gebhart/patrepeval huggingface dataset:
Notch3 Inhibition in Myelin-Reactive T Cells Down-Regulates Protein Kinase Cθ and Attenuates Experimental Autoimmune Encephalomyelitis (2008)

Among its varied functions, Notch signaling is involved in peripheral T cells responses. The activation and polarization of CD4(+) T cells toward a Th1 lineage are essential steps in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Inhibition of all four Notch receptors with a gamma-secretase inhibitor was shown to block Th1-type polarization and to attenuate the symptoms of experimental autoimmune encephalomyelitis. In this study, we have examined the role of individual Notch receptors in proliferation, cytokine production, and encephalitogenic potential of PLP-reactive T cells. Specific induction of Notch1 and Notch3 transcripts were noted in PLP-reactive T cells upon Ag stimulation. However, using gamma-secretase inhibitor and Abs blocking distinct Notch receptors, we have found that selective inhibition of Notch3, but not Notch1, receptor abrogated proliferation, Th1- and Th17-type responses of PLP-reactive T cells. Moreover, Notch3 inhibition in T cells correlated with the down-regulated expression of protein kinase Ctheta, a kinase with important regulatory function within mature T cells. Thus, selective inhibition of the Notch3 receptor may have important effects on peripheral T cell responses and may offer a new attractive target in treating autoimmune diseases, including multiple sclerosis.
Role of Ca2+ channels in the ability of membrane depolarization to prevent neuronal death induced by trophic-factor deprivation: evidence that levels of internal Ca2+ determine nerve growth factor dependence of sympathetic ganglion cells. (1989)

Sympathetic neurons depend on nerve growth factor (NGF) for their survival both in vivo and in vitro; these cells die upon acute deprivation of NGF. We studied the effects of agents that cause membrane depolarization on neuronal survival after NGF deprivation. High-K+ medium (greater than or equal to 33 mM) prevented cell death; the effect of K+ was dose-dependent (EC50 = 21 mM). The protection by high K+ was abolished either by withdrawal of extracellular Ca2+ or by preloading the cells with a Ca2+ chelator. The involvement of Ca2+ flux across membranes in high-K+ saving of NGF-deprived neurons was also supported by experiments using Ca2+-channel antagonists and agonists. The Ca2+ antagonists nimodipine and nifedipine effectively blocked the survival-promoting effect of high K+. The Ca2+ agonists Bay K 8644 and (S)-202-791 did not by themselves save neurons from NGF deprivation but did strongly augment the effect of high K+; EC50 was shifted from 21 mM to 13 mM. These data suggest that dihydropyridine-sensitive L-type Ca2+ channels play a major role in the high-K+ saving. The depolarizing agents choline (EC50 = 1 mM) and carbamoylcholine (EC50 = 1 microM), acting through nicotinic cholinergic receptors, also rescued NGF-deprived neurons. The saving effect of nicotinic agonists was not blocked by withdrawal of extracellular Ca2+ but was counteracted by a chelator of intracellular Ca2+, suggesting the possible involvement of Ca2+ release from internal stores. Based on these findings we propose a "Ca2+ set-point hypothesis" for the degree of trophic-factor dependence of sympathetic neurons in vitro.
Animatronic Shader Lamps Avatars (2009)

Applications such as telepresence and training involve the display of real or synthetic humans to multiple viewers. When attempting to render the humans with conventional displays, non-verbal cues such as head pose, gaze direction, body posture, and facial expression are difficult to convey correctly to all viewers. In addition, a framed image of a human conveys only a limited physical sense of presence - primarily through the display's location. While progress continues on articulated robots that mimic humans, the focus has been on the motion and behavior of the robots. We introduce a new approach for robotic avatars of real people: the use of cameras and projectors to capture and map the dynamic motion and appearance of a real person onto a humanoid animatronic model. We call these devices Animatronic Shader Lamps Avatars (SLA).We present a proof-of-concept prototype comprised of a camera, a tracking system, a digital projector, and a life-sized styrofoam head mounted on a pan-tilt unit. The system captures imagery of a moving, talking user and maps the appearance and motion onto the animatronic SLA, delivering a dynamic, real-time representation of the user to multiple viewers.
Molecular and genetic pathways in gliomas: the future of personalized therapeutics (2014)

