gebhart/patrepeval huggingface dataset:
Modeling Brain Pathologies Using Neural Stem Cells (2003)

The study of the mechanisms underlying neurodegenerative diseases is a highly demanding goal, complicated by the complexity and heterogeneity of the nervous system and by the long period of time over which these pathologies develop in humans. The use of“simplified” in vitro cell models is therefore often mandatory and useful to investigate aspects of the pathology. Yet, it is a matter of debate how truly informative is this so-called“reductionist approach” to the pathology, especially in the case of complex diseases like those affecting the central nervous system. It is undeniable that in vitro cell cultures lack that unique microenvironment affecting cell behavior and survival in vivo and, of course, extrapolation of results obtained in vitro to the in vivo situation is difficult. Nevertheless, it is just the potential absence of any kind of complicating factors that make it possible to observe and measure the many fundamental biological processes that occur, for example, in the presence of a mutant protein involved in a disease. Another advantage of in vitro models is that they are extremely easy to handle and surely represent the first choice when initially screening for therapeutic compounds.
Automotive applications of chromogenic materials (1990)

Automobiles present both opportunities and challenges for large-area chromogenics. Opportunities include optical and thermal control of vehicle glazing along with optical control of rearview mirrors and privacy glass. Challenges include cost-effectively meeting automotive safety, performance, and reliability standards. Worldwide automobile production' for 1987 is listed in Table 1. Of the roughly 33 million cars produced annually, approximately 8% are luxury models which are candidates for features such as auto- matically dimming rearview mirrors or variable opacity sunroofs. Thus copious commercial opportunities await whatever chromogenic technologies qualify for use in automobiles. This review will describe the performance, safety, and reliability/durability required for automotive use. Commercial opportunities and challenges will be discussed including cost factors and specifications. Chromogenic technologies such as electrochromism, liquid crystals and thermochromism will be reviewed in terms of how publicly announced technical developments match automotive needs and expectations. Construction and performance of ex- isting or imminent chromogenic devices will be described. Finally, how opportunities and challenges of the automotive environment translate to other applications for chromogenic materials such as architectural or information display devices will be discussed. The objective is to generally review the applications, the technologies appropriate to these applications, and the automotive chromogenic devices available at the time of writing to match these applications.
A short course of BG9588 (anti–CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis (2003)

A short course of BG9588 treatment in patients with proliferative lupus nephritis reduces anti-dsDNA antibodies, increases C3 concentrations, and decreases hematuria, suggesting that the drug has immunomodulatory action. Additional studies will be needed to evaluate its long-term effects.
Phenotypic and genotypic analysis of clinical HIV-1 isolates reveals extensive protease inhibitor cross-resistance: a survey of over 6000 samples (2000)

Extensive use of first-generation PIs leads to the emergence of HIV-1 isolates possessing cross-resistance to all members of this class. Identification of particular mutational profiles among these isolates may assist in the design of new generation inhibitors with specific activity against protease-mutant HIV strains.
Cytotoxic T-cell response and AIDS-free survival in simian immunodeficiency virus-infected macaques (1993)

These data suggest that a cytotoxic response may predict a better clinical outcome.
[Simulation of temporal-spatial variation characteristics of surface runoff in Changbai Mountain based on process model for landscape scale]. (2003)

