gebhart/patrepeval huggingface dataset:
Interaction of the Wiskott–Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells (2007)

The Wiskott-Aldrich syndrome protein (WASp) plays a major role in coupling T cell antigen receptor (TCR) stimulation to induction of actin cytoskeletal changes required for T cell activation. Here, we report that WASp inducibly binds the sorting nexin 9 (SNX9) in T cells and that WASp, SNX9, p85, and CD28 colocalize within clathrin-containing endocytic vesicles after TCR/CD28 costimulation. SNX9, implicated in clathrin-mediated endocytosis, binds WASp via its SH3 domain and uses its PX domain to interact with the phosphoinositol 3-kinase regulatory subunit p85 and product, phosphoinositol (3,4,5)P3. The data reveal ligation-induced CD28 endocytosis to be clathrin- and phosphoinositol 3-kinase-dependent and TCR/CD28-evoked CD28 internalization and NFAT activation to be markedly enhanced by SNX9 overexpression, but severely impaired by expression of an SNX9 mutant (SNX9DeltaPX) lacking p85-binding capacity. CD28 endocytosis and CD28-evoked actin polymerization also are impaired in WASp-deficient T cells. These findings suggest that SNX9 couples WASp to p85 and CD28 so as to link CD28 engagement to its internalization and to WASp-mediated actin remodeling required for CD28 cosignaling. Thus, the WASp/SNX9/p85/CD28 complex enables a unique interface of endocytic, actin polymerizing, and signal transduction pathways required for CD28-mediated T cell costimulation.
Practical enzyme-based syntheses of uridine 5'-diphosphogalactose and uridine 5'-diphospho-N-acetylgalactosamine on a gram scale (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPractical enzyme-based syntheses of uridine 5'-diphosphogalactose and uridine 5'-diphospho-N-acetylgalactosamine on a gram scaleJurgen E. Heidlas, Watson J. Lees, and George M. WhitesidesCite this: J. Org. Chem. 1992, 57, 1, 152–157Publication Date (Print):January 1, 1992Publication History Published online1 May 2002Published inissue 1 January 1992https://pubs.acs.org/doi/10.1021/jo00027a029https://doi.org/10.1021/jo00027a029research-articleACS PublicationsRequest reuse permissionsArticle Views443Altmetric-Citations56LEARN 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
Entropy in biological binding processes: Estimation of translational entropy loss (1994)

The loss of translational degrees of freedom makes an important, unfavorable contribution to the free energy of binding. Examination of experimental values suggest that calculation of this entropy using the Sackur-Tetrode equation produces largely overestimated values. Better agreement is obtained using the cratic entropy. Theoretical considerations suggest that the volumes available for the movement of a ligand in solution and in a complex are rather similar, suggesting also that the cratic entropy provides the best estimate of the loss of translational entropy.
FliT Acts as an Anti-FlhD 2 C 2 Factor in the Transcriptional Control of the Flagellar Regulon in Salmonella enterica Serovar Typhimurium (2006)

Flagellar operons are divided into three classes with respect to their transcriptional hierarchy in Salmonella enterica serovar Typhimurium. The class 1 gene products FlhD and FlhC act together in an FlhD(2)C(2) heterotetramer, which binds upstream of the class 2 promoters to facilitate binding of RNA polymerase. Class 2 expression is known to be enhanced by a disruption mutation in a flagellar gene, fliT. In this study, we purified FliT protein in a His-tagged form and showed that the protein prevented binding of FlhD(2)C(2) to the class 2 promoter and inhibited FlhD(2)C(2)-dependent transcription. Pull-down and far-Western blotting analyses revealed that the FliT protein was capable of binding to FlhD(2)C(2) and FlhC and not to FlhD alone. We conclude that FliT acts as an anti-FlhD(2)C(2) factor, which binds to FlhD(2)C(2) through interaction with the FlhC subunit and inhibits its binding to the class 2 promoter.
Microrelief diffraction structure recording in LC reactive mesogen (2002)

Reactive liquid crystal (LC) mesogen (trade mark C6M of Merck) is shown to possess efficient relief formation properties. Photosensitive formulation was made by mixing of the reactive LC mesogen C6M with 2% of photoinitiator (Irgacure 651). Photosensitive layer (thickness 70 micrometers ) was obtained by melting the formulation in the gap between two glass substrates. One of the substrates contained a photosensitive silver-halide layer, in which the amplitude mask was recorded with the resolution Fequals40 lines/mm. The amplitude function of the mask represented a phase function of the desired CO<SUB>2</SUB> laser focusing element, designed for wavelength 10.6 micrometers and 45 degrees incidence . Exposure of the reactive mesogen layer through the mask was carried out at elevated temperature of Tequals85 degrees C by UV source (wavelength 365 nm). Immediately after exposure a substrate with photomask was removed and the relief structure in the exposed layer was measured to be ca. hequals1 micrometers deep. After that a dark self-development was allowed resulting in the increase of relief depth h up to 15 micrometers within several hours. The desired hequals7.5 micrometers needed for the most efficient performance of CO<SUB>2</SUB> laser focusing element at 10.6 micrometers and 45 degrees incidence, was stabilized by interrupting self-development with uniform UV exposure of the recorded structure.
Human Embryonic Germ Cell Derivatives Facilitate Motor Recovery of Rats with Diffuse Motor Neuron Injury (2003)

