gebhart/patrepeval huggingface dataset:
Role of Activating Protein-1 in the Regulation of the Vascular Cell Adhesion Molecule-1 Gene Expression by Tumor Necrosis Factor-α (1998)

Endothelial cell surface expression of VCAM-1 is one of the initial steps in the pathogenesis of atherosclerosis. The inflammatory response transcription factor nuclear factor (NF)-kappaB plays an important role in the regulation of VCAM-1 expression by various stimuli including tumor necrosis factor (TNF)-alpha. Other transcription factors may modulate this response through interaction with NF-kappaB factors. Since c-Fos/c-Jun (activating protein-1 (AP-1)) are expressed in vascular endothelium during proinflammatory conditions, we investigated the role of AP-1 proteins in the expression of VCAM-1 by TNF-alpha in SV40 immortalized human microvascular endothelial cells (HMEC). TNF-alpha induced expression of both early protooncogenes, c-fos and c-jun. The ability of TNF-alpha to activate the kappaB-motif (kappaL-kappaR)-dependent VCAM-1 promoter-chloramphenicol acetyltransferase (CAT) reporter gene lacking a consensus AP-1 element was markedly inhibited by co-transfection of the expression vector encoding c-fos ribozyme, which decreases the level of c-fos by degrading c-fos mRNA, or c-fos or c-jun oligonucleotides. Conversely, co-transfection of c-Fos and c-Jun encoding expression vectors potentiated the p65/NF-kappaB-mediated transactivation of the VCAM-1 promoter-CAT reporter gene. Furthermore the c-Fos encoding expression vector potentiated by 2-fold the transactivation activity of a chimeric transcriptional factor Gal/p65 (containing the transactivation domain of p65 and the DNA binding domain of the yeast transcriptional factor Gal-4). Consistent with the promoter studies, curcumin and NDGA, inhibitors of AP-1 activation, markedly inhibited the ability of TNF-alpha to activate the expression of VCAM-1 mRNA levels at concentrations that did not inhibit the activation of NF-kappaB. In gel mobility supershift assays, the antibodies to c-Fos or c-Jun inhibited the binding of TNF-alpha-activated nuclear NF-kappaB to the kappaL-kappaR, suggesting that both c-Fos and c-Jun interacted with NF-kappaB. These results suggest that AP-1 proteins may mediate the effect of TNF-alpha in the regulation of VCAM-1 expression through interaction with NF-kappaB factors in endothelial cells.
Affordable health: The way forward (1998)

‘Everyone has the right to a standard of living adequate for the health and well being of himself and of his family’ (Article 25, Universal Declaration of Human Rights). In this article, we examine the past determinants of health in the United Kingdom, the rise of public health and the impact medical technology has had on health. We discuss the rationing of health care, and apply the principles of health economics to the wider context of the delivery of health, rather than health care. With a background of rising demand for health care and rationing of resources in the UK, combined with widespread variation in life expectancy and distribution of income across the world, we conclude that, in the context of improving world health, environmental regulation ‐ including sanitation and water supply, improved nutrition, control of fertility and better education ‐ must come first in the priorities for achieving a healthy population.
A Model Selection Approach to Real-Time Macroeconomic Forecasting Using Linear Models and Artificial Neural Networks (1997)

We take a model selection approach to the question of whether a class of adaptive prediction models (artificial neural networks) is useful for predicting future values of nine macroeconomic variables. We use a variety of out-of-sample forecast-based model selection criteria, including forecast error measures and forecast direction accuracy. Ex ante or real-time forecasting results based on rolling window prediction methods indicate that multivariate adaptive linear vector autoregression models often outperform a variety of (1) adaptive and nonadaptive univariate models, (2) nonadaptive multivariate models, (3) adaptive nonlinear models, and (4) professionally available survey predictions. Further, model selection based on the in-sample Schwarz information criterion apparently fails to offer a convenient shortcut to true out-of-sample performance measures.
The Radiochemistry of Monoclonal Antibodies and Peptides (2010)