The seasonal dynamics and spatial distribution characteristics of surface runoff in Changbai Mountain simulated by the process model (EPPML), and the relationships between surface runoff and environmental conditions were analyzed. The results showed that the seasonal variation of surface runoff in Changbai Mountain presented obvious three-peak pattern, i.e., the lowest values in June and September, peak values in August (2.58 mm.d-1), similar to that of soil water content. Total trend of surface runoff for different vegetations in the growing season was in order of grass and shrub > coniferous forest > broad-leaved forest > mixed broad-leaved and Korean pine forest, highly correlated to LAI. Annual surface runoff in 1995 was estimated to be 0.203 m.yr.-1, mostly ranging from 0.0 to 0.246.m.yr.-1, accounting for 69.3%. The trend of spatially increasing annual surface runoff along with increasing altitude was obvious. The maximum annual surface runoff appeared in alpine grass (0.619 m.yr.-1), minimum in mixed broad-leaved and Korean pine (Pinus koraiensis) forest (0.081 m.yr.-1), others being alpine tundra, Betula ermanii forest, meadow, shrub, mixed spruce (Picea asperata) and fir (Abies nephrolepis) forest, Changbai larch (Larix olgensis) forest and broad-leaved forest. Vegetation and environmental conditions controlled the main trend of the spatial distribution of annual surface runoff in Changbai Mountain. There was very strong negative exponential correlativity between annual surface runoff and LAI (R2 = 0.857). The more LAI, the more literfall, the more precipitation intercepted by litter, thus, the less surface runoff. Annual surface runoff was highly negatively correlated with air temperature and total solar radiation (R2 being 0.965 and 0.836 respectively), however, it was highly positively correlated with precipitation, relative humidity and wind speed (R2 being more than 0.950). And annual surface runoff was also strongly correlated to soil characteristics.
Dimer Formation in Immunoglobulin Preparations and Speculations on the Mechanism of Action of Intravenous Immune Globulin in Autoimmune Diseases (1994)

IgG dimers occurring in therapeutic Ig preparations have been characterized as Id-anti-Id, in that the sites of interaction are localized to the distal tips of the Fab arms. The observation that such dimers are prevalent in Ig or Igi.v. prepared from large plasma pools, but absent in preparations from a single individual, supports the notion that the individual immune repertoire is small with respect to the species repertoire. A crude mathematical model that attempts to relate Id-dimer content to the number of donors is presented. This model suggests that Id-pairs may be much more prevalent in Ig than is reflected by the Id-dimer content, inasmuch as the concentrations of the individual Ids and anti-Ids may limit the equilibrium level of dimer. The model further suggests that the antibody diversity in Ig derived from thousands of donors may be representative of the species repertoire; hence, virtually all specificities, including anti-Id specificities, will be included. Because Ig is derived from normal healthy donors, it should be relatively free of pathogenic autoantibodies. However, there is no reason to suspect that anti-Ids to such autoantibodies would not occur, and indeed the presence of such anti-Ids has been demonstrated. Several mechanisms have been proposed by which such anti-Ids might ameliorate autoimmune disease. They may directly inhibit the binding of autoantibody to its target antigen, or they may target for destruction those cells expressing or secreting autoantibody. It may well be that anti-Ids play no role in the mechanism of action of Igi.v. in autoimmune disease. Such appears to have been demonstrated, for example, in the treatment of ITP. There is an obvious need for additional studies in order to elucidate the mechanism of action of Igi.v. in various autoimmune diseases. Experimental animal models of autoimmune disease, such as the mouse model for systemic lupus erythematosus (Mozes et al. 1993), might be very useful in this regard. Finally, it needs to be emphasized that the usefulness of high doses of Igi.v. in many autoimmune diseases remains to be established by controlled clinical trials. Because Igi.v. is a limited resource, and one which cannot be produced through biotechnological advances (at least in the foreseeable future), its widespread use should be restricted to the treatment of diseases for which efficacy has been demonstrated. To do otherwise might deprive appropriate patients of a valuable therapy.
Arginine-395 is required for efficient in vivo and in vitro aminoacylation of tRNAs by Escherichia coli methionyl-tRNA synthetase (1991)

