gebhart/patrepeval huggingface dataset:
Susceptibility to Neurodegeneration in a Glaucoma Is Modified by Bax Gene Dosage (2005)

In glaucoma, harmful intraocular pressure often contributes to retinal ganglion cell death. It is not clear, however, if intraocular pressure directly insults the retinal ganglion cell axon, the soma, or both. The pathways that mediate pressure-induced retinal ganglion cell death are poorly defined, and no molecules are known to be required. DBA/2J mice deficient in the proapoptotic molecule BCL2-associated X protein (BAX) were used to investigate the roles of BAX-mediated cell death pathways in glaucoma. Both Bax+/- and Bax-/- mice were protected from retinal ganglion cell death. In contrast, axonal degeneration was not prevented in either Bax+/- or Bax-/- mice. While BAX deficiency did not prevent axonal degeneration, it did slow axonal loss. Additionally, we compared the effects of BAX deficiency on the glaucoma to its effects on retinal ganglion cell death due to two insults that are proposed to participate in glaucoma. As in the glaucoma, BAX deficiency protected retinal ganglion cells after axon injury by optic nerve crush. However, it did not protect retinal ganglion cells from N-methyl-D-aspartate (NMDA)-induced excitotoxicity. BAX is required for retinal ganglion cell death in an inherited glaucoma; however, it is not required for retinal ganglion cell axon degeneration. This indicates that distinct somal and axonal degeneration pathways are active in this glaucoma. Finally, our data support a role for optic nerve injury but not for NMDA receptor-mediated excitotoxicity in this glaucoma. These findings indicate a need to understand axon-specific degeneration pathways in glaucoma, and they suggest that distinct somal and axonal degeneration pathways may need to be targeted to save vision.
The Catalytic Effect of Bromide in the Hypochlorite Oxidation of Linear Dextrins and Inulin (1994)

Abstract The effect of bromide in the hypochlorite oxidation of amylodextrins (short chain amylose) and inulin on the reaction rate was investigated. It was found both in the linear dextrins and inulin oxidation that the rate increases linearly with the sodium bromide concentration, which proves the catalytic effect of this substance. The origin of the catalysis is the rapid Br − /OCl − conversion. The second‐order rate constant of the reaction Carbohydrate + HOBr/OBr − → polycarboxylates + HBr/Br − was determined at pH 9.0 and 294‐298 K. The activation energy for the oxidation of amylodextrins amounts to 67 kJ.mole −1 . The highest rate was found at pH 8.25. The reaction rate is almost independent of pH in the region 8.5–9.5. Because of the simultaneous occurrence of bromine, Br 3 − . hypobromous acid and hypobromite in the pH region investigated, it is difficult to elucidate the oxidation mechanism.
Quantitative Regulation of Intracellular Endothelial Nitric-oxide Synthase (eNOS) Coupling by Both Tetrahydrobiopterin-eNOS Stoichiometry and Biopterin Redox Status (2008)

Tetrahydrobiopterin (BH4) is a critical determinant of endothelial nitric-oxide synthase (eNOS) activity. In the absence of BH4, eNOS becomes "uncoupled" and generates superoxide rather than NO. However, the stoichiometry of intracellular BH4/eNOS interactions is not well defined, and it is unclear whether intracellular BH4 deficiency alone is sufficient to induce eNOS uncoupling. To address these questions, we developed novel cell lines with tet-regulated expression of human GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme in BH4 synthesis, to selectively induce intracellular BH4 deficiency by incubation with doxycycline. These cells were stably co-transfected to express a human eNOS-green fluorescent protein fusion protein, selecting clones expressing either low (GCH/eNOS-LOW) or high (GCH/eNOS-HIGH) levels. Doxycycline abolished GTPCH mRNA expression and GTPCH protein, leading to markedly diminished total biopterin levels and a decreased ratio of BH4 to oxidized biopterins in cells expressing eNOS. Intracellular BH4 deficiency induced superoxide generation from eNOS, as assessed by N-nitro-L-arginine methyl ester inhibitable 2-hydroxyethidium generation, and attenuated NO production. Quantitative analysis of cellular BH4 versus superoxide production between GCH/eNOS-LOW and GCH/eNOS-HIGH cells revealed a striking linear relationship between eNOS protein and cellular BH4 stoichiometry, with eNOS uncoupling at eNOS:BH4 molar ratio >1. Furthermore, increasing the intracellular BH2 concentration in the presence of a constant eNOS:BH4 ratio was sufficient to induce eNOS-dependent superoxide production. This specific, reductionist approach in a cell-based system reveals that eNOS:BH4 reaction stoichiometry together with the intracellular BH4:BH2 ratio, rather than absolute concentrations of BH4, are the key determinants of eNOS uncoupling, even in the absence of exogenous oxidative stress.
Primary squamous cell carcinoma of the stomach: A case report (2014)

