gebhart/patrepeval huggingface dataset:
Interferon: Immunobiology and Clinical Significance (1982)

Interferons are proteins elaborated by infected cells that protect noninfected cells from viral infection. These proteins produce a temporary "antiviral state" by altering nucleotide metabolism and cytoplasmic enzyme induction. Interferons appear early after viral infection locally and systematically to limit spread of viral infection; they also affect cell differentiation, growth, surface, antigen expression, morphologic findings, and immunoregulation. Several human disorders have diminished interferon production. Newborns have normal interferon alpha but deficient interferon gamma production. Infants with congenital infections may also have defects in interferon production. Immunosuppressed patients receiving transplants (marrow, heart, of kidney) have diminished interferon production, particularly immediately after transplant. Deficiencies of interferon have also been noted in Down's syndrome, cellular immunodeficiencies, uremia, malnutrition, and hematopoietic malignancy. Leukocyte interferon has been of therapeutic value in herpes zoster infections, in patients with cancer, and in patients with hepatitis B infection. Interferon has not been proved to help children with congenital cytomegalovirus or rubella. Interferon can shrink lymphoid tumors, particularly non-Hodgkin's lymphoma.
A New Low Density Lipoprotein Receptor Related Protein, LRP5, Is Expressed in Hepatocytes and Adrenal Cortex, and Recognizes Apolipoprotein E (1998)

The isolation and characterization of rabbit and human cDNAs revealed a new low density lipoprotein receptor (LDLR)-related protein (LRP) designated as LRP5. Human LRP5 cDNA encodes a 1, 616-amino acid type I membrane-like protein with three ligand binding repeats in its extracellular region. LDLR-deficient cells transduced by recombinant adenovirus containing human LRP5 exhibited increased binding of apolipoprotein E (apoE)-enriched beta-migrating very low density lipoprotein. Northern blotting and in situ hybridization revealed a high level of LRP5 expression in hepatocytes and the adrenal gland cortex. In LDLR-deficient Watanabe heritable hyperlipidemic rabbits, LRP5 mRNA was increased in the liver and accumulated in cholesterol-laden foam cells of atherosclerotic lesions.
An in‐scene method for atmospheric compensation of thermal hyperspectral data (2002)

Interpretation of surface radiation characteristics by overhead hyperspectral imagery often requires a compensation of the measured radiance data for the absorption and emission effects of the intervening atmosphere. We describe a procedure that accounts for these effects by direct use of the hyperspectral radiance data without recourse to ancillary meteorological data or atmospheric modeling. This in‐scene atmospheric compensation (ISAC) procedure is applicable to a broad class of problems. The present work concerns terrestrial surface characterization by remote sensing in the 8–13 μm atmospheric window band. A complete ISAC analysis is carried out in two steps. In the first step, unscaled atmospheric compensation spectra (transmittance and upwelling radiance) are extracted from the data. The step is carried out by application of a specially designed, line‐fitting procedure to a scatterplot constructed from the hyperspectral data. The compensation spectra are defined in terms of the slope and intercept parameters of the line. In the second step, these unscaled compensation spectra are scaled to quantitative compensation spectra. Here, this step is carried out using the strength of absorption in the 11.7‐μm water band. The compensation procedure is demonstrated by application to hyperspectral imagery obtained with the Aerospace Corporation's Spatially Enhanced Broadband Array Spectrograph System (SEBASS) hyperspectral imaging sensor at the Department of Energy's (DOE) Atmospheric Radiation Measurement (ARM) facility. Example applications demonstrate the ability of the method to remove atmospheric spectral structure from the observed data and reveal the spectral structure intrinsic to the underlying surface. This removal is demonstrated both for near‐blackbody surfaces composed of grass and for surfaces containing limestone gravel and Red Clay soil.
ac liquid-crystal light valve (1973)

An ac-operated liquid-crystal light valve has been constructed and operated. The multilayer structure, consisting of a photoconductor, light-absorbing layer, dielectric mirror, and liquid crystal, is capable of efficiently modulating a high-intensity light beam with a comparatively weak light source. The dielectric mirror and absorbing layer provide high reflectance and optical isolation without the use of a metal mosaic reflector. The use of ac and insulated electrodes promises long lifetime. The light valve is applicable to television projection display and optical data processing.
The A736V TMPRSS6 polymorphism influences hepcidin and iron metabolism in chronic hemodialysis patients: TMPRSS6 and hepcidin in hemodialysis (2013)

The A736V TMPRSS6 genotype influences hepcidin levels, erythropoiesis, and anemia management in CHD patients. Evaluation of the effect of TMPRSS6 genotype on clinical outcomes in prospective studies in CHD may be useful to predict the outcomes of hepcidin manipulation, and to guide treatment personalization by optimizing anemia management.
Modeling Dravet syndrome using induced pluripotent stem cells (iPSCs) and directly converted neurons (2013)

