gebhart/patrepeval huggingface dataset:
Screening of budesonide nanoformulations for treatment of inflammatory bowel disease in an inflamed 3D cell-culture model (2012)

Drug formulation screenings for treatment of inflammatory bowel disease (IBD) are mostly conducted in chemically induced rodent models that represent acute injury-caused inflammation instead of a chronic condition. To accurately screen drug formulations for chronic IBD, a relevant model that mimics the chronic condition in vitro is urgently needed. In an effort to reduce and potentially replace this scientifically and ethically questionable animal testing for IBD drugs, our laboratory has developed an in vitro model for the inflamed intestinal mucosa observed in chronic IBD, which allows high-throughput screening of anti-inflammatory drugs and their formulations. The in vitro model consists of intestinal epithelial cells, human blood-derived macrophages, and dendritic cells that are stimulated by the inflammatory cytokine interleukin-1β. In this study, the model was utilized for evaluation of the efficacy and deposition of budesonide, an anti-inflammatory drug, in three different pharmaceutical formulations: (1) a free drug solution, (2) encapsulated into PLGA nanoparticles, and (3) encapsulated into liposomes. The in vitro model of the inflamed intestinal mucosa demonstrated its ability to differentiate therapeutic efficacy among the formulations while maintaining the convenience of conventional in vitro studies and adequately representing the complex pathophysiological changes observed in vivo.
Locally Generated Angiotensin II in the Adrenal Gland Regulates Basal, Corticotropin-, and Potassium-Stimulated Aldosterone Secretion (1995)

The zona glomerulosa cells of the adrenal gland have an intrinsic renin-angiotensin system that appears to modulate the aldosterone response to potassium and corticotropin. The actions of circulating angiotensin II (Ang II) are mediated by the activation of the Ang II type 1 (AT1) receptor on the adrenal cortex. In this study we examined the effects of the AT1 receptor antagonist DuP 753 and other antagonists on aldosterone secretion in cultured bovine zona glomerulosa cells. Zona glomerulosa cells were cultured in PFMR-4 medium containing 10% fetal calf serum for 72 hours, and the medium was replaced with serum-free medium for the next 24-hour experimental period. DuP 753 (10 mumol/L) inhibited basal aldosterone secretion (from 88.6 +/- 7.1 to 54.8 +/- 9.6 pg/10(6) cells per hour; 38% inhibition). EXP 3174, an active metabolite of DuP 753, also inhibited aldosterone dose dependently (from 88.6 +/- 7.1 to 55.9 +/- 8.4 at 1 mumol/L and 88.6 +/- 7.1 to 21.7 +/- 3.3 at 100 mumol/L; 37% and 75% inhibition, respectively). Another and more potent AT1 receptor antagonist, L158,809, showed significant inhibition at 100 nmol/L, and at 10 mumol/L it inhibited basal aldosterone secretion (from 144.7 +/- 18.2 to 83.4 +/- 17.1 pg/10(6) cells per hour; 42% inhibition). DuP 753 inhibited Ang II (100 nmol/L)-stimulated aldosterone production in a dose-dependent fashion, with a 30% reduction at 100 nmol/L and complete inhibition at 100 mumol/L. DuP 753 also inhibited potassium (12 nmol/L) and corticotropin (1 nmol/L) stimulation of aldosterone in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
Cognitive engineering in the design of human-computer interaction and expert systems (1987)

Computers in Organizational Settings. Organizational Demands and Stress. Software Ergonomics. Ergonomic Demands. Cognitive Demands.Socio-Technical Aspects. Author Index.
Stochastic Resonance in a Neuronal Network from Mammalian Brain (1996)

Stochastic resonance, a nonlinear phenomenon in which random noise optimizes a system's response to a signal, has been postulated to provide a role for noise in information processing in the brain. In these experiments, a time varying electric field was used to deliver both signal and noise directly to a network of neurons from mammalian brain. As the magnitude of the stochastic component of the field was increased, resonance was observed in the response of the neuronal network to a weak periodic signal. This is the first demonstration of stochastic resonance in neuronal networks from the brain.
Fatigue and the delivery of medical care. (2011)

