gebhart/patrepeval huggingface dataset:
pH-dependent denaturation of thrombin-activated porcine factor VIII. (1990)

Thrombin-activated porcine factor VIII (fVIIIaIIa) is a stable, active, 160-kDa heterotrimer at concentrations exceeding 2 x 10(-7) M in 0.7 M NaCl, 0.01 M histidine Cl, 5 mM CaCl2, pH 6.0, at 4 degrees C or 20 degrees C. Two of the subunits, fVIIIA1 and fVIIIA2, are derived from the heavy chain of the plasma-derived, heterodimeric fVIII precursor. The third subunit, fVIIIA3-C1-C2, is derived from the fVIII light chain. We now find that fVIIIaIIa undergoes a sharp decline in coagulant activity between pH 7 and 8. At pH 7.5, the activity of fVIIIaIIa at 3 x 10(-7) M decays within a few hours to a stable level that is approximately 70% of the value at pH 6.0, whereas at pH 8.0, greater than 99% of the activity is lost. The activity cannot be restored by readjusting the pH to 6.0. The loss of activity at pH 8.0 coincides with dissociation of the fVIIIA2 subunit since an inactive fVIIIA1/A3-C1-C2 heterodimer can be isolated by Mono S high performance liquid chromatography. After prolonged incubation at pH 8.0, the fVIIIA1 subunit also dissociates. The free fVIIIA2 fragment appears to be poorly soluble which may explain the irreversible loss of activity. Analytical velocity sedimentation of the pH-inactivated fVIIIaIIa preparation also is consistent with dissociation and precipitation of the fVIIIA2 fragment. We propose that denaturation of fVIIIaIIa by pH-dependent subunit dissociation may provide a major mechanism of inactivation of fVIIIaIIa under physiologic conditions.
Use of the Syrian Hamster as an Animal Model for Oncolytic Adenovirus Vectors (2007)

Oncolytic adenoviruses (Ads) are promising candidates for cancer therapy. However, current animal models to evaluate these vectors have substantial limitations. Because Ad replication is generally species-specific, oncolytic Ads are usually examined in immunodeficient mice bearing human xenograft tumors. However, this model suffers because the animals are immunodeficient and normal and cancerous mouse tissues are poorly permissive to human Ad replication. We have recently developed a Syrian hamster model that is both immunocompetent and permissive to human Ad replication in normal and cancerous tissues. The Syrian hamster is also permissive for Ad5 replication in the lung, which is the natural site of infection in humans. Human Ads replicate well in vitro in the Syrian hamster cell lines examined and demonstrate significant antitumor efficacy following injection into Syrian hamster tumors in vivo. In this chapter we describe the maintenance of these Syrian hamster cell lines in culture and how to assess oncolytic Ad vector replication in these cells in vitro. We also describe detailed methods for growth of these cell lines as subcutaneous tumors, for intravenous and intratumoral injections in hamsters, and for evaluation of the efficacy, replication, and biodistribution of oncolytic Ad vectors following administration in hamsters. In addition, we describe how to assess replication in normal tissues such as the lungs and give helpful tips on handling, anesthesia, and general care of Syrian hamsters.
Induction of Protective Immunity againstChlamydia trachomatisGenital Infection by a Vaccine Based on Major Outer Membrane Protein–Lipophilic Immune Response-Stimulating Complexes (2000)

The significance of delivery systems in modern vaccine design strategies is underscored by the fact that a promising vaccine formulation may fail in vivo due to an inappropriate delivery method. We evaluated the immunogenicity and efficacy of a candidate vaccine comprising the major outer membrane protein (MOMP) of Chlamydia trachomatis delivered with the lipophilic immune response-stimulating complexes (ISCOMs) as a vehicle with adjuvant properties, in a murine model of chlamydial genital infection. Immunocompetent BALB/c mice were immunized intranasally (IN) or intramuscularly (IM) with MOMP, MOMP-ISCOMs, and live or heat-inactivated C. trachomatis serovar D. The level of local genital mucosal Th1 response was measured by assaying for antigen-specific Th1 cell induction and recruitment into the genital mucosa at different times after immunization. Immunization with MOMP-ISCOMs by the IM route induced the greatest and fastest local genital mucosal Th1 response, first detectable 2 weeks after exposure. Among the other routes and regimens tested, only IN immunization with MOMP-ISCOMs induced detectable and statistically significant levels of local genital mucosal Th1 response during the 8-week test period (P < 0.001). In addition, when T cells from immunized mice were adoptively transferred into syngeneic naive animals and challenged intravaginally with Chlamydia, recipients of IM immunization of MOMP-ISCOMs cleared their infection within 1 week and were resistant to reinfection. Animals that received IN immunization of MOMP-ISCOMs were partially protected, shedding fewer chlamydiae than did control mice. Altogether, the results suggested that IM delivery of MOMP-ISCOMs may be a suitable vaccine regimen potentially capable of inducing protective mucosal immunity against C. trachomatis infection.
TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines (2009)

