gebhart/patrepeval huggingface dataset:
Anticoagulant effects and tissue factor pathway inhibitor after intrapulmonary low-molecular-weight heparin (1996)

The present study was designed to investigate the anticoagulant action of inhaled low-molecular-weight (LMW) heparin on the release of tissue factor pathway inhibitor (TFPI) and on antifactor Xa activity, Heptest, activated partial thromboplastin time (APTT) and thrombin clotting time (TCT) in healthy volunteers. 3000 IU (group 1), 9000 IU (group 2), 27,000 IU (group 3) or 54,000 IU (group 4) LMW-heparin were given to 20 healthy volunteers each at 4 weeks intervals by inhalation. For safety reasons a dose escalating design was chosen. APTT and TCT did not change after inhalation of any dose of LMW-heparin as well as all parameters in group 1. In group 2, Heptest coagulation times were prolonged from 18.7 +/- 2.0 s before to 26.1 +/- 5.2 s 6 h and 20.5 +/- 1.9 s 24 h after inhalation and the other parameters remained uneffected. In group 3, S2222 method and the protamine assay increased from 0.01 to about 0.1 IU/ml 6 h after inhalation and returned to normal values after 24 h. TFPI antigen increased from 74.1 +/- 13.9 to 80.5 +/- 14.2 ng/ml 3 h after inhalation. TFPI activity remained unchanged. Heptest coagulation values were prolonged to 42 +/- 7.6 s after 6 h and returned to normal within 72 h after inhalation. In group 4, the following changes were observed: antifactor Xa activity increased to 0.343 +/- 0.196 U/ml after 6 h and normalized after 72 h. The protamine assay detected 0.2 +/- 0.18 U LMWH/ml after 6 h, TFPI antigen increased to 103 +/- 17.9 ng/ml and TFPI activity to 1.14 +/- 0.23 U 3 h after inhalation. All tests were normal after 24 h. Heptest coagulation values increased to 77.5 +/- 11.8 s 6 h after inhalation and normalized after 144 h. The area under the activity time curve of the S2222 method and of the Heptest assay increased with increasing doses (r = 0.677 and r = 0.571), respectively. The calculated elimination half-life of the aXa-effect was 7.5 h using S2222-, Heptest- and protamine assays. The data demonstrate a resorption of LMW-heparin by intrapulmonary route in man. The dose to produce antifactor Xa levels, prolongations of Heptest coagulation values and in releasing TFPI is about ten-fold higher than after subcutaneous administration.
SMT-compatible large-tolerance "OptoBump" interface for interchip optical interconnections (2003)

A new optical interface called OptoBump has been developed to couple optoelectronic packages to an optoelectronic printed circuit board, thus enabling economical chip-to-chip optical interconnections. The optoelectronic packages have vertical-cavity surface-emitting laser (VCSEL) and PD-array chips in their cavity and an large scale integrated (LSI) mounted on top. A package converts high-speed electrical signals from the LSI into an array of optical signals, which are emitted from the bottom. The PCB contains integrated polymer optical waveguides to optically connect packages, and the use of surface-mount technology (SMT) to mount packages on the printed circuit board (PCB) keeps assembly costs low. The key to making the OptoBump interface fully compatible with SMT is the integration of microlens arrays directly into both packages and the PCB. A wide, collimated optical beam couples a package to the board across a narrow air gap and provides a large tolerance to misalignment during the SMT process. This paper explains the concept of the OptoBump interface, the optical coupling design by ray-trace simulation, and the fabrication of polymer microlenses and polymer waveguides. Experimental results revealed that the OptoBump interface provides a large tolerance of /spl plusmn/50 /spl mu/m, which is large enough for use with SMT. The OptoBump interface can replace high-speed electrical wiring at the chip level and also offers the benefit of not having any optical fibers or connectors on the board. Thus, it has the potential to bring about a revolutionary change in optoelectronic packaging.
Object-oriented video (1992)

Graphics and live video are widely employed in remotely-controlled systems like industrial plants. Interaction with live video is, however, more limited compared with graphics as users cannot interact with objects being observed in the former. Object-Oriented Video techniques are described allowing object-oriented interactions, including the use of real-world objects in live video as reference cues, direct manipulation of them, and graphic overlays based on them, which enable users to work in a real spatial context conveyed by the video. Users thereby understand intuitively what they are operating and see the result of their operation.
On the relationship between the Fourier and fractional Fourier transforms (1996)

