gebhart/patrepeval huggingface dataset:
Expression of c‐fos, c‐jun, and N‐terminal kinase (JNK) in a Development Model of Induced Apoptotic Death in Neurons of the Substantia Nigra (1999)

The transcription factors c-fos and c-jun have been proposed to play a role in the initiation of programmed cell death in neurons. We have shown that programmed cell death, with the morphology of apoptosis, occurs in dopamine neurons of the substantia nigra (SN) during normal postnatal development and that this death event can be induced by early striatal target injury. We have investigated the relationship between c-fos and c-jun protein expression and induced death in neurons of the SN. Although c-fos is induced, it is unlikely to play a role in cell death, because its expression is not well correlated with apoptotic death either temporally or at a cellular level. Expression of c-jun, however, is both temporally and regionally correlated with induction of death, and, at a cellular level, it colocalizes with apoptotic morphology. The increased expression of c-jun is likely to be functionally significant, because it is associated with increased c-jun N-terminal kinase (JNK) and phosphorylated c-jun expression. JNK expression also colocalizes with apoptotic morphology. We conclude that c-jun is likely to play a role in the initiation of apoptotic cell death in these neurons.
Antiphospholipid Antibodies in an in vivo Thrombosis Model in Mice (1994)

The mouse model described in this study offers a unique method of determining the characteristics and mechanism(s) of action of aCL antibodies in thrombosis in vivo. In addition, this animal model enables the study of the kinetics of formation and dissolution of thrombus, as well as clot area, to be studied in a dynamic fashion. Other models for evaluation of thrombus formation rely on measurements of thrombus size and weight in ligated vessel segments where flow may be interrupted artificially. In addition, two important findings can be extracted from the study. (1) The size of the thrombi were significantly larger in mice that were passively immunized with IgG-APS (four patient samples examined) and with IgM-APS (two patient samples examined) compared with mice injected with saline or with immunoglobulin from control patients. (2) The clot persisted significantly for longer periods of time (total time) in animals injected with IgG-APS or IgM-APS when compared with control animals. Based on in vitro experiments, it is possible that these antibodies may inhibit protein C activation, neutralize the inhibitory activity action of beta 2 glycoprotein I (beta 2GPI), or activate platelets at the site of the femoral vein injury. Because this model enables to study the dynamics of thrombus formation, it is possible that these hypotheses and other mechanisms by which aPL antibodies are thrombogenic be investigated. Future studies will also include the effects of different levels of antibodies, as well as effects of affinity purified and monoclonal aPL antibodies on thrombus formation.
Toward Personalized Lymphoma Immunotherapy: Identification of Common Driver Mutations Recognized by Patient CD8+ T Cells (2015)

Abstract Purpose: A fundamental challenge in the era of next-generation sequencing (NGS) is to design effective treatments tailored to the mutational profiles of tumors. Many newly discovered cancer mutations are difficult to target pharmacologically; however, T-cell–based therapies may provide a valuable alternative owing to the exquisite sensitivity and specificity of antigen recognition. To explore this concept, we assessed the immunogenicity of a panel of genes that are common sites of driver mutations in follicular lymphoma, an immunologically sensitive yet currently incurable disease. Experimental Design: Exon capture and NGS were used to interrogate tumor samples from 53 patients with follicular lymphoma for mutations in 10 frequently mutated genes. For 13 patients, predicted mutant peptides and proteins were evaluated for recognition by autologous peripheral blood T cells after in vitro priming. Results: Mutations were identified in 1–5 genes in 81% (43/53) of tumor samples. Autologous, mutation-specific CD8+ T cells were identified in 23% (3/13) of evaluated cases. T-cell responses were directed toward putative driver mutations in CREBBP and MEF2B. Responding T cells showed exquisite specificity for mutant versus wild-type proteins and recognized lymphoma cells expressing the appropriate mutations. Responding T cells appeared to be from the naïve repertoire, as they were found at low frequencies and only at single time points in each patient. Conclusions: Patients with follicular lymphoma harbor rare yet functionally competent CD8+ T cells specific for recurrent mutations. Our results support the concept of using NGS to design individualized immunotherapies targeting common driver mutations in follicular lymphoma and other malignancies. Clin Cancer Res; 22(9); 2226–36. ©2015 AACR.
Strategies to Address Chimeric Antigen Receptor Tonic Signaling (2018)

