gebhart/patrepeval huggingface dataset:
Using leases to support server-driven consistency in large-scale systems (2002)

The paper introduces volume leases as a mechanism for providing cache consistency for large scale, geographically distributed networks. Volume leases are a variation of leases, which were originally designed for distributed file systems. Using trace driven simulation, we compare two new algorithms against four existing cache consistency algorithms and show that our new algorithms provide strong consistency while maintaining scalability and fault tolerance. For a trace based workload of Web accesses, we find that volumes can reduce message traffic at servers by 40% compared to a standard lease algorithm, and that volumes can considerably reduce the peak load at servers when popular objects are modified.
Structure of the Rat Interleukin 6 Gene and Its Expression in Macrophage-derived Cells (1989)

Rat peritoneal exudate cells produce two interleukin 6 (IL6) messenger RNA species, a major 1200 nucleotide and a 5-fold less abundant, 2400-nucleotide species. A cDNA clone representing the major species was isolated, and sequenced. The 1055-base pair insert covered the 3'-nontranslated region, the 211 triplet coding region and most of the 5'-nontranslated region. The derived rat IL6 amino acid sequence was 93 and 58% identical, respectively, with mature murine and human IL6. Rat IL6 lacks N-glycosylation sites but contains a fifth cysteinyl residue in addition to the 4 residues shared in conserved positions with murine and human IL6. Stable murine L cell and human HeLa-derived cell lines were established by cotransfection with rat IL6 cDNA and a selectable neomycin resistance marker. These lines secrete 9-fold increased amounts of functional IL6 over their respective parental cells. A stable rat macrophage-derived cell line, RM-SV1, was established by transformation with simian virus 40. IL6 and Il1 mRNA levels are inducible 20- and 3.5-fold, respectively, in this line by treatment with lipopolysaccharide with kinetics characteristic of macrophages. A set of three overlapping genomic DNA clones was isolated and a 10-kilobase DNA segment was sequenced containing the rat IL6 gene plus 2.9 kilobases of 5'-flanking and 1.3 kilobases of 3'-flanking sequences. The two transcription start sites used in RM-SV1 cells were mapped within 5 base pairs of each other. The exon/intron boundaries are conserved with the murine and human IL6 genes. The two IL6 mRNA species are generated by alternative polyadenylation at sites separated by a distance of 1.2 kilobases. The intervening region contains a repetitive element 72-80% identical with the rat and murine consensus L1 family sequences.
Neurohumoral mechanisms in deoxycorticosterone acetate (DOCA)–salt hypertension in rats (2009)

This brief review describes the role of neural and non-neural mechanisms during different phases of deoxycorticosterone acetate (DOCA)-salt hypertension. There are contradictory data for and against a role of the sympathetic nervous system and neurohumoral agents, including endothelin and vasopressin. Elucidating the factors responsible for DOCA-salt hypertension will be helpful in understanding the causes of hypertension resulting from hypervolaemia, hyperaldosteronism and high salt intake.
Changes in nasopharyngeal flora during otitis media of childhood. (1990)

The nasopharyngeal flora of healthy children were compared with flora in children with otitis media caused by nontypable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Forty healthy children were followed prospectively and compared with 70 children with 43 episodes of nontypable H. influenzae, 21 episodes of S. pneumoniae and 28 episodes of M. catarrhalis otitis media. Carriage of nontypable H. influenzae (95% vs. 65%, P less than 0.001), S. pneumoniae (91% vs. 52%, P less than 0.005) and M. catarrhalis (86% vs. 52%, P less than 0.001) increased significantly during episodes of otitis media compared with healthy periods. The quantity of nontypable H. influenzae, S. pneumoniae and M. catarrhalis in nasopharyngeal secretions also increased during active infection compared with healthy periods: 3.0 vs. 2.0, P less than 0.005; 3.2 vs. 2.1, P less than 0.001; and 3.3 vs. 2.5, P less than 0.01, respectively. At the same time, nonpathogens of the resident flora, in particular viridans streptococci, declined in carriage: 65% vs. 22%, P less than 0.001. These data suggest that respiratory pathogens become relatively more important in the microenvironment of the nasopharynx during episodes of otitis media. Furthermore the absence of a middle ear pathogen in a nasopharyngeal culture strongly suggests that the pathogen is not present in the middle ear space (negative predictive value greater than 0.96).
Direct detection and quantitation of a distinct T-cell epitope derived from tumor-specific epithelial cell-associated mucin using human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T cells. (2002)

