gebhart/patrepeval huggingface dataset:
Duokines: a novel class of dual-acting co-stimulatory molecules acting in cis or trans (2018)

Co-stimulatory signals induced by ligands of the tumor necrosis factor superfamily (TNFSF) play a central role in T cell activation and have emerged as a promising strategy in cancer immunotherapy. Here, we established a novel class of bifunctional co-stimulatory fusion proteins with the aim to boost T cell activation at the level of T cell - antigen-presenting cell (APC) interaction. These novel dual-acting cytokine fusion proteins were created by connecting two different homotrimeric TNFSF ligands to form homotrimeric bifunctional molecules (Duokines) or by connecting single-chain derivatives of two different homotrimeric TNFSF with a single, flexible linker (single-chain Duokines, scDuokines). By linking the TNFSF ligands 4-1BBL, OX40L and CD27L in all possible combinations, cis-acting Duokines were generated that act on the same or adjacent T cells, while combining CD40L with 4-1BBL, OX40L and CD27L resulted in trans-acting Duokines acting simultaneously on APCs and T cells. <i>In vitro</i>, co-stimulation of T cells was seen for cis- and trans-acting Duokines and scDuokines in an antigen-independent as well as antigen-specific setting. Trans-acting molecules furthermore activated B cells, which represent a subclass of APCs. In a pilot experiment using the syngeneic B16-FAP mouse tumor model scDuokines displayed antitumoral activity in vivo in combination with a primary T cell-activating bispecific antibody, evident from reduced number of lung metastasis compared to the antibody-only treated group. Our data show that the bifunctional, co-stimulatory duokines are capable to enhance T cell-mediated anti-tumor immune responses, suggesting that they can serve as a new class of immuno-stimulatory molecules for use in cancer immunotherapy strategies.
Identification of sites for exponential translation in living dendrites (2001)

Neuronal processes contain mRNAs and membrane structures, and some forms of synaptic plasticity seem to require protein synthesis in dendrites of hippocampal neurons. To quantitate dendritic protein synthesis, we used multiphoton microscopy of green fluorescent protein synthesized in living isolated dendrites. Transfection of dendrites with mRNA encoding green fluorescent protein resulted in fluorescence that exponentially increased on stimulation with a glutamate receptor agonist; a reaction attenuated by the translation inhibitors anisomycin and emetine. Comparable experiments on whole neurons revealed that (RS)-3,5-dihydroxy-phenylglycine 0.5 H(2)O (DHPG)-stimulated fluorescence was linear in cell bodies relative to the exponential increase seen in dendrites. Detailed spatial analysis of the subdendritic distribution of fluorescence revealed "hotspots," sites of dendritic translation that were spatially stable. However, detailed temporal analysis of these hotspots revealed heterogeneous rates of translation. A double-label protocol counterstaining for ribosomes indicated that sites of "fastest" translation correlated with increased ribosome density, consistent with ribosome subunit assembly for initiation, the first step of translation. We propose that dendrites have specific sites specialized for fast translation.
Efficient equalizer update algorithms for acoustic communication channels of varying complexity (2002)

Underwater acoustic communication channels vary from stationary with sparse arrivals to rapidly varying and fully reverberant. A receiver structure capable of operating over this wide range of characteristics has evolved and consists of a fractionally-spaced multi-channel combiner, a sparse DFE, and an embedded PLL. At the computational heart of this receiver is an adaptation algorithm, used to update the various equalizer parameters, The adaptation algorithm may use one of the standard strategies such as adaptive step-size LMS, RLS, adaptive memory RLS, or a hybrid of these. The choice of algorithm involves trade-offs between training time, tracking-rate, operating SNR, and computational requirements of the receiver. To maximize the receiver throughput, we wish to select the least computational algorithm for which the error-rate is still acceptable and, given the volatility of the underwater channel, this choice should be made for each received packet, In this paper, we compare the performance of several LMS and RLS adaptation algorithms over a range of real acoustic data. We show that the computationally-efficient adaptive step-size LMS performs well for many channel classes, but that the faster tracking of RLS is essential for some complex non-stationary channels. The results provide a first step towards the automatic selection of adaptation algorithm, as would be required in a fully autonomous receiver.
Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration (2019)

Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further.
Finding set of &#8220;core genes&#8221; for Nematoda, Trematoda and Cestoda (2018)

