gebhart/patrepeval huggingface dataset:
Toward a universal inhibitor of retroviral proteases: Comparative analysis of the interactions of LP‐130 complexed with proteases from HIV‐1, FIV, and EIAV (1998)

One of the major problems encountered in antiviral therapy against AIDS is the emergence of viral variants that exhibit drug resistance. The sequences of proteases (PRs) from related retroviruses sometimes include, at structurally equivalent positions, amino acids identical to those found in drug-resistant forms of HIV-1 PR. The statine-based inhibitor LP-130 was found to be a universal, nanomolar-range inhibitor against all tested retroviral PRs. We solved the crystal structures of LP-130 in complex with retroviral PRs from HIV-1, feline immunodeficiency virus, and equine infectious anemia virus and compared the structures to determine the differences in the interactions between the inhibitor and the active-site residues of the enzymes. This comparison shows an extraordinary similarity in the binding modes of the inhibitor molecules. The only exceptions are the different conformations of naphthylalanine side chains at the P3/P3' positions, which might be responsible for the variation in the Ki values. These findings indicate that successful inhibition of different retroviral PRs by LP-130 is achieved because this compound can be accommodated without serious conformational differences, despite the variations in the type of residues forming the active-site region. Although strong, specific interactions between the ligand and the enzyme might improve the potency of the inhibitor, the absence of such interactions seems to favor the universality of the compound. Hence, the ability of potential anti-AIDS drugs to inhibit multiple retroviral PRs might indicate their likelihood of not eliciting drug resistance. These studies may also contribute to the development of a small-animal model for preclinical testing of antiviral compounds.
Laboratory Testing of Urea-SCR Formulations to Meet Tier 2 Bin 5 Emissions (2007)

&lt;div class="htmlview paragraph"&gt;Urea-based Selective Catalytic Reduction (SCR) has the potential to meet U.S. Diesel Tier 2 Bin 5 emission standards for NOx in 2010. The operating and driving conditions of light-duty and heavy-duty vehicles make it necessary to customize catalyst features to the application. This paper reviews the selection of SCR catalyst technology for the U.S. and the appropriate aging and poisoning protocols for current supplier SCR catalysts. Generally, light-duty applications require SCR catalysts to function well at low temperature whereas heavy-duty applications require functionality at high temperature and high space velocity. One main durability requirement of SCR formulations involves withstanding the high temperature process of regenerating particulate filters from accumulated soot. Unrefined engine exhaust temperature control coupled with the inexact temperature measurement may also expose SCR catalysts to additional over-temperature conditions. Therefore, base metal/zeolite formulations are more appropriate for U.S. diesel applications than vanadia-containing formulations. On the basis of performance, two important parameters for selecting the proper SCR formulation involve the exhaust temperature profile and the NO&lt;sub&gt;2&lt;/sub&gt;/NOx ratio expected during typical driving conditions. Other operating parameters such as oxygen level, water level, and amount of ammonia on the catalyst surface all have influence on the system performance. A detailed comparison is made between the basic catalytic activity of Cu/zeolite and Fe/zeolite formulations, and their durability to poisons such as sulfur and hydrocarbons is investigated.&lt;/div&gt;
Fluorescence decay kinetics of tyrosinate and tyrosine hydrogen-bonded complexes (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescence decay kinetics of tyrosinate and tyrosine hydrogen-bonded complexesK. J. Willis and A. G. SzaboCite this: J. Phys. Chem. 1991, 95, 4, 1585–1589Publication Date (Print):February 1, 1991Publication History Published online1 May 2002Published inissue 1 February 1991https://pubs.acs.org/doi/10.1021/j100157a015https://doi.org/10.1021/j100157a015research-articleACS PublicationsRequest reuse permissionsArticle Views379Altmetric-Citations52LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Ectopic Expression of the Proto-oncogene Mer in Pediatric T-Cell Acute Lymphoblastic Leukemia (2006)

Transforming Mer signals may contribute to T-cell leukemogenesis, and abnormal Mer expression may be a novel therapeutic target in pediatric ALL therapy.
Understanding Allergic Asthma from Allergen Inhalation Tests (2007)

The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors' involvement with the allergen challenge include confirmation of the immunoglobulin E-dependence of the late asthmatic response, importance of (nonallergic) airway hyper-responsiveness as a determinant of the airway response to allergen, identification of allergen-induced increase in airway hyper-responsiveness, documentation of beta(2)-agonist-induced increase in airway response to allergen (including eosinophilic inflammation), advances in understanding the pathophysiology and kinetics of allergen-induced airway responses, and development of a multicentre clinical trial group devoted to using the allergen challenge for investigating promising new therapeutic strategies for asthma.
Random sampling techniques for space efficient online computation of order statistics of large datasets (1999)

