gebhart/patrepeval huggingface dataset:
Selection of High-Level Resistance to Human Immunodeficiency Virus Type 1 Protease Inhibitors (2003)

Protease inhibitors represent some of the most potent agents available for therapeutic strategies designed to inhibit human immunodeficiency virus type 1 (HIV-1) replication. Under certain circumstances the virus develops resistance to the inhibitor, thereby negating the benefits of this therapy. We have carried out selections for high-level resistance to each of three protease inhibitors (indinavir, ritonavir, and saquinavir) in cell culture. Mutations accumulated over most of the course of the increasing selective pressure. There was significant overlap in the identity of the mutations selected with the different inhibitors, and this gave rise to high levels of cross-resistance. Virus particles from the resistant variants all showed defects in processing at the NC/p1 protease cleavage site in Gag. Selections with pairs of inhibitors yielded similar patterns of resistance mutations. A virus that could replicate at near-toxic levels of the three protease inhibitors combined was selected. The pro sequence of this virus was similar to that of the viruses that had been selected for high-level resistance to each of the drugs singly. Finally, a molecular clone carrying the eight most common resistance mutations seen in these selections was characterized. The sequence of this virus was relatively stable during selection for revertants in spite of displaying poor processing at the NC/p1 site and having significantly reduced fitness. These results reveal patterns of drug resistance that extend to near the limits of attainable selective pressure with these inhibitors and confirm the patterns of cross-resistance for these three inhibitors and the attenuation of virion protein processing and fitness that accompanies high-level resistance.
Rapid and Sensitive Detection of Plesiomonas shigelloides by Loop-Mediated Isothermal Amplification of the hugA Gene (2012)

Plesiomonas shigelloides is one of the causative agents of human gastroenteritis, with increasing number of reports describing such infections in recent years. In this study, the hugA gene was chosen as the target to design loop-mediated isothermal amplification (LAMP) assays for the rapid, specific, and sensitive detection of P. shigelloides. The performance of the assay with reference plasmids and spiked human stools as samples was evaluated and compared with those of quantitative PCR (qPCR). No false-positive results were observed for the 32 non-P. shigelloides strains used to evaluate assay specificity. The limit of detection for P. shigelloides was approximately 20 copies per reaction in reference plasmids and 5×10(3) CFU per gram in spiked human stool, which were more sensitive than the results of qPCR. When applied in human stool samples spiked with 2 low levels of P. shigelloides, the LAMP assays achieved accurate detection after 6-h enrichment. In conclusion, the LAMP assay developed in this study is a valuable method for rapid, cost-effective, and simple detection of P. shigelloides in basic clinical and field laboratories in the rural areas of China.
Discovery of Potent Orally Active Thrombin Receptor (Protease Activated Receptor 1) Antagonists as Novel Antithrombotic Agents (2005)

Structurally novel thrombin receptor (protease activated receptor 1, PAR-1) antagonists based on the natural product himbacine are described. The prototypical PAR-1 antagonist 55 showed a Ki of 2.7 nM in the binding assay, making it the most potent PAR-1 antagonist reported. 55 was highly active in several functional assays, showed excellent oral bioavailability in rat and monkey models, and showed complete inhibition of agonist-induced ex vivo platelet aggregation in cynomolgus monkeys after oral administration.
Fiber-based Bessel beams with controllable diffraction-resistant distance (2011)

We experimentally generate n=0 Bessel beams via higher-order cladding mode excitation with a long period fiber grating. Our method allows >99% conversion efficiency, wide or narrow conversion bandwidth, and accurate control of the number of rings in the beam. This latter property is equivalent to tuning the beam cone angle and allows for control of width and propagation distance of the center spot. We generate Bessel-like beams from LP(0,5) to LP(0,15) cladding modes and measure their propagation-invariant characteristics as a function of mode order, which match numerical simulations and a simple geometric model. This yields a versatile tool for tuning depth of focus out of fiber tips, with potential uses in endoscopic microscopy.
MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction (2002)

