gebhart/patrepeval huggingface dataset:
A Human CD4 Monoclonal Antibody for the Treatment of T-Cell Lymphoma Combines Inhibition of T-Cell Signaling by a Dual Mechanism with Potent Fc-Dependent Effector Activity (2007)

Zanolimumab is a human IgG1 antibody against CD4, which is in clinical development for the treatment of cutaneous and nodal T-cell lymphomas. Here, we report on its mechanisms of action. Zanolimumab was found to inhibit CD4+ T cells by combining signaling inhibition with the induction of Fc-dependent effector mechanisms. First, T-cell receptor (TCR) signal transduction is inhibited by zanolimumab through a fast, dual mechanism, which is activated within minutes. Ligation of CD4 by zanolimumab effectively inhibits early TCR signaling events but, interestingly, activates signaling through the CD4-associated tyrosine kinase p56lck. An uncoupling of p56lck from the TCR by anti-CD4 allows the kinase to transmit direct inhibitory signals via the inhibitory adaptor molecules Dok-1 and SHIP-1. Second, CD4+ T cells are killed by induction of antibody-dependent cell-mediated cytotoxicity, to which CD45RO+ cells are more sensitive than CD45RA+ cells. Finally, zanolimumab induces down-modulation of CD4 from cell surfaces via a slow Fc-dependent mechanism. In conclusion, zanolimumab rapidly inhibits T-cell signaling via a dual mechanism of action combined with potent Fc-dependent lysis of CD4+ T cells and may act long-term by down-regulating CD4.
Discovery of Fragment Molecules That Bind the Human Peroxiredoxin 5 Active Site (2010)

The search for protein ligands is a crucial step in the inhibitor design process. Fragment screening represents an interesting method to rapidly find lead molecules, as it enables the exploration of a larger portion of the chemical space with a smaller number of compounds as compared to screening based on drug-sized molecules. Moreover, fragment screening usually leads to hit molecules that form few but optimal interactions with the target, thus displaying high ligand efficiencies. Here we report the screening of a homemade library composed of 200 highly diverse fragments against the human Peroxiredoxin 5 protein. Peroxiredoxins compose a family of peroxidases that share the ability to reduce peroxides through a conserved cysteine. The three-dimensional structures of these enzymes ubiquitously found throughout evolution have been extensively studied, however, their biological functions are still not well understood and to date few inhibitors have been discovered against these enzymes. Six fragments from the library were shown to bind to the Peroxiredoxin 5 active site and ligand-induced chemical shift changes were used to drive the docking of these small molecules into the protein structure. The orientation of the fragments in the binding pocket was confirmed by the study of fragment homologues, highlighting the role of hydroxyl functions that hang the ligands to the Peroxiredoxin 5 protein. Among the hit fragments, the small catechol molecule was shown to significantly inhibit Peroxiredoxin 5 activity in a thioredoxin peroxidase assay. This study reports novel data about the ligand-Peroxiredoxin interactions that will help considerably the development of potential Peroxiredoxin inhibitors.
Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia (2008)

A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.
On the integration of structure indexes and inverted lists (2004)

Recently, there has been a great deal of interest in the development of techniques to evaluate path expressions over collections of XML documents. In general, these path expressions contain both structural and keyword components. Several methods have been proposed for processing path expressions over graph/tree-structured XML data. These methods can be classified into two broad classes. The first involves graph traversal where the input query is evaluated by traversing the data graph or some compressed representation. The other class involves information-retrieval style processing using inverted lists. In this framework, structure indexes have been proposed to be used as a substitute for graph traversal. Here, we focus on a subclass of CAS queries consisting of simple path expressions. We study algorithmic issues in integrating structure indexes with inverted lists for the evaluation of these queries, where we rank all documents that match the query and return the top k documents in order of relevance.
Evaluation and Prognostic Significance of Circulating Tumor Cells in Patients With Non–Small-Cell Lung Cancer (2011)

CTCs are detectable in patients with stage IV NSCLC and are a novel prognostic factor for this disease. Further validation is warranted before routine clinical application.
Development of a Universal Nucleobase and Modified Nucleobases for Expanding the Genetic Code (2002)

This unit presents protocols for the synthesis and characterization of nucleosides with unnatural bases in order to develop bases for the expansion of the genetic alphabet or for nonselective pairing opposite natural bases. Protocols describe the design, synthesis, and characterization of unnatural base pairs involving 1-beta-D-2-deoxyribosyl-N- and -C-nucleosides. Determination of the thermodynamic and kinetic parameters of unnatural nucleosides is accomplished by incorporation into oligonucleotides and subsequent evaluation as described herein.
DNA-Binding and Dimerization Domains of Adenosine 3′, 5′- Cyclic Monophosphate-Responsive Protein CREB Reside in the Carboxyl-Terminal 66 Amino Acids (1990)

