gebhart/patrepeval huggingface dataset:
Mechanisms of self-association of a human monoclonal antibody CNTO607 (2012)

Some antibodies have a tendency to self-associate leading to precipitation at relatively low concentrations. CNTO607, a monoclonal antibody, precipitates irreversibly in phosphate-buffered saline at concentrations above 13 mg/ml. Previous mutagenesis work based on the Fab crystal structure pinpointed a three residue fragment in the heavy chain CDR-3, (99)FHW(100a), as an aggregation epitope that is anchored by two salt bridges. Biophysical characterization of variants reveals that F99 and W100a, but not H100, contribute to the intermolecular interaction. A K210T/K215T mutant designed to disrupt the charge interactions in the aggregation model yielded an antibody that does not precipitate but forms reversible aggregates. An isotype change from IgG1 to IgG4 prevents the antibody from precipitating at low concentration yet the solution viscosity is elevated. To further understand the nature of the antibody self-association, studies on the Fab fragment found high solubility but significant self- and cross-interactions remain. Dynamic light scattering data provides evidence for higher order Fab structure at increased concentrations. Our results provide direct support for the aggregation model that CNTO607 precipitation results primarily from the specific interaction of the Fab arms of neighboring antibodies followed by the development of an extensive network of antibodies inducing large-scale aggregation and precipitation.
Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis (2009)

These data demonstrate that bladder-associated pelvic pain is attenuated by antagonists of NK1R and H2R. Therefore, NK1R and H2R represent direct therapeutic targets for pain in IC/PBS and potentially other chronic pain conditions.
Toward Universal Vaccination against Hepatitis B Virus (1989)

The first vaccine against human hepatitis B virus was licensed for use in the United States in 1981 and became commercially available in 1982.1 The development of this vaccine represented a milestone in medicine and was the product of two decades of intensive research into the structure and biology of hepatitis B virus. The first vaccine consisted of particles of purified and inactivated hepatitis B surface antigen (HBsAg) extracted from pooled plasma from long-term carriers of HBsAg. A second milestone was reached in 1984 with the development of a recombinant hepatitis B vaccine, the first human vaccine produced with molecular . . .
Electrotransformation studies in Clostridium cellulolyticum (2001)

Electropermeabilization of Clostridium cellulolyticum was optimized using ATP leakage assays. Electrotransformation was then performed under optimized conditions (6 to 7.5 kV x cm(-1) field strength applied during 5 ms to a mixture containing methylated plasmids and late exponential phase cell suspensions (10 molecules:1 cell) in a sucrose-containing buffer). Transformants were only obtained when 7 or 7.5 kV x cm(-1) pulses were applied. Transformation efficiencies evaluated from the growth curves of transformed cells were between 10(5) and 10(7) transformants per microgram of plasmid DNA for five different replicon-based plasmids. Restriction nuclease digestion patterns of pJIR418 purified from transformed Clostridia and Escherichia coli were indistinguishable, indicating that heterologous DNA was structurally stable in the Clostridium strain. Copy numbers of 130, 70 and 10 were estimated from purification yield for pCTC1, pKNT19 and pJIR418, respectively.
An old game (1879)

An old game Get access A. A. Search for other works by this author on: Oxford Academic Google Scholar Notes and Queries, Volume s5-XI, Issue 281, 17 May 1879, Page 398, https://doi.org/10.1093/nq/s5-XI.281.398h Published: 17 May 1879
Complement activation by a B cell superantigen (1996)

Staphylococcal protein A (SpA), acting as a B cell superantigen, binds to the Fab region of human VH3+ Igs. Using SpA abrogated of its IgG Fc binding activity (Mod SpA) as a model B cell superantigen, we determined whether such an interaction causes complement activation. Addition of Mod SpA to human serum led to complement consumption and the generation of C3a. To determine whether this complement activation 1) was due to an interaction between VH3+ Igs and the Fab binding site of SpA and 2) proceeded via the classical complement pathway, we tested a panel of monoclonal IgM proteins for the ability to hind C1q following interaction with SpA. C1q binding was restricted to SpA-reactive, VH3+ IgM proteins. To formally determine whether the binding of SpA to the reactive VH3+ IgM proteins led to complement activation, we reconstituted the serum from a hypogammaglobulinemic patient with monoclonal IgM proteins and measured complement consumption and C3a generation following the addition of Mod SpA. We observed complement consumption and C3a production only in Mod SpA-treated serum reconstituted with a VH3+, SpA-binding, IgM protein. Taken together, these results provide compelling evidence that the interaction of the Fab binding site of SpA and VH3+ Igs can lead to complement activation via the classical pathway. This novel interaction may have significant implications for the in vivo properties of a B cell superantigen.
Animal cells: culture and media. (1994)