We have previously shown that the anticodon of methionine tRNAs contains the major recognition site required for aminoacylation of tRNAs by Escherichia coli methionyl-tRNA synthetase (MetRS) and have located part of the anticodon binding domain on the enzyme at a site close to Trp461 [Schulman, L. H., & Pelka, H. (1988) Science 242, 765-768; Ghosh, G., Pelka, H., & Schulman, L.H. (1990) Biochemistry 29, 2220-2225]. In order to gain information about other possible sites of contact between MetRS and its tRNA substrates, we have examined the effects of mutations at a series of positively charged residues on the surface of the C-terminal domain of the enzyme. Conversion of Arg356, Arg366, Arg380, or Arg453 to Gln had little or no effect on enzyme activity. Similarly, conversion of Lys402 or Lys439 to Asn failed to significantly alter aminoacylation activity. Conversion of Arg380 to Ala or Arg442 to Gln produced a 5-fold reduction in kcat/Km for aminoacylation of tRNAfMet, with no effect on methionine activation, indicating a possible minor role for these residues in interaction of the enzyme with the tRNA substrate. In contrast, mutation of a phylogenetically conserved residue, Arg395, to Gln increased the Km for aminoacylation of tRNAfMet about 30-fold and reduced kcat/Km by 25,000-fold. The mutant enzyme was also shown to be highly defective by its inability to complement a strain of E. coli having an altered chromosomal MetRS gene.(ABSTRACT TRUNCATED AT 250 WORDS)
Flow cytometric method to demonstrate whether anti-HIV-1 agents inhibit virion binding to T4+ cells. (1989)

The first step in the replicative cycle of human immunodeficiency virus type 1 (HIV-1) is binding of the virions to the cellular CD4 receptor. This process may be considered as an important target for chemotherapeutic agents against acquired immune deficiency syndrome (AIDS). A method has now been devised whereby virion binding to the cell membrane was visualized by an indirect immunofluorescence assay using human anti-HIV-1 serum, rabbit anti-human-IG-F(ab')2-fluorescein isothiocyanate, and flow cytometry. Heparin, dextran sulfate, and pentosan polysulfate suppressed HIV-1 binding to MT-4 cells at concentrations that protected the cells against HIV-1 cytopathogenicity. Dextran and dermatan sulfate, two compounds that are inactive against HIV-1, had no inhibitory effect on the binding of HIV-1 to the cells. The potent and selective HIV-1 inhibitor azidothymidine (AZT) did not affect virus binding to the cells, whereas suramin partially blocked HIV-1 binding to the cells at concentrations that fully protected MT-4 cells against destruction of HIV-1. Our immunofluorescence assay thus demonstrated that suramin not only acts as an inhibitor of reverse transcriptase but also interferes with virus-cell binding. Also, Evans blue, an anionic dye structurally related to suramin, partially inhibited HIV-1 attachment to the cells. The present method permits a quantitative determination of the inhibitory effect of anti-HIV-1 agents on virion-cell binding.
Recent advances of electrochemical mass spectrometry (2013)

This review article surveys some recent developments of electrochemistry (EC) in combination with mass spectrometry (MS) including instrumentation and bioanalytical applications.
Enhancing Perception in Minimally Invasive Robotic Surgery through Self-Calibration of Surgical Instruments (2007)

In minimally invasive surgery (MIS) the 3D perception and hand-eye coordination is reduced. A high degree of sensory-motor skills is required by the surgeon to mediate action and perception. The incorporation of robotic assistants is capable of integrating the required egocentric information to aid the surgeon providing a sense of presence. In this work we propose a robotic vision system as a tool to locate surgical instruments with respect to the surgeon. It estimates the absolute position of the port of entry, in which surgical instruments are inserted to access the patient body. The proposed algorithm shows that it is possible to estimate the orientation of the instruments with respect to the laparoscopic camera applying determined movements through the robotic assistant.
Analysis of the functional domains of complement receptor type 1 (C3b/C4b receptor; CD35) by substitution mutagenesis. (1994)