Microtubule-associated protein 2 (MAP2) is a major component of cross-bridges between microtubules in dendrites, and is known to stabilize microtubules. MAP2 also has a binding domain for the regulatory subunit II of cAMP-dependent protein kinase (PKA). We found that there is reduction in microtubule density in dendrites and a reduction of dendritic length in MAP2-deficient mice. Moreover, there is a significant reduction of various subunits of PKA in dendrites and total amounts of various PKA subunits in hippocampal tissue and cultured neurons. In MAP2-deficient cultured neurons, the induction rate of phosphorylated CREB after forskolin stimulation was much lower than in wild-type neurons. Therefore, MAP2 is an anchoring protein of PKA in dendrites, whose loss leads to reduced amount of dendritic and total PKA and reduced activation of CREB.
Water-Soluble Gadofullerenes:  Toward High-Relaxivity, pH-Responsive MRI Contrast Agents (2004)

The water-soluble endohedral gadofullerene derivatives, Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), have been characterized with regard to their MRI contrast agent properties. Water-proton relaxivities have been measured in aqueous solution at variable temperature (278-335 K), and for the first time for gadofullerenes, relaxivities as a function of magnetic field (5 x 10(-4) to 9.4 T; NMRD profiles) are also reported. Both compounds show relaxivity maxima at high magnetic fields (30-60 MHz) with a maximum relaxivity of 10.4 mM(-1) s(-1) for Gd@C(60)[C(COOH)(2)](10) and 38.5 mM(-1) s(-1) for Gd@C(60)(OH)(x) at 299 K. Variable-temperature, transverse and longitudinal (17)O relaxation rates, and chemical shifts have been measured at three magnetic fields (B = 1.41, 4.7, and 9.4 T), and the results point exclusively to an outer sphere relaxation mechanism. The NMRD profiles have been analyzed in terms of slow rotational motion with a long rotational correlation time calculated to be tau(R)(298) = 2.6 ns. The proton exchange rate obtained for Gd@C(60)[C(COOH)(2)](10) is k(ex)(298) = 1.4 x 10(7) s(-1) which is consistent with the exchange rate previously determined for malonic acid. The proton relaxivities for both gadofullerene derivatives increase strongly with decreasing pH (pH: 3-12). This behavior results from a pH-dependent aggregation of Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), which has been characterized by dynamic light scattering measurements. The pH dependency of the proton relaxivities makes these gadofullerene derivatives prime candidates for pH-responsive MRI contrast agent applications.
Fat and Beyond: The Diverse Biology of PPARγ (2008)

The nuclear receptor PPARgamma is a ligand-activated transcription factor that plays an important role in the control of gene expression linked to a variety of physiological processes. PPARgamma was initially characterized as the master regulator for the development of adipose cells. Ligands for PPARgamma include naturally occurring fatty acids and the thiazolidinedione (TZD) class of antidiabetic drugs. Activation of PPARgamma improves insulin sensitivity in rodents and humans through a combination of metabolic actions, including partitioning of lipid stores and the regulation of metabolic and inflammatory mediators termed adipokines. PPARgamma signaling has also been implicated in the control of cell proliferation, atherosclerosis, macrophage function, and immunity. Here, we review recent advances in our understanding of the diverse biological actions of PPARgamma with an eye toward the expanding therapeutic potential of PPARgamma agonist drugs.
Antigen Arrays for Profiling Autoantibody Repertoires (2016)

Autoantibodies are a key component for the diagnosis, prognosis and monitoring of various diseases. In order to discover novel autoantibody targets, highly multiplexed assays based on antigen arrays hold a great potential and provide possibilities to analyze hundreds of body fluid samples for their reactivity pattern against thousands of antigens in parallel. Here, we provide an overview of the available technologies for producing antigen arrays, highlight some of the technical and methodological considerations and discuss their applications as discovery tools. Together with recent studies utilizing antigen arrays, we give an overview on how the different types of antigen arrays have and will continue to deliver novel insights into autoimmune diseases among several others.
CW periodically poled LiNbO/sub 3/ optical parametric oscillator model with strong idler absorption (1998)

