gebhart/patrepeval huggingface dataset:
Construction and Molecular Analysis of Gene Transfer Systems Derived from Bovine Immunodeficiency Virus (2001)

Because lentiviruses are able to infect nondividing cells, these viruses might be utilized in gene therapy applications where the target cell does not divide. However, it has been suggested that the introduction of primate lentivirus sequences, particularly those of human immunodeficiency virus, into human cells may pose a health risk for the patient. To avoid this concern, we have constructed gene transfer systems based on a nonprimate lentivirus, bovine immunodeficiency virus. A panel of vectors and packaging constructs was generated and analyzed in a transient expression system for virion production and maturation, vector expression and encapsidation, and envelope protein pseudotyping. Virion preparations were also analyzed for transduction efficiency in a panel of human and nonhuman primary cells and immortalized cell lines. The virion preparations transduced most of the target cell types, with efficiencies up to 90% and with titers of unconcentrated virus up to 5 x 10(5) infectious doses/ml. In addition, infection of nondividing human cells, including unstimulated hematopoietic stem cells and irradiated endothelial cells, was observed.
Simultaneous Transmission and Reception for Improvedwireless Network Performance (2007)

One of the limiting factors in ad hoc wireless mesh networks using traditional physical layer techniques is the inability to transmit and receive at the same frequency simultaneously. As a consequence, careful time-slot or frequency-reuse planning is required. This has adverse network data-rate and latency implications. The focus of this paper is a demonstration of signal processing techniques that enable simultaneous transmission and reception. These techniques employ informed-transmittermultiple-input multiple-output (MIMO) links. A combination of adaptive transmit and receive antenna array approaches is exploited. A number of important types of networking limitations can be resolved given simultaneous transmit and receive technology. The first example is the simultaneous link problem. By employing transmit and receive spatial adaptivity, two links can operate in close proximity using the same frequency at the same time. Another example is the full duplex relay node. Using the same frequency for both links, a given node can simultaneously receive packets from one node while forwarding them to another. For practical systems, two issues dominate performance: channel estimation error, often caused by stale estimates of the channel at the transmitter, and dynamic range limitations of the transmitter and receiver. These issues are investigated. Theoretical, simulated, and experimental results are presented.
Diminishing adenovirus gene expression and viral replication by promoter replacement (1997)

The adenovirus E4 promoter was replaced by a synthetic promoter composed of a minimal TATA box and five consensus 17-mer yeast GAL4-binding-site elements. The viral vectors, which also contained human factor IX (hFIX) cDNA driven by Rous sarcoma virus long terminal repeat in the E1 region, were then constructed and expanded in 293 cells permanently expressing GAL4/VP16 fusion protein. Viral replication and expression of adenovirus E4 genes and late genes (hexon and fiber) were evaluated in vitro in the human lung carcinoma cell line H1299. Viral replication and viral gene expression were dramatically reduced in the cells transduced by vectors with a replaced E4 promoter compared to the levels in the cells transduced by vectors with the wild-type E4 promoter. The levels of transgene (hFIX) expression remained similar between vectors with or without E4 promoter replacement. These results indicate that diminution of viral gene expression and viral replication is achievable by promoter replacement.
Exploring the thermal impact on manycore processor performance (2010)

Performance of processors with many simple parallel cores is limited by the serial part of the workload, requiring an asymmetric core organization with one or more aggressive “primary” cores for better serial performance. A primary core introduces power-hungry microarchitectural structures and usually causes severe local hot spots. This paper explores the thermal impact on manycore processor architecture and evaluates its performance. Preliminary results show that thermal constraints reduce performance as expected, but also make performance almost insensitive to the complexity of the primary core across a diverse degrees of parallelism, which greatly reduces design complexity.
Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer (2018)

B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the <i>BCL2A1</i> gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces death, which is of potential therapeutic importance. These findings indicate that MUC1-C is a target for the treatment of TNBCs unresponsive to agents that inhibit anti-apoptotic members of the BCL-2 family.
Back-to-Front Display of Voxel Based Objects (1985)

This straightforward 3-D display algorithm traverses voxels slice by slice to project each voxel on the screen. No surface detection or z-buffer is needed.
HPV-positive status associated with inflamed immune microenvironment and improved response to anti-PD-1 therapy in head and neck squamous cell carcinoma (2019)

Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.
Epicardial-Derived Cell Epithelial-to-Mesenchymal Transition and Fate Specification Require PDGF Receptor Signaling (2011)

Signaling through both PDGF receptors is necessary for epicardial EMT and formation of epicardial-mesenchymal derivatives. PDGF receptors also have independent functions in the development of specific epicardial-derived cell fates.
Tailored polymeric membranes for Mycobacterium smegmatis porin A (MspA) based biosensors (2015)

Nanopores based on protein channels inserted into lipid membranes have paved the way towards a wide-range of inexpensive biosensors, especially for DNA sequencing. A key obstacle in using these biological ion channels as nanodevices is the poor stability of lipid bilayer membranes. Amphiphilic block copolymer membranes have emerged as a robust alternative to lipid membranes. While previous efforts have shown feasibility, we demonstrate for the first time the effect of polymer composition on MspA protein functionality. We show that membrane-protein interaction depends on the hydrophobic-hydrophilic ratio (f-ratio) of the block copolymer. These effects are particularly pronounced in asymmetric protein pores like MspA compared to the cylindrical α-Hemolysin pore. A key effect of membrane-protein interaction is the increased 1/f<sup>α</sup> noise. After first showing increases in 1/f<sup>α</sup> behaviour arise from increased substate activity, the noise power spectral density <i>S(f)</i> was used as a qualitative tool for understanding protein-membrane interactions in polymer membranes. Polymer compositions with f-ratios close to lipid membranes caused noise behaviour not observed in lipid membranes. However, by modifying the f-ratio using a modular synthetic approach, we were able to design a block copolymer exhibiting noise properties similar to a lipid membrane, albeit with better stability. Thus, by careful optimization, block copolymer membranes can emerge as a robust alternative for protein-pore based nano-biosensors.
The Resurrection and Moral Theology: Does it Make any Difference (2007)

The following is an excerpt from the forthcoming book, The Resurrection-Effect in Christian Life and Thought. In a concluding chapter, the strange absence of reference to the resurrection in ethical and moral deliberations is considered. Here, we take up this question and consider more positively the resurrection-effect in the theory and practice of Christian morality, and in the discernment of the ethical values which profoundly influence world history.
Global and local model quality estimation at CASP8 using the scoring functions QMEAN and QMEANclust (2009)

Identifying the best candidate model among an ensemble of alternatives is crucial in protein structure prediction. For this purpose, scoring functions have been developed which either calculate a quality estimate on the basis of a single model or derive a score from the information contained in the ensemble of models generated for a given sequence (i.e., consensus methods). At CASP7, consensus methods have performed considerably better than scoring functions operating on single models. However, consensus methods tend to fail if the best models are far from the center of the dominant structural cluster. At CASP8, we investigated whether our hybrid method QMEANclust may overcome this limitation by combining the QMEAN composite scoring function operating on single models with consensus information. We participated with four different scoring functions in the quality assessment category. The QMEANclust consensus scoring function turned out to be a successful method both for the ranking of entire models but especially for the estimation of the per-residue model quality. In this article, we briefly describe the two scoring functions QMEAN and QMEANclust and discuss their performance in the context of what went right and wrong at CASP8. Both scoring functions are publicly available at http://swissmodel.expasy.org/qmean/.
A neuromorphic controller with a human teacher (1988)

Trainable adaptive controllers (TACs) are a subset of process controllers in which much of the design is done online by means of training rather than programming. The authors show how a neural-network-based architecture may be used to implement a general-purpose TAC. An example of controlling a cart-pole system (an inverted pendulum mounted on a cart) is provided. It is found that filtering of the human-teacher training data, using a dynamic model of the teacher, significantly improves the neuromorphic TAC's performance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An HIV-1 Replication Pathway Utilizing Reverse Transcription Products That Fail To Integrate (2013)

