gebhart/patrepeval huggingface dataset:
Cyclobenzaprinium chloride (2011)

In the title mol-ecular salt [systematic name: 3-(5H-dibenzo[a,d]cyclo-hepten-5-yl-idene)-N,N-dimethyl-propan-aminium chloride], C(20)H(22)N(+)·Cl(-), two cation-anion pairs make up the asymmetric unit. The dihedral angles between the mean planes of the two fused benzene rings of the cation are 49.5 (1) and 50.9 (1)°. The cystal packing is stabilized by N-H⋯Cl hydrogen bonds and weak C-H⋯Cl inter-actions.
Long-term Follow-up of the Safety of Delayed-Release Dimethyl Fumarate in RRMS: Interim Results from the ENDORSE Extension Study. (P7.235) (2015)

OBJECTIVE: To report safety outcomes from ENDORSE, investigating long-term effects of delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) in patients with relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: DMF demonstrated broad efficacy and an acceptable safety profile in the Phase 3 DEFINE/CONFIRM studies. ENDORSE is an 8-year extension of DEFINE/CONFIRM. DESIGN/METHODS: Patients randomized to DMF 240 mg twice (BID) or three times daily (TID) in DEFINE/CONFIRM continued on the same dosage in ENDORSE. Patients randomized to placebo (PBO; DEFINE/CONFIRM) or glatiramer acetate (GA; CONFIRM) were re-randomized 1:1 to DMF 240 mg BID or TID. Adverse events (AEs) were analyzed according to treatment received in the parent/extension study: BID/BID (n=501), TID/TID (n=501), PBO/BID (n=249), PBO/TID (n=248), GA/BID (n=118), and GA/TID (n=119). RESULTS: As of May 14, 2014, total follow-up in ENDORSE for all groups was 4,980.7 patient-years. Overall incidence of AEs was as follows: BID/BID, 91[percnt]; TID/TID, 92[percnt]; PBO/BID, 95[percnt]; PBO/TID, 93[percnt]; GA/BID, 88[percnt]; and GA/TID, 85[percnt]. Incidence of serious AEs was: BID/BID, 22[percnt]; TID/TID, 25[percnt]; PBO/BID, 24[percnt]; PBO/TID, 16[percnt]; GA/BID, 16[percnt]; and GA/TID, 19[percnt]. Incidence of AEs leading to discontinuation was 6-7[percnt] and 14-26[percnt] in patients continuing and new to DMF, respectively. Incidence of serious infections was ≤4[percnt] in all groups, with no confirmed opportunistic infections. There were no new findings in hematologic outcomes compared with DEFINE/CONFIRM. Hepatic AEs occurred in ≤3[percnt] of patients in any group; there was no evidence of increased risk of renal or urinary events. There were 27 malignancies in 26 patients (18 continuing treatment and eight new to DMF). There were five deaths, none of which was considered related to study drug. CONCLUSIONS: Sustained treatment with DMF continues to demonstrate an acceptable safety profile with no new or worsening safety signals in patients with RRMS. Study Supported by: Biogen Idec
Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms (1995)

Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.
Blind Identification of Source Cell-Phone Model (2008)

The various image-processing stages in a digital camera pipeline leave telltale footprints, which can be exploited as forensic signatures. These footprints consist of pixel defects, of unevenness of the responses in the charge-coupled device sensor, black current noise, and may originate from proprietary interpolation algorithms involved in color filter array. Various imaging device (camera, scanner, etc.) identification methods are based on the analysis of these artifacts. In this paper, we set to explore three sets of forensic features, namely binary similarity measures, image-quality measures, and higher order wavelet statistics in conjunction with SVM classifiers to identify the originating camera. We demonstrate that our camera model identification algorithm achieves more accurate identification, and that it can be made robust to a host of image manipulations. The algorithm has the potential to discriminate camera units within the same model.
Structure‐antinociceptive activity studies with neurotensin (1984)

The antinociceptive effects of synthetic neurotensin (NT), its fragments and analogues administered into the lateral cerebroventricle have been compared in the conscious mouse. Intracerebroventricular (i.c.v.) administration of NT produced a dose-dependent antinociceptive effect in the tail pressure test. The NT fragments and analogues, NT(8-13), NT(8-10), NT(9-13), NT(9-11), NT(8-11) NHEt and NT(9-11) NHEt were also effective antinociceptive peptides. The potency of NT(8-13) and the duration of its effects were found to be approximately equal to those of NT. The antinociceptive effects produced by NT, NT(8-13) and NT(9-13) were significantly reversed by the opioid antagonist naloxone but not by thyrotropin releasing hormone. It is concluded that NT(8-13) is required for the full expression of the antinociceptive effects of NT which may be mediated in part through the brain opioid system.
Regulation and Functional Expression of Cinnamate 4-Hydroxylase from Parsley (1999)