This chapter contains sections titled: Introduction Tumor and Normal Tissue Uptake of Monoclonal Antibodies and Peptides Selection of a Radionuclide for Tumor Imaging Selection of a Radionuclide for Targeted Radiotherapy Labeling Antibodies and Peptides with Radiohalogens Labeling Antibodies and Peptides with Radiometals Characterization of Radiolabeled mAbs and Peptides Summary Acknowledgments References
The politics of comments (2011)

Political views frequently conflict in the coverage of contentious political issues, potentially causing serious social problems. We present a novel social annotation analysis approach for identification of news articles' political orientation. The approach focuses on the behavior of individual commenters. It uncovers commenters' sentiment patterns towards political news articles, and predicts the political orientation from the sentiments expressed in the comments. It takes advantage of commenters' participation as well as their knowledge and intelligence condensed in the sentiment of comments, thereby greatly reduces the high complexity of political view identification. We conduct extensive study on commenters' behaviors, and discover predictive commenters showing a high degree of regularity in their sentiment patterns. We develop and evaluate sentiment pattern-based methods for political view identification.
‘Antifreeze’ glycoproteins from polar fish (2003)

Antifreeze glycoproteins (AFGPs) constitute the major fraction of protein in the blood serum of Antarctic notothenioids and Arctic cod. Each AFGP consists of a varying number of repeating units of (Ala-Ala-Thr)n, with minor sequence variations, and the disaccharide beta-D-galactosyl-(1-->3)-alpha-N-acetyl-D-galactosamine joined as a glycoside to the hydroxyl oxygen of the Thr residues. These compounds allow the fish to survive in subzero ice-laden polar oceans by kinetically depressing the temperature at which ice grows in a noncolligative manner. In contrast to the more widely studied antifreeze proteins, little is known about the mechanism of ice growth inhibition by AFGPs, and there is no definitive model that explains their properties. This review summarizes the structural and physical properties of AFGPs and advances in the last decade that now provide opportunities for further research in this field. High field NMR spectroscopy and molecular dynamics studies have shown that AFGPs are largely unstructured in aqueous solution. While standard carbohydrate degradation studies confirm the requirement of some of the sugar hydroxyls for antifreeze activity, the importance of following structural elements has not been established: (a) the number of hydroxyls required, (b) the stereochemistry of the sugar hydroxyls (i.e. the requirement of galactose as the sugar), (c) the acetamido group on the first galactose sugar, (d) the stereochemistry of the beta-glycosidic linkage between the two sugars and the alpha-glycosidic linkage to Thr, (e) the requirement of a disaccharide for activity, and (f) the Ala and Thr residues in the polypeptide backbone. The recent successful synthesis of small AFGPs using solution methods and solid-phase chemistry provides the opportunity to perform key structure-activity studies that would clarify the important residues and functional groups required for activity. Genetic studies have shown that the AFGPs present in the two geographically and phylogenetically distinct Antarctic notothenioids and Arctic cod have evolved independently, in a rare example of convergent molecular evolution. The AFGPs exhibit concentration dependent thermal hysteresis with maximum hysteresis (1.2 degrees C at 40 mg x mL-1) observed with the higher molecular mass glycoproteins. The ability to modify the rate and shape of crystal growth and protect cellular membranes during lipid-phase transitions have resulted in identification of a number of potential applications of AFGPs as food additives, and in the cryopreservation and hypothermal storage of cells and tissues.
Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients (2014)

ClinicalTrial.gov, number NCT00632333.
Surface Analysis by Plasma Assisted Desorption Ionisation Mass Spectrometry (PADI-MS) (2007)

Plasma assisted desorption/ionisation mass spectrometry (PADI-MS) is a surface analysis technique that yields sample information under ambient conditions of pressure and humidity without any surface preparation. It is achieved by directing a non-thermal atmospheric plasma onto the surface of interest. Desorption occurs from the surface and the subsequent ionisation products are detected in real time by using an atmospheric sampling quadrupole mass spectrometer. We have demonstrated the detection of active ingredients in a range of pharmaceutical and other samples, demonstrating the potential of the technique for high throughput screening in a pharmaceutical or forensics environment.
A second chain of human CD8 is expressed on peripheral blood lymphocytes. (1988)

