gebhart/patrepeval huggingface dataset:
Intravenous immunoglobulin therapy for Guillain-Barr� syndrome with IgG anti-GM1 antibody (2001)

To compare the effects of intravenous immunoglobulin (IVIg) therapy and plasmapheresis for the IgG anti-GM1-positive subtype of Guillain-Barré syndrome (GBS), clinical and electrophysiological recoveries were analyzed in 24 patients treated with IVIg (n = 10) or plasmapheresis (n = 14). At entry, there were no significant differences between the two patient groups in age, sex, clinical severity (Hughes grade), sum scores of distally evoked amplitudes of compound muscle action potentials (CMAPs), and frequency of Campylobacter jejuni infection. The patients treated with IVIg had significantly lower Hughes grade scores 1, 3, and 6 months after onset (P = 0.03), and a higher probability to regain independent locomotion at 6 months [P(logrank) = 0.044]. In the IVIg group, markedly rapid recovery (improvement by two or more Hughes grade scores within 4 weeks) was more frequent (6 of 10 vs. 3 of 14, P = 0. 03), and delayed recovery (unable to walk independently at 6 months) was less frequent (0 of 10 vs. 4 of 14, P = 0.06). CMAP sum score at 6 months tended to be greater for the IVIg group (P = 0.07). For the IgG anti-GM1-positive subgroup of GBS patients, IVIg therapy may be a more efficacious treatment than plasmapheresis.
Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy (2014)

Signaling through programmed death 1 (PD-1) expressed by activated T lymphocytes inhibits their function and is a major mechanism for suppressing antitumor T cell responses in the tumor microenvironment. Recent clinical trials show that blockade of the B7-H1(programmed death ligand 1 [PD-L1])/PD-1 pathway with anti-PD-1 or anti-PD-L1 is active in several malignancies and produces durable responses in a subset of patients. Clinical response to these agents may be limited by other mechanisms of T-lymphocyte suppression in the tumor microenvironment, or absence of a significant tumor-specific T cell response in the tumor. Combinations with other therapies are likely to address at least several of the major mechanisms of resistance, supported by abundant preclinical data in animal tumor model systems. The combination of anti-PD-1 with anti-CTLA-4 demonstrated promising activity in metastatic melanoma and is being tested in multiple other malignancies. Other combinations based on PD-1/PD-L1 blockade are either in early clinical development or in planning stages. Many of the combinations based on PD-1/PD-L1 blockade are expected to produce a higher incidence of autoimmune-like toxicities, but clinical experience with agents such as ipilimumab suggests that toxicities will be manageable and reversible and the overall risk-benefit ratio will be acceptable.
A Short-Term Study of the Safety, Pharmacokinetics, and Efficacy of Ritonavir, an Inhibitor of HIV-1 Protease (1995)

In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.
FastV: From‐point Visibility Culling on Complex Models (2009)

Abstract We present an efficient technique to compute the potentially visible set (PVS) of triangles in a complex 3D scene from a viewpoint. The algorithm computes a conservative PVS at object space accuracy. Our approach traces a high number of small, volumetric frusta and computes blockers for each frustum using simple intersection tests. In practice, the algorithm can compute the PVS of CAD and scanned models composed of millions of triangles at interactive rates on a multi‐core PC. We also use the visibility algorithm to accurately compute the reflection paths from a point sound source. The resulting sound propagation algorithm is 10–20X faster than prior accurate geometric acoustic methods.
Precoat filtration with organic filter aids (1997)

Filter aids for precoat filtration can be produced from a wide variety of raw materials. Important quality criteria are consistent product quality, sufficient clarity, high retention capability, high flow rate, problem-free handling and environmentally friendly disposal as well as physiological safety. This article describes a range of filter aids and their applications, and discusses a new organic alternative to the mineral-based filter aid.
CONTROL OF RNA INITIATION AND ELONGATION AT THE HIV-1 PROMOTER (1994)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Evaluation of a new 3-h hybridization method for detecting the mecA gene in Staphylococcus aureus and comparison with existing genotypic and phenotypic susceptibilty testing methods (1999)

