gebhart/patrepeval huggingface dataset:
Atomic Structure of PDE4: Insights into Phosphodiesterase Mechanism and Specificity (2000)

Cyclic nucleotides are second messengers that are essential in vision, muscle contraction, neurotransmission, exocytosis, cell growth, and differentiation. These molecules are degraded by a family of enzymes known as phosphodiesterases, which serve a critical function by regulating the intracellular concentration of cyclic nucleotides. We have determined the three-dimensional structure of the catalytic domain of phosphodiesterase 4B2B to 1.77 angstrom resolution. The active site has been identified and contains a cluster of two metal atoms. The structure suggests the mechanism of action and basis for specificity and will provide a framework for structure-assisted drug design for members of the phosphodiesterase family.
Prostacyclin and thromboxane biosynthesis in mild essential hypertension. (1990)

The possibility that prostacyclin or thromboxane biosynthesis is abnormal in patients with established mild essential hypertension was investigated in 46 patients. These eicosanoids have opposing effects both on vascular smooth muscle and on platelets. An imbalance in their biosynthesis could therefore influence both vascular tone and predisposition to thrombosis. We studied the relation between blood pressure and the biosynthesis of prostacyclin and thromboxane A2 by measuring urinary excretion rates of stable breakdown products of prostacyclin (6-oxo-prostaglandin F1 alpha and 2,3-dinor-6-oxo-prostaglandin F1 alpha) and of thromboxane A2 (thromboxane B2 and 2,3-dinor-thromboxane B2) using immunoaffinity chromatography and gas chromatography/electron capture mass spectrometry. Excretion rates of both of the prostacyclin-derived products ranged from less than 5 to more than 100 ng/g creatinine; each was significantly negatively correlated with blood pressure (r = 0.36-0.45). A reduction of 2,3-dinor-6-oxo-prostaglandin F1 alpha excretion of 100 ng/g creatinine was associated with an increase in arterial pressure of 14 mm Hg (systolic) and 8 mm Hg (diastolic) in patients who had been without antihypertensive medication for 2 weeks. The same reduction in 6-oxo-prostaglandin F1 alpha excretion was associated with an increased pressure of 19 mm Hg (systolic) and 12 mm Hg (diastolic) (2p less than 0.05 for diastolic pressure and 2p less than 0.01 for systolic pressure in each case). There were similar correlations between the excretion rates of these products and blood pressure in the same patients while they were receiving antihypertensive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Left Ventricular or Biventricular Pacing Improves Cardiac Function at Diminished Energy Cost in Patients With Dilated Cardiomyopathy and Left Bundle-Branch Block (2000)

Ventricular resynchronization by left ventricular or biventricular pacing/stimulation in DCM patients with left bundle-branch block acutely enhances systolic function while modestly lowering energy cost. This should prove valuable for treating DCM patients with basal dyssynchrony.
Internalization of tenecin 3 by a fungal cellular process is essential for its fungicidal effect onCandida albicans (2001)

Tenecin 3 is a glycine-rich, antifungal protein of 78 residues isolated from the insect Tenebrio molitor larva. As an initial step towards understanding the antifungal mechanism of tenecin 3, we examined how this protein interacts with the pathogenic fungus Candida albicans to exert its antifungal action. Tenecin 3 did not induce the release of a fluorescent dye trapped in the artificial membrane vesicles and it did not perturb the membrane potential of C. albicans by the initial interaction. Fluorescence confocal microscopy and flow cytometric analysis revealed that tenecin 3 is rapidly internalized into the cytoplasmic space in energy-dependent and temperature-dependent manners. This internalization is also dependent on the ionic environment and cellular metabolic states. These results suggest that the internalization of tenecin 3 into the cytoplasm of C. albicans is mediated by a fungal cellular process. The internalized tenecin 3 is dispersed in the cytoplasm, and the loss of cell viability occurs after this internalization.
High Throughput CABAC Entropy Coding in HEVC (2012)

