gebhart/patrepeval huggingface dataset:
Cancerous Inhibitor of Protein Phosphatase 2A, an Emerging Human Oncoprotein and a Potential Cancer Therapy Target (2013)

Protein phosphatase 2A (PP2A) complexes function as tumor suppressors by inhibiting the activity of several critical oncogenic signaling pathways. Consequently, inhibition of the PP2A phosphatase activity is one of many prerequisites for the transformation of normal human cells into cancerous cells. However, mechanisms for PP2A inactivation in human cancers are poorly understood. The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified endogenous PP2A inhibitor in malignant cells, is one such mechanism. Various independent studies have validated CIP2A's role in promoting tumor growth and resistance to apoptosis and senescence-inducing therapies. Notably, high CIP2A expression predicts poor patient prognosis in several human cancer types. Among the oncogenic proteins dephosphorylated by PP2A, the MYC oncoprotein, which is phosphorylated at serine 62, has surfaced as a marker for the oncogenic activity of CIP2A. The positive-feedback loop between CIP2A and MYC augments the activity of MYC in cancer cells. In addition, CIP2A promotes the phosphorylation and activity of additional oncoproteins, including E2F1 and AKT. However, CIP2A is not essential for normal mouse growth and development. These findings indicate that CIP2A is a novel anticancer target based on PP2A reactivation and inhibition of the oncogenic activity of its downstream effectors. The potential approaches and feasibility of targeting CIP2A are discussed here.
Basic Terminology of Stereochemistry (2016)

This is a glossary of the more important, and most widely-used, stereochemical terms. It extends the list of those defined in the IUPAC Nomenclature of Organic Chemistry, Section E: Stereochemistry (Recommendations 1974)[1.] and includes some terms from the Glossary of Terms used in Physical Organic Chemistry (Recommendations 1994).[4.] Additional terms have been added from inorganic and macromolecular chemistry. Some misleading terms are included together with guidance on correct usage or acceptable alternatives.
Suppression of Clostridium difficile by Normal Hamster Cecal Flora and Prevention of Antibiotic-Associated Cecitis (1981)

Administration of normal cecal homogenates decreased numbers of viable Clostridium difficile and prevented cecitis in antibiotic-challenged hamsters. Cecal anaerobes appeared to suppress C. difficile.
Resurgent Vector-Borne Diseases as a Global Health Problem (1998)

Vector-borne infectious diseases are emerging or resurging as a result of changes in public health policy, insecticide and drug resistance, shift in emphasis from prevention to emergency response, demographic and societal changes, and genetic changes in pathogens. Effective prevention strategies can reverse this trend. Research on vaccines, environmentally safe insecticides, alternative approaches to vector control, and training programs for health-care workers are needed.
A multi‐scale method for automatic correction of intensity non‐uniformity in MR images (2001)

In this paper, a novel multi-scale method for coil sensitivity profile correction is presented based on wavelet transform. A magnetic resonance (MR) image can be decomposed into two spaces by the wavelet transform: approximate space and residual space. The approximate templates in approximate space can be thought of as multi-scale sensitivity profiles of the surface coil for coil correction. When we choose a suitable filter for decomposition, one of the sensitivity profiles should be optimal among the multi-scale sensitivity profiles. The optimal sensitivity profile can be chosen automatically by an analysis of the contents of the two spaces. The multi-scale method does not rely on any data other than the image generated by the MR scanner. The experiment showed promising results based on one-dimensional simulation and images of phantom and human images.
FLAVOR VOLATILES OF SOME COOKED VEGETABLES (1970)

SUMMARY– Using previously described sampling techniques, the flavor volatiles of a number of cooked vegetables were collected and analyzed by gas chromatography. The vegetables investigated were Brussels sprouts, cauliflower and runner beans and, in addition to the fresh vegetables, some preserved samples were examined. Quantitative measurements were made of the individual flavor components and the results were compared with those for fresh cabbage.
Design and experimental results of a 2V-operation single-chip GaAs T/R-MMIC front-end for 1.9-GHz personal communications (2002)