In recent years, the fractional Fourier transform has been the focus of many research papers. In this letter, we show that the fractional Fourier transform is nothing more than a variation of the standard Fourier transform and, as such, many of its properties, such as its inversion formula and sampling theorems, can be deduced from those of the Fourier transform by a simple change of variable.
Prophylactic Lactobacillus GGReduces Antibiotic-Associated Diarrhea in Children With Respiratory Infections: A Randomized Study (1999)

On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (chi(2) = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was -11% (-21%-0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3-6) and the duration of diarrhea (mean: 4 days; range: 2-8). The activities of fecal urease and beta-glucuronidase, but not beta-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. (ABSTRACT TRUNCATED)
A compact, high performance atomic magnetometer for biomedical applications (2013)

We present a highly sensitive room-temperature atomic magnetometer (AM), designed for use in biomedical applications. The magnetometer sensor head is only 2 × 2 × 5 cm3 and is constructed using readily available, low-cost optical components. The magnetic field resolution of the AM is <10 fT Hz–1/2, which is comparable to cryogenically cooled superconducting quantum interference device (SQUID) magnetometers. We present side-by-side comparisons between our AM and a SQUID magnetometer, and show that equally high quality magnetoencephalography and magnetocardiography recordings can be obtained using our AM.
Encapsulation and capsular types in isolates of Staphylococcus aureus from different sources and relationship to phage types (1985)

The relationship of capsular types of Staphylococcus aureus to type of infection, carrier state, and phage type was studied in a collection of 477 isolates from 380 infection sites. Capsular polysaccharides were demonstrated by precipitation and agglutination with 11 monospecific antisera. When only one isolate from each infection was considered, 63% were of type 8 and 16% were of type 5. Of all the isolates tested, over 90% were encapsulated. We did not demonstrate any marked difference in the distribution of capsular types between isolates from the blood stream or purulent processes and isolates from healthy carriers or food. Most isolates from bovine mastitis milk had nontypeable capsules. The capsular type seemed stable in culture, and encapsulation had no apparent influence on susceptibility to phages. Of 27 phage-propagating strains maintained via culture transfer on artificial media over many years, 16 (59%) produced capsules. A striking association between certain phage patterns and capsular types was demonstrated.
The global health burden of infection‐associated cancers in the year 2002 (2006)

Several infectious agents are considered to be causes of cancer in humans. The fraction of the different types of cancer, and of all cancers worldwide and in different regions, has been estimated using several methods; primarily by reviewing the evidence for the strength of the association (relative risk) and the prevalence of infection in different world areas. The estimated total of infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of the global cancer burden. The principal agents are the bacterium Helicobacter pylori (5.5% of all cancer), the human papilloma viruses (5.2%), the hepatitis B and C viruses (4.9%), Epstein-Barr virus (1%), human immunodeficiency virus (HIV) together with the human herpes virus 8 (0.9%). Relatively less important causes of cancer are the schistosomes (0.1%), human T-cell lymphotropic virus type I (0.03%) and the liver flukes (0.02%). There would be 26.3% fewer cancers in developing countries (1.5 million cases per year) and 7.7% in developed countries (390,000 cases) if these infectious diseases were prevented. The attributable fraction at the specific sites varies from 100% of cervix cancers attributable to the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide) caused by liver flukes.
Laser-scanning parameters and latitudes in laser xerography (1982)

The operating parameters required of a laser-scanning system to give optimum line and pixel reproduction are calculated. The shapes of isolated lines and pixels are predicted as a function of the output scanning parameters. Isophote maps for these lines and pixels are given for a sampling of scanning parameters. A sensitivity analysis demonstrates the effect of variations in laser power and variations in photoreceptor sensitivity. It is shown that laser-scanned xerographic systems are least sensitive to variations in laser power and to inhomogeneities in photoreceptor sensitivity when the system is operated in tight-focus conditions, i.e., the percent intensity at overlap is < or =50%.
Conserved primary sequences of the DNA terminal proteins of five different human adenovirus groups (1979)