A previously isolated parsley (Petroselinum crispum) cDNA with high sequence similarity to cinnamate 4-hydroxylase (C4H) cDNAs from several plant sources was expressed in yeast (Saccharomyces cerevisiae) containing a plant NADPH:cytochrome P450 oxidoreductase and verified as encoding a functional C4H (CYP73A10). Low genomic complexity and the occurrence of a single type of cDNA suggest the existence of only one C4H gene in parsley. The encoded mRNA and protein, in contrast to those of a functionally related NADPH:cytochrome P450 oxidoreductase, were strictly coregulated with phenylalanine ammonia-lyase mRNA and protein, respectively, as demonstrated by coinduction under various conditions and colocalization in situ in cross-sections from several different parsley tissues. These results support the hypothesis that the genes encoding the core reactions of phenylpropanoid metabolism form a tight regulatory unit.
Joint SFM and detection cues for monocular 3D localization in road scenes (2015)

We present a system for fast and highly accurate 3D localization of objects like cars in autonomous driving applications, using a single camera. Our localization framework jointly uses information from complementary modalities such as structure from motion (SFM) and object detection to achieve high localization accuracy in both near and far fields. This is in contrast to prior works that rely purely on detector outputs, or motion segmentation based on sparse feature tracks. Rather than completely commit to tracklets generated by a 2D tracker, we make novel use of raw detection scores to allow our 3D bounding boxes to adapt to better quality 3D cues. To extract SFM cues, we demonstrate the advantages of dense tracking over sparse mechanisms in autonomous driving scenarios. In contrast to complex scene understanding, our formulation for 3D localization is efficient and can be regarded as an extension of sparse bundle adjustment to incorporate object detection cues. Experiments on the KITTI dataset show the efficacy of our cues, as well as the accuracy and robustness of our 3D object localization relative to ground truth and prior works.
Hypothalamic Deep Brain Stimulation Reduces Weight Gain in an Obesity-Animal Model (2012)

Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.
Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway (2012)

The presence of DNA in the cytoplasm of mammalian cells is a danger signal that triggers host immune responses such as the production of type I interferons. Cytosolic DNA induces interferons through the production of cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein STING. Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltransferase family. Overexpression of cGAS activated the transcription factor IRF3 and induced interferon-β in a STING-dependent manner. Knockdown of cGAS inhibited IRF3 activation and interferon-β induction by DNA transfection or DNA virus infection. cGAS bound to DNA in the cytoplasm and catalyzed cGAMP synthesis. These results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP.
Focusing of therapeutic ultrasound through a human skull: A numerical study (1998)

A numerical model was developed which can use digitized layer interfaces to calculate ultrasound wave absorption, diffraction, reflection, and refraction. This model was used to evaluate the feasibility of ultrasound therapy and surgery through a human skull. A digitized human skull profile was obtained from magnetic resonance (MR) images and used to calculate the ultrasound field in the brain of a volunteer from a spherically curved phased array. With no phase correction, the focus of the array was shifted and defocused. The phased array technique was used to correct focal shift, reduce side lobes, and enhance focal amplitude. The optimum source element width was estimated for each frequency to obtain a near optimium focus, and an appropriate frequency range for transskull ultrasound therapy and surgery was determined. Acoustic pressure amplitude on the skull surfaces was examined, and it was shown that the skull heating problem could be overcome. Despite high attenuation, complex interface shape, and nonuniform thickness of a human skull, a sharply focused transskull ultrasound field can be generated for noninvasive ultrasound therapy and surgery in the brain.
A Novel Monoclonal Antibody Against the Second Extracellular Loop of Occludin Disrupts Epithelial Cell Polarity (2007)

