gebhart/patrepeval huggingface dataset:
Topology of receptor binding domains of mouse IFN- <i>gamma</i> . (1990)

IFN-gamma is an essential immunoregulatory lymphokine for a variety of immunologic functions including upregulation of MHC Ag. The elucidation of the structure, particularly the receptor binding domains, should further enhance our understanding of its mechanism of action, and provide a rational basis for modulation of its activity by alteration of its structure. A predicted model of murine IFN-gamma structure has been constructed based on data derived from our synthetic peptide studies, circular dichroism spectra, and predictive algorithms for secondary structure, surface accessibility, and tertiary structure, as well as predicted structural similarities to IL-2. Direct synthetic peptide competition studies using five overlapping peptides that encompassed the entire IFN-gamma sequence of 133 amino acids showed that only the N-terminus of IFN-gamma, IFN-gamma(1-39), blocked binding to receptor, suggesting that the N-terminus is directly involved in receptor binding. Rabbit antibodies to the N-terminal (IFN-gamma(1-39)) and C-terminal (IFN-gamma(95-133)) peptides neutralized IFN-gamma activity, whereas antibodies to the three peptides that spanned the internal region, sequence 36-107, were without effect. Thus, the antibody data support the involvement of the N-terminus as a receptor binding domain and also suggest that the C-terminus of the molecule is also a binding domain. Predictive algorithms assign six alpha-helices and five turns to the molecule and circular dichroism spectra of both intact human and murine IFN-gamma and synthetic peptides of murine IFN-gamma showed that the molecule is mainly alpha-helical in structure. Drawing mainly on the four alpha-helix bundle model, a common motif in globular proteins such as IFN-gamma and IL-2 (whose crystalline structure is known), we constructed a simple model of the tertiary structure of IFN-gamma that fits well with our synthetic peptide and circular dichroism data. The model consists of the four-alpha-helical bundle along with N- and C-terminal helices that are predicted to be closely associated and together form the receptor binding domains. The model presented should contribute to further understanding the molecular basis of IFN-gamma action and allow us to begin modulating the function of IFN-gamma through the design of agonists and antagonists.
Facile synthesis and in vivo evaluation of biodegradable dendritic MRI contrast agents (2012)

Dendritic gadolinium chelates as magnetic resonance imaging (MRI) contrast agents (CAs) have shown great potential in blood pool and tumor imaging due to their enhanced relaxivities (R1s), prolonged blood circulation time, and homogeneous pharmaceutical properties. However, the non-biodegradability of the currently used dendrimers causes long-term retention of toxic gadolinium ions, limiting their clinical applications. Herein, we report a facile synthesis of biodegradable polyester dendrimer-based CAs. The prepared dendritic CAs have nano-sized structures with the hydrodynamic diameters ranging from 2.8 to 8.6 nm, and show high R1s up to 11.7 mM−1 s−1, approximately 2.7 times that of a clinically used small molecule CA (Magnevist). They are slowly hydrolyzed at an acidic pH, but rapidly hydrolyzed at pH 7.4, especially in the presence of esterase. The in vivo evaluation indicates they not only provide much better MRI contrast enhancement than Magnevist, but also show minimal tissue retention of Gd, which is much lower than those of non-biodegradable CAs.
Effects of antenna height, antenna gain, and pattern downtilting for cellular mobile radio (1996)

Results of wideband path loss and delay spread measurements using high gain, high and low antenna heights with pattern tilting are presented. The measurements were done in the frequency range 905-915 MHz, at two existing cellular mobile radio (CMR) sites. Also presented are potential approaches for analyzing data from high gain antennas. It is shown that, to a large extent, existing models can be used to predict path loss for high gain antennas with downtilting. The results further support the notion that high sites together with high gain antennas and suitably selected pattern tilting can result in a significant reduction in path loss and delay spread, as well as reduction in power transmitted from the cell site and reduction in system interference.
The Sagnac interferometer as a two-parameter sensor (1995)

