gebhart/patrepeval huggingface dataset:
Taxonomy and Implementation of Redirection Techniques for Ubiquitous Passive Haptic Feedback (2008)

Traveling through immersive virtual environments (IVEs) by means of real walking is an important activity to increase naturalness of VR-based interaction. However, the size of the virtual world often exceeds the size of the tracked space so that a straightforward implementation of omni-directional and unlimited walking is not possible. Redirected walking is one concept to solve this problem of walking in IVEs by inconspicuously guiding the user on a physical path that may differ from the path the user visually perceives. When the user approaches a virtual object she can be redirected to a real proxy object that is registered to the virtual counterpart and provides passive haptic feedback. In such passive haptic environments, any number of virtual objects can be mapped to proxy objects having similar haptic properties, e.g., size, shape and texture. The user can sense a virtual object by touching its real world counterpart. Redirecting a user to a registered proxy object makes it necessary to predict the user's intended position in the IVE. Based on this target position we determine a path through the physical space such that the user is guided to the registered proxy object. We present a taxonomy of possible redirection techniques that enable user guidance such that inconsistencies between visual and proprioceptive stimuli are imperceptible. We describe how a user's target in the virtual world can be predicted reliably and how a corresponding real-world path to the registered proxy object can be derived.
Profiling the humoral immune response to infection by using proteome microarrays: High-throughput vaccine and diagnostic antigen discovery (2005)

Despite the increasing availability of genome sequences from many human pathogens, the production of complete proteomes remains at a bottleneck. To address this need, a high-throughput PCR recombination cloning and expression platform has been developed that allows hundreds of genes to be batch-processed by using ordinary laboratory procedures without robotics. The method relies on high-throughput amplification of each predicted ORF by using gene specific primers, followed by in vivo homologous recombination into a T7 expression vector. The proteins are expressed in an Escherichia coli-based cell-free in vitro transcription/translation system, and the crude reactions containing expressed proteins are printed directly onto nitrocellulose microarrays without purification. The protein microarrays are useful for determining the complete antigen-specific humoral immune-response profile from vaccinated or infected humans and animals. The system was verified by cloning, expressing, and printing a vaccinia virus proteome consisting of 185 individual viral proteins. The chips were used to determine Ab profiles in serum from vaccinia virus-immunized humans, primates, and mice. Human serum has high titers of anti-E. coli Abs that require blocking to unmask vaccinia-specific responses. Naive humans exhibit reactivity against a subset of 13 antigens that were not associated with vaccinia immunization. Naive mice and primates lacked this background reactivity. The specific profiles between the three species differed, although a common subset of antigens was reactive after vaccinia immunization. These results verify this platform as a rapid way to comprehensively scan humoral immunity from vaccinated or infected humans and animals.
Phosphorylation of glycogen synthase kinase-3 β at serine 9 confers cisplatin resistance in ovarian cancer cells (2007)

Cisplatin is commonly used in the treatment of advanced ovarian carcinoma. A major limitation of the use of cisplatin is the development of resistance in tumors. Glycogen synthase kinase-3 beta (GSK-3beta) is a multi-functional serine/threonine kinase. Its activity is regulated negatively by the phosphorylation of serine 9 (pGSK-3beta-ser-9) and positively by the phosphorylation of tyrosine 216 (pGSK-3beta-tyr-216). We compared the expression/phosphorylation of GSK-3beta between the cisplatin-sensitive ovarian carcinoma cell line A2780 and its cisplatin-resistant derivative CP70. The expression levels of total GSK-3beta and pGSK-3beta-tyr-216 were similar in these cells; however, CP70 cells had a much higher expression of pGSK-3beta-ser-9 than A2780 cells. Lithium chloride, which is a GSK-3beta inhibitor and stimulates pGSK-3beta-ser-9, significantly increased the IC50 of cisplatin and counteracted cisplatin-induced apoptosis of A2780 and CP70 cells. In contrast, overexpression of a constitutively active S9A GSK-3beta mutant increased the sensitivity of CP70 cells to cisplatin and significantly enhanced cisplatin-mediated apoptosis. It is suggested that the cisplatin-resistance of CP70 cells is mediated by stabilizing p53. We demonstrated that GSK-3beta negatively regulated the expression of p53. Therefore, pGSK-3beta-ser-9 may confer the cisplatin resistance of ovarian carcinomas through the stabilization of p53 expression. Our study establishes a potential role of GSK-3beta in the development of cisplatin resistance in initially sensitive tumors.
Generation of glucocorticoid-responsive Moloney murine leukemia virus by insertion of regulatory sequences from murine mammary tumor virus into the long terminal repeat (1985)