Adoptive cell transfer using chimeric antigen receptors (CAR) has emerged as one of the most promising new therapeutic modalities for patients with relapsed or refractory B-cell malignancies. Thus far, results in patients with advanced solid tumors have proven disappointing. Constitutive tonic signaling in the absence of ligand is an increasingly recognized complication when deploying these synthetic fusion receptors and can be a cause of poor antitumor efficacy, impaired survival, and reduced persistence <i>in vivo</i> In parallel, ligand-dependent tonic signaling can mediate toxicity and promote T-cell anergy, exhaustion, and activation-induced cell death. Here, we review the mechanisms underpinning CAR tonic signaling and highlight the wide variety of effects that can emerge after making subtle structural changes or altering the methodology of CAR transduction. We highlight strategies to prevent unconstrained tonic signaling and address its deleterious consequences. We also frame this phenomenon in the context of endogenous TCR tonic signaling, which has been shown to regulate peripheral tolerance, facilitate the targeting of foreign antigens, and suggest opportunities to coopt ligand-dependent CAR tonic signaling to facilitate <i>in vivo</i> persistence and efficacy. <i>Mol Cancer Ther; 17(9); 1795-815. ©2018 AACR</i>.
Acute Administration of 25-Hydroxycholecalciferol in Man (1976)

Serum 25-hydroxyvitamin D responses to oral doses of 25-hydroxycholecalciferol were measured in healthy volunteers. Peak serum 25-hydroxyvitamin D levels occurred 4 to 8 hours after doses of 1.5, 5, and 10 μg per kg of body weight. The mean increments above baseline serum 25-hydroxyvitamin D concentrations at 4 hours were linear over this dose range. Following a single oral dose, serum 25-hydroxyvitamin D levels fell to 33% of their peak values after one week. The serum 25-hydroxyvitamin D responses measured by competitive protein-binding radioassay were similar to the serum 3H responses exhibited by three volunteers who received simultaneous oral doses of 3H 25-hydroxycholecalciferol and 14C-cholecalciferol. The appearance of 14C in plasma was slower and less marked compared with 3H, probably reflecting a more rapid plasma clearance of the 14C-cholecalciferol. The disappearance of 25-hydroxycholecalciferol from the circulation of two volunteers following acute intravenous delivery of 1.0 mg of 25-hydroxycholecalciferol was multiphasic over 10 days. 60% of the dose administered remained in the circulation 24 hours after the dose. When analyzed several days after single 10 μg/kg oral doses of 25-hydroxycholecalciferol to 4 volunteers, the mean rate of decline of total serum 25-hydroxycholecalciferol was slow (t1/2 = 22 days). When baseline serum 25-hydroxyvitamin D levels were subtracted, however, the apparent serum half-life of administered 25-hydroxycholecalciferol was 12 days, similar to that reported after tracer doses of 3H-25-hydroxycholecalciferol. The rapid and predictable serum 25-hydroxyvitamin D increases following the oral administration of 25-hydroxycholecalciferol suggest its possible therapeutic advantages compared with vitamin D administration.
Performance effects of plan-based displays in commercial aviation (1993)

The experiment reported here examines the performance consequences of alignment between display formats and the methods used during descent. Twelve commercial pilots flew one of nine Standard Terminal Arrival Routes on a stand-alone flight simulator run on a Sparc II workstation. Three different methods for descent (Manual Control, Autopilot and Spoilers) were crossed with three methods according to scope, resolution, and bandwidth properties in the display of critical information. Performance variability in speed control supports our claim that the effectiveness of a display is not an independent property of the display itself, but rather, a function of the interaction of the display and the particular methods used for achieving task goals.
Intercellular adhesion molecule‐3 is the predominant co‐stimulatory ligand for leukocyte function antigen‐1 on human blood dendritic cells (1995)