Integration is a central event in the replication of retroviruses, yet ≥ 90% of HIV-1 reverse transcripts fail to integrate, resulting in accumulation of unintegrated viral DNA in cells. However, understanding what role, if any, unintegrated viral DNA plays in the natural history of HIV-1 has remained elusive. Unintegrated HIV-1 DNA is reported to possess a limited capacity for gene expression restricted to early gene products and is considered a replicative dead end. Although the majority of peripheral blood CD4(+) T cells are refractory to infection, nonactivated CD4 T cells present in lymphoid and mucosal tissues are major targets for infection. Treatment with cytokine interleukin-2 (IL-2), IL-4, IL-7, or IL-15 renders CD4(+) T cells permissive to HIV-1 infection in the absence of cell activation and proliferation and provides a useful model for infection of resting CD4(+) T cells. We found that infection of cytokine-treated resting CD4(+) T cells in the presence of raltegravir or with integrase active-site mutant HIV-1 yielded de novo virus production following subsequent T cell activation. Infection with integration-competent HIV-1 naturally generated a population of cells generating virus from unintegrated DNA. Latent infection persisted for several weeks and could be activated to virus production by a combination of a histone deacetylase inhibitor and a protein kinase C activator or by T cell activation. HIV-1 Vpr was essential for unintegrated HIV-1 gene expression and de novo virus production in this system. Bypassing integration by this mechanism may allow the preservation of genetic information that otherwise would be lost.
Gene and cytokine therapy for heart failure: molecular mechanisms in the improvement of cardiac function (2012)

Despite significant advances in pharmacological and clinical treatment, heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Many new therapeutic strategies, including cell transplantation, gene delivery, and cytokines or other small molecules, have been explored to treat HF. Recent advancement of our understanding of the molecules that regulate cardiac function uncover many of the therapeutic key molecules to treat HF. Furthermore, a theory of paracrine mechanism, which underlies the beneficial effects of cell therapy, leads us to search novel target molecules for genetic or pharmacological strategy. Gene therapy means delivery of genetic materials into cells to achieve therapeutic effects. Recently, gene transfer technology in the cardiovascular system has been improved and several therapeutic target genes have been started to examine in clinical research, and some of the promising results have been emerged. Among the various bioactive reagents, cytokines such as granulocyte colony-stimulating factor and erythropoietin have been well examined, and a number of clinical trials for acute myocardial infarction and chronic HF have been conducted. Although further research is needed in both preclinical and clinical areas in terms of molecular mechanisms, safety, and efficiency, both gene and cytokine therapy have a great possibility to open the new era of the treatment of HF.
Characterization of an interleukin-6-mediated autocrine growth loop in the human multiple myeloma cell line, U266 (1991)

It has been reported recently that freshly isolated human myeloma cell cultures proliferate in response to added interleukin-6 (IL-6). Endogenous levels of IL-6 found in the same cultures suggested that an autocrine growth loop may contribute to cell growth. However, the lack of homogenous cell populations in primary myeloma cultures has made it difficult to distinguish between paracrine and autocrine growth mechanisms. To precisely address the autocrine growth issue we have evaluated the growth of the human myeloma cell line, U266. We have found that a neutralizing anti-IL-6 monoclonal antibody can inhibit U266 proliferation. Furthermore, the addition of IL-6 antisense oligonucleotides also inhibits U266 proliferation. These effects are reversed by adding IL-6, suggesting the presence of an autocrine loop. Using bioassays with two different IL-6-dependent cell lines, we were able to detect IL-6 in concentrated U266 supernatants. IL-6 mRNA was detected by polymerase chain reaction amplification of cDNA. Cell cycle parameter analysis shows that IL-6 acts to release a block in G1. Taken together these results present conclusive evidence for IL-6-mediated autocrine growth in the U266 human myeloma cell line.
Research and implementation of a scalable secure active network node (2003)

Active networks are packet-switched networks. It allows users to inject customized programs into the intermediate node of the network. The important difference of active network from traditional network is that active network consists of a series of active network nodes that are able to execute active codes and compute them. So, an active network node is the key of the architecture of active networks. This paper presents a scalable and secure active network node that provides the required flexibility of active network technology for dynamic services customized by users deployment and application-specific data processing and forwarding. In this paper, the composing components and services request interface and active application API are introduced, which make the active network node scalable, and the functions of the composing components can be dynamically extended. By describing the process procedure of capsules, we discuss the communication among these composing components. We develop a high performance active network node with a new mechanism to load an active code. We make the active network node secure by using a digital signature and secure execution engine that can authenticate the identities of principals and authorize to control resources accessing.
Growth and gastrointestinal nematode parasitism in lambs grazing either lucerne (Medicago sativa) or sulla (Hedysarum coronarium) which contains condensed tannins (1995)

