gebhart/patrepeval huggingface dataset:
Long-Term Testosterone Gel (AndroGel) Treatment Maintains Beneficial Effects on Sexual Function and Mood, Lean and Fat Mass, and Bone Mineral Density in Hypogonadal Men (2004)

Transdermal testosterone (T) delivery represents an effective alternative to injectable androgens. We studied 163 hypogonadal men who applied 5, 7.5, or 10 g AndroGel (T gel) 1% CIII per day for up to 42 months. Efficacy data were presented in 123 subjects considered evaluable. Continuous AndroGel treatment normalized mean serum T and free T levels. Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased, mean serum estradiol/T ratio doubled, and mean serum FSH and LH levels were suppressed by T replacement. Sexual function and mood parameters improved rapidly and were maintained throughout T treatment. Lean body mass increased (P = 0.0001) and fat mass decreased (P = 0.0001), and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength. Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine (P = 0.0001) than the hip (P = 0.0004). Mild local skin irritation occurred in 12 subjects, resulting in discontinuation in only one subject. Except for the anticipated increase in hematocrit and hemoglobin, there were no clinically significant changes in blood counts or biochemistry. In three subjects with elevated serum prostate-specific antigen, prostate biopsies showed cancer. We conclude that continued application of AndroGel resulted in beneficial effects similar to those with injectables and other transdermal preparations. This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk. Thus, monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men.
Protective Effects of Sphingosine 1-Phosphate in Murine Endotoxin-induced Inflammatory Lung Injury (2004)

Our prior in vitro studies indicate that sphingosine 1-phosphate (S1P), a phospholipid angiogenic factor, produces endothelial cell barrier enhancement through ligation of endothelial differentiation gene family receptors. We hypothesized that S1P may reduce the vascular leak associated with acute lung injury and found that S1P infusion produced a rapid and significant reduction in lung weight gain (more than 50%) in the isolated perfused murine lung. The effect of S1P was next assessed in a murine model of LPS-mediated microvascular permeability and inflammation with marked increases in parameters of lung injury at both 6 and 24 hours after intratracheal LPS. Each parameter assessed was significantly reduced by intravenous S1P (1 microM final) and in selected experiments by the S1P analogue FTY720 (0.1 mg/kg, intraperitoneally) delivered 1 hour after LPS. S1P produced an approximately 40-50% reduction in LPS-mediated extravasation of Evans blue dye albumin, bronchoalveolar lavage protein content, and lung tissue myeloperoxidase activity (reflecting phagocyte infiltration). Consistent with systemic barrier enhancement, S1P significantly decreased Evans blue dye albumin extravasation and myeloperoxidase content in renal tissues of LPS-treated mice. These studies indicate that S1P significantly decreases pulmonary/renal vascular leakage and inflammation in a murine model of LPS-mediated acute lung injury and may represent a novel therapeutic strategy for vascular barrier dysfunction.
The effect of sodium ions on the electrical activity of the giant axon of the squid (1949)

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Bacterial Adaptation during Chronic Respiratory Infections (2015)

Chronic lung infections are associated with increased morbidity and mortality for individuals with underlying respiratory conditions such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The process of chronic colonisation allows pathogens to adapt over time to cope with changing selection pressures, co-infecting species and antimicrobial therapies. These adaptations can occur due to environmental pressures in the lung such as inflammatory responses, hypoxia, nutrient deficiency, osmolarity, low pH and antibiotic therapies. Phenotypic adaptations in bacterial pathogens from acute to chronic infection include, but are not limited to, antibiotic resistance, exopolysaccharide production (mucoidy), loss in motility, formation of small colony variants, increased mutation rate, quorum sensing and altered production of virulence factors associated with chronic infection. The evolution of Pseudomonas aeruginosa during chronic lung infection has been widely studied. More recently, the adaptations that other chronically colonising respiratory pathogens, including Staphylococcus aureus, Burkholderia cepacia complex and Haemophilus influenzae undergo during chronic infection have also been investigated. This review aims to examine the adaptations utilised by different bacterial pathogens to aid in their evolution from acute to chronic pathogens of the immunocompromised lung including CF and COPD.
Neutrophil Dysfunction in the Airways of Children with Acute Respiratory Failure Due to Lower Respiratory Tract Viral and Bacterial Coinfections (2019)

Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (ARDS) where they acquire an activated pro-survival phenotype with an enhanced respiratory burst thought to contribute to ARDS pathophysiology. Our in vitro model enables blood neutrophil transepithelial migration into cell-free tracheal aspirate fluid from patients to recapitulate the primary airway neutrophil phenotype observed in vivo. Neutrophils transmigrated through our model toward airway fluid from children with lower respiratory viral infections coinfected with bacteria had elevated levels of neutrophil activation markers but paradoxically exhibited an inability to kill bacteria and a defective respiratory burst compared with children without bacterial coinfection. The airway fluid from children with bacterial coinfections had higher levels of neutrophil elastase activity, as well as myeloperoxidase levels compared to children without bacterial coinfection. Neutrophils transmigrated into the aspirate fluid from children with bacterial coinfection showed decreased respiratory burst and killing activity against H. influenzae and S. aureus compared to those transmigrated into the aspirate fluid from children without bacterial coinfection. Use of a novel transmigration model recapitulates this pathological phenotype in vitro that would otherwise be impossible in a patient, opening avenues for future mechanistic and therapeutic research.
Malaria Vaccine Research (1994)

In our report "Activation of Raf as a result of recruitment to the plasma membrane" (3 June, p. 1463) (1), panels E and F of figure 1 on page 1464 were incorrect. The correct photographs appear below. In addition, the [See figure in the PDF file] second sentence of the legend to figure 1 should have read, "The Raf constructs were tagged at the COOH-terminus with a Glu-Glu epitope (MEYMPME) (24) for c-Raf, or at the NH(2)-terminus with both the Glu-Glu and the Myc (MEQKLISEEDL) (23) epitopes for RafCAAX"; the next-to-the-last sentence of the legend to figure 1 should have read, "The c-Raf constructs in (A through D) are Glu-Glu-tagged and were detected by using an anti Glu-Glu antibody, and the RafCAAX and Raf6QCAAX constructs used in E and F were detected by using the antibody to Raf COOH-terminal peptide"; and the third sentence of note 26 should have read, "After blocking with 5% milk in phosphate-buffered saline (M-PBS), cells were incubated with a mouse monoclonal antibody to Glu-Glu or a rabbit polyclonal antibody to a 20-amino acid COOH-terminal peptide of Raf-1 (Santa Cruz Biotechnology, Santa Cruz, California), washed, and incubated with donkey antibodies to mouse or rabbit IgG combined with Texas Red (Jackson) in M-PBS, washed, and mounted in FITC-Guard (Testog)."
Regulation of Vascular Smooth Muscle Cell Migration and Proliferation In Vitro and in Injured Rat Arteries by a Synthetic Matrix Metalloproteinase Inhibitor (1996)

Abstract Smooth muscle cell (SMC) migration and proliferation and extracellular matrix remodeling are essential aspects of the arterial response to injury, vessel development, and atherogenesis. Matrix metalloproteinase (MMP) expression is associated with SMC proliferation and migration after arterial injury. To assess the role of MMPs in SMC proliferation and migration and intimal thickening, we measured the effect of the synthetic MMP inhibitor BB94 (Batimastat) on DNA synthesis and migration of SMCs in vitro as well as the formation of a neointima after balloon injury to the rat carotid artery. BB94 dose-dependently inhibited SMC migration induced by platelet-derived growth factor (PDGF)–BB through a filter coated with a thick basement membrane matrix (Matrigel) layer but did not show any inhibitory effect on SMC migration through a lightly coated filter. At concentrations up to 1 μmol/L, BB94 did not alter DNA synthesis induced by PDGF-AA or PDGF-BB. Treatment with 30 mg BB94·kg −1 ·d −1 IP for 7 or 14 days after balloon injury to the rat carotid artery decreased the total number of intimal SMC nuclei and suppressed intimal thickening. SMC proliferation (5-bromo-2′-deoxyuridine labeling) was decreased in the media at 2 days, whereas it was increased in the intima at 7 but not 14 days. These results suggest that BB94 inhibits intimal thickening after arterial injury by decreasing SMC migration and proliferation and support the conclusion that MMPs play a significant role in regulating intimal thickening in injured arteries.
Utility of Immunohistochemistry in the Pancreatobiliary Tract (2014)