The tight junction (TJ) regulates epithelial cell polarity and paracellular permeability. In the present study, to investigate whether the second extracellular loop of occludin affects the localization of carcinoembryonic antigen (CEA) and CD26 expressed on apical membranes, and the fence function of the TJ, the human intestinal epithelial cell line T84 was treated with the monoclonal anti-occludin antibody (MAb) 1H8, corresponding to the second extracellular loop of occludin. In T84 cells treated with MAb 1H8, occludin disappeared, and CEA and CD26 were observed to diffuse from the apical membrane to the basolateral membrane. Furthermore, a decrease in the fence function of TJ was observed without changes in the TJ strands and barrier function. When T84 cells precultured in low calcium (Ca) medium were recultured in normal Ca medium in the presence of MAb 1H8, recruitment of occludin to the apical-most membranes and recovery in distribution of CEA and CD26 were markedly retarded compared with the control. These results suggested that MAb 1H8 against the second extracellular loop of occludin selectively affected formation of the apical/basolateral intramembrane diffusion barrier and that the second extracellular loop of occludin plays a crucial role in the maintenance of epithelial cell polarity by the TJ.
世界道德公民的养成——基于学术研究、学校实践和日常生活三个维度的考察 (2007)

全球化的生活背景意味着我们现在是世界公民。但我们是否已经做好准备并有能力成为有道德的世界公民呢？近年来，世界上不少国家对公民教育的强调已经危害到了道德教育。成为世界公民的必要条件是培养青少年的伦理感、道德习惯、价值观和理想。公民概念，尤其是世界公民的概念，道德性是其根源和前提条件；没有道德性，（世界）公民概念的论证将会非常无力，而且也难以落实。在关于提高道德技能和道德素养以便成为道德公民的德育研究中，有哪些是关键信息？学校能够提供什么帮助？在日常生活中我们又能做些什么？对这些问题的研究是以中、英两国的案例为基础进行的，但它会有所超越并扩展到全球范围。
The Role of Cytokines and Adhesion Molecules for Mobilization of Peripheral Blood Stem Cells (2000)

CD34(+) hematopoietic stem cells from peripheral blood are commonly used for autologous or allogeneic transplantation following high-dose therapy in malignant diseases. The introduction of hematopoietic growth factors such as G-CSF has greatly facilitated the mobilization of CD34(+) cells. The mechanism of stem cell mobilization is not yet clear. It seems to be a multistep process with a crosstalk between cytokines and adhesion molecules. In this review, the role of hematopoietic growth factors, chemokines, and adhesion molecules for mobilization and homing of CD34(+) cells is summarized. In addition, factors influencing the cytokine-induced mobilization in patients and healthy donors are described. The review closes with an overview of new classes of mobilizing drugs such as monoclonal antibodies, specific peptides, or antisense oligonucleotides targeting adhesion molecules.
A single peptide from the major outer membrane protein of Chlamydia trachomatis elicits T cell help for the production of antibodies to protective determinants (1991)

The protective immune response to infection with Chlamydia trachomatis is associated with antibody reactivity to serovar-specific determinants on the major outer membrane protein (MOMP). Because this immunity is T cell dependent, it is essential to define those Th cell determinants that promote natural boosting of the protective antibody response. The gene for MOMP of serovar B was separated into nine overlapping fragments that represent the five C and four V regions. These fragments were expressed as fusion peptides with GST and used to identify the regions of the MOMP that contain T cell determinants recognized in BALB/c mice. We identified peptides that elicit a T cell response to Chlamydia by immunizing mice with the fusion peptides and testing the proliferative response of T cells in vitro to intact organism. For analysis of determinants seen after infection, animals were inoculated with live organism and the T cell proliferative response to each fusion peptide was measured in vitro. In contrast to proliferative analysis in which several regions of the MOMP elicited T cell responses, functional analysis demonstrated that a single fusion peptide, containing V segment three, elicited T cell help in vivo for the production of high titered antisera, specific for protective determinants on the MOMP.
Affinity Maturation of Antibodies: Optimized Methods to Generate High-Quality ScFv Libraries and Isolate IgG Candidates by High-Throughput Screening (2012)