The recent characterization of MHC-displayed tumor-associated antigens that recognize effector cells of the immune system has created new perspectives for cancer therapy. Antibodies that recognize these tumor-associated MHC-peptide complexes with the same specificity as the T-cell antigen receptor will therefore be valuable tools for immunotherapy, as well as for studying antigen presentation in human cancers. Most tumor-associated antigens are expressed in only one or a few tumor types; however, specific T-cell epitopes derived from the Mucin-1 tumor-associated antigen (MUC1) that are widely expressed in many cancers were identified and shown to be recognized by CTLs. We selected a large nonimmune repertoire of phage Fab antibodies on recombinant human class I HLA-A2 complexes displaying an antigenic T-cell epitope derived from MUC1. High frequency of anti-MHC-peptide binders was observed (84%), and surprisingly, a high percentage (80%) of antibodies was fully specific for the MUC1 epitope. We isolated a surprisingly large panel of 16 different high-affinity human recombinant Fab antibodies that exhibited peptide-specific, MHC-restricted binding characteristics of T cells. The analyzed Fabs not only recognize the cognate MHC-peptide complex in a recombinant soluble form but also the native complex as displayed on the surface of antigen-presenting cells and breast tumor cells. Therefore, these findings demonstrate the ability to transform the unique fine specificity but low intrinsic affinity of T-cell receptors on T cells into high-affinity soluble antibody molecules endowed with a T-cell antigen receptor-like specificity. These molecules may prove to be very important and widely applicable for monitoring the expression of specific MHC-peptide complexes on the surface of tumor and immune cells for structure-function studies of T-cell receptor-peptide-MHC interactions, as well as for developing new targeting agents for immunotherapy.
Interleukin 2 regulates immune interferon (IFN gamma) production by normal and suppressor cell cultures. (1982)

A Lyt-2+ lymphocyte is responsible for immune interferon (IFN gamma) production in mitogen-stimulated mouse spleen cell cultures. A Lyt-1+ helper cell is required for the induction of IFN gamma. Interleukin 2 (IL 2) can specifically replace the Lyt 1 cell requirement. IL 2 will also abrogate suppressor cell inhibition of IFN gamma production. IFN gamma production appears to be regulated by a dynamic interaction between helper cells (source of IL 2), suppressor cells (absorption of IL 2?) and IFN gammna-producer cells.
A Model for HCO3− Accumulation and Photosynthesis in the Cyanobacterium Synechococcus sp (1985)

A simple model based on HCO(3) (-) transport has been developed to relate photosynthesis and inorganic carbon fluxes for the marine cyanobacterium, Synechococcus sp. Nägeli (strain RRIMP N1). Predicted relationships between inorganic carbon transport, CO(2) fixation, internal carbonic anhydrase activity, and leakage of CO(2) out of the cell, allow comparisons to be made with experimentally obtained data. Measurements of inorganic carbon fluxes and internal inorganic carbon pool sizes in these cells were made by monitoring time-courses of CO(2) changes (using a mass spectrometer) during light/dark transients. At just saturating CO(2) conditions, total inorganic carbon transport did not exceed net CO(2) fixation by more than 30%. This indicates CO(2) leakage similar to that estimated for C(4) plants.For this leakage rate, the model predicts the cell would need a conductance to CO(2) of around 10(-5) centimeters per second. This is similar to estimates made for the same cells using inorganic carbon pool sizes and CO(2) efflux measurements. The model predicts that carbonic anhydrase is necessary internally to allow a sufficiently fast rate of CO(2) production to prevent a large accumulation of HCO(3) (-). Intact cells show light stimulated carbonic anhydrase activity when assayed using (18)O-labeled CO(2) techniques. This is also supported by low but detectable levels of carbonic anhydrase activity in cell extracts, sufficient to meet the requirements of the model.
Flexing the Electrified Meniscus:  The Birth of a Jet in Electrosprays (2004)