Culture Media Supplements to Media Culture Vessels Cells Culturing Cells Manufacturers and Suppliers References Appendix Index.
World Conference on Hospitality, Tourism, &, Event Research and International Convention & Expo Summit Bangkok, Thailand May 25-28, 2013 (2014)

Meetings, incentives, conventions, and exhibitions (MICE) industry executives and researchers from around the world gathered from May 25 to 28 along the banks of the Chao Phraya River in the specta...
Toward a common language: surgical wound bed preparation and debridement (2006)

ABSTRACT Wound management encompasses a number of disciplines. As new concepts and innovative technologies develop within this exciting field, it is important to share them in spite of the divergence of clinical perspectives between the expert disciplines. One such divergence exists between surgeons and nonsurgical wound specialists. As a result, there is a need to develop a common language between these two groups. How can we develop a common language that unites surgical expertise within medical wound management? One route may be through the principles of wound bed preparation, which we believe have great potential for the communication of effective surgical techniques. Another is through sharing our concepts of surgical debridement as it is applied to different wounds by a variety of surgical disciplines. In this monograph, we try to bring these two themes together. We discuss how wound bed preparation has added to our understanding of the pathophysiology of the nonhealing wound and has provided us with some general clinical concepts. We discuss what role debridement, and then specifically surgical debridement, has to play within wound bed preparation, before analyzing the importance of surgical debridement in tissue preservation and the control of infection. We finally look at ongoing work that examines the cost of various surgical debridement techniques. We will also review a new hydrosurgery system (VERSAJET ® , Smith and Nephew, Hull, UK), which we believe has an important role to play in the surgical preparation of the wound. We also expect that this paper will remind our medical colleagues about the critical role played by surgery in wound management.
Antihistaminic effect of terfenadine: A new piperidine‐type antihistamine (1982)

Abstract The antihistaminic effect of terfenadine was studied in the isolated guinea pig ileum, histamine skin wheals in guinea pigs and monkeys, and i.v. histamine‐induced death in guinea pigs. In the guinea pig ileum, terfenadine, 1 × 10 −7 M, shifted the histamine dose‐response curve to the right in a parallel fashion without affecting the dose‐response curve of acetylcholine and barium chloride. However, as the dose of terfenadine was increased (3.16 × 10 −7 and 1 × 10 −6 M) the histamine dose‐response curves were displaced to the right with a depression of the maximum response and a reduction of the slope. Thus an unsurmountable type of antagonism was observed. Acetylcholine was also antagonized in a similar fashion by these two concentrations. In contrast, terfenadine appeared to displace the barium chloride dose‐response curve to the right in a parallel fashion. At 0.4 and 0.8 mg/kg p.o., terfenadine shifted the histamine skin wheal dose‐response curves to the right in a parallel fashion, but at 1.6 to 6.4 mg/kg, terfenadine antagonized the histamine wheal dose‐response curves with a depression of the maximum and the slope of the curve. These results were also similar to those of cyproheptadine but were different from those of chlorpheniramine, which produced parallel shifts. In monkeys, terfenadine produced a substantially greater effect on the histamine wheal than did chlorpheniramine (both administered at 30 mg/kg p.o.). Terfenadine also completely protected against i.v. histamine‐induced death in guinea pigs. Terfenadine produced no atropine‐like effect against pilocarpine‐induced salivation in rabbits, no demonstrable histamine H 2 antagonism, no antiserotonin activity, no α or β antagonism, and no untoward cardiovascular effects. Most significantly, terfenadine had no overt central nervous system (CNS) effects in mice, rats, guinea pigs, or monkeys; whereas chlorpheniramine produced tremors and convulsions in mice and monkeys when tested at much lower doses than those used for terfenadine. It is concluded that terfenadine is an effective and specific antihistaminic compound with the potential advantage of a lack of CNS sedative effects.
M Proteins Of Group G Streptococci: Mechanisms Of Resistance To Phagocytosis (1995)

Group G streptococci that express M protein and resist phagocytosis in human blood (virulent strains) were compared with strains of groups G and A that are readily phagocytosed (avirulent). Virulent group G streptococci were less effective (P < .05) as activators of the alternative complement pathway (ACP) than were avirulent streptococci. In immunofluorescence studies, C3 bound more avidly to avirulent than to virulent group G streptococci. Resistance of virulent group G strains to ACP opsonization and to phagocytosis was markedly diminished by removal with pepsin of the type-specific portion of the M molecule. Preincubation with fibrinogen did not diminish ACP activation or C3 binding by virulent group G and A streptococci but did exert an antiphagocytic effect. Given the similarity of M proteins of groups G and A in structure and function, other microbial constituents are likely responsible for differences in the spectra of illnesses attributable to the two serogroups.
Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock (2004)