Lack of sleep has well established effects on physiological, cognitive and behavioural functionality. Sleep
deprivation can adversely affect clinical performance as severely as alcohol according to some sources. Sleep
deficiency may be due to loss of one nightâ s sleep or repeated interruptions of sleep. Chronic sleep degrades the
ability to recognise oneâ s ability to recognise the impairments induced by sleep loss. The problem of sleep
deprivation has vexed acute medical practice for decades. Improvement has been painfully slow. The problem is that
all 168 hours throughout every week of every year have to be covered and there are a finite number of doctors to
shoulder the burden. There are many strongly held views about how best to provide night-time and week-end care.
Constructive innovations are thin on the ground. The biggest gap is between administration and doctors with financial
considerations being the limiting factor. It is, however, generally accepted on all sides that sleep loss and fatigue
can have adverse effects on both patients and doctors.
The role of CD8+ T‐cell replicative senescence in human aging (2005)

The strict limit in proliferative potential of normal human somatic cells - a process known as replicative senescence - is highly relevant to the immune system, because clonal expansion is fundamental to adaptive immunity. CD8(+) T cells that undergo extensive rounds of antigen-driven proliferation in cell culture invariably reach the end stage of replicative senescence, characterized by irreversible cell-cycle arrest and a critically short telomere length. Cultures of senescent CD8(+) T cells also show resistance to apoptosis, permanent loss of CD28 expression, altered cytokine profiles, reduced ability to respond to stress, and various functional changes. Cells with similar characteristics accumulate during normal aging as well as in younger persons infected with human immunodeficiency virus, suggesting that the process of replicative senescence is not an artifact of cell culture but is also occurring in vivo. Interestingly, in elderly persons, the presence of high proportions of CD8(+) T cells with characteristics of replicative senescence is correlated with reduced antibody responses to vaccines as well as with osteoporotic fractures. CD8(+)CD28(-) T cells also accumulate in patients with certain types of cancer. The emerging picture is that senescent CD8(+) T cells may modulate both immune and non-immune functions, contributing not only to reduced anti-viral immunity but also to diverse age-related pathologies.
Endogenous patterns of mechanical stress are required for branching morphogenesis (2010)

Spatial patterning of cell behaviors establishes the regional differences within tissues that collectively develop branched organs into their characteristic treelike shapes. Here we show that the pattern of branching morphogenesis of three-dimensional (3D) engineered epithelial tissues is controlled in part by gradients of endogenous mechanical stress. We used microfabrication to build model mammary epithelial tissues of defined geometry that branched in a stereotyped pattern when induced with growth factors. Branches initiated from sites of high mechanical stress within the tissues, as predicted numerically and measured directly using 3D traction force microscopy. Branch sites were defined by activation of focal adhesion kinase (FAK), inhibition of which disrupted morphogenesis. Stress, FAK activation, and branching were all altered by manipulating cellular contractility, matrix stiffness, intercellular cohesion and tissue geometry. These data suggest that the pattern and magnitude of mechanical stress across epithelial tissues cooperate with biochemical signals to specify branching pattern.
A Complex of the Bacteriophage T7 Primase-Helicase and DNA Polymerase Directs Primer Utilization (2001)

The lagging strand of the replication fork is initially copied as short Okazaki fragments produced by the coupled activities of two template-dependent enzymes, a primase that synthesizes RNA primers and a DNA polymerase that elongates them. Gene 4 of bacteriophage T7 encodes a bifunctional primase-helicase that assembles into a ring-shaped hexamer with both DNA unwinding and primer synthesis activities. The primase is also required for the utilization of RNA primers by T7 DNA polymerase. It is not known how many subunits of the primase-helicase hexamer participate directly in the priming of DNA synthesis. In order to determine the minimal requirements for RNA primer utilization by T7 DNA polymerase, we created an altered gene 4 protein that does not form functional hexamers and consequently lacks detectable DNA unwinding activity. Remarkably, this monomeric primase readily primes DNA synthesis by T7 DNA polymerase on single-stranded templates. The monomeric gene 4 protein forms a specific and stable complex with T7 DNA polymerase and thereby delivers the RNA primer to the polymerase for the onset of DNA synthesis. These results show that a single subunit of the primase-helicase hexamer contains all of the residues required for primer synthesis and for utilization of primers by T7 DNA polymerase.
1.1 Computing's energy problem (and what we can do about it) (2014)

