gebhart/patrepeval huggingface dataset:
Technical Details of Intraoperative Lymphatic Mapping for Early Stage Melanoma (1992)

The initial route of metastases in most patients with melanoma is via the lymphatics to the regional nodes. However, routine lymphadenectomy for patients with clinical stage I melanoma remains controversial because most of these patients do not have nodal metastases, are unlikely to benefit from the operation, and may suffer troublesome postoperative edema of the limbs. A new procedure was developed using vital dyes that permits intraoperative identification of the sentinel lymph node, the lymph node nearest the site of the primary melanoma, on the direct drainage pathway. The most likely site of early metastases, the sentinel node can be removed for immediate intraoperative study to identify clinically occult melanoma cells. We successfully identified the sentinel node(s) in 194 of 237 lymphatic basins and detected metastases in 40 specimens (21%) on examination of routine hematoxylin-eosin-stained slides (12%) or exclusively in immunohistochemically stained preparations (9%). Metastases were present in 47 (18%) of 259 sentinel nodes, while nonsentinel nodes were the sole site of metastasis in only two of 3079 nodes from 194 lymphadenectomy specimens that had an identifiable sentinel node, a false-negative rate of less than 1%. Thus, this technique identifies, with a high degree of accuracy, patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy.
Activation of the Aryl Hydrocarbon Receptor Suppresses Sensitization in a Mouse Peanut Allergy Model (2011)

Food allergy is an increasing health problem in Western countries. Previously, it has been shown that the intensity of food allergic reactions can be regulated by regulatory T (T(reg)) cells. In addition, it has been shown that activation of the aryl hydrocarbon receptor (AhR) regulates T-cell responses by induction of T(reg) cells. Therefore, we hypothesized that activation of the AhR pathway can suppress development of food allergic responses through the induction of T(reg) cells. This was investigated by using a mouse model for peanut allergy. C3H/HeOuJ mice (AhR(b)(-2)) were sensitized to peanut by administering peanut extract (PE) by gavage in the presence of cholera toxin and were treated with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.6, 1.7, 5, and 15 μg/kg body weight) on days 3 and 11 orally. The functional role of CD4(+)CD25(+)Foxp3(+) T(reg) cells was investigated by depleting these cells with anti-CD25 mAb during sensitization to PE. TCDD treatment dose dependently suppressed sensitization to peanut (PE-specific IgE, IgG1, and IgG2a and PE-induced IL-5, IL-10, and IL-13, respectively). The percentage, but not the number, of CD4(+)CD25(+)Foxp3(+) T(reg) cells dose dependently increased by AhR activation in both spleen and mesenteric lymph nodes. Depletion of CD4(+)CD25(+)Foxp3(+) T(reg) cells markedly reversed the suppressive effect of TCDD on PE-specific antibody levels and PE-induced IL-5, IL-10, and IL-13 cytokine production. Present data demonstrate for the first time that activation of the AhR by TCDD suppressed the development of Th2-mediated food allergic responses. A functional shift within the CD4(+) cell population toward CD4(+)CD25(+)Foxp3(+) T(reg) cells appeared to underlie this effect. This suggests that the AhR pathway might provide potential therapeutic targets to treat food allergic diseases.
Distribution of Cell-Free and Cell-Associated HIV Surrogates in the Female Genital Tract After Simulated Vaginal Intercourse (2012)

We demonstrate the feasibility of dual-isotope SPECT/CT and MR imaging to determine the distribution of HIV and semen surrogates after simulated intercourse without disrupting vaginal contents. Surrogate distribution suggests topical microbicides do not need to reach the uterus for efficacy.
Positioning of the MinE binding site on the MinD surface suggests a plausible mechanism for activation of the Escherichia coli MinD ATPase during division site selection (2004)

Division site selection in Escherichia coli requires that the MinD protein interact with itself and with MinC and MinE. MinD is a member of the NifH-ArsA-Par-MinD subgroup of ATPases. The MinE-MinD interaction results in activation of MinD ATPase activity in the presence of membrane vesicles. The sites within MinD responsible for its interaction with MinC and MinE were studied by site-directed mutagenesis and yeast two-hybrid analysis, guided by the known three-dimensional structure of MinD proteins. This provided evidence that MinC and MinE bind to overlapping sites on the MinD surface. The results also suggested that MinE and the invariant Lys11 residue in the ATPase P-loop of MinD compete for binding to a common site within the MinD structure, thereby providing a plausible structural basis for the ability of MinE to activate the ATPase activity of MinD.
Development of methods for synthesis of surface-modified fluoropolymer-containing composite materials (2009)

