gebhart/patrepeval huggingface dataset:
Fibrinogen mediated activation of platelet aggregation and thromboxane A2 release: pathological implications in vascular disease. (1985)

The effect of a human fibrinogen preparation on in vitro platelet aggregation was assessed. Platelets were obtained from healthy volunteers. Human fibrinogen induced platelet aggregation in 65% of platelet rich plasma samples and enhanced submaximal platelet aggregation induced by heparin or by several conventional agonists in all samples. Aggregation induced by fibrinogen alone was reversed by the in vitro addition of human albumin. Fibrinogen induced aggregation was associated with the release of the vasoconstrictor, thromboxane A2. Preincubation with indomethacin inhibited both the aggregation and the release of thromboxane A2. Fibrinogen had no effect on in vitro vascular prostaglandin I2 synthesis (rat aortic rings) during a 60 minute incubation. The observed effects of fibrinogen on platelet function may be relevant to clinical conditions in which hyperaggregability of platelets is associated with hyperfibrinogenemia and thrombosis.
siRNA-Based Therapy Ameliorates Glomerulonephritis (2010)

RNA interference by short interfering RNAs (siRNAs) holds promise as a therapeutic strategy, but use of siRNAs in vivo remains limited. Here, we developed a system to target delivery of siRNAs to glomeruli via poly(ethylene glycol)-poly(l-lysine)-based vehicles. The siRNA/nanocarrier complex was approximately 10 to 20 nm in diameter, a size that would allow it to move across the fenestrated endothelium to access to the mesangium. After intraperitoneal injection of fluorescence-labeled siRNA/nanocarrier complexes, we detected siRNAs in the blood circulation for a prolonged time. Repeated intraperitoneal administration of a mitogen-activated protein kinase 1 (MAPK1) siRNA/nanocarrier complex suppressed glomerular MAPK1 mRNA and protein expression in a mouse model of glomerulonephritis; this improved kidney function, reduced proteinuria, and ameliorated glomerular sclerosis. Furthermore, this therapy reduced the expression of the profibrotic markers TGF-beta1, plasminogen activator inhibitor-1, and fibronectin. In conclusion, we successfully silenced intraglomerular genes with siRNA using nanocarriers. This technique could aid the investigation of molecular mechanisms of renal disease and has potential as a molecular therapy of glomerular diseases.
The Zebra striped network file system (1993)

Zebra is a network file system that increases throughput by striping file data across multiple servers. Rather than striping each file separately, Zebra forms all the new data from each client into a single stream, which it then stripes using an approach similar to a log-structured file system. This provides high performance for writes of small files as well as for reads and writes of large files. Zebra also writes parity information in each stripe in the style of RAID disk arrays; this increases storage costs slightly but allows the system to continue operation even while a single storage server is unavailable. A prototype implementation of Zebra, built in the Sprite operating system, provides 4--5 times the throughput of the standard Sprite file system or NFS for large files and a 20%-3x improvement for writing small files.
Delayed and nonunion fractures. (1992)

Failures in bone healing can result from technical problems, biologic failures, or a combination of the two. Inadequate stabilization of bone fragments against the effects of rotational forces is a common cause of nonunion. Early identification of a pseudoarthrosis can be difficult; the diagnosis is usually delayed, thus the morbidity associated with this disorder is significant. Often, the nonunion is complicated by atrophy of surrounding soft tissues, muscle contracture, and stiff joints. The goals in the treatment of the nonunion are to identify and correct the underlying causes, with the primary objective being the return of function. The type of treatment depends on the classification of the pseudarthrosis, including the condition of the surrounding soft tissues, blood supply, and viability of the nonunion, location, and presence or absence of infection.
Metrics on RNA Secondary Structures (2000)

Many different programs have been developed for the prediction of the secondary structure of an RNA sequence. Some of these programs generate an ensemble of structures, all of which have free energy close to that of the optimal structure, making it important to be able to quantify how similar these different structures are. To deal with this problem, we define a new class of metrics, the mountain metrics, on the set of RNA secondary structures of a fixed length. We compare properties of these metrics with other well known metrics on RNA secondary structures. We also study some global and local properties of these metrics.
Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model (2014)

Immunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor have shown great promise for a subset of patients with cancer. However, robust and safe combination therapies are still needed to bring the benefit of cancer immunotherapy to broader patient populations. To search for an optimal strategy of combinatorial immunotherapy, we have compared the antitumor activity of the anti-4-1BB/anti-PD-1 combination with that of the anti-PD-1/anti-LAG-3 combination in the poorly immunogenic B16F10 melanoma model. Pronounced tumor inhibition occurred only in animals receiving anti-PD-1 and anti-4-1BB concomitantly, while combining anti-PD-1 with anti-LAG-3 led to a modest degree of tumor suppression. The activity of the anti-4-1BB/anti-PD-1 combination was dependent on IFNγ and CD8(+) T cells. Both 4-1BB and PD-1 proteins were elevated on the surface of CD8(+) T cells by anti-4-1BB/anti-PD-1 cotreatment. In the tumor microenvironment, an effective antitumor immune response was induced as indicated by the increased CD8(+)/Treg ratio and the enrichment of genes such as Cd3e, Cd8a, Ifng, and Eomes. In the spleen, the combination treatment shaped the immune system to an effector/memory phenotype and increased the overall activity of tumor-specific CD8(+) CTLs, reflecting a long-lasting systemic antitumor response. Furthermore, combination treatment in C57BL/6 mice showed no additional safety signals, and only minimally increased severity of the known toxicity relative to 4-1BB agonist alone. Therefore, in the absence of any cancer vaccine, anti-4-1BB/anti-PD-1 combination therapy is sufficient to elicit a robust antitumor effector/memory T-cell response in an aggressive tumor model and is therefore a candidate for combination trials in patients.
Film Structure and Conductometric Hydrogen-Gas-Sensing Characteristics of Ultrathin Platinum Films (1999)

The structure and hydrogen-induced conductometric response of thin nanoparticulate platinum films has been investigated. Platinum films with a nominal thickness of 35 Å were deposited on silicon oxide and stabilized by thermal treatment in air at 673 K, resulting in an average platinum particle diameter of approximately 30 nm. These platinum films exhibited a positive temperature coefficient of resistance and resistance values intermediate between ultrathin and thick films. Exposure to ppm levels of hydrogen in the presence of 5% oxygen with nitrogen as the carrier gas caused decreases in electrical resistance. In the temperature range between 300 and 570 K, the relative response became more pronounced with increasing temperature, indicating that the response mechanism for hydrogen sensing is an activated process. In the temperature range of 370−470 K, the hydrogen concentration dependence of resistance changes can be divided into two nearly linear regimes. From 10 to 200 ppm of hydrogen, the response (ΔR/R0/CH2) is 0.36/1000 ppm H2, while above 200 ppm, the response is 0.01/1000 ppm. The decreased response at higher hydrogen concentrations can be attributed to saturation of the active sites for hydrogen oxidation. The response is significantly decreased in the absence of oxygen, suggesting that the surface-catalyzed hydrogen−oxygen reaction plays an important role in the sensing mechanism.
Purification of IgG Using Protein A or Protein G (2009)

Some strains of Staphylococcus aureus synthesize protein A, a group-specific ligand that binds to the Fc region of IgG from many species (1, 2). Protein A does not bind all subclasses of IgG, e.g., human IgG3, mouse IgG3, sheep IgG1, and some subclasses bind only weakly, e.g., mouse IgG1. For some species, IgG does not bind to protein A at all, e.g., rat, chicken, goat, and some MAbs show abnormal affinity for the protein. These properties make the use of protein A for IgG purification limited in certain cases, although it can be used to an advantage in separating IgG subclasses from mouse serum (3). Protein G (derived from groups C and G Streptococci) also binds to IgG Fc with some differences in species specificity from protein A. Protein G binds to IgG of most species, including rat and goat, and recognizes most subclasses (including human IgG3 and mouse IgG1), but has a lower binding capacity. Protein G also has a high affinity for albumin, although recombinant DNA forms now exist in which the albumin-binding site has been spliced out, and are therefore very useful for affinity chro-matography. Other streptococcal immunoglobulin binding proteins are protein H (binds IgG Fc), protein B, which binds IgA and protein Arp, which binds IgG & IgA. These are not generally available for immunochemical use.
Some corrections to the record on insect repellents and attractants. (1988)

Fifteen apparent errors of observation, reporting, interpretation, or attribution occurring in the insect repellent and attractant literature were examined. Topics discussed are the boiling point effect, solvents and solutions, repellent-treated netting, terpineol and diphenyl oxide, lactic acid, the smell and feel of deet (diethylmethylbenzamide), effective half-life, protection time, protection time of deet for men and women, McGuire's formula, "plussing out", King's classification, exorbitant doses, extrapolated doses, and extreme observations. The decay constant (1.36 hr-1) and half-life (0.51 hr) of a mosquito-repellent bath oil (Skin-So-Soft) are reported for the first time.
Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity (2018)

