gebhart/patrepeval huggingface dataset:
Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance. (1991)

A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells. At a concentration of 10% of its own IC50 (mean concentration of drug that causes 50% inhibition of cell growth compared to controls), Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively. Solutol HS 15 was relatively much more potent than the prototypic reversing agent, verapamil, for reversing colchicine resistance, compared to the ability of each agent to reverse colchicine resistance, compared to the ability of each agent to reverse vinblastine resistance. Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific. Considering their different structure and different relative potency for reversing colchicine resistance, Solutol HS 15 and verapamil probably reverse multidrug resistance by different mechanisms. Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo.
The surface epithelium of teleostean fish gills. Cellular and junctional adaptations of the chloride cell in relation to salt adaptation. (1979)

Various species of teleostean fishes were adapted to fresh or salt water and their gill surface epithelium was examined using several techniques of electron microscopy. In both fresh and salt water the branchial epithelium is mostly covered by flat respiratory cells. They are characterized by unusual outer membrane fracture faces containing intramembranous particles and pits in various stages of ordered aggregation. Freeze fracture studies showed that the tight junctions between respiratory cells are made of several interconnecting strands, probably representing high resistance junctions. The organization of intramembranous elements and the morphological characteristics of the junctions do not vary in relation to the external salinity. Towards the base of the secondary gill lamellae, the layer of respiratory cells is interrupted by mitochondria-rich cells ("chloride cells"), also linked to respiratory cells by multistranded junctions. There is a fundamental reorganization of the chloride cells associated with salt water adaptation. In salt water young adjacent chloride cells send interdigitations into preexisting chloride cells. The apex of the seawater chloride cell is therefore part of a mosaic of sister cells linked to surrounding respiratory cells by multistranded junctions. The chloride cells are linked to each other by shallow junctions made of only one strand and permeable to lanthanum. It is therefore suggested that salt water adaptation triggers a cellular reorganization of the epithelium in such a way that leaky junctions (a low resistance pathway) appear at the apex of the chloride cells. Chloride cells are characterized by an extensive tubular reticulum which is an extension of the basolateral plasma membrane. It is made of repeating units and is the site of numerous ion pumps. The presence of shallow junctions in sea water-adapted fish makes it possible for the reticulum to contact the external milieu. In contrast in the freshwater-adapted fish the chloride cell's tubular reticulum is separated by deep apical junctions from the external environment. Based on these observations we discuss how solutes could transfer across the epithelium.
Autonomous Multielectrode System for Monitoring the Interactions of Isoflavonoids with Lung Cancer Cells (2004)

The cytotoxic effect of isoflavonoids in the development of different forms of cancer has been reported by epidemiological and dietary studies. Consequently, there is a search for an accurate and reliable method for monitoring the interactions of these chemicals with cancerous cells. We have developed and optimized a fully autonomous electrochemical biosensor for studying the role of isoflavonoids on A549 lung adenocarcinoma cell line. This advanced biosensor uses a prototype 96-electrode (DOX-96) well-type device that allows the measurement of cell respiratory activity via the consumption of dissolved oxygen. The system provides a continuous, real-time monitoring of cell activity upon exposure to naturally occurring polyphenols, specifically resveratrol, genistein, and quercetin. The system is equipped with a multipotentiostat, a 96-electrode well for measurements and cell culturing with 3 disposable electrodes fitted into each well. A comparison with classical "cell culture" techniques indicates that the biosensor provides real-time measurement with no added reagents. A detection limit of 1 x 10(4) was recorded versus 200 and 6 x 10(3) cells/well for MTT and fluorescence assays, respectively. This method was optimized with respect to cell stability, reproducibility, applied potential, cell density per well, volume/composition of cell culture medium per well, and incubation. Others include total measuring time, temperature, and sterilization procedure. This study represents a basic research tool that may allow researchers to study the type, level, and specific influence of isoflavonoids on cells.
Near‐infrared study of fluctuations in cerebral hemodynamics during rest and motor stimulation: Temporal analysis and spatial mapping (2000)

We have noninvasively studied the motor cortex hemodynamics in human subjects under rest and motor stimulation conditions using a multichannel near-infrared tissue spectrometer. Our instrument measures optical maps of the cerebral cortex at two wavelengths (758 and 830 nm), with an acquisition time of 160 ms per map. We obtained optical maps of oxy- and deoxy-hemoglobin concentration changes in terms of amplitudes of folding average, power spectrum and coherence at the stimulation repetition frequency, and the phase synchronization index. Under periodic motor stimulation conditions, we observed coherence and frequency or phase synchronization of the local hemodynamic changes with stimulation. Our main findings are the following: (1) The amplitude of the hemodynamic response to the motor stimulation is comparable to the amplitude of the fluctuations at rest. (2) The spatial patterns of the oxy- and deoxy-hemoglobin responses to the stimulation are different. (3) The hemodynamic response to stimulation shows a spatial localization and a level of phase synchronization with the motor stimulation that depends on the stimulation period.
De novo identification of VRC01 class HIV-1–neutralizing antibodies by next-generation sequencing of B-cell transcripts (2013)

