gebhart/patrepeval huggingface dataset:
Stat2 Binding to the Interferon-α Receptor 2 Subunit Is Not Required for Interferon-α Signaling (2002)

The interferon-alpha (IFNalpha) receptor consists of two subunits, the IFNalpha receptor 1 (IFNaR1) and 2 (IFNaR2) chains. Following ligand binding, IFNaR1 is phosphorylated on tyrosine 466, and this site recruits Stat2 via its SH2 domain. In contrast, IFNaR2 binds Stat2 constitutively. In this study we have characterized the Stat2-IFNaR2 interaction and examined its role in IFNalpha signaling. Stat2 binds the major IFNaR2 protein but not a variant containing a shorter cytoplasmic domain. The interaction does not require a STAT SH2 domain. Both tyrosine-phosphorylated and non-phosphorylated Stat2 bind IFNaR2 in vitro; however, relatively little phosphorylated Stat2 associates with IFNaR2 in vivo. In vitro binding assays defined IFNaR2 residues 418-444 as the minimal interaction domain and site-specific mutation of conserved acidic residues within this domain disrupted in vitro and in vivo binding. An IFNaR2 construct carrying these mutations was either (i) overexpressed in 293T cells or (ii) used to complement IFNaR2-deficient U5A cells. Unexpectedly, the activity of an IFNalpha-dependent reporter gene was not reduced but, instead, was enhanced up to 2-fold. This suggests that this particular IFNaR2-Stat2 interaction is not required for IFNalpha signaling, but might act to negatively inhibit signaling. Finally, a doubly truncated recombinant fragment of Stat2, spanning residues 136-702, associated with IFNaR2 in vitro, indicating that the interaction with IFNaR2 is direct and occurs in a central region of Stat2 marked by a hydrophobic core.
Demonstration of the extrinsic coagulation pathway in teleostei: Identification of zebrafish coagulation factor VII (2001)

It is not known whether the mammalian mechanism of coagulation initiation is conserved in fish. Identification of factor VII is critical in providing evidence for such a mechanism. A cDNA was cloned from a zebrafish (teleost) library that predicted a protein with sequence similarity to human factor VII. Factor VII was shown to be present in zebrafish blood and liver by Western blot analysis and immunohistochemistry. Immunodepletion of factor VII from zebrafish plasma selectively inhibited thromboplastin-triggered thrombin generation. Heterologous expression of zebrafish factor VII demonstrated a secreted protein (50 kDa) that reconstituted thromboplastin-triggered thrombin generation in immunodepleted zebrafish plasma. These results suggest conservation of the extrinsic coagulation pathway between zebrafish and humans and add credence to the zebrafish as a model for mammalian hemostasis. The structure of zebrafish factor VIIa predicted by homology modeling was consistent with the overall three-dimensional structure of human factor VIIa. However, amino acid disparities were found in the epidermal growth factor-2/serine protease regions that are present in the human tissue factor-factor VIIa contact surface, suggesting a structural basis for the species specificity of this interaction. In addition, zebrafish factor VII demonstrates that the Gla-EGF-EGF-SP domain structure, which is common to coagulation factors VII, IX, X, and protein C, was present before the radiation of the teleosts from the tetrapods. Identification of zebrafish factor VII significantly narrows the evolutionary window for development of the vertebrate coagulation cascade and provides insight into the structural basis for species specificity in the tissue factor-factor VIIa interaction.
Selective Java applet filtering on Internet (2003)

Proposes a proxy-based solution to selectively filter out Java applets from retrieved Web pages. Selective Java applet filtering is desired mainly for two reasons: (i) for low bandwidth users, background audio, animation and 3D Java applets for Web page decoration usually result in very long Web access delays; and (ii) for personal privacy reason, Web surfers would like to filter Java applets that are used for server monitoring and tracking. By sampling and analyzing the usage patterns of these applets in current Web page design, a set of good heuristic rules for their identification can be obtained. Based on these heuristics, selective filtering of unwanted applets can be done through the proxy server automatically. To handle the situation when a wrong filtering decision is made, a simple and effective recovery mechanism is supported in the proxy server. The Web surfer just needs to click the browser's "reload" button. If the difference between the time of receiving the reload signal and the previous access time of a "filtered" Web page is within some threshold value, the proxy loads back the filtered applet(s) to the Web surfer. A sample implementation of this filtering proxy solution based on the SQUID proxy server is also described in order to help understand the system design and tradeoff issues. Such system is important because it gives Web surfers an easy way to enjoy Java technology and to protect their privacy and bandwidth usage at the same time.
Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up. (2003)