An analytical model is described for predicting the gain and performance of CW singly resonant optical parametric oscillators with strong idler absorption, strong pump depletion, and thermally induced dephasing. Pump and signal beam focusing effects are included by using the Guha et al. h/sub sm/ parameters. It is shown that significant parametric gain can be generated with an idler absorption-length product exceeding 10, and in some cases idler absorption is seen to enhance the pump depletion by impeding back conversion. The model accurately predicts current experimental results with weak idler absorption. Validation with strong idler absorption awaits experimental measurements to be completed.
Cooperative Caching: Using Remote Client Memory (1994)

Emerging high-speed networks will allow machines to access remote data nearly as quickly as they can access local data. This trend motivates the use of cooperative caching: coordinating the file caches of many machines distributed on a LAN to form a more effective overall file cache. In this paper we examine four cooperative caching algorithms using a trace-driven simulation study. These simulations indicate that for the systems studied cooperative caching can halve the number of disk accesses, improving file system read response time by as much as 73%. Based on these simulations we conclude that cooperative caching can significantly improve file system read response time and that relatively simple cooperative caching algorithms are sufficient to realize most of the potential performance gain.
ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration (2008)

The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes in the Schwann cell. These events are thought to be mainly controlled by axonal signals. But how signals on the axons are coordinately organized and transduced to promote proliferation, migration, radial sorting, and myelination is unknown. We describe that the axonal signal neuregulin-1 (NRG1) controls Schwann cell migration via activation of the atypical Dock180-related guanine nucleotide exchange factor (GEF) Dock7 and subsequent activation of the Rho guanine triphosphatases (GTPases) Rac1 and Cdc42 and the downstream c-Jun N-terminal kinase. We show that the NRG1 receptor ErbB2 directly binds and activates Dock7 by phosphorylating Tyr-1118. Dock7 knockdown, or expression of Dock7 harboring the Tyr-1118-to-Phe mutation in Schwann cells, attenuates the effects of NRG1. Thus, Dock7 functions as an intracellular substrate for ErbB2 to promote Schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of Rho GTPase-GEFs of the Dock180 family.
Isolation of High-Affinity Peptide Antagonists of 14-3-3 Proteins by Phage Display (1999)

The 14-3-3 proteins interact with diverse cellular molecules involved in various signal transduction pathways controlling cell proliferation, transformation, and apoptosis. To aid our investigation of the biological function of 14-3-3 proteins, we have set out to identify high-affinity antagonists. By screening phage display libraries, we have identified a set of peptides which bind 14-3-3 proteins. One of these peptides, termed R18, exhibited a high affinity for different isoforms of 14-3-3 with estimated K(D) values of 7-9 x 10(-)(8) M. Recognition of multiple isoforms of 14-3-3 suggests the targeting of R18 to a structure that is common among 14-3-3 proteins, such as the conserved ligand-binding groove. Indeed, mutations that alter critical residues in the ligand-binding site of 14-3-3 drastically decreased the level of 14-3-3-R18 association. R18 efficiently blocked the binding of 14-3-3 to the kinase Raf-1, a physiological ligand of 14-3-3, and effectively abolished the protective role of 14-3-3 against phosphatase-induced inactivation of Raf-1. The cocrystal structure of R18 in complex with 14-3-3zeta revealed the occupancy of the general binding groove of 14-3-3zeta by R18, explaining the potent inhibitory effect of R18 on 14-3-3-ligand interactions. Such a well-defined peptide will be an effective tool for probing the role of 14-3-3 in various signaling pathways, and may lead to the development of 14-3-3 antagonists with pharmacological applications.
A 0.1 μm CMOS with a step channel profile formed by ultra high vacuum CVD and in-situ doped ions (2002)

In this paper, a novel O.1 /spl mu/m CMOS device with a step channel profile is proposed in order to attain low gate depletion layer capacitance and high punchthrough immunity. The step channel profile of boron for n-MOSFET, phosphorus for p-MOSFET was formed, utilizing ultra high vacuum (UHV) CVD and in-situ doped ions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Microwave Ablation: Results with a 2.45-GHz Applicator in ex Vivo Bovine and in Vivo Porcine Liver (2006)

Large zones of ablation can be achieved with the 2.45-GHz microwave applicator used by the authors. For higher-power ablations, larger zones of coagulation were achieved for in vivo liver than for ex vivo liver with short energy applications, a finding previously not seen with other ablation devices, to the authors' knowledge.
Two minor NQO1 and NQO2 alleles predict poor response of breast cancer patients to adjuvant doxorubicin and cyclophosphamide therapy (2011)