Human CD8 has been thought to consist of disulfide-linked homodimers and homomultimers of a single polypeptide chain homologous to mouse and rat CD8 alpha. In contrast, mouse and rat CD8 are composed of disulfide-linked heterodimers of alpha and beta chains. We have now isolated and sequenced cDNA clones encoding a human homologue of mouse and rat CD8 beta. One such clone was inserted into an expression vector and its encoded product was shown to be expressed on the cell surface after cotransfection into L cells with the human CD8 alpha gene. A second form of human CD8 beta cDNA encoding a protein with an altered cytoplasmic tail was similarly transfected, but its product could not be demonstrated on the cell surface. CD8 beta was further shown to be expressed on the surface of almost all CD8+ human peripheral blood T cells. These data provide the first evidence that human CD8 is a heterodimeric protein.
Bispecific F(ab′γ)3 antibody derivatives for redirecting unprimed cytotoxic T cells (1991)

Bispecific F(ab'gamma)3 derivatives have been constructed by selective coupling of monoclonal antibody Fab'gamma fragments, using the cross-linker o-phenylenedimaleimide attached to hinge-region sulfhydryl groups. All the derivatives were designed to redirect the cytotoxic activity of circulating human T lymphocytes, via their CD2, CD3 or CD5 molecules, against 51Cr-labeled chicken red blood cells (CRBC) or the human lymphoblastoid cell line, Namalwa. The composition of F(ab'gamma)3 molecules was controlled by the selection of Fab'gamma for initial attachment of cross-linker, allowing production of derivatives with either two anti-effector and one anti-target Fab'gamma arms or vice versa. Bispecific F(ab'gamma)3 derivatives, recruiting peripheral blood lymphocytes (PBL) via CD3 as effectors against CRBC, gave titers in redirected cellular cytotoxicity assays which were consistently 25-100 times higher than those given by an equivalent F(ab'gamma)2 reagent, with full activity being retained down to antibody concentrations of 1 ng/ml. The allocation of valencies--two anti-target/one anti-effector or the converse--was not important in determining the increase in titer. No significant lysis was seen when recruiting PBL via CD2 or CD5. It was notable that these CD3-specific derivatives yielded good tumor-cell lysis when using fresh, unprimed PBL as effectors. The increased activity over a bispecific F(ab'gamma)2 was apparent both in titer and the maximum level of lysis achieved. Blocking studies with excess Fab'gamma suggested that the potency of F(ab'gamma)3 derivatives lie in the strength of bridging between effector and target cells. This high avidity contact could favor metabolic activation in either the target or effector cell, or could increase the efficiency of lytic machinery already triggered.
ChemInform Abstract: USEFUL PROCEDURES FOR THE OXIDATION OF ALCOHOLS INVOLVING PYRIDINIUM DICHROMATE IN APROTIC MEDIA (1979)

Abstract Pyridiniumdichromat (II) wird zur Oxidation von Alkoholen eingesetzt und mit Pyridiniumchlorchromat (I) verglichen.
Optical radiative crosstalk in integrated photonic waveguides (2014)

We report on the comprehensive experimental characterization of optical crosstalk between waveguides caused by scattering. Our results reveal that a strong power exchange between close-placed waveguides due to sidewall roughness exists also for high-quality, low-loss waveguides. We derive a power-law dependence of the coupling on the distance between the waveguides, confirmed by an ad hoc developed electromagnetic model. Further, we demonstrate higher order mode excitation caused by scattered light and the appearance of decorrelation between the guided modes propagating in waveguides coupled via radiative mechanism, providing a full description of this phenomenon.
Adiabatic domain wall motion and Landau-Lifshitz damping (2007)

Recent theory and measurements of the velocity of current-driven domain walls in magnetic nanowires have reopened the unresolved question of whether Landau-Lifshitz damping or Gilbert damping provides the more natural description of dissipative magnetization dynamics. In this paper, we argue that (as in the past) experiment cannot distinguish the two, but that Landau-Lifshitz damping, nevertheless, provides the most physically sensible interpretation of the equation of motion. From this perspective, (i) adiabatic spin-transfer torque dominates the dynamics with small corrections from nonadiabatic effects, (ii) the damping always decreases the magnetic free energy, and (iii) microscopic calculations of damping become consistent with general statistical and thermodynamic considerations.
Influence of Catheter and Arterial Diameter on Flow Distal to an Intra-Aortic Balloon Insertion Site (1998)

