gebhart/patrepeval huggingface dataset:
Brain-Derived Neurotrophic Factor Regulates the Onset and Severity of Motor Dysfunction Associated with Enkephalinergic Neuronal Degeneration in Huntington's Disease (2004)

The mechanism that controls the selective vulnerability of striatal neurons in Huntington's disease is unclear. Brain-derived neurotrophic factor (BDNF) protects striatal neurons and is regulated by Huntingtin through the interaction with the neuron-restrictive silencer factor. Here, we demonstrate that the downregulation of BDNF by mutant Huntingtin depends on the length and levels of expression of the CAG repeats in cell cultures. To analyze the functional effects of these changes in BDNF in Huntington's disease, we disrupted the expression of bdnf in a transgenic mouse model by cross-mating bdnf(+/ -) mice with R6/1 mice. Thus, we compared transgenic mice for mutant Huntingtin with different levels of BDNF. Using this double mutant mouse line, we show that the deficit of endogenous BDNF modulates the pathology of Huntington's disease. The decreased levels of this neurotrophin advance the onset of motor dysfunctions and produce more severe uncoordinated movements. This behavioral pathology correlates with the loss of striatal dopamine and cAMP-regulated phosphoprotein-32-positive projection neurons. In particular, the insufficient levels of BDNF cause specific degeneration of the enkephalinergic striatal projection neurons, which are the most affected cells in Huntington's disease. This neuronal dysfunction can specifically be restored by administration of exogenous BDNF. Therefore, the decrease in BDNF levels plays a key role in the specific pathology observed in Huntington's disease by inducing dysfunction of striatal enkephalinergic neurons that produce severe motor dysfunctions. Hence, administration of exogenous BDNF may delay or stop illness progression.
25Gb/s 1V-driving CMOS ring modulator with integrated thermal tuning (2011)

We report a high-speed ring modulator that fits many of the ideal qualities for optical interconnect in future exascale supercomputers. The device was fabricated in a 130 nm SOI CMOS process, with 7.5 μm ring radius. Its high-speed section, employing PN junction that works at carrier-depletion mode, enables 25 Gb/s modulation and an extinction ratio >5 dB with only 1V peak-to-peak driving. Its thermal tuning section allows the device to work in broad wavelength range, with a tuning efficiency of 0.19 nm/mW. Based on microwave characterization and circuit modeling, the modulation energy is estimated ~7 fJ/bit. The whole device fits in a compact 400 μm2 footprint.
Potential ganglioside antigens associated with human gliomas (1986)

Gangliosides in human gliomas were investigated and found to have an altered composition and concentration as compared to normal grey and white matter of brain. The major gangliosides GM1, GD1a, and GT1b were markedly reduced in the tumour tissue and in contrast there was an increase of gangliosides GM3 and GD3, which often appeared as the dominating ones. Moreover, the tumours contained gangliosides, both mono- and oligosialylated, which could not be detected in the normal brain. The concentration of gangliosides, 0.7 +/- 0.4 mumol sialic acid/g, was significantly lower as compared to normal brain grey (p less than 0.001) and white matter (p less than 0.01), which contained 3.5 +/- 0.3 and 1.2 +/- 0.3 mumol sialic acid/g respectively. The tumour tissue concentration of phospholipids was 14 +/- 8 and of cholesterol 19 +/- 12 mumol/g. The appearance in glioma tissue of gangliosides that are not found in normal brain tissue suggests that these are tumour associated and might serve as surface antigens detectable by specific monoclonal antibodies.
Regulation of CHK2 by DNA-dependent Protein Kinase (2005)

