gebhart/patrepeval huggingface dataset:
Human Immunodeficiency Virus Integrates Directly into Naive Resting CD4+T Cells but Enters Naive Cells Less Efficiently than Memory Cells (2009)

Resting CD4(+) T cells restrict human immunodeficiency virus (HIV) infection at or before reverse transcription, resulting in slower kinetics of reverse transcription. In a previous study, we showed that, despite this restriction at reverse transcription, HIV integration occurs in resting CD4(+) T cells, albeit with slower kinetics. In that study, the resting T cells were a mixture of memory and naïve cells. Here we asked whether the more quiescent naïve cell subset could be directly infected by HIV and, if so, whether the level of integration in naïve cells was comparable to that in memory cells. We found that HIV integrates in the naïve subset of resting CD4(+) T cells without prior activation of the cells. The level of integration (proviruses/cell) in naïve cells was lower than that in memory cells. This difference between naïve and memory cells was observed whether we inoculated the cells with R5 or X4 HIV and could not be explained solely by differences in coreceptor expression. The presence of endogenous dendritic cells did not change the number of proviruses/cell in memory or naïve cells, and deoxynucleoside pools were equally limiting. Our results instead indicate the existence of a novel restriction point in naïve T cells at viral fusion that results in reduced levels of fusion to naïve CD4(+) T cells. We conclude that HIV can integrate into both naïve and memory cells directly. Our data further support our hypothesis that integrated proviral infection of resting T cells can be established without T-cell activation.
Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis (2002)

The protein defective in hereditary hemochromatosis, called HFE, is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). Its association with beta2M was previously shown to be necessary for its stability, normal intracellular processing, and cell surface expression in transfected COS cells. Here we use stably transfected Chinese hamster ovary cell lines expressing both HFE and beta2M or HFE alone to study the effects of beta2M on the stability and maturation of the HFE protein and on the role of HFE in transferrin receptor 1 (TfR1)-mediated iron uptake. In agreement with prior studies on other cell lines, we found that overexpression of HFE, without overexpressing beta2M, resulted in a decrease in TfR1dependent iron uptake and in lower iron levels in the cells, as evidenced by ferritin and TfR1 levels measured at steady state. However, overexpression of both HFE and beta2M had the reverse effect and resulted in an increase in TfR1-dependent iron uptake and increased iron levels in the cells. The HFE-beta2M complex did not affect the affinity of TfR1 for transferrin or the internalization rate of transferrin-bound TfR1. Instead, HFE-beta2M enhanced the rate of recycling of TfR1 and resulted in an increase in the steady-state level of TfR1 at the cell surface of stably transfected cells. We propose that Chinese hamster ovary cells provide a model to explain the effect of the HFE-beta2M complex in duodenal crypt cells, where the HFE-beta2M complex appears to facilitate the uptake of transferrin-bound iron to sense the level of body iron stores. Impairment of this process in duodenal crypt cells leads them to be iron poor and to signal the differentiating enterocytes to take up iron excessively after they mature into villus cells in the duodenum of hereditary hemochromatosis patients.
Novel Strategies for the Prevention and Treatment of Biofilm Related Infections (2013)

Biofilm formation by human bacterial pathogens on implanted medical devices causes major morbidity and mortality among patients, and leads to billions of dollars in healthcare cost. Biofilm is a complex bacterial community that is highly resistant to antibiotics and human immunity. As a result, novel therapeutic solutions other than the conventional antibiotic therapies are in urgent need. In this review, we will discuss the recent research in discovery of alternative approaches to prevent or treat biofilms. Current anti-biofilm technologies could be divided into two groups. The first group focuses on targeting the biofilm forming process of bacteria based on our understanding of the molecular mechanism of biofilm formation. Small molecules and enzymes have been developed to inhibit or disrupt biofilm formation. Another group of anti-biofilm technologies focuses on modifying the biomaterials used in medical devices to make them resistant to biofilm formation. While these novel anti-biofilm approaches are still in nascent phases of development, efforts devoted to these technologies could eventually lead to anti-biofilm therapies that are superior to the current antibiotic treatment.
Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. (2001)