We show the Sagnac interferometer as a two-parameter sensing device where nonreciprocal and reciprocal effects can be independently and simultaneously monitored. Phase shifts induced by nonreciprocal effects affect differently the counterpropagating beams in the loop and are accurately detected by a phase sensitive detection scheme. A probe for reciprocal effects is built by introducing a birefringence modulator inside the polarization-maintaining loop with its axes rotated with respect to the axes of the loop fiber. The resulting quadrature component of the demodulated signal is proportional to the phase shift induced by reciprocal effects at the probe site, making the interferometer suitable for dual parameter sensing. Demonstration of a electric/magnetic field sensor is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Functionalized, Swellable Hydrogel Layers as a Platform for Cell Studies (2009)

This paper reports the design, synthesis and characterization of thin films as a platform for studying the separate influences of physical and chemical cues of a matrix on the adhesion, growth and final phenotype of cells. Independent control of the physical and chemical properties of functionalized, swellable hydrogel thin films was achieved using initiated Chemical Vapor Deposition (iCVD). The systematic variation in crosslink density is demonstrated to control the swelling ability of the iCVD hydrogel films based on 2-hydroxyethyl methacrylate (HEMA). At the same time, the incorporation of controllable concentrations of the active ester pentafluorophenyl methacrylate (PFM) allows easy immobilization of aminated bioactive motifs, such as bioactive peptides. Initial cell culture results with Human Umbilical Vein Endothelial Cells (HUVEC) indicated that the strategy of using PFM to immobilize a cell-adhesion peptide motif onto the hydrogel layers promotes proper HUVEC growth and enhances their phenotype.
흡기근육 훈련이 아마추어 축구선수들의 최대 유산소 운동능력에 미치는 영향 (2012)

The aim of this investigation was to determine the effects of inspiratory muscle training(IMT) on maximal aerobic exercise performance in amateur soccer players. 14 male soccer players were randomly assigned to Inspiratory muscle training group(IMTG, n=7) or Control group(CG, n=7). Both group performed incremental treadmill test using Bruce protocol to examine maximal aerobic exercise performance before and following 8 weeks of intervention. IMTG were given inspiratory pressure threshold device(POWERbreathe) for IMT. All subjects also completed the winter training programme during the 8 weeks intervention. After intervention, there was significant change in VO2/kg between groups(p=0.006). IMTG showed significant changes in VO2/kg(22.15%, p=0.046), METS(21.53%, p=0.048), VT(22.36%, p=0.035) in measured AT values. There was significant change in treadmill exercise time between groups(p=0.001) and IMTG had significant change in treadmill exercise time(19.26%, p=0.001) after 8 weeks intervention. These results support evidence that inspiratory muscle training(IMT) has beneficial effects on VO2/kg, METS, VT and treadmill exercise time and might be a factor that improve soccer players` exercise performance.
Phosphoproteomics Identifies Driver Tyrosine Kinases in Sarcoma Cell Lines and Tumors (2012)

Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine phosphorylation are poorly understood. To better understand the signaling pathways active in sarcoma, we examined global tyrosine phosphorylation in sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were used to purify tyrosine phosphorylated peptides, which were then identified by liquid chromatography and tandem mass spectrometry. The findings were validated with RNA interference, rescue, and small-molecule tyrosine kinase inhibitors. We identified 1,936 unique tyrosine phosphorylated peptides, corresponding to 844 unique phosphotyrosine proteins. In sarcoma cells alone, peptides corresponding to 39 tyrosine kinases were found. Four of 10 cell lines showed dependence on tyrosine kinases for growth and/or survival, including platelet-derived growth factor receptor (PDGFR)α, MET, insulin receptor/insulin-like growth factor receptor signaling, and SRC family kinase signaling. Rhabdomyosarcoma samples showed overexpression of PDGFRα in 13% of examined cases, and sarcomas showed abundant tyrosine phosphorylation and expression of a number of tyrosine phosphorylated tyrosine kinases, including DDR2, EphB4, TYR2, AXL, SRC, LYN, and FAK. Together, our findings suggest that integrating global phosphoproteomics with functional analyses with kinase inhibitors can identify drivers of sarcoma growth and survival.
A framework for integrating arrival, departure, and surface operations scheduling (2014)

