gebhart/patrepeval huggingface dataset:
The structure and function of immunoglobulin domains. II. The importance of interchain disulfide bonds and the possible role of molecular flexibility in the interaction between immunoglobulin G and complement. (1975)

The observation that reduction of the inter-chain disulfides in rabbit antibody destroys its ability to interact with complement was confirmed and shown to be true also of human meyloma IgG1 subclass proteins. In the latter case a C1-binding assay was used. Further studies indicated that it was the interheavy chain disulfides which were essential for complement-binding activity: Non-covalently reassembled IgG (LHHL) was devoid of C1-fixing activity whereas molecules formed from covalently linked heavy chain dimers, and reduced and alkylated light chains (ie., LH-HL) were as active as the parent intact IgG. Fc fragments from IgG1 bound C1 and this activity was insensitive to the presence or absence of intact interchain disulfides. These bonds therefore are neither directly involved in C1 binding nor essential for the integrity of the binding site. We have also shown that although IgG4 does not bind C1, Fc fragments derived from this subclass fix C1 with an affinity comparable to that of the corresponding fragment from IgG1. These data suggest that quaternary interaction with other regions of the molecule (ie., Fab) may modulate the activity of the C1-binding site.
Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation (2001)

The proteins of the hedgehog (Hh) family regulate various aspects of development. Recently, members of this family have been shown to regulate skeletal formation in vertebrates and to control both chondrocyte and osteoblast differentiation. In the present study, we analyzed the effect of Sonic hedgehog (Shh) on the osteoblastic and adipocytic commitment/differentiation. Recombinant N-terminal Shh (N-Shh) significantly increased the percentage of both the pluripotent mesenchymal cell lines C3H10T1/2 and ST2 and calvaria cells responding to bone morphogenetic protein 2 (BMP-2), in terms of osteoblast commitment as assessed by measuring alkaline phosphatase (ALP) activity. This synergistic effect was mediated, at least partly, through the positive modulation of the transcriptional output of BMPs via Smad signaling. Furthermore, N-Shh was found to abolish adipocytic differentiation of C3H10T1/2 cells both in the presence or absence of BMP-2. A short treatment with N-Shh was sufficient to dramatically reduce the levels of the adipocytic-related transcription factors C/EBPalpha and PPARgamma in both C3H10T1/2 and calvaria cell cultures. Given the inverse relationship between marrow adipocytes and osteoblasts with aging, agonists of the Hh signaling pathway might constitute potential drugs for preventing and/or treating osteopenic disorders.
Design and optimization of tapered light pipes (2004)

In illumination systems for projection display, it is often necessary to tailor the aperture size and angle of light to suit the system requirements such as an imager panel. One way to do that is to use lenses, but depending on the angle and area this may not be achieved economically in terms of space and costs. Non-imaging optics is often used to perform such function. A compound parabolic concentrator (CPC), which is simple to use and small in size, is one example of such approach, but it has the disadvantage of non-uniform output intensity profile and not conserving brightness. A tapered light pipe (TLP) is often used instead to alleviate such shortcomings, but such light pipe would need to be infinitely long to conserve brightness, which makes it quite impractical. In this paper, a lensed tapered light pipe is described that change the area and angle of light with minimal loss of brightness and provide a very uniform output intensity profile at the output. Numerical modeling using ray tracing computer program is used to optimize the TLP for each applications.
Leroy Smith, M.D. (1913–1993) (1995)

Cohen, I. Kelman M.D.; Mehrhof, Austin I. Jr. D.D.S., M.D.; Ware, J. Latane M.D. Author Information
Smart Sensor System for Structural Condition Monitoring of Wind Turbines: 30 May 2002--30 April 2006 (2006)

This report describes the efforts of the University of Cincinnati, North Carolina A&T State University, and NREL to develop a structural neural system for structural health monitoring of wind turbine blades.
A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1 (2017)