These findings suggest that the presence of high levels of functionally active TREM-1 in RA synovium may contribute to the development or maintenance of RA, or both. Inhibiting TREM-1 activity may, therefore, have a therapeutic effect on RA. High levels of soluble TREM-1 in the plasma of RA patients compared with healthy volunteers may indicate disease activity.
Wettability and Silicone Hydrogel Lenses (2012)

One of the major breakthroughs in the development of silicone hydrogel contact lenses has related to the ability of manufacturers to overcome the surface hydrophobicity that occurred with silicone elastomer lenses. However, the wettability of silicone hydrogel lenses continues to be of interest as a potential link between in vivo lens performance and contact lens-related comfort. This article will review some of the knowledge we have gained in the area of contact lens wettability over the past decade and will discuss some of the challenges related to its measurement.
Quantum Fluctuations and Noise in Parametric Processes. I. (1961)

A quantum mechanical model for parametric interactions is used to evaluate the effect of the measuring (amplifying) process on the statistical properties of radiation. Parametric amplification is shown to be ideal in the sense that it allows a simultaneous determination of the phase and number of quanta of an electromagnetic wave with an accuracy which is limited only by the uncertainty principle. Frequency conversion via parametric processes is shown to be free of zero-point fluctuations.
Purinergic Receptor Stimulation Reduces Cytotoxic Edema and Brain Infarcts in Mouse Induced by Photothrombosis by Energizing Glial Mitochondria (2010)

Treatments to improve the neurological outcome of edema and cerebral ischemic stroke are severely limited. Here, we present the first in vivo single cell images of cortical mouse astrocytes documenting the impact of single vessel photothrombosis on cytotoxic edema and cerebral infarcts. The volume of astrocytes expressing green fluorescent protein (GFP) increased by over 600% within 3 hours of ischemia. The subsequent growth of cerebral infarcts was easily followed as the loss of GFP fluorescence as astrocytes lysed. Cytotoxic edema and the magnitude of ischemic lesions were significantly reduced by treatment with the purinergic ligand 2-methylthioladenosine 5' diphosphate (2-MeSADP), an agonist with high specificity for the purinergic receptor type 1 isoform (P2Y(1)R). At 24 hours, cytotoxic edema in astrocytes was still apparent at the penumbra and preceded the cell lysis that defined the infarct. Delayed 2MeSADP treatment, 24 hours after the initial thrombosis, also significantly reduced cytotoxic edema and the continued growth of the brain infarction. Pharmacological and genetic evidence are presented indicating that 2MeSADP protection is mediated by enhanced astrocyte mitochondrial metabolism via increased inositol trisphosphate (IP(3))-dependent Ca(2+) release. We suggest that mitochondria play a critical role in astrocyte energy metabolism in the penumbra of ischemic lesions, where low ATP levels are widely accepted to be responsible for cytotoxic edema. Enhancement of this energy source could have similar protective benefits for a wide range of brain injuries.
Design and application of 60mer oligonucleotide microarray in SARS coronavirus detection (2003)

60mer oligonucleotide microarray 被设计并且适用于 SARS (严重急性呼吸症候群) 检测 coronavirus。三十 60mer 特定的 oligos 被设计盖住首先提交的 coronavirus 种类的整个染色体，根据 TOR2 的顺序(GENEBANK 同意：AY274119 ) 。这些教材与 2 看到的 12 脳 1 被综合并且打印进 microarray。RNA 从喉咙拖把和 SARS 病人的漱喉的液体被提取并且进双海滨 cDNAs 反向抄本。cDNAs 是由限制显示(RD ) 限制了 cDNA 碎片被准备技术并且用 Cy5 通用的教材由 PCR 标记。标记的样品然后为杂交被用于 oligo microarray。microarray 的诊断能力在洗并且扫描的步以后被评估。扫描结果证明 SARS 病人的样品是有 microarray 上的多重 SARS 探针的 hybridized，并且否定、空白的控制上没有信号。这些结果显示 SARS coronavirus 的染色体能被 60mer oligonucleotide microarray 在平行检测，它能改进诊断的积极比率。oligo microarray 能也被用于在疾病地位的不同阶段监视病毒基因的行为。
Broadband ISDN — service visions and technological realities (1988)