We have investigated the potential of human pluripotent cells to restore function in rats paralyzed with a virus-induced motor neuronopathy. Cells derived from embryonic germ cells, termed embryoid body-derived (EBD) cells, introduced into the CSF were distributed extensively over the rostrocaudal length of the spinal cord and migrated into the spinal cord parenchyma in paralyzed, but not uninjured, animals. Some of the transplanted human cells expressed the neuroglial progenitor marker nestin, whereas others expressed immunohistochemical markers characteristic of astrocytes or mature neurons. Rare transplanted cells developed immunoreactivity to choline acetyltransferase (ChAT) and sent axons into the sciatic nerve as detected by retrograde labeling. Paralyzed animals transplanted with EBD cells partially recovered motor function 12 and 24 weeks after transplantation, whereas control animals remained paralyzed. Semi-quantitative analysis revealed that the efficiency of neuronal differentiation and extension of neurites could not account for the functional recovery. Rather, transplanted EBD cells protected host neurons from death and facilitated reafferentation of motor neuron cell bodies. In vitro, EBD cells secrete transforming growth factor-alpha (TGF-alpha) and brain-derived neurotrophic factor (BDNF). Neutralizing antibodies to TGF-alpha and to BDNF abrogated the ability of EBD-conditioned media to sustain motor neuron survival in culture, whereas neutralizing antibodies to BDNF eliminated the axonal outgrowth from spinal organotypics observed with direct coculture of EBD cells. We conclude that cells derived from human pluripotent stem cells have the capacity to restore neurologic function in animals with diffuse motor neuron disease via enhancement of host neuron survival and function.
Gram-positive and gram-negative bacterial toxins in sepsis (2013)

Bacterial sepsis is a major cause of fatality worldwide. Sepsis is a multi-step process that involves an uncontrolled inflammatory response by the host cells that may result in multi organ failure and death. Both gram-negative and gram-positive bacteria play a major role in causing sepsis. These bacteria produce a range of virulence factors that enable them to escape the immune defenses and disseminate to remote organs, and toxins that interact with host cells via specific receptors on the cell surface and trigger a dysregulated immune response. Over the past decade, our understanding of toxins has markedly improved, allowing for new therapeutic strategies to be developed. This review summarizes some of these toxins and their role in sepsis.
Ribozyme-mediated attenuation of pancreatic beta-cell glucokinase expression in transgenic mice results in impaired glucose-induced insulin secretion. (1994)

Phosphorylation of glucose to glucose 6-phosphate by glucokinase (GK; EC 2.7.1.2) serves as a glucose-sensing mechanism for regulating insulin secretion in beta cells. Recent findings of heterozygous GK gene mutations in patients with maturity-onset diabetes of the young (MODY), a form of type II (non-insulin-dependent) diabetes characterized by autosomal dominant inheritance, have raised the possibility that a decrease in beta-cell GK activity may impair the insulin secretory response of these cells to glucose. To generate an animal model for MODY we have expressed in transgenic mice a GK antisense RNA with a ribozyme element under control of the insulin promoter. Mice in two independent lineages had about 30% of the normal islet GK activity. Insulin release in response to glucose from in situ-perfused pancreas was impaired; however, the plasma glucose and insulin levels of the mice remained normal. These mice are likely to be predisposed to type II diabetes and may manifest increased susceptibility to genetic and environmental diabetogenic factors. They provide an animal model for studying the interaction of such factors with the reduced islet GK activity.
Robust time-optimal control of uncertain flexible spacecraft (1992)

A new approach for computing time-optimal open-loop control inputs for uncertain flexible spacecraft is developed. In particular, the single-axis, rest-to-rest maneuvering problem of flexible spacecraft in the presence of uncertainty in model parameters is investigated. Robust time-optimal control inputs are obtained by solving a parameter optimization problem subject to robustness constraints. A simple dynamical system with a rigidbody mode and one flexible mode is used to illustrate the concept.
Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure (2009)