Spraying of liquids through an electrified meniscus has become a method of choice to produce ions from large biomolecules. Using mass spectrometry, the generated ions can be analyzed to provide detailed information on their composition and structure. This technique enables high-throughput protein analysis that is a prerequisite for answering the questions presented by proteomics. In this report, Taylor cone deformations are shown to play a central role in the mechanism of electrostatic spraying. Spontaneous spray current oscillations are known to exist in most electrospray regimes and affect the stream of ions introduced into the mass spectrometer. Fast time-lapse imaging of the Taylor cone throughout its evolution indicates the presence of a nodal line and standing waves on its surface. Four phases of the cone pulsation cycle (liquid accumulation, cone formation, ejection of a jet, relaxation) are established. Based on image analysis, apex velocities, curvatures, and opening angles are determined. During jet ejection, the apex velocity and the curvature exhibit singularities. Furthermore, the pulsation frequencies of the Taylor cone deformations are determined using Fourier analysis of light refraction measurements. The oscillation frequency of the electrospray current collected by the counter electrode shows close correlation to the cone deformations, providing the first direct evidence that links spray current oscillations to Taylor cone pulsation. Thus, monitoring the oscillation frequency throughout the spraying process and adjusting the spray parameters can be used to stabilize the spray. Furthermore, synchronizing the injection of ions in time-of-flight systems with the spontaneous spray oscillations may improve the signal-to-noise ratio in the collected mass spectra.
Biosynthesis of Nonribosomal Peptides (2004)

Bacteria and fungi use large multifunctional enzymes, the so-called nonribosomal peptide synthetases (NRPSs), to produce peptides of broad structural and biological activity. Biochemical studies have contributed substantially to the understanding of the key principles of these modular enzymes that can draw on a much larger number of catalytic tools for the incorporation of unusual features compared with the ribosomal system. Several crystal structures of NRPS-domains have yielded deep insight into the catalytic mechanisms involved and have led to a better prediction of the products assembled and to the construction of hybrid enzymes. In addition to the structure-function relationship of the core- and tailoring-domains of NRPSs, which is the main focus of this review, different biosynthetic strategies and essential enzymes for posttranslational modification and editing are discussed.
A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9 (2017)

The Cas9 endonuclease is widely used for genome engineering applications by programming its single-guide RNA, and ongoing work is aimed at improving the accuracy and efficiency of DNA targeting. DNA cleavage of Cas9 is controlled by the conformational state of the HNH nuclease domain, but the mechanism that governs HNH activation at on-target DNA while reducing cleavage activity at off-target sites remains poorly understood. Using single-molecule Förster resonance energy transfer, we identified an intermediate state of <i>Streptococcus pyogenes</i> Cas9, representing a conformational checkpoint between DNA binding and cleavage. Upon DNA binding, the HNH domain transitions between multiple conformations before docking into its active state. HNH docking requires divalent cations, but not strand scission, and this docked conformation persists following DNA cleavage. Sequence mismatches between the DNA target and guide RNA prevent transitions from the checkpoint intermediate to the active conformation, providing selective avoidance of DNA cleavage at stably bound off-target sites.
The Role of Flagellin versus Motility in Acute Lung Disease Caused byPseudomonas aeruginosa (2007)