Chromosomal instability is believed to be a common feature of most human tumors, but the stage at which such instability originates has not been defined. At the molecular level, chromosomal instability is characterized by allelic imbalance (AI), representing losses or gains of defined chromosomal regions. We have assessed AI in early colorectal tumors using newly developed methods for assessing AI in complex cell populations. A total of 32 adenomas of average size (2 mm; range, 1-3 mm) were studied. AI of chromosome 5q markers occurred in 55% of tumors analyzed, consistent with a gatekeeping role of the adenomatous polyposis coli tumor suppressor gene located at chromosomal position 5q21. AI was also detected in each of the other four chromosomes tested. The fractions of adenomas with AI of chromosomes 1p, 8p, 15q, and 18q were 10,19, 28, and 28%, respectively. Over 90% of the tumors exhibited AI of at least one chromosome, and 67% had allelic imbalance of a chromosome other than 5q. These findings demonstrate that AI is a common event, even in very small tumors, and suggest that chromosomal instability occurs very early during colorectal neoplasia.
Effective handling of dialogue state in the hidden information state POMDP-based dialogue manager (2011)

Effective dialogue management is critically dependent on the information that is encoded in the dialogue state. In order to deploy reinforcement learning for policy optimization, dialogue must be modeled as a Markov Decision Process. This requires that the dialogue state must encode all relevent information obtained during the dialogue prior to that state. This can be achieved by combining the user goal, the dialogue history, and the last user action to form the dialogue state. In addition, to gain robustness to input errors, dialogue must be modeled as a Partially Observable Markov Decision Process (POMDP) and hence, a distribution over all possible states must be maintained at every dialogue turn. This poses a potential computational limitation since there can be a very large number of dialogue states. The Hidden Information State model provides a principled way of ensuring tractability in a POMDP-based dialogue model. The key feature of this model is the grouping of user goals into partitions that are dynamically built during the dialogue. In this article, we extend this model further to incorporate the notion of complements. This allows for a more complex user goal to be represented, and it enables an effective pruning technique to be implemented that preserves the overall system performance within a limited computational resource more effectively than existing approaches.
Small antibody fusion proteins with complementarity-determining regions and lidamycin for tumor targeting therapy (2013)

Gelatinases are overexpressed in several types of maligancies and tumor stromal cells. Lidamycin is an enediyne antitumor antibiotic, which is composed of an apoprotein (LDP) and an active chromophore (AE). It is known that the heavy-chain complementarity-determining region-3 (CDR3) domain of scFv is important in antibody affinity. The aim of this study was to prepare the enediyne-energized fusion proteins with a heavy-chain CDR3 domain of anti-gelatinases scFv and lidamycin, and to evaluate their antitumor efficiency. Fusion proteins comprising the CDR3 domain and the lidamycin apoprotein were generated, and ELISA, immunofluorescence and FACS were used to analyze the binding of the fusion protein with antigen gelatinases. The purified fusion proteins were assembled with the lidamycin chromophore, and the antitumor effects were evaluated <i>in vitro</i> and <i>in vivo</i>. It was found that the CDR3-LDP and CDR3-LDP-CDR3 fusion proteins demonstrated high affinity towards antigen gelatinases. Following stimulation of CDR3-LDP with enediyne, the results of MTT showed potent cytotoxicity towards tumor cells; the IC50 values of CDR3-LDP-AE to HepG2 and Bel-7402 tumor cells were 1.05×10<sup>-11</sup> and 6.6×10<sup>-14</sup> M, respectively. In addition, CDR3-LDP-AE displayed a potent antitumor effect in H22 cell xenografts in mice; the combination of CDR3-LDP (10 mg/kg) and CDR3-LDP-AE (0.25 and 0.5 mg/kg) revealed that the tumor inhibitory rates were 85.2 and 92.7%, respectively (P<0.05 compared with CDR3-LDP-AE). In conclusion, these results suggest that the CDR3-LDP fusion protein and its analog CDR3-LDP-AE may both be promising candidates for tumor targeting therapy.
Complete Response of Colorectal Liver Metastases After Chemotherapy: Does It Mean Cure? (2006)