The 31 human adenoviruses (Ad) from five groups (A-E) whose DNAs are <20% homologous by molecular hybridization. Ad5 (group C) DNA contains a 55,000-dalton protein probably covalently bound to each 5' terminus. This covalently bound protein may be analogous to polypeptides found in other viral and nonviral systems that are covalently bound to genomic DNAs or RNAs and that are thought to function in DNA or RNA replication. Because of the importance of proteins linked to nucleic acids, we have investigated whether DNAs from all five groups of human adenoviruses have terminal proteins, as well as the peptide relationships among the different terminal proteins. We show here that DNAs from Ad12, 7, 2, 19, and 4, representing Ad groups A-E, respectively, all contain covalently bound proteins of about 55,000 daltons. To investigate the peptide relatedness among the terminal proteins, we prepared microgram quantities of covalently bound protein from Ads in groups A-E and compared their chymotryptic and tryptic (125)I-labeled peptide maps. We find that the covalently bound protein maps of the five Ad groups are highly related and possibly identical. On the other hand, the tryptic and chymotryptic peptide maps of the major virion protein II and the core proteins V and VII of groups B, C, and E Ads show considerable heterology. Assuming that the covalently bound protein is virally coded, the conserved primary sequence of these proteins suggests a major functional role for the protein in Ad replication. Because the genetic origin of the Ad covalently bound proteins is not established, our data are also consistent with the possibility that the protein is coded by a cellular gene.
Immunobiology of Human Melanoma Antigens MART-1 and gp100 and their Use for Immuno-Gene Therapy (1997)

Two genes encoding human melanoma antigens MART-1 and gp100 recognized by HLA-A2 restricted melanoma reactive CTL derived from tumor infiltrating lymphocytes (TIL) were isolated by cDNA expression cloning methods. Multiple unmutated self peptides were identified as T cell epitopes in these melanocyte/melanoma specific proteins (2 from MART-1 and 5 from gp100). Most of these melanoma epitopes contain non-dominant anchor amino acids at the primary anchor positions and have intermediate binding affinity to HLA-A2.1. Melanoma reactive CTL were efficiently induced from PBL and TIL of patients by in vitro stimulation with PBMC pulsed with these epitopes. There is a significant correlation between vitiligo development and clinical response to IL2 based immunotherapy, suggesting that autoreactive T cells are involved in melanoma regression in vivo. These results have implications for understanding the nature of tumor antigens recognized by T cells and for the development of new cancer immunotherapies.
A phase 1b study of the anti-PD-1 monoclonal antibody BGB-A317 (A317) in combination with the PARP inhibitor BGB-290 (290) in advanced solid tumors. (2017)

3013 Background: The release of tumor-associated antigens may enhance the response to immunotherapy. BGB-A317, a humanized IgG4 variant monoclonal antibody engineered to have no Fc gamma receptor binding, targets the programmed cell death-1 (PD-1) receptor. It is being developed in solid and hematologic malignancies at a dose of 200 mg IV Q3W. BGB-290, a potent inhibitor of PARP 1/2, is hypothesized to promote neoantigen release that will potentially increase the efficacy of BGB-A317. A phase 1 study identified 60mg BID as the recommended Phase 2 dose (RP2D) for BGB-290. This study consists of initial dose escalation to determine the maximum-tolerated dose (MTD), safety, PK profile, and preliminary anti-tumor activity of the combination, followed by expansion into ovarian, breast, prostate, gastric, bladder, pancreatic and small cell lung cancers. Methods: Cohorts of 6 -12 pts with advanced solid tumors were treated in each of 5 planned dose levels (DLs). In DLs 1-3, BGB-290 doses ranged between 20-60mg PO BID with BGB-A317 2mg/kg IV Q3W. In DLs 4 - 5, BGB-290 doses were 40 or 60 mg BID; A317 was given at 200 mg IV Q3W based on PK data from a single agent Phase 1 study. Results: As of 16 Jan 2017, 38 pts [median age 59 years (34-75)] were treated in DLs 1-4; enrollment to DL5 is ongoing. One DLT of persistent Gr 2 nausea was reported in DL 4. The most common adverse event (AE) considered related to both study drugs was fatigue (10.5%). Immune-related AEs were Gr 3 hypophysitis (n = 1), Gr 3 or 4 autoimmune hepatitis(n = 2), and Gr 2 elevated AST/ALT (n = 1). Decreases in tumor burden have been observed in 16 pts; 7 achieved a PR (5 with ovarian and one each with uterine and pancreatic cancer) and one CR was observed in ovarian cancer. Six pts had SD for &gt; 6 months including 2 pts with pancreatic cancer who received BGB-A317+BGB-290 for 189 and 281 days. Plasma/serum exposure of BGB-290 and BGB-A317 were consistent with those in single-agent trials. Conclusions: BGB290 and BGB-A317 can be combined. Dose expansion in multiple tumor types is planned to commence in 2017 once the RP2D is determined. Clinical trial information: NCT02660034.
Disulfide Bond Assignment in Human Interleukin-7 by Matrix-assisted Laser Desorption/Ionization Mass Spectroscopy and Site-directed Cysteine to Serine Mutational Analysis (1997)

