gebhart/patrepeval huggingface dataset:
Broadband absolute absorption measurements of atmospheric continua with millimeter wave cavity ringdown spectroscopy (2005)

An instrument for the measurement of continua effects in the millimeter and submillimeter (a.k.a. terahertz) spectral region for mixtures of gases is described. In addition to their scientific interest, these continua are important because they contribute more than 50% of the opacity in the atmospheric windows important in remote sensing and communications. The instrument is based upon a fast scanning cavity ringdown approach that makes possible the measurement of continua and broad line absorptions at ∼6000 distinct cavity frequencies from 170to260GHz in ∼3s. The instrument’s 10m Fabry–Perot cavity (Q∼5×106) is in a chamber whose temperature can be controlled between −80 and +100°C and whose pressure can be varied between ∼10−5Torr and 10atm. The 3s scan results in statistical uncertainty in the absorptions of ∼2×10−7cm−1 at each of the 6000 frequencies. From these data an uncertainty of less than 1% for the weakest atmospheric continua (the dry air continuum) can be determined. For comparison, the continuum parameters that might be considered for inclusion in atmospheric remote sensing retrievals vary over a range of 10% to more than 50%. This uncertainty significantly impacts quality and validity of atmospheric retrievals from a variety of remote sensing platforms. While much lower statistical uncertainties are achievable with modest additional observation times, it is much more important that the near simultaneous measurements at many frequencies produce a data set that contains, without the use of parameters from other experiments, all of the required experimental information. This approach significantly reduces systematic effects and makes possible more realistic assessment of uncertainties.
A concrete security treatment of symmetric encryption (2002)

We study notions and schemes for symmetric (ie. private key) encryption in a concrete security framework. We give four different notions of security against chosen plaintext attack and analyze the concrete complexity of reductions among them, providing both upper and lower bounds, and obtaining tight relations. In this way we classify notions (even though polynomially reducible to each other) as stronger or weaker in terms of concrete security. Next we provide concrete security analyses of methods to encrypt using a block cipher, including the most popular encryption method, CBC. We establish tight bounds (meaning matching upper bounds and attacks) on the success of adversaries as a function of their resources.
TRPA1: A Gatekeeper for Inflammation (2012)

Tissue damage evokes an inflammatory response that promotes the removal of harmful stimuli, tissue repair, and protective behaviors to prevent further damage and encourage healing. However, inflammation may outlive its usefulness and become chronic. Chronic inflammation can lead to a host of diseases, including asthma, itch, rheumatoid arthritis, and colitis. Primary afferent sensory neurons that innervate target organs release inflammatory neuropeptides in the local area of tissue damage to promote vascular leakage, the recruitment of immune cells, and hypersensitivity to mechanical and thermal stimuli. TRPA1 channels are required for neuronal excitation, the release of inflammatory neuropeptides, and subsequent pain hypersensitivity. TRPA1 is also activated by the release of inflammatory agents from nonneuronal cells in the area of tissue injury or disease. This dual function of TRPA1 as a detector and instigator of inflammatory agents makes TRPA1 a gatekeeper of chronic inflammatory disorders of the skin, airways, and gastrointestinal tract.
Regulation of drug release from polymer matrices by oscillating magnetic fields (1985)

The reproducible regulation of release of a macromolecule (bovine serum albumin) from biocompatible polymer systems has been demonstrated. Small magnetic spheres or cylindrical magnets were embedded within the polymer matrix which was then subjected to an oscillating magnetic field. In this fashion baseline release rates could be increased 5- to 10-fold with 5-10% standard error. Parameters critical to the regulation of this release included the position, orientation, and magnetic strength of the embedded objects and the amplitude and frequency of the applied magnetic field. Scanning electronmicrographs of the polymer matrix surface reveal that a gap, approximately 100/microns wide, is formed between the embedded object and adjacent polymer material after repeated exposure to an oscillating magnetic field.
Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways fromDrosophilato vertebrates (2005)

Although the framework of the Hedgehog (Hh) signaling pathway is evolutionarily conserved, recent studies indicate that fundamental differences exist between Drosophila and vertebrates in the way signals are transduced from the membrane protein Smoothened (Smo) to the Ci/Gli transcription factors. For example, Smo structure and the roles of fused and Suppressor of fused have diverged. Recently, many vertebrate-specific components have been identified that act between Smo and Gli. These include intra-flagellar transport proteins, which link vertebrate Hh signaling to cilia. Because abnormal Hh signaling can cause birth defects and cancer, these vertebrate-specific components may have roles in human health.
IL-2 Immunotoxin Therapy Modulates Tumor-Associated Regulatory T Cells and Leads to Lasting Immune-Mediated Rejection of Breast Cancers in neu -Transgenic Mice (2006)