Pure squamous cell carcinoma (SCC) of the stomach is rare and resembles SCC arising elsewhere in the body. The pathogenesis of SCC remains unclear and controversial. At present, <100 cases of primary SCC of the stomach have been reported. The current study presents a case of SCC of the stomach in a 61-year-old male. Total gastrectomy was performed and a 7.0×6.7×4.5-cm tumor with a superiorly located ulcer was identified in the cardia. Upon histological examination, a moderately-differentiated SCC was observed. Tumor cells extended to the serosa, and the perigastric regional lymph node was also involved. No evidence of human papillomavirus (HPV) or Epstein-Barr virus (EBV) infection was identified using a DNA microarray and <i>in situ</i> hybridization, respectively. A post-operative computed tomography scan four months after the gastrectomy revealed tumor recurrence and dissemination of the tumor to the jejunum and pancreas. The patient succumbed to the disease six months later despite the administration of low-dose adjuvant 5-fluorouracil/cisplatin chemotherapy.
IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. (1998)

IL-18 is a product of macrophages and with IL-12 strikingly induces IFN-gamma production from T, B, and NK cells. Furthermore, IL-18 and 1L-12 synergize for IFN-gamma production from Th1 cells, although this combination fails to affect Th2 cells. In this study, we show that IL-12 and IL-18 promptly and synergistically induce T and B cells to develop into IFN-gamma-producing cells without engaging their Ag receptors. We also studied the mechanism underlying differences in IL-18 responsiveness between Th1 and Th2 cells. Pretreatment of T or B cells with IL-12 rendered them responsive to IL-18, which induces cell proliferation and IFN-gamma production. These IL-12-stimulated cells had both high and low affinity IL-18R and an increased IL-18R mRNA expression. In particular, IL-12-stimulated T cells strongly and continuously expressed IL-18R mRNA. However, when T cells developed into Th1 cells after stimulation with anti-CD3 and IL-12, they lowered this IL-12-induced-IL-18R mRNA expression. Then, such T cells showed a dominant response to anti-CD3 by IFN-gamma production when they were subsequently stimulated with anti-CD3 and IL-18. In contrast, Th2 cells did not express IL-18R mRNA and failed to produce IFN-gamma in response to anti-CD3 and IL-18, although they produced a substantial amount of IFN-gamma in response to anti-CD3 and IL-12. However, when Th1 and Th2 cells were stimulated with anti-CD3, IL-12, and IL-18, only the Th1 cells markedly augmented IFN-gamma production in response to IL-18, suggesting that IL-18 responsiveness between Th1 and Th2 cells resulted from their differential expression of IL-18R.
Synthesis of the Phosphoramidite Derivative of 2‘-Deoxy-2‘-C-β-methylcytidine (2003)

2'-Deoxy-2'-C-beta-methylnucleosides elicit interest as potential therapeutic agents and as analogues for the analysis of nucleic acid structure and function. An efficient route for the synthesis of 2'-deoxy-2'-C-methyluridine (11), 2'-deoxy-2'-C-methylcytidine (12), and the phosphoramidite derivative of 2'-deoxy-2'-C-beta-methylcytidine (10, 46% overall yield) from 1,2,3,5-tetra-O-benzoyl-2-C-beta-methylribofuranose (1) is described.
Intramolecular cross‐linking experiments on cytochrome c and ribonuclease A using an isotope multiplet method (2001)