In the last few decades, we have seen significant advances in brain imaging, which have resulted in more detailed anatomic and functional localization of gliomas in relation to the eloquent cortex, as well as improvements in microsurgical techniques and enhanced delivery of adjuvant stereotactic radiation. While these advancements have led to a relatively modest improvement in clinical outcomes for patients with malignant gliomas, much more work remains to be done. As with other types of cancer, we are now rapidly moving past the era of histopathology dictating treatment for brain tumors and into the realm of molecular diagnostics and associated targeted therapies, specifically based on the genomic architecture of individual gliomas. In this review, we discuss the current era of molecular glioma characterization and how these profiles will allow for individualized, patient-specific targeted treatments.
The Open Reading Frame III Product of Cauliflower Mosaic Virus Forms a Tetramer through a N-terminal Coiled-coil (1998)

The open reading frame III product of cauliflower mosaic virus is a protein of 15 kDa (p15) that is essential for the virus life cycle. It was shown that the 34 N-terminal amino acids are sufficient to support protein-protein interaction with the full-length p15 in the yeast two-hybrid system. A corresponding peptide was synthesized and a recombinant p15 was expressed in Escherichia coli and purified. Circular dichroism spectroscopy showed that the peptide and the full-length protein can assume an alpha-helical conformation. Analytical centrifugation allowed to determine that p15 assembles as a rod-shaped tetramer. Oxidative cross-linking of N-terminal cysteines of the peptide generated specific covalent oligomers, indicating that the N terminus of p15 is a coiled-coil that assembles as a parallel tetramer. Mutation of Lys22 into Asp destabilized the tetramer and put forward the presence of a salt bridge between Lys22 and Asp24 in a model building of the stalk. These results suggest a model in which the stalk segment of p15 is located at its N terminus, followed by a hinge that provides the space for presenting the C terminus for interactions with nucleic acids and/or proteins.
Managing approximate models in evolutionary aerodynamic design optimization (2002)

Approximate models have to be used in evolutionary optimization when the original fitness function is computationally very expensive. Unfortunately, the convergence property of the evolutionary algorithm is unclear when an approximate model is used for fitness evaluation because approximation errors are involved in the model. What is worse, the approximate model may introduce false optima that lead the evolutionary algorithm to a wrong solution. To address this problem, individual and generation based evolution control are introduced to ensure that the evolutionary algorithm using approximate fitness functions will converge correctly. A framework for managing approximate models in generation-based evolution control is proposed. This framework is well suited for parallel evolutionary optimization in which evaluation of the fitness function is time-consuming. Simulations on two benchmark problems and one example of aerodynamic design optimization demonstrate that the proposed algorithm is able to achieve a correct solution as well as a significantly reduced computation time.
A real-time one-step reverse transcriptase-polymerase chain reaction method to quantify c-erbB-2 expression in human breast cancer. (2000)

We developed a real-time one-step reverse transcriptase-polymerase chain reaction (RT-PCR) method for the routine quantification of c-erbB-2 oncogene expression in breast cancer, using a 7700 ABI PRISM Sequence Detector System (Perkin Elmer-Applied Biosystems, Courtaboeuf, France). The real-time quantification of the polymerase chain reaction products is based on the TaqMan 5' nuclease assay. The optimal experimental conditions we determined were as follows: 6 mM MgCl2, 200 nM of fluorogenic probe, 200 nM of each primer, and 12.5 units MuLV reverse transcriptase. The GAPDH housekeeping gene was used for normalization of c-erbB-2 expression. In human breast cancer cell lines, the normalized expression of c-erbB-2 ranged from 8 x 10(-6) to 2,600 x 10(-6), the two highest values corresponding to the c-erbB-2 overexpressing cells MDA-MB-453 and SK-BR-3. In a series of 100 breast cancer samples, c-erbB-2 normalized expression was found to range from 0.4 x 10(-6) to 350 x 10(-6). A close correlation was observed between this real-time one-step quantitative RT-PCR method and both semiquantitative conventional RT-PCR (N = 22; r = 0.8543; P < .0001) and c-erbB-2 protein expression (p185) quantified by an enzyme immunoassay (EIA) (N = 27; r = 0.71; P < .0001). The current realtime RT-PCR assay is rapid, sensitive, and reproducible and appears particularly suitable to quantify gene expression in large series of samples.
Under the spotlight: The organic–inorganic hybrid halide perovskite for optoelectronic applications (2015)

