gebhart/patrepeval huggingface dataset:
Generation of human autologous melanoma-specific cytotoxic T-cells using HLA-A2-matched allogeneic melanomas. (1990)

Autologous tumor-specific cytotoxic T-lymphocytes (CTLs), generated by repeated stimulation with autologous melanoma and expanded in interleukin 2, are major histocompatibility complex restricted. These CTLs recognize a common tumor-associated antigen in the presence of HLA class I determinants, suggesting that allogeneic melanomas which express the restricting HLA-A region antigen could substitute for the autologous tumor in the generation of CTLs. This was investigated in the HLA-A2 system. Four T-cell lines were established by stimulation of lymphocytes with either autologous tumor or an HLA-A2-matched allogeneic melanoma. Allogeneic stimulated CTLs specifically lysed the autologous tumor and demonstrated an identical pattern of HLA-A2 restriction, when compared to the autologous stimulated CTLs. Lysis by the allogeneic stimulated CTLs was blocked by a monoclonal antibody to HLA class I antigens; lysis was also inhibited by both autologous tumor or HLA-A2 allogeneic melanomas when evaluated in cold target competition studies. The allogeneic stimulated CTLs proliferated in response to both autologous tumor and HLA-A2 melanomas, but not in response to HLA-A2 nonmelanomas. By phenotypic analysis these CTLs were CD3+ and predominantly CD8+ cells. We conclude that autologous tumor-specific CTLs can be generated using HLA-A region-matched allogeneic melanomas for stimulation. Since established, HLA-typed melanoma tumor lines can be used in the absence of autologous tumor; this procedure can be applied clinically to a broad patient population and may prove useful in the adoptive immunotherapy of melanoma.
Automated Multiphasic Screening and Diagnosis (1964)

Automated Multiphasic Screening and Diagnosis Morris F. Collen, DirectorB.E.E.M.D., Leonard Rubin, ChiefM.D.Ph.D., Jerzy Neyman, Professor of Statistics, DirectorPh.D., George B. Dantzig, ChairmanPh.D., Robert M. Baer, ConsultantPh.D., and A. B. Siegelaub, BiostatisticianM.S. CopyRight https://doi.org/10.2105/AJPH.54.5.741 Published Online: August 29, 2011
Absorption by simultaneous diffusion and chemical reaction (1950)

The first page of this article is displayed as the abstract.
Assessing Thrombin Generation at the Point of Care (2009)

Point-of-care testing (POCT)1 draws vitality from the invention of new biosensors and, in this issue of Clinical Chemistry , takes a major step forward with the introduction of an amperometric test strip that assesses thrombin generation (1). Historically, on-site whole-blood measurements, such as the activated coagulation time (2)(3) and ionized calcium, improved our understanding of the complex pathophysiology occurring during surgery and massive transfusion (4). Gaps have persisted, however, in our ability to decipher hemostasis events. Fortunately, we now have an opportunity to improve bedside decision-making.

Potential applications include hemostatic treatment for hemophilias, inflammation and vascular remodeling, surgical microvascular bleeding, disseminated intravascular coagulation, thrombosis, drug therapy (e.g., hirudin and activated protein C), and severe sepsis, where previous insight into hyper- or hypocoagulable states has been difficult, if not impossible, with nonintegrative tests such as prothrombin time (PT) and activated partial thromboplastin time, and impractical with reagent- and labor-intensive thrombin assays requiring time-consuming processing steps and large sample volumes. Of course, we still must gain clinical experience with this new electrochemical thrombin biosensor and its benefits at the point of care (POC), whether hospital or home.