VEGF-D expression is associated with lymph node metastasis and may be a novel prognostic factor in breast cancer. VEGF-D may be useful in the treatment of breast cancer as a decision-making biomarker for aggressive treatment after operation.
Synthesis and Immunosuppressive Activity of New Artemisinin Derivatives. 1. [12(β or α)-Dihydroartemisininoxy]phen(ox)yl Aliphatic Acids and Esters (2005)

A series of novel dihydroartemisinin derivatives were synthesized and evaluated on their immunosuppressive activity in the search for potential immunosuppressive agents with high efficacy and low toxicity. These compounds were assayed in their cytotoxicity of lymphocyte, inhibition activity on concanavalin A (ConA) induced T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation. Among them, 11b, 13b, 14d, 15b, 16, and 17 remarkably exhibited lower cytotoxicity and higher inhibition activity on the mitogen-induced T cell and B cell proliferation in comparison with artemisinin, artesunate, and artemether in vitro. More significantly, compound 11b displayed reduced cytotoxicity by over 100-fold compared with cyclosporin A (CsA) and comparable inhibition activity (SI = 848) on ConA-induced T cell proliferation to CsA (SI = 963) and more than 4000 times the inhibitory effect (SI = 28473) on LPS-induced B cell proliferation compared with CsA (SI = 7) in vitro. The in vivo experimental results showed that compound 16 could inhibit 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reaction and sheep red blood cell (SRBC) induced antibody production, respectively. The structure and activity relationships (SAR) of these compounds were also discussed.
Experimental Uremia (1980)

A model is described for the induction in the rat of varying degrees of stable uremia using controlled resection of renal tissue. Three degrees of uremia have been attained: 'mild--blood urea 40--80 mg/100 ml (6.68--13.36 mmol/1); 'moderate'--blood urea 100--200 mg/100 ml (16.7--33.4 mmol/1), and 'severe'--blood urea greater than 200 mg/100 ml (> 33.4 mmol/1). Mild uremia was produced by unilateral nephrectomy; moderate uremia required the resection of 80 +/- 2% of the total renal mass, and severe uremia was produced by 88 +/- 2% nephrectomy. A sham-operative procedure provided an appropriate control for the model. Evaluation of the model has been carried out using analyses of renal function (GFR, concentrating capacity), blood biochemistry, hematological parameters and histological examination. The ability to induce a standardized, stable uremia at predetermined levels, uncomplicated by the administration of nephrotoxic material, represents an advance on existing methods for producing experimental renal failure.
High-Capacity Separation of Homogeneous Cell Subpopulations by Centrifugal Elutriation (1991)

The feasibility of obtaining a very large quantity (>108) of homogeneous cell populations by the Beckman JE-10X elutriator system was evaluated by 5-15 μm latex spheres and Chinese hamster ovary (CHO) cells. The evaluation was based on 1) recovery, 2) elution loss during loading, 3) homogeneity of the size distributions, and 4) the relationship of the median volume of eluted particles or cells to the rotor speed and the collection fluid velocity. The results indicated that a minimum number of 2 x 108 cells was required for any reasonable separation. More than 90% of the particles or cells were always recovered when more than 5 x 108 total cells were loaded into the system. The homogeneity of separated fractions as determined by the coefficient of variation (CV) of volume distributions showed a limiting CV of 7% for latex spheres and 11.5% for CHO cells. Fractions containing 95% G1 cells, 82% S cells, and 78% G2M cells were obtained from asynchronous CHO cells with this method.
TARGETING THE α 1 SUBUNIT OF THE SODIUM PUMP TO COMBAT GLIOBLASTOMA CELLS (2008)