Our challenge is clear: The drive for performance and the end of voltage scaling have made power, and not the number of transistors, the principal factor limiting further improvements in computing performance. Continuing to scale compute performance will require the creation and effective use of new specialized compute engines, and will require the participation of application experts to be successful. If we play our cards right, and develop the tools that allow our customers to become part of the design process, we will create a new wave of innovative and efficient computing devices.
Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor α (PPARα)-independent pathway (2001)

Liver carnitine palmitoyltransferase I (L-CPT I) catalyses the transfer of long-chain fatty acid (LCFA) for translocation across the mitochondrial membrane. Expression of the L-CPT I gene is induced by LCFAs as well as by lipid-lowering compounds such as clofibrate. Previous studies have suggested that the peroxisome-proliferator-activated receptor α (PPARα) is a common mediator of the transcriptional effects of LCFA and clofibrate. We found that free LCFAs rather than acyl-CoA esters are the signal metabolites responsible for the stimulation of L-CPT I gene expression. Using primary culture of hepatocytes we found that LCFAs failed to stimulate L-CPT I gene expression both in wild-type and PPARα-null mice. These results suggest that the PPARα-knockout mouse does not represent a suitable model for the regulation of L-CPT I gene expression by LCFAs in the liver. Finally, we determined that clofibrate stimulates L-CPT I through a classical direct repeat 1 (DR1) motif in the promoter of the L-CPT I gene while LCFAs induce L-CPT I via elements in the first intron of the gene. Our results demonstrate that LCFAs can regulate gene expression through PPARα-independent pathways and suggest that the regulation of gene expression by dietary lipids is more complex than previously proposed.
Multi-stream coding for MIMO OFDM systems with space-time-frequency spreading (2003)

We propose a coding strategy for MIMO OFDM systems that exploits full spatial (transmit and receive) diversity, as well as frequency and time diversity, through the combination of binary codes and linear precoding. The proposed scheme, based on streams (layers/threads), was designed to make iterative decoding with interference-cancellation relatively simple, while preserving most of the diversity available from the channel. It accommodates any number of transmit and receive antennas. Nevertheless, it is a full-rate scheme, since no redundancy is added by the linear precoding operations.
Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events (2012)

Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.
Epidermal Growth Factor Receptor Gene and Protein and Gefitinib Sensitivity in Non–Small-Cell Lung Cancer (2005)

High EGFR gene copy number identified by FISH may be an effective molecular predictor for gefitinib efficacy in advanced NSCLC.
Peramivir (BCX-1812, RWJ-270201): potential new therapy for influenza (2002)

The cyclopentane peramivir (BCX-1812, RWJ-270201) is a highly selective inhibitor of influenza A and B virus neuraminidases and a potent inhibitor of influenza A and B virus replication in cell culture. The in vitro potency appears to be greater than either zanamivir or oseltamivir carboxylate based on the generally lower EC(50) values seen using peramivir in studies run in parallel with each compound. In mice infected with influenza A or B viruses, oral treatment with peramivir was highly effective in preventing death, signs of the disease and in lowering lung virus titres. Similar effects were seen in influenza A virus-infected ferrets. Efficacy was seen in mice when therapy began after virus exposure. Peramivir is non-toxic in mice and rats at doses of 1000 mg/kg/day and ferrets tolerated doses of 100 mg/kg/day. Doses of 100 mg/kg/day do not appear to affect murine immune parameters. A pharmacokinetic study of this compound in influenza virus-infected mice indicates once-, twice- or thrice-daily oral dosing was equal in efficacy; once-daily dosing has been recommended in clinical trials of influenza therapy. Treatment of influenza virus infections in cyclophosphamide-immunosuppressed mice was effective in inhibiting the infection; an infection induced in severe combined immunodeficient mice was only weakly affected. Development of viral resistance to peramivir can occur by serial cell culture passage of the virus in the presence of the compound but the resistant virus was less virulent than the wild type virus. Viruses with neuraminidase mutations are not necessarily all cross-resistant to peramivir, zanamivir and oseltamivir carboxylate. In Phase I studies, peramivir was well-tolerated, with single or multiple oral doses up to 800 mg/kg/day evaluated. In clinical trials with patients experimentally infected with influenza A or B viruses, oral treatment with peramivir significantly reduced nasal wash virus titres with no adverse effects. Phase III clinical trials are underway.
Insulin Receptors Mediate Growth Effects in Cultured Fetal Neurons. I. Rapid Stimulation of Protein Synthesis* (1989)