Next-generation sequencing of antibody transcripts provides a wealth of data, but the ability to identify function-specific antibodies solely on the basis of sequence has remained elusive. We previously characterized the VRC01 class of antibodies, which target the CD4-binding site on gp120, appear in multiple donors, and broadly neutralize HIV-1. Antibodies of this class have developmental commonalities, but typically share only ∼50% amino acid sequence identity among different donors. Here we apply next-generation sequencing to identify VRC01 class antibodies in a new donor, C38, directly from B cell transcript sequences. We first tested a lineage rank approach, but this was unsuccessful, likely because VRC01 class antibody sequences were not highly prevalent in this donor. We next identified VRC01 class heavy chains through a phylogenetic analysis that included thousands of sequences from C38 and a few known VRC01 class sequences from other donors. This "cross-donor analysis" yielded heavy chains with little sequence homology to previously identified VRC01 class heavy chains. Nonetheless, when reconstituted with the light chain from VRC01, half of the heavy chain chimeric antibodies showed substantial neutralization potency and breadth. We then identified VRC01 class light chains through a five-amino-acid sequence motif necessary for VRC01 light chain recognition. From over a million light chain sequences, we identified 13 candidate VRC01 class members. Pairing of these light chains with the phylogenetically identified C38 heavy chains yielded functional antibodies that effectively neutralized HIV-1. Bioinformatics analysis can thus directly identify functional HIV-1-neutralizing antibodies of the VRC01 class from a sequenced antibody repertoire.
Tesseract: a 4D network control plane (2007)

We present Tesseract, an experimental system that enables the direct control of a computer network that is under a single administrative domain. Tesseract’s design is based on the 4D architecture, which advocates the decomposition of the network control plane into decision, dissemination, discovery,anddata planes. Tesseract provides two primary abstract services to enable direct control: the dissemination service that carries opaque control information from the network decision element to the nodes in the network, and the node configuration service which provides the interface for the decision element to command the nodes in the network to carry out the desired control policies. Tesseract is designed to enable easy innovation. The neighbor discovery, dissemination and node configuration services, which are agnostic to network control policies, are the only distributed functions implemented in the switch nodes. A variety of network control policies can be implemented outside of switch nodes without the need for introducing new distributed protocols. Tesseract also minimizes the need for manual node configurations to reduce human errors. We evaluate Tesseract’s responsiveness and robustness when applied to backbone and enterprise network topologies in the Emulab environment. We find that Tesseract is resilient to component failures. Its responsiveness for intra-domain routing control is sufficiently scalable to handle a thousand nodes. Moreover, we demonstrate Tesseract’s flexibility by showing its application in joint packet forwarding and policy based filtering for IP networks, and in link-cost driven Ethernet packet forwarding. 1
Recent developments of collagen-based materials for medical applications and drug delivery systems (1996)

In this review, an attempt was made to summarize some of the recent developments in the application of collagen as a biomaterial and in drug delivery systems. The main applications covered include: collagen for burn/wound cover dressings; osteogenic and bone filling materials; antithrombogenic surfaces; and immobilization of therapeutic enzymes. Recently, collagen used as a carrier for drug delivery has attracted many researchers throughout the world. The use of collagen for various drug delivery systems has also been reviewed in this article. Collagen-based drug delivery systems include: injectable microspheres based on gelatin (degraded form of collagen); implantable collagen-synthetic polymer hydrogels; interpenetrating networks of collagen; and synthetic polymers collagen membranes for ophthalmic delivery. Recent efforts to use collagen-liposomal composites for controlled drug delivery, as well as collagen as controlling membranes for transdermal delivery, were also reviewed. In this review, the main emphasis was on the work done in our laboratory.
A physical model for shear‐wave velocity prediction1 (1996)