Inhibition of the Na+/K+ -ATPase alpha1 subunit in human GBM cells impairs both cell migration and cell proliferation.
Speech Coding: Fundamentals and Applications (2003)

Abstract In this chapter, we present an overview of the most widely used algorithms, standards, and applications of wideband and narrowband speech coding. Algorithms for speech coding are classified into four broad headings: (1) waveform coding techniques (including PCM, companded PCM, and DPCM), which are typically used for landline telephony, internet telephony, and secure military communications; (2) subband coding, including perceptually transparent multi‐rate and embedded coding which is mainly used for internet and digital audio applications; (3) linear predictive analysis by synthesis coding (LPC‐AS) algorithms, including multipulse LPC, CELP, SELP, VSELP, and low‐delay CELP, which are typically used for digital cellular and telephony; and (4) LPC vocoders, including advanced vocoder algorithms (e.g., MELP, MBE, and PWI) are used for applications such as secure telephony and satellite telephony. Applications in areas such as voiceover IP (VoIP) and digital cellular are emerging and require a speech coder to gracefully adapt to rapidly changing channel conditions—a need that is met by embedded and multirate speech coders associated with joint source‐channel coding algorithms. Measures of speech coder perceptual quality include subjective measures of intelligibility (DRT and DALT) and naturalness (MOS and DAM), as well as objective measures such as segmental SNR, Bark spectral distortion, PSQM, and PESQ. Speech coding standards are set by organizations including the ITU (for landline telephony), MPEG (for multimedia applications), ETSI (for European digital cellular), TIA (for U.S. digital cellular), and DDVPC (for United States military applications).
Analytical approach to estimate normal tissue complication probability using best fit of normal tissue tolerance doses into the NTCP equation of the linear quadratic model. (2005)

A fairly good correspondence is found between the curves of 2 sets of data for brain, heart and rectum. Hence the model may, therefore, be used to interpolate clinical data to provide an estimate of NTCP for these organs for any altered fractionated treatment schedule.
The tacking CCD: a new CCD concept (1991)

The tacking CCD is a new type of charge transport mechanism that is suitable for junction- and MOS-type CCDs. A specific form, the trenched tacking CCD (TTCCD), promises high pixel density and high charge handling capability per unit of surface area. The charge handling capability is improved by using a trench to increase the charge storage area. With the new design concept it becomes possible to put the gates entirely into trenches, while simultaneously using the trenches as channel stops. The TTCCD structure is suitable for making new types of solid-state image sensors with increased light sensitivity, and it may be possible to incorporate a vertical overflow drain. First samples of the TTCCD have been realized, and its functionality has been confirmed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel. (1988)

A series of human chromosome 3-specific DNA fragments isolated and characterized from a lamda phage genomic library were regionally localized on human chromosome 3. This was accomplished using filter hybridization blot analysis of a human chromosome 3 hybrid cell deletion mapping panel. Twenty-three new anonymous DNA fragments were assigned to one of four physical regions of chromosome 3. Seventeen DNA fragments were mapped to the long arm of chromosome 3, including one DNA fragment that demonstrated a restriction fragment length polymorphism (RFLP). Five DNA fragments were assigned to 3p14.2----pter, including one highly polymorphic fragment sublocalized at 3p25----pter by in situ hybridization. This DNA fragment is the second reported distal 3p polymorphic probe. One DNA fragment was localized to 3p14----p14.2. In addition, three fragments previously assigned to chromosome 3 were confirmed. Polymorphic DNA probes DNF15S2 (formerly D1S1) and D3S2 were mapped to 3p14.2----pter. The previous 3p25 in situ localization of the c-raf-1 oncogene was supported by deletion panel mapping. The physical localization of these twenty-three new DNA fragments has more than doubled the number of cloned DNA fragments assigned to chromosome 3. These and future regional assignments of DNA fragment probes will facilitate construction of both a physical and genetic linkage map of chromosome 3. They may also be useful in characterizing the chromosomal and molecular aberrations involved in small-cell lung cancer (SCLC), renal cell carcinoma, other malignancies, and the 3p14.2 common fragile site.
Agent Orange Exposure and Attributed Health Effects in Vietnam Veterans (2011)