A new 3-h hybridization assay for detection of the staphylococcal mecA gene and the Staphylococcus aureus nuclease gene was evaluated by comparing the assay with existing genotypic and phenotypic methods. A total of 275 S. aureus strains were tested, including 257 epidemiologically unrelated strains (135 mecA-positive and 122 mecA-negative; collection I), and 18 strains with known borderline resistance to methicillin (collection II). Complete agreement was obtained for both collections when comparing the new assay with genotypic methods. We further evaluated a range of phenotypic susceptibility methods recommended in Europe and/or USA using the presence of the mecA gene as the defining standard. For collection I a high degree of agreement was found for both Etests (256 strains) and the oxacillin screen plate test (255 strains); the degree of agreement was lower for agar dilution methicillin (250 strains) and oxacillin 1 microg discs (239 strains). For the borderline strains a high degree of agreement was only obtained by the oxacillin screen plate test (17 of 18 strains). The other tests were less accurate, in the following order: agar dilution methicillin, Etest methicillin, Etest oxacillin and oxacillin discs with disagreement for four, five, nine and 13 strains, respectively. In conclusion, the new hybridization assay is a rapid and exact method for detecting the mecA gene and the S. aureus nuclease gene. This study confirms that phenotypic tests for methicillin resistance in S. aureus strains creates both false-susceptible and false-resistant results, especially for borderline resistant strains.
RF MEMS-based tunable filters (2001)

This paper overviews the application of RF MEMS switches in tunable filters as well as circuit developments for bandpass filters covering 110 MHz to 2.8 GHz. RF MEMS have several desirable features, including small size, low power requirements, and low loss. The basic operation of Raytheon's RF MEMS capacitive membrane switch is described. An overview of the technique used to integrate the switch into a variable capacitor structure with sixteen capacitance states is provided. Variable capacitor structures are used to construct multipole lumped bandpass filter designs, each with sixteen states. Finally, measured data from two representative five- and six-pole bandpass filters are presented. Characterization data demonstrates that the insertion loss for the five-pole filter using on-chip inductors was between 6.6 and 7.3 dB, and between 3.7 and 4.2 dB for the six-pole filter using off-chip inductors. © 2001 John Wiley & Sons, Inc. Int J RF and Microwave CAE 11: 276–284, 2001
Regulation of Kainate Receptors by cAMP-Dependent Protein Kinase and Phosphatases (1991)

In the mammalian central nervous system, receptors for excitatory amino acid neurotransmitters such as the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA)-kainate receptor mediate a large fraction of excitatory transmission. Currents induced by activation of the AMPA-kainate receptor were potentiated by agents that specifically stimulate adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase A (PKA) activity or were supported by intracellular application of the catalytic subunit of PKA by itself or in combination with cAMP. Furthermore, depression of these currents by a competitive inhibitor of PKA indicates that AMPA-kainate receptors are regulated by endogenous PKA. Endogenous protein phosphatases also regulate these receptors because an inhibitor of cellular phosphates enhanced kainate currents. Modulation of PKA and phosphatases may regulate the function of these receptors and thus contribute to synaptic plasticity in hippocampal neurons.
Failure to inhibit endotoxin-induced uveitis with antibodies that neutralize tumor necrosis factor. (1994)

Many of the effects of bacterial endotoxin are attributed to the cytokines that it induces. Tumor necrosis factor alpha (TNF alpha) may be responsible for many of the pathophysiologic effects of endotoxin because antibodies that neutralize TNF alpha reduce endotoxin-induced mortality in experimental animals and many of the activities of endotoxin can be mimicked by the infusion of TNF alpha. Accordingly, we tested the ability of an antibody that neutralizes TNF alpha in a well characterized rat model, endotoxin-induced uveitis. Rats receiving subcutaneous endotoxin had a prompt rise in serum TNF alpha that was eliminated by the monoclonal antibody. Small quantities of TNF alpha were detectable in aqueous humor after either subcutaneous or intravitreal injection of endotoxin. Endotoxin-induced uveitis as quantitated by cells and protein in aqueous humor was, however, not affected by the antibody. Similarly, intraocular inflammation was not reduced by the intravitreal injection of the neutralizing antibody. Although TNF alpha may mediate many of the systemic effects of endotoxin, its role in the intraocular inflammatory effects of endotoxin should be questioned.
Urinary Excretion of Ecgonine Methyl Ester, a Major Metabolite of Cocaine in Humans* (1984)