Design and experimental results of a 2-V operation single-chip GaAs T/R-MMIC front-end are described for 1.9-GHz personal communication terminals. This chip, fabricated with planar self-aligned gate FET process useful for low-cost and high-volume production, integrates RF front-end analog circuits-a power amplifier, a T/R-switch, and a low-noise amplifier. Additionally integrated are a newly designed voltage doubler-negative voltage generator (VDNVG) and a control logic circuit to control transmit and receive functions. The chip is capable of delivering 21-dBm output power at 39 % efficiency with 2-V single power supply in transmit mode. By utilizing up-voltage and negative voltages generated from the generator, the new interface circuit enables the switch to handle high power outputs over 24 dBm with 0.55-dB insertion loss.
Increased Persistence in Escherichia coli Caused by Controlled Expression of Toxins or Other Unrelated Proteins (2006)

Bacterial populations contain persisters, cells which survive exposure to bactericidal antibiotics and other lethal factors. Persisters do not have a genetic resistance mechanism, and their means to tolerate killing remain unknown. In exponentially growing populations of Escherichia coli the frequency of persister formation usually is 10(-7) to 10(-5). It has been shown that cells overexpressing either of the toxic proteins HipA and RelE, both members of the bacterial toxin-antitoxin (TA) modules, have the ability to form more persisters, suggesting a specific role for these toxins in the mechanism of persistence. However, here we show that cells expressing proteins that are unrelated to TA modules but which become toxic when ectopically expressed, chaperone DnaJ and protein PmrC of Salmonella enterica, also form 100- to 1,000-fold more persisters. Thus, persistence is linked not only to toxicity caused by expression of HipA or dedicated toxins but also to expression of other unrelated proteins.
Vasopressin and terlipressin: pharmacology and its clinical relevance (2004)

Vasopressin and its analogue, terlipressin, are potent vasopressors that may be useful therapeutic agents in the treatment of cardiac arrest, septic and catecholamine-resistant shock and oesophageal variceal haemorrhage. The aim of this article is to review the physiology and pharmacology of vasopressin and summarise its efficacy and safety in clinical trials and its subsequent therapeutic use. Recent studies indicate that the use of vasopressin during cardiopulmonary resuscitation may improve the survival of patients with asystolic cardiac arrest. Vasopressin deficiency can contribute to refractory shock states associated with sepsis, cardiogenic shock and cardiac arrest. Low doses of vasopressin and terlipressin can restore vasomotor tone in conditions that are resistant to catecholamines, with preservation of renal blood flow and urine output. They are also useful in reducing bleeding and mortality associated with oesophageal variceal haemorrhage. The long-term outcome of the use of these drugs is not known.
Fabrication of Nanopores in Silicon Chips Using Feedback Chemical Etching (2006)

Silicon nanopores (see image) are fabricated by feedback chemical etching. The electric current through a silicon chip separating a standard buffer from an etchant is monitored in the etching process such that the size of the nanopore can be controlled. This approach offers a simple method of fabricating solid-state nanopores for detecting and characterizing biomolecules. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2296/2007/z600268_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Memory of Extracellular Adenosine A2A Purinergic Receptor-mediated Signaling in Murine T Cells (1997)

Accumulation of extracellular and intracellular adenosine (Ado) under hypoxic conditions or in the absence of adenosine deaminase results in lymphocyte depletion and in severe combined immunodeficiency, which are currently explained by direct intracellular lymphotoxicity of Ado metabolites. In support of the alternative, "signaling" mechanism, we show that extracellular Ado (extAdo) suppresses all tested T cell receptor (TCR)-triggered effector functions of T lymphocytes including the TCR-triggered FasL mRNA up-regulation in cytotoxic T lymphocytes. Strong evidence against the intracellular lymphotoxicity of Ado (and in support of the signaling model) is provided by abrogation of TCR-triggered growth inhibition in Ado-exposed T cells. The brief exposure to Ado was sufficient to observe inhibition of TCR-triggered effector functions. The "memory" of T cells to exposure to extAdo is best explained by sustained increases in cAMP. Selective agonist (CGS21680) and antagonist (ZM241385) of A2A adenosine receptor were used in functional assays and cDNA probes for different sybtypes of adenosine receptors were used in Northern blot studies. A2A receptors are identified as the predominantly expressed subtype of Gs-coupled Ado receptors in T cells. The demonstration of cross-talk between the A2A receptors and TCR in both directions support the possible role of A2A receptors in mechanisms of extAdo-mediated immunosuppression in vivo under adenosine deaminase deficiency and hypoxic conditions in, e.g., solid tumors.
Treatment of experimental canine endotoxin shock with ibuprofen, a cyclooxygenase inhibitor. (1984)