In most patients receiving chemotherapy for colorectal LMs, a complete response on CT scan does not mean cure.
Gremlin1 promotes carcinogenesis of glioma in vitro (2016)

As the most prevalent and lethal type of brain tumours, gliomas, especially malignant ones, are relatively resistant to conventional therapies. Gremlin 1 (GREM1) is a secreted glycoprotein that is implicated in the maintenance of cancer stem cells in tumour hierarchy. In the current study, the role of GREM1 in the carcinogenesis of glioma was studied using a knockdown approach. We first examined the expression level of GREM1 in the clinical samples, and then evaluated the effect of GREM1 knockdown on the viability and colony formation capacity of U87-MG cells. Moreover, the migration ability, invasiveness, cell cycle, and apoptosis of GREM1-silenced cells were assessed. Furthermore, the involvement of functional GREM1 in the epithelial-mesenchymal transition (EMT) process of glioma was investigated by detecting the expression levels of glioma-associated oncogene homologue 3 (GLI3) and EMT-related molecules. Our results demonstrated that knockdown of GREM1 reduced cell viability, suppressed migration and invasion, and inhibited GLI3 expression and the EMT process in U87-MG cells. Meanwhile, GREM1 silencing promoted apoptosis in U87-MG cells through the accumulation of Bax, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) as well as the downregulation of Bcl-2. In addition, GREM1 knockdown abolished transforming growth factor (TGF)-β1-mediated activation of the Smad pathway, which may underlie the mechanism of GREM1-regulated EMT. In conclusion, GREM1 plays an important role in the development of glioma, and it may serve as a potential target in glioma therapy.
Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock (2001)

Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.
Si- and Ge-Doped GaN Films Grown with GaN Buffer Layers (1992)

Si- and Ge-doped GaN films were grown with GaN buffer layers. Si-doped GaN films, of which the carrier concentration was as high as 2×10 19 /cm 3 , were obtained. Every Si-doped GaN film showed a surface morphology that was smooth and mirrorlike. Ge-doped GaN films, of which the carrier concentration was as high as 1×10 19 /cm 3 , were obtained. Surface morphology of Ge-doped GaN films became poor around this carrier concentration. Both dopings showed good linearity of the carrier concentration as a function of the flow rate of GeH 4 and SiH 4 . Therefore, Ge and Si are suitable n-type dopants for GaN.
Bernoulli levitation (2003)

Bernoulli levitation is the basis of many popular counter-intuitive physics demonstrations. However, few of these lend themselves to a quantitative description without recourse to computational fluid dynamics. Levitation of a flat plate is the exception, and we present an analysis that illustrates several principles of fluid mechanics in a pedagogically useful way.
Identification of cultured progenitor cells from human marrow stroma (2002)

The marrow stromal cells (MSC) are essential for regulation of bone remodeling and hematopoiesis. It is of prime importance to isolate MSC and to expand the proliferating cells ex vivo. In this study, we analyzed cultured MSC for various cellular parameters, including cell morphology, cell cycle, and expression of cell surface antigens by flow cytometry. MSC were divided based on cell size to small (S-cells) and large (L-cells) and were visualized by light and electron microscope. The S-cells were proliferating cells correlated with G0/G1 phase of cell cycle, and expressed cFOS. The expression of surface markers CD-34, -44, -51, -61, -62E, -62P, -62L was quantified using flow cytometry. CD-44 was ubiquitously expressed by S and L cells, CD-51 and -61 were expressed by 30%-38% of S-cells. CD-34 and -62 expressed 20% positive of the analyzed cells that were of the proliferating progenitors (S-cells). This study enables the identification of subpopulations from MSC with special attention paid to the proliferating cells from ex vivo cultures of marrow stroma.
Control of pH and PIP2Gating in Heteromeric Kir4.1/Kir5.1 Channels by H-Bonding at the Helix-Bundle Crossing (2007)