Context-adaptive binary arithmetic coding (CAB-AC) is a method of entropy coding first introduced in H.264/AVC and now used in the newest standard High Efficiency Video Coding (HEVC). While it provides high coding efficiency, the data dependencies in H.264/AVC CABAC make it challenging to parallelize and thus, limit its throughput. Accordingly, during the standardization of entropy coding for HEVC, both coding efficiency and throughput were considered. This paper highlights the key techniques that were used to enable HEVC to potentially achieve higher throughput while delivering coding gains relative to H.264/AVC. These techniques include reducing context coded bins, grouping bypass bins, grouping bins with the same context, reducing context selection dependencies, reducing total bins, and reducing parsing dependencies. It also describes reductions to memory requirements that benefit both throughput and implementation costs. Proposed and adopted techniques up to draft international standard (test model HM-8.0) are discussed. In addition, analysis and simulation results are provided to quantify the throughput improvements and memory reduction compared with H.264/AVC. In HEVC, the maximum number of context-coded bins is reduced by 8×, and the context memory and line buffer are reduced by 3× and 20×, respectively. This paper illustrates that accounting for implementation cost when designing video coding algorithms can result in a design that enables higher processing speed and lowers hardware costs, while still delivering high coding efficiency.
Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis (2012)

Genome-wide gene expression profile analyses using a cDNA microarray containing 27,648 genes or expressed sequence tags identified MMS22L (methyl methanesulfonate-sensitivity protein 22-like) to be overexpressed in the majority of clinical lung and esophageal cancers, but not expressed in normal organs except testis. Transfection of siRNAs against MMS22L into cancer cells suppressed its expression and inhibited cell growth, while exogenous expression of MMS22L enhanced the growth of mammalian cells. MMS22L protein was translocated to the nucleus and stabilized by binding to C-terminal portion of NFKBIL2 [nuclear factor of kappa (NFKB) light polypeptide gene enhancer in B-cells inhibitor-like 2]. Expression of a C-terminal portion of NFKBIL2 protein including the MMS22L-interacting site in cancer cells could reduce the levels of MMS22L in nucleus and suppressed cancer cell growth. Interestingly, reduction of MMS22L by siRNAs in cancer cells inhibited the TNF-α-dependent activation of RelA/p65 in the NFKB pathway and expression of its downstream anti-apoptotic molecules such as Bcl-XL and TRAF1. In addition, knockdown of MMS22L expression also enhanced the apoptosis of cancer cells that were exposed to DNA-damaging agents including 5-FU and CDDP. Our data strongly suggest that targeting MMS22L as well as its interaction with NFKBIL2 could be a promising strategy for novel cancer treatments, and also improve the efficacy of DNA damaging anticancer drugs.
The erbB3 gene product is a receptor for heregulin. (1994)

ErbB3 is a member of the epidermal growth factor (EGF) receptor subfamily of receptor tyrosine kinases and is believed to be a receptor for an unknown ligand. We have tested the possibility that heregulin, a growth factor possessing an EGF-like domain, is a ligand for ErbB3. We have found that the iodinated recombinant EGF-like domain of heregulin-beta 1 (125I-rHRG beta 1(177-244) bound specifically to insect cell-expressed bovine ErbB3 with a dissociation constant of 0.85 nM. Moreover, 125I-rHRG beta 1(177-244) bound to NIH3T3 fibroblasts stably transfected with bovine erbB3 with a dissociation constant of 60 pM, but did not bind to parental cells. 125I-rHRG beta 1(177-244) could be chemically cross-linked to a 170-180 kDa protein in erbB3-transfected fibroblasts, and the cross-linked product could be immunoprecipitated with antibodies specific for ErbB3. Finally, rHRG beta 1 stimulated the tyrosine phosphorylation of both ErbB3 and endogenous p185erbB2/neu in transfectants but not in parental cells. We conclude that ErbB3 is a receptor for HRG and is capable of mediating HRG-stimulated tyrosine phosphorylation of itself and p185erbB2/neu in cells that express both receptors.
Glycobiology : a practical approach (1993)