In this paper, we show that plasma from patients with severe sepsis and septic shock but not normal plasma supports lipopolysaccharide (LPS) activation of epithelial cells expressing Toll-like receptor 4 (TLR4). Recombinant soluble myeloid differentiation protein-2 (MD-2) complemented normal plasma and allowed LPS activation of epithelial cells to levels measured with "septic" plasma, whereas soluble MD-2-depleted plasma lost its effects. The same "MD-2 activity" was found in urine from a patient with septic shock and in lung edema fluids from patients with adult respiratory distress syndrome (ARDS). Recombinant soluble MD-2 enabled LPS-dependent activation of epithelial cells bearing TLR4. LPS-binding protein (LBP) and soluble CD14 increased the sensitivity of TLR4-expressing epithelial cells to LPS but were not able to mediate LPS activation of these cells in the absence of soluble MD-2. An anti-MD-2 monoclonal antibody blocked LPS activation of TLR4-expressing cells only in the presence of septic plasma or septic urine. These results suggest that septic plasma containing soluble MD-2 leaking into the extravascular space supports LPS activation of TLR4-expressing epithelial cells. We therefore propose that soluble MD-2 is an important mediator of organ inflammation during sepsis.
Beneficial effect of retinoic acid on the outcome of experimental acute renal failure (2004)

RA exerted beneficial effects on the duration and severity of renal damage induced by PD in a model of renal failure resembling ARF in humans. The protective effect of RA may be mediated by diminished lipoperoxidative damage.
Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors (2017)

<b>Purpose:</b> This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors.<b>Experimental Design:</b> Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event continual reassessment method.<b>Results:</b> Twenty-three patients received combination treatment with no dose-limiting toxicities. Treatment-emergent adverse events were mostly grades 1 to 2, without any treatment-related discontinuations. Six patients (26.1%) had confirmed complete or partial responses. Pharmacokinetics and immunogenicity of utomilumab and pembrolizumab were similar when administered alone or in combination. A trend toward higher levels of activated memory/effector peripheral blood CD8<sup>+</sup> T cells was observed in responders versus nonresponders.<b>Conclusions:</b> The safety, tolerability, and clinical activity demonstrated by utomilumab in combination with pembrolizumab support further investigation in patients with advanced solid tumors. <i>Clin Cancer Res; 23(18); 5349-57. ©2017 AACR</i><i>See related commentary by Pérez-Ruiz et al., p. 5326</i>.
Original Articles: Epidemiology and Neurobiology of Female Sexual Dysfunction (2007)

We are improving our understanding of the contributions of the CNS neuroendocrine and neurotransmitter systems that modulate sexual behavior.
Handling model uncertainty in model predictive control for energy efficient buildings (2014)

Model uncertainty is a significant challenge to more widespread use of model predictive controllers (MPC) for optimizing building energy consumption. This paper presents two methodologies to handle model uncertainty for building MPC. First, we propose a modeling framework for online estimation of states and unknown parameters leading to a parameter-adaptive building (PAB) model. Second, we propose a robust model predictive control (RMPC) formulation to make a building controller robust to model uncertainties. The results from these two approaches are compared with those from a nominal MPC and a common building rule based control (RBC). The results are then used to develop a methodology for selecting a controller type (i.e. RMPC, MPC, or RBC) as a function of building model uncertainty. RMPC is found to be the superior controller for the cases with an intermediate level of model uncertainty (30–67%), while the nominal MPC is preferred for the cases with a low level of model uncertainty (0–30%). Further, a common RBC outperforms MPC or RMPC if the model uncertainty goes beyond a certain threshold (e.g. 67%).
Enone mesylates. Precursors to .beta.-substituted cyclohexenones (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnone mesylates. Precursors to .beta.-substituted cyclohexenonesConrad J. Kowalski and Kevin W. FieldsCite this: J. Org. Chem. 1981, 46, 1, 197–201Publication Date (Print):January 1, 1981Publication History Published online1 May 2002Published inissue 1 January 1981https://pubs.acs.org/doi/10.1021/jo00314a051https://doi.org/10.1021/jo00314a051research-articleACS PublicationsRequest reuse permissionsArticle Views1555Altmetric-Citations44LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Breaking Stress of Glass Determined from Dimensions of Fracture Mirrors (1959)

Relations previously have been shown between the size of the fracture mirror and the nominal breaking stress. In the present paper, this relation is derived analytically involving one unknown quantity which must be determined experimentally. This quantity is δ m √ρ where δ m is the intrinsic strength of the glass and the effective radius of the crack tip. Tests on glass rods indicated that the breaking stress could be determined from the radius of the fracture mirror. For 80% of the specimens the values obtained were within 8% of those obtained from the test loads.
Aerodynamic, Stability and Flying Quality Evaluation on a Small Blended Wing-body Aircraft with Canard Foreplanes (2014)