The complement receptor type 1 (CR1; CD35), carrying 30 short consensus repeats (SCRs), has two sites. Site 1 contains SCR-1 and SCR-2 and binds C4b. Site 2 contains SCR-8 and SCR-9 and was reported to bind mainly C3b (Klickstein, L. B., Bartow, T. J., Miletic, V., Rabson, L. D., Smith, J. A., and Fearon, D. T. (1988) J. Exp. Med. 168, 1699-1717). For the functional analysis we used two constructs, each with one site. CR1-4, composed of eight and one-half initial SCRs, carries site 1, binds C4b, and is cofactor for C4b cleavage. CR1-4(8,9), obtained from CR1-4 by converting site 1 to site 2, binds iC3/C3b and, unexpectedly, C4b. It is a cofactor for cleavage of both ligands. Its cofactor activity for C4b cleavage is greater than that of site 1. Analysis of the mutants constructed by interchanging homologous peptides between the two sites identified no sequences necessary for cofactor activity other than those required for binding. In site 2, peptides important for both ligands were found. Some modifications of either site led to higher activity for both ligands. Thus the activity of complement regulators can be increased by changing a few amino acids within SCRs, an important step toward the generation of more effective inhibitors of complement activation. Knowledge of the active sites of CR1 should be applicable to other SCR-containing proteins and should provide insights into the evolution of these proteins.
Macrophage colony stimulatory factor and interferon‐γ trigger distinct mechanisms for augmentation of β‐amyloid‐induced microglia‐mediated neurotoxicity (2004)

Dysregulated stimulation of microglia, the resident macrophages in the brain, can lead to excessive induction of inflammatory agents and subsequently damage to neurons. Fibrillar beta-amyloid peptide (fA beta), a major component of senile plaques in Alzheimer's disease (AD) brain, is known to induce microglial-mediated neurotoxicity under certain conditions. Microglial 'priming' by macrophage colony stimulatory factor (MCSF) or interferon-gamma (IFN gamma) appears to be required for this fA beta-induced microglia mediated neurotoxicity in vitro. We report here that while both MCSF and IFN gamma induce microglial-mediated fA beta neurotoxicity, their mechanisms of toxicity differ. The enhancement of neurotoxicity by IFN gamma or MCSF is not due to enhanced A beta ingestion by microglia or to the direct effect of proinflammatory cytokine production. The neurotoxicity resulting from IFN gamma/fA beta treatment was blocked by pretreatment with nitric oxide synthase inhibitor L-N-5-(1-iminoethyl) ornithine hydrochloride (L-NIO), consistent with a role for nitric oxide in the IFN gamma-mediated toxicity mechanism. In contrast, no induction of nitric oxide production was detected for microglia treated with MCSF/fA beta. Furthermore, inhibiting the generation of reactive oxygen species (ROS) using the specific NADPH oxidase inhibitor apocynin reversed fA beta/MCSF-induced neurotoxicity while L-NIO had little effect. As MCSF is endogenously expressed within the brain, and both its level and that of the MCSF receptor are dramatically increased in the AD brain, the neurotoxicity resulting from ROS release by fA beta/MCSF coactivated microglia may be a more appropriate model for assessing fA beta-induced microglial-mediated neuropathology in AD.
Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis (2006)

ClinicalTrials.gov Identifier: NCT00240318.
Inhibition of Staphylococcus aureus gene expression and growth using antisense peptide nucleic acids (2004)

Gene function studies in bacteria lag behind progress in genome sequencing, in part because current reverse genetics technology based on genome disruption does not allow subtle control of gene expression for all genes in a range of species. Essential genes and clustered regions are particularly problematic. Antisense technology offers an attractive alternative for microbial genomics. Unfortunately, bacteria lack RNAi mechanisms and conventional oligonucleotides are not taken up efficiently. However, in Escherichia coli, efficient and gene-specific antisense knock down is possible using antisense peptide nucleic acids (PNAs) attached to carrier peptides (KFFKFFKFFK). Carrier peptides can enter a range of microbial species, and in this study we asked whether peptide-PNAs could mediate antisense effects in Staphylococcus aureus. Using low micromolar concentrations we observed dose- and sequence-dependent inhibition of the reporter gene gfp and endogenous gene phoB. Also, antisense peptide-PNAs targeted to the essential genes fmhB, gyrA, and hmrB were growth inhibitory. Control peptide-PNAs were much less effective, and sequence alterations within the PNA and target mRNA sequences reduced or eliminated inhibition. Further development is needed to raise the antibacterial potential of PNAs, but the present results show that the approach can be used to study gene function and requirement in this important pathogen.
PORCINE NEONATAL PANCREATIC CELL CLUSTERS IN TISSUE CULTURE: BENEFITS OF SERUM AND IMMOBILIZATION IN ALGINATE HYDROGEL1 (2001)