Dendritic cells (DC) are potent stimulators of primary T lymphocyte responses to foreign antigen. The initial DC-T lymphocyte interaction involves the binding of the adhesion molecule leukocyte function antigen-1 (LFA-1; CD11a/CD18) on the T lymphocyte to an intercellular adhesion molecule (ICAM) on the DC. Although blood and tonsil DC express ICAM-1 (CD54) and ICAM-2 (CD102) on their surface, anti-ICAM-1 and anti-ICAM-2 monoclonal antibodies (mAb) have little inhibitory activity on the DC-stimulated mixed leukocyte reaction (MLR). We therefore examined the expression of the more recently identified LFA-1 ligand, ICAM-3 (CD50), in comparison to ICAM-1 and ICAM-2 on blood DC and sought a functional role for ICAM-3 in DC-mediated T lymphocyte responses. Resting blood DC expressed significantly more ICAM-3 than ICAM-1 or ICAM-2 as assessed by flow cytometry. Treatment of resting DC with interferon-gamma led to increased expression of ICAM-1; however, ICAM-2 and ICAM-3 levels remained relatively constant. Solid-phase recombinant chimeric molecules ICAM-1-, ICAM-2- and ICAM-3-Fc were able to co-stimulate CD4+ T lymphocyte proliferation in conjunction with suboptimal solid-phase CD3 mAb 64.1. However, the anti-ICAM-3 mAb CAL 3.10 inhibited a DC-stimulated MLR to a greater extent than anti-ICAM-1 or anti-ICAM-2 reagents and appeared to act by blocking the DC ICAM-3- T lymphocyte LFA-1 interaction. As ICAM-3 is the predominant LFA-1 ligand on resting blood DC, we postulate that DC may utilize ICAM-3 for initial DC- T lymphocyte interactions, and that ICAM-1, which is up-regulated upon DC activation, and/or ICAM-2, may contribute to DC migration or later phases of the T lymphocyte activation process.
Dual-band printed antenna for mobile telephone applications (2000)

A compact, lightweight, low-cost, dual-band antenna for GSM and DCS cellular telephone system applications is presented. The antenna, printed on a flexible printed circuit material and shaped round a foam former, is derived from the inverted-F geometry but has a much reduced conductor area. The software design package IE3D was used for design purposes and there was good agreement with measured results. The wide bandwidths required for this application are readily achieved using the antenna geometry. Radiation patterns give omni-directional coverage in the azimuth plane.
Pulsed Acceleration Charge Detection Mass Spectrometry:  Application to Weighing Electrosprayed Droplets (2007)

We describe a new approach to measuring the masses of individual macroions. The method employs a pulsed acceleration tube located between two sensitive image charge detectors. The charge and velocity of the macroion are recorded with the first image charge detector. The ion is pulse accelerated through a known voltage drop, and then the charge and velocity are remeasured using the second image charge detector. The mass of the ion is deduced from its charge and its initial and final velocities. The approach has been used to measure masses in the 10(10)-10(14) Da range with z = 10(3)-10(6) and m/z = 10(6)-10(9). It should be extendable to masses of <10(6) Da. We have used the method to determine the size and charge of water droplets transmitted through a capillary interface and an aperture interface. The droplets detected from the aperture interface are approximately 1 order of magnitude smaller in mass than those detected from the capillary interface. The droplets from both interfaces have relatively low charges, particularly with the capillary interface where they are only charged to a small fraction of the Rayleigh limit. These results suggest that the aerodynamic breakup of the droplets plays a significant role in the mechanism of electrospray ionization.
ChemInform Abstract: A Novel Series of 4‐Phenoxyquinolines: Potent and Highly Selective Inhibitors of PDGF Receptor Autophosphorylation. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Regulation of Expression of the 2-Deoxy- d -Ribose Utilization Regulon, deoQKPX , from Salmonella enterica Serovar Typhimurium (2003)