Abstract Two forces, service needs and technological advances, are driving the extension of the Integrated Services Digital Network (ISDN) into the broadband area. First, this paper identifies several business and residential services which provide a market pull for broadband ISDN (BISDN). Secondly, it reviews recent advances in optical transmission and broadband switching which provide a technological push. Finally, it describes an experimental broadband prototype constructed to help us better understand the transmission, switching, signaling protocol, software, and service capabilities required for BISDN.
Monodisperse FePt Nanoparticles and Ferromagnetic FePt Nanocrystal Superlattices (2000)

Synthesis of monodisperse iron-platinum (FePt) nanoparticles by reduction of platinum acetylacetonate and decomposition of iron pentacarbonyl in the presence of oleic acid and oleyl amine stabilizers is reported. The FePt particle composition is readily controlled, and the size is tunable from 3- to 10-nanometer diameter with a standard deviation of less than 5%. These nanoparticles self-assemble into three-dimensional superlattices. Thermal annealing converts the internal particle structure from a chemically disordered face-centered cubic phase to the chemically ordered face-centered tetragonal phase and transforms the nanoparticle superlattices into ferromagnetic nanocrystal assemblies. These assemblies are chemically and mechanically robust and can support high-density magnetization reversal transitions.
The RhoGAP Protein DLC-1 Functions as a Metastasis Suppressor in Breast Cancer Cells (2005)

The identification of molecular signatures characteristic of tumor cells that are capable of metastatic spread is required for the development of therapeutic interventions to abrogate this lethal process. To facilitate this, we have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 are spontaneously occurring sublines of the MDA-MB-435 cell breast tumor cell line that exhibit phenotypic differences in growth, invasion, and metastatic efficiency in athymic mice. In this study, transcriptional profiles of these cell lines were created using oligonucleotide microarrays representing over 12,000 genes. Intensity modeling and hierarchical clustering analysis identified a 171-gene expression signature that correlated with metastatic phenotype and highlighted several GTPase signaling components. Restoration of one of these GTPases, deleted in liver cancer-1 (DLC-1), in metastatic M4A4 cells to levels observed in the nonmetastatic NM2C5 cell line resulted in the inhibition of migration and invasion in vitro and a significant reduction in the ability of these cells to form pulmonary metastases in athymic mice. These studies show the utility of expression profiling, in an appropriate experimental system, to identify genetic determinants of metastatic sufficiency. The finding that DLC-1 can act as a metastasis-suppressor gene supports an influential role for GTPase signaling in tumor progression.
Histological and molecular evaluation of iron as degradable medical implant material in a murine animal model (2012)

A small animal model was established to evaluate the potential of iron as a degradable implant material. After insertion into the tail of mice, the implants gradually degraded over a clinically relevant time period of several months. Histological analysis and gene expression data from whole-genome microarray analyses indicated a limited inflammatory reaction. No evidence of cellular responses to excess iron ions was detected, suggesting that the iron degradation products were metabolically inactive. Iron-rich compounds could be detected in the vicinity of the implant and in individual cells distant from the implantation site. These results demonstrate that the mouse model could be useful for the primary in vivo evaluation of novel implant materials and that iron degradation products can accumulate in diverse organs of the body.
Concurrent Multi-Channel Transmission (CMCT) MAC Protocol in Wireless Mobile Ad Hoc Networks (2007)

In IEEE 802.11 MANET, mobile nodes can communicate with each other by multi-hop relaying without any infrastructure, in which all nodes share a common channel. However, increasing the number of mobile nodes significantly degrades the performance, due to shared channel congestion. Hence, the multi-channel approaches have been proposed to scatter network traffic over non-overlapping channels. This work presents a novel multiple channel transmission method, called concurrent multi-channel transmission (CMCT). CMCT guarantees that the data packet transmissions are collision-free, and can be sent concurrently on different channels.
Using half-metallic manganite interfaces to reveal insights into spintronics (2007)