The dawn of a new era in optoelectronic technologies has emerged with the recent development of the organic–inorganic hybrid halide perovskite. Its exceptional attributes, including high carrier mobility, an adjustable spectral absorption range, long diffusion lengths, and the simplicity and affordability of fabrication render it one of the most exceptional and market-competitive optoelectronic materials for applications in photovoltaics, light emitting diodes (LED), photodetectors, lasers, and more. Moreover, its versatility in device architecture and ability to achieve relatively high performance devices via various processing techniques makes perovskites a highly promising material for various practical applications. Here, we review the organic–inorganic hybrid halide perovskite and delve into its recent progress and relevant applications.
Roflumilast for the treatment of chronic obstructive pulmonary disease (2010)

Roflumilast is a new phosphodiesterase 4 inhibitor that has recently completed Phase III trials for the treatment of chronic obstructive pulmonary disease (COPD). Preclinical studies have shown that roflumilast targets inflammatory processes in COPD, with beneficial effects on tobacco-induced lung inflammation, lung fibrosis and remodeling, mucociliary malfunction and oxidative stress. Two recent, 1-year Phase III trials in COPD have shown that roflumilast reduces exacerbations and improves lung function in patients with COPD who have symptoms of chronic bronchitis and a history of exacerbations. Two other 6-month Phase III trials have demonstrated the beneficial effects of roflumilast in patients already receiving treatment with the long-acting &#x03B2;-agonist salmeterol or the long-acting muscarinic antagonist tiotropium. This article reviews the pharmacology, pharmacokinetics and preclinical pharmacology of roflumilast, the clinical studies supporting its use in COPD and its side-effect profile.
Clinical Use of Erythropoietic Stimulating Agents in Myelodysplastic Syndromes (2011)

Myelodysplastic syndromes (MDS) are heterogeneous clonal diseases characterized by cytopenias resulting from ineffective hemopoiesis. Anemia affects the vast majority of patients with MDS and contributes substantially to their symptoms. For more than 20 years, recombinant human erythropoietin has been available for clinical use, and it has been employed in an attempt to relieve MDS-related anemia. Erythropoietin-alpha, erythropoietin-beta, and more recently darbepoetin have been found to increase hemoglobin levels and abolish transfusion dependence in 19%-68% of MDS cases. This wide range in clinical response depends on several biological and clinical variables that allow the selection of patients with the highest probability of successful treatment. These agents are a mainstay in MDS therapy, but many issues are still open in terms of the initiation of therapy, the optimal dosage of erythropoietic stimulating agents (ESAs), the most efficient type of ESA, and the duration and outcome of such treatments. In this review, the mechanisms of response and predictive factors as well as an analysis of the clinical activity of ESAs in MDS therapy are presented.
Gravity and magnetic calculations (1942)

Abstract In the earlier geophysical literature, many schemes were published for the calculation of gravity and magnetic effects. For the most part these were either the curves for the effects of certain definite geometric bodies or various charts and diagrams by which the effects for a body of any shape could be determined graphically. It is probable that these schemes have had comparatively little actual application in the interpretation of magnetic and gravity surveys. This is because of the fact that unless certain controls other than the gravity and magnetic data are available the inherent ambiguities of the physically possible distributions of material which can produce the observed effects make an accurate calculation meaningless, even though the geophysical data may be of any desired precision. Furthermore, it is often possible to calculate, from rather generalized forms, geophysical effects which are in agreement with those observed within the precision of the observations. In fact, unless two conditions are fulfilled, i.e., (1) observed data are of high precision and spaced at distances substantially less than the horizontal dimensions or depth of the disturbing body, and (2) some other control is available, there is little point to using any of the more refined methods of calculation.
Chelating Self-Assembled Monolayers on Gold Generated from Spiroalkanedithiols (1999)

