gebhart/patrepeval huggingface dataset:
Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson’s Disease (2017)

Parkinson's disease (PD) is a chronic and progressive disorder characterized neuropathologically by loss of dopamine neurons in the substantia nigra, intracellular proteinaceous inclusions, reduction of dopaminergic terminals in the striatum, and increased neuroinflammatory cells. The consequent reduction of dopamine in the basal ganglia results in the classical parkinsonian motor phenotype. A growing body of evidence suggest that neuroinflammation mediated by microglia, the resident macrophage-like immune cells in the brain, play a contributory role in PD pathogenesis. Microglia participate in both physiological and pathological conditions. In the former, microglia restore the integrity of the central nervous system and, in the latter, they promote disease progression. Microglia acquire different activation states to modulate these cellular functions. Upon activation to the M1 phenotype, microglia elaborate pro-inflammatory cytokines and neurotoxic molecules promoting inflammation and cytotoxic responses. In contrast, when adopting the M2 phenotype microglia secrete anti-inflammatory gene products and trophic factors that promote repair, regeneration, and restore homeostasis. Relatively little is known about the different microglial activation states in PD and a better understanding is essential for developing putative neuroprotective agents. Targeting microglial activation states by suppressing their deleterious pro-inflammatory neurotoxicity and/or simultaneously enhancing their beneficial anti-inflammatory protective functions appear as a valid therapeutic approach for PD treatment. In this review, we summarize microglial functions and, their dual neurotoxic and neuroprotective role in PD. We also review molecules that modulate microglial activation states as a therapeutic option for PD treatment.
MICROFAB~CATE~ CYCLICAL ELECTRICAL FIELD FLOW' FRACTIONATION (2003)

A cyclical electrical field flow fractionation (CEFFF) microsystem is demonstrated for the first time in this paper. Retention of polystyrene nanoparticles is accomplished and the effect of varying parameters such frequency is explored. This new sub-micron size particle separation technique can be used to separate cellular components, viruses and bacteria, proteins and DNA, colloids and emulsions; and thus, can be used as a lab-on-a-chip sample preparation method. Due to handling of smaller sample volumes in the system, the separation is faster than in comparable macrosystem.
Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions (2017)

Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction.
创新还是妥协？——路虎Range-e (2011)

很难说这是一次创新，因为混合动力早已不是汽车业界的新鲜词，但的的确确是路虎的第一次，打心眼里，我愿意接受这是一次妥协，是路虎向大环境低头的表现，不过幸运的是路虎的混合动力车型，其性能还是值得我们期待。
Peptides and Peptide Hormones for Molecular Imaging and Disease Diagnosis (2010)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTPeptides and Peptide Hormones for Molecular Imaging and Disease DiagnosisSeulki Lee, Jin Xie, and Xiaoyuan Chen*View Author Information Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, Maryland 20892-2281* To whom correspondence should be addressed. Phone: (301) 451-4246. Fax: (301) 480-1613. E-mail: [email protected]Cite this: Chem. Rev. 2010, 110, 5, 3087–3111Publication Date (Web):March 15, 2010Publication History Received4 November 2009Published online15 March 2010Published inissue 12 May 2010https://pubs.acs.org/doi/10.1021/cr900361phttps://doi.org/10.1021/cr900361preview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views8694Altmetric-Citations268LEARN 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 SUBJECTS:Biological imaging,Peptides and proteins,Probes,Receptors,Tumors Get e-Alerts
Propagation losses of silicon nitride waveguides in the near-infrared range (2005)

Si 3 N 4 ∕ SiO 2 waveguides have been fabricated by low pressure chemical vapor deposition within a complementary metal–oxide–semiconductor fabrication pilot line. Propagation losses for different waveguide geometries (channel and rib loaded) have been measured in the near infrared as a function of polarization, waveguide width, and light wavelength. A maximum thickness of single Si3N4 of 250 nm is allowed by the large stress between Si3N4 and SiO2. This small thickness turns into significant propagation losses at 1544 nm of about 4.5dB∕cm because of the poor optical mode confinement factor. Strain release and control is possible by using multilayer waveguides by alternating Si3N4 and SiO2 layers. In this way, propagation losses of about 1.5dB∕cm have been demonstrated thanks to an improved optical mode confinement factor and the good quality of the interfaces in the waveguide.
Development of a simple and rapid extraction method of glucosinolates from radish roots (2011)