The glucocorticoid-regulatory sequences from the murine mammary tumor virus long terminal repeat (MMTV LTR) were introduced into the LTR of Moloney murine leukemia virus (M-MuLV) by recombinant DNA techniques. The site of insertion was in the M-MuLV LTR U3 region at -150 base pairs with respect to the RNA cap site. Infectious M-MuLVs carrying the altered LTRs (Mo + MMTV M-MuLVs) were recovered by transfection of proviral clones into NIH-3T3 cells. The Mo + MMTV M-MuLVs were hormonally responsive in that infection was 3 logs more efficient when performed in the presence of dexamethasone, irrespective of the orientation of the inserted MMTV sequences. However, even in the presence of hormone, the Mo + MMTV M-MuLVs were less infectious than wild-type M-MuLV. In contrast to the large effect on infectivity, dexamethasone induced virus-specific RNA levels in chronically Mo + MMTV M-MuLV-infected cells only two- to fourfold. Fusion plasmids between the altered LTRs and the bacterial chloramphenicol acetyltransferase gene allowed the investigation of LTR promoter strength by the transient chloramphenicol acetyltransferase expression assay. The chloramphenicol acetyltransferase assays indicated that the insertion of MMTV sequences into the M-MuLV LTR reduced promoter activity in the absence of glucocorticoids but that promoter activity could be induced two- to fivefold by dexamethasone. The Mo + MMTV M-MuLVs were also tested for the possibility that viral DNA synthesis or integration during initial infection was enhanced by dexamethasone. However, no significant difference was detected between cultures infected in the presence or absence of hormone. The insertion of MMTV sequences into an M-MuLV LTR deleted of its enhancer sequences did not yield infectious virus or active promoters, even in the presence of dexamethasone.
Fabrication of 10 nm enclosed nanofluidic channels (2002)

We made uniform arrays of nanometer scale structures using nanoimprint lithography over large areas (100 mm wafers). The nanofluidic channels were further narrowed and sealed by techniques that are based on nonuniform deposition. The resulting sealed channels have a cross section as small as 10 nm by 50 nm, of great importance for confining biological molecules into ultrasmall spaces. These techniques can be valuable fabrication tools for Nanoelectromechanical Systems and Micro/Nano Total Analysis Systems.
Fast intra mode decision of HEVC based on hierarchical structure (2011)

In this paper, we propose a fast intra mode decision for high efficiency video coding (HEVC) to reduce its encoding complexity. It proposes an early termination method under its hierarchical structure that uses the intra prediction mode (IPM) of corresponding previous-depth prediction unit (PU) and block size of current-depth transform unit (TU). To reduce even more complexity, the number of candidates of the rough mode decision (RMD) is further reduced for RD optimization, and the IPM of corresponding previous-depth PU is always included in the list of candidates for intra mode decision. Experimental results show that the encoding complexity can be reduced by up to 22.99% in high efficiency (HE) condition and 26.16% in low complexity (LC) condition with only a little bit-rate increment compared to the full intra mode decision of HM 3.0.
Synthesis of daunorubicin analogs with novel 9-acyl substituents (1979)