Sets of core genes were de ned for nematodes, trematodes and cestodes for use as training sets for gene prediction.
Reactivity of Group 4 acyl complexes with alkylaluminum reagents: synthesis of zirconium ketone complexes (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactivity of Group 4 acyl complexes with alkylaluminum reagents: synthesis of zirconium ketone complexesRobert M. Waymouth, Karl R. Clauser, and Robert H. GrubbsCite this: J. Am. Chem. Soc. 1986, 108, 20, 6385–6387Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October 1986https://pubs.acs.org/doi/10.1021/ja00280a044https://doi.org/10.1021/ja00280a044research-articleACS PublicationsRequest reuse permissionsArticle Views252Altmetric-Citations32LEARN 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
The C-terminal Residues of Bacteriophage T7 Gene 4 Helicase-Primase Coordinate Helicase and DNA Polymerase Activities (2006)

The gene 4 protein of bacteriophage T7 plays a central role in DNA replication by providing both helicase and primase activities. The C-terminal helicase domain is not only responsible for DNA-dependent dTTP hydrolysis, translocation, and DNA unwinding, but it also interacts with T7 DNA polymerase to coordinate helicase and polymerase activities. The C-terminal 17 residues of gene 4 protein are critical for its interaction with the T7 DNA polymerase/thioredoxin complex. This C terminus is highly acidic; replacement of these residues with uncharged residues leads to a loss of interaction with T7 DNA polymerase/thioredoxin and an increase in oligomerization of the gene 4 protein. Such an alteration on the C terminus results in a reduced efficiency in strand displacement DNA synthesis catalyzed by gene 4 protein and T7 DNA polymerase/thioredoxin. Replacement of the C-terminal amino acid, phenylalanine, with non-aromatic residues also leads to a loss of interaction of gene 4 protein with T7 DNA polymerase/thioredoxin. However, neither of these modifications of the C terminus affects helicase and primase activities. A chimeric gene 4 protein containing the acidic C terminus of the T7 gene 2.5 single-stranded DNA-binding protein is more active in strand displacement synthesis. Gene 4 hexamers containing even one subunit of a defective C terminus are defective in their interaction with T7 DNA polymerase.
Structural Characterization of Niobium Phosphate Catalysts used for the Oxidative Dehydrogenation of Ethane to Ethylene (2011)

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.
Dynamic insulin sensitivity index: importance in diabetes (2009)

The classical minimal model (MM) index of insulin sensitivity, S(I), does not account for how fast or slow insulin action takes place. In a recent work, we proposed a new dynamic insulin sensitivity index, S(I)(D), which is able to take into account the dynamics of insulin action as well. The new index is a function of two MM parameters, namely S(I) and p(2), the latter parameter governing the speed of rise and decay of insulin action. We have previously shown that in normal glucose tolerant subjects S(I)(D) provides a more comprehensive picture of insulin action on glucose metabolism than S(I). The aim of this study is to show that resorting to S(I)(D) rather S(I) is even more appropriate when studying diabetic patients who have a low and slow insulin action. We analyzed insulin-modified intravenous glucose tolerance test studies performed in 10 diabetic subjects and mixed meal glucose tolerance test studies exploiting the triple tracer technique in 14 diabetic subjects. We derived both S(I) and S(I)(D) resorting to Bayesian and Fisherian identification strategies. The results show that S(I)(D) is estimated more precisely than S(I) when using the Bayesian approach. In addition, the less labor-intensive Fisherian approach can still be used to obtain reliable point estimates of S(I)(D) but not of S(I). These results suggest that S(I)(D) yields a comprehensive, precise, and cost-effective assessment of insulin sensitivity in subjects with impaired insulin action like impaired glucose tolerant subjects or diabetic patients.
Biomarker-Based Nanotechnology for the Improvement of Reproductive Performance in Beef and Dairy Cattle (2013)

