gebhart/patrepeval huggingface dataset:
How Can (−)-Epigallocatechin Gallate from Green Tea Prevent HIV-1 Infection? Mechanistic Insights from Computational Modeling and the Implication for Rational Design of Anti-HIV-1 Entry Inhibitors (2006)

Possible inhibitors preventing human immunodeficiency virus type 1 (HIV-1) entry into the cells are recognized as hopeful next-generation anti-HIV-1 drugs. It is highly desirable to develop a potent inhibitor blocking binding of glycoprotein CD4 of the cell with glycoprotein gp120 of HIV-1, because the gp120-CD4 binding is the initial step of HIV-1 entry into the cells. It has been recently reported that (-)-epigallocatechin gallate (EGCG) from green tea is an inhibitor blocking gp120-CD4 binding. But the inhibitory mechanism remains unknown. For understanding the inhibitory mechanism, extensive molecular docking, molecular dynamics simulations, and binding free-energy calculations have been performed in this study to predict the most favorable structures of CD4-EGCG, gp120-CD4, and gp120-CD4-EGCG binding complexes in water. The results reveal that EGCG binds with CD4 in such a way that the calculated binding affinity of gp120 with the CD4-EGCG complex is negligible. So, the favorable binding of EGCG with CD4 can effectively block gp120-CD4 binding. The calculated CD4-EGCG binding affinity (DeltaG(bind) = -5.5 kcal/mol, K(d) = 94 microM) is in excellent agreement with available experimental data suggesting IC(50) approximately 100 microM for EGCG-blocking CD4-gp120 binding. These results and insights provide a rational basis for future design of novel, more potent inhibitors to block gp120-CD4 binding.
Calcium‐Catalyzed Cycloisomerization of Enynes (2013)

Abstract A cycloisomerization of enynes with a benign calcium catalyst is presented exploring a complementary reactivity to that usually found in transition and noble metal‐catalyzed reactions. Thereby, a systematic investigation of the π‐activation of alkynes with reactive carbocations has been realized and ketones of various ring sizes were easily accessed. We are certain that these basic investigations will pave the way for the elaboration of further reactions based on the reaction principles discovered in the area of noble metal catalysis.
Guanidinoethane sulfate: brain pH alkaline shifter (1993)

A new category of agents, brain pH alkaline shifters, is described. Using the prototype agent, guanidinoethane sulfate (GES), the actual alkaline shift in pH was demonstrated in adult mice brain by 31-phosphorus (31P) nuclear magnetic resonance (NMR) in vivo spectroscopy. This alkaline shift was also shown to effectively reduce the extent of brain intracellular lactic acidosis brought about by anoxic insult. These findings support the notion that a pH alkaline shift may protect the brain against the deleterious effects of lactic acidosis. Since higher pH has been shown to significantly reduce beta-amyloid deposition, alkaline shifters may also have therapeutic potential in Alzheimer's disease.
Demonstration of extracellular chymotrypsin-like activity from various Legionella species (1982)

Concentrated extracellular supernatants from Legionella pneumophila, L. bozemanii, L. dumoffi, L. gormanii, but not L. micdadei, exhibited a strong chymotrypsin-like activity upon synthetic chromogenic tri- and tetrapeptides. Bacterial cell sonic extracts showed low protease activities, different from those of the extracellular concentrates. Extracellular concentrates were also tested in the API ZYM system, where weak protease activity only was recorded. Protease inhibitors decreased the activity of the extracellular Legionella proteases upon the chromogenic peptides.
Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate (2005)

This study suggests that a regimen of three-month cycles of parathyroid hormone alternating with three-month cycles without parathyroid hormone causes the early phase of action of parathyroid hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with parathyroid hormone increase spinal bone mineral density.
Sphenopalatine Ganglion Block in Traumatic Trigeminal Neuralgia and the Outcome to Radiosurgical Ablation (2009)

Zarembinski, Christopher J. M.D.; Graff-Radford, Steven D.D.S.; Ananda, Ajay M.D.; Hakimian, Behrooz M.D.; Rosner, Howard M.D.
Preclinical ex vivo expansion of cord blood hematopoietic stem and progenitor cells: duration of culture; the media, serum supplements, and growth factors used; and engraftment in NOD/SCID mice (2001)

The data supported the strategy of expansion. The optimized condition may be applicable to clinical expansion for the abrogation or reduction of posttransplant cytopenia.
Neutrophil elastase induces mucin production by ligand-dependent epidermal growth factor receptor activation (2002)