The expression of genes in response to cAMP is mediated by one or more trans-activator proteins, CREBs, that bind to cAMP-responsive enhancers (CREs) of the general motif 5'-TGACGTCA-3'. The carboxyl-terminal amino acid sequences of two isoforms of CREB, CREB-327 and CREB-341, deduced from the cDNAs consist of a positively charged (basic) region adjacent to a leucine zipper motif. Three peptides corresponding to the hypothetical DNA-binding and dimerization domains of CREB-327 were synthesized. A peptide that includes both the basic and leucine zipper domains binds to the CRE specifically. Moreover, this peptide readily forms CRE-binding heterodimers with full-length CREB both synthesized by in vitro cell-free translation and isolated from PC-12 cells, but did not heterodimerize with in vitro translated jun or fos. Two other peptides, either partially or totally lacking the basic region, but containing the intact leucine zipper domain, readily form dimers but do not bind to the CRE. We conclude that the carboxy-terminal basic and leucine zipper regions are necessary and sufficient for specific binding of CREB to the CRE as a homodimer. The leucine zipper domain is responsible for the dimerization, and the basic region confers binding specificity for the CRE. Heterodimerization of CREB-327 does not form heterodimers with jun or fos.
Hyaluronan on the surface of tumor cells is correlated with metastatic behavior. (1995)

In the present study, we examined the metastatic potential of tumor cells expressing different levels of cell surface hyaluronan. We used flow cytometry to isolate subsets of the B16-F1 mouse melanoma cell line that expressed either high (HA-H) or low (HA-L) amounts of hyaluronan on their surfaces. These two subsets of cells showed a 32-fold difference in the amount of cell surface hyaluronan, due to its rate of synthesis. However, these cell lines did not differ from each other with regard to their in vitro growth rates, susceptibility to natural killer-mediated cytotoxicity, or the expression of the cell surface proteins CD44, ICAM-1, and GMP-140. When these cells were injected s.c., they both formed s.c. tumors of approximately the same size. However, when injected into the tail vein of mice, the HA-H cells formed a greater number of nodules in the lungs and caused a faster rate of mortality than the HA-L cells. The presence of hyaluronan did enhance the interaction of the HA-H cells with cultured endothelial cells that expressed CD44. Thus, it is possible that enhanced interactions between hyaluronan and CD44 promoted the formation of tumor embolisms which, in turn, increased the chances that the tumor cells would be trapped in the lungs. Taken together, these results suggest that hyaluronan may play a critical role in the process of tumor metastasis.
Generation of effector CD8+ T cells and their conversion to memory T cells (2010)

Immunological memory is a cardinal feature of adaptive immunity. We are now beginning to elucidate the mechanisms that govern the formation of memory T cells and their ability to acquire longevity, survive the effector-to-memory transition, and mature into multipotent, functional memory T cells that self-renew. Here, we discuss the recent findings in this area and highlight extrinsic and intrinsic factors that regulate the cellular fate of activated CD8+ T cells.
The enzyme-linked immunosorbent assay (ELISA) test for the identification of blood-meals of haematophagous insects (1986)

Abstract A sandwich enzyme-linked immunosorbent assay (ELISA) test was developed to detect blood-meals in insects and identify the host fed on. The test proved both sensitive and specific. Very small quantities of fresh blood (about 0·02 μl) can be detected; in practice, this enables blood in mosquitoes which are about three-quarters gravid to be identified. In trials in both Zambia and Britain, positive reactions were easily identified visually; consequently, this enabled the ELISA technique to be used as a routine field test. In addition to those of mosquitoes, blood-meals of a few Culicoides species were also successfully identified.
Performance of Immuno–Positron Emission Tomography with Zirconium-89-Labeled Chimeric Monoclonal Antibody U36 in the Detection of Lymph Node Metastases in Head and Neck Cancer Patients (2006)

In this study, immuno-PET with (89)Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.
Inglorious Installers: Security in the Application Marketplace (2010)

From mobile phones to social networks, installing and running third-party applications can be risky. Installing applications often requires running unverified, untrustworthy code with the privilege of a system administrator, allowing it to compromise the security of user data and the operating system. Once installed, applications on most platforms can access anything that a user can: a web browser can read users ’ e-mail and an e-mail client can access browsing history. Computer scientists have been developing systems for decades which follow the “principle of least authority, ” yet few consumer computing platforms adopt their techniques. In this paper, we examine the application markets for ten computing platforms, including personal computers, mobile phones, social networks and web browsers. We identify economic causes for the wide variation in their installation and sandboxing techniques, and we propose measures to align the incentives
Image Convolution with CUDA (2007)