Inhibition by intracellular H(+) (pH gating) and activation by phosphoinositides such as PIP(2) (PIP(2)-gating) are key regulatory mechanisms in the physiology of inwardly-rectifying potassium (Kir) channels. Our recent findings suggest that PIP(2) gating and pH gating are controlled by an intra-subunit H-bond at the helix-bundle crossing between a lysine in TM1 and a backbone carbonyl group in TM2. This interaction only occurs in the closed state and channel opening requires this H-bond to be broken, thereby influencing the kinetics of PIP(2) and pH gating in Kir channels. In this addendum, we explore the role of H-bonding in heteromeric Kir4.1/Kir5.1 channels. Kir5.1 subunits do not possess a TM1 lysine. However, homology modelling and molecular dynamics simulations demonstrate that the TM1 lysine in Kir4.1 is capable of H-bonding at the helix-bundle crossing. Consistent with this, the rates of pH and PIP2 gating in Kir4.1/Kir5.1 channels (two H-bonds) were intermediate between those of wild-type homomeric Kir4.1 (four H-bonds) and Kir4.1(K67M) channels (no H-bonds) suggesting that the number of H-bonds in the tetrameric channel complex determines the gating kinetics. Furthermore, in heteromeric Kir4.1(K67M)/Kir5.1 channels, where the two remaining H-bonds are disrupted, we found that the gating kinetics were similar to Kir4.1(K67M) homomeric channels despite the fact that these two channels differ considerably in their PIP(2) affinities. This indicates that Kir channel PIP(2) affinity has little impact on either the PIP(2) or pH gating kinetics.
Polyplexes Assembled with Internally Quaternized PAMAM-OH Dendrimer and Plasmid DNA Have a Neutral Surface and Gene Delivery Potency (2003)

Interior tertiary amine groups of PAMAM-OH dendrimers (hydroxyl-terminated polyamidoamine, PAMAM) were modified by methylation to make these polymers have a more cationic character, which enabled electrostatic interaction between PAMAM-OH and plasmid DNA. A methylation reaction was dose-dependent, producing internally quaternized PAMAM-OH (QPAMAM-OH), thereby making tertiary amine/quaternary amine ratio adjustment possible. More highly condensed particles of plasmid DNA were formed as the degree of quaternization increased, whereas unmodified polymer (PAMAM-OH) could not. The location of positive charges in the internal position of QPAMAM-OH resulted in the formation of neutral polyplexes in which zeta potential leveled off near the zero value even at high charge ratios (+/-) of 10. A light scattering experiment showed that the polyplex formed by QPAMAM-OH was very small with the size of 53.3 nm at the optimum condition. QPAMAM-OH/DNA polyplexes were round-shaped with the more compact and small particles formed as the charge ratio increased. QPAMAM-OH showed much reduced cytotoxicity compared with starburst PAMAM and branched polyethyleneimine (PEI) in which shielding of interior positive charges by surface hydroxyls might be the reason for this favorable result. These results suggest that QPAMAM-OH could be a promising tool as a nonviral vector both by itself and in conjugated form with targeting ligands.
The Chinese Internet (2020)