A simple and rapid method for the extraction of crude glucosinolates from powder of freeze-dried radish roots was developed using a common solvent, methanol/water = 80: 20 (v/v) at room temperature. Hot methanol is not required for the extraction procedure of this new method. Both 4-methylthio-3-butenyl glucosinolate, which is a major glucosinolate in radish root, and total glucosinolates of Japanese radish cv. ‘Karami 199’ were quantified using HPLC. The amounts of glucosinolate extracted using this new method were 4–6% higher than those obtained using the conventional method with hot methanol. To compare the new method with the conventional method, the amounts of glucosinolate extracted from roots of eight cultivars in Japanese radish and five breeding lines were estimated. A high positive correlation was found between them. This simple and rapid method 1) obviates hot methanol for glucosinolate extraction and 2) requires only one-third of the extraction time of the conventional method, enabling glucosinolate extraction from about 150 samples by one person in a single day.
Huffman v. Western Nuclear, Inc.: An Examination of the Domestic Uranium Industry's Recent Defeat (1989)

elements of radium and vanadium, which are used, respectively, in medicine and metallurgy.
Four-leaf clover qRT-PCR: A convenient method for selective quantification of mature tRNA (2015)

Transfer RNAs (tRNAs) play a central role in translation and also recently appear to have a variety of other functions in biological processes beyond translation. Here we report the development of Four-Leaf clover qRT-PCR (FL-PCR), a convenient PCR-based method, which can specifically quantify individual mature tRNA species. In FL-PCR, T4 RNA ligase 2 specifically ligates a stem-loop adapter to mature tRNAs but not to precursor tRNAs or tRNA fragments. Subsequent TaqMan qRT-PCR amplifies only unmodified regions of the tRNA-adapter ligation products; therefore, FL-PCR quantification is not influenced by tRNA post-transcriptional modifications. FL-PCR has broad applicability for the quantification of various tRNAs in different cell types, and thus provides a much-needed simple method for analyzing tRNA abundance and heterogeneity.
OCT-measured plaque free wall angle is indicative for plaque burden: overcoming the main limitation of OCT? (2016)

The aim of this study was to investigate the relationship between the plaque free wall (PFW) measured by optical coherence tomography (OCT) and the plaque burden (PB) measured by intravascular ultrasound (IVUS). We hypothesize that measurement of the PFW could help to estimate the PB, thereby overcoming the limited ability of OCT to visualize the external elastic membrane in the presence of plaque. This could enable selection of the optimal stent-landing zone by OCT, which is traditionally defined by IVUS as a region with a PB < 40 %. PB (IVUS) and PFW angle (OCT and IVUS) were measured in 18 matched IVUS and OCT pullbacks acquired in the same coronary artery. We determined the relationship between OCT measured PFW (PFWOCT) and IVUS PB (PBIVUS) by non-linear regression analysis. An ROC-curve analysis was used to determine the optimal cut-off value of PFW angle for the detection of PB < 40 %. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. There is a significant correlation between PFWOCT and PBIVUS (r(2) = 0.59). The optimal cut-off value of the PFWOCT for the prediction of a PBIVUS < 40 % is ≥220° with a PPV of 78 % and an NPV of 84 %. This study shows that PFWOCT can be considered as a surrogate marker for PBIVUS, which is currently a common criterion to select an optimal stent-landing zone.
Lipopolysaccharide synergizes with tumour necrosis factor-alpha in cytotoxicity assays. (1992)

Lipopolysaccharide (LPS) from Escherichia coli was found to synergize with human recombinant tumour necrosis factor-alpha (TNF-alpha) in the lysis of L929 and WEHI 164 (clone 13) murine fibroblasts, two cell lines classically used in TNF-alpha bioassays. The effect was noted with TNF-alpha at low (sublytic or lightly lytic) concentrations and was significant for LPS concentrations in the ng range. The LPS effect could be inhibited by polymyxin B, and was not observed when the TNF-alpha assay was performed in the absence of actinomycin D. Enhancement of TNF-alpha lysis by LPS occurred in several assays for determining TNF-alpha, including MTT cleavage, crystal violet staining and lactate dehydrogenase release. Synergism was obtained only when LPS and TNF-alpha were added to cells simultaneously, but not when applied in sequence. The reported synergism may be relevant for TNF-alpha determinations by bioassay, and for the understanding of pathophysiology of Gram-negative sepsis.
Pharmacological evidence for CGRP uptake into perivascular capsaicin sensitive nerve terminals (2001)