Isolation and characterization of glycoproteins / Sven R. Carlsson -- Compositional analysis of glycoproteins / Adriana E. Manzi, Ajit Varki -- Isolation and fractionation of N-linked oligosaccharides from glycoproteins -- Release of N-linked oligosaccharides and fractionation by gel filtration / Akira Kobata, Tamao Endo -- Fractionation of oligosaccharides by serial affinity chromatography with use of immobilized lectin columns / Akira Kobata, Katsuko Yamashita -- Fractionation of glycopeptides and oligosaccharides from glycoproteins by HPLC / Yuan C. Lee, Kevin G. Rice -- Structural characterization of oligosaccharides from glycoproteins -- Glycosidase treatment and other methods, including methylation analysis / Akira Kobata, Seiichi Takasaki -- FAB-MS and ES-MS of glycoproteins / Anne Dell ... [et al.] -- Nuclear magnetic resonance spectroscopy of glycoprotein-derived carbohydrate chains / Karl Hard, Johannes F.G. Vliegenthart -- Structural characterization of N-glycans obtained from metabolically-radiolabelled glycoproteins / Richard D. Cummings.
Nonlinear optical mapping of silicon carbide polytypes in 6H-SiC epilayers (1996)

A fast and noninvasive mapping tool based on spatially resolved optical second-harmonic generation is presented for the detection of silicon carbide polytypes in 6H-SiC epilayers. 3C-SiC microcrystallites of different orientations are identified from second-harmonic rotational anisotropy scans. The method reported can be used as an efficient in situ control of SiC growth processes.
The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice (1998)

Neuropeptide Y (NPY) and the endogenous melanocortin receptor antagonist, agouti gene-related protein (AGRP), coexist in the arcuate nucleus, and both exert orexigenic effects. The present study aimed primarily at determining the brain distribution of AGRP. AGRP mRNA-expressing cells were limited to the arcuate nucleus, representing a major subpopulation (95%) of the NPY neurons, which also was confirmed with immunohistochemistry. AGRP-immunoreactive (-ir) terminals all contained NPY and were observed in many brain regions extending from the rostral telencephalon to the pons, including the parabrachial nucleus. NPY-positive, AGRP-negative terminals were observed in many areas. AGRP-ir terminals were reduced dramatically in all brain regions of mice treated neonatally with monosodium glutamate as well as of mice homozygous for the anorexia mutation. Terminals immunoreactive for the melanocortin peptide alpha-melanocyte-stimulating hormone formed a population separate from, but parallel to, the AGRP-ir terminals. Our results show that arcuate NPY neurons, identified by the presence of AGRP, project more extensively in the brain than previously known and indicate that the feeding regulatory actions of NPY may extend beyond the hypothalamus.
Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes. (1991)

To determine whether endothelin-1 (ET-1) induces hypertrophy of cardiomyocytes, the effects of ET-1 on the expression of muscle-specific genes and a proto-oncogene, c-fos, in cultured neonatal rat cardiomyocytes were examined by Northern blot analysis. ET-1 (10(-7) M) induced about twofold to fourfold increases in the gene expression of myosin light chain 2, alpha-actin, and troponin I after 6 hours, which continued up to 24 hours. The ET-1-induced increases in mRNA levels for these muscle-specific genes were dose dependent (10(-9) to 10(-7) M). Run-on transcriptional assay showed that the changes in mRNA level for three muscle-specific genes were regulated, at least in part, at the transcriptional level. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a potent protein kinase C activator, and the Ca2+ ionophore ionomycin also increased mRNA levels of three muscle-specific genes. ET-1, TPA, and ionomycin similarly induced the expression of c-fos after 30 minutes, which returned to an undetectable level after 6 hours. ET-1 remarkably and dose-dependently stimulated accumulation of total inositol phosphates in cardiomyocytes. Morphometrical evaluation showed that ET-1 significantly increased surface area of cardiomyocytes without cell proliferation. ET-1 also dose-dependently stimulated the synthesis of protein and DNA, which was unaffected by the L-type calcium channel blocker nicardipine. These data suggest that ET-1 induces hypertrophy of cardiomyocytes associated with the induction of muscle-specific gene transcripts through the possible involvement of protein kinase C activation or intracellular Ca2+ mobilization.
Formation of Silver Nanoparticles under Structured Amino Groups in Pseudo-dendritic Poly(allylamine) Derivatives (2003)

The syntheses of silver nanoparticles stabilized by poly(allylamine) (PAA) and by polyethyleneiminated poly(allylamine) (PAA(EI)n (n = 2, 5.8)) are reported. The architectural effects in particle on the nanoparticle size, size distribution, and agglomeration behavior are determined from the UV−vis plasmon absorption band and transmission electron microscopic (TEM) analyses. The data show that PAA(EI)n display better stabilizing effects than PAA to prevent silver particles from agglomeration. Different phenomena of the polymer-protected nanoparticles at various silver ion concentrations are observed and are explained in terms of a mechanism of structure-dependent stabilization.
Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells (2013)

Recent clinical trials have shown that evasion of CD8(+) T-cell responses against viral capsid is critical for successful liver-directed gene therapy with adeno-associated viral (AAV) vectors for hemophilia. Preclinical models to test whether use of alternate serotypes or capsid variants could avoid this deleterious response have been lacking. Here, the ability of CD8(+) T cells ("cap-CD8," specific for a capsid epitope presented by human B*0702 or murine H2-L(d) molecules) to target AAV-infected hepatocytes was investigated. In a murine model based on adoptive transfer of ex vivo expanded cap-CD8, AAV2-transduced livers showed CD8(+) T-cell infiltrates, transaminitis, significant reduction in factor IX transgene expression, and loss of transduced hepatocytes. AAV8 gene transfer resulted in prolonged susceptibility to cap-CD8, consistent with recent clinical findings. In contrast, using an AAV2(Y-F) mutant capsid, which is known to be less degraded by proteasomes, preserved transgene expression and largely avoided hepatotoxicity. In vitro assays confirmed reduced major histocompatibility complex class I presentation of this capsid and killing of human or murine hepatocytes compared with AAV2. In conclusion, AAV capsids can be engineered to substantially reduce the risk of destruction by cytotoxic T lymphocytes, whereas use of alternative serotypes per se does not circumvent this obstacle.
TLR4 and Insulin Resistance (2010)

Chronic inflammation is a key feature of insulin resistance and obesity. Toll-Like Receptor 4 (TLR4), involved in modulating innate immunity, is an important mediator of insulin resistance and its comorbidities. TLR4 contributes to the development of insulin resistance and inflammation through its activation by elevated exogenous ligands (e.g., dietary fatty acids and enteric lipopolysaccharide) and endogenous ligands (e.g., free fatty acids) which are elevated in obese states. TLR4, expressed in insulin target tissues, activates proinflammatory kinases JNK, IKK, and p38 that impair insulin signal transduction directly through inhibitory phosphorylation of insulin receptor substrate (IRS) on serine residues. TLR4 activation also leads to increased transcription of pro-inflammatory genes, resulting in elevation of cytokine, chemokine, reactive oxygen species, and eicosanoid levels that promote further insulin-desensitization within the target cell itself and in other cells via paracrine and systemic effects. Increased understanding of cell type-specific TLR4-mediated effects on insulin action present the opportunity and challenge of developing related therapeutic approaches for improving insulin sensitivity while preserving innate immunity.
Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma (2007)

Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P < or = .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P < or = .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95% confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.
Over-the-counter foot remedies. (2001)

Several effective and inexpensive over-the-counter treatments are available for minor but troubling foot problems. In most cases, one week of therapy with topical terbinafine is effective for interdigital tinea pedis. Treatment of plantar warts with 17 percent salicylic acid with lactic acid in a collodion base is as effective as cryotherapy, but treatment must be sustained for several months. Toe sleeves and toe spacers can relieve pain from hard or soft corns. Metatarsal pads can relieve the pressure associated with plantar keratoses. Heel cups often can relieve pain caused by age-related thinning of the heel fat pad. Plantar fasciitis is a common cause of anteromedial heel pain caused by repetitive strain on the plantar fascia. Although the mainstay of therapy is stretching exercises, ready-made arch supports and insoles can be helpful adjuncts.
The potential of chitosan for the oral administration of peptides (2005)

Over recent years, a major challenge in drug delivery has been the design of appropriate vehicles for the oral administration of macromolecular drugs (peptides and proteins). Indeed, despite the increasing market value of these complex molecules, their clinical use has been highly limited by their reduced oral bioavailability. Among the different delivery approaches explored so far, those based on the use of the polysaccharide chitosan have opened promising alternatives towards this ambitious goal. This is due to the interesting physicochemical and biopharmaceutical properties of this polymer. This article describes the advances that have been made in the design of chitosan-based systems specially adapted for the oral administration of peptides. These systems include solutions, microspheres, nanoparticles, nanocapsules and liposomes. More specifically, this article discusses the efficacy of the different delivery approaches for improving the absorption of peptides, and analyses the various mechanisms that have been proposed for the understanding of their efficacy.
[Comparison of the in vitro activities of ammonium humate and of enzymically oxidized chlorogenic and caffeic acids against type 1 and type 2 human herpes virus (author's transl)]. (1981)

Ammonium humate (prepared from marsh water humic acids) as well as enzymically oxidized diphenolic compounds such as the oxidation products of chlorogenic and caffeic acids have strong antiviral activities in vitro. The effective concentrations lie considerably outside the cytotoxic range of the compounds mentioned.
Recent Developments in Fully-Integrated RF Self-Interference Cancellation for Frequency-Division and Full-Duplex Radios (2015)

RF self-interference cancellation (SIC) relaxes duplexer isolation requirements in frequency- division-duplex (FDD) radios, enabling compact/tunable duplexers. RF SIC is also critical for full-duplex radios where extremely-high levels of SIC must be achieved, necessitating SIC at various points in the receiver chain. While active RF SIC is potentially compact and highly reconfigurable, the use of active circuitry in the canceller introduces noise, distortion and power dissipation challenges. Furthermore, and particularly for fully-integrated silicon-based SIC implementations, the bandwidth (BW) of RF SIC is limited by the frequency selectivity of the antenna interface and the wireless self-interference channel. In this paper, we present recent developments in fully-integrated RF SIC techniques that address these challenges.
Patterning Hybrid Surfaces of Proteins and Supported Lipid Bilayers (2000)

Two methods for patterning surfaces with supported lipid bilayers and immobilized protein are described. First, proteins are used to fabricate corrals for supported lipid bilayers. Poly(dimethylsiloxane) stamps are used to deposit arbitrarily shaped patterns of thin layers of immobilized protein onto glass surfaces. This is followed by vesicle fusion into the regions that are not coated with proteins. Second, supported bilayer membranes are blotted to remove patterned regions of the membrane,1 and the blotted regions are filled in or caulked with protein from solution. In both cases, the lipid bilayer regions exhibit lateral fluidity, but each region is confined or corralled by the protein. These two methods can be combined and used iteratively to create arrays with increasing lateral complexity in both the fixed protein and mobile-supported membrane regions for biophysical studies or cell-based assays.
The design of eco-feedback technology (2010)

Eco-feedback technology provides feedback on individual or group behaviors with a goal of reducing environmental impact. The history of eco-feedback extends back more than 40 years to the origins of environmental psychology. Despite its stated purpose, few HCI eco-feedback studies have attempted to measure behavior change. This leads to two overarching questions: (1) what can HCI learn from environmental psychology and (2) what role should HCI have in designing and evaluating eco-feedback technology? To help answer these questions, this paper conducts a comparative survey of eco-feedback technology, including 89 papers from environmental psychology and 44 papers from the HCI and UbiComp literature. We also provide an overview of predominant models of proenvironmental behaviors and a summary of key motivation techniques to promote this behavior.