The flagellum of Pseudomonas aeruginosa has been implicated in acute pneumonia, and its flagellin is known to cause lung inflammation. However, its proinflammatory role, versus its motility function, as a cause of death by a whole bacterium has not been demonstrated. This issue was examined in a lung model of acute infection using different flagellar mutants. We found that the absence of motility does not significantly alter the LD(50), whereas the production of excess amounts of flagellin lowers it and results in early death. Next, we found that the absence of the Toll-like receptor 5 (TLR5) ligand, flagellin, results in slower clearance of this organism from the lungs and a delay in the time to death. These findings demonstrate the dual role of flagellin in host defense and in disease and suggest that the death in this model may be biphasic with flagellin playing a role early in the disease.
Low pressure DNA shearing: a method for random DNA sequence analysis (1990)

Journal Article Low pressure DNA shearing: a method for random DNA sequence analysis Get access Lawrence A. Schriefer, Lawrence A. Schriefer Department of Genetics, Washington University School of MedicineSt Louis, MO 63110, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Beth K. Gebauer, Beth K. Gebauer Department of Genetics, Washington University School of MedicineSt Louis, MO 63110, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Lisa Q.Q. Qiu, Lisa Q.Q. Qiu Department of Genetics, Washington University School of MedicineSt Louis, MO 63110, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert H. Waterston, Robert H. Waterston Department of Genetics, Washington University School of MedicineSt Louis, MO 63110, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard K. Wilson Richard K. Wilson * Department of Genetics, Washington University School of MedicineSt Louis, MO 63110, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 24, 1 December 1990, Pages 7455–7456, https://doi.org/10.1093/nar/18.24.7455 Published: 01 January 1990 Article history Published: 01 January 1990 Accepted: 05 November 1990
TCP Vegas: end to end congestion avoidance on a global Internet (1995)

Vegas is an implementation of TCP that achieves between 37 and 71% better throughput on the Internet, with one-fifth to one-half the losses, as compared to the implementation of TCP in the Reno distribution of BSD Unix. This paper motivates and describes the three key techniques employed by Vegas, and presents the results of a comprehensive experimental performance study, using both simulations and measurements on the Internet, of the Vegas and Reno implementations of TCP.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy (2016)

This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.
Aluminum contamination in parenteral products (2014)

Unlike the rapid response to eliminating aluminum toxicity in the dialysis patient population, similar successes have not been realized in patients receiving parenteral nutrition solutions. Product formulation changes have been slow to emerge from manufacturers. It remains the responsibility of healthcare practitioners to recognize the patient populations at risk for toxicity and act accordingly. Monitoring aluminum status and purchasing products known to possess the least amount of aluminum are two such approaches.
Strong Regularities in World Wide Web Surfing (1998)

One of the most common modes of accessing information in the World Wide Web is surfing from one document to another along hyperlinks. Several large empirical studies have revealed common patterns of surfing behavior. A model that assumes that users make a sequence of decisions to proceed to another page, continuing as long as the value of the current page exceeds some threshold, yields the probability distribution for the number of pages that a user visits within a given Web site. This model was verified by comparing its predictions with detailed measurements of surfing patterns. The model also explains the observed Zipf-like distributions in page hits observed at Web sites.
Parathyroid hormone signaling through low-density lipoprotein-related protein 6 (2008)

Intermittent administration of PTH stimulates bone formation, but the precise mechanisms responsible for PTH responses in osteoblasts are only incompletely understood. Here we show that binding of PTH to its receptor PTH1R induced association of LRP6, a coreceptor of Wnt, with PTH1R. The formation of the ternary complex containing PTH, PTH1R, and LRP6 promoted rapid phosphorylation of LRP6, which resulted in the recruitment of axin to LRP6, and stabilization of beta-catenin. Activation of PKA is essential for PTH-induced beta-catenin stabilization, but not for Wnt signaling. In vivo studies confirmed that PTH treatment led to phosphorylation of LRP6 and an increase in amount of beta-catenin in osteoblasts with a concurrent increase in bone formation in rat. Thus, LRP6 coreceptor is a key element of the PTH signaling that regulates osteoblast activity.
Quantitative analysis of scrolling techniques (2002)