Bispecific antibodies combine two different antigen-binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action, and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability, and pharmacokinetic properties. Here, we describe a new approach for generating bispecific antibodies using a common light chain format and exploiting the stable architecture of human immunoglobulin G<sub>1</sub> We used iterative experimental validation and computational modeling to identify multiple Fc variant pairs that drive efficient heterodimerization of the antibody heavy chains. Accelerated stability studies enabled selection of one Fc variant pair dubbed "DEKK" consisting of substitutions L351D and L368E in one heavy chain combined with L351K and T366K in the other. Solving the crystal structure of the DEKK Fc region at a resolution of 2.3 Å enabled detailed analysis of the interactions inducing CH3 interface heterodimerization. Local shifts in the IgG backbone accommodate the introduction of lysine side chains that form stabilizing salt-bridge interactions with substituted and native residues in the opposite chain. Overall, the CH3 domain adapted to these shifts at the interface, yielding a stable Fc conformation very similar to that in wild-type IgG. Using the DEKK format, we generated the bispecific antibody MCLA-128, targeting human EGF receptors 2 and 3. MCLA-128 could be readily produced and purified at industrial scale with a standard mammalian cell culture platform and a routine purification protocol. Long-term accelerated stability assays confirmed that MCLA-128 is highly stable and has excellent biophysical characteristics.
Mutations in the human homologue of the Drosophila patched gene in esophageal squamous cell carcinoma. (1998)

The human homologue (PTCH) of the Drosophila segment polarity gene patched has recently been identified as a tumor-suppressor gene for nevoid basal cell carcinoma syndrome and for sporadic basal cell carcinomas of the skin. We analyzed 30 esophageal squamous cell carcinomas (ESCC) for intrageneic mutations of the PTCH gene by polymerase chain reaction-single-strand conformation polymorphism analysis followed by DNA sequencing. We identified two somatic PTCH mutations (7%) in 30 ESCC. These were a nonsense mutation (CAG to TAG at codon 361) in exon 8 and a missense mutation (CAG to CTG, Gln to Leu at codon 816) in exon 14. These tumors exhibited loss of heterozygosity at the polymorphic site of the PTCH gene. These results indicate that inactivation of the PTCH gene via a two-hit mechanism occurs in a subset of ESCC.
Membrane topology of the epithelial sodium channel in intact cells (1994)

The highly selective amiloride-sensitive epithelial sodium channel is formed of three homologous subunits termed alpha-, beta-, and gamma-rENaC. Each subunit has two putative transmembrane domains (M1 and M2), yielding a protein with a large (approximately 50 kDa) hydrophilic loop (between M1 and M2) and short hydrophilic NH2- and COOH-termini (9 and 10 kDa). All three subunits are glycosylated in a cell-free translation assay, demonstrating that they share in vitro a common pattern of membrane insertion. The membrane topology of the alpha-rENaC subunit in intact cells was studied in Xenopus laevis oocytes. We demonstrate that 1) all six potential N-linked glycosylation sites (N190, N259, N320, N339, N424, and N538) of the large hydrophilic loop are used in intact cells; 2) the glycosylation of alpha-rENaC does not play a significant role in the functional expression of the channel; and 3) the two hydrophobic domains M1 (A109-F131) and M2 (S588-L612) serve in intact cells as start- and stop-transfer signals, respectively. We conclude that alpha-rENaC spans the membrane twice with the short NH2- and COOH-terminal ends on the cytoplasmic side and a large hydrophilic loop in the extracellular space.
Cloning, nucleotide sequence, and transcriptional analysis of the Pediococcus acidilactici L-(+)-lactate dehydrogenase gene (1995)

Recombinant plasmids containing the Pediococcus acidilactici L-(+)-lactate dehydrogenase gene (ldhL) were isolated by complementing for growth under anaerobiosis of an Escherichia coli lactate dehydrogenase-pyruvate formate lyase double mutant. The nucleotide sequence of the ldhL gene predicted a protein of 323 amino acids showing significant similarity with other bacterial L-(+)-lactate dehydrogenases and especially with that of Lactobacillus plantarum. The ldhL transcription start points in P. acidilactici were defined by primer extension, and the promoter sequence was identified as TCAAT-(17 bp)-TATAAT. This sequence is closely related to the consensus sequence of vegetative promoters from gram-positive bacteria as well as from E. coli. Northern analysis of P. acidilactici RNA showed a 1.1-kb ldhL transcript whose abundance is growth rate regulated. These data, together with the presence of a putative rho-independent transcriptional terminator, suggest that ldhL is expressed as a monocistronic transcript in P. acidilactici.
Signal detection theory and psychophysics (1966)

Book on statistical decision theory and sensory processes in signal detection theory and psychophysics
Ion Sieving Effects in the Electrical Double Layer of Porous Carbon Electrodes:  Estimating Effective Ion Size in Electrolytic Solutions (2001)