Miniaturized technologies developed and implemented for use in handheld POC instruments …
Quantum Machine Learning in Feature Hilbert Spaces (2019)

A basic idea of quantum computing is surprisingly similar to that of kernel methods in machine learning, namely, to efficiently perform computations in an intractably large Hilbert space. In this Letter we explore some theoretical foundations of this link and show how it opens up a new avenue for the design of quantum machine learning algorithms. We interpret the process of encoding inputs in a quantum state as a nonlinear feature map that maps data to quantum Hilbert space. A quantum computer can now analyze the input data in this feature space. Based on this link, we discuss two approaches for building a quantum model for classification. In the first approach, the quantum device estimates inner products of quantum states to compute a classically intractable kernel. The kernel can be fed into any classical kernel method such as a support vector machine. In the second approach, we use a variational quantum circuit as a linear model that classifies data explicitly in Hilbert space. We illustrate these ideas with a feature map based on squeezing in a continuous-variable system, and visualize the working principle with two-dimensional minibenchmark datasets.
Correction: Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3) (2009)

Background: Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes.
Alzheimer's Presenilin 1 Mutations Impair Kinesin-Based Axonal Transport (2003)

Several lines of evidence indicate that alterations in axonal transport play a critical role in Alzheimer's disease (AD) neuropathology, but the molecular mechanisms that control this process are not understood fully. Recent work indicates that presenilin 1 (PS1) interacts with glycogen synthase kinase 3beta (GSK3beta). In vivo, GSK3beta phosphorylates kinesin light chains (KLC) and causes the release of kinesin-I from membrane-bound organelles (MBOs), leading to a reduction in kinesin-I driven motility (Morfini et al., 2002b). To characterize a potential role for PS1 in the regulation of kinesin-based axonal transport, we used PS1-/- and PS1 knock-inM146V (KIM146V) mice and cultured cells. We show that relative levels of GSK3beta activity were increased in cells either in the presence of mutant PS1 or in the absence of PS1 (PS1-/-). Concomitant with increased GSK3beta activity, relative levels of KLC phosphorylation were increased, and the amount of kinesin-I bound to MBOs was reduced. Consistent with a deficit in kinesin-I-mediated fast axonal transport, densities of synaptophysin- and syntaxin-I-containing vesicles and mitochondria were reduced in neuritic processes of KIM146V hippocampal neurons. Similarly, we found reduced levels of PS1, amyloid precursor protein, and synaptophysin in sciatic nerves of KIM146V mice. Thus PS1 appears to modulate GSK3beta activity and the release of kinesin-I from MBOs at sites of vesicle delivery and membrane insertion. These findings suggest that mutations in PS1 may compromise neuronal function by affecting GSK-3 activity and kinesin-I-based motility.
The Rise of Chemodiversity in Plants (2012)

Plants possess multifunctional and rapidly evolving specialized metabolic enzymes. Many metabolites do not appear to be immediately required for survival; nonetheless, many may contribute to maintaining population fitness in fluctuating and geographically dispersed environments. Others may serve no contemporary function but are produced inevitably as minor products by single enzymes with varying levels of catalytic promiscuity. The dominance of the terrestrial realm by plants likely mirrored expansion of specialized metabolism originating from primary metabolic pathways. Compared with their evolutionarily constrained counterparts in primary metabolism, specialized metabolic enzymes may be more tolerant to mutations normally considered destabilizing to protein structure and function. If this is true, permissiveness may partially explain the pronounced chemodiversity of terrestrial plants.
Synthesis and Characterization of PEGylated Toll Like Receptor 7 Ligands (2011)

Toll-like receptor 7 (TLR7) is located in the endosomal compartment of immune cells. Signaling through TLR7, mediated by the adaptor protein MyD88, stimulates the innate immune system and shapes adaptive immune responses. Previously, we characterized TLR7 ligands conjugated to protein, lipid, or poly(ethylene glycol) (PEG). Among the TLR7 ligand conjugates, the addition of PEG chains reduced the agonistic potency. PEGs are safe in humans and widely used for improvement of pharmacokinetics in existing biologics and some low molecular weight compounds. PEGylation could be a feasible method to alter the pharmacokinetics and pharmacodynamics of TLR7 ligands. In this study, we systematically studied the influence of PEG chain length on the in vitro and in vivo properties of potent TLR7 ligands. PEGylation increased solubility of the TLR7 ligands and modulated protein binding. Adding a 6-10 length PEG to the TLR7 ligand reduced its potency toward induction of interleukin (IL)-6 by murine macrophages in vitro and IL-6 and tumor necrosis factor (TNF) in vivo. However, PEGylation with 18 or longer chain restored, and even enhanced, the agonistic activity of the drug. In human peripheral blood mononuclear cells, similar effects of PEGylation were observed for secretion of proinflammatory cytokines, IL-6, IL-12, TNF-α, IL-1β, and type 1 interferon, as well as for B cell proliferation. In summary, these studies demonstrate that conjugation of PEG chains to a synthetic TLR ligand can impact its potency for cytokine induction depending on the size of the PEG moiety. Thus, PEGylation may be a feasible approach to regulate the pharmacological properties of TLR7 ligands.
Lower Ordovician Brachiopoda from the Tourmakeady Limestone, Co. Mayo, Ireland (1985)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Droplet Microfluidics for Fabrication of Non‐Spherical Particles (2009)