Porcine neonatal pancreatic cell clusters (NPCCs) may be a suitable source of insulin producing tissue for transplantation in diabetic patients. The possible beneficial effect of serum on maturation of NPCCs in vitro is difficult to achieve because of cell clumping, which can be avoided by immobilization in alginate hydrogel matrix. Collagenase treated pancreata, cultured for 4 days, formed NPCCs that were embedded in alginate cross-linked with CaCl2 and cultured in modified Ham's F10 medium with 10% fetal calf serum (FCS) for 10 days. NPCCs cultured as suspension in F10+ with 0.5% bovine serum albumin or with 10% FCS were used as control. To prevent the aggregation when cultured with serum, NPCCs were kept as a very diluted suspension. At the beginning and end of the culture, samples were taken for insulin and DNA content and immunostained for beta and non-beta cells. The culture of NPCCs immobilized in alginate resulted with 3-fold increase in insulin content and 9-fold increase in insulin/DNA ratio. Histology revealed evident increase of number of insulin- and other hormone-positive cells compared with the control. Even though 2 weeks in culture resulted in impaired glucose-induced insulin release, the amount of insulin secreted by clusters cultured in the presence of serum was 4-fold higher than in serum-free conditions. After transplantation, NPCCs retrieved from alginate reversed hyperglycemia similarly to NPCCs cultured in standard conditions. In conclusion, this study shows the feasibility of in vitro immobilization of NPCCs in alginate three-dimensional matrix, allowing cell clusters to be cultured at least two times higher density compared with culture in suspension.
An Improved Methodology for the Design of Power System Damping Controllers (2005)

This paper presents a set of significant improvements made over a previously developed methodology for the design of controllers to damp electromechanical oscillations in power systems. This previous methodology was able to fulfil several practical requirements of the oscillation damping problem, related to robustness, decentralization, and output feedback structure. However, problems related to an adequate controller gain (to avoid interactions with unmodeled dynamics) and disturbance rejection (allowing the use of noisy input signals, such as the rotor speed measurements) were not treated in this previously reported methodology, and are now addressed in this work. Moreover, the requirement of zero gain in steady-state conditions is now met in a more efficient way. The results of the nonlinear simulations show the satisfactory performance of the designed controllers with respect to the mentioned practical requirements.
Combined Deficiency of p50 and cRel in CD4+ T Cells Reveals an Essential Requirement for Nuclear Factor κB in Regulating Mature T Cell Survival and In Vivo Function (2003)

Signaling pathways involved in regulating T cell proliferation and survival are not well understood. Here we have investigated a possible role of the nuclear factor (NF)-kappaB pathway in regulating mature T cell function by using CD4+ T cells from p50-/- cRel-/- mice, which exhibit virtually no inducible kappaB site binding activity. Studies with these mice indicate an essential role of T cell receptor (TCR)-induced NF-kappaB in regulating interleukin (IL)-2 expression, cell cycle entry, and survival of T cells. Our results further indicate that NF-kappaB regulates TCR-induced expression of antiapoptotic Bcl-2 family members. Strikingly, retroviral transduction of CD4+ T cells with the NF-kappaB-inducing IkappaB kinase beta showed that NF-kappaB activation is not only necessary but also sufficient for T cell survival. In contrast, our results indicate a lack of involvement of NF-kappaB in both IL-2 and Akt-induced survival pathways. In vivo, p50-/- cRel-/- mice showed impaired superantigen-induced T cell responses as well as decreased numbers of effector/memory and regulatory CD4+ T cells. These findings provide the first demonstration of a role for NF-kappaB proteins in regulating T cell function in vivo and establish a critically important function of NF-kappaB in TCR-induced regulation of survival.