OX40 and its ligand are members of the TNF/TNF receptor superfamily, which includes various molecules influencing cellular signaling and function of both tumor and immune cells. The ability of OX40 to promote proliferation and differentiation of activated T cells fueled present attempts to modulate this immune checkpoint to reinforce antitumor immunity. While we recently found evidence for the involvement of OX40 in pathophysiology of acute myeloid leukemia including natural killer (NK) cell immunosurveillance, less is known on its role in acute lymphoblastic leukemia (ALL). In the present study, OX40 expression on ALL cells was significantly associated with positivity for the adverse risk factor BCR-ABL. In line, signaling via OX40 increased metabolic activity of primary ALL cells and resulted in release of cytokines involved in disease pathophysiology. Furthermore, interaction of ALL-expressed OX40 with its cognate ligand on NK cells stimulated ALL cell lysis. The data presented thus not only identify the yet unknown involvement of OX40/OX40L in ALL pathophysiology and NK cell immunosurveillance but also point to the necessity to thoroughly consider the consequences of modulating the OX40/OX40L molecule system beyond its effects on T cells when developing OX40-targeting approaches for cancer immunotherapy.
A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement. (1995)

A monoclonal antibody, RE2, raised by immunizing a rat with cell lysate of a mouse T cell clone, was found to directly kill interleukin 2-dependent T cell clones without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments with anti-rat immunoglobulin reconstituted the cytotoxicity. The cytotoxicity was temperature dependent: the antibody could kill target cells at 37 degrees C but not at 0 degrees C. Sodium azide, ethylenediaminetetraacetic acid, and forskolin did not affect the cytolytic activity of RE2, while the treatment of target cells with cytochalasin B and D completely blocked the activity. This suggested that the cell death involves a cytoskeleton-dependent active process. Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. The antibody also killed T cell lymphomas and T and B cell hybridomas only when these cells were preactivated with concanavalin A, lipopolysaccharide, or phorbol myristate acetate. Preactivated peripheral T and B cells were sensitive to the cytotoxicity of RE2, while resting T and B cells were insensitive. These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation.
Packaging of bio-MEMS: strategies, technologies, and applications (2005)

Biomicroelectromechanical systems (bio-MEMS) are MEMS which are designed for medical or biological applications. As with other MEMS, bio-MEMS frequently, have to be packaged to provide an interface to the macroscale world of the user. Bio-MEMS can be roughly divided in two groups. Bio-MEMS can be pure technical systems applied in a biological environment or technical systems which integrate biological materials as one functional component of the system. In both cases, the materials which have intimate contact to biological matter have to be biocompatible to avoid unintentional effects on the biological substances, which in case of medical implants, could harm the patient. In the case of biosensors, the use of nonbiocompatible materials could interfere with the biological subcomponents which would affect the sensor's performance. Bio-MEMS containing biological subcomponents require the use of "biocompatible" technologies for assembly and packaging; e.g., high temperatures occurring, for instance, during thermosonic wire bonding and other thermobonding processes would denature the bioaffinity layers on biosensor chips. This means that the use of selected or alternative packaging and assembly methods, or new strategies, is necessary for a wide range of bio-MEMS applications. This paper provides an overview of some of the strategies, technologies, and applications in the field of bio-MEMS packaging. It includes the following: strategies for the partitioning of subsystems within integrated microsystems for (bio)chemical analysis/synthesis; methods for microassembly of bio-MEMS; technologies for bonding of polymer bio-MEMS components; packaging of miniature medical devices; packaging of biosensors for in vitro applications; packaging of micropumps as a bio-MEMS component. The applications discussed are derived from different fields to demonstrate the plethora of bio-MEMS considerations. In commercial production, packaging is possibly the major cost factor of bio-MEMS-based products, and its development requires special attention.
Murine cardiac progenitor cells require visceral embryonic endoderm and primitive streak for terminal differentiation (1997)

Cardiac progenitor cells in avian and amphibian embryos are known to commit to cardiac lineage during gastrulation or early neurulation. These cells require cell interaction with anterior endoderm for their differentiation into cardiomyocytes. However, little is known about cell interaction in mammalian cardiogenesis. We investigated the staging of murine cardiomyocyte commitment and the role of cell interaction in differentiation of cardiac progenitor cells into cardiomyocytes, using cultures of various embryonic regions at 7.25 and 7.5 days post coitum (p.c.), respectively. To evaluate the terminal differentiation of cardiac progenitor cells, we employed three parameters; expression of spontaneous beating, myosin heavy chain (MHC) protein, and cardiac-specific genes (alpha myosin heavy chain, Csx/Nkx2.5 and myosin light chain 2V genes). mRNAs of cardiac-specific genes were detected in 7.25-day p.c. mesoderm by RT-PCR, suggesting that the genetic specification to cardiac lineage initiated in the mesoderm by 7.25 days p.c. The 7.25-day p.c. isolated mesoderm in 48 hr culture, however, failed to differentiate into spontaneous beating cardiomyocytes and exhibited non-organized MHC protein in 19% of these culture. In contrast, all of the 7.5-day p.c. isolated mesoderm differentiated into beating cardiomyocytes even in 24 hr culture. The 7.25-day p.c. mesoderm associated with primitive streak increased MHC protein expression in 93% of these cultures, although they formed beating foci in 3%. The 7.25-day p.c. explants containing both visceral embryonic endoderm and primitive streak succeeded in terminal differentiation into spontaneous beating cardiomyocytes. Our study suggests that cardiac progenitor cells obtain the potency to complete terminal differentiation autonomously at 7.5 days p.c., as a consequence of the multistep induction by cell interactions with both the primitive streak and visceral embryonic endoderm, following the genetic specification to cardiac lineage in the early gastrula stage.
3'-modified antisense oligodeoxyribonucleotides complementary to calmodulin mRNA alter behavioral responses in Paramecium. (1992)