The formation of self-assembled monolayers (SAMs) on gold from the adsorption of a series of specifically designed 2,2-dialkylpropanedithiol derivatives, [CH3(CH2)n]2C[CH2SH]2 where n = 0, 3, 7, and 11−15, is reported. The SAMs were characterized by optical ellipsometry, contact angle goniometry, and polarization modulation infrared reflection absorption spectroscopy. These data, when compared to those collected on SAMs generated from normal alkanethiols (CH3(CH2)mSH) of similar chain length, suggest that the new SAMs are highly oriented and well packed. They exhibit, however, slightly less crystallinity than their alkanethiolate-based analogues. A preliminary description of the kinetics of adsorption and desorption of these new SAMs is presented.
Simple and Rapid Colorimetric Biosensors Based on DNA Aptamer and Noncrosslinking Gold Nanoparticle Aggregation (2007)

The color purple. Upon binding of the target +, negatively charged DNA aptamers (shown in purple) dissociate from a gold nanoparticle surface; this results in nanoparticle aggregation and a color change at a chosen salt concentration.
Adenosine Receptor 2A Blockade Increases the Efficacy of Anti–PD-1 through Enhanced Antitumor T-cell Responses (2015)

Immunotherapy is rapidly emerging as a cancer treatment with high potential. Recent clinical trials with anti-CTLA-4 and anti-PD-1/PD-L1 antibodies (mAbs) suggest that targeting multiple immunosuppressive pathways may significantly improve patient survival. The generation of adenosine by CD73 also suppresses antitumor immune responses through the activation of A2A receptors on T cells and natural killer (NK) cells. We sought to determine whether blockade of A2A receptors could enhance the efficacy of anti-PD-1 mAb. The expression of CD73 by tumor cells limited the efficacy of anti-PD-1 mAb in two tumor models, and this was alleviated with concomitant treatment with an A2A adenosine receptor antagonist. The blockade of PD-1 enhanced A2A receptor expression on tumor-infiltrating CD8(+) T cells, making them more susceptible to A2A-mediated suppression. Thus, dual blockade of PD-1 and A2A significantly enhanced the expression of IFNγ and Granzyme B by tumor-infiltrating CD8(+) T cells and, accordingly, increased growth inhibition of CD73(+) tumors and survival of mice. The results of our study indicate that CD73 expression may constitute a potential biomarker for the efficacy of anti-PD-1 mAb in patients with cancer and that the efficacy of anti-PD-1 mAb can be significantly enhanced by A2A antagonists. We have therefore revealed a potentially novel biomarker for the efficacy of anti-PD-1 that warrants further investigation in patients. Because our studies used SYN-115, a drug that has already undergone phase IIb testing in Parkinson disease, our findings have immediate translational relevance for patients with cancer.
Printing and Prototyping of Tissues and Scaffolds (2012)

New manufacturing technologies under the banner of rapid prototyping enable the fabrication of structures close in architecture to biological tissue. In their simplest form, these technologies allow the manufacture of scaffolds upon which cells can grow for later implantation into the body. A more exciting prospect is the printing and patterning in three dimensions of all the components that make up a tissue (cells and matrix materials) to generate structures analogous to tissues; this has been termed bioprinting. Such techniques have opened new areas of research in tissue engineering and regenerative medicine.
Comparative genetics in the grasses (1998)

Genetic mapping of wheat, maize, and rice and other grass species with common DNA probes has revealed remarkable conservation of gene content and gene order over the 60 million years of radiation of Poaceae. The linear organization of genes in some nine different genomes differing in basic chromosome number from 5 to 12 and nuclear DNA amount from 400 to 6,000 Mb, can be described in terms of only 25 “rice linkage blocks.” The extent to which this intergenomic colinearity is confounded at the micro level by gene duplication and micro-rearrangements is still an open question. Nevertheless, it is clear that the elucidation of the organization of the economically important grasses with larger genomes, such as maize (2 n = 10, 4,500 Mb DNA), will, to a greater or lesser extent, be predicted from sequence analysis of smaller genomes such as rice, with only 400 Mb, which in turn may be greatly aided by knowledge of the entire sequence of Arabidopsis , which may be available as soon as the turn of the century. Comparative genetics will provide the key to unlock the genomic secrets of crop plants with bigger genomes than Homo sapiens.
A fully mobile, GPS enabled, vehicle-to-vehicle measurement platform for characterization of the 5.9 GHz DSRC channel (2007)