Hepatitis E virus (HEV) is a causative agent of acute hepatitis. The crystal structure of HEV-like particles (HEV-LP) consisting of capsid protein was determined at 3.5-A resolution. The capsid protein exhibited a quite different folding at the protruding and middle domains from the members of the families of Caliciviridae and Tombusviridae, while the shell domain shared the common folding. Tyr-288 at the 5-fold axis plays key roles in the assembly of HEV-LP, and aromatic amino acid residues are well conserved among the structurally related viruses. Mutational analyses indicated that the protruding domain is involved in the binding to the cells susceptive to HEV infection and has some neutralization epitopes. These structural and biological findings are important for understanding the molecular mechanisms of assembly and entry of HEV and also provide clues in the development of preventive and prophylactic measures for hepatitis E.
Bisacylphosphine oxides as bifunctional photoinitiators for block copolymer synthesis (1999)

Block copolymers of styrene (St) and methyl methacrylate (MMA) were prepared via a two-step procedure by using bisacylphosphine oxide (BAPO) as photoinitiator. Photolysis of BAPO at λ = 420 nm in the presence of St yielded polymers with monoacylphosphine oxide terminal groups. Subsequent irradiation of the polymers in the presence of MMA at λ = 380 nm produced block copolymers. Block copolymer formation was evidenced by spectral measurements and GPC analysis. Blockcopolymere aus Styrol (St) und Methylmethacrylat (MMA) wurden in einer zweistufigen Reaktion mit Bisacylphosphinoxid (BAPO) als Photoinitiator hergestellt. Die Photolyse von BAPO bei λ = 420 nm in Gegenwart von Styrol führte zu Polymeren mit Monoacylphosphinoxid-Endgruppen. Durch anschließende Bestrahlung der Polymeren in Gegenwart von MMA bei λ = 380 nm wurden Blockcopolymere erhalten. Die Blockcopolymerbildung wurde mit Spektralanalyse und GPC nachgewiesen.
High Sensitivity Collisionally‐activated Decomposition Tandem Mass Spectrometry on a Novel Quadrupole/Orthogonal‐acceleration Time‐of‐flight Mass Spectrometer (1996)

Consideration of the special problems encountered in ultra-high sensitivity biopolymer sequencing studies has led to the development of a novel quadrupole/orthogonal-acceleration time-of-flight tandem mass spectrometer described for the first time here. The performance characteristics of this new geometry are demonstrated, including fully resolved daughter-ion spectra with mass accuracies of 0.1 dalton, which allow removal of interpretation ambiguities and easy differentiation of charge states even in weak collisionally-activated decomposition tandem mass spectra. The instrument has been applied to a variety of biopolymer research problems, including the structure determination of major histocompatibility complex peptide antigens using liquid chromatography/electrospray mass spectrometry and nanoflow-electrospray tandem mass spectrometry, and sequencing capability in the low-femtomole and attomole ranges is demonstrated.
Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe Respiratory Syncytial Virus Bronchiolitis (2011)

RSV infection induces significant down-regulation of the airway antioxidant system in vivo, likely resulting in lung oxidative damage. Modulation of oxidative stress may pave the way toward important advances in the therapeutic approach of RSV-induced acute lung disease.
Effects of the par Locus on the Growth Rate and Structural Stability of Recombinant Cells (1993)

A decreased growth rate of recombinant cells is observed when a cloned gene protein encoded in a multicopy plasmid is induced from a strong promoter. This negative effect on the cell growth rate may be the consequence of alternate use or reallocation of energy, precursor metabolites, and protein synthesizing machinery. In order to analyze the causes for this adverse effect, we have studied how genetic elements present in multicopy plasmids affect the growth of recombinant Escherichia coli (K12 delta H1 delta trpEA). Turning on of the PL promoter, whether or not protein-coding sequences were present downstream of the promoter, decreased the growth of the recombinant cells by 15-50%. This result suggests that the essential factor(s) for cell growth may be sequestered by the genetic elements present in the plasmids and thus may cause the decreased growth. The negative effect of the de-repressed PL promoters on cell growth was partially reversed when the par sequence from pSC101 was inserted into the same plasmid. In each case when the plasmid carried only the PL promoter, the PL promoter followed by the N-terminal part of the protein-coding region, or the PL promoter followed by complete sequences encoding a protein, the par sequence exhibited a positive effect on the growth rate of the recombinant cells, which usually grow at a slower rate than the host cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Microneedle arrays for intracellular recording applications (2008)