Synthetic approaches to anthracyclines bearing novel 9-acyl substituents were investigated. Reaction of the lithium enolate of N-(trifluoroacetyl)daunorubicin (9) with methyl iodide in tetrahydrofuran afforded only the 9-propionyl derivative 10 in high yield. Reaction of 10 under identical conditions cleanly afforded the 9-isobutyryl derivative 11. Extension of this procedure to other alkylating agents (ethyl iodide, benzyl bromide, and heptyl iodide) required hexamethylphosphoramide as cosolvent and afforded mixtures of mono- and dialkylated products as well as recovered 9. The amino group was deblocked with NaOH in aqueous tetrahydrofuran, except in the case of the dibenzyl derivative 13 which was inert under these conditions. The 9-formyl analogue 23 was prepared via NaIO4 cleavage of 13-dihydroadriamycin (21). Antitumor evaluation against P388 leukemia in mice showed 23 to have activity comparable to the parent compounds, while the C-alkylated analogues were less active.
Emerging pharmacologic therapies for osteoporosis (2007)

Osteoporotic fractures are an important public health problem, contributing substantially to morbidity and mortality in an ageing world population and consuming considerable health resources. Presently available pharmacologic therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Considerable efforts are being made to develop new, more effective treatments for osteoporosis, and to refine/optimize existing therapies. These novel treatments include an expanding array of drugs that primarily inhibit osteoclastic bone resorption: estrogenic compounds, bisphosphonates, inhibitors of receptor activator of NF-kappaB ligand signaling, cathepsin K inhibitors, c-src kinase inhibitors, integrin inhibitors and chloride channel inhibitors. The advent of intermittent parathyroid hormone (PTH) therapy has provided proof-of-principle that osteoblast-targeted (anabolic) agents can effectively prevent osteoporotic fractures, and is likely to be followed by the introduction of other therapies based on PTH (orally active PTH analogs, antagonists of the calcium sensing receptor, PTH-related peptide analogs) and/or agents that induce osteoblast anabolism by means of pathways involving key, recently identified, molecular targets (wnt-low-density lipoprotein receptor-related protein 5 signaling, sclerostin and matrix extracellular phosphoglycoprotein).
Susceptibility of HIV-2, Siv and Shiv to Various Anti-HIV-1 Compounds: Implications for Treatment and Postexposure Prophylaxis (2004)

Limited information is available on the activity of antiretroviral drugs against human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) strains to guide their use in treatment or prophylaxis. We evaluated the antiviral activity of 16 approved drugs and one experimental drug, AMD3100, against two wild-type HIV-2 (ROD and EHO) isolates, two strains of SIV (mac251 and B670), and two strains of simian-human immunodeficiency virus (SHIV) that contain the reverse transcriptase (RTSHIV) or envelope glycoprotein (SHIV89.6) of human immunodeficiency virus type 1 (HIV-1) in a SIV(mac239) background. Drug susceptibility was measured conventionally by the MT-4/MTT assay, and results were analysed as fold changes in 50% effective concentration (EC50) relative to the EC50 for HIV-1 (IIIB). The nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine, lamivudine, stavudine, didanosine, zalcitabine and abacavir as well as the nucleotide reverse transcriptase inhibitor tenofovir retained full activity against all six viruses except for SIV and SHIV89.6 that showed low-level resistance to didanosine. The protease inhibitors (PIs) ritonavir, indinavir, saquinavir and nelfinavir were found to be active against some HIV-2 or SIV strains. However, a significant reduction in susceptibility was seen with indinavir against SHIV89.6 (3.3-fold), and with amprenavir against HIV-2(ROD) (8.8-fold). All viruses except for RTSHIV showed a >200-fold decrease in susceptibility for the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine, delavirdine and efavirenz, indicating high-level resistance. AMD3100, a CXCR4 antagonist, was active against HIV-2 and SHIV89.6, a finding consistent with the use of the CXCR4 co-receptor by these isolates, but was inactive against SIV strains. In contrast, enfuvirtide (T-20) was active against SHIV89.6 but had reduced inhibitory activity against both HIV-2 and SIV strains predicting little therapeutic value against these viruses. These findings support the use of NRTIs, tenofovir, but not NNRTIs, for treating HIV-2-infected persons or for prophylaxis against HIV-2 and SIV. The clinical significance of the low-level resistance of HIV-2 and SIV to some PIs is unclear. Co-receptor antagonists such as AMD3100 show promising anti-HIV-2 therapeutic modalities. Both AMD3100 and enfuvirtide could be used for prophylaxis against SHIV89.6.
Administration of n-3 Fatty Acids in the Diets of Rats or Directly to Hepatocyte Cultures Results in Different Effects on Hepatocellular ApoB Metabolism and Secretion (1999)