In a recent paper [MRL98], we had described a general framework for single pass approximate quantile finding algorithms. This framework included several known algorithms as special cases. We had identified a new algorithm, within the framework, which had a significantly smaller requirement for main memory than other known algorithms. In this paper, we address two issues left open in our earlier paper. First, all known and space efficient algorithms for approximate quantile finding require advance knowledge of the length of the input sequence. Many important database applications employing quantiles cannot provide this information. In this paper, we present a novel non-uniform random sampling scheme and an extension of our framework. Together, they form the basis of a new algorithm which computes approximate quantiles without knowing the input sequence length. Second, if the desired quantile is an extreme value (e.g., within the top 1% of the elements), the space requirements of currently known algorithms are overly pessimistic. We provide a simple algorithm which estimates extreme values using less space than required by the earlier more general technique for computing all quantiles. Our principal observation here is that random sampling is quantifiably better when estimating extreme values than is the case with the median.
Gradient‐Preserving Color Transfer (2009)

Abstract Color transfer is an image processing technique which can produce a new image combining one source image's contents with another image's color style. While being able to produce convincing results, however, Reinhard et al.'s pioneering work has two problems—mixing up of colors in different regions and the fidelity problem. Many local color transfer algorithms have been proposed to resolve the first problem, but the second problem was paid few attentions. In this paper, a novel color transfer algorithm is presented to resolve the fidelity problem of color transfer in terms of scene details and colors. It's well known that human visual system is more sensitive to local intensity differences than to intensity itself. We thus consider that preserving the color gradient is necessary for scene fidelity. We formulate the color transfer problem as an optimization problem and solve it in two steps—histogram matching and a gradient‐preserving optimization. Following the idea of the fidelity in terms of color and gradient, we also propose a metric for objectively evaluating the performance of example‐based color transfer algorithms. The experimental results show the validity and high fidelity of our algorithm and that it can be used to deal with local color transfer.
H3K9me3 Inhibition Improves Memory, Promotes Spine Formation, and Increases BDNF Levels in the Aged Hippocampus (2016)

Cognitive decline is a debilitating condition associated with not only neurodegenerative diseases but also aging in general. However, effective treatments have been slow to emerge so far. In this study, we demonstrate that epigenetic regulation of key synaptic proteins may be an underlying, yet reversible, cause of this decline. Our findings suggest that histone 3 trimethylation is a probable target for pharmacological intervention that can counteract cognitive decline in the aging brain. Finally, we provide support to the hypothesis that, by manipulating the enzyme that regulates H3K9me3 (using a newly developed specific inhibitor of SUV39H1), it is possible to alter the chromatin state of subjects and restore memory and synaptic function in the aging brain.
The Stanford Medical Linear Accelerator (1959)

The electron linear accelerator is an instrument for the acceleration of electrons to high energies by means of guided electromagnetic waves. It may serve as a source of both energetic electrons and x-rays, the latter being obtained by bremsstrahlung conversion in materials of high atomic number. Both types of radiation are of interest in the field of cancer therapy. Although very high energies have been achieved with linear accelerators (1) to serve the purposes of investigations in nuclear physics, moderate energies are sufficient for medical purposes. Thus, for x-ray work all the advantages of supervoltage therapy may be realized in the energy range of 3-10 MEV, while technics which make use of direct electron irradiation require energies up to about 30 MEV. On the basis of such considerations, the Stanford medical accelerator was designed to operate at 6 MEV. At this energy, it serves primarily as a source of supervoltage x-rays, and secondarily as a source of low-energy electrons which may be employed in the treatment of superficial skin lesions. The electron applications are currently under development and will not be discussed in this report. Various technical considerations which influenced the final design of this accelerator are described by Ginzton, Mallory, and Kaplan (2). The machine was completed in 1955 and installed at Stanford Hospital. The treatment of patients began in early 1956. It has been customary to operate the accelerator at an energy between 4 and 5 MEV. At 4.2 MEV, the forward intensity of the x-ray beam is 0.38 milliwatts/sq. cm. (corresponding to 65 rads/min. at the maximum of the transition curve in water) for an average electron current of 16 microamperes at the target. Under these conditions, the corresponding x-ray dose distributions are similar to those described by Greene and Tranter (3) and by Murison and Hughes (4). Magnetic analysis of the electron beam indicated that satisfactory operation is obtainable in the range of 2 to 5.5 MEV. Linear accelerators must be operated under pulsed conditions. In the present design, the electron beam is incident on the target in bursts of approximately one microsecond duration, repeated 480 times per second. Thus, the x-ray intensity during the pulse is about 2,000 times higher than the average intensity. This report is intended as a description of the physical characteristics of the machine and the relevant instrumentation and technics that have evolved. What is described here is not to be interpreted as optimum in any sense but rather as a step toward the development of a useful tool in radiation therapy. The Accelerator Since descriptions of the physical and electrical characteristics of linear electron accelerators have already been given (1, 2), only those features which are pertinent to radiotherapeutic applications will be described.
Intercellular adhesion molecule 1 knockout abrogates radiation induced pulmonary inflammation (1997)

Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is induced by exposure to ionizing radiation. The lung was used as a model to study the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like response. ICAM-1 expression increased in the pulmonary microvascular endothelium and not in the endothelium of larger pulmonary vessels following treatment of mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression, we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody labeling of pulmonary microvascular endothelial cells from human cadaver donors (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify the fluorescence intensity of ICAM in the irradiated lung. These studies showed a dose- and time-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium. Peak expression occurred at 24 h, while threshold dose was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was administered by tail vein injection to mice following thoracic irradiation. Inflammatory cells were quantified by immunofluorescence for leukocyte common antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed attenuation of inflammatory cell infiltration into the lung in response to ionizing radiation exposure. To verify the requirement of ICAM-1 in the inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM-1 was not expressed in the lungs of ICAM-1-deficient mice following treatment with thoracic irradiation. ICAM-1 knockout mice had no increase in the inflammatory cell infiltration into the lung in response to thoracic irradiation. These studies demonstrate a radiation dose-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium, and show that ICAM-1 is required for inflammatory cell infiltration into the irradiated lung.
Bortezomib (PS-341): A Novel, First-in-Class Proteasome Inhibitor for the Treatment of Multiple Myeloma and Other Cancers (2003)

Proteasome inhibition is a promising new investigational avenue for cancer therapy. Bortezomib is currently available for the treatment of relapsed and refractory MM. Further trials are underway to assess the safety and efficacy of this agent in MM and a range of other cancers.
MPI on BlueGene/L: Designing an efficient general purpose messaging solution for a large cellular system (2003)

The Blue Gene/L supercomputer uses system-on-a-chip integration and a highly scalable 65,536 node cellular architecture to deliver 360 Teraflops of peak computing power. Efficient operation of the machine requires a fast, scalable and standards compliant MPI library. Researchers at IBM and Argonne National Labs are porting the MPICH2 library to Blue Gene/L . We present the current state of the design and project the features critical to achieving performance and scalability.
Free-space beam shaping for precise control and conversion of modes in optical fiber (2015)

We consider the general problem of free-space beam shaping for coupling in and out of higher order modes (HOMs) in optical fibers with high purity and low loss. We compare the performance of two simple phase structures - binary phase plates (BPPs) and axicons - for converting Gaussian beams to HOMs and vice versa. Both axicons and BPPs allow for excitation of modes with high purity (>15 dB parasitic mode suppression), or conversion of HOMs to near-Gaussian beams (M2 < 1.25). Axicon coupling in single-clad fibers allows for lower loss (0.85 ± 0.1 dB) conversion than BPPs (1.7 ± 0.1 dB); but BPPs are compatible with any fiber design, and allow for rapid switching between modes. The experiments detailed here use all commercial components and fibers, allowing for a simple means to investigate the unique properties of multi-mode fibers.
Comparison of intranasal azelastine to intranasal fluticasone propionate for symptom control in moderate-to-severe seasonal allergic rhinitis (2012)

Intranasal corticosteroids are considered the most effective therapy for moderate-to-severe seasonal allergic rhinitis (SAR) and recommended first line in guidelines. It is uncertain whether intranasal antihistamines have comparable efficacy. This study was designed to compare the efficacy of azelastine (AZE; 137 μg/spray) and fluticasone propionate (FP; 50 μg/spray), both given as 1 spray/nostril bid (i.e., approved dosing regimen in the United States), in SAR via a post hoc analysis of data from a previously published direct-comparison study. Six hundred ten moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, parallel-group trial. The primary efficacy variable was change from baseline in reflective total nasal symptom score (rTNSS (morning and evening), over 14 days. Reflective total ocular symptom score (rTOSS) was a key secondary variable. Reflective total of seven symptom scores (rT7SS [nasal plus ocular symptoms]) and time to ≥50% reduction from baseline in these key parameters were also analyzed. AZE and FP reduced rTNSS from baseline by a similar degree (-3.25 versus -3.84; p = 0.2014). Patients experienced comparable improvement in rTOSS (-2.62 versus -2.17; p = 0.2371) and rT7SS (-5.83 versus -6.05; p = 0.7820). FP was superior to AZE in alleviating rhinorrhea (-1.15 versus -0.87; p = 0.0433), but AZE showed comparable efficacy for all other nasal and ocular symptoms. There was no clinically or statistically significant difference between AZE (-1.17) and FP (-1.43) for reduction in the overall rhinitis quality of life questionnaire score (although FP, but not AZE, significantly differed from placebo). A similar proportion of patients in the AZE and FP groups achieved a 50% reduction in rTNSS. However, more AZE patients (53.0%) exhibited a 50% reduction in rTOSS by day 14 versus FP (39.6%), and ≤3 days faster (p = 0.028). Intranasal AZE (137 micrograms/spray) and intranasal FP (50 micrograms/spray), both 1 spray/nostril b.i.d., had comparable efficacy in symptom control in moderate-to-severe SAR.
Mechanisms of Lipid Antigen Presentation by CD1 (1999)