SUMMARY Two grazing experiments were undertaken to evaluate the effects of sulla ( Hedysarum coronarium ) which contains condensed tannins (CT) and lucerne ( Medicago sativa ), which does not contain CT, on the performance of parasitized and non-parasitized lambs. The work was carried out near Palmerston North, New Zealand in 1992 and 1993. Experiment 1 used lambs which were either genetically ‘conventional’ or ‘resistant’ to gastrointestinal nematodes and which had a naturally acquired heavy parasite burden (faecal egg count (FEC) 1300–2500 eggs per gram faeces (epg)). They were either drenched to remove all the parasites or remained undrenched when allocated to pure swards of either sulla or lucerne for the 28-day experimental period. Liveweight gains of drenched lambs were higher with sulla (mean 302 g/day) than with lucerne (mean 245 g/day; P &lt; 0·02) and rates of gain were not reduced ( P = 0·10) by genetic resistance to nematodes. Undrenched lambs had mean faecal egg counts of 1090–2220 epg after 28 days, with higher counts in lambs grazing lucerne than in those grazing sulla ( P &lt; 0·05). Lambs grazing lucerne also had a much lower average daily gain (ADG) (mean 50 g/day) than those grazing sulla (mean 206 g/day; P &lt; 0·0001). Resistant lambs had reduced ( P = 0·07) ADG in the sulla treatment only. In Expt 2, lambs with a relatively low worm burden (average FEC 250 epg) were either drenched to remove all worms or dosed with 20 000 Trichostrongylus colubriformis infective larvae and grazed on pure sulla or lucerne swards for 42 days. Drenched lambs had a similar liveweight gain (mean 190 g/day) and wool growth when grazing either sulla or lucerne. Undrenched lambs grazing sulla had a greater ADG (mean 129 g/day) than those grazing lucerne (mean −39 g/day; P &lt; 0·0001) and a higher rate of wool growth from mid-side patches ( P &lt; 0·009) and larger wool fibre diameter ( P &lt; 0·05) than those grazing lucerne. Undrenched lambs grazing sulla had lower FECs ( P &lt; 0·05) on days 14, 21, 35 and 42 than those grazing lucerne and lower ( P &lt; 0·05) Trichostrongylus colubriformis worm burdens at slaughter. Undrenched lambs had less perineal faecal contamination when grazing sulla rather than lucerne. Parasite-induced anorexia was evident in the lambs grazing lucerne but not in those grazing sulla. These findings demonstrate that the performance of lambs infected with nematode parasites can vary substantially when given feeds of a similar chemical composition. The superior performance of lambs grazing sulla was probably caused by condensed tannins, which decrease protein degradation in the rumen and can increase post-ruminal protein availability.
Genetic Characterization of Natural Gases (1983)

Natural gases can be characterized genetically using four properties: C2+ concentration, carbon and hydrogen isotope variations in methane, and carbon isotope variation in ethane. Three diagrams for genetic characterization of gases have been designed in which the carbon isotopic composition of methane is correlated with the other parameters. In these diagrams, compositional fields have been defined for primary gases (biogenic, thermogenic associated, and thermogenic nonassociated) and for gases which result from mixing of these gases. These fields are strictly empirical and comprise compositional variations found in about 500 natural gases. The isotopic and compositional variations in natural gases can be described in terms of (1) processes during formation of the gases such as bacterial fermentation or maturation of organic matter, and (2) processes during secondary migration. Mixing of primary gases is an important and common process. Migration of gases predominantly affects the C2+ concentration, whereas the isotopic properties of gaseous hydrocarbons primarily remain unchanged, allowing an assessment of the origin of migrated gases and properties of their source rocks. The formation of gas from humic organic matter and coals is not yet clear from published data. The diagrams use data from various basins and areas. Interstitial gases from the Gulf of California are entirely of bacterial origin: traces of thermogenic gases are formed only in the vicinity of dolerite sills; gases in the south German Molasse basin and in the Vienna basin are of bacterial, mixed, and thermogenic origins. Data from the north Italian Po basin provide examples for genetic characterization of migrated gases.
Generalised electrophilic fluorination by fluoroxy-compounds (1972)

Several different types of fluoroxy-compounds have been shown to behave in solution as electrophilic fluorinating agents; of the reagents studied bis(fluoroxy)-difluoromethane shows promise on the grounds of economy and efficiency.