To understand the characteristics of vehicle-to-vehicle channels, in this paper, we describe a mobile channel measurement platform operating at the 5.9 GHz designated dedicated short range communications (DSRC) frequency band. Our system uses programmable instrumentation for both the transmitter and receiver, enabling the use of a wide range of waveforms. Our system permits the generation and analysis of arbitrary waveforms with instantaneous bandwidth up to 40 MHz. Our system also has several key features which distinguish it from other similar systems. First, our RF measurement system is operating in the 5.9 GHz frequency band designated for DSRC. Second, we have taken the additional step of incorporating location-based information via GPS receivers. The GPS receiver provides far richer statistics to characterize the channel, which allows us to better understand the relationship between this highly mobile V2V channel and location information.
Direct structural observation of an acyl-enzyme intermediate in the hydrolysis of an ester substrate by elastase. (1994)

The method of X-ray crystallographic cryoenzymology has been used to determine the crystal structure of a kinetically significant species on the reaction pathway of a crystalline enzyme. The structure of a specific acyl-enzyme intermediate in the elastase-catalyzed hydrolysis of the N-carbobenzoxy-L-alanine p-nitrophenyl ester has been determined and refined against X-ray diffraction data at 2.3-A resolution. The difference Fourier electron density map clearly shows electron density for the trapped acyl-enzyme. The acyl-enzyme was formed at -26 degrees C and was stabilized at -55 degrees C during data collection, taking advantage of the glass transition in protein dynamics that occurs at around -50 degrees C.
含甲硫氨酸肽的色谱分离用于无凝胶蛋白质组分析：鉴定超过800个大肠杆菌蛋白质* s (2002)

一种新的无凝胶蛋白质组学技术用于鉴定5000万多个蛋白质Escherichia coli在单一分析中K12细胞。首先从总未被解锁的细胞裂解物获得肽混合物，并且仅通过质谱和数据库搜索分离和鉴定含甲硫氨酸的肽。分选程序基于对角线色谱的概念，但适于高度复杂的混合物。统计分析预测，我们已经确定了超过40％的表达蛋白质组，包括可溶性和膜结合的蛋白质。在高度丰富的蛋白质旁边，我们还检测到低拷贝数组件，如E. coli乳糖操纵器压缩机，说明了高动态范围。该方法比基于二维凝胶的方法更敏感的约100倍，并且是完全自动化的。然而，最强的点是肽分选化学的灵活性，其可以针对含有可修饰氨基酸的各类肽的定量蛋白质组学的技术靶向，例如磷酸肽，氨基末端肽等，添加新的尺寸未来的蛋白质组研究。
Decreased expression of bone morphogenetic protein (BMP) receptor type II correlates with insensitivity to BMP-6 in human renal cell carcinoma cells. (2003)

These results demonstrate that human RCC tissues frequently have decreased levels of expression of BMP-RII and that the human RCC cell lines 117 and 181 are resistant to the growth-inhibitory effect of BMP-6 because they have decreased levels of expression of BMP-RII.
ChemInform Abstract: Neuroimmunophilin Ligands as Novel Therapeutics for the Treatment of Degenerative Disorders of the Nervous System (1997)

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.
The Reactions of Mesitoyl Nitrate and Other Hindered Acyl Nitrates with Nucleophilic Reagents1 (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Reactions of Mesitoyl Nitrate and Other Hindered Acyl Nitrates with Nucleophilic Reagents1Jeremiah P. Freeman, William D. Emmons, and Robert M. RossCite this: J. Am. Chem. Soc. 1955, 77, 22, 6062–6064Publication Date (Print):November 1, 1955Publication History Published online1 May 2002Published inissue 1 November 1955https://pubs.acs.org/doi/10.1021/ja01627a084https://doi.org/10.1021/ja01627a084research-articleACS PublicationsRequest reuse permissionsArticle Views96Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
l -2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer (2014)

Here, we report elevations of the putative oncometabolite l-2HG in the most common subtype of kidney cancer and describe a novel mechanism for the regulation of DNA 5hmC levels. Our findings provide new insight into the metabolic basis for the epigenetic landscape of renal cancer.