We propose a formal experimental paradigm designed to help evaluate scrolling interaction techniques. Such a method is needed by interaction designers to quantify scrolling performance, thereby providing a tool to evaluate and improve upon new techniques. We systematically vary the scrolling distance as well as the required tolerance of scrolling. Distance and tolerance are the parameters of Fitts' Law, which traditionally has been applied to the evaluation of pointing devices in tasks involving rapid, aimed movement to visible targets. Scrolling involves acquisition of targets well beyond the edges of the screen, yet Fitts' Law models our experimental data very wellWe apply our paradigm to the IBM ScrollPoint and the IntelliMouse Wheel. Our experimental approach reveals a crossover effect in performance versus distance, with the Wheel performing best at short distances but the ScrollPoint performing best at long distances. We also demonstrate that the performance of the Wheel can be significantly improved using an acceleration algorithm. These results show that our approach yields a practical and rigorous method for the evaluation of scrolling techniques.
Simplified Electrochemically Mediated Atom Transfer Radical Polymerization using a Sacrificial Anode (2015)

Simplification of electrochemically mediated atom transfer radical polymerization was achieved efficiently under either potentiostatic or galvanostatic conditions using an aluminum wire sacrificial anode (seATRP) immersed directly into the reaction flask without separating the counter electrode. seATRP polymerizations were carried out under different applied potentials, Eapps = E1/2, Epc, Epc -40 mV, and Epc -80 mV. As the rate of polymerization (Rp) can be modulated by applying different Eapp potentials, more reducing conditions resulted in faster Rp. The polymerization results showed similar narrow molecular-weight distribution throughout the reactions, similar to results observed for n-butyl acrylate (BA) polymerization under conventional eATRP. High-molecular-weight PBA and diblock copolymers were synthesized by seATRP with more than 90% monomer conversion. Furthermore, galvanostatic conditions were developed for synthesizing PBA with the two-electrode system.
Development of a direct assay for alpha-amylase. (1988)

We describe a direct colorimetric assay for alpha-amylase, with 2-chloro-4-nitrophenyl-alpha-maltotrioside as substrate. Both human pancreatic and salivary amylase split this substrate without the use of helper enzymes, yielding free 2-chloro-4-nitrophenol, which is monitored at 405 nm. The performance of this reagent compares well with that of Pantrak Amylase (Behring Diagnostics) for both serum and urine samples. The reagent is very stable in dry powder form and is stable for one month at 2 to 8 degrees C after reconstitution. Because of the rapid color development and linear kinetics (less than 30 s), the assay is easily automated. Results can be obtained in less than 5 min.
Oxidative post‐translational modifications of α‐synuclein in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of Parkinson's disease (2001)

Structural and functional alterations of alpha-synuclein is a presumed culprit in the demise of dopaminergic neurons in Parkinson's disease (PD). Alpha-synuclein mutations are found in familial but not in sporadic PD, raising the hypothesis that effects similar to those of familial PD-linked alpha-synuclein mutations may be achieved by oxidative post-translational modifications. Here, we show that wild-type alpha-synuclein is a selective target for nitration following peroxynitrite exposure of stably transfected HEK293 cells. Nitration of alpha-synuclein also occurs in the mouse striatum and ventral midbrain following administration of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Conversely, beta-synuclein and synaptophysin were not nitrated in MPTP-intoxicated mice. Our data demonstrate that alpha-synuclein is a target for tyrosine nitration, which, by disrupting its biophysical properties, may be relevant to the putative role of alpha-synuclein in the neurodegeneration associated with MPTP toxicity and with PD.