Severe myoclonic epilepsy of infancy (SMEI, also known as Dravet syndrome) and genetic epilepsy with febrile seizures plus (mild febrile seizures) can both arise due to mutations of SCN1A, the gene encoding alpha 1 pore-forming subunit of the Nav1.1 voltage-gated sodium channel. Owing to the inaccessibility of patient brain neurons, the precise mechanism of mild febrile seizures and SMEI remains elusive, and there is no effective pharmacotherapy. Induced pluripotent stem cells (iPSCs) and induced neurons (iNs) have been successfully generated from patients and applied for modeling various neuronal diseases. In this study, we established iPSC lines from one SMEI patient and one mild febrile seizures patient, respectively. Functional glutamatergic neurons were subsequently differentiated from these iPSCs. Electrophysiological analysis of patient iPSC-derived glutamatergic neurons revealed a hyperexcitable state of enlarged and persistent sodium channel activation, more intensive evoked action potentials and typical epileptic spontaneous action potentials. In consistent with the severity of the symptoms, the hyperexcitability of the neurons derived from SMEI patient was more serious than that of mild febrile seizures patient. Furthermore, the hyperexcitability of the neurons can be alleviated by treatment with phenytoin, a conventional antiepileptic drug. In parallel, iNs were directly converted from patient fibroblasts which also showed a delayed inactivation of sodium channels. Our results demonstrate that both iPSC-derived neurons and iNs from mild febrile seizures and SMEI patients exhibited a hyperexcitable state. More importantly, patient iPSC-derived neurons can recapitulate the neuronal pathophysiology and respond to drug treatment, indicating that these neurons can be potentially used for screening appropriate drugs for personalized therapies.
CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics (1997)

The structurally related T cell surface molecules CD28 and CTLA-4 interact with cell surface ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APC) and modulate T cell antigen recognition. Preliminary reports have suggested that CD80 binds CTLA-4 and CD28 with affinities (Kd values approximately 12 and approximately 200 nM, respectively) that are high when compared with other molecular interactions that contribute to T cell-APC recognition. In the present study, we use surface plasmon resonance to measure the affinity and kinetics of CD80 binding to CD28 and CTLA-4. At 37 degrees C, soluble recombinant CD80 bound to CTLA-4 and CD28 with Kd values of 0.42 and 4 microM, respectively. Kinetic analysis indicated that these low affinities were the result of very fast dissociation rate constants (k(off)); sCD80 dissociated from CD28 and CTLA-4 with k(off) values of > or = 1.6 and > or = 0.43 s-1, respectively. Such rapid binding kinetics have also been reported for the T cell adhesion molecule CD2 and may be necessary to accommodate-dynamic T cell-APC contacts and to facilitate scanning of APC for antigen.
A low-bandwidth network file system (2001)

Users rarely consider running network file systems over slow or wide-area networks, as the performance would be unacceptable and the bandwidth consumption too high. Nonetheless, efficient remote file access would often be desirable over such networks---particularly when high latency makes remote login sessions unresponsive. Rather than run interactive programs such as editors remotely, users could run the programs locally and manipulate remote files through the file system. To do so, however, would require a network file system that consumes less bandwidth than most current file systems.This paper presents LBFS, a network file system designed for low-bandwidth networks. LBFS exploits similarities between files or versions of the same file to save bandwidth. It avoids sending data over the network when the same data can already be found in the server's file system or the client's cache. Using this technique in conjunction with conventional compression and caching, LBFS consumes over an order of magnitude less bandwidth than traditional network file systems on common workloads.
Cannabis: Pharmacology and Interpretation of Effects (1985)

A selective introductory review of the Cannabis literature is presented. Subjects reviewed include the relative psychoactivities of Cannabis constituents, the disposition and distribution of THC and its metabolites, the relative psychoactivities of THC metabolites, and the use of cannabinoid concentrations in physiological fluids in interpretations of the significance of Cannabis-induced effects. The pharmacology of cannabinoids in humans is emphasized.
Three Amino Acid Substitutions in the L Protein of the Human Parainfluenza Virus Type 3 cp 45 Live Attenuated Vaccine Candidate Contribute to Its Temperature-Sensitive and Attenuation Phenotypes (1998)

