without application-specific code in the augmented network interface by using application-level wakeup triggers. A further class of applications, such as instant messaging and peer-to-peer file sharing, can be supported with modest processing and memory resources in the network interface. Experiments using our prototype Somniloquy implementation, a USB-based network interface, demonstrates energy savings of 60 % to 80 % in most commonly occuring scenarios. This translates to significant cost savings for PC users.
Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice (2008)

Mucin-type O-glycans (O-glycans) are highly expressed in vascular ECs. However, it is not known whether they are important for vascular development. To investigate the roles of EC O-glycans, we generated mice lacking T-synthase, a glycosyltransferase encoded by the gene C1galt1 that is critical for the biosynthesis of core 1-derived O-glycans, in ECs and hematopoietic cells (termed here EHC T-syn(-/-) mice). EHC T-syn(-/-) mice exhibited embryonic and neonatal lethality associated with disorganized and blood-filled lymphatic vessels. Bone marrow transplantation and EC C1galt1 transgene rescue demonstrated that lymphangiogenesis specifically requires EC O-glycans, and intestinal lymphatic microvessels in EHC T-syn(-/-) mice expressed a mosaic of blood and lymphatic EC markers. The level of O-glycoprotein podoplanin was significantly reduced in EHC T-syn(-/-) lymphatics, and podoplanin-deficient mice developed blood-filled lymphatics resembling EHC T-syn(-/-) defects. In addition, postnatal inactivation of C1galt1 caused blood/lymphatic vessel misconnections that were similar to the vascular defects in the EHC T-syn(-/-) mice. One consequence of eliminating T-synthase in ECs and hematopoietic cells was that the EHC T-syn(-/-) pups developed fatty liver disease, because of direct chylomicron deposition via misconnected portal vein and intestinal lymphatic systems. Our studies therefore demonstrate that EC O-glycans control the separation of blood and lymphatic vessels during embryonic and postnatal development, in part by regulating podoplanin expression.
Encyclopedic Dictionary of Plant Breeding and Related Subjects (2003)

From Abaxial to Zymogram, make sense out of the confusing terminology of plant breeding! The Encyclopedic Dictionary of Plant Breeding and Related Subjects is the first comprehensive book that contains clear and useful definitions of the terms associated with plant breeding and related scientific/technological disciplines. This well-organi
Cloning and functional expression of the cDNA encoding an inwardly‐rectifying potassium channel expressed in pancreatic β‐cells and in the brain (1995)

A cDNA clone encoding an inwardly-rectifying K-channel (BIR1) was isolated from insulinoma cells. The predicted amino acid sequence shares 72% identity with the cardiac ATP-sensitive K-channel rcKATP (KATP-1;[6]). The mRNA is expressed in the brain and insulinoma cells. Heterologous expression in Xenopus oocytes produced currents which were K(+)-selective, time-independent and showed inward rectification. The currents were blocked by external barium and caesium, but insensitive to tolbutamide and diazoxide. In inside-out patches, channel activity was not blocked by 1 mM internal ATP. The sequence homology with KATP-1 suggests that BIR1 is a subunit of a brain and beta-cell KATP channel. However, pharmacological differences and the lack of ATP-sensitivity, suggest that if, this is the case, heterologous subunits must exert strong modulatory influences on the native channel.
JAM-B regulates maintenance of hematopoietic stem cells in the bone marrow (2011)

In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow (BM) and are maintained in a quiescent and undifferentiated state through adhesive interactions with specialized microenvironmental niches. Although junctional adhesion molecule-C (JAM-C) is expressed by HSCs, its function in adult hematopoiesis remains elusive. Here, we show that HSCs adhere to JAM-B expressed by BM stromal cells in a JAM-C dependent manner. The interaction regulates the interplay between HSCs and BM stromal cells as illustrated by the decreased pool of quiescent HSCs observed in jam-b deficient mice. We further show that this is probably because of alterations of BM stromal compartments and changes in SDF-1α BM content in jam-b(-/-) mice, suggesting that JAM-B is an active player in the maintenance of the BM stromal microenvironment.