In this study we have examined the effects of insulin on protein synthesis in cultured fetal chick neurons. Protein synthesis was monitored by measuring the incorporation of [3H]leucine (3H-leu) into trichloroacetic acid (TCA)-precipitable protein. Upon addition of 3H-leu, there was a 5-min lag before radioactivity occurred in protein. During this period cell-associated radioactivity reached equilibrium and was totally recovered in the TCA-soluble fraction. After 5 min, the incorporation of 3H-leu into protein was linear for 2 h and was inhibited (98%) by the inclusion of 10 micrograms/ml cycloheximide. After 24 h of serum deprivation, insulin increased 3H-leu incorporation into protein by approximately 2-fold. The stimulation of protein synthesis by insulin was dose dependent (ED50 = 70 pM) and seen within 30 min. Proinsulin was approximately 10-fold less potent than insulin on a molar basis in stimulating neuronal protein synthesis. Insulin had no effect on the TCA-soluble fraction of 3H-leu at any time and did not influence the uptake of [3H]aminoisobutyric acid into neurons. The isotope ratio of 3H-leu/14C-leu in the leucyl tRNA pool was the same in control and insulin-treated neurons. Analysis of newly synthesized proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that insulin uniformly increased the incorporation of 14C-leu into all of the resolved neuronal proteins. We conclude from these data that 1) insulin rapidly stimulates overall protein synthesis in fetal neurons independent of amino acid uptake and aminoacyl tRNA precursor pools; 2) stimulation of protein synthesis is mediated by the brain subtype of insulin receptor; and 3) insulin is potentially an important in vivo growth factor for fetal central nervous system neurons.
An n‐dimensional retrieval model (1976)

Abstract This paper reports a technique which expands W. Goffman's Indirect Method search strategy by using means other than index terms to reflect document content. The four basic measures of document relatedness were: (1) Index terms, (2) Journals in which the documents appeared, (3) Closeness of the authors of the documents and (4) Closeness of citations. In the experiment a distance function between documents is defined, based on the properties of the documents themselves. The proximity between pairs of documents is then determined by calculating the Euclidean distance. Based on the results of this experiment, authors or authors with journals are the best measures of document relatedness. This aspect should be explored further.
Salt-soluble elastin from lathyritic chicks (1974)

The isolation of a salt-soluble homogeneous elastin from the aortas of lathyritic chicks by chromatography on DEAE-cellulose and salt precipitation is described. These new techniques, as well as some previously published by other workers, were evaluated with the help of antiserum raised in sheep against insoluble chick elastin. The purified elastin was very basic and behaved in a predictable manner in coacervation studies. The protein migrated in sodium dodecyl sulphate-polyacrylamide gels as a single band moving slightly faster than pyruvate kinase (mol.wt. 57000).
Adeno-associated virus vectors for vascular gene delivery. (1997)

A variety of delivery systems have been used to genetically modify vascular endothelial cells and smooth muscle cells (SMCs), but currently available systems suffer from either inefficient in vivo gene transfer, transient episomal vector expression, or significant immune responses and inflammation. In the present study, we evaluated an alternate vector system, recombinant adeno-associated virus (rAAV) for transduction of vascular cells in culture and in vivo. Primary cultures of rabbit, monkey, and human SMCs; macaque and human microvascular endothelial cells; and human umbilical vein endothelial cells were efficiently transduced at a dose of 100 to 1000 DNase-resistant particles per cell. rAAV-mediated transduction of the vasculature in vivo was observed after intraluminal gene delivery or after intra-adventitial injection in carotid arteries of atherosclerotic cynomolgus monkeys. Whether vector delivery was intraluminal or adventitial, transduction was observed in the adventitia, particularly within microvessels (vasa vasorum) but not in cells of the intima or media. Transduction of adventitial microvessels was enhanced by balloon injury 4 days before gene transfer. This was particularly true for adventitial delivery. We have previously shown that adventitial cell proliferation increases significantly 4 days after balloon injury (45%) in this animal model. Together, these data suggest that cell proliferation may enhance AAV transduction in vivo in the vasculature. AAV vectors exhibited a tropism in vivo for the microvascular endothelium at the doses used in the present study, which may provide the opportunity for targeting gene delivery. In summary, we have demonstrated the utility of rAAV vectors for ex vivo vascular cell gene delivery and present an initial experience with rAAV for in vivo vascular gene delivery. This alternate vector system may overcome some of the limitations hampering the development of gene therapy for vascular disorders.
Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), a novel Hsp90-client tyrosine kinase: down-regulation of NPM-ALK expression and tyrosine phosphorylation in ALK(+) CD30(+) lymphoma cells by the Hsp90 antagonist 17-allylamino,17-demethoxygeldanamycin. (2002)