This paper proposes a framework for integrating scheduling between arrival, departure, and surface operations to address the drawbacks of domain segregated scheduling. The framework organizes scheduling tasks by time horizon rather than domain. The four-level framework hierarchy includes the configuration schedule, flight schedule, flight schedule update, and schedule conformance. Current NASA research gaps within this framework are discussed and key areas are proposed where future research should focus to facilitate scheduler integration.
Interdependent latch setup/hold time characterization via Euler-Newton curve tracing on state-transition equations (2007)

Interdependent characterization of latch setup/hold times is a core component of techniques for pessimism reduction via Setup/Hold Interdependence Aware Static Timing Analysis (SHIA-STA) [1], [2]. We present an efficient and novel method for such characterization, by formulating the interdependent setup-hold time problem as an underdetermined nonlinear equation h(τs, τh) = 0, which we derive from the latch's state-transition function. We solve this equation numerically using a Moore-Penrose Newton method. Further, we use null-space information from the Newton's Jacobian matrix to efficiently find constant-clock-to-Q contours (in the setup/hold time plane), via an Euler-Newton curve tracing procedure. We validate the method on TSPC and C2MOS registers, obtaining speedups of more than 20 x over prior approaches while achieving superior accuracy. This speedup increases linearly with the precision with which curve tracing is desired. In view of the importance and large computational expense of latch characterization in industry today, the new technique represents a significant enabling technology for dramatically speeding up industrial timing closure flows.
CELL-MEDIATED DELIVERY OF PROGRAMMED CELL DEATH SIGNALS FOLLOWING GENE TRANSFER OF A MEMBRANE-ANCHORED SINGLE-CHAIN ANTIBODY SPECIFIC FOR CLASS I MHC (1999)

821 Introduction. Gene transfer of death signaling molecules has not been reliably successful in protecting allogenic cellular and tissue transplants from immune rejection. We describe the use of a membrane anchored, single-chain antibody (5H7Fv-GPI) that delivers human lymphoid programmed cell death (PCD) signals by ligation of class I MHC. 5H7Fv-GPI is derived from 5H7, a mAb specific for the α3 domain of class I MHC that induces veto-like PCD signals in human lymphoid cells. Derivation of a single-chain version of 5H7 provides a means for achieving cell surface expression of the 5H7 idiotype on cells that lack the machinery to properly assemble whole mAb. Methods. Chinese Hamster Ovary (CHO) cells were stably transfected with pC5H7Fv-GPI (5H7Fv coupled to CD58-derived glycosylphosphotidylinostitol (GPI)). Lymphoid PCD was assessed by co-culture of CHO-v5 (pC5H7Fv-GPI transfected) or CHO-neo (control vector pCDNA 3.1 transfected) cells with lymphoid targets. Competitive release of target cells from CHO cells was achieved by addition of A2.4, an anti-idiotypic mAb specific for the 5H7 idiotype. PCD morphology was determined by fluorescence microscopy following ethidium bromide/acridine orange staining and confirmed by Annexin V-FITC flow cytometric measurements. Results. CHO-v5 cells actively bound recombinant-derived soluble class I MHC, as determined flow cytometry. CHO-v5 cells induced PCD in Jurkat and BeVD lymphoid tumor cell lines, but not in control Daudi cells (class I MHC deficient). Jurkat cell PCD is not observed with use of whole 5H7 mAb, suggesting that 5H7Fv-GPI provides a modified or augmented PCD signal, when compared to parental mAb. Observations from several studies indicate that 5H7Fv-GPI delivers PCD signal with a potency comparable to that of the parental 5H7 mAb. Human PBMC were also susceptible to class I MHC-induced PCD following exposure to CHO-v5 cells. Preactivation of PBMC with immobilized anti-CD28 and anti-CD3 mAbs augmented PCD after co-culture with CHO-v5, a finding similar to that observed with the 5H7 mAb. The specificity of class I MHC signalling was addressed by the addition of excess A2.4 mAb, which reduced lymphoid PCD to background levels. Splenocytes derived from B6 mice transgenic for class I HLA-B27 also underwent PCD after coculture with CHO-v5, while splenocytes from transgene negative littermates did not show PCD. Thus, the inability of CHO-v5 to induce PCD in Daudi cells, B6 non-transgenic mice splenocytes, and the inhibition of PCD by A2.4 mAb confirm that CHO-v5 mediates PCD via class I MHC. Conclusions. 1) Cell surface expression of the 5H7Fv-GPI gene reconstitutes the 5H7 idiotype and retains ability to bind to class I MHC. 2) 5H7Fv-GPI PCD induces PCD in lymphoid cells that express class I MHC 3) Gene transfer of 5H7Fv-GPI provides a promising approach for modulating immune responses to human allografts.
The Wisconsin Wind Tunnel project (1994)