Certain microporous carbons have pores of molecular dimensions, the size of which can be adjusted over a wide range to fit the dimensions of a large variety of molecules. With knowing the dimensions of these molecules, size-calibrated porous carbons can be produced. In this work, we took advantage of the electronic conductivity of carbon in using it as an electrode in electrolytic solutions. By changing the electrode potential, we could induce electroadsorption and electrodesorption of ions of different dimensions into pore-calibrated carbons, thus enabling us to estimate effective ion sizes. A few fundamental questions such as whether ions accommodated in the electrodes' pores are in a solvated state, which is important for novel electrochemical energy storage devices and for microbiological systems, could be addressed. Analysis of the results indicates that all the cations that are employed are electroadsorbed in the electrode pores in hydrated states. Compared with the monovalent cations, the bivalent cations exhibit dimensions that make them almost twice as big. Monovalent anions are basically adsorbed in a nonhydrated state. The doubly charged sulfate anion is adsorbed in the hydrated state. The nitrate, a multiatom planar anion, has a smaller effective dimension than the monoatomic halogen anions, in accordance with the observation that the pores in many activated carbons are slit-shaped. The analysis of the results enabled us to establish a scale of ionic effective dimensions in aqueous media, as presented below (MTBE stands for methyl tert-butyl ether): cations, [3.62 Å, N2] < Cs+ < K+ < Na+ < Li+ < [4.21 Å, CF4] < [5.05 Å, SF6] < [5.8 Å, MTBE] < Ba2+, Ca2+, and Mg2+; anions, [3.62 Å, N2] < NO3- < Cl- < F- < Br- < [4.21 Å, CF4] < ClO4- < [5.05 Å, SF6] < [5.8 Å, MTBE] < SO2-. We discovered that as long as the pore size is considerably greater than the ion size, the electric double-layer capacity at moderate concentrations is independent of both the size and charge of the ions in solutions.
Prokaryotic Ubiquitin-Like ThiS Fusion Enhances the Heterologous Protein Overexpression and Aggregation in Escherichia coli (2013)

Fusion tags are commonly employed to enhance target protein expression, improve their folding and solubility, and reduce protein degradation in expression of recombinant proteins. Ubiquitin (Ub) and SUMO are highly conserved small proteins in eukaryotes, and frequently used as fusion tags in prokaryotic expression. ThiS, a smaller sulfur-carrier protein involved in thiamin synthesis, is conserved among most prokaryotic species. The structural similarity between ThiS and Ub provoked us into expecting that the former could be used as a fusion tag. Hence, ThiS was fused to insulin A and B chains, murine Ribonuclease Inhibitor (mRI) and EGFP, respectively. When induced in Escherichia coli, ThiS-fused insulin A and B chains were overexpressed in inclusion bodies, and to higher levels in comparison to the same proteins fused with Ub. On the contrast, ThiS fusion of mRI, an unstable protein, resulted in enhanced degradation that was not alleviated in protease-deficient strains. While the degradation of Ub- and SUMO-fused mRI was less and seemed protease-dependent. Enhanced degradation of mRI did not occur for the fusions with half-molecules of ThiS. When ThiS-tag was fused to the C-terminus of EGFP, higher expression, predominantly in inclusion bodies, was observed again. It was further found that ThiS fusion of EGFP significantly retarded its refolding process. These results indicated that prokaryotic ThiS is able to promote the expression of target proteins in E. coli, but enhanced degradation may occur in case of unstable targets. Unlike eukaryotic Ub-based tags usually increase the solubility and folding of proteins, ThiS fusion enhances the expression by augmenting the formation of inclusion bodies, probably through retardation of the folding of target proteins.
Traceless Solid-Phase Synthesis of 1,2,4-Triazoles Using a Novel Amine Resin (2001)

[reaction: see text]. A solid-phase route to 5-aryl-3-arylthiomethyl-1,2,4-triazoles has been developed that permits the incorporation of two elements of diversity. The heterocycle was constructed upon a novel 4-benzyloxy-2-methoxybenzylamine (BOMBA) resin, from which traceless cleavage could be effected with dilute TFA. A library of 96 triazoles was produced with an average yield of 26% (84% yield per step) and an average purity of 80%. In a direct comparison, the new BOMBA resin proved to be markedly superior to Rink Amide resin for this application.
Chiral Brønsted Acid-Catalyzed Allylboration of Aldehydes (2010)

The catalytic enantioselective allylation of aldehydes is a long-standing problem of considerable interest to the chemical community. We disclose a new high-yielding and highly enantioselective chiral Brønsted acid-catalyzed allylboration of aldehydes. The reaction is shown to be highly general, with a broad substrate scope that covers aryl, heteroaryl, alpha,beta-unsaturated, and aliphatic aldehydes. The reaction conditions are also shown to be effective for the catalytic enantioselective crotylation of aldehydes. We believe that the high reactivity of the allylboronate is due to protonation of the boronate oxygen by the chiral phosphoric acid catalyst.
Petaops and Exaops: supercomputing on the Web (1997)