Neutrophil products are implicated in hypersecretory airway diseases. To determine the mechanisms linking a proteolytic effect of human neutrophil elastase (HNE) and mucin overproduction, we examined the effects of HNE on MUC5AC mucin production in human airway epithelial (NCI-H292) cells. Stimulation with HNE for 5-30 min induced MUC5AC production 24 h later, which was prevented by HNE serine active site inhibitors, implicating a proteolytic effect of HNE. MUC5AC induction was preceded by epidermal growth factor receptor (EGFR) tyrosine phosphorylation and was prevented by selective EGFR tyrosine kinase inhibitors, implicating EGFR activation. HNE-induced MUC5AC production was inhibited by a neutralizing transforming growth factor-alpha (TGF-alpha, an EGFR ligand) antibody and by a neutralizing EGFR antibody but not by oxygen free radical scavengers, further implicating TGF-alpha and ligand-dependent EGFR activation in the response. HNE decreased pro-TGF-alpha in NCI-H292 cells and increased TGF-alpha in cell culture supernatant. From these results, we conclude that HNE-induced MUC5AC mucin production occurs via its proteolytic activation of an EGFR signaling cascade involving TGF-alpha.
Distributed joint source-channel coding of video (2005)

Based on recent works on source-channel coding for Wyner-Ziv coding, we consider the case with noisy channel in Wyner-Ziv coding and address distributed joint source-channel coding, while targeting at the important application of video transmission over packet erasure channels. The idea is to use a single channel code for both Slepian-Wolf coding (or source coding with side information at the decoder) and erasure protection. We choose Raptor codes - the best approximation to a digital fountain - for the targeted application and study both encoder and decoder designs under the new setting of distributed joint source-channel coding. Our work represents the first in capitalizing the latest in distributed source coding (e.g., Wyner-Ziv video coding) and near-capacity channel coding (e.g., fountain codes) for robust video transmission over erasure channels.
650. Diazaindenes and their quaternary salts. Part I. The preparation of 2,3,3-trimethyl-3H-1,7-diazaindene, and its methiodides and derived cyanine dyes (1959)

G. E. Ficken and J. D. Kendall, J. Chem. Soc., 1959, 3202 DOI: 10.1039/JR9590003202
Current-Day Prevalence of Ménière’s Syndrome (2010)

Previously reported prevalence rates of Ménière's syndrome (MS) have ranged from 3.5 per 100000 to 513 per 100000. Recent data regarding the prevalence in the United States are lacking. To further assess the current-day prevalence of MS in the US, data from a medical and pharmaceutical claims database containing information for over 60 million unique patients were analyzed. Patients in the database are representative of the national, commercially insured population on a variety of demographic measures including age, gender, health plan type, and geographic location. A 3-year period from 2005 to 2007 was analyzed. The prevalence of MS was 190 per 100000 with a female:male ratio of 1.89:1. The prevalence increased with increasing age, ranging from 9 per 100000 for patients under age 18 to 440 per 100000 for patients 65 years and older.
Increased frequency (12%) of circulating chronic lymphocytic leukemia–like B-cell clones in healthy subjects using a highly sensitive multicolor flow cytometry approach (2009)

Monoclonal B-cell lymphocytosis (MBL) indicates the presence of less than 5 x 10(9)/L circulating monoclonal B cells in otherwise healthy subjects. Recently, it has been reported that circulating chronic lymphocytic leukemia (CLL)-like B cells can be detected using 4- or 5-multicolor flow cytometry in 5% to 7% of adults with normal lymphocyte counts. We investigated the frequency of circulating monoclonal B cells in 608 healthy subjects older than 40 years with normal blood counts, using a highly sensitive 8-color flow cytometry approach and systematic screening for total PB leukocyte count higher than 5 x 10(6). We show that the frequency of PB monoclonal B cells is markedly higher than previously reported (12% for CLL-like B cells, found at frequencies of 0.17 +/- 0.13 x 10(9) cells/L), the incidence progressively increasing with age. Most cases (62%) showed clonal B-cell levels below the maximum sensitivity of the techniques described by others (< 0.01%), supporting the notion that detection of MBL may largely depend on the sensitivity of the flow cytometry approach used.
The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney (2005)