Chk2 is a critical mediator of diverse cellular responses to DNA damage. Activation of Chk2 by DNA damage requires phosphorylation at sites including Thr68. In earlier work, we found that an activity present in rabbit reticulocyte lysates phosphorylates and activates Chk2. We now find that hypophosphorylated Chk2 can be phosphorylated at Thr68 by various subcellular fractions of HEK293 cells. This activity is sensitive to the phosphatidylinositol 3'-kinase-like kinase inhibitor wortmannin, but not to caffeine. DNA enhances the Chk2 phosphorylation by cellular fractions in vitro. The wortmannin-sensitive Chk2 kinase activity is present in fractions from ATM-deficient cells. In contrast, Chk2 was not efficiently phosphorylated at Thr68 in vitro by fractions from cells with a defective DNA-dependent protein kinase (DNA-PK) catalytic subunit. Chk2 is phosphorylated by purified DNA-PK in vitro. Endogenous Chk2 coimmunoprecipitates Ku70 and Ku80. In a series of matched cell lines having and lacking functional DNA-PK, Chk2 activation by exposure of cells to ionizing radiation, or to camptothecin was consistently diminished in the absence of DNA-PK. Down-regulation of DNA-PK(cs) by either siRNA or a chemical inhibitor attenuated radiation-induced Chk2 phosphorylation. Ionizing radiation-induced Chk2 phosphorylation was wortmannin-sensitive in ATM-defective cells with depleted ATR. These results suggest that DNA-PK augments ATM and ATR in activation of Chk2 by DNA damage.
Rapid Development of Piperidine Carboxamides as Potent and Selective Anaplastic Lymphoma Kinase Inhibitors (2012)

Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC(50) = 0.174 μM) during high throughput screening, with selectivity over the related kinase insulin-like growth factor-1 (IGF1R). The X-ray cocrystal structure of 1 with the ALK kinase domain revealed an unusual DFG-shifted conformation, allowing access to an extended hydrophobic pocket. Structure-activity relationship (SAR) studies were focused on the rapid parallel optimization of both the right- and left-hand side of the molecule, culminating in molecules with improved potency and selectivity over IGF1R.
Ablation of the Complementarity-Determining Region H3 Apex of the Anti-HIV-1 Broadly Neutralizing Antibody 2F5 Abrogates Neutralizing Capacity without Affecting Core Epitope Binding (2010)

The identification and characterization of broadly neutralizing antibodies (bnAbs) against HIV-1 has formed a major research focus, with the ultimate goal to help in the design of an effective AIDS vaccine. One of these bnAbs, 2F5, has been extensively characterized, and residues at the apex of its unusually long complementarity-determining region (CDR) H3 loop have been shown to be crucial for neutralization. Structural studies, however, have revealed that the (100)TLFGVPI(100F) apex residues of the CDR H3 loop do not interact directly with residues of its core gp41 epitope. In an attempt to gain better insight into the functional role of this element, we have recombinantly expressed native 2F5 Fab and two mutants in which either the apical Phe100B(H) residue was changed to an alanine or the CDR H3 residues (100)TLFGVPI(100F) were replaced by a Ser-Gly dipeptide linker. Isothermal titration calorimetry (ITC) and competitive-binding enzyme-linked immunosorbent assays (ELISAs) rendered strikingly similar affinity constants (K(d) [dissociation constant] of approximately 20 nM) for linear peptide epitope binding by 2F5 Fabs, independent of the presence or absence of the apex residues. Ablation of the CDR H3 apex residues, however, abolished the cell-cell fusion inhibition and pseudovirus neutralization capacities of 2F5 Fab. We report competitive ELISA data that suggest a role of 2F5 CDR H3 apex residues in mediating weak hydrophobic interactions with residues located at the C terminus of the gp41 membrane proximal external region and/or membrane components in the context of core epitope binding. The present data therefore imply an extended 2F5 paratope that includes weak secondary interactions that are crucial for neutralization of Env-mediated fusion.
Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. (1989)