We describe new developments for controlled fabrication of monodisperse non-spherical particles using droplet microfluidics. The high degree of control afforded by microfluidic technologies enables generation of single and multiple emulsion droplets. We show that these droplets can be transformed to non-spherical particles through further simple, spontaneous processing steps, including arrested coalescence, asymmetric polymer solidification, polymerization in microfluidic flow, and evaporation-driven clustering. These versatile and scalable microfluidic approaches can be used for producing large quantities of non-spherical particles that are monodisperse in both size and shape; these have great potential for commercial applications.
Modulation of ecotropic murine retroviruses by N-linked glycosylation of the cell surface receptor/amino acid transporter (1996)

The cell surface receptor for ecotropic host-range (infection limited to mice or rats) murine leukemia viruses (MuLVs) is the widely expressed system y+ transporter for cationic amino acids (CAT-1). Like other retroviruses, ecotropic MuLV infection eliminates virus-binding sites from cell surfaces and results in complete interference to superinfection. Surprisingly, infection causes only partial (ca 40 to 60%) loss of mouse CAT-1 transporter activity. The NIH/Swiss mouse CAT-1 (mCAT-1) contains 622 amino acids with 14 hydrophobic potential membrane-spanning sequences, and it is known that the third extracellular loop from the amino terminus is required for virus binding. Although loop 3 is hypervariable in different species and mouse strains, consistent with its proposed role in virus-host coevolution, loop 3 sequences of both susceptible and resistant species contain consensus sites for N-linked glycosylation. Both of the consensus sites in loop 3 of mCAT-1 are known to be glycosylated and to contain oligosaccharides with diverse sizes (J. W. Kim and J. M. Cunningham, J. Biol. Chem. 268:16316-16320, 1993). We confirmed by several lines of evidence that N-linked glycosylation occludes a potentially functional virus-binding site in the CAT-1 protein of hamsters, thus contributing to resistance of that species. To study the role of receptor glycosylation in animals susceptible to infection, we eliminated loop 3 glycosylation sites by mutagenesis of an mCAT-1 cDNA clone, and we expressed wild-type and mutant receptors in mink fibroblasts and Xenopus oocytes. These receptors had indistinguishable transport properties, as determined by kinetic and voltage-jump electrophysiological studies of arginine uptake in oocytes and by analyses Of L-[3H]arginine uptake in mink cells. Bindings of ecotropic envelope glycoprotein gp7O to the accessible receptor sites on surfaces of mink cells expressing wild-type or mutant mCAT-1 were not significantly different in kinetics or in equilibrium affinities (i.e., K(D) approximately 3.7 X 10(-10) to 7.5 X 10(-10) M). However, when values were normalized to the same levels of mCAT-1 transporter expression, cells with wild-type glycosylated mCAT-1 had only approximately 50% as many sites for gp70 binding as cells with unglycosylated mCAT-1. Although infection with ecotropic MuLV had no effect on activity of the mink CAT-1 transporter that does not bind virus, it caused partial down-modulation of wild-type mCAT-1 and complete down-modulation of unglycosylated mutant mCAT-1. These results suggest that N-linked glycosylation causes wild-type mCAT-1 heterogeneity and that a significant proportion is inaccessible to virus. In part because only the interactive fraction of mCAT-1 can be down-modulated, infected murine cells conserve an amino acid transport capability that supports their viability.
The development of a panel of human cell lines expressing specific human cytochrome P450 cDNAs. (1990)