To better guide therapeutic decisions and predict the prognostic outcome, it is crucial to make an accurate diagnosis of a pancreatic neoplasm. Application of appropriate immunohistochemical panels enables pathologists to differentiate pancreaticobiliary adenocarcinomas from reactive conditions and to identify rare types of pancreatic neoplasms. Knowing the utilities and pitfalls of each tumor-associated biomarker is essential to avoiding a potential diagnostic error because an absolutely cancer-specific biomarker does not exist. This article reviews frequently used tumor-associated biomarkers, provides lists of effective immunohistochemical panels, and recommends a diagnostic algorithm as a standard approach to pancreatic neoplasms.
A cluster-based multiple deep neural networks method for large vocabulary continuous speech recognition (2013)

Recently a pre-trained context-dependent hybrid deep neural network (DNN) and HMM method has achieved significant performance gain in many large-scale automatic speech recognition (ASR) tasks. However, the error back-propagation (BP) algorithm for training neural networks is sequential in nature and is hard to parallelize into multiple computing threads. Therefore, training a deep neural network is extremely time-consuming even with a modern GPU board. In this paper we have proposed a new acoustic modelling framework to use multiple DNNs instead of a single DNN to compute the posterior probabilities of tied HMM states. In our method, all tied states of context-dependent HMMs are first grouped into several disjoined clusters based on the training data associated with these HMM states. Then, several hierarchically structured DNNs are trained separately for these disjoined clusters of data using multiple GPUs. In decoding, the final posterior probability of each tied HMM state can be calculated based on output posteriors from multiple DNNs. We have evaluated the proposed method on a 64-hour Mandarin transcription task and 309-hour Switchboard Hub5 task. Experimental results have shown that the new method using clusterbased multiple DNNs can achieve over 5 times reduction in total training time with only negligible performance degradation (about 1-2% in average) when using 3 or 4 GPUs respectively.
Mammalian Plasma Membrane Ecto-nucleoside Triphosphate Diphosphohydrolase 1, CD39, Is Not Active Intracellularly (2001)

CD39 is a member of the membrane-bound ecto-nucleoside triphosphate diphosphohydrolase family. The active site for native CD39 is located on the outer surface of the cellular plasma membrane; however, it is not yet known at what stage this enzyme becomes active along the secretory pathway to the plasma membrane. In this study, sucrose density fractionations performed on CD39-transfected COS-7 cell membranes suggest that CD39 activity resides primarily in the plasma membrane. Furthermore, we have created recombinant, soluble versions of CD39, one that is secreted and others that are retained in the endoplasmic reticulum, to demonstrate that CD39 is not active until it reaches the plasma membrane both in yeast and COS-7 cells. Moreover, the secreted active soluble CD39 in COS-7 cells is found to receive a higher degree of N-glycan addition than the inactive form retained intracellularly. When COS-7 cells were treated with tunicamycin to prevent N-glycosylation, soluble CD39 was not detected in the extracellular medium and remained inactive intracellularly. Surface biotinylation analysis also revealed that surface-expressed wild type CD39 receives a higher degree of N-glycosylation than intracellular forms and that inhibition of N-glycosylation prevents its plasma membrane localization. In addition, both intact and digitonin-permeablized COS-7 cells transfected with CD39 possess similar ecto-ATPase activities, further supporting the conclusion that only surface-expressed CD39 is enzymatically active. All of these data suggest that intracellular CD39 is inactive and that only a fully glycosylated CD39 has apyrase activity and is localized at the cell surface.
Sonic Hedgehog-induced Activation of the Gli1Promoter Is Mediated by GLI3 (1999)