Mass spectral analysis of tryptic digests of cross-linked proteins offers considerable promise as a simple technique to probe protein structure and study protein-protein interactions. We describe the use of a 1:1 mixture of isotopically labeled and unlabeled cross-linkers, disuccinimidyladipate (DSA) and dimethyladipimidate (DMA), to enhance visualization of cross-linked peptides in a tryptic digest. Optimized intramolecular reactions of cytochrome c and ribonuclease A (RNase A) with DSA yielded an average of two cross-links per protein molecule. After digestion of the cross-linked cytochrome c with trypsin and analysis by liquid chromatography/mass spectrometry (LC/MS) and matrix-assisted laser desorption/ionization (MALDI), eight modified peptides, five cross-linked and two end-capped, were detected by virtue of their doublet character. An eighth modified peptide's identity remained ambiguous because of its inability to fragment. The lysine-lysine distance constraints obtained are discussed in the context of the known NMR and X-ray structures of cytochrome c. Analysis of cross-linked RNase A by LC/MS and MALDI yielded nine modified peptides, four of which were modified twice, as indicated by the isotopic triplets. Although seven of these peptides contained cross-links, few distance constraints were gained due to the fact that the cross-linked products were variations of modification of the same three lysine residues.
Holography and Holographic Interferometry with a near IR Sentitive photopolymer System (1997)

Holographic images of test targets were reconstructed from a new, self-processing photopolymer material. A laser diode operating at 780 nm was used in the experiments. Possible effects of the polarization of the construction beams on the reconstructed image were also studied. The applicability of this material to real time holographic interferometry was demonstrated.
Cutting Edge: A Major Fraction of Human Bone Marrow Lymphocytes Are Th2-Like CD1d-Reactive T Cells That Can Suppress Mixed Lymphocyte Responses (2001)

Murine bone marrow (BM) NK T cells can suppress graft-vs-host disease, transplant rejection, and MLRs. Human BM contains T cells with similar potential. Human BM was enriched for NK T cells, approximately 50% of which recognized the nonpolymorphic CD1d molecule. In contrast to the well-characterized blood-derived CD1d-reactive invariant NK T cells, the majority of human BM CD1d-reactive T cells used diverse TCR. Healthy donor invariant NK T cells rapidly produce large amounts of IL-4 and IFN-gamma and can influence Th1/Th2 decision-making. Healthy donor BM CD1d-reactive T cells were Th2-biased and suppressed MLR and, unlike the former, responded preferentially to CD1d(+) lymphoid cells. These results identify a novel population of human T cells which may contribute to B cell development and/or maintain Th2 bias against autoimmune T cell responses against new B cell Ag receptors. Distinct CD1d-reactive T cell populations have the potential to suppress graft-vs-host disease and stimulate antitumor responses.
Expression of bovine leukemia virusENVglycoprotein in insect cells by recombinant baculovirus (1998)

The gp51-p30 glycoprotein constituting BLV envelope was expressed in Sf-21 insect cells by means of recombinant baculoviruses. Post-infection cell lysates were analyzed, in order to define the immunologic reactivity of recombinant products. Oligosaccharide chains, containing N-acetylglucosamine, mannose, galactose and sialic acid were found on recombinant gp51-p30. In order to investigate the timing of transcription and translation of the glycoprotein, kinetic assays were carried out on cell lysates and directly in situ on Sf-21 cells during the course of baculovirus infection. The use of different solubilizing reagents was also evaluated in order to rescue recombinant glycoprotein from its subcellular location.
Protein Analysis and Purification: Benchtop Techniques (1996)

New technologies and the manner in which scientific research is conducted have been fully incorporated into this thoroughly revised second edition of PROTEIN ANALYSIS AND PURIFICATION. Among the many topics introduced to this new edition are the use of robotics in the lab, the impact of the codification of the human genome, functional proteomics, mass spectrometry, and the expanding use of bioinformatics as a tool to improve efficiency and productivity. The author has also included an annotated appendix of the educational materials and technical databases available online to enhance the researcher's benchside access to the latest resources. With solid explanations of the science asking the "why" and literally dozens of step-by-step protocols providing the "how," this new edition is a complete resource for the benchside.
Interactive video in language learning (1988)

Abstract Ten years ago the revolutionary development of the videotape and the videodisc occurred simultaneously with the development of the personal computer. The PC, with its microprocessor, provided computer power and the ability to harness and exploit the video pictures from the videodisc player, It was coincidental but fortuitous that videodiscs and the PC burst on to the scene around the same time, allowing the technologies to develop along parallel and, lately, on converging tracks to foster the new and exotic technology of Interactive Video (V). The hybrid nature of this new medium exploits the properties of the videodisc and combines the benefits with the processing power of the PC providing, for the first time, the foreign language learner with the most advanced tool for the delivery of authentic and natural speed language completely under learner control.
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) (2016)