We have isolated a human cytochrome P450IIE1 cDNA. This cDNA was transfected to AHH-1 human lymphoblasts and recombinant cell lines were isolated. Two means of selection for the presence of the vector were used, resistance to histidinol and resistance to hygromycin. Histidinol selection was found to give higher vector copy number than hygromycin B selection. AHH-1 cells expressing the P450IIE1 cDNA were sensitive to the cytotoxic and mutagenic effects of exposure to DMN at concentrations of 10 to 30 ng/ml for 28 hours. This system is more sensitive to DMN than systems using hepatocyte mediated activation.
Specific Ion Effects on the Water Solubility of Macromolecules:  PNIPAM and the Hofmeister Series (2005)

Aqueous processes ranging from protein folding and enzyme turnover to colloidal ordering and macromolecular precipitation are sensitive to the nature and concentration of the ions present in solution. Herein, the effect of a series of sodium salts on the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide), PNIPAM, was investigated with a temperature gradient microfluidic device under a dark-field microscope. While the ability of a particular anion to lower the LCST generally followed the Hofmeister series, analysis of solvent isotope effects and of the changes in LCST with ion concentration and identity showed multiple mechanisms were at work. In solutions containing sufficient concentrations of strongly hydrated anions, the phase transition of PNIPAM was directly correlated with the hydration entropy of the anion. On the other hand, weakly hydrated anions were salted-out through surface tension effects and displayed improved hydration by direct ion binding.
Induction of cytotoxic T cell precursors in vivo. Role of T helper cells. (1983)

Strain AS rats respond with two populations of cytotoxic T lymphocytes to stimulation in vitro by the major histocompatibility complex (MHC)-incompatible strain HL rat tumor (HL-A2T2). One is specific for MHC alloantigens present on both HL-A2T2 and normal HL targets, the other is tumor specific. The activation of these killer cells requires helper T lymphocytes. The tumor-specific helper cells depend on syngeneic radioresistant accessory cells to present the tumor antigens in an immunogenic form. The appropriate helper-accessory cell interaction results in the production of soluble factors which then induce the maturation of precursor cells into effective killer cells. Studies with a procedure for inducing negative selection of T cells in vivo showed that short-term exposure to HL-A2T2 tumor induced selection only for TH but not cytotoxic T lymphocyte precursors (CTLp). Simultaneous injection of supernatants from concanavalin A-activated spleen cell cultures, however, did produce selection of CTLp. These and other findings suggest that under normal circumstances in vivo, both signals (recognition of antigen and acceptance of maturation factors) are provided in the vicinity of an antigen presenting macrophage-like accessory cell.
The feasibility of using image parameters for test pattern selection during OPC model calibration (2010)

Model based optical proximity correction (MB-OPC) is essential for the production of advanced integrated circuits (ICs). Calibration of these OPC resist models uses empirical fitting of measured test pattern data. It seems logical that to produce OPC models, acquiring more data will always improve the OPC model accuracy; on the other hand, reducing metrology and model build time is also a critical and continually escalating requirement with the constant increase in the complexity of the IC development process. A trade off must therefore be made to obtain adequate number of data points that produce accurate OPC models without overloading the metrology tools and resources. In this paper, we are examining the feasibility of using the image parameters (IPs) to select the test patterns. The approach is to base our test pattern selection only on the IPs and verify that the resulting OPC model is accurate. Another approach is to reduce the data gradually in different steps using IP considerations and see how the OPC model performance changes. A third, compromise approach is to specify a test pattern set based on IPs and add to that set few patterns based on different considerations. The three approaches and their results are presented in details in this paper.
Effects of pore fluid flow and chemistry on compaction creep of calcite by pressure solution at 150°C (2011)

