gebhart/patrepeval huggingface dataset:
Nerve Growth Factor Promotes the Survival of Sympathetic Neurons through the Cooperative Function of the Protein Kinase C and Phosphatidylinositol 3-Kinase Pathways (2004)

The signaling pathways activated by nerve growth factor (NGF) that account for its ability to promote the survival of neurons are not completely understood. Phosphatidylinositol 3-kinase (PI3K) is critical for the survival of several cell types, including neurons. To determine whether additional signaling pathways cooperate with PI3K to promote survival, we examined other pathways known to be activated by NGF. NGF activated protein kinases C (PKCs) in sympathetic neurons, and pharmacologic PKC activation rescued neurons from apoptosis induced by the withdrawal of NGF. Inhibition of PKCs did not inhibit the survival of NGF-maintained neurons. Similarly, inhibition of PI3K caused only a modest attrition of neurons in the presence of NGF. In contrast, the simultaneous inhibition of both PKCs and PI3K induced the apoptotic death of NGF-maintained sympathetic neurons. Inhibition of both PI3K and PKCs promoted the expression and phosphorylation of the proapoptotic transcription factor c-Jun, indicating that these pathways inhibit programmed cell death at the stage of proapoptotic gene expression. In culture conditions under which PI3K inhibition alone kills NGF-maintained neurons, PKC inhibition also led to a significant loss of viability, indicating that both pathways are required. Therefore, PKC and PI3K, regardless of the culture conditions, cooperate to promote the NGF-dependent survival of sympathetic neurons.
Synthesis and Evaluation of Benzothiazole-Based Analogues as Novel, Potent, and Selective Fatty Acid Amide Hydrolase Inhibitors (2008)

High-throughput screening (HTS) identified benzothiazole analogue 3 as a potent fatty acid amide hydrolase (FAAH) inhibitor. Structure-activity relationship (SAR) studies indicated that the sulfonyl group, the piperidine ring and benzothiazole were the key components to their activity, with 16j being the most potent analogue in this series. Time-dependent preincubation study of compound 3 was consistent with it being a reversible inhibitor. Activity-based protein-profiling (ABPP) evaluation of 3 in rat tissues revealed that it had exceptional selectivity and no off-target activity with respect to other serine hydrolases. Molecular shape overlay of 3 with a known FAAH inhibitor indicated that these compounds might act as transition-state analogues, forming putative hydrogen bonds with catalytic residues and mimicking the charge distribution of the tetrahedral transition state. The modeling study also indicated that hydrophobic interactions of the benzothiazole ring with the enzyme contributed to its extraordinary potency. These compounds may provide useful tools for the study of FAAH and the endocannabinoid system.
N‐glycans of recombinant human interferon‐γ change during batch culture of chinese hamster ovary cells (1995)

A recombinant Chinese hamster ovary (CHO) cell line making human interfron-gamma (IFN-gamma) was grown in 12-L stirred tank fermentors in three batch fermentations under conditions of constant temperature, pH, and dissolved oxygen tension. In addition to cell growth, metabolite, and productivity data, a detailed analysis of the carbohydrate structures attached to each glycosylation site of IFN-gamma was achieved using matrix-assisted laser desorption mass spectrometry (MALDI-MS) in combination with exoglycosidase array sequencing. Complex biantennary oligosaccharides (particularly Gal(2)GlcNAc(4)Man(3) which was core alephl-6 fucosylated at Asn(25) but not at Asng(97)) were most prevalent at both glycosylation sites. However, considerable microheterogeneity arising from the presence of triantennary and truncated glycan structures was also observed. The proportion of the dominant core glycan structure (Gal(2)GlcNAc(4)Man(3) +/- Fuc(1)) decreased by 15-26% during batch culture, with increases in the proportion of oligomannose and truncated glycans over the same time period. Prolonged culture resulting from an extended lag phase led to further accumulation of oligomannose and truncated structures, reaching up to 52% of total glycans attached to Asng(97) by 240 h of culture. The implications of these glycosylation changes for optimizing the time for harvesting cell cultures, and for the clearance of recombinant therapeutic products in vivo are discussed. (c) 1995 John Wiley & Sons, Inc.
Correction of chromosomal mutation and random integration in embryonic stem cells with helper-dependent adenoviral vectors (2005)