Drosophila transcription factor cubitus interruptus (Ci) and its co-activator CRE (cAMP response element)-binding protein (CBP) activate a group of target genes on the anterior-posterior border in response to hedgehog protein (Hh) signaling. In the anterior region, in contrast, the carboxyl-truncated form of Ci generated by protein processing represses Hh expression. In vertebrates, three Ci-related transcription factors (glioblastoma gene products (GLIs) 1, 2, and 3) were identified, but their functional difference in Hh signal transduction is unknown. Here, we report distinct roles for GLI1 and GLI3 in Sonic hedgehog (Shh) signaling. GLI3 containing both repression and activation domains acts both as an activator and a repressor, as does Ci, whereas GLI1 contains only the activation domain. Consistent with this, GLI3, but not GLI1, is processed to generate the repressor form. Transcriptional co-activator CBP binds to GLI3, but not to GLI1. The trans-activating capacity of GLI3 is positively and negatively regulated by Shh and cAMP-dependent protein kinase, respectively, through a specific region of GLI3, which contains the CBP-binding domain and the phosphorylation sites of cAMP-dependent protein kinase. GLI3 directly binds to the Gli1 promoter and induces Gli1 transcription in response to Shh. Thus, GLI3 may act as a mediator of Shh signaling in the activation of the target gene Gli1.
Update : Recombinant Antibodies: From the Laboratory to the Clinic (2006)

The development of recombinant antibodies has facilitated the exploitation of the Ab-Ag interaction specificity for targeted therapies. A fully human antibody, with custom integrated designs, can be obtained in one-third the time, compared to development of antibodies by hybridoma technology. Recombinant antibodies can be tailored for specific applications, "armed" with cytotoxic agents in a controllable fashion, and used for extracellular and intracellular targeting. Multitargeted and combination therapies are rapidly evolving for the treatment of cancer. Antibody therapeutics, costly to develop and produce, have proven beneficial in the clinic.
Photo-Cross-Linking of Rabbit Skeletal Troponin I Deletion Mutants with Troponin C and Its Thiol Mutants:  The Inhibitory Region Enhances Binding of Troponin I Fragments to Troponin C (1996)

Contraction of vertebrate striated muscle is regulated by the strong Ca(2+)-dependent interaction between troponin I (TnI) and troponin C (TnC). To critically evaluate this interaction, we generated four recombinant deletion fragments of rabbit fast skeletal TnI: the NH2-terminal fragment (TnI1-94), the NH2 terminus and the inhibitory region (TnI1-120), the inhibitory region and the COOH terminus (TnI96-181), and the COOH-terminal fragment (TnI122-181) containing amino acid residues 1-94, 1-120, 96-181, and 122-181, respectively. Native TnC and seven thiol mutants, containing single cysteine residues in the two globular domains and in the central helix of TnC, e.g., Cys-12, Cys-21, Cys-57, Cys-89, Cys-122, Cys-133, and Cys-158, were labeled with 4-maleimidobenzophenone, and their interaction with the recombinant TnI fragments and the synthetic inhibitory peptide (TnI98-114, residues 98-114) was studied by photo-cross-linking. Extensive cross-linking occurred between various domains of TnC and TnI. The cross-linking patterns (a) showed that both NH2- and COOH-terminal fragments of TnI are accessible to both of the globular domains of TnC, (b) indicated that linkage of the NH2- and COOH-terminal sequences to the inhibitory region of TnI (TnIir) caused marked enhancement of cross-linking with native TnC and all seven thiol mutants, and (c) identified the region in TnC where TnIir binds as that containing residues 98, 133, 158, and 57. Thus, the results suggest that TnI and TnC may adopt flexible and dynamic conformations in which multiple interactions involving various domains of the two polypeptides occur and TnIir acting as a linker facilitates these interactions. The interaction of TnI and its fragments with actin, TnC, and TnT, considered together with the biological activity indicates that residues 96-120 represent a key structural and functional region of TnI. Whereas the NH2-terminal region of TnI stabilizes binding to TnC and TnT, the COOH-terminal region stabilizes TnC and actin binding.
Addressing noise decoupling in mixed-signal IC's: power distribution design and cell customization (1995)