This study suggests that both NQO1 and NQO2 modulate the efficacy of AC therapy and that NQO2 is associated with tamoxifen toxicity.
Therapeutic hypothermia following cardiac arrest: a review of the evidence (2008)

All adult patients who have return of spontaneous circulation and remain unconscious following cardiac arrest should be considered for TH between 32 degrees C and 34 degrees C for at least 12-24 h as this will improve patient mortality and morbidity. Acute hospitals need to devise policies and guidelines on the use of TH following cardiac arrest that include methods on how to achieve effective cooling by cold i.v. infusions, ice packs or purchasing specific cooling mattresses.
Preparation and Evaluation Of Drug-Containing Chitosan Beads (1989)

Sulfadiazine beads were prepared by dropping drug-containing solutions of the positively charged polysaccharide, chitosan, into tripolyphosphate (TPP) solutions. The droplets instantaneously formed gelled spheres by ionotropic gelation, entrapping the drug within a three-dimensional network of the ionically linked polymer. To achieve maximum drug content, high payloads, short gelation times, low TPP concentrations, and a low internal to external phase ratio were required. The chitosan beads showed pH-dependent swelling and dissolution behavior. The beads swelled and dissolved in 0.1N HCl, while they stayed intact in simulated intestinal fluid. The release of sulfadiazine in 0.1N HCl decreased with increasing concentration of TPP, but was independent of the TPP concentration in intestinal fluids. The morphology of the beads was investigated by scanning electron microscopy. The porosity of the beads depended on the method of drying.
On the Evaluation of Probabilities of Convex Polyhedra Under Multivariate Normal and t Distributions (1966)

Summary It is noted that probabilities of convex polyhedra in p-dimensional space can be expressed in terms of a function V(h1, h2, …, hp), if the distribution is normal, and in terms of a function Vn(h1, h2, …, hp), if the distribution is the t-distribution with n degrees of freedom. Formulae expressing V(h1, h2, …, hp) and Vn(h1, h2, …, hp) in terms of similar functions of lower order are obtained. An asymptotic expansion of Vn(h1,…, hp) in powers of n-1 is also included. The final section contains formulae connecting Vn(h1, h2, …, hp) with Vn±2(h1, K2, …, hp).
Lubrication of Low Emission Diesel Engines Part 3 (1990)

&lt;div class="htmlview paragraph"&gt;Analytical information supplemental to data previously described in Parts 1 &amp;amp; 2 (SAE &lt;a href="http://www.sae.org/technical/papers/900814" target="_blank"&gt;900814&lt;/a&gt;) is presented. Solid-sample injection gas chromatography and X-ray fluorescence were employed to characterize the particulates collected on Pallflex and Fluoropore filters. The complete preweighed filter was thermally desorbed and separated by capillary GC with simultaneous flame ionization (FID), thermal conductivity (TCD), nitrogen/phosphorus (NPD), and flame photometric (FPD) detection. Results are reviewed in terms of: % non-volatiles, % volatiles (fuel and lube oil contributions correlated to various engine speeds and loads), as well as detectable nitrogen, phosphorus, or sulfur compounds.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;XRF data were obtained from the Fluoropore filters to determine the concentrations of typical additive metals Mg, Ca, P, and Zn present in the particulate that would be indicative of oil consumption mechanisms and any tendencies for additive-sourced materials to selectively be captured as particulate matter.&lt;/div&gt;
Human and rat mast cell high-affinity immunoglobulin E receptors: characterization of putative alpha-chain gene products. (1988)

We have cloned and determined the entire nucleotide sequence of cDNAs corresponding to the putative alpha subunits of the human and rat mast cell high-affinity IgE receptors. Both human and rat cDNAs encode an NH2-terminal signal peptide, two immunoglobulin-like extracellular domains (encoded by discrete exons), a hydrophobic transmembrane region, and a positively charged cytoplasmic tail. The human and rat alpha subunits share an overall homology with one another and the immunoglobulin gene family, suggesting that they arose from a common ancestral gene and continue to share structural homology with their ligands. In addition, the rat gene is transcribed into at least three distinct forms, each of which yields a somewhat different coding sequence.
Safety, Pharmacokinetics, and Pharmacodynamics of E5564, a Lipid A Antagonist, during an Ascending Single‐Dose Clinical Study (2003)