Interleukin-7 (IL-7) is a proteinaceous biological response modifier that has a bioactive tertiary structure dependent on disulfide bond formation. Disulfide bond assignments in human (h)IL-7 are based upon the results of matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy and Cys to Ser mutational analyses. A gene encoding the hIL-7 was synthesized incorporating Escherichia coli codon usage bias and was used to express biologically active protein as determined by stimulation of precursor B-cell proliferation. MALDI mass spectroscopic analysis of trypsin-digested hIL-7 was performed and compared with the anticipated results of a simulated tryptic digestion. Many of the anticipated hIL-7 tryptic fragments were detected including one with a molecular mass equivalent to the sum of two polypeptides linked through a disulfide bond formed from Cys residues (Cys3 and Cys142). Subsequently, Cys to Ser substitution mutational analyses were performed. A hIL-7 variant with all six Cys substituted with Ser was found to be biologically inactive (EC50 > 1 x 10(-7) M). In contrast, a family of single disulfide bond-forming variants of hIL-7 were constructed by reintroducing Cys pairs (Cys3-Cys142, Cys35-Cys130, and Cys48-Cys93), and each could stimulate cell proliferation with an EC50 of 4 x 10(-9), 2 x 10(-8), and 2 x 10(-9) M, respectively. In single disulfide bond-forming mutants of hIL-7, the ability to stimulate cell proliferation was abolished in the presence of 2 mM dithiothreitol. The results presented strongly suggest that only a single disulfide bond is required for hIL-7 to form a tertiary structure capable of stimulating precursor B-cell proliferation.
Pigs with von Willebrand disease may be resistant to experimental infective endocarditis. (1992)

Indirect evidence suggests that the blood platelet is important in the pathogenesis of experimental infective endocarditis. Mechanical injury to the endocardial surface causes deposition of fibrin and platelets; injected microorganisms quickly localize to this lesion. Endocarditis pathogens also bind to and activate platelets. We used our previously described animal model for inducing infective endocarditis in normal pigs and applied it to animals with severe von Willebrand disease. The model uses catheter-induced trauma to the aortic valve and endocardium, followed by intravenous injection of group C streptococci. Control animals all showed typical clinical and laboratory evidence of endocarditis. In contrast, in pigs with von Willebrand disease (n = 4) endocarditis failed to develop. Studies in vitro of platelet-bacteria interactions showed that platelets derived from both normal and diseased pigs were equal in their ability to bind to and be activated by group C streptococci. These data suggest that normal platelet function is important in the pathogenesis of experimental infective endocarditis.
Extracellular matrix mediates a molecular balance between vascular morphogenesis and regression (2008)

Extracellular matrix-derived signals lead to critical morphologic changes mediated through cytoskeletal rearrangements that control the shape, function and signaling events in endothelial cell-lined vessels regulating tube formation, remodeling, stabilization and regression. These signals control both vascular morphogenic and regression events, and thus a molecular balance exists to control the extent and function of vascular tube networks within tissues.
Synthesis of novel cyclic sulfone dihydropyridines facilitated by a selective ethyl diazoacetate ring expansion (1990)