Specific mechanisms, providing reuptake of cathecholamine and amino acid neurotransmitters (e.g. serotonin and glutamate) into cells of the central nervous system are well known, whereas neuronal uptake of neuropeptide transmitters have not previously been reported. In the present study we present evidence for uptake of the 37 amino acid neuropeptide, calcitonin gene-related peptide (CGRP) into perivascular terminals of capsaicin sensitive nerve fibres, innervating the guinea-pig basilar artery. Release of CGRP from perivascular nerve terminals was obtained by capsaicin-induced vanilloid receptor-stimulation and detected as CGRP receptor-mediated dilation of isolated segments of the guinea-pig basilar artery. Following three repeated capsaicin challenges, CGRP-depleted segments were incubated with CGRP. This caused significant reappearance of capsaicin-induced vasodilatory responses. These responses were dependent on duration and concentration of the preceding CGRP incubation and were inhibited by the CGRP receptor antagonist, CGRP(8 - 37). The CGRP-re-depletion was significantly reduced when CGRP(8 - 37) was present during the preceding CGRP incubation. Thus, presynaptic CGRP receptors are likely to be involved in neuronal CGRP uptake. Incubating the artery segments with (125)I-CGRP allowed subsequent detection of capsaicin-induced (125)I-release. Immunohistochemical experiments showed that only terminal CGRP is subject to capsaicin-induced depletion in vitro, whereas CGRP-immunoreactivity endures in the nerve fibres.
Complement-Fixing Elicited Antibodies Are a Major Component in the Pathogenesis of Xenograft Rejection (1998)

Hamster to rat cardiac xenografts undergo delayed rejection as compared with the hyperacute rejection of discordant xenografts. Elicited xenoreactive Abs (EXA) are thought to initiate hamster to rat cardiac xenograft rejection. In this study, we demonstrate that following transplantation of a hamster heart, rats generated high levels of EXA. Adoptive transfer into naive recipients of purified IgM, IgG2b, or IgG2c, but not IgG1 or IgG2a EXA, induced xenograft rejection in a complement-dependent manner. Ability of EXA to cause rejection correlated with complement activation, platelet aggregation, and P-selectin expression in the xenograft endothelium. Cyclosporin A (CyA) administration, after transplantation, totally suppressed IgG1, IgG2a, IgG2b, and IgG2c EXA, and inhibited IgM EXA production, but failed to overcome rejection. Administration of cobra venom factor (CVF), 1 day before and at the time of transplantation, resulted in complement inhibition during 3 days after transplantation, which failed to overcome rejection. Combination of CyA and CVF, which we have previously shown to overcome rejection, resulted in suppression of IgG EXA production and in the return of IgM XNA to preimmunization serum levels, 3 to 7 days after xenotransplantation, while complement remained inhibited. Thus, under CyA/CVF treatment, complement activation by hamster cells was suppressed following xenotransplantation, and presumably for this reason xenograft rejection did not occur. In conclusion, our data demonstrate that EXA play a pivotal role in the pathogenesis of xenograft rejection and that CyA and CVF suppress xenograft rejection by preventing exposure of xenograft endothelial cells to complement activation by EXA.
Antigenic Analysis of the Major Outer Membrane Protein of Chlamydia spp (1982)

The major outer membrane proteins (MOMPs) of several Chlamydia trachomatis serotypes (B, D, G, H, and L2) and of the C. psittaci meningopneumonitis strain were purified by preparatory sodium dodecyl sulfate-(SDS)-polyacrylamide gel electrophoresis. The isolated SDS-polypeptide complexes, which varied in their apparent subunit molecular weights, were used as immunogens to raise hyperimmune rabbit antisera. The specificities of these antisera were determined both by rocket immunoelectrophoresis with the soluble SDS-polypeptide complex as antigen and by micro-immunofluorescence with whole organisms. By rocket immunoelectrophoresis, each of the soluble C. trachomatis MOMPs was immunologically related; however, no immunological cross-reactions occurred with the C. psittaci meningopneumonitis polypeptide, indicating that the MOMPs are antigenically distinct among members of these two chlamydial species. The same antisera were highly reactive with intact organisms by micro-immunfluorescence, demonstrating that at least some of the antibodies raised with SDS-polypeptide complexes reacted with native antigenic sites of these surface proteins. By micro-immunofluorescence, anti-MOMP sera remained species specific; but, unlike the results observed by rocket immunoelectrophoresis, distinct differences in the reactivity and specificity of these antisera were observed among C. trachomatis serotypes. C. trachomatis isolates were separated into two distinct serogroups on the basis of their reactivity with anti-MOMP sera. B complex organisms (B, Ba, D, E, F, G, K, L1, L2, and L3) all reacted strongly with anti-MOMP sera of the B, D, G, and L2 serotypes. In contrast, these same antisera were poorly reactive with the C complex serotypes A, C, H, I, and J. Anti-H MOMP serum was the most serospecific, since high-antibody titers were found only against the homologous H serotype organism. These findings indicate that MOMPs of different strains of C. trachomatis are antigenically complex and that antigenic heterogeneity exists among the surface-exposed portions of the protein.
Protein Trafficking in Plant Cells (1987)