Uni-axial compaction creep experiments were performed on crushed limestone and analytical grade calcite powders at 150°C, a pore fluid pressure of 20 MPa, and effective axial stresses of 30 and 40 MPa. Previous experiments have shown that compaction under these conditions is dominated by intergranular pressure solution (IPS). The aim of the present tests was to determine the inter-relationship between pore fluid chemistry, compaction rate and the rate-controlling process of IPS. Intermittent flow-through runs conducted using CaCO3 solution showed no effect on creep rate at low strains (<4–5%) but a major acceleration at high strains (5–10%). Measurements of the Ca concentration present in fluid samples revealed the build-up of a high super-saturation of CaCO3 during compaction under zero flow conditions, especially at high strains. Active flow-through led to a drop in Ca concentration, which corresponded with creep acceleration. Addition of NaCl to the pore fluid, at a concentration of 0.5 m, increased the creep rate of the analytical grade calcite samples roughly in proportion to the enhancement of calcite solubility. Addition of Mg2+ and to the pore fluid, in concentrations of 0.05 and 0.001 m, respectively, caused major retardation of compaction creep. Integrating our mechanical, flow-through and chemical data points strongly to diffusion-controlled IPS being the dominant deformation mechanism in the calcite-water system under closed-system (zero flow) conditions at low strains (<4–5%), giving way to precipitation control at higher strains. Our fluid composition data suggest that this transition is because of accumulation of impurities in the pore fluid. As Mg2+ and phosphate ions are common in natural pore fluids, it is likely that retarded precipitation will be the rate-limiting step of IPS in carbonates in nature. To quantify diagenetic compaction and porosity-permeability reduction rates by IPS in carbonates needs to account for this.
Analysis of p53 mutation status in human cancer cell lines: a paradigm for cell line cross-contamination (2008)

Cancer cell lines are essential tools used in many areas of biomedical research. Using the last release of the UMD_p53 database (2007) (http://p53.free.fr), we analysed the p53 status of 1,211 cell lines published between 1989 and 2007. p53 mutations in cell lines from various types of cancers display a striking similarity in the distribution of mutations and in the pattern of mutational events compared to tumors, indicating that they are representative of the cells from which they were derived. Analysis of the residual transcriptional activity of p53 mutants identified in cell lines that displayed two different p53 mutations show that there is a high frequency of weak mutations that are paired with more potent mutations suggesting a driver/passenger configuration. Strikingly, we found discrepancies in the p53 status for 23% (88/384) of cell lines, for which the p53 status was established independently in two laboratories. Using the NCI-60 cell line panel as a model widely used in the literature, the p53 status could not be ascertained for 13 cell lines due to a lack of homogeneous data in the literature. Our study clearly confirms that misidentified cell lines are still a silent and neglected danger and that extreme care should be taken as a wrong p53 status could lead to disastrous experimental interpretations. The p53 web site has been updated with new sections describing the p53 status in the majority of cell lines and a special section devoted to cell lines with controversial p53 status.
Applications of Micro‐ and Nanofluidics in the Food Industry (2015)

Micro- and nanofluidics applications in the food industry represent a very interesting example of a multidisciplinary approach for development, involving engineering, chemistry, physics, biochemistry, microbiology, nanotechnology and biotechnology. Initially mutuated from semiconductor industry, these technologies are designed to manipulate small volumes of fluids. They are gaining momentum year after year and today they cover a wide range of applications, from real-time and on-site analysis for food safety to food processing and microstructuring. In this chapter the physical bases of microfluidics are introduced and a review of applications in the food industry is provided, illustrating successes, perspectives and challenges.
Role of α-Dystroglycan as a Schwann Cell Receptor for Mycobacterium leprae (1998)

alpha-Dystroglycan (alpha-DG) is a component of the dystroglycan complex, which is involved in early development and morphogenesis and in the pathogenesis of muscular dystrophies. Here, alpha-DG was shown to serve as a Schwann cell receptor for Mycobacterium leprae, the causative organism of leprosy. Mycobacterium leprae specifically bound to alpha-DG only in the presence of the G domain of the alpha2 chain of laminin-2. Native alpha-DG competitively inhibited the laminin-2-mediated M. leprae binding to primary Schwann cells. Thus, M. leprae may use linkage between the extracellular matrix and cytoskeleton through laminin-2 and alpha-DG for its interaction with Schwann cells.