A half-metal has been defined as a material with propagating electron states at the Fermi energy only for one of the two possible spin projections, and as such has been promoted as an interesting research direction for spin electronics. This review details recent advances on manganite thin film research within the field of spintronics, before presenting the structural, electronic and spin-polarized solid-state tunnelling transport studies that we have performed on heterostructures involving La(2/3)Sr(1/3)MnO(3) thin films separated by SrTiO(3) barriers. These experiments demonstrate that, with a polarization of spin [Formula: see text] electrons at the Fermi level that can reach 99%, the La(2/3)Sr(1/3)MnO(3)/SrTiO(3) interface for all practical purposes exhibits half-metallic behaviour. We offer insight into the electronic structure of the interface, including the electronic symmetry of any remaining spin [Formula: see text] states at the Fermi level. Finally, we present experiments that use the experimental half-metallic property of manganites as tools to reveal novel features of spintronics.
Ceramide induces apoptosis in PC12 cells (1997)

The novel lipid second messenger, ceramide, induced apoptosis in PC12 cells as determined morphologically by nuclear appearance and internucleosomal DNA fragmentation. Apoptosis was induced by exogenous C2-ceramide in a dose- and time-dependent manner. Natural ceramide and C6-ceramide had a similar effect. This response was specific since the structural analog C2-dihydroceramide and other related lipids failed to initiate apoptosis. The apoptotic effect of ceramide also depends critically on cell plating density. Furthermore, the peptide inhibitor of interleukin-1beta converting enzyme (ICE)-like proteases, Z-VAD.FMK, completely prevented the nuclear changes induced by ceramide, implicating the involvement of ICE-like protease activation in ceramide-induced apoptosis in PC12 cells.
Validation of Genomics-Based Prognostic Tests in Malignant Pleural Mesothelioma (2005)

The data support the use of gene ratios in translating gene expression data into easily reproducible, statistically validated clinical tests for the prediction of outcome in MPM.
Molecular changes in neurons in multiple sclerosis: Altered axonal expression of Na v 1.2 and Na v 1.6 sodium channels and Na + /Ca 2 + exchanger (2004)

Although voltage-gated sodium channels are known to be deployed along experimentally demyelinated axons, the molecular identities of the sodium channels expressed along axons in human demyelinating diseases such as multiple sclerosis (MS) have not been determined. Here we demonstrate changes in the expression of sodium channels in demyelinated axons in MS, with Nav1.6 confined to nodes of Ranvier in controls but with diffuse distribution of Nav1.2 and Nav1.6 along extensive regions of demyelinated axons within acute MS plaques. Using triple-labeled fluorescent immunocytochemistry, we also show that Nav1.6, which is known to produce a persistent sodium current, and the Na+/Ca2+ exchanger, which can be driven by persistent sodium current to import damaging levels of calcium into axons, are colocalized with beta-amyloid precursor protein, a marker of axonal injury, in acute MS lesions. Our results demonstrate the molecular identities of the sodium channels expressed along demyelinated and degenerating axons in MS and suggest that coexpression of Nav1.6 and Na+/Ca2+ exchanger is associated with axonal degeneration in MS.
Structure-Guided Deimmunization of Therapeutic Proteins (2013)

Therapeutic proteins continue to yield revolutionary new treatments for a growing spectrum of human disease, but the development of these powerful drugs requires solving a unique set of challenges. For instance, it is increasingly apparent that mitigating potential anti-therapeutic immune responses, driven by molecular recognition of a therapeutic protein's peptide fragments, may be best accomplished early in the drug development process. One may eliminate immunogenic peptide fragments by mutating the cognate amino acid sequences, but deimmunizing mutations are constrained by the need for a folded, stable, and functional protein structure. These two concerns may be competing, as the mutations that are best at reducing immunogenicity often involve amino acids that are substantially different physicochemically. We develop a novel approach, called EpiSweep, that simultaneously optimizes both concerns. Our algorithm identifies sets of mutations making such Pareto optimal trade-offs between structure and immunogenicity, embodied by a molecular mechanics energy function and a T-cell epitope predictor, respectively. EpiSweep integrates structure-based protein design, sequence-based protein deimmunization, and algorithms for finding the Pareto frontier of a design space. While structure-based protein design is NP-hard, we employ integer programming techniques that are efficient in practice. Furthermore, EpiSweep only invokes the optimizer once per identified Pareto optimal design. We show that EpiSweep designs of regions of the therapeutics erythropoietin and staphylokinase are predicted to outperform previous experimental efforts. We also demonstrate EpiSweep's capacity for deimmunization of the entire proteins, case analyses involving dozens of predicted epitopes, and tens of thousands of unique side-chain interactions. Ultimately, Epi-Sweep is a powerful protein design tool that guides the protein engineer toward the most promising immunotolerant biotherapeutic candidates.
Adiponectin, obesity and atherosclerosis (2007)