The hydro-thermal synthesis and crystal structure of the simple inorganic compound CaHPO<sub>3</sub>, which crystallizes in the chiral space group <i>P</i>4<sub>3</sub>2<sub>1</sub>2, are reported. The structure is built up from distorted CaO<sub>7</sub> capped trigonal prisms and HPO<sub>3</sub> pseudo pyramids, which share corners and edges to generate a three-dimensional network.
Heteroditopic ruthenium(II) bipyridyl receptor with adjacent saccharide and phosphate binding sites (1998)

A luminescent ruthenium(II) bipyridyl receptor with pendant boronic acids is synthesized and shown to bind phosphorylated sugars in water. The association constant for fructose-6-phosphate is log Ka = 3.1 M−1 at 298 °K. The receptor simultaneously binds saccharidephophate sitive cooperativity.
Electrochemical Codeposition of Copper-Strontium Hydroxide Films from Dimethylsulfoxide Solutions (2004)

The cathodic electrodeposition technique has been applied to the binary system in nitrate-dimethylsulfoxide solution, with use of voltammetry as a prerequisite to thin-film synthesis. The electrochemical study was performed under diffusion and convection regimes as a function of the concentration ratio and resulted in the choice of a solution with for deposition experiments. Films were grown potentiostatically and galvanostatically at room temperature on silver tapes. Electrolytic deposition was followed by annealing for 4 min in air at 880°C. Both series were then analyzed by chronoamperometry, X-ray diffraction, electron microprobe analysis, and scanning electron microscopy. Inside the parameter ranges determined by electrochemistry, as-grown and annealed films were homogeneous, pinhole-free, and adherent. The best quality was seen in the galvanostatic mode due to accurate control of the overall deposition rate. Copper was electrodeposited as a metal by diffusion-limited reduction of Cu(II) ions, while strontium was precipitated as a hydroxide by electrogeneration of base in the water reduction range. Codeposition was found to give rise to separated phases, involving a microcrystalline strontium hydroxide layer surrounding a nanocrystalline copper underlayer, which was surrounded by copper surface clusters. Annealed films were composed of various mixtures of strontium cuprate phases, whose composition was directly related to the strontium-copper atomic ratio in the precursor films. © 2004 The Electrochemical Society. All rights reserved.
Analysis of natural killer cells isolated from human decidua: evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function (2006)

While during the first trimester of pregnancy natural killer (NK) cells represent the most abundant lymphocyte population in the decidua, their actual function at this site is still debated. In this study we analyzed NK cells isolated from decidual tissue for their surface phenotype and functional capability. We show that decidual NK (dNK) cells express normal surface levels of certain activating receptors, including NKp46, NKG2D, and 2B4, as well as of killer cell immunoglobulin-like receptors (KIRs) and CD94/NKG2A inhibitory receptor. In addition, they are characterized by high levels of cytoplasmic granules despite their CD56(bright) CD16- surface phenotype. Moreover, we provide evidence that in dNK cells, activating NK receptors display normal triggering capability whereas 2B4 functions as an inhibitory receptor. Thus, cross-linking of 2B4 resulted in inhibition of both cytolytic activity and interferon-gamma (IFN-gamma) production. Clonal analysis revealed that, in the majority of dNK cell clones, the 2B4 inhibitory function is related to the deficient expression of signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) mRNA. Moreover, biochemical analysis revealed low levels of SAP in the dNK polyclonal population. This might suggest that dNK cells, although potentially capable of killing, are inhibited in their function when interacting with cells expressing CD48.
Interleukin 21: A Key Player in Lymphocyte Maturation (2004)

The common gamma chain family of cytokine receptors plays a plethora of roles during the early development, activation, and terminal differentiation of the lymphocyte lineages. The most recently identified member of this family, the IL-21R, is expressed to varying degrees on B, T lymphocytes, and natural killer (NK) cells, whereas IL-21, is reportedly only produced by activated CD4+ T cells. In keeping with this expression pattern the IL-21:IL-21R interaction is important for the latter stages and function of all three lymphoid lineages. IL-21 is a regulator of A-cell differentiation to plasma cells as well as immunoglobulin class switching. In contrast, within the T-cell lineage, IL-21 acts as a co-stimulator of proliferation, enhances memory response, and modulates homeostasis. Within the innate immune system IL-21 has a role in the terminal differentiation of NK cells, enhancing cytotoxic function while also decreasing cellular viability. These immune maturation and stimulating functions have resulted in IL-21 being tested in a variety of models of immunity. In these contexts, IL-21 has shown very promising efficacy in a number of antitumor immune responses mediated by NK and or T lymphocytes.
Carbon Nanotube Transistor Circuits: Circuit-Level Performance Benchmarking and Design Options for Living with Imperfections (2007)