For gene therapy of inherited diseases, targeted integration/gene repair through homologous recombination (HR) between exogenous and chromosomal DNA would be an ideal strategy to avoid potentially serious problems of random integration such as cellular transformation and gene silencing. Efficient sequence-specific modification of chromosomes by HR would also advance both biological studies and therapeutic applications of a variety of stem cells. Toward these goals, we developed an improved strategy of adenoviral vector (AdV)-mediated HR and examined its ability to correct an insertional mutation in the hypoxanthine phosphoribosyl transferase (Hprt) locus in male mouse ES cells. The efficiency of HR was compared between four types of AdVs that contained various lengths of homologies at the Hprt locus and with various multiplicities of infections. The frequency of HR with helper-dependent AdVs (HD AdVs) with an 18.6-kb homology reached 0.2% per transduced cell at a multiplicity of infection of 10 genomes per cell. Detection of random integration at DNA levels by PCR revealed extremely high efficiency of 5% per cell. We also isolated and characterized chromosomal sites where HD AdVs integrated in a random manner. In contrast to retroviral, lentiviral, and adeno-associated viral vectors, which tend to integrate into genes, the integration sites of AdV was distributed randomly inside and outside genes. These findings suggest that HR mediated by HD AdVs is efficient and relatively safe and might be a new viable option for ex vivo gene therapy as well as a tool for chromosomal manipulation of a variety of stem cells.
Inhibition of pathologic retinal neovascularization by alpha-defensins. (2005)

Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that alpha-defensins interfere with alpha5beta1-FN interactions and dependent endothelial cell functions. Here, alpha-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, alpha-defensins specifically inhibited alpha5beta1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrin-matrices. An up-regulation of beta1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and local administration of alpha-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of alpha5beta1-blocking antibody. alpha-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that alpha-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies.
Thigh Muscle Activity, Knee Motion, and Impact Force During Side-Step Pivoting in Agility-Trained Female Basketball Players (2009)

Agility training improved medial hamstrings activity in female intramural basketball players during a side-step pivot maneuver. Agility training that improves hamstrings activity might have implications for reducing anterior cruciate ligament sprain injury associated with side-step pivots.
Modal Warping: Real-Time Simulation of Large Rotational Deformation and Manipulation (2004)

This paper proposes a real-time simulation technique for large deformations. Green's nonlinear strain tensor accurately models large deformations; however, time stepping of the resulting nonlinear system can be computationally expensive. Modal analysis based on a linear strain tensor has been shown to be suitable for real-time simulation, but is accurate only for moderately small deformations. In the present work, we identify the rotational component of an infinitesimal deformation and extend traditional linear modal analysis to track that component. We then develop a procedure to integrate the small rotations occurring at the nodal points. An interesting feature of our formulation is that it can implement both position and orientation constraints in a straightforward manner. These constraints can be used to interactively manipulate the shape of a deformable solid by dragging/twisting a set of nodes. Experiments show that the proposed technique runs in real-time, even for a complex model, and that it can simulate large bending and/or twisting deformations with acceptable realism.
Skin deep: enhanced sleep depth by cutaneous temperature manipulation (2008)