As a growing number of therapeutic antibodies are developed, robust methods to efficiently improve the affinity and/or specificity of antibody candidates are needed. Here we describe our powerful platform that combines scFv affinity maturation and IgG high-throughput screening. After creating diversity with our random mutagenesis technology (MutaGen™), the scFv libraries are fully cleaned using a fusion system introducing the beta-lactamase gene to select in-frame and stop codon free variants on the basis of ampicillin resistance. The high-quality scFv libraries thereby constructed are then selected on the target in vitro using phage display technology. Contrary to standard procedures, instead of producing a limited number of affinity matured scFv as IgG molecules, we developed a cloning system to directly transfer the entire pool of selected scFv into an IgG expression vector permitting rapid IgG small-scale production (96 wells) in mammalian cells. Our integrated process allows us to generate high-quality scFv libraries and test numerous IgG variants, increasing the chances to select the best therapeutic antibody candidate.
Enantioselective Synthesis of Unsaturated Cyclic Tertiary Ethers By Mo-Catalyzed Olefin Metathesis (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEnantioselective Synthesis of Unsaturated Cyclic Tertiary Ethers By Mo-Catalyzed Olefin MetathesisDustin R. Cefalo, Andrew F. Kiely, Margarita Wuchrer, Jennifer Y. Jamieson, Richard R. Schrock, and Amir H. HoveydaView Author Information Department of Chemistry, Merkert Chemistry Center Boston College, Chestnut Hill, Massachusetts 02467 Department of Chemistry Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Cite this: J. Am. Chem. Soc. 2001, 123, 13, 3139–3140Publication Date (Web):March 13, 2001Publication History Received10 November 2000Published online13 March 2001Published inissue 1 April 2001https://doi.org/10.1021/ja0039177Copyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1752Altmetric-Citations119LEARN 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 InReddit Read OnlinePDF (48 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Catalysts,Enantioselective synthesis,Hydrocarbons,Metathesis,Stereoselectivity Get e-Alerts
Near-infrared Theranostic Photoimmunotherapy (PIT): Repeated Exposure of Light Enhances the Effect of Immunoconjugate (2012)

Armed antibody-based targeted molecular therapies offer the possibility of effective tumor control with a minimum of side effects. Photoimmunotherapy (PIT) employs a monoclonal antibody-phototoxic phthalocyanine dye, IR700 conjugate, that is activated by focal near-infrared (NIR) light irradiation after antibody binding to the targeted tumor cell surface leading to rapid necrotic cell death. Therapy by single NIR light irradiation was effective without significant side effects; however, recurrences were seen in most treated mice probably because of inhomogeneous distribution of panitumumab-IR700 immunoconjugate in the tumor, leading to ineffective PIT. We describe here an optimized regimen of effective PIT method for the same HER1-overexpressing tumor model (A431) with fractionated administration of panitumumab-IR700 conjugate followed by systematic repeated NIR light irradiation to the tumor based on timing of antibody redistribution into the remnant tumor under the guidance of IR700 fluorescence signal. Eighty percent of the A431 tumors were eradicated with repeated PIT without apparent side effects and survived tumor-free for more than 120 days even after stopping therapy at day 30. Therapeutic effects were monitored using IR700 fluorescent signal. PIT is a promising highly selective and clinically feasible theranostic method for treatment of mAb-binding tumors with minimal off-target effects.
Adoption of social media in the Australian and New Zealand wine industries (2015)

Purpose - This paper examines the adoption of social media technologies across the Australasian wine industries, how wineries are using social media, and the issues that limit adoption. Design/methodology/approach - Data for this exploratory study was obtained from a survey of wineries across Australia and New Zealand. Findings - The level of social media adoption by wineries is the same across both nations (65%), with Facebook and Twitter being the most adopted platforms. Wineries are predominantly utilising social media to communicate and provide event information to existing customers, as well as to advertise and gain new customers. Originality/value – This study adds to current knowledge regarding the use of social media in the wine industry, including a comparison of t he use across Australasian wineries to wineries in other nations. It also identifies the main barriers affecting the use of social media by wineries; time constraints, effectiveness, and lack of knowledge.
Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine (2007)

It has recently been suggested that neurogenesis in the dentate gyrus is decreased in schizophrenia and this phenomenon may contribute to the pathogenesis of the disorder. Since repeated administration of psychostimulants such as phencyclidine (PCP), MK-801, and methamphetamine (METH) induces schizophrenia-like behavioral changes in animals, we investigated whether repeated administration of these psychostimulants affects neurogenesis in the dentate gyrus of mice. Newborn cells were labeled by bromodeoxyuridine (BrdU) and detected by immunohistochemistry. Repeated administration of PCP and MK-801, but not METH, resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus. PCP-induced decrease in the number of BrdU-labeled cells was negated by co-administration of clozapine, but not haloperidol, although repeated antipsychotics treatment by themselves had no effect. Furthermore, co-administration of D-serine and glycine, but not L-serine, inhibited the PCP-induced decrease in the number of BrdU-labeled cells. These results suggest that chronic dysfunction of NMDA receptors causes a decrease in neurogenesis in the dentate gyrus.