The arachidonic acid derivative thromboxane A2, a very potent platelet aggregator, is increased in endotoxin shock. Ibuprofen blocks the formation of thromboxane A2 and has antiplatelet and antileukocyte aggregability properties. The effects of ibuprofen on pulmonary platelet trapping, platelet and leukocyte counts, platelet aggregability, hematocrit, and blood pressure were evaluated in endotoxin-shocked dogs. The initial decrease in blood pressure and in leukocyte and platelet counts seen in endotoxin shock was not altered by ibuprofen treatment. At 2 h the ibuprofen-treated dogs had less hypotension compared to endotoxin control. Platelet counts were also higher in the ibuprofen-treated dogs at 2 h. Significant recovery of leukocytes was seen only when pretreatment was used. Pulmonary platelet trapping was significantly lower in the ibuprofen-treated dogs compared to endotoxin controls and not significantly different from the sham dogs when ibuprofen was given before endotoxin injection. This study demonstrates the efficacy of ibuprofen not only in reducing pulmonary platelet trapping but also in obviating the late hypotension in experimental endotoxin shock.
Pressure-Induced Amorphization and Negative Thermal Expansion in ZrW 2 O 8 (1998)

It has recently been shown that zirconium tungstate (ZrW2O8) exhibits isotropic negative thermal expansion over its entire temperature range of stability. This rather unusual behavior makes this compound particularly suitable for testing model predictions of a connection between negative thermal expansion and pressure-induced amorphization. High-pressure x-ray diffraction and Raman scattering experiments showed that ZrW2O8 becomes progressively amorphous from 1.5 to 3.5 gigapascals. The amorphous phase was retained after pressure release, but the original crystalline phase returned after annealing at 923 kelvin. The results indicate a general trend between negative thermal expansion and pressure-induced amorphization in highly flexible framework structures.
Stochastic Pooling for Regularization of Deep Convolutional Neural Networks (2013)

We introduce a simple and effective method for regularizing large convolutional neural networks. We replace the conventional deterministic pooling operations with a stochastic procedure, randomly picking the activation within each pooling region according to a multinomial distribution, given by the activities within the pooling region. The approach is hyper-parameter free and can be combined with other regularization approaches, such as dropout and data augmentation. We achieve state-of-the-art performance on four image datasets, relative to other approaches that do not utilize data augmentation.
Design of a Long-Acting and Selective MEG-Fatty Acid Stapled Prolactin-Releasing Peptide Analog (2019)

Anorexigenic peptides offer promise as potential therapies targeting the escalating global obesity epidemic. Prolactin-releasing peptide (PrRP), a novel member of the RFamide family secreted by the hypothalamus, shows therapeutic potential by decreasing food intake and body weight in rodent models via GPR10 activation. Here we describe the design of a long-acting PrRP using our recently developed novel multiple ethylene glycol-fatty acid (MEG-FA) stapling platform. By incorporating serum albumin binding fatty acids onto a covalent side chain staple, we have generated a series of MEG-FA stapled PrRP analogs with enhanced serum stability and <i>in vivo</i> half-life. Our lead compound <b>18-S4</b> exhibits good <i>in vitro</i> potency and selectivity against GPR10, improved serum stability, and extended <i>in vivo</i> half-life (7.8 h) in mouse. Furthermore, <b>18-S4</b> demonstrates a potent body weight reduction effect in a diet-induced obesity (DIO) mouse model, representing a promising long-acting PrRP analog for further evaluation in the chronic obesity setting.
Potassium channels: Gene family, therapeutic relevance, high-throughput screening technologies and drug discovery (2002)