The results of studies into development of methods for synthesizing new modified fluoropolymer-containing composite materials were summarized. The issues covered include: new modes and initiation methods of graft polymerization of fluoromonomers onto the surface of items of various nature and dispersity without homopolymer formation; nature of the surface active centers of the modified material and how it affects the kinetics and mechanism of both postradiation graft polymerization of tetrafluoroethylene and the subsequent chemical modification of the graft-polymer; major mechanisms and methods of blocking the terminal radicals of the grafted fluoropolymer layer, including those based on reaction with some perfluoroolefins at their double bond, yielding stable long-lived radicals, which allows controlling the physicochemical properties of composite materials; and new methods of synthesis of selective biocompatible sorbents with specific adsorption properties. Accelerating effect of oxygen on polymerization was analyzed, and the phenomenon of ozone initiation of low-temperature polymerization of tetrafluoroethylene was revealed and examined; a new class of high-performance polymerization initiators, namely, perflouroolefin ozonides, was synthesized; and new methods of initiation of polymerization and copolymerization of fluoromonomers, as well as of some other monomers with their use were developed.
Inflammasome is a central player in the induction of obesity and insulin resistance (2011)

Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in proinflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in caspase-1 activation and production of proinflammatory cytokines IL-1β and IL-18. Here, we showed that mice deficient in Nlrp3, apoptosis-associated speck-like protein, and caspase-1 were resistant to the development of high-fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Furthermore, hepatic triglyceride content, adipocyte size, and macrophage infiltration in adipose tissue were all reduced in mice deficient in inflammasome components. Monocyte chemoattractant protein (MCP)-1 is a key molecule that mediates macrophage infiltration. Indeed, defective inflammasome activation was associated with reduced MCP-1 production in adipose tissue. Furthermore, plasma leptin and resistin that affect energy use and insulin sensitivity were also changed by inflammasome-deficiency. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance, and suggest inhibition of the inflammasome as a potential therapeutic strategy.
Reliable tracking of human arm dynamics by multiple cue integration and constraint fusion (2002)

The use of hard gestures provides an attractive means of interacting naturally with a computer generated display. Using one or more video cameras, the hand movements can potentially be interpreted as meaningful gestures. One key problem in building such am interface without a restricted setup is the ability to localize and track the human arm robust in image sequences. This paper proposes a multiple cite-based localization scheme combined with a tracking framework to reliably track the human arm dynamics in unconstrained environments. The localization scheme integrates the multiple cues of motion, shape, and color for locating a set of key image features. Using constraint fusion, these features are tracked by a modified Extended Kalman Filter that exploits the articulated structure of the arm. We also propose an interaction scheme between tracking and localization for improving the estimation process while reducing the computational requirements. The performance of the frameworks is validated with the help of extensive experiments and simulations.
Predicting nucleosome positioning using a duration Hidden Markov Model (2010)

Simulation studies show that modeling the linker length distribution and utilizing a base composition re-scaling method both improve the prediction of nucleosome positioning regarding sensitivity and false discovery rate. NuPoP provides a user-friendly software tool for predicting the nucleosome occupancy and the most probable nucleosome positioning map for genomic sequences of any size. When compared with two existing methods, NuPoP shows improved performance in sensitivity.
Novel Peroxisome Proliferator-activated Receptor (PPAR) γ and PPARδ Ligands Produce Distinct Biological Effects (1999)

The peroxisome proliferator-activated receptors (PPARs) include three receptor subtypes encoded by separate genes: PPARalpha, PPARdelta, and PPARgamma. PPARgamma has been implicated as a mediator of adipocyte differentiation and the mechanism by which thiazolidinedione drugs exert in vivo insulin sensitization. Here we characterized novel, non-thiazolidinedione agonists for PPARgamma and PPARdelta that were identified by radioligand binding assays. In transient transactivation assays these ligands were agonists of the receptors to which they bind. Protease protection studies showed that ligand binding produced specific alterations in receptor conformation. Both PPARgamma and PPARdelta directly interacted with a nuclear receptor co-activator (CREB-binding protein) in an agonist-dependent manner. Only the PPARgamma agonists were able to promote differentiation of 3T3-L1 preadipocytes. In diabetic db/db mice all PPARgamma agonists were orally active insulin-sensitizing agents producing reductions of elevated plasma glucose and triglyceride concentrations. In contrast, selective in vivo activation of PPARdelta did not significantly affect these parameters. In vivo PPARalpha activation with WY-14653 resulted in reductions in elevated triglyceride levels with minimal effect on hyperglycemia. We conclude that: 1) synthetic non-thiazolidinediones can serve as ligands of PPARgamma and PPARdelta; 2) ligand-dependent activation of PPARdelta involves an apparent conformational change and association of the receptor ligand binding domain with CREB-binding protein; 3) PPARgamma activation (but not PPARdelta or PPARalpha activation) is sufficient to potentiate preadipocyte differentiation; 4) non-thiazolidinedione PPARgamma agonists improve hyperglycemia and hypertriglyceridemia in vivo; 5) although PPARalpha activation is sufficient to affect triglyceride metabolism, PPARdelta activation does not appear to modulate glucose or triglyceride levels.
Enhanced Inflammatory Response to Coronary Angioplasty in Patients With Severe Unstable Angina (1998)

Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.
An efficient online path profiling framework for Java just-in-time compilers (2003)

Collecting hot paths is important for restructuring and optimizing the target program effectively. It is, however, challenging for Just-In-Time (JIT) compilers, which must collect path profiles on the fly at runtime. In this paper, we propose an efficient online path profiling technique, called structural path profiling (SPP), suitable for JIT compilers. The key idea is to partition the target method into a hierarchy of the nested graphs based on the loop structure, and then to profile each graph independently. With SPP, we can collect accurate path profiles efficiently with low overhead. The experimental results show that our technique can collect path profiles with an accuracy of around 90% compared to the offline complete path profiles, while it incurs only 2-3% overhead on average in the active profiling phase.
A fluorogenic assay for endothelin-converting enzyme. (1992)

The potent vasoconstrictor peptide endothelin-1 is proposed to arise via proteolysis of a precursor molecule, "big endothelin," at a unique cleavage site. To aid in the identification of a putative endothelin-converting enzyme, we have developed an assay that mimics the relevant cleavage reaction. The assay takes advantage of the intramolecular fluorescence energy transfer between the scissile-site tryptophan and a dansyl moiety present in the same synthetic substrate. Cleavage of the peptide chain separates the fluorophore and quencher, resulting in an increase in fluorescence. The assay has been validated using chymotrypsin as a model protease and has been employed in the identification of novel endothelin-converting enzyme activities.
Pain and Nociception: Mechanisms of Cancer-Induced Bone Pain (2014)

Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.
Drugs and Disease as Mosquito Repellents in Man (1968)

SummaryHospitalized patients with various diseases and taking various medications were surveyed for their attractiveness to mosquitoes by a mosquito-probing technique. No drug was found that induced unattractiveness, and no disease was associated with unattractiveness, with the possible exception of untreated myxedema. Vitamins, expecially B1, in biting and probing tests were found inactive systemic mosquito repellents.
Mapping the Learning Pathways of Larval Zebrafish through Positively Stimulating Their Reward Pathways Using Paramecium (2016)

Zebrafish rely on visual acuity to hunt for prey all of their lives, for this reason, their eyesight develops when they are embryos. The zebrafish in this experiment are between 5 and 20 days old. Once their egg yolks are completely reabsorbed the zebrafish have a need to eat, and only then will they have an interest in eating Paramecium. The zebrafishes’ eyes will be able to see clearly by 5 days post fertilization as well, so when food is introduced to them, a certain colored light will be simultaneously shined in the same direction as the one the food is coming from.\nThe purpose of this experiment is to use different colored visual cues to train larval zebrafish into expecting food whenever they are shone. The usage of lights also tests their extraordinary visual abilities. Red lights will be associated with a food reward in one group of larvae, and in the second group, green lights will be associated with a food reward, demonstrating associative learning. The zebrafishes’ unconditioned response (eating Paramecium when they appear) will be trained into a conditioned response (looking to eat Paramecium when the light is shined). After they have been conditioned to respond to these signals, the zebrafishes’ brains will be studied to find changes in their neural pathways.\nThe expected results of this experiment should lead to the fish thinking Paramecium are coming at just the glimpse of a light.
Characterization of the H-kininogen-binding Site on Factor XI (2002)

Factor XI (FXI), the zymogen of the blood coagulation protease FXIa, and the structurally homologous protein plasma prekallikrein circulate in plasma in noncovalent complexes with H-kininogen (HK). HK binds to the heavy chains of FXI and of prekallikrein. Each chain contains four apple domains (F1-F4 for FXI and P1-P4 for prekallikrein). Previous studies indicated that the HK-binding site on FXI is located in F1, whereas the major HK-binding site on prekallikrein is in P2. To determine the contribution of each FXI apple domain to HK-FXI complex formation, we examined binding of recombinant single apple domain-tissue plasminogen activator fusion proteins to HK. The order of affinity from highest to lowest is F2 F4 > F1 F3. Monoclonal antibodies against F2 are superior to F4 or F1 antibodies as inhibitors of HK binding to FXI. Antibody alphaP2, raised against prekallikrein, cross-reacts with FXI F2 and inhibits FXI-HK binding with an IC(50) of 8 nm. HK binding to a platelet-specific FXI variant lacking the N-terminal half of F2 is reduced > 5-fold compared with full-length FXI. A chimeric FXI molecule in which F2 is replaced by P2 is cleaved within P2 during activation by factor XIIa, resulting in greatly reduced HK binding capacity. In contrast, wild-type FXI is not cleaved within F2, and its binding capacity for HK is unaffected by factor XIIa. Our data show that HK binding to FXI involves multiple apple domains, with F2 being most important. The findings demonstrate a similarity in mechanism for FXI and prekallikrein binding to HK.
Autoimmune diseases: MIF as a therapeutic target (2010)