Studies in cancer patients have suggested that breast tumors recruit regulatory T cells (Tregs) into the tumor microenvironment. The extent to which local Tregs suppress antitumor immunity in breast cancer is unknown. We questioned whether inhibiting systemic Tregs with an IL-2 immunotoxin in a model of neu-mediated breast cancer, the neu-transgenic mouse, could impact disease progression and survival. As in human breast cancer, cancers that develop in these mice attract Tregs into the tumor microenvironment to levels of approximately 10-25% of the total CD4+ T cells. To examine the role of Tregs in blocking immune-mediated rejection of tumor, we depleted CD4+CD25+ T cells with an IL-2 immunotoxin. The treatment depleted Tregs without concomitant lymphopenia and markedly inhibited tumor growth. Depletion of Tregs resulted in a persistent antitumor response that was maintained over a month after the last treatment. The clinical response was immune-mediated because adoptive transfer of Tregs led to a complete abrogation of the therapeutic effects of immunotoxin treatment. Further, Treg down-modulation was accompanied by increased Ag-specific immunity against the neu protein, a self Ag. These results suggest that Tregs play a major role in preventing an effective endogenous immune response against breast cancer and that depletion of Tregs, without any additional immunotherapy, may mediate a significant antitumor response.
Vagal, sympathetic and somatic sensory inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys (1996)

1. Myocardial ischemia activates vagal and sympathetic cardiac afferent fibers. The purpose of this study was to determine a neuro physiological basis for cardiac pain referred to C1-C3 somatic dermatomes. We hypothesized that afferent fibers traveling in vagal or sympathetic nerves transmit nociceptive information to C1-C3 spinothalamic tract (STT) neurons. 2. Electrical stimulation of the left stellate ganglion to excite cardiopulmonary sympathetic afferent fibers increased extracellular activity of 44 of 77 C1-C3 STT neurons examined in 33 anesthetized male monkeys (Macaca fascicularis); responses increased as stimulus strength increased. Additionally, this stimulus inhibited 5 cells, increased/decreased activity of 2 cells, and did not affect 26 cells. 3. Electrical stimulation of the left (ipsilateral) thoracic vagus nerve excited 41 of 78 C1-C3 STT neurons, inhibited 4 neurons, increased/decreased activity of 2 neurons, and did not affect 31 neurons. Responses increased with increasing stimulus strength Contralateral vagal stimulation excited 7 of 39 cells tested, inhibited 4 cells and did not affect 28 cells. 4. Effects of stimulating one or more vagal branches were examined on 22 C1-C3 STT neurons excited by input from left thoracic vagus nerve. Stimulation of the cardiac branch excited 11 of 16 cells tested; stimulation of the recurrent laryngeal nerve excited 11 of 18 cells; stimulation of vagal fibers just rostral to the diaphragm excited 8 of 19 cells. 5. Excitatory somatic receptive fields ranged from small ipsilateral fields to large, sometimes bilateral or noncontinuous fields. Many fields included the ipsilateral neck and/or inferior jaw. Thirty-nine of 74 neurons examined were wide dynamic range (WDR), 21 were high threshold (HT), 6 were low threshold (LT), and 8 did not respond to brushing or noxious pinching of somatic tissues. Most (38 of 39) WDR cells responded to stimulation of the stellate ganglion or vagal fibers, as did 18 of 21 HT cells, 3 of 6 LT cells, and 2 of 8 cells unresponsive to brush or pinch stimuli. 6. Results of this study supported the concept that vagal and/ or sympathetic afferent activation of C1-C3 STT neurons might provide a neural mechanism for referred pain that originates in the heart or other visceral organs but is perceived in the neck and jaw region. Additionally, C1-C3 STT neurons processed sensory information from widespread regions of the body.
Intrathecal Interferon in Multiple Sclerosis (1982)

Human fibroblast interferon (IFN-beta) was administered by serial lumbar puncture to ten patients with multiple sclerosis (MS). Their clinical courses were compared with those of ten MS control patients who did not receive IFN-beta. As of this writing, the recipients have been followed up for 1.8 to 2.0 years (mean, 1.9 years), and the controls for 1.5 to 1.7 years (mean, 1.6 years). During the study, two recipients suffered four exacerbations, and six controls suffered 11 exacerbations. The recipients' rates of exacerbation during the study were significantly less than their rates both for the entire prestudy duration of the disease and for the 1.8 to 2.0 years immediately preceding entry into the study. The controls' rates of exacerbation before the study and during the study period did not differ significantly. Clinically, the conditions of five recipients and two controls improved, those of three recipients and four controls were unchanged, and those of two recipients and four controls worsened. Headaches, sometimes accompanied by fever and rarely by nausea and vomiting, occurred after injections of IFN-beta. Toxic symptoms usually disappeared within 24, hours; rarely, they persisted for seven to ten days. Each recipient had transient CSF pleocytosis and elevated levels to total protein (the latter remaining elevated in seven). These findings show that intrathecal administration of IFN-beta is feasible in patients with MS, warrant cautious optimism that intrathecal IFN-beta may be effective in altering the course of the disease, and support concepts of a viral or dysimmune cause of MS.
Neuronal nicotinic acetylcholine receptors as drug targets (2004)