Hepatocytes derived either from rats fed a diet enriched in n-3 fatty acids or from rats fed a low-fat diet and cultured with an n-3 fatty acid (eicosapentaenoic acid, EPA) in vitro were used to distinguish between the dietary effects and the direct effects of n-3 fatty acids on hepatocellular apolipoprotein (apo) B metabolism and secretion. ApoB-48 and apoB-100 synthesis, degradation, and secretion as large (d<1.006) and small (d>1.006) particles were determined after a pulse label with [35S]methionine. These effects were compared with changes in triacylglycerol (TAG) synthesis and secretion and with changes in de novo fatty acid synthesis (using 3H2O incorporation) under identical conditions. When n-3 fatty acid was given via the dietary route, apoB-48 very low density lipoprotein (VLDL) secretion was inhibited, but there was no effect on the secretion of apoB-100 VLDL. There was no effect on the secretion of either apoB-48 or apoB-100 as small, dense particles (d>1.006). Cellular TAG synthesis was significantly inhibited under these conditions, and fatty acid synthesis de novo was inhibited by 80%. By contrast, after direct addition of EPA to hepatocytes from normal rats, the secretion of both apoB-48 and apoB-100 VLDL was suppressed. The secretion of apoB-48, but not of apoB-100, as dense particles was also inhibited. However, there was little or no effect on TAG synthesis nor on fatty acid synthesis de novo. In addition, whereas dietary administration of n-3 fatty acid gave rise to decreased net synthesis and degradation of apoB-48, direct administration in vitro resulted in increased degradation with no effect on net synthesis. We conclude that the effects of n-3 fatty acids on hepatic lipid and apoB metabolism differ according to whether they are administered in vivo, via the dietary route, or in vitro, via direct addition to hepatocyte cultures.
Genomic Insights into Methanotrophy: The Complete Genome Sequence of Methylococcus capsulatus (Bath) (2004)

Methanotrophs are ubiquitous bacteria that can use the greenhouse gas methane as a sole carbon and energy source for growth, thus playing major roles in global carbon cycles, and in particular, substantially reducing emissions of biologically generated methane to the atmosphere. Despite their importance, and in contrast to organisms that play roles in other major parts of the carbon cycle such as photosynthesis, no genome-level studies have been published on the biology of methanotrophs. We report the first complete genome sequence to our knowledge from an obligate methanotroph, Methylococcus capsulatus (Bath), obtained by the shotgun sequencing approach. Analysis revealed a 3.3-Mb genome highly specialized for a methanotrophic lifestyle, including redundant pathways predicted to be involved in methanotrophy and duplicated genes for essential enzymes such as the methane monooxygenases. We used phylogenomic analysis, gene order information, and comparative analysis with the partially sequenced methylotroph Methylobacterium extorquens to detect genes of unknown function likely to be involved in methanotrophy and methylotrophy. Genome analysis suggests the ability of M. capsulatus to scavenge copper (including a previously unreported nonribosomal peptide synthetase) and to use copper in regulation of methanotrophy, but the exact regulatory mechanisms remain unclear. One of the most surprising outcomes of the project is evidence suggesting the existence of previously unsuspected metabolic flexibility in M. capsulatus, including an ability to grow on sugars, oxidize chemolithotrophic hydrogen and sulfur, and live under reduced oxygen tension, all of which have implications for methanotroph ecology. The availability of the complete genome of M. capsulatus (Bath) deepens our understanding of methanotroph biology and its relationship to global carbon cycles. We have gained evidence for greater metabolic flexibility than was previously known, and for genetic components that may have biotechnological potential.
Pathophysiology of cardiac dysfunction in congestive heart failure. (1993)