Percutaneous placement of an intra-aortic balloon (IAB) through a femoral artery of a patient is associated with a risk of reduction of blood flow distal to the balloon insertion site. If this reduction is severe, it ultimately causes limb ischemia and necessitates IAB removal. Although clinicians intuitively know that larger catheters cause higher flow restrictions, very few studies have examined this situation quantitatively. The authors theoretically analyzed the insertion site geometry in relationship to the catheter diameter and other factors effecting distal flow. To verify the findings, in vitro flow tests were conducted with various IAB catheters currently available on the market, as well as their respective sheaths and hemostasis plugs. This was done using a blood analog solution in an array of polyvinyl chloride tubing sizes. Diameters of the vessel and catheter have a profound and nonlinear effect on the distal flow. For example, a 12.2 Fr catheter in a 0.187 in. vessel only allows 19.9% of normal flow, whereas a 6.1 Fr catheter in the same size vessel allows a 92.0% flow. As the catheter diameter increases, the physical resistance suddenly grows, which causes a significant drop in distal flow. These results are accurately predicted by a mathematical model that gives flow percentage results to within 15% of those measured experimentally. In general, vessels larger than 5 mm in diameter do not exhibit substantial flow reduction for most IABs with and without sheaths. In smaller vessels, however, this reduction may be significant. Sheathless insertion is extremely effective in improving distal blood flow in such a situation. Hemostasis plugs restrict the distal flow similar to respective sheaths, thus diminishing the benefits of sheathless insertion.
Characterization of a Broadly Neutralizing Monoclonal Antibody That Targets the Fusion Domain of Group 2 Influenza A Virus Hemagglutinin (2014)

The influenza hemagglutinin is the major antigenic target of the humoral immune response. However, due to continuous antigenic changes that occur on the surface of this glycoprotein, influenza viruses can escape the immune system and cause significant disease to the host. Toward the development of broad-spectrum therapeutics and vaccines against influenza virus, elucidation of conserved regions of influenza viruses is crucial. Thus, defining these types of epitopes through the generation and characterization of broadly neutralizing monoclonal antibodies (MAbs) can greatly assist others in highlighting conserved regions of hemagglutinin. Here, we demonstrate that MAb 9H10 that targets the hemagglutinin stalk has broadly neutralizing activity against group 2 influenza A viruses in vitro and in vivo.
Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. (1983)

We have developed a quantitative assay to monitor the oxidative burst (H2O2 production) of polymorphonuclear leukocytes (PMNL) using single cell analysis by flow cytometry, and have examined whether PMNL respond to membrane stimulation with an all-or-none oxidative burst. During incubation with normal neutrophils, dichlorofluorescin diacetate diffused into the cells, was hydrolyzed to 2',7'-dichlorofluorescin (DCFH) and was thereby trapped within the cells. The intracellular DCFH, a nonfluorescent fluorescein analogue, was oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF) by PMNL stimulated by phorbol myristate acetate (PMA). That the oxidative product was DCF was shown by excitation/emission spectra and by mass spectrometry of the product from PMA-stimulated PMNL. Normal resting and PMA-stimulated PMNL oxidized 6.9 +/- 0.7 and 160 +/- 13 attomoles DCF per cell, respectively, in 15 min. Absence of calcium and magnesium ions and/or addition of 2 mM EDTA did not inhibit DCF formation by PMNL stimulated by 100 ng/ml PMA. Since EDTA prevented aggregation of PMNL (even when stimulated by 100 ng/ml PMA), which would prevent accurate flow cytometric analysis, further experiments were performed with EDTA in the medium. A close correlation between average DCFH oxidation and hexose monophosphate shunt stimulation was demonstrated using cells from patients whose PMNL had oxidative metabolic defects of varying severity. Intracellular DCFH was also oxidized by reagent H2O2 or oxygen derivatives generated by glucose oxidase + glucose or by xanthine oxidase + acetaldehyde; DCFH oxidation by these systems was inhibited by catalase but unchanged by superoxide dismutase. The data indicate that the DCFH oxidation assay is quantitatively related to the oxidative metabolic burst of PMNL, and they strongly suggest that the reaction is mediated by H2O2 generated by the PMNL. Incubation of PMNL with varying concentrations of PMA caused graded responses by all PMNL present; i.e., 1 ng/ml PMA caused a mean response of 34% maximal with a single population of responding PMNL (rather than 66% resting and 34% fully stimulated as predicted by the all-or-none hypothesis). Thus, with these assay conditions, oxidative product formation by PMNL occurs as a graded response to membrane stimulation by PMA.
A simple theoretical framework for understanding heterogeneous differentiation of CD4+ T cells (2012)