Salmonella enterica, in contrast to Escherichia coli K12, can use 2-deoxy-D-ribose as the sole carbon source. The genetic determinants for this capacity in S. enterica serovar Typhimurium include four genes, of which three, deoK, deoP, and deoX, constitute an operon. The fourth, deoQ, is transcribed in the opposite direction. The deoK gene encodes deoxyribokinase. In silico analyses indicated that deoP encodes a permease and deoQ encodes a regulatory protein of the deoR family. The deoX gene product showed no match to known proteins in the databases. Deletion analyses showed that both a functional deoP gene and a functional deoX gene were required for optimal utilization of deoxyribose. Using gene fusion technology, we observed that deoQ and the deoKPX operon were transcribed from divergent promoters located in the 324-bp intercistronic region between deoQ and deoK. The deoKPX promoter was 10-fold stronger than the deoQ promoter, and expression was negatively regulated by DeoQ as well as by DeoR, the repressor of the deoxynucleoside catabolism operon. Transcription of deoKPX but not of deoQ was regulated by catabolite repression. Primer extension analysis identified the transcriptional start points of both promoters and showed that induction by deoxyribose occurred at the level of transcription initiation. Gel retardation experiments with purified DeoQ illustrated that it binds independently to tandem operator sites within the deoQ and deoK promoter regions with K(d) values of 54 and 2.4 nM, respectively.
Streaming video and rate scalable compression: what are the challenges for watermarking? (2004)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
Common Carotid Intima-Media Thickness and Risk of Stroke and Myocardial Infarction (1997)

The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events.
Triplet and radical ion properties of styrylnaphthalenes and their aza-derivatives: a laser flash photolytic study (1992)

Laser flash photolysis was used to produce and investigate the lowest excited triplet state (T1) and radical ions (DAE˙+ and DAE˙–) of some diarylethylenes (DAE). In particular, the two trans-styrylnaphthalene isomers (n-StN, where n= 1 or 2 on the naphthalene) and four trans-1-(n-naphthyl)-2-(n′-pyridyl)ethylenes (n,n′-NPE, with n,n′= 1,4′; 2,2′; 2,3′ and 2,4′) were studied. The transients were characterized in terms of their absorption spectra, decay kinetics, molar absorption coefficients (for DAE˙+ and DAE˙–) and formation quantum yields (for T1 and DAE˙+). Except for 1-StN, under direct excitation in the absence of quenchers (λexc= 308 and 347 nm), T1→ Tn absorption was undetectable and DAE˙+ was the only transient observed, even though it was produced in low yield (ϕPI⩽ 0.06). The triplet state T1 of the DAEs was characterized in n-hexane, in the presence of 4-bromo-N, N-dimethylaniline (BrDMA) which enhances the intersystem-crossing quantum yields, while DAE˙– was produced and studied in acetonitrile, by laser excitation at 347 nm, in the presence of diethylaniline (DEA) and BrDMA.
Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin. (1998)

To probe the physiological role of calsequestrin in excitation-contraction coupling, transgenic mice overexpressing cardiac calsequestrin were developed. Transgenic mice exhibited 10-fold higher levels of calsequestrin in myocardium and survived into adulthood, but had severe cardiac hypertrophy, with a twofold increase in heart mass and cell size. In whole cell-clamped transgenic myocytes, Ca2+ channel- gated Ca2+ release from the sarcoplasmic reticulum was strongly suppressed, the frequency of occurrence of spontaneous or Ca2+ current-triggered "Ca2+ sparks" was reduced, and the spark perimeter was less defined. In sharp contrast, caffeine-induced Ca2+ transients and the resultant Na+-Ca2+ exchanger currents were increased 10-fold in transgenic myocytes, directly implicating calsequestrin as the source of the contractile-dependent pool of Ca2+. Interestingly, the proteins involved in the Ca2+-release cascade (ryanodine receptor, junctin, and triadin) were downregulated, whereas Ca2+-uptake proteins (Ca2+-ATPase and phospholamban) were unchanged or slightly increased. The parallel increase in the pool of releasable Ca2+ with overexpression of calsequestrin and subsequent impairment of physiological Ca2+ release mechanism show for the first time that calsequestrin is both a storage and a regulatory protein in the cardiac muscle Ca2+-signaling cascade. Cardiac hypertrophy in these mice may provide a novel model to investigate the molecular determinants of heart failure.
Oxide-confined vertical-cavity surface-emitting lasers, quantum dots, and the Purcell effect: can scaling the mode size improve laser performance? (1999)