It is generally accepted that iron homeostasis is mainly controlled in the gastrointestinal tract by absorption of dietary iron. However, recent studies have shown that the kidneys are also involved in iron metabolism. Since the iron-regulatory and antimicrobial peptide hormone hepcidin was originally isolated from human urine we have investigated the expression as well as the zonal and cellular localization of hepcidin in the mammalian kidney and developed an ELISA assay to analyze hepcidin concentrations in serum and urine. The expression of hepcidin was shown by RT-PCR and immunoblot experiments; its cellular localization was studied by immunocytochemistry in human, mouse and rat kidney, which revealed similar patterns of immunoreactivity. Hepcidin expression was absent from the proximal tubule and descending and ascending thin limbs. There was strong expression in the thick ascending limb of the cortex and in connecting tubules. Moderate expression was noted in the thick ascending limb and collecting ducts of the medulla and in collecting ducts of the papilla. Importantly, the cells of the macula densa were unstained. At the cellular level, hepcidin was localized to the apical cell pole of the renal epithelial cells. Based on its presence in urine, hepcidin may be released apically into the urine. Enhanced levels of hepcidin were determined in patients with chronic renal insuffciency (156.8 ng/ml, controls 104.2 ng/ml) indicating that the kidneys may metabolize and/or eliminate the circulating peptide. From the expression of hepcidin in the mammalian kidney, we have concluded that the iron-regulatory hormone is an intrinsic renal peptide which is not only eliminated by the kidney but is also synthesized in the kidney tubular system. Localization of hepcidin in the kidney implicates an iron-regulatory role of this peptide hormone in the renal tubular system, possibly in connection with the iron transporter divalent metal transporter-1.
Blue light generated by frequency doubling of laser diode light in a lithium niobate channel waveguide (1989)

Blue light was generated in a LiNbO/sub 3/ channel waveguide by frequency doubling radiation from a laser diode in a guided to guided wave interaction, utilizing first-order quasi-phase-matching in a periodically domain inverted structure. A fabrication method that does not depend on the use of titanium was used. A periodic pattern of silicon oxide on the positive c-face of LiNbO/sub 3/ was used in combination with a heat treatment to achieve a periodic outdiffusion and domain reversal in the surface layer. A channel guide was subsequently formed by proton exchange.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Assessment of renal oxygenation during partial nephrectomy using DLP hyperspectral imaging (2011)

Digital Light Processing (DLP&reg;) hyperspectral imaging (HsI) is a non-invasive method used to construct a highly sensitive, real-time tissue oxygenation map through the measurement of the percentage of oxyhemoglobin. We have demonstrated that this technology can detect the oxyhemoglobin in the blood vessels on the surface of the kidney and we have used this to monitor renal perfusion during kidney cancer operations, where the blood supply to the kidney is interrupted for a period of time. This technology may allow us to "personalize" surgery based on the oxygenation profile.
Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with aHeterologous Trimerization Motif: Characterization and Ligand Binding Analysis (2005)

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, mediates binding to the viral receptors and, along with the transmembrane glycoprotein gp41, is a major target for neutralizing antibodies. We asked whether replacing the gp41 fusion/trimerization domain with a stable trimerization motif might lead to a more stable gp120 trimer that would be amenable to structural and immunologic analysis. To obtain stable gp120 trimers, a heterologous trimerization motif, GCN4, was appended to the C terminus of YU2gp120. Biochemical analysis indicated that the gp120-GCN4 trimers were superior to gp140 molecules in their initial homogeneity, and trilobed structures were observable by electron microscopy. Biophysical analysis of gp120-GCN4 trimers by isothermal titration calorimetry (ITC) and ultracentrifugation analyses indicated that most likely two molecules of soluble CD4 could bind to one gp120-GCN4 trimer. To further examine restricted CD4 stoichiometric binding to the gp120-GCN4 trimers, we generated a low-affinity CD4 binding trimer by introducing a D457V change in the CD4 binding site of each gp120 monomeric subunit. The mutant trimers could definitively bind only one soluble CD4 molecule, as determined by ITC and sedimentation equilibrium centrifugation. These data indicate that there are weak interactions between the gp120 monomeric subunits of the GCN4-stabilized trimers that can be detected by low-affinity ligand sensing. By similar analysis, we also determined that removal of the variable loops V1, V2, and V3 in the context of the gp120-GCN4 proteins allowed the binding of three CD4 molecules per trimer. Interestingly, both the gp120-GCN4 variants displayed a restricted stoichiometry for the CD4-induced antibody 17b of one antibody molecule binding per trimer. This restriction was not evident upon removal of the variable loops V1 and V2 loops, consistent with conformational constraints in the wild-type gp120 trimers and similar to those inherent in the functional Env spike. Thus, the gp120-GCN4 trimers demonstrate several properties that are consistent with some of those anticipated for gp120 in the context of the viral spike.
The Mechanism of Superantigen-Mediated Toxic Shock: Not a Simple Th1 Cytokine Storm (2005)