Blended wing-body (BWB) concept promises up to 30 percent increase in aerodynamic efficiency and reduction in fuel cost by having planform geometry optimized to increase lift and to reduce drag. Many claimed to have achieved the target of increasing lift-to-drag ratio better than current conventionally-configured airplanes either large airliners or small unmanned airplane. However, achieving good balance of aerodynamic efficiency, stability and flying quality is harder then one might expect. Over years of studying small BWB aircrafts in Universiti Teknologi MARA (UiTM), it is found that unconventional behaviour of aerodynamic characteristics leads to limitations to BWB aircraft's flight envelope. In this paper, a short overview of aerodynamic, stability and flying quality of UiTM's BWB aircraft design is highlighted. Lessons learned from its unsusual lift-angle of attack curves, stability reversals, the effect of canard to flight stability and poor longitudinal flying quality (short-period mode and phugoid mode) are discussed. A classical control solution to improve it flying quality has been proposed and simulated and the result shows that both short-period and phugoid modes are able to achieve damping ratios within 0.6 to 0.8 exceeding minimum Level 1 damping ratios of 0.35 and 0.04 respectively. Design flaws of this aircraft and recommendations to be implemented on the next evolution of aircraft design conclude this paper.
Roller nanoimprint lithography (1998)

An alternative approach to flat nanoimprint lithography (NIL)—roller nanoimprint lithography (RNIL) is demonstrated. Compared with flat NIL, RNIL has the advantage of better uniformity, less force, and the ability to repeat a mask continuously on a large substrate. Two methods for RNIL are developed: (a) rolling a cylinder mold on a flat, solid substrate; (b) putting a flat mold directly on a substrate and rolling a smooth roller on top of the mold. Using our current roller nanoimprint system, sub-100 nm resolution pattern transfer has been achieved.
Animal Model for Infection with Listeria monocytogenes (2000)

This unit describes methods for infecting mice with L. monocytogenes. Optimal media for growth and methods to maintain bacterial virulence by passage through mice are included. Methods for determining the severity of splenic and hepatic infection are detailed, with strategies for distinguishing innate from specific immune responses following L. monocytogenes infection. This infection induces MHC class I-restricted CD8(+) cytolytic T lymphocytes that clear infection and provide long-term immunity. This unit describes methods that can be used for in vitro expansion of L. monocytogenes-specific T cells.
Localization of Collagen XVIII and the Endostatin Portion of Collagen XVIII in Aged Human Control Eyes and Eyes with Age-Related Macular Degeneration (2004)

These data suggest that reduced levels of the endostatin portion of coll XVIII in Bruch's membrane, RPE basal lamina, intercapillary septa, and choriocapillaris in eyes with AMD may be permissive for choroidal neovascularization.
Tsg101 Is Essential for Cell Growth, Proliferation, and Cell Survival of Embryonic and Adult Tissues (2002)

Tumor susceptibility gene 101 (Tsg101) was identified in a random mutagenesis screen for potential tumor suppressors in NIH 3T3 cells. Altered transcripts of this gene have been detected in sporadic breast cancers and many other human malignancies. However, the involvement of this gene in neoplastic transformation and tumorigenesis is still elusive. Using gene targeting, we generated genetically engineered mice with a floxed allele of Tsg101. We investigated essential functions of this gene in vivo and examined whether the loss of function of Tsg101 results in tumorigenesis. Conventional knockout mice were generated through Cre-mediated excision of the first coding exon in the germ line of mouse mammary tumor virus (MMTV)-Cre transgenic mice. The complete ablation of Tsg101 in the developing embryo resulted in death around implantation. In contrast, mammary gland-specific knockout mice developed normally but were unable to nurse their young as a result of impaired mammogenesis during late pregnancy. Neither heterozygous null mutants nor somatic knockout mice developed mammary tumors after a latency of 2 years. The Cre-mediated deletion of Tsg101 in primary cells demonstrated that this gene is essential for the growth, proliferation, and survival of mammary epithelial cells. In summary, our results suggest that Tsg101 is required for normal cell function of embryonic and adult tissues but that this gene is not a tumor suppressor for sporadic forms of breast cancer.
Experimental Investigation of Velocity Distributions of Downstream of Single Duct Bends (1948)

Report presenting measurements of the velocity distributions at the outlet of a large number of duct elbows of round and elliptical as well as square and rectangular cross section at a range of Reynolds numbers. Special investigations include measurements of the decay of velocity patterns produced by curved ducts and the effect of asymmetrical upstream velocity distributions. Results regarding typical distributions, tabulation of principal results, and special investigations are provided.