Reproductive performance of livestock animals, including dairy and beef cattle, influences the productivity of agriculture in the US and worldwide. Artificial insemination (AI) is one technology with great potential to improve livestock reproductive efficiency. Particularly, gains in reproductive performance of AI sires can be made by identifying and eliminating bulls with inferior fertility/semen quality by testing and discarding individual semen collections/ejaculates with inferior fertilization potential and by eliminating defective spermatozoa from semen collected for AI. Both sire fertility testing and semen purification can potentially be improved through the application of nanotechnology. The necessary first step in this process is the identification and validation of sperm quality biomarkers; they are the differentially expressed sperm-borne proteins/ligands that can be objectively quantitated to measure sperm quality and to estimate future fertility. Proteins expressed on the sperm surface can be targeted using magnetic nanoparticles to allow for rapid, efficient removal of defective spermatozoa from semen. This article reviews recent progress in the identification of such biomarkers (e.g., ligands of lectins from Arachis hypogaea and Lens culinaris, sperm proteins ubiquitin and post-acrosomal, WW domain-binding protein [PAWP]), and also describes recent trials of nanoparticle-based technologies for fertility testing and the nanopurification of bull semen for commercial AI.
Constitutive Chemokine Production Results in Activation of Leukocyte Function-Associated Antigen-1 on Adult T-Cell Leukemia Cells (1998)

Adult T-cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium, and integrins are tightly regulated by several stimuli, such as inflammatory chemokines. However, the exact mechanisms that enhance adherence of leukemic cells to the endothelium and infiltration into tissues remain to be fully understood. We investigated the mechanisms of extravasation of leukemic cells using ATL cells and report the following novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. ATL cells spontaneously adhered to endothelial cells without exogenous stimulation. Integrin leukocyte function-associated antigen-1 (LFA-1) on ATL cells was spontaneously activated. ATL cells produced high amounts of chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Adhesion of ATL cells to endothelial cells and the expression of activated form of LFA-1 were reduced by pretreatment with pertussis toxin, wortmannin, or anti-MIP-1alpha and MIP-1beta antibodies or transfection with antisense of MIP-1alpha or MIP-1beta. Spontaneous polymerization of cytoskeletal F-actin was observed in ATL cells, which was also inhibited by pertussis toxin and wortmannin. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of phosphoinositide 3-kinases in an autocrine manner. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.
A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9 (2017)

Abstract The Cas9 endonuclease is widely utilized for genome engineering applications by programming its single-guide RNA and ongoing work is aimed at improving the accuracy and efficiency of DNA targeting. DNA cleavage of Cas9 is controlled by the conformational state of the HNH nuclease domain, but the mechanism that governs HNH activation at on-target DNA while reducing cleavage activity at off-target sites remains poorly understood. Using single-molecule FRET, we identified an intermediate state of S. pyogenes Cas9, representing a conformational checkpoint between DNA binding and cleavage. Upon DNA binding, the HNH domain transitions between multiple conformations before docking into its active state. HNH docking requires divalent cations, but not strand scission, and this docked conformation persists following DNA cleavage. Sequence mismatches between the DNA target and guide RNA prevent transitions from the checkpoint intermediate to the active conformation, providing selective avoidance of DNA cleavage at stably bound off-target sites.
Synthetic Tyrosine tRNA Molecules with Noncanonical Secondary Structures (2018)

The L-shape form of tRNA is maintained by tertiary interactions occurring in the core. Base changes in this domain can cause structural defects and impair tRNA activity. Here, we report on a method to safely engineer structural variations in this domain utilizing the noncanonical scaffold of tRNA<sup>Pyl</sup>. First, we constructed a naïve hybrid between archaeal tRNA<sup>Pyl</sup> and tRNA<sup>Tyr</sup>, which consisted of the acceptor and T stems of tRNA<sup>Tyr</sup> and the other parts of tRNA<sup>Pyl</sup>. This hybrid tRNA efficiently translated the UAG codon to 3-iodotyrosine in <i>Escherichia coli</i> cells, when paired with a variant of the archaeal tyrosyl-tRNA synthetase. The amber suppression efficiency was slightly lower than that of the "bench-mark" archaeal tRNA<sup>Tyr</sup> suppressor assuming the canonical structure. After a series of modifications to this hybrid tRNA, we obtained two artificial types of tRNA<sup>Tyr</sup>: ZtRNA had an augmented D (auD) helix in a noncanonical form and the D and T loops bound by the standard tertiary base pairs, and YtRNA had a canonical auD helix and non-standard interloop interactions. It was then suggested that the ZtRNA scaffold could also support the glycylation and glutaminylation of tRNA. The synthetic diversity of tRNA would help create new tRNA⁻aminoacyl-tRNA synthetase pairs for reprogramming the genetic code.
The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia (2021)