An important and largely unexplored aspect of power distribution synthesis is cell customization. Through automatic cell customization, power I/O cell assignments and local substrate and power supply decoupling may be tailored to reduce deleterious noise effects on analog circuits in mixed-signal environments. Techniques for simultaneous power grid design (topology and sizing) and cell configuration/customization are described that allow designers to handle more difficult chip-level noise problems. Synthesis results on an industrial mixed-signal example demonstrate the effectiveness of this approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pulse Inhibition of Histone Deacetylases Induces Complete Resistance to Oxidative Death in Cortical Neurons without Toxicity and Reveals a Role for Cytoplasmic p21waf1/cip1in Cell Cycle-Independent Neuroprotection (2008)

Histone deacetylase (HDAC) inhibitors are currently in human clinical trials as antitumor drugs because of their ability to induce cell dysfunction and death in cancer cells. The toxic effects of HDAC inhibitors are also apparent in cortical neurons in vitro, despite the ability of these agents to induce significant protection in the cells they do not kill. Here we demonstrate that pulse exposure of cortical neurons (2 h) in an in vitro model of oxidative stress results in durable neuroprotection without toxicity. Protection was associated with transcriptional upregulation of the cell cycle inhibitor, p21(waf1/cip1), both in this model and in an in vivo model of permanent ischemia. Transgenic overexpression of p21(waf1/cip1) in neurons can mimic the protective effect of HDAC inhibitors against oxidative stress-induced toxicity, including death induced by glutathione depletion or peroxide addition. The protective effect of p21(waf1/cip1) in the context of oxidative stress appears to be unrelated to its ability to act in the nucleus to inhibit cell cycle progression. However, although p21(waf1/cip1) is sufficient for neuroprotection, it is not necessary for HDAC inhibitor neuroprotection, because these agents can completely protect neurons cultured from p21(waf1/cip1)-null mice. Together these findings demonstrate (1) that pulse inhibition of HDACs in cortical neurons can induce neuroprotection without apparent toxicity; (2) that p21(waf1/cip1) is sufficient but not necessary to mimic the protective effects of HDAC inhibition; and (3) that oxidative stress in this model induces neuronal cell death via cell cycle-independent pathways that can be inhibited by a cytosolic, noncanonical action of p21(waf1/cip1).
Querying structured text in an XML database (2003)

XML databases often contain documents comprising structured text. Therefore, it is important to integrate "information retrieval style" query evaluation, which is well-suited for natural language text, with standard "database style" query evaluation, which handles structured queries efficiently. Relevance scoring is central to information retrieval. In the case of XML, this operation becomes more complex because the data required for scoring could reside not directly in an element itself but also in its descendant elements.In this paper, we propose a bulk-algebra, TIX, and describe how it can be used as a basis for integrating information retrieval techniques into a standard pipelined database query evaluation engine. We develop new evaluation strategies essential to obtaining good performance, including a stack-based TermJoin algorithm for efficiently scoring composite elements. We report results from an extensive experimental evaluation, which show, among other things, that the new TermJoin access method outperforms a direct implementation of the same functionality using standard operators by a large factor.
Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells (2010)

Both innate and adaptive immune systems are considered important for cancer prevention, immunosurveillance, and control of cancer progression. It is known that, although both systems initially eliminate emerging tumor cells efficiently, tumors eventually escape immune attack by a variety of mechanisms, including differentiation and recruitment of immunosuppressive CD11b(+)Gr-1(+) myeloid suppressor cells into the tumor microenvironment. However, we show that CD11b(+)Gr-1(+) cells found in ascites of epithelial ovarian cancer-bearing mice at advanced stages of disease are immunostimulatory rather than being immunosuppressive. These cells consist of a homogenous population of cells that morphologically resemble neutrophils. Moreover, like dendritic cells, immunostimulatory CD11b(+)Gr-1(+) cells can strongly cross-prime, augmenting the proliferation of functional CTLs via signaling through the expression of costimulatory molecule CD80. Adoptive transfer of these immunostimulatory CD11b(+)Gr-1(+) cells from ascites of ovarian cancer-bearing mice results in the significant regression of s.c. tumors even without being pulsed with exogenous tumor Ag prior to adoptive transfer. We now show for the first time that adaptive immune responses against cancer can be augmented by these cancer-induced granulocyte-like immunostimulatory myeloid (CD11b(+)Gr-1(+)) cells, thereby mediating highly effective antitumor immunity in an adoptive transfer model of immunity.