CD1 is a family of cell surface glycoproteins that are related in structure and evolutionary origin to the major histocompatibility complex (MHC)-encoded antigen-presenting molecules. In contrast to MHC-encoded antigen-presenting molecules, CD1 binds and presents lipid and glycolipid antigens for specific recognition by T cell antigen receptors. Recent work shows that several CD1 family members colocalize with MHC class II proteins within the endocytic system of antigen-presenting cells. Detailed studies of the intracellular trafficking of CD1 proteins reveal new mechanisms controlling delivery of antigen-presenting molecules to particular compartments within cells. The combination of overlapping yet distinct trafficking routes for the various CD1 family members, combined with emerging information on the heterogeneity of CD1-presented lipid antigens, suggest a model whereby different members of the CD1 family could present antigens that occur in various cellular compartments. Furthermore, the CD1 family as a group may present antigens from pathogens that are not normally accessible to or efficiently surveyed by the MHC Class I or II systems. The discovery of this third pathway for antigen presentation, together with the appreciation of a previously unrecognized universe of nonpeptide lipid antigens for T cell responses, are likely to have broad implications for our understanding of the cell-mediated immune response and its role in health and disease.
p-Aminobenzoic acid and chloramphenicol biosynthesis in Streptomyces venezuelae: gene sets for a key enzyme, 4-amino-4-deoxychorismate synthase The GenBank accession number for the sequence reported in this paper is AF189258. (2001)

Amplification of sequences from Streptomyces venezuelae ISP5230 genomic DNA using PCR with primers based on conserved prokaryotic pabB sequences gave two main products. One matched pabAB, a locus previously identified in S. venezuelae. The second closely resembled the conserved pabB sequence consensus and hybridized with a 3·8 kb NcoI fragment of S. venezuelae ISP5230 genomic DNA. Cloning and sequence analysis of the 3·8 kb fragment detected three ORFs, and their deduced amino acid sequences were used in BLAST searches of the GenBank database. The ORF1 product was similar to PabB in other bacteria and to the PabB domain encoded by S. venezuelae pabAB. The ORF2 product resembled PabA of other bacteria. ORF3 was incomplete; its deduced partial amino acid sequence placed it in the MocR group of GntR-type transcriptional regulators. Introducing vectors containing the 3·8 kb NcoI fragment of S. venezuelae DNA into pabA and pabB mutants of Escherichia coli, or into the Streptomyces lividans pab mutant JG10, enhanced sulfanilamide resistance in the host strains. The increased resistance was attributed to expression of the pair of discrete translationally coupled p-aminobenzoic acid biosynthesis genes (designated pabB/pabA) cloned in the 3·8 kb fragment. These represent a second set of genes encoding 4-amino-4-deoxychorismate synthase in S. venezuelae ISP5230. In contrast to the fused pabAB set previously isolated from this species, they do not participate in chloramphenicol biosynthesis, but like pabAB they can be disrupted without affecting growth on minimal medium. The gene disruption results suggest that S. venezuelae may have a third set of genes encoding PABA synthase.
Distillation with Sublogarithmic Overhead (2018)

It has been conjectured that, for any distillation protocol for magic states for the T gate, the number of noisy input magic states required per output magic state at output error rate ε is Ω[log(1/ε)]. We show that this conjecture is false. We find a family of quantum error correcting codes of parameters ⟦∑[under i=w+1][over m](m/i),∑[under i=0][over w](m/i),∑[under i=w+1][over r+1](r+1/i)⟧ for any integers m>2r, r>w≥0, by puncturing quantum Reed-Muller codes. When m>νr, our code admits a transversal logical gate at the νth level of Clifford hierarchy. In a distillation protocol for magic states at the level ν=3 (T gate), the ratio of input to output magic states is O(log^{γ}(1/ε)), where γ=log(n/k)/log(d)<0.678 for some m, r, w. The smallest code in our family for which γ<1 is on ≈2^{58} qubits.