Existing drugs that modulate ion channels represent a key class of pharmaceutical agents across many therapeutic areas and there is considerable further potential for potassium channel drug discovery. Potassium channels represent the largest and most diverse sub-group of ion channels and they play a central role in regulating the membrane potential of cells. Recent advances in genomics have greatly added to the number of these potential drug targets, but selecting a suitable potassium channel for drug discovery research is a key step. In particular, the potential therapeutic relevance of a potassium channel should be taken into account when selecting a target for screening. Potassium channel drug discovery is being driven by a need to identify lead compounds that can provide tractable starting points for medicinal chemistry. Furthermore, advances in laboratory automation have brought significant opportunities to increase screening throughput for potassium channel assays, but careful assay configuration to model drug-target interactions in a physiological manner is an essential consideration. Several potassium channel screening platforms are described in this review in order to provide some insight into the variety of formats available for screening, together with some of their inherent advantages and limitations. Particular emphasis is placed on the mechanistic basis of drug-target interaction and those aspects of structure/function that are of prime importance in potassium channel drug discovery.
Computation of the binding of fully flexible peptides to proteins with flexible side chains (1997)

Docking algorithms play an important role in the process of rational drug design and in understanding the mechanism of molecular recognition. An important determinant for successful docking is the extent to which the configurational space (including conformational changes) of the ligand/receptor system is searched. Here we describe a new, combinatorial method for flexible docking of peptides to proteins that allows full rotation around all single bonds of the peptide ligand and around those of a large set of receptor side chains. We have simulated the binding of several viral peptides to murine major histocompatibility complex class I H-2Kb. In addition, we have explored the limits of our method by simulating a complex between calmodulin and an 18-residue long helical peptide from calmodulin-dependent protein kinase IIalpha. The calculated peptide conformations generally matched well with the X-ray structures. Essential information about local flexibility and about residues that are responsible for strong binding was obtained. We have frequently observed considerable side-chain flexibility during the simulations, showing the need for a flexible treatment of the receptor. Our method may also be useful whenever the receptor side-chain conformation is not available or uncertain, as illustrated by the docking of an H-2Kb binding nonapeptide to the receptor structure taken from an octapeptide/H-2Kb complex.
pplacer: linear time maximum-likelihood and Bayesian phylogenetic placement of sequences onto a fixed reference tree (2010)

Pplacer enables efficient phylogenetic placement and subsequent visualization, making likelihood-based phylogenetics methodology practical for large collections of reads; it is freely available as source code, binaries, and a web service.
Energetic Fitness of Histidine Protonation States in PDB Structures (2004)

The energetic fitness of histidine in each of its three protonation states has been investigated for NMR-determined protein structures by using molecular mechanics calculations. The protein structures have been taken from the Protein Data Bank (PDB). For the proteins in the database, we generated all isomers, considering all combinations of protonation forms of each histidine. The energy of each isomer has been determined by conjugate gradient minimization using a well-established all-atom force field. We find that, in general, the isomer reported in the PDB is not the most stable isomer. The statistical distribution of isomer energies minus that of the PDB isomer behaves as though the sequence of the histidine forms reported in the PDB was chosen at random. We also show that our molecular mechanics method is a valid approach to predicting the protonation state of histidines buried in the protein core.
Local macrophage proliferation correlates with increased renal M‐CSF expression in human glomerulonephritis (2001)

Glomerular and tubulointerstitial M-CSF expression is up-regulated in human glomerulonephritis, being most prominent in proliferative forms of disease. This correlated with local macrophage proliferation, suggesting that increased renal M-CSF production plays an important role in regulating local macrophage proliferation in human glomerulonephritis.
Pancreatic cancer and FOLFIRINOX: a new era and new questions (2015)