Serum dioxin studies of Vietnam (VN) veterans, military historical records of tactical herbicide use in Vietnam, and the compelling evidence of the photodegradation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aspects of environmental fate and low bioavailability of TCDD are consistent with few, if any, ground troop veterans being exposed to Agent Orange. That conclusion, however, is contrary to the presumption by the Department of Veterans Affairs (DVA) that military service in Vietnam anytime from January 9, 1962 to May 7, 1975 is a proxy for exposure to Agent Orange. The DVA assumption is inconsistent with the scientific principles governing determinations of disease causation. The DVA has nonetheless awarded Agent Orange-related benefits and compensation to an increasing number of VN veterans based on the presumption of exposure and the published findings of the Institute of Medicine that there is sufficient evidence of a "statistical association" (a less stringent standard than "causal relationship") between exposure to tactical herbicides or TCDD and 15 different human diseases. A fairer and more valid approach for VN veterans would have been to enact a program of "Vietnam experience" benefits for those seriously ill, rather than benefits based on the dubious premise of injuries caused by Agent Orange.
Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin (2002)

Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
Artificial Neural Network for Temporal Impedance Recognition of Neurotoxins (2006)

The design, development and in-vitro evaluation of an impedimetric neurotoxicity cell-based biosensor that is designed for real time monitoring of changes in electrophysiological behavior under the influence of neurotoxins is described. The electrical cell impedance sensing (ECIS) system [ECIS 8W1E element array of gold electrodes] is used as a substrate for the culture of rat pheochromocytoma (PC 12) cells. The neurotoxicity biosensor is a microfabricated solid state device that mimics the natural environment of PC 12 cells that are responsive to neurotoxins. The PC 12 neurotoxicity biosensors are complemented by artificial neural networks (ANNs) to recognize the impedance profiles of the cells under the influence of a neurotoxin. The neurotoxins were rotenone (Rot), okadaic acid (OA) and peroxynitrite (Per), which are all known to induce cell death in PC 12 cells. Three multilayer feedforward artificial neural network models were developed using a back-propagation algorithm for pattern recognition of neurotoxins. The neurotoxin network (NTN) and the neurotoxin concentration network (NTCN), were trained with data from all the neurotoxins and the cascade network (NTN_NTCN) was developed by combining both the NTN and NTCN. The cascade network was developed to screen against false positives. The neurotoxicity biosensor coupled with these networks allowed for the action of unknown agents (neurotoxins) to be deduced by the measured cellular response. Using back-propagation ANNs to distinguish neurotoxins under the cascade network, the highest success recognition rate for concentration identification were 96% for peroxynitrite, 88% for rotenone, and 96% for okadaic acid. The recognition rate for neurotoxin identification was 98%. The ANN models required less than ten minutes to train and demonstrated that back-propagation ANNs can be handled by commercially-available computers to train and assimilate neurotoxin impedance information, permitting high success rates in the neurotoxin recognition problems.
Directed (R)‐ or (S)‐Selective Dynamic Kinetic Enzymatic Hydrolysis of 1,2,3,4‐Tetrahydroisoquinoline‐1‐carboxylic Esters (2008)

Abstract The first synthesis of both enantiomers of 6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐1‐carboxylic acid was accomplished through dynamic kinetic resolution in procedures based on CAL‐B‐ or subtilisin Carlsberg‐catalysed enantioselective hydrolysis of the corresponding ethyl esters in aqueous NH 4 OAc buffer at pH 8.5. The products were obtained with high enantiopurity (92–93 % ee ) in good yields (85–92 %). ( R )‐1,2,3,4‐Tetrahydroisoquinoline‐1‐carboxylic acid was obtained with high enantiopurity (98 % ee ) and in good yield (85 %) in a CAL‐B‐catalysed process, under similar conditions.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)
Invertebrate immunity (1980)

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Fibroblast Growth Factor 23 Is a Counter-Regulatory Phosphaturic Hormone for Vitamin D (2006)