1D carbon nanotube FET (CNFET)-based circuits offer 4.6times faster FO4 speed and 12times energy-delay product improvement over 32nm node Si CMOS (including diameter and doping variations), provided circuits can be built that are immune to misaligned and metallic nanotubes. A design technique that guarantees correct logic operation in the presence of misaligned nanotubes is also presented.
A systematic study of the N-glycosylation sites of HIV-1 envelope protein on infectivity and antibody-mediated neutralization (2013)

This report provides the first systematic experimental account of the biological role of the entire PNGS on an HIV-1 Env, which should provide valuable insights for understanding the function of Env in HIV infection cycle and for developing future anti-HIV strategies.
Discretized streams: an efficient and fault-tolerant model for stream processing on large clusters (2012)

Many important “big data ” applications need to process data arriving in real time. However, current programming models for distributed stream processing are relatively low-level, often leaving the user to worry about consistency of state across the system and fault recovery. Furthermore, the models that provide fault recovery do so in an expensive manner, requiring either hot replication or long recovery times. We propose a new programming model, discretized streams (D-Streams), that offers a high-level functional programming API, strong consistency, and efficient fault recovery. D-Streams support a new recovery mechanism that improves efficiency over the traditional replication and upstream backup solutions in streaming databases: parallel recovery of lost state across the cluster. We have prototyped D-Streams in an extension to the Spark cluster computing framework called Spark Streaming, which lets users seamlessly intermix streaming, batch and interactive queries. 1
Identification of the Iron-Responsive Element for the Translational Regulation of Human Ferritin mRNA (1987)

Regulated translation of messenger RNA offers an important mechanism for the control of gene expression. The biosynthesis of the intracellular iron storage protein ferritin is translationally regulated by iron. A cis-acting element that is both necessary and sufficient for this translational regulation is present within the 5' nontranslated leader region of the human ferritin H-chain messenger RNA. In this report the iron-responsive element (IRE) was identified by deletional analysis. Moreover, a synthetic oligodeoxynucleotide was shown to be able to transfer iron regulation to a construct that would otherwise not be able to respond to iron. The IRE has been highly conserved and predates the evolutionary segregation between amphibians, birds, and man. The IRE may prove to be useful for the design of translationally regulated expression systems.
Tissue ingrowth of replamineform implants (1975)

The Replamineform process, a new technique for the fabrication of porous hard tissue implant materials which replicates the skeletal configuration of certain marine invertebrates, was used to manufacture 1 cm long by 0.5 cm diam cylinders. The inherent advantages of porous configurations obtained through this process are controlled, uniform pore size, controlled pore-microstructure ratio, and complete interconnection of pores. The specific materials studied were chrome-cobalt-molybdenum alloy, alphaA103, hydroxyapatite prepared by hydrothermal conversion, and the basic (aragonite) CaCO3 skeleton of the coral genus Porities. The implants were placed in the canellous bone of the distal femora and proximal tibiae of adult, mongrel dogs and analyzed at 8 weeks for tissue response and ingrowth. Uniformly, new bone was found to grow into the pores of these materials and become normally mineralized. These findings were determined by microradiography, scanning electron microscopy, electron microprobe analysis, and histology. No evidences of infection, rejection, or encapsulation were seen. In the case of those CaCO3 implants left in place for 1 year, there was almost complete resorption of the cylinders, with both bony trabeculae and unmineralized collagen (presumably osteoid) found at the sites of insertion.
Type I Shorthorn Sculpin Antifreeze Protein (2002)

A number of structurally diverse classes of "antifreeze" proteins that allow fish to survive in sub-zero ice-laden waters have been isolated from the blood plasma of cold water teleosts. However, despite receiving a great deal of attention, the one or more mechanisms through which these proteins act are not fully understood. In this report we have synthesized a type I antifreeze polypeptide (AFP) from the shorthorn sculpin Myoxocephalus scorpius using recombinant methods. Construction of a synthetic gene with optimized codon usage and expression as a glutathione S-transferase fusion protein followed by purification yielded milligram amounts of polypeptide with two extra residues appended to the N terminus. Circular dichroism and NMR experiments, including residual dipolar coupling measurements on a 15N-labeled recombinant polypeptide, show that the polypeptides are alpha-helical with the first four residues being more flexible than the remainder of the sequence. Both the recombinant and synthetic polypeptides modify ice growth, forming facetted crystals just below the freezing point, but display negligible thermal hysteresis. Acetylation of Lys-10, Lys-20, and Lys-21 as well as the N terminus of the recombinant polypeptide gave a derivative that displays both thermal hysteresis (0.4 degrees C at 15 mg/ml) and ice crystal faceting. These results confirm that the N terminus of wild-type polypeptide is functionally important and support our previously proposed mechanism for all type I proteins, in which the hydrophobic face is oriented toward the ice at the ice/water interface.