The development of vertical-cavity surface-emitting lasers (VCSELs) has led to new types of low power, high efficiency light sources for data communication. The small size, low power, and surface-normal emission of VCSELs has enabled relatively dense 2D arrays for highly parallel data communication and optical signal processing. In this paper we examine the issues of device scaling on VCSEL performance. We look specifically at what benefits may be derived from continued scaling of the active volume down to minimum sized dimensions, and what device schemes may be required to obtain the scaling. Laser rate equations are used to show that when the VCSEL mode volume is reduced to wavelength cubed dimensions, a significant improvement in modulation speed is predicted based on the radiative lifetime change due to the Purcell effect. However, several parasitic effects must be controlled in order to realize these benefits. Most important are control of the optical loss due to diffraction or scattering, and control of the electronic losses due to carrier diffusions and surface effects. Novel optical confinement schemes based on oxide- apertures, photonic bandgaps, and/or closely coupled 2D arrays may be useful for controlling optical loss, while self-assembled quantum dots are attractive for controlling electronic diffusion to dimensions within the minimum optical mode volume.
Fourier transform multipixel spectroscopy for quantitative cytology (1996)

A Fourier transform multipixel spectroscopy system was set up and applied to fluorescence microscopy of single living cells. Continuous fluorescence spectra for all pixels of the cell image were recorded simultaneously by the system. Multiple frames of data were first acquired and stored as a set of interferograms for each pixel of the image; they were then Fourier transformed and used as a spatially organized set of fluorescence spectra. Practical spectral resolution of 5 nm was achieved, typically, for 10 4 pixels in a single cell. The net result was I ( x y ,λ), the fluorescence intensity ( I ) for each pixel of the image ( x y ), as function of wavelength (λ). The present study demonstrates that multipixel spectroscopy can reveal dynamic processes of the food‐digestive cycle in the unicellular Paramecium vulgaris fed with algae. Spectral variability of fluorescence intensity at different cytoplasmic sites pinpointed the location of cellular deposits of chlorophyll (630 nm) and of pheophytin (695 nm), a digestive product of the chlorophyll. Localization of compartmental spectral changes was achieved using a ‘similarity mapping’ algorithm, followed by enhanced image construction. Similarity mapping based on the fluorescence spectrum of native chlorophyll revealed a highlighted image of the cell cytopharynx structure where algae were ingested. Phagolysosomes, migrating vacuoles and the cytoproct, each containing different ratios of pheophytin, were similarly imaged.
Histidyl-proline diketopiperazine (His-Pro DKP) immunoreactivity is present in the glucagon-containing cells of the human fetal pancreas. (1987)

Histidyl-proline diketopiperazine (His-Pro DKP) cells in the pancreas of human fetuses aged between 12 and 19 wk were localized by the indirect antibody-enzyme method on semithin sections. To study their fine structure, two techniques were used: a superimposition technique consisting of comparison of the same cells in semithin and electron microscopic preparations, and an immunocytochemical technique on ultrathin sections using the unlabeled antibody peroxidase-antiperoxidase method. Our results show that (a) the same cells are positive for both His-Pro DKP and glucagon/glicentin, (b) His-Pro DKP immunoreactive cells possess extremely electron-opaque secretory granules, implying that these cells correspond to the A cells, and (c) His-Pro DKP immunoreactivity is found over the secretory granules. We hypothesize that the two peptides His-Pro DKP and thyrotropin-releasing hormone (TRH) have independent origins, since TRH is found in the B cells.
Wound Healing in an Animal Model of Glaucoma Fistulizing Surgery in the Rabbit (1989)

We developed a model of glaucoma fistulizing surgery in the rabbit. As is the case with wound healing in general, there was inflammation followed by repair. The sclerostomy and bleb closed due to bulk filling by granulation tissue and contraction by migratory fibroblasts (observed at three days) and by myofibroblasts (observed at ten and 17 days). Fifty-eight percent of blebs had collapsed by ten days, and 94% by 17 days. The fibroblasts were migrating from the episcleral tissues, from the epimysium of the superior rectus, and from subconjunctival connective tissue. Intraocular pressure and facility of aqueous outflow were measured, but we concluded that intraocular pressure is not a reliable indicator of bleb function or of a patent sclerostomy in this model.