These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.
Shape from Shading: A Well-Posed Problem? (2005)

Shape from shading is known to be an ill-posed problem. We show in this paper that if we model the problem in a different way than it is usually done, more precisely by taking into account the 1/r/sup 2/ attenuation term of the illumination, shape from shading becomes completely well-posed. Thus the shading allows to recover (almost) any surface from only one image (of this surface) without any additional data (in particular, without the knowledge of the heights of the solution at the local intensity "minima", contrary to [P. Dupuis et al. (1994), E. Prados et al. (2004), B. Horn (1986), E. Rouy et al. (1992), R. Kimmel et al. (2001)]) and without regularity assumptions (contrary to [J. Oliensis et al. (1993), R. Kimmel et al. (1995)], for example). More precisely, we formulate the problem as that of solving a new partial differential equation (PDE), we develop a complete mathematical study of this equation and we design a new provably convergent numerical method. Finally, we present results of our new shape from shading method on various synthetic and real images.
A monolithic video A/D converter (1979)

The design and measured performance of a fully parallel monolithic 8-bit A/D converter is reported. The required comparators and combining logic were designed and fabricated with a standard high-performance triple-diffused technology. A bipolar comparator circuit giving good performance with high input impedance is described. Circuit operation is reported at sample rates up to 30 megasamples per second (MS/s), with analog input signal power at frequencies up to 6 MHz. Full 8-bit linearity was achieved. An SNR of 42-44 dB was observed at input signal frequencies up to 5.3 MHz.
Dose titration using the Disease Activity Score (DAS28) in rheumatoid arthritis patients treated with anti‐TNF‐α (2002)

Dose titration of anti-TNF-alpha treatment using the DAS28 is feasible and leads to overall dose reduction while maintaining clinical efficacy. This approach will save costs and possibly prevent long-term side-effects.
Potent neutralization of SARS‐CoV‐2 including variants of concern by vaccines presenting the receptor‐binding domain multivalently from nanoscaffolds (2021)

The persistence of the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought to the forefront the need for safe and effective vaccination strategies. In particular, the emergence of several variants with greater infectivity and resistance to current vaccines has motivated the development of a vaccine that elicits a broadly neutralizing immune response against all variants. In this study, we used a nanoparticle-based vaccine platform for the multivalent display of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein, the primary target of neutralizing antibodies. Multiple copies of RBD were conjugated to the SpyCatcher-mi3 protein nanoparticle to produce a highly immunogenic nanoparticle-based vaccine. RBD-SpyCatcher-mi3 vaccines elicited broadly cross-reactive antibodies that recognized the spike proteins of not just an early isolate of SARS-CoV-2, but also three SARS-CoV-2 variants of concern as well as SARS-CoV-1. Moreover, immunization elicited high neutralizing antibody titers against an early isolate of SARS-CoV-2 as well as four variants of concern, including the delta variant. These results reveal the potential of RBD-SpyCatcher-mi3 as a broadly protective vaccination strategy.
Physically Self-assembled Ag Nanorod Arrays for Tunable Plasmonic Sensors (2005)

We have established a process to fabricate Ag nanorod arrays with tunable morphology, hence tunable plasmonic properties. Based on a dynamic oblique deposition (DOD) technique, the nanorods are aligned in a way where their major axis is quasi-parallel. The aspect ratio of the nanorods is adjusted by choosing an appropriate DOD condition to show plasma resonance in the wavelength region around the Raman scattering at the excitation wavelength of 785 nm. The nanorod arrays thus tuned provide intense surface enhanced Raman scattering useful for practical applications to biochemical sensors. [DOI: 10.1380/ejssnt.2005.280]
Monocyte Chemotactic Protein-2 Activates CCR5 and Blocks CD4/CCR5-mediated HIV-1 Entry/Replication (1998)