There are large-scale computation problems that could benefit from the power of the Web. The authors have chosen the year 2007 to set a hardware scenario where petaflops performance could be obtained by a variety of architectures, including an ATM-connected corporate intranet. They classify the kinds of parallelism found in different applications, arguing that the Web has advantages in the expression of general forms of parallelism that make it suitable as the software environment of choice for these applications on all hardware platforms. They conclude by analyzing Web software approaches in some detail, taking an inevitably nearer term perspective. Their purpose is to show how the Web and MPP can be advanced synergistically to solve different problems.
Solid-phase synthesis of benzodiazepines (1993)

RETURN TO ISSUEPREVNewsNEXTSolid-phase synthesis of benzodiazepinesRUDY BAUMCite this: Chem. Eng. News 1993, 71, 3, 33–34Publication Date (Print):January 18, 1993Publication History Published online12 November 2010Published inissue 18 January 1993https://pubs.acs.org/doi/10.1021/cen-v071n003.p033https://doi.org/10.1021/cen-v071n003.p033newsACS PublicationsCopyright © 1993 American Chemical SocietyArticle Views16Altmetric-Citations1LEARN 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 options SUBJECTS:Combinatorial synthesis,Nucleic acids,Organic compounds,Reaction products,Solid phase synthesis Get e-Alerts
Optimization Methodology for Cyclic Steam Injection with Horizontal Wells (2000)

Abstract Horizontal wells are becoming a very important component in the thermal recovery of heavy oil reservoirs. The success of a cyclic steam injection project depends strongly on the selection of key parameters, such as cycle length and amount of steam injected. The numerical simulation of horizontal wells, especially under non-isothermal conditions, is computationally demanding. When optimization is combined with numerical simulation, the computing time requirement may be prohibitive and it is not guaranteed that the optimal conditions will be found. In this research, a new methodology has been developed for optimizing the cyclic steam injection process for vertical and horizontal wells. The procedure integrates oil production characterization using numerical simulation, net present value maximization through a Quasi-Newton method, and model validation/tuning. The three-stage procedure provides the optimum number and/or duration of cycles, the optimal amounts of steam to be injected in each cycle and the optimal value of the overall economic indicator. The optimization algorithm was successfully validated with published results obtained from the discrete maximum principle. The methodology was then applied to determine the optimal conditions of cyclic steam injection for a horizontal well located in Bachaquero field, Venezuela.
Stability Results for a Class of Differential Equation and Application in Medicine (2009)

A Chemostat system incorporating hepatocellular carcinomas is discussed. The model generalizes the classical Chemostat model, and it assumes that the Chemostat is an increasing function of the concentration. The asymptotic behavior of solutions is determined. Sufficient conditions for the local and global asymptotic stability of equilibrium and numerical simulation are obtained, which is used to select the disease control tactics.
Underwater 3D SLAM through entropy minimization (2006)

The aquatic realm is ideal for testing autonomous robotic technology. The challenges presented in this environment are numerous due to the highly dynamic nature of the medium. Applications for underwater robotics include the autonomous inspection of coral reef, ships, pipelines, and other environmental assessment programs. In this paper we present current results in using 6DOF entropy minimization SLAM (simultaneous localization and mapping) for creating dense 3D visual maps of underwater environments that are suitable for such applications. The proposed SLAM algorithm exploits dense information coming from a stereo system, and performs robust egomotion estimation and global-rectification following an optimization approach
Enterovirus infections and enterovirus specific T-cell responses in infancy (1998)

The development of enterovirus specific T-cell and antibody responses were examined in a cohort of 60 healthy infants at the ages of 3, 6, 9, and 12 months. By the age of 6 months, 68% of the infants had developed T-cell responses against enterovirus antigens by lymphocyte proliferation test, whereas only 30% had serological evidence of an enterovirus infection. By this age, only 7% of the infants had adenovirus specific T-cell responses and 3% had serologically verified adenovirus infection. Enterovirus specific T-cell responses correlated with the lack of enterovirus antibodies in cord blood and the number of sibs reflecting protection by maternal antibodies and the rate of exposures, respectively. T-cell responses cross-reacted between different enterovirus serotypes. The results show that enterovirus infections occur frequently in infancy and induce T-cell immunity. Cellular immunity may be a more sensitive indicator of neonatal enterovirus infections than antibodies.
Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery. (1996)

Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.