This book discusses the use of the internet in China, the complicated power relations in online political communications, and the interactions and struggles between the government and the public over the use of the internet. It argues that there is a "semi-structured" online public sphere, in which there is a certain amount of equal and liberal political communication, but that the online political debates are also limited by government control and censorship, as well as by inequality and exclusions, and moreover that the government rarely engages in the political debates. Based on extensive original research, and considering specific debates around particular issues, the book analyses how Chinese net-users debate about political issues, how they problematize the government’s actions and policies, what language they use, what online discourses are produced, and how the debates and online discourses are limited. Overall, the book provides a rich picture of the current state of online political communication in China.
A sequence-specific molecular light switch: tethering of an oligonucleotide to a dipyridophenazine complex of ruthenium(II) (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA sequence-specific molecular light switch: tethering of an oligonucleotide to a dipyridophenazine complex of ruthenium(II)Yonchu Jenkins and Jacqueline K. BartonCite this: J. Am. Chem. Soc. 1992, 114, 22, 8736–8738Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October 1992https://doi.org/10.1021/ja00048a077RIGHTS & PERMISSIONSArticle Views489Altmetric-Citations105LEARN 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 PDF (415 KB) Get e-Alerts Get e-Alerts
Fast and Accurate Genomic Analyses using Genome Graphs (2017)

Abstract The human reference genome serves as the foundation for genomics by providing a scaffold for alignment of sequencing reads, but currently only reflects a single consensus haplotype, which impairs read alignment and downstream analysis accuracy. Reference genome structures incorporating known genetic variation have been shown to improve the accuracy of genomic analyses, but have so far remained computationally prohibitive for routine large-scale use. Here we present a graph genome implementation that enables read alignment across 2,800 diploid genomes encompassing 12.6 million SNPs and 4.0 million indels. Our Graph Genome Pipeline requires 6.5 hours to process a 30x coverage WGS sample on a system with 36 CPU cores compared with 11 hours required by the GATK Best Practices pipeline. Using complementary benchmarking experiments based on real and simulated data, we show that using a graph genome reference improves read mapping sensitivity and produces a 0.5% increase in variant calling recall, or about 20,000 additional variants being detected per sample, while variant calling specificity is unaffected. Structural variations (SVs) incorporated into a graph genome can be genotyped accurately under a unified framework. Finally, we show that iterative augmentation of graph genomes yields incremental gains in variant calling accuracy. Our implementation is a significant advance towards fulfilling the promise of graph genomes to radically enhance the scalability and accuracy of genomic analyses.
Lysophosphatidic Acid Acyltransferase from Coconut Endosperm Mediates the Insertion of Laurate at the sn-2 Position of Triacylglycerols in Lauric Rapeseed Oil and Can Increase Total Laurate Levels (1999)

Expression of a California bay laurel (Umbellularia californica) 12:0-acyl-carrier protein thioesterase, bay thioesterase (BTE), in developing seeds of oilseed rape (Brassica napus) led to the production of oils containing up to 50% laurate. In these BTE oils, laurate is found almost exclusively at the sn-1 and sn-3 positions of the triacylglycerols (T.A. Voelker, T.R. Hayes, A.C. Cranmer, H.M. Davies [1996] Plant J 9: 229-241). Coexpression of a coconut (Cocos nucifera) 12:0-coenzyme A-preferring lysophosphatitic acid acyltransferase (D.S. Knutzon, K.D. Lardizabal, J.S. Nelsen, J.L. Bleibaum, H.M. Davies, J.G. Metz [1995] Plant Physiol 109: 999-1006) in BTE oilseed rape seeds facilitates efficient laurate deposition at the sn-2 position, resulting in the acccumulation of trilaurin. The introduction of the coconut protein into BTE oilseed rape lines with laurate above 50 mol % further increases total laurate levels.
A low thermal budget, fully self-aligned lateral BJT on thin film SOI substrate for low power BiCMOS applications (2002)

A novel SDE LBJT on TFSOI substrate has been demonstrated. The fabrication process is self-aligned, with a minimum thermal budget, and is fully compatible with an SOI CMOS process. Good electrical results were obtained. The devices are expected to have good current drive and high frequency performance for low power applications.