Studies were initiated to define the genetic basis of the temperature-sensitive (ts), cold adaptation (ca), and attenuation (att) phenotypes of the human parainfluenza virus type 3 (PIV3) cp45 live attenuated vaccine candidate. Genetic data had previously suggested that the L polymerase protein of cp45, which contains three amino acid substitutions at positions 942, 992, and 1558, contributed to its temperature sensitivity (R. Ray, M. S. Galinski, B. R. Heminway, K. Meyer, F. K. Newman, and R. B. Belshe, J. Virol. 70:580-584, 1996; A. Stokes, E. L. Tierney, C. M. Sarris, B. R. Murphy, and S. L. Hall, Virus Res. 30:43-52, 1993). To study the individual and aggregate contributions that these amino acid substitutions make to the ts, att, and ca phenotypes of cp45, seven PIV3 recombinant viruses (three single, three double, and one triple mutant) representing all possible combinations of the three amino acid substitutions were recovered from full-length antigenomic cDNA and analyzed for their ts, att, and ca phenotypes. None of the seven mutant recombinant PIVs was cold adapted. The substitutions at L protein amino acid positions 992 and 1558 each specified a 105-fold reduction in plaque formation in cell culture at 40 degrees C, whereas the substitution at position 942 specified a 300-fold reduction. Thus, each of the three mutations contributes individually to the ts phenotype. The triple recombinant which possesses an L protein with all three mutations was almost as temperature sensitive as cp45, indicating that these mutations are the major contributors to the ts phenotype of cp45. The three individual mutations in the L protein each contributed to restricted replication in the upper or lower respiratory tract of hamsters, and this likely contributes to the observed stability of the ts and att phenotypes of cp45 during replication in vivo. Importantly, the recombinant virus possessing L protein with all three mutations was as restricted in replication as was the cp45 mutant in both the upper and lower respiratory tracts of hamsters, indicating that the L gene of the cp45 virus is a major attenuating component of this candidate vaccine.
Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D:Cdk4/6 complexes results in active pRb (1997)

In cycling cells, the retinoblastoma protein (pRb) is un- and/or hypo-phosphorylated in early G1 and becomes hyper-phosphorylated in late G1. The role of hypo-phosphorylation and identity of the relevant kinase(s) remains unknown. We show here that hypo-phosphorylated pRb associates with E2F in vivo and is therefore active. Increasing the intracellular concentration of the Cdk4/6 specific inhibitor p15(INK4b) by transforming growth factor beta treatment of keratinocytes results in G1 arrest and loss of hypo-phosphorylated pRb with an increase in unphosphorylated pRb. Conversely, p15(INK4b)-independent transforming growth factor beta-mediated G1 arrest of hepatocellular carcinoma cells results in loss of Cdk2 kinase activity with continued Cdk6 kinase activity and pRb remains only hypo-phosphorylated. Introduction of the Cdk4/6 inhibitor p16(INK4a) protein into cells by fusion to a protein transduction domain also prevents pRb hypo-phosphorylation with an increase in unphosphorylated pRb. We conclude that cyclin D:Cdk4/6 complexes hypo-phosphorylate pRb in early G1 allowing continued E2F binding.
Inhibitory Effects of Capsaicinoids on Fatty Acid Desaturation in a Rat Liver Cell Line (2001)

The inhibitory effects of such vanillylamides as capsaicin and nine capsaicinoids on fatty acid desaturation in liver cells were investigated by using the cultured rat liver cell line, BRL-3A. When capsaicin was added to the medium, it had a relatively strong inhibitory effect on delta6 desaturation and clear inhibitory effects on delta5 and C24delta16 desaturation (delta16 desaturation of C24-polyunsaturated fatty acids). Capsaicinoids with side carbon chain lengths of C10:0 and C12:0 expressed the maximum inhibitory effects of the nine capsaicinoids on fatty acid desaturation in the BRL-3A cells. The inhibitory effects of the capsaicinoids were not correlated with their pungency.
DNA microarray analysis of gene expression profiles in deep endometriosis using laser capture microdissection (2004)

Endometriosis, a common gynecological disorder that causes infertility and pelvic pain, is defined as the presence of endometrial glands and stroma within extra-uterine sites. However, despite extensive studies its etiology and pathogenesis are not completely understood. Differentially expressed genes were investigated in epithelial and stromal cells from deep endometriosis and matched eutopic endometrium using cDNA microarrays and laser capture microdissection. Validation of results of several up- and down-regulated genes was performed by quantitative real-time RT-PCR. Our data showed that platelet-derived growth factor receptor alpha (PDGFRA), protein kinase C beta1 (PKC beta1) and janus kinase 1 (JAK1) were upregulated, and Sprouty2 and mitogen-activated protein kinase kinase 7 (MKK7) were downregulated in endometriosis stromal cells, suggesting the involvement of the RAS/RAF/MAPK signaling pathway through PDGFRA in endometriosis pathophysiology. In addition, two potential negative regulators of aromatase expression, chicken ovalbumin upstream promoter transcription factor 2 (COUP-TF2) and prostaglandin E2 receptor subtype EP3 (PGE2EP3), were downregulated in endometriosis epithelial cells, which might result in increased local production of estrogen in endometriosis epithelial cells. Furthermore, three potential candidate genes that might be involved in endometriosis related pain were identified: tyrosine kinase receptor B (TRkB) in endometriosis epithelial cells, and serotonin transporter (5HTT) and mu opioid receptor (MOR) in endometriosis stromal cells were all upregulated. One of the candidate genes, MOR, may be involved in a defective immune system in endometriosis. This study has provided new insights into endometriosis pathophysiology.
Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis. (2015)

CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been reported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by multivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.
Inhibitors of HSP90 and other chaperones for the treatment of cancer (2004)

Molecular chaperones are proteins that ensure the appropriate folding, stability and function of other proteins in the cell. There is increasing evidence that molecular chaperones are not only important in normal cell homeostasis and response to stresses, such as heat shock, but can also be involved in disease pathology. In particular, HSP90 has emerged as an important potential drug target in oncology. This is because it is essential for the stability of a long list of ‘client proteins’, including ErbB2/human epithelial growth factor receptor (HER)2, Raf-1, Akt/protein kinase B (PKB), Polo-1, Met, mutant p53 and human telomerase reverse transcriptase (hTERT), as well as the oestrogen and androgen receptor. Inhibition of HSP90 leads to depletion of these oncogenic clients by the ubiquitin proteasome pathway, thereby providing a simultaneous combinatorial attack on all of the hallmark phenotypic traits of cancer cells. Because of the rapid progress made, this review focuses on the patents dealing with the discovery and application of small molecule inhibitors of HSP90, although limited coverage of other applications in the area of HSP90 and additional chaperones is also included. Pioneering work with natural products, namely geldanamycin and related ansamycin antibiotics together with radicicol macrocycle derivatives, established the therapeutic potential of inhibiting the essential N-terminal ATPase of HSP90 by competing at the nucleotide binding site. A geldanamycin analogue, 17-(desmethoxy), 17-allylamino geldanamycin (17AAG), is completing Phase I clinical trials with promising initial results. The use of high-throughput screening and rational design based on X-ray crystal structures of HSP90 has led to the discovery of small molecule HSP90 inhibitors based on purine and pyrazole scaffolds. The continued progression of these various compound classes into clinical trials should help to establish proof of concept for inhibition of HSP90 as a viable therapeutic approach for the treatment of cancer and potentially other diseases. This would in turn validate protein folding as a strategy for drug development and encourage additional chaperones to be explored as molecular targets.
Absorption of Nitrogen Oxides in Aqueous Amines (2014)

Nitric oxide (NO) and nitrogen dioxide (NO2) were absorbed into aqueous amine to determine the absorbing species, the absorption kinetics, and the aqueous products at the ppm-level NOx concentrations typical of flue gas from fossil fuel power plants. At flue gas conditions of 0.5-5 ppm of NO2, absorption is dominated by free radical absorption of NO2 as nitrite. NO2 absorption kinetics are first order in NO2 partial pressure, half order in free amine concentration, and fastest in methyldiethanolamine (MDEA). The reaction-enhanced liquid mass transfer coefficient for NO2 absorption in 8 m piperazine (PZ) at absorber conditions is 9.7*10-7 mol/s·m2·Pa, yielding 92% NO2 absorption at a typical A/G of 3.3*106 s·Pa·m2/mol. Similarly, a 9 m monoethanolamine (MEA) solvent will absorb roughly 70% of the inlet NO2 while a 7 m MDEA/2 m PZ solvent will absorb over 99% of the NO2. Nitrite and nitrate are the main NOx absorption products in MDEA with nitrite dominating at low NO2 partial pressures. In PZ, the amine free radical formed during NO2 absorption will react with NO to directly form n-nitrosopiperazine (MNPZ) or react with itself to form 2-piperazinol (2-PZOH). Typical nitrosamine yields in 5 m PZ are around 15% of total absorbed NOx and can be halved with the addition of 200 mM Inhibitor A, a free radical scavenger. Nitrate and nitramine are minor products of NOx absorption, accounting for less than 5% of total absorbed NOx.
Resilient peer-to-peer streaming (2004)

We consider the problem of distributing "live" streaming media content to a potentially large and highly dynamic population of hosts. Peer-to-peer content distribution is attractive in this setting because the bandwidth available to serve content scales with demand. A key challenge, however, is making content distribution robust to peer transience. Our approach to providing robustness is to introduce redundance; both in network paths and in data. We use multiple, diverse distribution trees to provide redundancy in network paths and multiple description coding (MDC) to provide redundancy in data. We present a simple tree management algorithm that provides the necessary path diversity and describe an adaptation framework for MDC based on scalable receiver feedback. We evaluate these using MDC applied to real video data coupled with real usage traces from a major news site that experienced a large flash crowd for live streaming content. Our results show very significant benefits in using multiple distribution trees and MDC, with a 22 dB improvement in PSNR in some cases.