In this study, cocaine, benzoylecgonine, and ecgonine methyl ester excretion in urine was measured after intravenous and intranasal administration of cocaine at 16, 32, 48, and 96 mg doses to healthy cocaine users. Ecgonine methyl ester and cocaine were analyzed by gas chromatography/mass spectrometry. Benzoylecgonine was measured by immunoassay (EMIT) and liquid chromatography. Urinary ecgonine methyl ester accounted for 26 to 60% of the cocaine dose. Ecgonine methyl ester had an elimination halflife of 4.2 hr, compared with 5.1 hr for benzoylecgonine. These results indicate that ecgonine methyl ester accounts for most of the previously unidentified urinary metabolic products of cocaine. The time course of ecgonine methyl ester excretion is such that its detection can substitute for benzoylecgonine detection as a marker of cocaine use.
Characterization and Comparison of Intercellular Adherent Junctions Expressed by Human Corneal Endothelial Cells In Vivo and In Vitro (2008)

In vivo and in vitro HCECs displayed distinct protein cytolocalization of N-, VE-, and E-cadherins, beta- and p120-catenins, and p190. Progressive maturation of adherent junctions was associated with a decline of the proliferative potential. This information allows us to devise new strategies to engineer in vitro HCECs by targeting these components.
QUERYING PARSE TREE DATABASE OF MEDLINE TEXT TO SYNTHESIZE USER-SPECIFIC BIOMOLECULAR NETWORKS (2008)

Curated biological knowledge of interactions and pathways is largely available from various databases, and network synthesis is a popular method to gain insight into the data. However, such data from curated databases presents a single view of the knowledge to the biologists, and it may not be suitable to researchers' specific needs. On the other hand, Medline abstracts are publicly accessible and encode the necessary information to synthesize different kinds of biological networks. In this paper, we propose a new paradigm in synthesizing biomolecular networks by allowing biologists to create their own networks through queries to a specialized database of Medline abstracts. With this approach, users can specify precisely what kind of information they want in the resulting networks. We demonstrate the feasibility of our approach in the synthesis of gene-drug, gene-disease and protein-protein interaction networks. We show that our approach is capable of synthesizing these networks with high precision and even finds relations that have yet to be curated in public databases. In addition, we demonstrate a scenario of recovering a drug-related pathway using our approach.
β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6 (1999)

Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human beta-defensins are also chemotactic for immature dendritic cells and memory T cells. Human beta-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The beta-defensin-induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by beta-defensin. Thus, beta-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.
A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy. (2019)