The calcium-binding protein calmodulin has been shown to modulate the Ca(2+)-dependent ion channels of Paramecium tetraurelia. Mutations in the calmodulin gene of Paramecium result in an altered pattern of behavioral responses. Antisense oligodeoxyribonucleotides (ODNs), complementary to calmodulin mRNA in Paramecium, were synthesized from a modified solid support that introduced a 3'-hydroxyhexyl phosphate. These 3'-modified ODNs were tested for their ability to alter the behavioral response of Paramecium. The microinjection of antisense ODNs temporarily reduced the backward swimming behavior of the cells in test solutions containing Na+. The injection of sense and random 3'-modified ODNs, or unmodified antisense ODNs, had no effect. The antisense ODN-induced effect was reversed by the injection of calmodulin protein. The pattern of response of the injected cells in various behavioral test solutions indicated that the calmodulin antisense ODNs reduce the Ca(2+)-dependent Na+ current. Antisense ODNs, complementary either to the 5' start site or to an internal sequence of the calmodulin mRNA, were similarly effective in altering behavior. These results show that antisense ODNs may be utilized in ciliated protozoa as a tool for reducing the expression of specific gene products. In addition, Paramecium represents a powerful model system with which to study and develop antisense ODN technology.
Genes Galore: A Summary of Methods for Accessing Results from Large-Scale Partial Sequencing of Anonymous Arabidopsis cDNA Clones (1994)

High-throughput automated partial sequencing of anonymous cDNA clones provides a method to survey the repertoire of expressed genes from an organism. Comparison of the coding capacity of these expressed sequence tags (ESTs) with the sequences in the public data bases results in assignment of putative function to a significant proportion of the ESTs. Thus, the more than 13,400 plant ESTs that are currently available provide a new resource that will facilitate progress in many areas of plant biology. These opportunities are illustrated by a description of the results obtained from analysis of 1500 Arabidopsis ESTs from a cDNA library prepared from equal portions of poly(A+) mRNA from etiolated seedlings, roots, leaves, and flowering inflorescences. More than 900 different sequences were represented, 32% of which showed significant nucleotide or deduced amino acid sequences similarity to previously characterized genes or proteins from a wide range of organisms. At least 165 of the clones had significant deduced amino acid sequence homology to proteins or gene products that have not been previously characterized from higher plants. A summary of methods for accessing the information and materials generated by the Arabidopsis cDNA sequencing project is provided.
Artificial Antigen Presenting Cells: An Off the Shelf Approach for Generation of Desirable T-Cell Populations for Broad Application of Adoptive Immunotherapy (2015)

Adoptive transfer of antigen specific T-cells can lead to eradication of cancer and viral infections. The broad application of this approach has further been hampered by the limited availability of adequate numbers of T-cells for treatment in a timely manner. This has led to efforts for the development of efficient methods to generate large numbers of T-cells with specificity for tumor or viral antigens that can be harnessed for use in cancer therapy. Recent studies have demonstrated that during encounter with tumor antigen, the signals delivered to T-cells by professional antigen-presenting cells can affect T-cell programming and their subsequent therapeutic efficacy. This has stimulated efforts to develop artificial antigen-presenting cells that allow optimal control over the signals provided to T-cells. In this review, we will discuss the cellular artificial antigen-presenting cell systems and their use in T-cell adoptive immunotherapy for cancer and infections.
Comparison of Three Methods for Measuring Factor VIII Levels in Plasma (2003)

We compared 1-stage clot-based, chromogenic, and immunoassay methods for measuring factor VIII in plasma with a focus on the measurement of elevated levels of factor VIII. The chromogenic assay showed the best interassay imprecision for factor VIII levels near 150 IU/dL. The best correlation was between the 1-stage clot-based and chromogenic factor VIII assays (r2 = 0.934), and the lowest correlation was between the 1-stage clot-based and antigenic factor VIII assays (r2 = 0.821). The presence of heparin, low-molecular-weight heparin, lepirudin, or lupus inhibitors in the sample resulted in major interference in the 1-stage clot-based assay but not the chromogenic or antigenic factor VIII assays. Overall, the chromogenic factor VIII activity assay was the optimal method, showing good precision, the best overall correlation with other assays, and no interference from heparin, low-molecular-weight heparin, lepirudin, or lupus inhibitors.