This document lists contributors to the Wisconsin Wind Tunnel Project, gives a brief description of the project, and presents references and abstracts to its principal papers, including how to obtain them online.
APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental <i>Coccidioides immitis</i> Pneumonia (2018)

Coccidioidomycosis is a systemic fungal infection caused by the inhalation of the arthroconidia of either of two closely related dimorphic fungi, <i>Coccidioides immitis</i> and <i>C. posadasii</i>, that are endemic in the southwestern United States and other areas in the Western Hemisphere. Chronic cavitary pulmonary infections and extrapulmonary sites of infection are very difficult to treat and often require lifelong azole therapy. APX001A is the first in a new class of broad-spectrum antifungal agents that inhibit Gwt1, an enzyme which is required for cell wall localization of glycosylphosphatidylinositol (GPI)-anchored mannoproteins in fungi. APX001A and several analogs were highly active against clinical isolates of <i>Coccidioides</i>, inhibiting hyphal growth at low nanogram/ml concentrations. APX001 is the N-phosphonooxymethyl prodrug of APX001A, currently in clinical trials for the treatment of invasive fungal infections. Mice were treated orally once daily with 26 mg/kg/day of APX001 and the prodrug analog APX2097, 2 h after administration of the pan-cytochrome P450 inhibitor 1-aminobenzotriazole, which was used to enhance drug half-life and exposures to more closely mimic human pharmacokinetics of APX001A. Five days of treatment reduced lung colony counts by nearly 3 logs and prevented dissemination, similar to the efficacy of fluconazole dosed orally at 25 mg/kg twice daily. In a survival experiment, both APX001- and APX2097-treated mice survived significantly longer than control and fluconazole-treated mice. APX001 and other members of this new class of antifungal agents may offer great promise as effective therapies for coccidioidomycosis.
Continuous-time sigma-delta modulators with reduced timing jitter sensitivity based on time delays (2003)

A novel continuous time sigma-delta modulator architecture is presented. This architecture employs a noise shaping filter based on time delays, which allows a high speed hardware implementation with transmission lines. This architecture is less sensitive to clock jitter and excess loop delay than the equivalent continuous time modulators based on integrators.
THE LOS ANGELES DERMATOLOGICAL SOCIETY (1974)

<h3>Angiolymphoid Hyperplasia With Eosinophilia. Presented by Stephen Schwartz, MD (by invitation).</h3> For 12 years, multiple pruritic nodules have been present on the scalp of a 57-year-old white woman. Initially, a biopsy specimen was diagnosed as chronic dermatitis, and x-ray therapy with 400 roent1-cm given at that time was ineffective. A 1-cm satellite nodule was excised two months ago. New papules are appearing. Skull roentgenograms have been reported to be normal. There is no similar history in the family. Other medical problems have been reflux esophagitis and hiatal hernia, and lipoprotein electrophoresis reveals findings of a hyperlipemia, type II b. The posterior scalp reveals multiple dermal nodules, clustered together and measuring from 5 mm to 3 cm, some of them superficially
Formation of 10−100 nm Size-Controlled Emulsions through a Sub-PIT Cycle (2009)