Abstract Human reproduction is controlled by ∼2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional 150-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Extrahypothalamic GnRH neurons were cholinergic. Though undetectable in adult rodents, the GnRH-GFP transgene was expressed transiently by caudate-putamen cholinergic interneurons in newborn transgenic mice. In slice electrophysiological studies, GnRH inhibited these interneurons via GnRHR1 autoreceptors. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen confirmed selective expression of GNRH1 and GNRHR1 autoreceptors in cholinergic cells and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher- order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. GnRH/GnRHR1 signaling as a potential therapeutic target in the treatment of neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson’s and Alzheimer’s diseases, needs to be explored.
RTC Provisioning Requirements (2006)

Real Time Communications (RTC) tools are becoming as prevalent and
essential for users on the Internet as email. While RTC tools can,
like email, be implemented directly by users in a point-to-point
fashion, they are often provided for or on behalf of a community of
users within an administrative domain. As the use of these tools
grows, users increasingly have the need to communicate with users not
only within their own community but with those in other communities as
well. In practice, each community is controlled by some authority, and
so there is a need to provide for easier establishment of connectivity
between communities, and the management of the inter- community link.
This document contains an initial list of requirements for
provisioning and managing connectivity between communities.
Microstructure and Mechanical Properties of Mg-Al-Ca-Sm Alloys at High Temperature (2007)

The aims of this research are to investigate the effect of Sm addition in Mg-Al-Ca alloys on microstructure and mechanical properties. Sm addition to Mg-5Al-3Ca based alloys results in the change from dendritic to equiaxed grain morphorlogy and formation of Al-Sm rich itermetallic compounds at grain boundary and α-Mg matrix. And these Al-Sm rich intermetallic compounds were dispersed homogeously and stabilized at high temperature. And maximum yield and ultimate strength value was obtained at Mg-5Al-3Ca-2Sm alloys at elevated temperature because of homogeneous dispersion of stable Al-Sm rich intermetallic compound at high temperature.
Automated analysis of free speech predicts psychosis onset in high-risk youths (2015)

Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry.
Approximation and compression of piecewise smooth images using a wavelet/wedgelet geometric model (2004)

Inherent to photograph-like images are two types of structures: large smooth regions and geometrically smooth edge contours separating those regions. Over the past years, efficient representations and algorithms have been developed that take advantage of each of these types of structure independently: quadtree models for 2D wavelets are well-suited for uniformly smooth images (C/sup 2/ everywhere), while quadtree-organized wedgelet approximations are appropriate for purely geometrical images (containing nothing but C/sup 2/ contours). This paper shows how to combine the wavelet and wedgelet representations in order to take advantage of both types of structure simultaneously. We show that the asymptotic approximation and rate-distortion performance of a wavelet-wedgelet representation on piecewise smooth images mirrors the performance of both wavelets (for uniformly smooth images) and wedgelets (for purely geometrical images). We also discuss an efficient algorithm for fitting the wavelet-wedgelet representation to an image; the convenient quadtree structure of the combined representation enables new algorithms such as the recent WSFQ geometric image coder.
Calcitonin gene-related peptide-induced selective inhibition of gastric acid secretion in dogs (1986)

Calcitonin gene-related peptide (CGRP) is a 37-residue peptide recently characterized in the brain and found in high concentrations in the gut, particularly in the stomach and pancreas. The effects of intravenous infusion of human and rat CGRP (260 pmol . kg-1 . h-1) on gastric secretion and emptying and pancreatic exocrine secretion were studied in conscious dogs. CGRP inhibited by 60-75% gastric acid secretion stimulated by a meal, sham feeding, or step doses of bombesin but did not modify acid response to step doses of histamine or bethanechol. The inhibitory effect of CGRP is not due to blockage of postprandial or bombesin-stimulated gastrin release. CGRP did not influence basal or meal-stimulated pancreatic exocrine secretion or the rate of gastric emptying of a saline meal. These results indicate that CGRP is a potent and selective inhibitor of gastrin-mediated acid secretion in dogs and, under these conditions, did not alter other gastrointestinal functions such as gastric emptying or pancreatic exocrine secretion.