Neuronal nicotinic acetylcholine receptors (nAChRs) are an important class of ion channels that have been associated with a number of neurological conditions. A great deal of research has been focused on attempting to understand the exact physiological role of these receptors. As drug targets, the nAChRs are quite complex, both in their structure (multiple receptor subtypes) and their physiological function. Initially, the difficulty encountered in identifying small-molecule modulators led to doubts about the validity of this class of receptors as drug targets. More recently, in vitro and in vivo data, homology modelling, and the identification of small-molecule agonists, have confirmed nAChRs as valid drug discovery targets. In fact, several compounds are now in clinical development for the treatment of pain, smoking cessation and cognitive disorders.
Yb^3+-ring-doped fiber for high-energy pulse amplification (1997)

We report what is to our knowledge the first demonstration of pulse amplification in a cw-pumped fiber in which the doped gain medium has a ring shape surrounding a single-mode core. For a given pump power, ring doping reduces the gain and hence the power lost to amplified spontaneous emission. Thereby, a significantly larger amount of energy can be stored in the amplifier. Using an Yb(3+)-doped fiber pumped by 540 mW of power at 1000 nm, we measured 69 microJ of extracted pulse energy at 1047 nm, the highest value reported to date from a single-mode Yb(3+)-doped fiber. We predict that a fiber cladding pumped by a diode bar can produce pulse energies in excess of 1 mJ.
Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR) (2013)

A novel series of small-molecule inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by molecular modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and demonstrates high levels of activity in cellular models of the double mutant form of EGFR. In addition, these compounds show significant activity against the activating mutations, which gefitinib and erlotinib target and inhibition of which gives rise to their observed clinical efficacy. A glutathione (GSH)-based assay was used to measure thiol reactivity toward the electrophilic functionality of the inhibitor series, enabling both the identification of a suitable reactivity window for their potency and the development of a reactivity quantitative structure-property relationship (QSPR) to support design.
Effect of an Inhibitor of Glucosylceramide Synthesis on Cultured Rabbit Skin Fibroblasts (1990)

1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), an effective inhibitor of UDP-glucose:ceramide glucosyltransferase, caused growth inhibition of cultured rabbit skin fibroblasts in a dose-dependent manner. At 50 microM both threo and erythro isomers of PDMP completely suppressed the cell growth. Major gangliosides of the fibroblasts, GM3 and GD3, were greatly reduced in amounts in the presence of threo-PDMP and accumulation of ceramides was observed. Surface labeling with galactose oxidase and [3H]NaBH4 demonstrated that neural glycosphingolipids with four or more sugars present on the surface of control cells were not detectable when the fibroblasts were grown in medium containing threo-PDMP. Metabolic labeling of cellular glycosphingolipids with [14C]-galactose showed reduced incorporation of radioactivity into gangliosides and neutral glycosphingolipids when threo-PDMP was present in the medium. In contrast, the erythro isomer of PDMP did not affect the biosynthesis of glycosphingolipids, a result suggesting that the inhibitory effect of erythro-PDMP on cell growth was due to a mechanism other than the inhibition of glucosyltransferase.
Image-based surrogate biomarkers for molecular subtypes of colorectal cancer (2017)

Supplementary data are available at Bioinformatics online.
Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria. (1998)

Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes.
Efficacy of recombinant human macrophage colony-stimulating factor in combination with whole-body hyperthermia in the treatment of mice infected with the polycythemia-inducing strain of the Friend virus complex. (1991)

Macrophage colony-stimulating factor (M-CSF, CSF-1) and whole-body hyperthermia (WBH) were evaluated, alone or in combination, for their capability to influence disease progression in mice inoculated with the polycythemia-inducing strain of the Friend virus complex (FVC-P). DBA/2 mice were injected i.v. with FVC-P and were treated with 20 micrograms/dose M-CSF s.c. twice a day for 5 days beginning 6 days after injection of FVC-P and/or with WBH (between 38.8 degrees C and 40.2 degrees C) given on days 5 and 12 after FVC-P injection. Fourteen days after viral inoculation, mice were sacrificed and spleen cells evaluated for: 1) spleen focus-forming virus (SFFV), by the spleen focus-forming unit assay (SFFU); 2) SFFV mRNA and genomic DNA using, respectively, Northern and Southern analysis with a B-E-SFFV DNA probe; and 3) natural killer (NK) cell activity, by 51Cr-release assay. Treatment with M-CSF or WBH alone had a small effect on SFFU numbers but little or no effect on SFFV mRNA expression and SFFV-specific DNA. However, dramatically decreased levels of SFFU and SFFV mRNA and specific DNA fragments were observed in mice treated with M-CSF in combination with WBH, and NK cell activity was restored to normal. These results suggest the possibility that M-CSF may have a therapeutic effect in combination with WBH in the in vivo treatment of certain hematologic malignancies and/or retroviral infections.
Surface Properties, Micellization, and Premicellar Aggregation of Gemini Surfactants with Rigid and Flexible Spacers (1996)