Abstract The clay‐sand mixture model of Xu and White is shown to simulate observed relationships between S‐wave velocity (or transit time), porosity and clay content. In general, neither S‐wave velocity nor S‐wave transit time is a linear function of porosity and clay content. For practical purposes, clay content is approximated by shale volume in well‐log applications. In principle, the model can predict S‐wave velocity from lithology and any pair of P‐wave velocity, porosity and shale volume. Although the predictions should be the same if all measurements are error free, comparison of predictions with laboratory and logging measurements show that predictions using P‐wave velocity are the most reliable. The robust relationship between S‐ and P‐wave velocities is due to the fact that both are similarly affected by porosity, clay content and lithology. Moreover, errors in the measured P‐wave velocity are normally smaller than those in porosity and shale volume, both of which are subject to errors introduced by imperfect models and imperfect parameters when estimated from logs. Because the model evaluates the bulk and shear moduli of the dry rock frame by a combination of Kuster and Toksöz’ theory and differential effective medium theory, using pore aspect ratios to characterize the compliances of the sand and clay components, the relationship between P‐ and S‐wave velocities is explicit and consistent. Consequently the model sidesteps problems and assumptions that arise from the lack of knowledge of these moduli when applying Gassmann's theory to this relationship, making it a very flexible tool for investigating how the v P ‐ v s relationship is affected by lithology, porosity, clay content and water saturation. Numerical results from the model are confirmed by laboratory and logging data and demonstrate, for example, how the presence of gas has a more pronounced effect on P‐wave velocity in shaly sands than in less compliant cleaner sandstones.
Mirk/dyrk1B Decreases the Nuclear Accumulation of Class II Histone Deacetylases during Skeletal Muscle Differentiation (2004)

Mirk/dyrk1B is a member of the dyrk/minibrain family of serine/threonine kinases that mediate the transition from growth to differentiation in lower eukaryotes and mammals. Depletion of endogenous Mirk from C2C12 myoblasts by RNA interference blocks skeletal muscle differentiation (Deng, X., Ewton, D., Pawlikowski, B., Maimone, M., and Friedman, E. (2003) J. Biol. Chem. 278, 41347-41354). We now demonstrate that knockdown of Mirk blocks transcription of the muscle regulatory factor myogenin. Co-expression of Mirk with MEF2C, but not MyoD or Myf5, enhanced activation of the myogenin promoter in a Mirk kinase-dependent manner. Mirk activated MEF2 not through direct phosphorylation of MEF2 but by phosphorylation of its inhibitors, the class II histone deacetylases (HDACs). MEF2 is sequestered by class II HDACs such as HDAC5 and MEF2-interacting transcriptional repressor (MITR). Mirk antagonized the inhibition of MEF2C by MITR, whereas kinase-inactive Mirk was ineffective. Mirk phosphorylates class II HDACs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner. Moreover, less mutant MITR phosphomimetic at the Mirk phosphorylation site localized in the nucleus than wild-type MITR. Regulation of class II HDACs occurs by multiple mechanisms. Others have shown that calcium signaling leads to phosphorylation of HDACs at 14-3-3-binding sites, blocking their association with MEF2 within the nucleus. Mirk provides another level of regulation. Mirk is induced within the initial 24 h of myogenic differentiation and enables MEF2 to transcribe the myogenin gene by decreasing the nuclear accumulation of class II HDACs.
Enhancing lifetime and security of PCM-based main memory with start-gap wear leveling (2009)

Phase Change Memory (PCM) is an emerging memory technology that can increase main memory capacity in a cost-effective and power-efficient manner. However, PCM cells can endure only a maximum of 107 - 108 writes, making a PCM based system have a lifetime of only a few years under ideal conditions. Furthermore, we show that non-uniformity in writes to different cells reduces the achievable lifetime of PCM system by 20x. Writes to PCM cells can be made uniform with Wear-Leveling. Unfortunately, existing wear-leveling techniques require large storage tables and indirection, resulting in significant area and latency overheads.
Adenoviral-mediated p53 tumor suppressor gene therapy of human ovarian carcinoma. (1996)

Mutations of p53 gene are reported in 50-60% of human cancers and reintroduction of wild-type p53 can suppress cell proliferation. In this study, replication deficient recombinant adenovirus encoding wild-type p53 (ACN53) under the control of the human cytomegalovirus (CMV) promoter was constructed. A specific incorporation of the p53 gene with ACN53 reduced 3 (deleted p53 gene) cells was observed. ACN53 reduced the colony-forming ability of SK-OV-3 cells 72-216 h after single infection. A highly aggressive ovarian xenograft model was established in which animals die between 25-45 days. A localization study with the adenovirus-containing beta galactosidase reporter gene showed effective gene transfer in the tumor tissues. Ex vivo treatment of SK-OV-3 cells with ACN53 followed by injection into nude mice, increased the survival of the p53 treated mice by more than 50% compared with control animals. Gene therapy with ACN53 in intraperitoneal model of SK-OV-3 cells in two independent experiments revealed that there were some long-term survivors in the group of mice [2/5 (66 and 120 days) and [2/8 (166 and 423 days)] treated with ACN53. These findings demonstrate the potential of the p53 tumor suppressor gene therapy in human ovarian carcinoma.
Sudden Death from Cardiac Arrest — Improving the Odds (2000)