With ageing, an increasingly disturbed sleep is reported as a significant complaint affecting the health and well-being of many people. The available treatments for sleep disturbance have their limitations, so we have adopted a different approach to the improvement of sleep. Since in animal and human studies skin warming has been found to increase neuronal activity in brain areas that are critically involved in sleep regulation, we investigated whether subtle skin temperature manipulations could improve human sleep. By employing a thermosuit to control skin temperature during nocturnal sleep, we demonstrate that induction of a mere 0.4 degrees C increase in skin temperature, whilst not altering core temperature, suppresses nocturnal wakefulness (P<0.001) and shifts sleep to deeper stages (P<0.001) in young and, especially, in elderly healthy and insomniac participants. Elderly subjects showed such a pronounced sensitivity, that the induced 0.4 degrees C increase in skin temperature was sufficient to almost double the proportion of nocturnal slow wave sleep and to decrease the probability of early morning awakening from 0.58 to 0.04. Therefore, skin warming strongly improved the two most typical age-related sleep problems; a decreased slow wave sleep and an increased risk of early morning awakening. EEG frequency spectra showed enhancement of low-frequency cortical oscillations. The results indicate that subtle feedback control of in-bed temperature through very mild manipulations could have strong clinical relevance in the management of disturbed sleep especially in the elderly, who have an attenuated behavioural response to suboptimal environmental temperature, which may hamper them from taking appropriate action to optimize their bed temperature.
Structure of the membrane channel porin from Rhodopseudomonas blastica at 2.0 Å resolution (1994)

The crystal structure of a membrane channel, homotrimeric porin from Rhodopseudomonas blastica has been determined at 2.0 A resolution by multiple isomorphous replacement and structural refinement. The current model has an R-factor of 16.5% and consists of 289 amino acids, 238 water molecules, and 3 detergent molecules per subunit. The partial protein sequence and subsequently the complete DNA sequence were determined. The general architecture is similar to those of the structurally known porins. As a particular feature there are 3 adjacent binding sites for n-alkyl chains at the molecular 3-fold axis. The side chain arrangement in the channel indicates a transverse electric field across each of the 3 pore eyelets, which may explain the discrimination against nonpolar solutes. Moreover, there are 2 significantly ordered girdles of aromatic residues at the nonpolar/polar borderlines of the interface between protein and membrane. Possibly, these residues shield the polypeptide conformation against adverse membrane fluctuations.
The effects of weak gate-to-drain(source) overlap on MOSFET characteristics (1986)

Recent studies showed that minor structural differences in the gate-to-drain (source) overlap of a MOSFET has unexpectedly strong influence on its characteristics. As the overlap is weakened, the drain drive degrades, the substrate and gate currents show abnormal behaviors, and the device lifetime suffers. A simple physical model is presented that adequately explains most of these observed high-field effects, including the asymmetry in device properties. Implications of the wear-overlap phenomena on future process and device designs are discussed.
Involvement of Vascular Endothelial Growth Factor in Kaposi's Sarcoma Associated with Acquired Immunodeficiency Syndrome (1996)

To examine the role of vascular endothelial growth factor (VEGF) in the development of edema associated with Kaposi's sarcoma (KS) in acquired immunodeficiency syndrome (AIDS), we exploited animal model systems to detect the activity that induces vascular hyper-permeability (VHP) using cultured AIDS-KS spindle cells. Cultured AIDS-KS spindle cells and conditioned medium (AIDS-KS-CM) that had been semi-purified through a heparin affinity column were tested for the ability to induce VHP in animals. The AIDS-KS spindle cells and AIDS-KS-CM induced VHP that was histamine-independent. The VHP-inducing activity was detected in the 0.5 M NaCl fraction from the heparin affinity column and was blocked by anti-VEGF neutralizing antibody. In addition, the production of VEGF was demonstrated in fresh AIDS-KS tissue as well as in cultured AIDS-KS cells, while control cells were negative for VEGF production. From these observations, we concluded that AIDS-KS cells produce a factor(s) that promotes VHP, and this factor could be VEGF.
An automated system for high-throughput single cell-based breeding (2013)

When establishing the most appropriate cells from the huge numbers of a cell library for practical use of cells in regenerative medicine and production of various biopharmaceuticals, cell heterogeneity often found in an isogenic cell population limits the refinement of clonal cell culture. Here, we demonstrated high-throughput screening of the most suitable cells in a cell library by an automated undisruptive single-cell analysis and isolation system, followed by expansion of isolated single cells. This system enabled establishment of the most suitable cells, such as embryonic stem cells with the highest expression of the pluripotency marker Rex1 and hybridomas with the highest antibody secretion, which could not be achieved by conventional high-throughput cell screening systems (e.g., a fluorescence-activated cell sorter). This single cell-based breeding system may be a powerful tool to analyze stochastic fluctuations and delineate their molecular mechanisms.
Microwave propagation in two-dimensional dielectric lattices (1991)