We expect that MIF antagonism by either small-molecule- or antibody-based approaches will find wide application in the treatment of autoimmune inflammatory diseases. Such therapy also may be informed by the MIF genotype of affected patients.
Topic themes for multi-document summarization (2005)

The problem of using topic representations for multi-document summarization (MDS) has received considerable attention recently. In this paper, we describe five different topic representations and introduce a novel representation of topics based on topic themes. We present eight different methods of generating MDS and evaluate each of these methods on a large set of topics used in past DUC workshops. Our evaluation results show a significant improvement in the quality of summaries based on topic themes over MDS methods that use other alternative topic representations.
Interferon–inducible T Cell Alpha Chemoattractant (I-TAC): A Novel Non-ELR CXC Chemokine with Potent Activity on Activated T Cells through Selective High Affinity Binding to CXCR3 (1998)

Chemokines are essential mediators of normal leukocyte trafficking as well as of leukocyte recruitment during inflammation. We describe here a novel non-ELR CXC chemokine identified through sequence analysis of cDNAs derived from cytokine-activated primary human astrocytes. This novel chemokine, referred to as I-TAC (interferon-inducible T cell alpha chemoattractant), is regulated by interferon (IFN) and has potent chemoattractant activity for interleukin (IL)-2-activated T cells, but not for freshly isolated unstimulated T cells, neutrophils, or monocytes. I-TAC interacts selectively with CXCR3, which is the receptor for two other IFN-inducible chemokines, the IFN-gamma-inducible 10-kD protein (IP-10) and IFN-gamma- induced human monokine (HuMig), but with a significantly higher affinity. In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig is demonstrated by transient mobilization of intracellular calcium as well as chemotactic migration in both activated T cells and transfected cell lines expressing CXCR3. Stimulation of astrocytes with IFN-gamma and IL-1 together results in an approximately 400,000-fold increase in I-TAC mRNA expression, whereas stimulating monocytes with either of the cytokines alone or in combination results in only a 100-fold increase in the level of I-TAC transcript. Moderate expression is also observed in pancreas, lung, thymus, and spleen. The high level of expression in IFN- and IL-1-stimulated astrocytes suggests that I-TAC could be a major chemoattractant for effector T cells involved in the pathophysiology of neuroinflammatory disorders, although I-TAC may also play a role in the migration of activated T cells during IFN-dominated immune responses.
Oxidative Damage to Behavior During Aging (1991)

The proposition that free radicals may be an important factor in aging remains to be rigorously proven; but the presence of increased amounts of oxidized proteins in aging biological systems supports the notion. The results of new experiments in Mongolian gerbils indicate that the accumulation of oxidatively damaged proteins during aging may be a cause of behavioral deficits in aging experimental animals and that this chronic oxidation may be reversible with compounds that react with and stabilize free radicals. PBN (N-tert-butyl-{alpha}-phenyl nitrone), a spin-trapping compound, reacts with free radicals and yields a stable nitroxyl product. PBN offers protection from, and traps free radicals during, ischemia-reperfusion-mediated injury to heart and brain of experimental animals. Daily administration of PBN to old gerbils causes a decrease in the amount of oxidized protein and an increase in both glutamine synthetase and neutral protease activity in brain, as well as a decrease in the number of errors made in the radial-arm maze test for memory. In other words, PBN administration reversed the chemical and behavioral parameters of the older gerbils to nearly those values observed in the younger gerbils. Furthermore, after cessation of PBN administration, the amount of both oxidized protein as well as glutaminemore » synthetase and neutral protease activities gradually returned to the values found in normal, older gerbils. PBN did not have these effects in young gerbils.« less
Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in Mice (2009)

We conclude that murine beta-cells' ability to proliferate in response to metabolic need (i.e. rising blood glucose concentrations) is remarkably well preserved during severe, chronic beta-cell autoimmunity. These data suggest that timely control of the destructive immune response after disease manifestation could allow spontaneous regeneration of sufficient beta-cell mass to restore normal glucose homeostasis.