Each year cardiovascular disease claims the lives of more than 950,000 people in the United States. Of these deaths, a substantial proportion are due to out-of-hospital cardiac arrest, and only 2 to 5 percent of the 225,000 persons who have sudden cardiac arrest outside a hospital are successfully resuscitated. For those with ventricular fibrillation, these dismal statistics are in stark contrast to the high success rate when defibrillation is performed immediately after the onset of ventricular fibrillation, as in the cardiac catheterization laboratory. It has been shown that for every minute that elapses before defibrillation, 7 to 10 percent of . . .
Toward a better understanding and quantification of methane emissions from shale gas development (2014)

The identification and quantification of methane emissions from natural gas production has become increasingly important owing to the increase in the natural gas component of the energy sector. An instrumented aircraft platform was used to identify large sources of methane and quantify emission rates in southwestern PA in June 2012. A large regional flux, 2.0-14 g CH4 s(-1) km(-2), was quantified for a ∼ 2,800-km(2) area, which did not differ statistically from a bottom-up inventory, 2.3-4.6 g CH4 s(-1) km(-2). Large emissions averaging 34 g CH4/s per well were observed from seven well pads determined to be in the drilling phase, 2 to 3 orders of magnitude greater than US Environmental Protection Agency estimates for this operational phase. The emissions from these well pads, representing ∼ 1% of the total number of wells, account for 4-30% of the observed regional flux. More work is needed to determine all of the sources of methane emissions from natural gas production, to ascertain why these emissions occur and to evaluate their climate and atmospheric chemistry impacts.
Complex Extracellular Matrices Promote Tissue‐Specific Stem Cell Differentiation (2005)

Most cells in tissues contact an extracellular matrix on at least one surface. These complex mixtures of interacting proteins provide structural support and biological signals that regulate cell differentiation and may be important for stem cell differentiation. In this study, we have grown a rhesus monkey embryonic stem cell line in the presence of various extracellular matrix components in monolayer, in a NASA-developed rotating wall vessel bioreactor in vitro, and subcutaneously in vivo. We find that individual components of the extracellular matrix, such as laminin-1 or collagen I, do not influence the growth or morphology of the cells. In contrast, a basement membrane extract, Matrigel, containing multiple extracellular matrix components, induces the cells within 4 days to form immature glandular- and tubular-like structures, many of which contain a lumen with polarized epithelium and microvilli. Such structures were seen in vitro when the cells were grown in the bioreactor and when the cells were injected into mice. These tubular- and glandular-like structures were polarized epithelia based on immunostaining for laminin and cytokeratin. The cell aggregates and tumors also contained additional mixed populations of cells, including mesenchymal cells and neuronal cells, based on immunostaining with vimentin and neuronal markers. An extract of cartilage, containing multiple cartilage matrix components, promoted chondrogenesis in vivo where alcian blue-stained cartilage nodules could be observed. Some of these nodules stained with von Kossa, indicating that they had formed calcified cartilage. We conclude that extracellular matrices can promote the differentiation of embryonic stem cells into differentiated cells and structures that are similar to the tissue from which the matrix is derived. Such preprogramming of cell differentiation with extracellular matrices may be useful in targeting stem cells to repair specific damaged organs.
Metabolism and thermoregulation during stages of sleep in humans exposed to heat and cold (1981)

Electrophysiological stages of sleep, oxygen consumption (VO2), and skin (Tsk) and rectal (Tre) temperatures were recorded from six virtually naked male subjects exposed to ambient temperatures (Ta) of 21, 24, 29, 34, and 37 degrees C. VO2 increased during sleep as a whole as Ta departed from thermoneutrality (29 degrees C) and was significantly greater during rapid-eye-movement (REM) sleep than during adjacent nonrapid-eye-movement (NREM) periods at low and high Ta but not at 29 degrees C. Tsk showed small but significant increases during REM sleep at 29, 34, and 37 degrees C, but Tre did not change during REM sleep at any Ta. Shivering was present during wakefulness at 21 and 24 degrees C but occurred only occasionally during stages 1 and 2 sleep at 21 degrees C. The increases in VO2 and the absence of marked changes in vasomotor tone during REM sleep in the cold were unexpected and possibly indicate that REM sleep is not as thermally disruptive in humans as in other mammals.
The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells (2005)

Treatment with synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) is remarkably protective against otherwise lethal infection. Here, we describe an essential role for the transcription factor T-bet in mediating the protective function of CpG ODNs. Loss of T-bet in conventional CD11c(hi) dendritic cells (DCs) and in plasmacytoid DCs impaired production of IFNs. Strikingly, in contrast to Rag2-/- mice, Rag2-/- mice that also lacked T-bet (DKO) could not be rescued from lethal Listeria monocytogenes infection by prior treatment with CpG ODN. Rescue was achieved by adoptive transfer of CD11c(hi) DCs from WT, but not T-bet-/-, CpG ODN-treated donor mice. We conclude that T-bet in DCs is required for the adjuvant activity of CpG ODN in infection, revealing its vital role in innate immunity.