The profound clinical consequences of Gram-positive toxic shock are hypothesized to stem from excessive Th1 responses to superantigens. We used a new superantigen-sensitive transgenic model to explore the role of TCRalphabeta T cells in responses to staphylococcal enterotoxin B (SEB) in vitro and in two different in vivo models. The proliferative and cytokine responses of HLA-DR1 spleen cells were 100-fold more sensitive than controls and were entirely dependent on TCRalphabeta T cells. HLA-DR1 mice showed greater sensitivity in vivo to two doses of SEB with higher mortality and serum cytokines than controls. When d-galactosamine was used as a sensitizing agent with a single dose of SEB, HLA-DR1 mice died of toxic shock whereas controls did not. In this sensitized model of toxic shock there was a biphasic release of cytokines, including TNF-alpha, at 2 h and before death at 7 h. In both models, mortality and cytokine release at both time points were dependent on TCRalphabeta T cells. Anti-TNF-alpha pretreatment was protective against shock whereas anti-IFN gamma pretreatment and delayed anti-TNF-alpha treatment were not. Importantly, anti-TNF-alpha pretreatment inhibited the early TNF-alpha response but did not inhibit the later TNF-alpha burst, to which mortality has previously been attributed. Splenic T cells were shown definitively to be the major source of TNF-alpha during the acute cytokine response. Our results demonstrate unequivocally that TCRalphabeta T cells are critical for lethality in toxic shock but it is the early TNF-alpha response and not the later cytokine surge that mediates lethal shock.
The Anticoagulant Effects of the Hookworm, Ancylostoma ceylanicum: Observations on Human and Dog Blood In Vitro and Infected Dogs In Vivo (1984)

Extracts of adult Ancylostoma ceylanicum prolonged the prothrombin time (PT) and partial thromboplastin time with kaolin ( PPTK ) of both human and dog plasmas in vitro. Excretory/secretory (E/S) products of these worms had similar effects while larval extract prolonged the PTTK only. Thus, the anticoagulant activities of this parasite are dependent upon the stage of the worm's life cycle. Collagen- and ADP-induced platelet aggregation were inhibited by adult and larval extracts. When the peripheral blood and bleeding times of dogs with varying worm burdens were examined, the only abnormality was shortening of the PTTK in the most heavily infected animals. Homogenates of dog small bowel subjacent to adult hookworms prolonged the PT of dog plasma and electron microscopical examination of this tissue revealed aggregation of platelets in blood venules without fibrin deposition. Thus, this study provides evidence that the anticoagulant properties of hookworms may have biological significance in infected animals.
Prediction of powder particle size during centrifugal atomisation using a rotating disk (2007)

The centrifugal atomisation of metallic melts using a rotating disk is an important process for powder production and spray deposition. The theoretical prediction of powder particle size is desirable for the design of atomisers. In this paper, wave theory was applied to analyse the disintegration of metallic melts in the film disintegration regime during centrifugal atomisation using a rotating disk. A mathematical model was proposed to predict the spray parameters. The governing equation for the fastest-growing wave number was developed and solved numerically. The effect of the variation in film thickness during film extension was taken into account. Film length and powder particle size were calculated and compared with available experimental data in the literature, and a good agreement was achieved. The influence of the break-up parameter was studied, and it is shown that the break-up parameter is not sensitive to the predicted powder particle size. Both simulated results and experimental data showed that fine powders can be produced by increasing disk speed.
Multiplex polymerase chain reaction: A practical approach (2002)

Considerable time and effort can be saved by simultaneously amplifying multiple sequences in a single reaction, a process referred to as multiplex polymerase chain reaction (PCR). Multiplex PCR requires that primers lead to amplification of unique regions of DNA, both in individual pairs and in combinations of many primers, under a single set of reaction conditions. In addition, methods must be available for the analysis of each individual amplification product from the mixture of all the products. Multiplex PCR is becoming a rapid and convenient screening assay in both the clinical and the research laboratory. The development of an efficient multiplex PCR usually requires strategic planning and multiple attempts to optimize reaction conditions. For a successful multiplex PCR assay, the relative concentration of the primers, concentration of the PCR buffer, balance between the magnesium chloride and deoxynucleotide concentrations, cycling temperatures, and amount of template DNA and Taq DNA polymerase are important. An optimal combination of annealing temperature and buffer concentration is essential in multiplex PCR to obtain highly specific amplification products. Magnesium chloride concentration needs only to be proportional to the amount of dNTP, while adjusting primer concentration for each target sequence is also essential. The list of various factors that can influence the reaction is by no means complete. Optimization of the parameters discussed in the present review should provide a practical approach toward resolving the common problems encountered in multiplex PCR (such as spurious amplification products, uneven or no amplification of some target sequences, and difficulties in reproducing some results). Thorough evaluation and validation of new multiplex PCR procedures is essential. The sensitivity and specificity must be thoroughly evaluated using standardized purified nucleic acids. Where available, full use should be made of external and internal quality controls, which must be rigorously applied. As the number of microbial agents detectable by PCR increases, it will become highly desirable for practical purposes to achieve simultaneous detection of multiple agents that cause similar or identical clinical syndromes and/or share similar epidemiological features.
The Function of GRB2 in Linking the Insulin Receptor to Ras Signaling Pathways (1993)

Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. Moreover, a dominant negative form of Ras (with Ser17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways.