gebhart/patrepeval huggingface dataset:
Charge transfer in photovoltaics consisting of interpenetrating networks of conjugated polymer and TiO2 nanoparticles (1999)

We study the effect of blended and layered titanium dioxide (TiO2) nanoparticles on charge transfer processes in conjugated polymer photovoltaics. A two order of magnitude increase in photoconductivity and sharp saturation is observed for layered versus blended structures, independent of the cathode work function. Using electrodes with similar work functions, we observe low dark currents and open circuit voltages of 0.7 V when a TiO2 nanoparticle layer is self-assembled onto the indium–tin–oxide electrode. Our results for the layered morphologies are consistent with charge collection by exciton diffusion and dissociation at the TiO2 interface.
An Anatomic Approach to Prevention of Atrial Fibrillation: Pulmonary Vein Isolation with Through-the-Balloon Ultrasound Ablation (TTB-USA) (1999)

Our current understanding is that atrial fibrillation (AF) is initiated most often by a focal trigger from the orifice of or within one of the pulmonary veins. Though mapping and ablation of these triggers appears to be curative in most patients with paroxysmal AF, there are a number of limitations to ablating focal triggers via mapping and ablating the earliest site of activation with a "point" radiofrequency lesion. One way to circumvent thesen limitations is an anatomically-guided ablative approach. By electrically isolating one or more pulmonary veins from the left atrium with a circumferential lesion, firing from within those veins would be unable to reach the body of the atrium, and thus could not trigger atrial fibrillation. We have developed a novel over-the-wire catheter design which integrates a cylindrical ultrasound transducer within a saline filled balloon, termed TTB-USA (through-the-balloon ultrasound ablation) in order to produce narrow circumferential zones of hyperthermic tissue death at the pulmonary vein ostia. Animal studies show great promise, and clinical trials will begin soon.
Effect of dimethyl sulfoxide on bladder tissue penetration of intravesical paclitaxel. (2003)

Our laboratory has shown that the efficacy of bladder cancer intravesical therapy is in part limited by the poor penetration of drugs into the urothelium. We further found that paclitaxel, because of its lipophilicity, shows a higher penetration than other commonly used drugs such as mitomycin C and doxorubicin. However, the commercial formulation of paclitaxel (i.e., Taxol) contains Cremophor, which forms micelles that entrap the drug and reduce its free fraction. The present study evaluated the effect of DMSO on paclitaxel release from Cremophor micelles and paclitaxel penetration in bladders of dogs given an intravesical dose of paclitaxel (500 microg/20 ml in 0.22% Cremophor, 0.21% ethanol, and 50% DMSO). Cremophor produced a concentration-dependent reduction of the free fraction of paclitaxel (reduced to 23% at 0.25% Cremophor). This Cremophor effect was reversed by DMSO in a concentration-dependent manner, resulting in a 92% free fraction at 50% DMSO. DMSO also increased the average size of Cremophor micelles from 13 nm to 230 nm at 50% DMSO. A comparison of the tissue penetration data in the presence of Cremophor and/or DMSO indicates the following effects of DMSO: (a). increase in urine production rate and, consequently, a 36% reduction of the final urine concentration; (b). 2-fold increase in paclitaxel penetration across bladder urothelium; (c). increase in drug removal from bladder tissues (30% more rapidly); and (d). a 60% increase of the amount of drug in bladder tissue. These results indicate that DMSO caused rearrangement of Cremophor micelles, reversed the entrapment of paclitaxel in Cremophor micelles and thereby increased the free fraction of paclitaxel in solution, enhanced the urine production rate and enhanced drug removal by the perfusing capillaries, with an overall effect of increasing the bladder tissue delivery of paclitaxel formulated in Cremophor.
Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers (1993)

Cartilaginous implants for potential use in reconstructive or orthopedic surgery were created using chondrocytes grown on synthetic, biodegradable polymer scaffolds. Chondrocytes isolated from bovine or human articular or costal cartilage were cultured on fibrous polyglycolic acid (PGA) and porous poly(L)lactic acid (PLLA) and used in parallel in vitro and in vivo studies. Samples were taken at timed intervals for assessment of cell number and cartilage matrix (sulfated glycosaminoglycan [S-GAG], collagen). The chondrocytes secreted cartilage matrix to fill the void spaces in the polymer scaffolds that were simultaneously biodegrading. In vitro, chondrocytes grown on PGA for 6 weeks reached a cell density of 5.2 x 10(7) cells/g, which was 8.3-fold higher than at day 1, and equalled the cellularity of normal bovine articular cartilage. In vitro, the cell growth rate was approximately twice as high on PGA as it was on PLLA; cells grown on PGA produced S-GAG at a high steady rate, while cells grown on PLLA produced only minimal amounts of S-GAG. These differences could be attributed to polymer geometry and biodegradation rate. In vivo, chondrocytes grown on both PGA and PLLA for 1-6 months maintained the three-dimensional (3-D) shapes of the original polymer scaffolds, appeared glistening white macroscopically, contained S-GAG and type II collagen, and closely resembled cartilage histologically. These studies demonstrate the feasibility of culturing isolated chondrocytes on biodegradable polymer scaffolds to regenerate 3-D neocartilage.
Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan (1997)

In a 12.5 cM genome-wide scan for psoriasis susceptibility loci, recombination-based tests revealed linkage to the HLA region (Zmax = 3.52), as well as suggestive linkage to two novel regions: chromosome 16q (60-83.1 cM from pter, Zmax = 2.50), and chromosome 20p (7.5-25 cM from pter, Zmax = 2.62). All three regions yielded P values < or = 0.01 by non-parametric analysis. Recombination-based and allele sharing methods also confirmed a previous report of a dominant susceptibility locus on distal chromosome 17q (108.2 cM from pter, Zmax = 2.09, GENEHUNTER P = 0.0056). We could not confirm a previously reported locus on distal chromosome 4q; however, a broad region of unclear significance was identified proximal to this proposed locus (153.6-178.4 cM from pter, Zmax = 1.01). Taken together with our recent results demonstrating linkage to HLA-B and -C, this genome-wide scan identifies a psoriasis susceptibility locus at HLA, confirms linkage to 17q, and recommends two novel genomic regions for further scrutiny. One of these regions (16q) overlaps with a recently-identified susceptibility locus for Crohn's disease. Psoriasis is much more common in patients with Crohn's disease than in controls, suggesting that an immunomodulatory locus capable of influencing both diseases may reside in this region.
Oral tolerance in experimental autoimmune uveoretinitis. Distinct mechanisms of resistance are induced by low dose vs high dose feeding protocols. (1993)

Studies of oral tolerance in LEW rat models of autoimmune diseases including S-antigen (S-Ag)-mediated experimental autoimmune uveoretinitis (EAU), and myelin basic protein-induced experimental autoimmune encephalomyelitis have produced conflicting evidence for the roles of clonal anergy and suppression. Using subpeptides from a region of S-Ag known to induce oral tolerance a protective site was localized to a nonamer of residues 347-355. This site was also uveitogenic, providing the basis for testable hypotheses for tolerance to be due to clonal anergy in pathogenic T cells specific for that site, or to suppression. Evidence for suppression was strongly supported by several observations. 1) Induction of oral tolerance with low dose feedings (250 micrograms/feeding) of peptide 343-362 conferred resistance to EAU induction by intact S-Ag, which should not be possible if only T cells specific for epitopes in 343-362 were rendered unresponsive, since there are several other pathogenic sites in S-Ag. 2) Low dose feeding induced resistance to EAU induction by a distinct, spatially separate peptide, residues 270-289, of S-Ag. 3) The requirement for linked recognition was shown by the inability of tolerance induced by feeding 343-362 to protect from EAU induction by a peptide, residues 521-540, derived from interphotoreceptor retinoid binding protein, a different uveitogenic retinal protein. 4) Resistance could be adoptively transferred. Conversely, induction of tolerance with high doses of peptide (5 mg/feeding) resulted in loss of resistance to EAU induced by S-Ag, although disease induction by the fed peptide was inhibited; observations that are consistent with clonal anergy. The apparent lack of suppression after high dose feeding could mean that suppressor T cells can also be rendered unresponsive or that induction of T suppressor cells is dependent on CD4+ Th cells, which were rendered anergic, leading to lack of T suppressor development. We suggest that oral tolerance operates by at least two distinct mechanisms that depend on the feeding dose; low doses induce suppression, whereas high doses induce unresponsiveness.
The ACCORD-Lipid study: implications for treatment of dyslipidemia in Type 2 diabetes mellitus (2011)

Patients with Type 2 diabetes mellitus (T2DM) are at high risk of developing cardiovascular disease (CVD). Treatment of diabetic dyslipidemia, comprised mainly of hypertriglyceridemia, and low HDL-C, with either statin or fibrate monotherapy, is moderately effective at reversing the abnormal lipid levels, but does not completely reverse the risk of CVD. Combination therapy with a statin and fibrate more effectively treats diabetic dyslipidemia; however, neither the impact on CVD risk nor the safety profile of statin-fibrate combined treatment had been tested in a large randomized trial. The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid trial tested the hypothesis that combination therapy with a fibrate and statin would more effectively prevent major CVD events in a high-risk population of patients with T2DM compared with statin monotherapy. In ACCORD-Lipid, over 5000 patients were treated with fenofibrate plus simvastatin versus simvastatin alone. Although combination therapy did not significantly reduce CVD event rates in the ACCORD-Lipid cohort as a whole, a predefined subgroup of participants with the combination of significant hypertriglyceridemia and low HDL-C experienced a 31% lower event rate with combination therapy. <i>Post hoc</i> analyses conducted in similar subsets in previous fibrate monotherapy trials were concordant with these findings in ACCORD-Lipid. Combination therapy was well tolerated and safe, with no detectable increase in myopathy. The implications of the ACCORD-Lipid findings for the treatment of dyslipidemia in patients with T2DM are discussed.
The threat to primates and other mammals from the bushmeat trade in Africa, and how this threat could be diminished (1999)

Abstract The threat that the bushmeat trade presents to primates and other taxa was assessed from the literature, including data from markets, village hunting studies and logging concessions in Central and West Africa. In many cases the numbers of both common and protected species of primate being killed throughout the region are thought to be unsustainable. This is also the case for other taxa involved in the bushmeat trade, which crosses geographic, cultural and economic boundaries. A suite of measures must be considered to mitigate the effects of this trade, and these measures will have to recognize the local, regional and national socio-economic importance of the trade if they are to result in long-term conservation success.
Osteopontin Promotes Hepatic Progenitor Cell Expansion and Tumorigenicity via Activation of β-Catenin in Mice (2015)

Upregulation of osteopontin (OPN) has been found in hepatic progenitor cells (HPCs) in several liver diseases with portal biliary proliferation. Here, we investigated the role of HPC-derived autocrine OPN in regulating HPC expansion, migration, and hepatocarcinogenesis in mice. Five-week-old, weighing between 18 and 20 g of either wild type (WT) or OPN gene knockout (OPN-KO) male mice were treated with modified choline-deficient, ethionine-supplemented diet (modified choline-deficient [MCDE]) for 2 weeks to induce HPC production, or 6-12 months to induce tumorigenesis. Epithelial cell adhesion molecule EpCAM(+) CD45(-) cells isolated from mouse liver and liver epithelial progenitor cells were used for in vitro study. OPN was blocked by specific antibody or RNAi-mediated silence to investigate the role of OPN. To evaluate correlation between OPN expression and β-catenin activity, expressions of OPN and β-catenin were assessed in human liver cancer specimens. We found autocrine OPN promotes HPC expansion and migration by decreasing membranous E-cadherin and increasing free cytoplasmic β-catenin via binding to αv integrin and activating Src activity. Depletion of OPN significantly attenuated MCDE-induced hepatocarcinogenesis. Clinical evidence revealed a strong correlation of high OPN expression with cytoplasmic/nuclear expression of β-catenin in 43 cases of human combined hepatocellular carcinoma and cholangiocarcinoma and mixed intrahepatic cholangiocarcinoma and 80 cases of hepatocellular carcinoma. Our results indicate that autocrine OPN plays a crucial role in HPC expansion, migration, and subsequent oncogenic transformation of HPCs, which may provide a new insight into hepatocarcinogenesis.
The mode of action of cytokine inhibitors. (2002)

Tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) are important mediators of inflammation and tissue damage in animal models of inflammatory arthritis and in patients with active rheumatoid arthritis (RA). Several inhibitors of these cytokines are now available for RA treatment, each having a different mode of action. Etanercept is a recombinant fusion protein of the soluble type II TNF receptor on a human IgG1 backbone, whereas infliximab is a chimeric anti-TNF-alpha monoclonal antibody containing a murine TNF-alpha binding region and human IgG1 backbone. Both agents potently and selectively bind TNF-alpha in the cellular microenvironment, thereby preventing TNF-alpha from interacting with membrane-bound TNF receptors on target cells. In comparison, anakinra is a recombinant human IL-1 receptor antagonist (IL-1Ra) that binds avidly to type 1 IL-1 receptors but does not stimulate any intracellular responses. Studies of these agents in animal models of inflammatory arthritis suggest that TNF-alpha plays a more important role in promoting inflammation, whereas IL-1 is more important in causing cartilage and bone destruction. However, these differential actions have not been borne out in clinical trials, where TNF-alpha blockers and anakinra similarly reduce clinical signs and symptoms of RA as well as slow radiographic evidence of disease progression.
A design of a fast and area efficient multi-input Muller C-element (1993)

A multi-input Muller C-element has frequently been used for joining signal transitions or completion time detection in self-timed circuits. An n-input Muller C-element design which uses the multilevel logic design technique and has a symmetric format for any integer n >or=2 is presented. In comparison with series-parallel MOS structure implementations and C-element tree implementations, the present design has fewer restrictions in terms of n, less path delay, less delay variance from inputs to output, and less area consumption. Experimental validation based on an industrial standard cell library is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hepoxilin A3 inhibits the rise in free intracellular calcium evoked by formyl-methionyl-leucyl-phenylalanine, platelet-activating factor and leukotriene B4 (1993)

We have previously shown that the hepoxilins are capable of increasing the intracellular free concentration of calcium ([Ca2+]i) in human neutrophils through a pertussis toxin-sensitive, extracellular calcium-independent pathway involving the mobilization of calcium from internal stores. A subsequent hepoxilin-induced and extracellular calcium-dependent influx of calcium is observed. In an effort to investigate further the role of these compounds in the human neutrophil, we investigated their potential effects on the action of known agonists such as formyl-methionine-leucine-phenylalanine (fMLP), platelet-activating factor (PAF) and leukotriene B4 (LTB4) on the mobilization of calcium. Hepoxilis dose-dependently inhibited the increases in [Ca2+]i induced by fMLP, PAF and LTB4. The hepoxilin concentration required for inhibition was around 100 ng/ml (3 x 10(-7) M). This concentration of hepoxilin did not cause any measurable change in [Ca2+]i. The extent of inhibition of the agonist-evoked rise in [Ca2+]i by hepoxilins was proportional to the increase in the calcium response evoked by hepoxilin beyond its threshold concentration. Additional experiments were carried out to investigate the mechanism for the hepoxilin effect. Using calcium-free medium and in the presence of sufficient amounts of thapsigargin (200 ng/ml) to maximally block the calcium pump (thereby achieving a constant rate of calcium leakage from stores), hepoxilin A3 increased further this rate of calcium leakage, indicating that hepoxilin acts by rapidly draining calcium from stores. Its potential (additional) thapsigargin-like action in blocking the pump, however, cannot be ruled out by these experiments. These observations suggest that the hepoxilins may serve an important negative regulatory function in the agonist-induced mobilization of calcium in these cells by depleting calcium stores.
A New Strategy for the Preparation of Peptide-Targeted Technetium and Rhenium Radiopharmaceuticals. The Automated Solid-Phase Synthesis, Characterization, Labeling, and Screening of a Peptide-Ligand Library Targeted at the Formyl Peptide Receptor (2005)

A new solid-phase synthetic methodology was developed that enables libraries of peptide-based Tc(I)/Re(I) radiopharmaceuticals to be prepared using a conventional automated peptide synthesizer. Through the use of a tridentate ligand derived from N-alpha-Fmoc-l-lysine, which we refer to as a single amino acid chelate (SAAC), a series of 12 novel bioconjugates [R-NH(CO)ZLF(SAAC)G, R = ethyl, isopropyl, n-propyl, tert-butyl, n-butyl, benzyl; Z = Met, Nle] that are designed to target the formyl peptide receptor (FPR) were prepared. Construction of the library was carried out in a multiwell format on an Advanced ChemTech 348 peptide synthesizer where multi-milligram quantities of each peptide were isolated in high purity without HPLC purification. After characterization, the library components were screened for their affinity for the FPR receptor using flow cytometry where the K(d) values were found to be in the low micromolar range (0.5-3.0 microM). Compound 5j was subsequently labeled with (99m)Tc(I) and the product isolated in high radiochemical yield using a simple Sep-Pak purification procedure. The retention time of the labeled compound matched that of the fully characterized Re-analogue which was prepared through the use of the same solid-phase synthesis methodology that was used to construct the library. The work reported here is a rare example of a method by which libraries of peptide-ligand conjugates and their rhenium complexes can be prepared.
Improved prediction of protein side‐chain conformations with SCWRL4 (2009)

Determination of side-chain conformations is an important step in protein structure prediction and protein design. Many such methods have been presented, although only a small number are in widespread use. SCWRL is one such method, and the SCWRL3 program (2003) has remained popular because of its speed, accuracy, and ease-of-use for the purpose of homology modeling. However, higher accuracy at comparable speed is desirable. This has been achieved in a new program SCWRL4 through: (1) a new backbone-dependent rotamer library based on kernel density estimates; (2) averaging over samples of conformations about the positions in the rotamer library; (3) a fast anisotropic hydrogen bonding function; (4) a short-range, soft van der Waals atom-atom interaction potential; (5) fast collision detection using k-discrete oriented polytopes; (6) a tree decomposition algorithm to solve the combinatorial problem; and (7) optimization of all parameters by determining the interaction graph within the crystal environment using symmetry operators of the crystallographic space group. Accuracies as a function of electron density of the side chains demonstrate that side chains with higher electron density are easier to predict than those with low-electron density and presumed conformational disorder. For a testing set of 379 proteins, 86% of chi(1) angles and 75% of chi(1+2) angles are predicted correctly within 40 degrees of the X-ray positions. Among side chains with higher electron density (25-100th percentile), these numbers rise to 89 and 80%. The new program maintains its simple command-line interface, designed for homology modeling, and is now available as a dynamic-linked library for incorporation into other software programs.
Aortic Carboxypeptidase-like Protein, a Novel Protein with Discoidin and Carboxypeptidase-like Domains, Is Up-regulated during Vascular Smooth Muscle Cell Differentiation (1998)

Phenotypic modulation of vascular smooth muscle cells plays an important role in the pathogenesis of arteriosclerosis. In a screen of proteins expressed in human aortic smooth muscle cells, we identified a novel gene product designated aortic carboxypeptidase-like protein (ACLP). The approximately 4-kilobase human cDNA and its mouse homologue encode 1158 and 1128 amino acid proteins, respectively, that are 85% identical. ACLP is a nonnuclear protein that contains a signal peptide, a lysine- and proline-rich 11-amino acid repeating motif, a discoidin-like domain, and a C-terminal domain with 39% identity to carboxypeptidase E. By Western blot analysis and in situ hybridization, we detected abundant ACLP expression in the adult aorta. ACLP was expressed predominantly in the smooth muscle cells of the adult mouse aorta but not in the adventitia or in several other tissues. In cultured mouse aortic smooth muscle cells, ACLP mRNA and protein were up-regulated 2-3-fold after serum starvation. Using a recently developed neural crest cell to smooth muscle cell in vitro differentiation system, we found that ACLP mRNA and protein were not expressed in neural crest cells but were up-regulated dramatically with the differentiation of these cells. These results indicate that ACLP may play a role in differentiated vascular smooth muscle cells.
The erythemal response of human skin to ultraviolet radiation (1985)

A reflectance instrument was used to measure objectively the erythemal response of human skin to ultraviolet radiation. Dose-response curves have been constructed for four radiation wavelengths. In each case, the measured increase in erythema was found to be linearly related to the logarithm of the dose of ultraviolet radiation. Significantly different slopes of response were obtained for radiation of 254 and 280 nm compared with 300 and 313 nm radiation. The relevance of these findings is discussed with relation to the mechanism of erythema production and the erythema action spectrum.