TPS2652 Background:PD-1/PD-L1 checkpoint inhibitors demonstrated remarkable anti-tumor activity, but only a minority of patients achieve full clinical benefit with deep and durable responses. Translational studies suggest resistance to cancer immunotherapy can be mediated by additional immune checkpoints e.g. lymphocyte-activation gene 3 (LAG-3). The combination of LAG-3 and PD-1 mAbs synergistically improved anti-tumor response in murine models and early clinical trials. In a small cohort, TIL LAG-3 expression enriched for responsiveness in PD-1/PD-L1 relapsed/refractory patients. FS118 is a novel bispecific antibody incorporating a LAG-3 binding Fc-region into a PD-L1-specific IgG1 antibody to potentially deliver superior anti-tumor efficacy while limiting immunotherapy-related adverse effects by dual targeting. Methods: The FiH study (NCT03440437) is being conducted in adult patients with solid tumors who failed prior PD-1/PD-L1 treatment. Primary objectives of the study are to determine safety, PK and the maximum tolerated/recommended Phase 2 dose of FS118. Secondary objectives include preliminary evidence of efficacy, immunogenicity, PD profile and exposure/response correlation. 50 subjects from four study sites in the USA are planned to enrol in dose escalation initiated with accelerated titration (5 single subject cohorts) followed by 3+3 design and expansion cohorts. FS118 is administered weekly IV in 21-day treatment cycles until progression, unacceptable toxicity, withdrawal, or death. Patients are followed for safety, overall survival and initiation of subsequent therapy. DLT clearance, dose escalation and cohort expansion (to further characterise safety, PK/PD or clinical efficacy) are supervised by a safety review committee (SRC). Translational studies assess PD-L1/LAG-3 receptor occupancy, soluble PD-L1/LAG-3 levels and the correlation of FS118 exposure with selected PD markers of target engagement and response. Translational endpoints include TIL analysis, transcriptomic profiles and target expression analyses on tumor tissues. Cohorts 1 through 6 have been completed, enrollment in cohort 7 began December 2018. Clinical trial information: NCT03440437.
Network Simulations for A Mobile Network Architecture for Vehicles (2000)

In this paper, we present a network architecture for vehicle communication based on Mobile IP. The special network environment of a car allows optimizations but also requires modifications of existing approaches. We identify these issues and discuss the integration of possible solutions into the framework. For example, location information provided by a car navigation system can be used to improve handoff decisions and connectivity. To evaluate the architecture, simulation studies were carried out with the ns Network Simulator. This paper also gives an overview of the necessary modifications and extensions to ns and additional tools to simplify future research in this area.
Stepwise Construction of Conductive Au Colloid Multilayers from Solution (1997)

Very highly conductive Au films on glass substrates have been prepared by stepwise, layer-by-layer immobilization of 11-nm diameter colloidal Au particles and a short organic cross-linker. Particle coverage, optical spectra, nanometer-scale topography, and electrical resistance have been measured as a function of the number of colloidal Au layers and reveal a rapid transition from insulating to metallic behavior.
Catalytic properties of MGAT3, a putative triacylgycerol synthase (2006)

Acyl-coenzyme A:monoacylglycerol acyltransferase 3 (MGAT3) is a member of the MGAT family of enzymes that catalyze the synthesis of diacylglycerol (DAG) from monoacylglycerol (MAG), a committed step in dietary fat absorption. Although named after the initial identification of its MGAT activity, MGAT3 shares higher sequence homology with acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) than with other MGAT enzymes, suggesting that MGAT3 may also possess significant DGAT activity. This study compared the catalytic properties of MGAT3 with those of MGAT1 and MGAT2 enzymes using both MAG and DAG as substrates. Our results showed that in addition to the expected MGAT activity, the recombinant MGAT3 enzyme expressed in Sf-9 insect cells displayed a strong DGAT activity relative to that of MGAT1 and MGAT2 enzymes in the order MGAT3 > MGAT1 > MGAT2. In contrast, none of the three MGAT enzymes recognized biotinylated acyl-CoA or MAG as a substrate. Although MGAT3 possesses full DGAT activity, it differs from DGAT1 in catalytic properties and subcellular localization. The MGAT3 activity was sensitive to inhibition by the presence of 1% CHAPS, whereas DGAT1 activity was stimulated by the detergent. Consistent with high sequence homology with DGAT2, the MGAT3 enzyme demonstrated a similar subcellular distribution pattern to that of DGAT2, but not DGAT1, when expressed in COS-7 cells. Our data suggest that MGAT3 functions as a novel triacylglycerol (TAG) synthase that catalyzes efficiently the two consecutive acylation steps in TAG synthesis.
Isolation and detection of single molecules on paramagnetic beads using sequential fluid flows in microfabricated polymer array assemblies (2011)