Anaplastic large cell lymphomas (ALCL) are characterized by the expression of a chimeric protein, NPM-ALK, which originates from fusion of the nucleophosmin (NPM) and the membrane receptor anaplastic lymphoma kinase (ALK) genes. The NPM-ALK kinase, on dimerization, shows phosphotransferase activity and, through its interaction with various ALK-adapter proteins, induces cell transformation and increases cell proliferation in vitro. The chaperones heat shock proteins 90 (Hsp90) and 70 (Hsp70) play a critical role in the folding and maturation of several oncogenic protein kinases, and perturbation of Hsp90 structure affects the stability and degradation of Hsp90- and Hsp70-bound substrates. This process is triggered by benzoquinone ansamycin antibiotics, Hsp90-binding small molecules. We have studied the effect of 17-allylamino,17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin, on NPM-ALK steady-state level in ALCL cells. Treatment with 17-AAG decreased NPM-ALK expression and phosphorylation, thus impairing its association with phospholipase C-gamma, Src homology 2 domain-containing protein (Shc), growth factor receptor-bound protein 2 (Grb2), and insulin receptor substrate-1 (IRS-1). We also observed that NPM-ALK associates with Hsp90, and incubation with 17-AAG disrupts this complex without affecting Hsp90 expression. As shown previously for other Hsp90 client proteins, destabilization of the Hsp90/NPM-ALK complex induced by 17-AAG resulted in increased binding of the chimeric protein to Hsp70, which is known to affect protein degradation. Hsp/NPM-ALK complex formation appears to be independent of NPM sequences, because we were unable to coimmunoprecipitate NPM with either Hsp90 or Hsp70. Similar to NPM-ALK, the exogenously expressed variant fusion protein TPR-ALK showed decreased expression and phosphorylation after 17-AAG treatment, suggesting that the effect of 17-AAG on ALK chimeric proteins depends on the ALK portion and not on the partner protein moiety. Our data demonstrate that NPM-ALK cell content is determined by its interaction with Hsp90 and Hsp70, and suggest that the alteration of such associations can interfere with NPM-ALK function in ALCL cells.
Maintenance of sterility in urinary drainage bags. (1982)

When the outlet tube of urinary drainage sets was kept full of 3 per cent hydrogen peroxide at all times, no evidence of bacterial growth in the urine of the collection bag was noted in at least 92.0 per cent of the patients and 93.3 per cent of the drainage periods in a group of 60 patients and 75 drainage periods. One patient had a positive urinary drainage bag culture and a positive bladder culture as a result of improper disconnection of the catheter, and four patients had bacterial growth from urinary drainage bag samples, two of which were possibly due to a faulty culture technique and one of which may have resulted from contamination of amphoteracin B irrigating solution. Hydrogen peroxide, 3 per cent, appears to approach 100 per cent effectiveness as an antibacterial barrier. Only one patient of 60 or 1.7 per cent had a urinary tract infection develop which was related to the improper handling of the drainage set.
Search for the optimal channel architecture for 0.18/0.12 μm bulk CMOS experimental study (2002)

Varied advanced architectures for 0.18/0.12 CMOS are investigated experimentally. Performances of heavy ion implanted, epitaxial and/or SiGe channels are compared through their electrical and physical characteristics. Conclusions on optimal 0.18/0.12 /spl mu/m channel architectures are drawn with respect to different applications. Very promising transport properties in SiGe channels are reported.