The circulating protein adiponectin has been the subject of immense interest ever since it was first discovered in the mid-1990s. The protein is uniquely produced and secreted by mature adipocytes and is believed to have important anti-inflammatory and anti-diabetic effects; low levels have been shown to be predictive of future type 2 diabetes and cardiovascular disease. This review discusses adiponectin in relation to obesity, inflammation, insulin resistance and atherosclerosis.
Selective Estrogen Receptor Modulators: An Update on Recent Clinical Findings (2008)

Recent clinical data on selective estrogen receptor modulators (SERMs) have provided the basis for reassessment of the SERM concept. The molecular basis of SERM activity involves binding of the ligand SERM to the estrogen receptor (ER), causing conformational changes which facilitate interactions with coactivator or corepressor proteins, and subsequently initiate or suppress transcription of target genes. SERM activity is intrinsic to each ER ligand, which accomplishes its unique profile by specific interactions in the target cell, leading to tissue selective actions. We discuss the estrogenic and anti-estrogenic effects of early SERMs, such as clomiphene citrate, used for treatment of ovulation induction, and the triphenylethylene, tamoxifen, which has ER antagonist activity in the breast, and is used for prevention and treatment of ER-positive breast cancer. Since the development of tamoxifen, other triphenylethylene SERMs have been studied for breast cancer prevention, including droloxifene, idoxifene, toremifene, and ospemifene. Other SERMs have entered clinical development more recently, including benzothiophenes (raloxifene and arzoxifene), benzopyrans (ormeloxifene, levormeloxifene, and EM-800), lasofoxifene, pipendoxifene, bazedoxifene, HMR-3339, and fulvestrant, an anti-estrogen which is approved for breast cancer treatment. SERMs have effects on tissues containing ER, such as the breast, bone, uterine and genitourinary tissues, and brain, and on markers of cardiovascular risk. Current evidence indicates that each SERM has a unique array of clinical activities. Differences in the patterns of action of SERMs suggest that each clinical end point must be evaluated individually, and conclusions about any particular SERM can only be established through appropriate clinical trials.
Manipulating both the inhibitory and stimulatory immune system towards the success of therapeutic vaccination against chronic viral infections (2008)

One potentially promising strategy to control chronic infections such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus is therapeutic vaccination, which aims to reduce persisting virus by stimulating a patient's own antiviral immune responses. However, this approach has fallen short of expectations, because antiviral T cells generated during chronic infections often become functionally exhausted and thus do not respond properly to therapeutic vaccination. Therefore, it is necessary to develop a therapeutic vaccine strategy to more effectively boost endogenous T-cell responses to control persistent viral infections. Studies to elucidate the cause of impaired T-cell function have pointed to sustained inhibitory receptor signaling through T-cell expression of programmed death 1 (PD-1). Recently, another inhibitory molecule, cytotoxic T lymphocyte antigen 4 (CTLA-4), and also an immunosuppressive cytokine, interleukin 10 (IL-10), have been reported to be potential factors of establishing immune suppression and viral persistence. Blocking these negative signaling pathways could restore the host immune system, enabling it to respond to further stimulation. Indeed, combining therapeutic vaccination along with the blockade of inhibitory signals could synergistically enhance functional CD8(+) T-cell responses and improve viral control in chronically infected mice, providing a promising strategy for the treatment of chronic viral infections. Furthermore, not only the ablation of negative signals but also the addition of stimulatory signals, such as interleukin 2 (IL-2), might prove to be a potentially promising strategy to augment the efficacy of therapeutic vaccination against chronic viral infections.
CHRONOBIOTIC EFFECTS OF THE MELATONIN AGONIST LY 156735 FOLLOWING A SIMULATED 9H TIME SHIFT: RESULTS OF A PLACEBO-CONTROLLED TRIAL (2002)

This pilot study demonstrates the chronobiotic efficacy of LY when taken at a dose of 5 mg/d.