We report a method for isolating individual paramagnetic beads in arrays of femtolitre-sized wells and detecting single enzyme-labeled proteins on these beads using sequential fluid flows in microfabricated polymer array assemblies. Arrays of femtolitre-sized wells were fabricated in cyclic olefin polymer (COP) using injection moulding based on DVD manufacturing. These arrays were bonded to a complementary fluidic structure that was also moulded in COP to create an enclosed device to allow delivery of liquids to the arrays. Enzyme-associated, paramagnetic beads suspended in aqueous solutions of enzyme substrate were delivered fluidically to the array such that one bead per well was loaded by gravity. A fluorocarbon oil was then flowed into the device to remove excess beads from the surface of the array, and to seal and isolate the femtolitre-sized wells containing beads and enzyme substrate. The device was then imaged using standard fluorescence imaging to determine which wells contained single enzyme molecules. The analytical performance of this device as the detector for digital ELISA compared favourably to the standard method, i.e., glass arrays mechanically sealed against a silicone gasket; prostate specific antigen (PSA) could be detected from 0.011 pg mL(-1) up to 100 pg mL(-1). The use of an enclosed fluidic device to isolate beads in single-molecule arrays offers a multitude of advantages for low-cost manufacturing, ease of automation, and instrument development to enable applications in biomarker validation and medical diagnosis.
Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31. (1994)

We have developed a low stringency polymerase chain reaction (LSPCR) to isolate the unknown neighboring region around a known DNA sequence, thus allowing efficient targeted gene walking. The method involves the polymerase chain reaction (PCR) with a single primer under conditions of low stringency for primer annealing (40 degrees C) for the first few cycles followed by more cycles at high stringency (55 degrees C). This enables the amplification of a targeted DNA fragment along with other nontargeted fragments. High stringency (55 degrees C) nested PCRs with end-labeled primers are then used to generate a ladder of radioactive bands, which accurately identifies the targeted fragment(s). We performed LSPCR on human placental DNA using a highly conserved sodium channel-specific primer for 5 cycles at 40 degrees C followed by 27 cycles at 55 degrees C for primer annealing. Subsequently, using higher stringency (55 degrees C) PCR with radiolabeled nested primers for 8 cycles, we have isolated a 0.66-kb fragment of a putative human sodium channel gene. Partial sequence (325 bp) of this fragment revealed a 270-bp region (exon) with homology to the rat brain sodium channel III alpha (RBIII) gene at the nucleotide (87%) and amino acid (92%) levels. Therefore, we putatively assign this sequence as a part of a gene coding the alpha-subunit of a human brain type III sodium channel (SCN3A). Using PCR on two human/rodent somatic cell hybrid panels with primers specific to this putative SCN3A gene, we have localized this gene to chromosome 2. Fluorescence in situ hybridization to human metaphase chromosomes was used to sublocalize the SCN3A gene to chromosome at 2q24-31. In conclusion, LSPCR is an efficient and sensitive method for targeted gene walking and is also useful for the isolation of homologous genes in related species.
Type I Interferons Keep Activated T Cells Alive (1999)

Antigen injection into animals causes antigen-specific T cells to become activated and, rapidly thereafter, die. This antigen-induced death is inhibited by inflammation. To find out how inflammation has this effect, various cytokines were tested for their ability to interfere with the rapid death of activated T cells. T cells were activated in vivo, isolated, and cultured with the test reagents. Two groups of cytokines were active, members of the interleukin 2 family and the interferons (IFNs) alpha and beta. This activity of IFN-alpha/beta has not been described previously. It was due to direct effects of the IFNs on the T cells and was not mediated by induction of a second cytokine such as interleukin 15. IFN-gamma did not slow the death of activated T cells, and therefore the activity of IFN-alpha/beta was not mediated only by activation of Stat 1, a protein that is affected by both classes of IFN. IFN-alpha/beta did not raise the levels of Bcl-2 or Bcl-XL in T cells. Therefore, their activity was distinct from that of members of the interleukin 2 family or CD28 engagement. Since IFN-alpha/beta are very efficiently generated in response to viral and bacterial infections, these molecules may be among the signals that the immune system uses to prevent activated T cell death during infections.