The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 +/- 8.1 to 213.8 +/- 14.6 pg/ml at 8 h (mean +/- SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH)(2)D(3) further increased circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH)(2)D(3) levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25(OH)(2)D(3). In osteoblast cell cultures, 1,25(OH)(2)D(3) but not calcium, phosphate, or parathyroid hormone stimulated FGF23 mRNA levels and resulted in a dose-dependent increase in FGF23 promoter activity. Overexpression of a dominant negative vitamin D receptor inhibited 1,25(OH)(2)D(3) stimulation of FGF23 promoter activity, and mutagenesis of the FGF23 promoter identified a vitamin D-responsive element (-1180 GGAACTcagTAACCT -1156) that is responsible for the vitamin D effects. These data suggest that 1,25(OH)(2)D(3) is an important regulator of FGF23 production by osteoblasts in bone. The physiologic role of FGF23 may be to act as a counterregulatory phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.
Hydroxyl radical footprinting of the sequence‐selective binding of netropsin and distamycin to DNA (1987)

Hydroxyl radicals, generated by allowing an iron (II).EDTA complex to react with hydrogen peroxide, have been employed to cleave the 160-base pair tyrT DNA fragment in the presence and absence of the minor groove-binding antibiotics netropsin and distamycin A. The control DNA cleavage pattern is practically independent of nucleotide sequence, which overcomes certain limitations of other footprinting techniques, so that additional information can be gained about the AT-rich sequence preference of the minor groove-binding ligands.
Naturally processed class II epitope from the tumor antigen MUC1 primes human CD4+ T cells. (1998)

Epithelial cell mucin MUC1 is expressed on adenocarcinomas in an underglycosylated form that serves as a tumor antigen in breast, pancreatic, ovarian, and other tumors. Two predominant MUC1-specific immune responses are found in patients: CD8+ CTLs, which recognize tandemly repeated epitopes on the MUC1 protein core, and IgM antibodies. There have been no reports to date of MUC1-specific CD4+ T-helper cells in cancer patients. We show here that MUC1-specific CD4+ T cells are neither deleted nor tolerized and that CD4+ T cell responses can be generated when an appropriate soluble form of MUC1 is used. Naive CD4+ T cells from healthy donors were primed in vitro to a synthetic MUC1 peptide of 100 amino acids, representing five unglycosylated tandem repeats, presented by dendritic cells. They produced IFN-gamma and had moderate cytolytic activity. We identified one core peptide sequence, PGSTAPPAHGVT, that elicits this response when it is presented by HLA-DR3.
Reversal of temporal and spatial heterogeneities in tumor perfusion identifies the tumor vascular tone as a tunable variable to improve drug delivery (2006)

Maturation of tumor vasculature involves the recruitment of pericytes that protect the endothelial tubes from a variety of stresses, including antiangiogenic drugs. Mural cells also provide mature tumor blood vessels with the ability to either relax or contract in response to substances present in the tumor microenvironment. The observed cyclic alterations in tumor blood flow and the associated deficit in chemotherapeutic drug delivery could in part arise from this vasomodulatory influence. To test this hypothesis, we focused on endothelin-1 (ET-1), which, besides its autocrine effects on tumor cell growth, is a powerful vasoconstrictor. We first document that an ET(A) receptor antagonist induced relaxation of microdissected tumor arterioles and selectively and quantitatively increased tumor blood flow in experimental tumor models. We then combined dye staining of functional vessels, fluorescent microsphere-based mapping, and magnetic resonance imaging to identify heterogeneities in tumor blood flow and to examine the reversibility of such phenomena. Data from all these techniques concurred to show that administration of an ET(A) receptor antagonist could reduce the extent of underperfused tumor areas, proving the key role of vessel tone variations in tumor blood flow heterogeneity. We also provide evidence that ET(A) antagonist administration could, despite an increase in tumor interstitial fluid pressure, improve access of cyclophosphamide to the tumor compartment and significantly influence tumor growth. In conclusion, tumor endogenous ET-1 production participates largely in the temporal and spatial variations in tumor blood flow. ET(A) antagonist administration may wipe out such heterogeneities, thus representing an adjuvant strategy that could improve the delivery of conventional chemotherapy to tumors.