The process in which several types of T helper cells are generated simultaneously to mount complex immune responses upon pathogenic challenges can be highly regulated, and a simple signaling network motif can be responsible for generating all possible types of heterogeneous populations with respect to a pair of master regulators controlling CD4+ T cell differentiation. The framework provides a mathematical basis for understanding the decision-making mechanisms of CD4+ T cells, and it can be helpful for interpreting experimental results. Mathematical models based on the framework make specific testable predictions that may improve our understanding of this differentiation system.
Role of Endogenous BDNF and NT3 for Synaptic Transmission and Plasticity in the Dentate gyrus (2002)

The neurotrophins, notably brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3), modulate synaptic transmission and synaptic plasticity in the adult mammalian brain. Recent data suggest that neurotrophins might be mediators of activity-dependent synaptic plasticity. Such plasticity is believed to be a cellular correlate for important processes like learning, but also for diseases, for instance epilepsy. Indeed, reduced levels of endogenous BDNF or NT3 seem to be protective against the development of epilepsy in animal models of the disorder. The aim of this thesis was to study the effect of endogenous BDNF and NT3 on synaptic transmission in an area of the brain that has been proposed to be involved in the development of epilepsy, the dentate gyrus in the hippocampal formation. We did this by using electrophysiological techniques to measure synaptic activity in brain slices from transgenic mice with lowered endogenous levels of BDNF or NT3, by applying BDNF scavenging agents or recombinant BDNF or NT3. Both BDNF and NT3 influenced short-term plasticity of excitatory synaptic transmission onto granule cells in the dentate gyrus. The effects of BDNF and NT3 were input specific. Thus, NT3 modulated synaptic transmission only in synapses between lateral perforant path and granule cells, whereas BDNF affected medial perforant path to granule cell synapses exclusively. Inhibitory synaptic transmission was altered in BDNF but not NT3 deficient mice. The former displayed an increased frequency of action potential independent spontaneous events, and also altered short-term plasticity of evoked inhibitory synaptic transmission. In animals induced to have an experimental form of epilepsy (kindled animals) no differences were observed in inhibitory synaptic transmission between BDNF deficient and wild-type mice. In conclusion, this thesis work shows specific influences of BDNF and NT3 on excitatory and inhibitory synaptic transmission and on short-lasting synaptic plasticity in the dentate gyrus. This would arguably have consequences on the excitability of this system, and could affect the gating properties of the dentate gyrus during epileptogenesis.
Formulation, characterization and pharmacokinetic evaluation of gentamicin sulphate loaded albumin microspheres (2006)

The aim of this investigation was to prepare and evaluate microsphere formulations of gentamicin using bovine serum albumin (BSA) as a polymer matrix and glutaraldehyde as a cross-linker. Microsphere formulations of gentamicin were prepared using a spray dryer and were evaluated for product yield, encapsulation efficiency, particle size and in vitro drug release. The anti-microbial testing was performed using a modified Kirby-Bauer technique which showed that encapsulated gentamicin had an equivalent anti-microbial activity against E. coli bacteria as compared to gentamicin solution. Since it was the goal to deliver a high drug load intra-cellularly, the formulation with the least burst release profile in PBS was evaluated for its pharmacokinetic performance in rats. The in vivo pharmacokinetic evaluation on rats demonstrated increased bioavailability with microsphere formulation in comparison to the traditional solution form. The significant increase in bioavailability shall enable one to reduce the frequency of gentamicin administration and would effectively reduce the dose related side effects of gentamicin such as ototoxicity and nephrotoxicity.