Micellization and premicellar behavior of the two series of cationic surfactants, each with two hydrophilic and two hydrophobic groups in the molecule (“gemini” surfactants), one series with a rigid, hydrophobic spacer, and second with a flexible, hydrophilic one, have been studied by use of surface tension measurements. The data show the expected regular increase in surface activity with an increase in alkyl chain length for the shorter chain homologs but show increased deviation from the regularity with an increase in chain length when the number of carbon atoms in the alkyl chain exceeds a certain number. This deviation in surface activity appears to be due to the formation of small, non-surface active aggregates. Equilibrium constants calculated for the aggregation reaction show that the conditions facilitating micelle formation also favor formation of these premicelles, such as lower temperature, stronger ionic strength of the solution, and increased alkyl chain length. Geminis with a flexible, hydrophilic spacer appear to aggregate more readily than geminis with a rigid, hydrophobic spacer. Their shorter homologs are also more surface active than those having a rigid, hydrophobic spacer.
Cloning of murine interferon gamma receptor cDNA: expression in human cells mediates high-affinity binding but is not sufficient to confer sensitivity to murine interferon gamma. (1989)

A full-length cDNA encoding the murine interferon gamma (IFN-gamma) receptor was isolated from a lambda gt11 library using a human IFN-gamma receptor cDNA probe. The deduced amino acid sequence of the murine IFN-gamma receptor shows approximately 53% homology to its human counterpart but no homology to other known proteins. Murine IFN-gamma receptor cDNA was expressed in human HEp-2 cells, which do not bind murine IFN-gamma and are insensitive to its action. Transfectants displayed the same binding properties as mouse cells. The biological responsiveness of such transfectants to various biological effects of both human and murine IFN-gamma was investigated, including modulation of major histocompatibility complex class I and class II antigen expression, inhibition of cell growth, and antiviral activity. Like parental HEp-2 cells, these transfectants responded only to human, but not to murine, IFN-gamma. Inversely, mouse L929 cells transfected with human IFN-gamma receptor cDNA were insensitive to human IFN-gamma. These results confirm and extend previous findings, suggesting that species-specific cofactors are needed for IFN-gamma-mediated signal transduction.
Site-Directed Mutagenesis and Functional Analysis of the Active-Site Residues of the E2 Component of Bovine Branched-Chain .alpha.-Keto Acid Dehydrogenase Complex (1994)

The catalytic domain of dihydrolipoamide transacylase (E2c) of bovine branched-chain alpha-keto acid dehydrogenase complex (BCKAD) was overexpressed in Escherichia coli. The E2c catalyzes a reversible acyl transfer reaction between acyl-CoA and dihydrolipoamide, which also occurs spontaneously with a much slower rate. The benzene extracts of both the enzyme-catalyzed and the spontaneous reactions mixture have identical ultraviolet absorbance spectra with a maximum at 233-234 nm, which is characteristic of S-acyldihydrolipoamide. The spontaneous reaction rate of various acyl-CoA is in the order of acetoacetyl-CoA > acetyl-CoA > isobutyryl-CoA > isovaleryl-CoA. In other words, the spontaneous acyl transfer is faster when the substituent (R) of acyl-CoA (R-CO-S-CoA) is a more electron-withdrawing group. This result indicates that a negative charge occurs in the substrate during the acyl transfer process. The function of the active-site histidine (His391) and serine (Ser338) of bovine E2c was analyzed by site-directed mutagenesis. Substitution of His391 or Ser338 with alanine caused drastic decreases in catalytic efficiencies by 3-4 orders of magnitude. The residual activity of H391A increased as the pH of the reaction buffer was elevated. These data support the base-catalyzed mechanism inferred from that of chloramphenicol acetyltransferase (CAT). In this reaction, the active-site histidine acts as a general base, and the active-site serine provides a hydrogen bond to the putative negatively charged tetrahedral transition state. Moreover, when Ala348 was changed to valine, the catalytic efficiency for isovaleryl-CoA decreased about 10-fold, and that for acetyl-CoA increased about 3-fold.(ABSTRACT TRUNCATED AT 250 WORDS)