Although various factors, such as myocardial infarction, pressure overload and volume overload, result in the development of congestive heart failure (CHF), the pathogenesis of contractile dysfunction in this situation is poorly understood. Loss of cardiac muscle due to myocardial infarction appears to activate several humoral and hormonal pathways, including the renin-angiotensin and sympathetic systems which serve as adaptive mechanisms to maintain cardiovascular performance at early stages of failure. However, under chronic conditions, an altered hormonal profile produces deleterious effects and permits transition from the compensated heart to the failing heart. Since several risk factors--such as hypertension, hypercholesteremia, stress, diabetes, smoking, ageing, obesity and lack of exercise--precipitate ischemic heart disease, it is possible that development of CHF due to myocardial infarction may vary according to the nature of these pathogenetic entities. While a great deal of research work remains in this area of investigation, it is becoming evident that cardiac dysfunction is intimately associated with calcium handling abnormalities of cardiac cells. In view of the role of sarcolemma, sarcoplasmic reticulum and mitochondria in regulating the intracellular concentration of Ca2+ and the importance of myofibrillar interaction with Ca2+, it appears that Ca2+ handling and Ca2+ interaction abnormalities in the failing heart are due to remodelling of different subcellular organelles. Such a remodelling of the subcellular organelles may be due to changes in gene expression for different protein components or the interactions of proteins with phospholipids. Accordingly, it is proposed that new interventions, which could prevent the remodelling of subcellular organelles, be developed for improving the therapy of CHF.
Two-Dimensional Intraventricular Flow Mapping by Digital Processing Conventional Color-Doppler Echocardiography Images (2010)

Doppler echocardiography remains the most extended clinical modality for the evaluation of left ventricular (LV) function. Current Doppler ultrasound methods, however, are limited to the representation of a single flow velocity component. We thus developed a novel technique to construct 2D time-resolved (2D+t) LV velocity fields from conventional transthoracic clinical acquisitions. Combining color-Doppler velocities with LV wall positions, the cross-beam blood velocities were calculated using the continuity equation under a planar flow assumption. To validate the algorithm, 2D Doppler flow mapping and laser particle image velocimetry (PIV) measurements were carried out in an atrio-ventricular duplicator. Phase-contrast magnetic resonance (MR) acquisitions were used to measure in vivo the error due to the 2D flow assumption and to potential scan-plane misalignment. Finally, the applicability of the Doppler technique was tested in the clinical setting. In vitro experiments demonstrated that the new method yields an accurate quantitative description of the main vortex that forms during the cardiac cycle (mean error for vortex radius, position and circulation). MR image analysis evidenced that the error due to the planar flow assumption is close to 15% and does not preclude the characterization of major vortex properties neither in the normal nor in the dilated LV. These results are yet to be confirmed by a head-to-head clinical validation study. Clinical Doppler studies showed that the method is readily applicable and that a single large anterograde vortex develops in the healthy ventricle while supplementary retrograde swirling structures may appear in the diseased heart. The proposed echocardiographic method based on the continuity equation is fast, clinically-compliant and does not require complex training. This technique will potentially enable investigators to study of additional quantitative aspects of intraventricular flow dynamics in the clinical setting by high-throughput processing conventional color-Doppler images.
Presence of a Potent Transcription Activating Sequence in the p53 Protein (1990)

The p53 gene is frequently mutated in a wide variety of human cancers. However, the role of the wild-type p53 gene in growth control is not known. Hybrid proteins that contain the DNA binding domain of yeast GAL4 and portions of p53 have been used to show that the p53 protein contains a transcription-activating sequence that functions in both yeast and mammalian cells. The NH2-terminal 73 residues of p53 activated transcription in mammalian cells as efficiently as the herpes virus protein VP16, which contains one of the strongest known activation domains. Combined with previous data that showed p53 is localized to the nucleus and can bind to DNA, these results support the idea that one function of p53 is to activate the transcription of genes that suppress cell proliferation.
Sulfated Hyaluronic Acid, a Potential Selectin Inhibitor, Ameliorates Experimentally Induced Crescentic Glomerulonephritis (2005)

Our results suggest that SHA inhibits intraglomerular infiltration of macrophages, and prevents progression of experimental crescentic glomerulonephritis. Sulfated polysaccharides might be beneficial for the treatment of crescentic glomerulonephritis.