The cells of higher plants contain distinct subcellular compartments (organelles) that perform specialized functions such as photosynthesis, carbohydrate and lipid metabolism, and so forth. The majority of the protein constituents of plant organelles are formed as cytosolic precursors with N-terminal extensions that direct transport across one or more membrane bilayers in a post- or co-translational fashion. Since the majority of proteins in plant cells are products of nuclear gene expression, there must be precise sorting mechanisms in the cytoplasm that direct proteins to their correct cellular locations. Based on recent studies of protein targeting to chloroplasts and vacuoles, the details of these intracellular sorting mechanisms are becoming clear. The ability to direct proteins to specific compartments within cells provides new opportunities for improvement of plants by genetic manipulation.
Dosage requirements of Ultrabithorax and bithoraxoid in the determination of segment identity in Drosophila melanogaster. (1990)

The wild-type Ultrabithorax (Ubx) and bithoraxoid (bxd) functions are primarily responsible for establishing the identity of parasegment 6 (PS6) in the Drosophila embryo and thus the identity of the posterior compartment of the third thoracic segment (pT3) and the anterior compartment of the first abdominal segment (aA1) in the adult. The experiments described were designed to test the ability of an increased dosage of Ubx+ and bxd+ to affect the transformation of PS5 toward PS6. The results are consistent with the ideas that (1) multiple copies of Ubx+ and bxd+ cause some cells within PS5 to take on the characteristics of PS6 cells but do not cause an overall parasegmental transformation of PS5 toward PS6, (2) cellular identity depends not only on the activity of Ubx+ but on its concentration as well, and (3) that an interaction between Ubx+ and the wild-type Antennapedia (Antp) gene establishes segmental identity in pT2. In the first instar larvae carrying eight copies of Ubx+ and bxd+ the fine hairs of the T3 setal belt are transformed toward the hook-like structures of the A1 setal belt. Other structures within this segment are unaffected. In the adult, the haltere is reduced in size. The transformation of pT2 cells (wing) toward pT3 cells (haltere) is seen in adults carrying eight doses of wild type Ubx and bxd by decreasing the amount of the bithorax complex (BX-C) regulator Polycomb (Pc). However, the transformation of the T3 setal belt is not enhanced in the larvae of these animals. The interaction between the genes of the Antennapedia complex (ANT-C) and the Ubx+ and bxd+ functions in pT2 is dosage sensitive only when the animals carry one copy of Pc. In these animals, the transformation of wing toward haltere is significantly enhanced.
Peroxisome proliferators as inducers and substrates of UDP‐glucuronosyltransferases (1993)

Peroxisome proliferators, despite their chemically unrelated structures, share the common property of being able to stimulate the glucuronidation of bilirubin in rodents and, probably, also in man. The aryloxycarboxylic acids (clofibric acid, fenofibrate, bezafibrate, ciprofibrate), tiadenol and probucol, all of which have hypolipidemic properties, as well as the fatty acid-like perfluorodecanoic acid all enhanced the expression of the UDP-glucuronosyltransferase (UGT) form involved in the conjugation of the pigment. This induction is manifested by an increase in the mRNA species encoding the protein with a subsequent increase in the neosynthesis of the corresponding protein in the endoplasmic reticulum. The induction process is concomitant with that of cytochrome P-450-IVA1 and cytosolic epoxide hydrolase, which, like bilirubin UGT, are mainly involved in the metabolism of endogenous substrates. With a series of carboxylic acids related to clofibric acid, it was possible to demonstrate that induction was mediated via specific interactions based on the physicochemical properties of the inducers. Until now, the molecular basis of induction of bilirubin UGT is not known. The peroxisome poliferators that possess a carboxyl group are good substrates of UGT, especially in man. The acylglucuronides formed are known for their instability and reactivity which could contribute to the toxicity encountered in some patients treated with the drugs. There is convincing evidence that UGT bilirubin does not catalyze the glucuronidation of these substances even if the two types of substrate form acylglucuronides.
Sprinter Mod III: A Model for the Analysis of New Frequently Purchased Consumer Products (1970)

This paper presents a model-based information system designed to analyze test-market results, to assist decision-making for a new frequently purchased consumer product, and to serve as an adaptive control mechanism during national introduction. The model, called SPRINTER, is based on the behavioral process of the diffusion of innovation and can be used normatively in an interactive search mode to find the best marketing strategy for a new product. The input is obtained from test-market data analyzed by statistics and combined with subjective judgments. A Go, On, or No decision is made on the basis of the estimated profit and risk produced by the best marketing strategy. During national introduction the model serves as a “problem-finding” mechanism. It uses early national sales and micro-level behavioral data to diagnose problems in the introduction. It also can be used to search for solutions to these problems as they are recognized. Finally, an application of this model to a real product is reported, this application using an on-line computer program that allows convenient man-system communication.