Abstract A series of novel cyclic sulfone dihydropyridines with five to nine membered rings have been synthesized. Anomalous intermediates isolated from the Hantzch condensation were found to vary depending on the sulfone ring size and aromatic substitution. Tin tetrachloride has been shown to be a superior Lewis acid catalyst for ethyl diazoacetate ring expansion of the requesite β‐keto cyclic sulfone precursors.
Bismuth subsalicylate in the treatment of H2 blocker resistant duodenal ulcers: role of Helicobacter pylori. (1992)

Fifty nine patients with Helicobacter pylori positive duodenal ulcers that failed to heal after a six week course of treatment with H2 blockers were randomly assigned to one of the following three regimens: (i) bismuth subsalicylate, 600 mg three times daily (n = 19), (ii) ranitidine, 300 mg at night (n = 20), (iii) bismuth subsalicylate plus ranitidine (n = 20). Cumulative ulcer healing rates after four and eight weeks respectively were as follows: bismuth subsalicylate 74% (14/19) and 95% (18/19), ranitidine 40% (8/20) and 65% (13/20), bismuth subsalicylate plus ranitidine 80% (16/20) and 95% (19/20). Bismuth subsalicylate treatment was better than ranitidine at both four and at eight weeks (p less than 0.05). The clearance rates for H pylori after four weeks were: bismuth subsubsalicylate 58%, ranitidine 0%, bismuth subsalicylate plus ranitidine 55%. After stopping bismuth therapy bacterial recrudescence frequently occurred. After bismuth treatment 86% (19/22) of ulcers had healed if H pylori had been cleared, whereas only 65% (11/17) had healed if H pylori persisted (NS). This study shows that bismuth subsalicylate is more effective in the treatment of resistant duodenal ulcers than standard dose ranitidine. It may be that suppression of H pylori by bismuth subsalicylate promotes ulcer healing.
Binary Mixtures of Rod-like Molecules with p-Methoxybenzylidene-p′-n-Butylaniline (1971)

Abstract We have studied the effect of various rod-like molecules on the nematic-isotropic transition temperature, T e, of p-methoxybenzylidene-p′-butylaniline (MBBA). Specifically, we have former binary systems of MBBA with the even alkanols, C2-C18, and the polypeptide, poly-γ-benzyl-l-glutamate (PBLG). The results are briefly: (a) all the alkanols contribute to a lowering of T e. Evidence is presented that the longer rods (if rigid) tend to depress T e less; (b) in the two-phase system of PBLG and MBBA, the large agglomerated regions of PBLG and MBBA appear to have a transition temperature slightly higher than the pure nematic region.
Secretion of a chimeric T-cell receptor-immunoglobulin protein. (1987)

To produce sufficient quantities of soluble T-cell receptor protein for detailed biochemical and biophysical analyses we have explored the use of immunoglobulin--T-cell receptor gene fusions. In this report we describe a chimeric gene construct containing a T-cell receptor alpha-chain variable (V) domain and the constant (C) region coding sequences of an immunoglobulin gamma 2a molecule. Cells transfected with the chimeric gene synthesize a stable protein product that expresses immunoglobulin and T-cell receptor antigenic determinants as well as protein A binding sites. We show that the determinant recognized by the anticlonotypic antibody A2B4.2 resides on the V alpha domain of the T-cell receptor. The chimeric protein associates with a normal lambda light chain to form an apparently normal tetrameric (H2L2, where H = heavy and L = light) immunoglobulin molecule that is secreted. Also of potential significance is the fact that a T-cell receptor V beta gene in the same construct is neither assembled nor secreted with the lambda light chain, and when expressed with a C kappa region it does not assemble with the chimeric V alpha C gamma 2a protein mentioned above. This indicates that not all T-cell receptor V regions are similar enough to immunoglobulin V regions for them to be completely interchangeable.
Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol (2011)

This study demonstrates for the first time that MDSCs play a critical role in attenuating acute inflammation in the liver, and that agents such as CBD, which trigger MDSCs through activation of TRPV1 vanilloid receptors may constitute a novel therapeutic modality to treat inflammatory diseases.
Gelatin nanoparticles as a new and simple gene delivery system. (2005)

Cationized gelatin nanoparticles have shown the potential of being a new effective carrier for nonviral gene delivery. The major benefit of gelatin nanoparticles is not only the very low cell toxicity, but also their simple production combined with low costs and multiple modification opportunities offered by the matrix molecule.