E5564, a structural analog of the lipid A portion of lipopolysaccharide (LPS), is a potent antagonist of the biochemical and physiologic effects of LPS in several in vitro and in vivo models and is currently under clinical development as a possible therapeutic for the treatment of sepsis and septic shock. The objectives of this study were to (1) assess the safety and tolerability of E5564 following a 30-minute intravenous (i.v.) infusion, (2) evaluate the pharmacokinetic profile of E5564, and (3) measure the ability of E5564 to block LPS stimulation ex vivo in blood taken from subjects up to 8 hours after ending the infusion. Healthy male volunteers (n = 7/dose group) were randomly assigned to each of four dose levels (350, 1000, 2000, or 3500 micrograms). Within each dose group, 5 subjects received drug and 2 received placebo. E5564 or matching placebo was administered by a 30-minute infusion, and blood samples were collected at predetermined time points. All doses of E5564 were demonstrated to be safe and well tolerated. E5564 plasma concentrations were determined using a validated LC/MS/MS method. The Cmax and AUC of E5564 increased in a dose-proportional manner. E5564 pharma-cokinetics were characterized by a slow clearance (0.67-0.95 mL/h/kg), a small volume of distribution (41-54 mL/kg), and a relatively long elimination half-life (42-51 h). As measured in the ex vivo assay, E5564 inhibited LPS-induced tumor necrosis factor-alpha (TNF-alpha) in a dose-dependent manner, and at the higher doses (2 and 3.5 mg), antagonistic activity was measurable up to 8 hours postinfusion. E5564 lacked LPS-like agonist activity at doses up to 3.5 mg. Taken together, we believe that E5564 is a safe, potent antagonist of LPS in blood and will likely benefit patients in the treatment of LPS-related diseases.
Community Asthma Initiative to Improve Health Outcomes and Reduce Disparities Among Children with Asthma (2016)

Black and Hispanic children are hospitalized with complications of asthma at much higher rates than white children. The Boston Children's Hospital Community Asthma Initiative (CAI) provides asthma case management and home visits for children from low-income neighborhoods in Boston, Massachusetts, to address racial/ethnic health disparities in pediatric asthma outcomes. CAI objectives were to evaluate 1) case management data by parent/guardian report for health outcomes and 2) hospital administrative data for comparison between intervention and comparison groups. Data from parent/guardian reports indicate that CAI decreased the number of children with any (one or more) asthma-related hospitalizations (decrease of 79% at 12 months) and any asthma-related emergency department visits (decrease of 56% at 12 months) among children served, most of whom were non-Hispanic black or Hispanic. Hospital administrative data also indicate that the number of asthma-related hospitalizations per child significantly decreased among CAI participants compared with a comparison group. The CAI model has been replicated in other cities and states with adaptations to local cultural and systems variations. Health outcome and cost data have been used to contribute to a business case to educate legislators and insurers about outcomes and costs for this enhanced approach to care. Strong partnerships with public health, community, and housing agencies have allowed CAI to leverage its outcomes to expand systemic changes locally and statewide to reduce asthma morbidity.
Pay Word and MicroMint : Two Simple Micropayment Schemes (1996)

1 Introduction We present two simple micropayment schemes, &amp;amp;quot;PayWord &amp;amp;quot; and &amp;amp;quot;MicroMint, &amp;amp;quot; for making small purchases over the Internet. We were inspired to work on this problem by DEC&amp;apos;s &amp;amp;quot;Millicent &amp;amp;quot; scheme[10]. Surveys of some electronic payment schemes can be found in HallamBaker [6], Schneier[16], and Wayner[18]. Our main goal is to minimize the number of public-key operations required per payment, using hash operations instead whenever possible. As a rough guide, hash functions are about 100 times faster than RSA signature verification, and about 10,000 times faster than RSA signature generation: on a typical workstation, one can sign two messages per second, verify 200 signatures per second, and compute 20,000 hash function values per second.