This paper reports on the fabrication and application of microneedles for the electroporation of adherently growing cells and intracellular recording with focus on the influence on external factors on the cell behavior. Patch-on-chip methods such as patch-clamp have been applied mostly to individual cells in suspension. However, in the human body most of cells are adherently growing cells, which motivated the development of a new chip design. The chip contains an array of 64 microneedles occupying a total area of approximately 1 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The microneedles are fabricated using dry etching of silicon, followed by an insulation, metallization and passivation. The passivation layer is opened at the tip of the needles in order to expose the metal for cell positioning via dielectrophoresis, cell electroporation, as well as intracellular recording. Various needles with diameters in the sub-micron range and heights below 10 mum have been fabricated. Heart muscle cells, fibroblasts, and primary neuronal cells of mice were grown on these microneedle arrays. To electrically access the intracellular space, the cells were electroporated with a voltage of plusmn2 V. Preliminary tests show that more than 80% of the cells could successfully be porated.
Control of Particle Size in Dispersion Polymerization Using Poly(Ethylene Oxide) Macromonomers (1995)

Abstract Dispersion copolymerization of styrene with a small amount of PEO macromonomer having p-styrylbutyl end group (Mn = 2000) in methanol/water (90/10 vol%) produced monodisperse microspheres of 0.5 to 3 μ in diameter. The particle size increased in proportion to Θ1/3W°2/3(r1/WD° Scrit)1/2, a theoretical model based on particles formation sterically stabilized by graft-copolymerized PEO chains on the particle surface, where Θ = styrene conversion, W° = styrene weight in feed, WD ° = macromonomer weight in feed, Scrit = critical occupancy area per grafted PEO chain, and r1 = monomer reactivity ratio of styrene before critical conversion. Quantitave agreement between theory and experiment was obtained with Scrit/r1 = 10 nm2.
A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon α (1999)

A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c. B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m. with mIFN-alpha pDNA. In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene.
Ipilimumab augments antitumor activity of bispecific antibody-armed T cells (2014)

Expansion of ATC in the presence of ipilimumab significantly improves not only the T cell proliferation but it also enhances cytokine secretion and the specific cytotoxicity of T cells armed with bispecific antibodies.
Prognostic Factors in Men with Stage D1 Prostate Cancer: Identification of Patients Less Likely to Have Prolonged Survival After Radical Prostatectomy (1994)

The role of radical prostatectomy in the management of stage D1 disease is controversial. Although cure is unlikely, some men survive for long intervals apparently free of metastatic disease. For this reason, effective palliation of the local lesion is desirable in men who will live long enough to benefit. In an effort to identify factors that correlated with interval to progression to distant metastases, we studied 113 men with stage D1 disease who underwent radical prostatectomy between 1974 and 1991. Progression of disease to distant metastases did not independently correlate with the size of the nodal metastases, number of positive lymph nodes or bilaterality of lymph node metastases. Only high Gleason score (8 to 10) on the preoperative biopsy correlated with rapid progression to distant metastases (p < or = 0.00001) in a multivariate analysis. If the Gleason score was less than 8, the likelihood of distant metastases was only 18% and 41% at 5 and 10 years, respectively, whereas 85% of men with a Gleason score of 8 to 10 had distant metastases by 5 years. For urologists who believe that radical prostatectomy is useful in providing local control in men with positive lymph nodes, frozen section analysis of lymph nodes is probably not necessary in men who are candidates for radical prostatectomy and have preoperative Gleason scores of less than 8. Conversely, in patients with a Gleason score of 8 to 10 on needle biopsy, careful analysis of lymph nodes is necessary to avoid radical prostatectomy in those who will derive little benefit.
Wellbore Cooling as a Means To Permanently Increase Fracture Gradient (2006)

Abstract In recent years, several techniques have been proposed to increase the fracture gradient by inducing changes in the near wellbore region (Alberty and McLean, 2004; Sweatman, et al., 2004;Benaissa et al., 2005). This process, often called "wellbore strengthening", has most recently been implemented by adding specially designed proppant material to the mud before raising its pressure above the fracture gradient. The goal was to induce short tensile fractures in the vicinity of the wellbore wall which are prevented from propagating; thus, creating a "stress cage". However, this method has often proven ineffective in low permeability formations where mainly uncontrolled fracture propagation occurs. The purpose of this paper is to propose and evaluate the use of wellbore cooling, in combination with more classical stengthening processes, to permanently increase the fracture gradient without the risk of circulation losses inherent in the "stress cage" method, as it is currently applied. This approach involves lowering the temperature of the drilling mud; thus, reducing the hoop stress at the borehole wall and then ‘setting’ the stress cage in the standard manner. Tensile cracks can then be induced at significant lower mud weights. Given the typical thermal conductivity properties of rocks,the tensile stresses induced by cooling (and consequently, the created fractures) will tend to be confined to the near wellbore region. This work presents an evaluation of the effect cooling has on the stress profile of a "solid" material and compares it with a fully coupled thermoporoelastic solution. The results of such analyses may then be used to design a field application to test this novel idea.