To determine the effects of immunomodulatory agents upon HIV replication in macrophages, cultured monocyte-derived macrophages were treated with various substances and then infected with a macrophage-tropic strain of HIV-1. Pretreatment with rIFN-alpha, IFN-beta, and IFN-gamma, or bacterial LPS prevented viral replication in macrophages. In treated cultures, little or no infectious HIV or p24 core antigen was released into the supernatant, no virions were seen by electron microscopy, no viral RNA or DNA was detectable in the cell lysates, and no cytopathology (as determined by multinucleated giant cell formation) occurred. In contrast, pretreatment with a wide dose range of recombinant IL-1 beta, IL-2, IL-4, IL-6, M-CSF, TNF, or lymphotoxin failed to protect macrophages from productive infection by HIV. A consistent effect of granulocyte/macrophage-CSF on HIV replication in macrophages was not observed. In dose response studies, pretreatment with approximately 100 U/ml of IFN-alpha, approximately 10 U/ml of IFN-beta, or approximately 100 U/ml of IFN-gamma was sufficient to prevent virion release maximally and to prevent cytopathology completely. In kinetic studies, IFN-alpha, IFN-gamma, or LPS were added to the macrophage cultures either before or after infection with HIV. Even when added 3 d after infection with a multiplicity of 1 50% tissue-culture infectious dose per cell, all three treatments markedly reduced virion release, suggesting that these agents act at a point in the viral life cycle beyond the early events of virus binding, penetration, and uncoating. These data indicate that HIV replication in previously uninfected macrophages may be regulated by an inducible host cell mechanism. These findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for interferons in the therapy of HIV infection.
Mechanistic Switch in Dual Gold Catalysis of Diynes: C(sp3)–H Activation through Bifurcation—Vinylidene versus Carbene Pathways (2013)

The other side of the mountain: Changing the framework of diyne systems opens up new cyclization modes for dual gold catalysis. Instead of a 5-endo cyclization and gold vinylidenes a 6-endo cyclization gives rise to gold-stabilized carbenes as key intermediates for selective C-H insertions.
Spectrally Beam-Combined Fiber Lasers for High-Average-Power Applications (2007)

Spectrally beam-combined (SBC) laser systems, wherein multiple laser outputs are spectrally multiplexed into a single high-quality beam, are rapidly advancing the power scaling frontier for high-average-power beam-combined fiber lasers with near-perfect beam quality. We describe two- and three-channel SBC fiber lasers featuring 93% power-combining efficiency, near-diffraction-limited beam quality, average output powers in excess of 500 W, and excellent prospects for additional power scaling. To our knowledge, this level of optical performance represents the highest combination of beam quality and average power obtained so far for a beam-combined fiber laser system.
The emerging role of electronic marketplaces on the Internet (1998)

Markets (electronic or otherwise) have three main functions, summarized in Table
NUTRITIONAL AND HORMONAL REGULATION OF ENZYMES IN FAT SYNTHESIS: Studies of Fatty Acid Synthase and Mitochondrial Glycerol-3-Phosphate Acyltransferase Gene Transcription (1998)

The activities of critical enzymes in fatty acid and triacylglycerol biosynthesis are tightly controlled by different nutritional, hormonal, and developmental conditions. Feeding previously fasted animals high-carbohydrate, low-fat diets causes a dramatic induction of enzymes-such as fatty acid synthase (FAS) and mitochondrial glycerol-3-phosphate acyltransferase (GPAT)-involved in fatty acid and triacylglycerol synthesis. During fasting and refeeding, transcription of these two enzymes is coordinately regulated by nutrients and hormones, such as glucose, insulin, glucagon, glucocorticoids, and thyroid hormone. Insulin stimulates transcription of the FAS and mitochondrial GPAT genes, and glucagon antagonizes the insulin effect through the cis-acting elements within the promoters and their bound trans-acting factors. This review discusses advances made in the understanding of the transcriptional regulation of FAS and mitochondrial GPAT genes, with emphasis on elucidation of the mechanisms by which multiple nutrients and hormones achieve their effects.
Single-Chain TNF, a TNF Derivative with Enhanced Stability and Antitumoral Activity (2008)

The inflammatory and proapoptotic cytokine TNF possesses a compelling potential as an antitumoral therapeutic agent. Possible target cells include the malignant cells themselves, the tumor vasculature, or the immune system. As the clinical use of TNF is limited by systemic toxicity, targeting strategies using TNF-based fusion proteins are currently used. A major obstacle, however, is that homotrimeric TNF ligands are prone to activity loss due to dissociation into their monomers. In this study, we report the construction of single-chain TNF molecule, a TNF mutant consisting of three TNF monomers fused by short peptide linkers. In comparison to wild-type TNF, single-chain TNF was found to possess increased stability in vitro and in vivo, displayed reduced systemic toxicity yet slightly enhanced antitumoral activity in mouse models. Creation of single-chain variants is a new approach for improvement of functional activity of therapeutics based on TNF family ligands.
Raman microscopy analysis of phase transformation mechanisms in vanadium dioxide (2002)