Human immunodeficiency virus, type I (HIV-1) cell-type tropism is dictated by chemokine receptor usage: T-cell line tropic viruses use CXCR4, whereas monocyte tropic viruses primarily use CCR5 as fusion coreceptors. CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed and secreted) inhibit CD4/CCR5-mediated HIV-1 cell fusion. MCP-2 is also a member of the CC chemokine subfamily and has the capacity to interact with at least two receptors including CCR-1 and CCR2B. In an effort to further characterize the binding properties of MCP-2 on leukocytes, we observed that MCP-2, but not MCP-1, effectively competed with MIP-1beta for binding to monocytes, suggesting that MCP-2 may interact with CCR5. As predicted, MCP-2 competitively inhibited MIP-1beta binding to HEK293 cells stably transfected with CCR5 (CCR5/293 cells). MCP-2 also bound to and induced chemotaxis of CCR5/293 cells with a potency comparable with that of MIP-1beta. Confocal microscopy indicates that MCP-2 caused remarkable and dose-dependent internalization of CCR5 in CCR5/293 cells. Furthermore, MCP-2 inhibited the entry/replication of HIV-1ADA in CCR5/293 cells coexpressing CD4. These results indicated that MCP-2 uses CCR5 as one of its functional receptors and is an additional potent natural inhibitor of HIV-1.
Transdermal progesterone: effects on menopausal symptoms and on thrombotic, anticoagulant, and inflammatory factors in postmenopausal women. (2015)

Conventional hormone replacement therapy increases a woman's risk of thrombotic events as evidenced in large prospective clinical trials, including HERS I and the Women's Health Initiative. A possible mechanism for this is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on factors involved in hemostatic balance and inflammation. The objective of this study was to examine the short-term effects of transdermal progesterone on menopausal symptoms and serum levels of hemostatic, inflammatory, and immune signaling factors. In a prospective, randomized, double-blinded, placebo-controlled, crossover study, 30 healthy postmenopausal women received either 20 mg/day of transdermal progesterone or placebo for 4 weeks, followed by a 4-week washout period, and were then crossed over to receive either placebo or active drug for an additional 4 weeks. Baseline, 4-week follow-up, and end-of-study values were obtained for the Greene Climacteric Scale, and for serum levels of total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin III, plasminogen activator inhibitor-1, C-reactive protein, interleukin-6, matrix metalloproteinase-9, and tumor necrosis factor-a. Transdermal progesterone significantly improved Greene Climacteric Scale scores. In sharp contrast to previous studies of conventional hormone replacement therapy, no detrimental effect was observed on any of the hemostatic or inflammatory components examined. Administration of transdermal progesterone at a daily dose of 20 mg significantly relieves menopausal symptoms in postmenopausal women without adversely altering prothrombotic potential. We suggest, therefore, that this treatment be seriously considered as an effective and safe alternative clinical therapy for women suffering from menopausal symptoms.
Gemin4 (2000)

The survival of motor neurons (SMN) protein, the product of the neurodegenerative disease spinal muscular atrophy (SMA) gene, is localized both in the cytoplasm and in discrete nuclear bodies called gems. In both compartments SMN is part of a large complex that contains several proteins including Gemin2 (formerly SIP1) and the DEAD box protein Gemin3. In the cytoplasm, the SMN complex is associated with snRNP Sm core proteins and plays a critical role in spliceosomal snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing by serving in the regeneration of spliceosomes. These functions are likely impaired in cells of SMA patients because they have reduced levels of functional SMN. Here, we report the identification by nanoelectrospray mass spectrometry of a novel component of the SMN complex that we name Gemin4. Gemin4 is associated in vivo with the SMN complex through a direct interaction with Gemin3. The tight interaction of Gemin4 with Gemin3 suggests that it could serve as a cofactor of this DEAD box protein. Gemin4 also interacts directly with several of the Sm core proteins. Monoclonal antibodies against Gemin4 efficiently immunoprecipitate the spliceosomal U snRNAs U1 and U5 from Xenopus oocytes cytoplasm. Immunolocalization experiments show that Gemin4 is colocalized with SMN in the cytoplasm and in gems. Interestingly, Gemin4 is also detected in the nucleoli, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly.
L2TP Disconnect Cause Information (2001)

This document provides an extension to the Layer 2 Tunneling Protocol ("L2TP"), a mechanism for tunneling Point-to-Point Protocol (PPP) sessions. L2TP lacks a mechanism for a host to provide PPP-related disconnect cause information to another host. This information, provided by the extension described in this document, can be useful for accounting and debugging purposes.