We have re-examined the phase inversion temperature (PIT) emulsification process. This is a low-energy method that uses a physicochemical drive to produce very fine oil/water emulsions in the absence of high shear flows. We used the polyoxyethylene 8 cetyl ether (C(16)E(8))/hexadecane/water system, which has a PIT of 76.2 degrees C. We find that successful emulsification depends on two conditions. First, the mixture must be stirred at low speed throughout the whole process: this makes it possible to produce emulsions at surfactant concentrations that are too low to form an equilibrium microemulsion. Second, the stirred mixtures must be heated above a threshold called the clearing boundary (CB) and then quenched to lower temperatures. The clearing boundary is determined experimentally by a minimum in the turbidity of the stirred mixture, which results from solubilization of all the oil into swollen micelles. This matches the emulsification failure boundary, and it is expressed mathematically by the condition R*C(0) = 1, where R* is the radius that results from the oil/surfactant composition for monodisperse spheres and C(0) is the spontaneous spherical curvature of the surfactant. Thus, we show that such cycles do not need to cross the PIT. In fact, sub-PIT cycles and cross-PIT cycles give exactly the same result. These conditions lead to emulsions that have a narrow size distribution and a mean diameter controlled by the oil/surfactant ratio. The typical range of those diameters is 20-100 nm. Moreover, these emulsions have an excellent metastability, in contrast with emulsions made with shorter oil and surfactant molecules.
Drug use among the young homeless: coping through self-medication (1998)

Research has shown that illicit drug use is now a common feature of homelessness. A main aim of the study was to examine the role that drugs played in the lives of young homeless people. Two hundred young homeless drug users (aged 14–25 years) were interviewed. Respondents reported a variety of health problems. Respiratory infections, aching limbs and weight loss were the most common, but of greater concern was mental health and 82% reported psychological symptoms: depression, sometimes severe and often chronic, anxiety and aggression. A very high proportion (43%) had attempted suicide, mostly through drug overdose. Three-quarters of the sample said they used drugs to self-medicate their symptoms. Drug use is one form of stress management that is widely adopted by many people, whether homeless or not, but the particular nature of the stressors endemic in the homeless lifestyle leads to a much increased vulnerability to such selfmedication when other coping strategies fail.
Javelus: A Low Disruptive Approach to Dynamic Software Updates (2012)

Practical software systems are subject to frequent updates for fixing their bugs or addressing new requirements. Updating a software system without stopping and restarting it is desired, as this helps reduce the redeployment cost as well as achieving the high availability. Existing techniques for dynamically updating Java programs may introduce noticeable pauses during which these programs are unable to function. We in this paper present Javelus, a dynamic Java update system with greatly reduced pausing time but without sacrificing update flexibility and system efficiency. Different from previous approaches, Javelus uses a lazy update mechanism with which an object-to-update will not be updated until it is really used. We implemented Javelus on top of an industry-strength OpenJDK HotSpot VM. We evaluated Javelus with real updates to Tomcat 7 and the same micro array benchmark used in evaluating Jvolve and DCE VM. The experiments report promising results that Javelus only incurred a pausing time two orders of magnitude smaller than those of Jvolve and DCE VM.
Capsaicin‐sensitive vagal stimulation‐induced gastric acid secretion in the rat: evidence for cholinergic vagal afferents (1991)

1. The effects of electrical vagal stimulation on frequency-dependent gastric acid secretion were investigated in urethane-anaesthetized rats in vivo. 2. Stimulation at 4, 16 or 32 Hz was performed in rats treated with atropine (1 mg kg-1, i.v.), hexamethonium (10 mg kg-1, i.v. bolus and 1 mg kg-1 min-1, i.v. infusion) or atropine and hexamethonium (doses as above); in some experiments pentagastrin (1.2 micrograms kg-1 h-1, i.v. infusion) was infused prior to stimulation. 3. Maximal acid secretion occurred at 16 Hz. This was significantly reduced but not abolished by atropine or hexamethonium and completely abolished after atropine and hexamethonium. In the presence of pentagastrin, the acid secretory response to 16 Hz stimulation was augmented, atropine or hexamethonium reduced stimulated secretion by about 70%, whereas atropine and hexamethonium completely abolished stimulated secretion. 4. In rats in which the vagus nerve was pretreated with capsaicin 10-14 days before experimentation there was a significant reduction (by about 40%) in stimulated acid secretion at 16 Hz, which was virtually abolished by atropine treatment. After acute treatment of the vagus nerve with capsaicin (at the time of experimentation) maximally stimulated acid secretion was significantly reduced by about 50%. 5. Taken together, these results indicate that capsaicin-sensitive afferent fibres contribute to the acid secretory response induced by electrical vagal stimulation in the rat. Based on pharmacological evidence, the capsaicin-sensitive afferent fibres may be cholinergic, since atropine and hexamethonium totally abolish vagal stimulation-induced acid secretion.