FOLFIRINOX (FFX) was introduced to clinical practice in 2010 following publication of the PRODIGE 4/ACCORD 11 study, which compared this novel regimen to gemcitabine in metastatic pancreatic cancer. Median overall survival, progression-free survival, and objective responses were all superior with FFX and there was improved time to definitive deterioration in quality of life. Despite initial concerns over toxicity, there has been rapid uptake of this regimen, both revolutionizing management and opening the door to innovative research. As experience with FFX has accrued, many questions have arisen including the management of toxicities, the impact of frequent modifications, the optimal number of cycles, integration with other regimens and modalities, interpretation of radiologic and serologic response, utility of molecular signatures, and potential benefit in unique clinical settings such as pre- and postsurgery. This review will closely examine these issues, not only to summarize current knowledge but also to fuel scientific debate.
Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis (2011)

In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.
Stress relaxation in Si-rich silicon nitride thin films (1998)

Si-rich silicon nitride thin films have been deposited by low pressure chemical vapor deposition, at 850 °C from mixtures of dichlorosilane and ammonia. The films’ elastic properties have been studied as a function of film composition. Fourier transform infrared spectroscopy and ellipsometric data indicate that the local atomic strain is a strong function of the calculated volume fraction of Si contained in the films. A relationship is observed that shows the strain to be inversely proportional to the cube root of the Si volume fraction. A model that accounts for distortion in Si–SixN4−x tetrahedra (x=0–4), upon substitution of silicon for nitrogen in the film is applied to the data. The model is shown to be consistent with measurements of intrinsic film stress across a compositional range from stoichiometric silicon nitride, Si3N4, to nitrogen-free amorphous silicon, a-Si.
Further antigenic similarities of Neisseria gonorrhoeae lipooligosaccharides and human glycosphingolipids (1992)

Anticarbohydrate monoclonal antibodies were tested for their ability to bind to various strains of Neisseria. A monoclonal antibody that binds to the ganglio-series glycosphingolipid, ganglio-N-triaosylceramide, also bound to strains of Neisseria gonorrhoeae but not to other species of Neisseria. An antibody specific for the globo-series glycosphingolipid, globotriaosylceramide, also bound to strains of N. gonorrhoeae, Neisseria meningitidis, Neisseria lactamica, and Branhamella catarrhalis but not to any other strains of nonpathogenic Neisseria.
Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow (1992)

Colonies of CD1a+ HLA-DR+/DQ+ CD4+ cells with the functional and some of the structural attributes of Langerhans cells are observed in human bone marrow cultures in semi-solid media and are assumed to be the progeny of an early progenitor, the dendritic/Langerhans cell CFU (CFU-DL). The cytokine-regulated growth of these cells has been studied using a chemically defined serum-free system to culture both unfractionated and highly enriched bone marrow progenitor cell populations. Although unfractionated cell growth was optimal in serum replete cultures with PHA-stimulated leukocyte-conditioned medium (PHA-LCM) suboptimal proliferation of CFU-DL was observed in serum even in the absence of PHA-LCM. No colonies were observed under serum-free conditions when granulocyte-macrophage CSF (GM-CSF), IL-3, granulocyte CSF (G-CSF), and macrophage CSF (M-CSF) were present at levels optimal for granulocyte colony-forming unit (CFU-G) and macrophage colony-forming unit (CFU-M) growth. Addition of IL-1 alpha to these cytokines stimulated a small number of CFU-DL. However, in the presence of GM-CSF and IL-3, TNF-alpha or TNF-beta (5 U/ml) were both highly effective in promoting growth up to 82% of optimal and CFU-G growth was also enhanced at these concentrations. TNF was only active during the first 3 days of culture and higher concentrations of TNF-alpha but not TNF-beta were inhibitory for both CFU-DL and CFU-G. CD34+ cell-enriched populations were also enriched for both myeloid progenitors (CFU-G + CFU-M) and CFU-DL to 36- and 48-fold, respectively, and single cell cultures of CD34+ cells yielded single colonies containing both CD1a+ dendritic cells and CD1a- macrophages. Thus dendritic/Langerhans progenitors in the bone marrow expresses CD34, have a capacity for both macrophage and dendritic cell differentiation, and depend on hemopoietic growth factors and TNF for their further development in vitro.