Raman microscopy is used to study the evolution of vibrational modes of vanadium dioxide single crystals and thin films in the vicinity of the phase transition. The results support the electron correlation model of phase transformation.
Surface stereo with soft segmentation (2010)

This paper proposes a new stereo model which encodes the simple assumption that the scene is composed of a few, smooth surfaces. A key feature of our model is the surface-based representation, where each pixel is assigned to a 3D surface (planes or B-splines). This representation enables several important contributions: Firstly, we formulate a higher-order prior which states that pixels of similar appearance are likely to belong to the same 3D surface. This enables to incorporate the very popular color segmentation constraint in a soft and principled way. Secondly, we use a global MDL prior to penalize the number of surfaces. Thirdly, we are able to incorporate, in a simple way, a prior which favors low curvature surfaces. Fourthly, we improve the asymmetric occlusion model by disallowing pixels of the same surface to occlude each other. Finally, we use the known fusion move approach which enables a powerful optimization of our model, despite the infinite number of possible labelings (surfaces).
Optically induced mask-controlled time-variable periodic microwave structures (2000)

Based on the distributed Bragg reflection performance of stationary light-induced periodic microwave structures, this paper presents different kinds of modified arrangements for the generation of time-variable plasma gratings. Initial experimental investigations concentrate on the alteration of the grating period as a function of time. It is realized by a photographic film slot-array mask of linearly graded slot width transversely moved across an light-emitting-diode-excited photosensitive coplanar waveguide. The characterization of such a mask-tuned filter configuration requires special measuring procedures, which are illustrated and discussed in detail. The principle of operation demonstrated at X-band frequencies offers the potential of being extended to the submillimeter-wave and low-terahertz ranges.
Activation of protein kinase C attenuates early signals in Fas‐mediated apoptosis (1997)

Activation of protein kinase C (PKC) has been reported to inhibit Fas (APO-1, CD95)-mediated apoptosis in different cellular systems. Human Jurkat leukemic T cells express the Fas antigen in the cell membrane and undergo apoptosis upon cross-linking by anti-Fas monoclonal antibodies (mAb). Cleavage of the apoptosis-associated protease CPP32 and its substrate poly(ADP-ribose)polymerase are observed after the engagement of Fas antigen with mAb. In this report, we show that all these effects are substantially inhibited by the activation of PKC with a phorbol ester. Bisindolylmaleimide, an inhibitor of PKC, prevents phorbol ester-induced down-regulation of Fas signaling. Inhibition of Fas-mediated cell death by phorbol ester is also observed in other human leukemic T cell lines. Cross-linking of Fas antigen by mAb results in the rapid increase in tyrosine phosphorylation of several protein substrates which is further elevated in the presence of the protein tyrosine phosphatase inhibitor, orthovanadate. Furthermore, orthovanadate markedly enhances the cell death response to Fas mAb in different human leukemic T cell lines and human T cell blasts. These effects of orthovanadate on early tyrosine phosphorylation and cell death are clearly diminished by PKC activation. These results strongly suggest that tyrosine phosphorylation is involved in Fas signaling in apoptosis and that PKC plays a negative role in Fas-mediated apoptosis by counteracting at a very early stage the signals generated following cross-linking of this receptor.
The stability of Seeman JX DNA topoisomers of paranemic crossover (PX) molecules as a function of crossover number (2004)

We use molecular dynamics simulations in explicit water and salt (Na+) to determine the effect of varying the number of crossover points on the structure and stability of the PX65 paranemic crossover DNA molecule and its JXM topoisomers (M denotes the number of missing crossover points), recently synthesized by the Seeman group at New York University. We find that PX65, with six crossover points, is the most stable, and that the stability decreases monotonically with the number of crossover points PX65 > JX1 > JX2 > JX3 > JX4, with 6, 5, 4, 3 and 2 crossover points, respectively. Thus, for PX65/JX1, the strain energy is approximately 3 kcal/mol/bp, while it is approximately 13 kcal/mol/bp for JX2, JX3 and JX4. Another measure of the stability is the change in the structure from the minimum energy structure to the equilibrium structure at 300 K, denoted as root-mean-square deviation in coordinates (CRMSD). We find that CRMSD is approximately 3.5 A for PX65, increases to 6 A for JX1 and increases to 10 A for JX2/JX3/JX4. As the number of crossover points decreases, the distance between the two double helical domains of the PX/JX molecules increases from approximately 20 A for PX65 to 23 A for JX4. This indicates that JX2, JX3 and JX4 are less likely to form, at least in with Na+. However, in all the cases, the two double helical domains have average helicoidal parameters similar to a typical B-DNA of similar length and base sequence.
Membranes for Hydrogen Separation (2009)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionMembranes for Hydrogen SeparationNathan W. Ockwig and Tina M. NenoffCite this: Chem. Rev. 2010, 110, 4, 2573–2574Publication Date (Web):April 3, 2009Publication History Published online3 April 2009Published inissue 14 April 2010https://pubs.acs.org/doi/10.1021/cr078108lhttps://doi.org/10.1021/cr078108lcorrectionACS PublicationsCopyright © 2009 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views5468Altmetric-Citations19LEARN 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 PDF (333 KB) Get e-AlertscloseSUBJECTS:Anions,Hydrogen,Membranes,Salts,Thickness Get e-Alerts
Handbook of Photosensory Receptors (2005)

Preface. List of Authors. 1. Microbial Rhodopsins: Phylogenetic and Functional Diversity (J. Spudich & K. Jung). 2. Sensory Rhodopsin Signaling in Green Flagellate Algae (O. Sineshchekov & J. Spudich). 3. Visual Pigments as Photoreceptor (M. Kumauchi & T. Ebrey). 4. Structural and Functional Aspects of the Mammalian Rod-Cell Photoreceptor Rhodopsin (N. Abdulaev & K. Ridge). 5. A Novel Light-Sensing Pathway in the eye: Conserved Features of Inner Retinal Photoreception in Rodents, Man, and Teleost Fish (M. Hankins & R. Foster). 6. The Phytochromes (S. Tu & J. Lagarias). 7. Phytochrome Signaling (E. Huq & P. Quail). 8. Phytochromes in Microorganisms (R. Vierstra & B. Karniol). 9. Light-activated Intracellular Movement of Phytochrome (E. Schafer & F. Nagy). 10. Plant Cryptochromes: Their Genes, Biochemistry, and Physiological Roles (A. Batschauer). 11. Plant Cryptochromes and Signaling (A. Cashmore). 12. Animal Cryptochromes (R. van Gelder & A. Sancar). 13. Blue-Light Sensing and Signaling by the Phototropins (J. Christie & W. Briggs). 14. LOV-domain Photochemistry (T. Swartz & R. Bogomolni). 15. LOV-domain Structure, Dynamics, and Diversity (S. Crosson). 16. The ZEITLUPE Family of Putative Photoreceptors (T. Schultz). 17. Photoreceptor Gene Families in Lower Plants (N. Suetsugu & M. Wada). 18. Neurospora Photoreceptors (J. Dunlap & J. Loros). 19. Photoactive Yellow Protein, THE Xanthopsin (M. van der Horst, et al.). 20. Hypericin-Like Photoreceptors (P. Song). 21. The Antirepressor AppA Uses the Novel Flavin-Binding BLUF domain as a Blue-Light-Absorbing Photoreceptor to Control Photosystem Synthesis (S. Masuda & C. Bauer). Discovery, Characterization, and Prospect of Photoactivated Adenylyl Cyclase (PAC), a Novel Blue-Light Receptor Flavoprotein from Euglena gracilis (M. Watanabe & M. Iseki).
Directed reduction of .beta.-hydroxy ketones employing tetramethylammonium triacetoxyborohydride (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirected reduction of .beta.-hydroxy ketones employing tetramethylammonium triacetoxyborohydrideD. A. Evans, K. T. Chapman, and E. M. CarreiraCite this: J. Am. Chem. Soc. 1988, 110, 11, 3560–3578Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/ja00219a035https://doi.org/10.1021/ja00219a035research-articleACS PublicationsRequest reuse permissionsArticle Views16512Altmetric-Citations844LEARN 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