We have calculated and measured the properties of X-band microwaves propagating in a 2D array of low-loss high-dielectric-constant cylinders. Transmission bands and photonic band gaps are conclusively identified in excellent agreement with the theoretical predictions. Detailed data on the properties of isolated defect states are also presented. We conclude that studies of this model scattering system allow the quantitative evaluation and testing of ideas regarding wave propagation and localization in strongly scattering media.
Oral administration of magnesium hydroxide to subjects with insulin-dependent diabetes mellitus: effects on magnesium and potassium levels and on insulin requirements. (1988)

Intra- and extracellular levels of magnesium and potassium were determined in 16 subjects with insulin-dependent type I diabetes mellitus (IDDM) and 30 healthy controls. Subjects with IDDM had lower levels of magnesium in muscle biopsies (p less than 0.001), plasma (p less than 0.001), and mononuclear cells (p less than 0.05), and higher urinary excretions of magnesium (p less than 0.01), and lower levels of potassium in muscle biopsies (p less than 0.001), and erythrocytes (p less than 0.05), as compared with those in controls. Magnesium hydroxide (500 mg/day) was administered orally to the diabetics. The levels of magnesium and potassium in muscle biopsies increased (p less than 0.001; p less than 0.001), while the plasma levels of magnesium and the urinary excretions of magnesium increased only temporarily, during 21 weeks of treatment. The requirements of insulin were reduced (p less than 0.001) during the course of the study, whereas the levels of glycosylated hemoglobin (HbA1c) and glucose were not changed. The findings indicate that administration of magnesium hydroxide is useful to treat muscular magnesium and potassium deficiency in diabetics.
Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells (1994)

Antizyme, a spermidine-induced protein that binds and stimulates ornithine decarboxylase degradation, is now shown also to mediate the rapid feedback inhibition of polyamine uptake into mammalian cells. Using a cell line (HZ7) transfected with truncated antizyme cDNA, and mutant ornithine decarboxylase cell lines, we demonstrate that this newly discovered action of antizyme is distinct from its role in modulating polyamine biosynthesis.
Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage (2004)

The retinal pigment epithelial cell (RPE cell) layer protects the photoreceptors of the retina against oxidative stress. The decline of this capacity is believed to be a major factor in the impairment of vision in age-related macular degeneration. Exposure of human adult RPE cells to UV light at predominantly 320-400 nm (UVA light) in the presence of all-trans-retinaldehyde results in photooxidative cytotoxicity. Significant protection of RPE cells was obtained by prior treatment with phase 2 gene inducers, such as the isothiocyanate sulforaphane or a bis-2-hydroxybenzylideneacetone Michael reaction acceptor. The degree of protection was correlated with the potencies of these inducers in elevating cytoprotective glutathione levels and activities of NAD(P)H:quinone oxidoreductase. In embryonic fibroblasts derived from mice in which the genes for the transcription factor Nrf2, the repressor Keap1, or both Nrf2 and Keap1 were disrupted, the magnitude of resistance to photooxidative damage paralleled the basal levels of glutathione and NAD(P)H:quinone oxidoreductase in each cell type. Demonstration of protection of RPE cells against photooxidative damage by induction of phase 2 proteins may shed light on the role of oxidative injury in ocular disease. Moreover, the finding that dietary inducers provide indirect antioxidant protection suggests novel strategies for preventing chronic degenerative diseases, such as age-related macular degeneration.
Copper-Catalyzed C(sp3)–C(sp3) Bond Formation Using a Hypervalent Iodine Reagent: An Efficient Allylic Trifluoromethylation (2011)

An efficient copper-catalyzed allylic trifluoromethylation reaction has been developed. This reaction provides a general and straightforward way to synthesize allylic trifluoromethylated compounds under mild conditions.
Social Network Sites: Definition, History, and Scholarship (2007)

Social network sites (SNSs) are increasingly attracting the attention of academic and industry researchers intrigued by their affordances and reach. This special theme section of the Journal of Computer-Mediated Communication brings together scholarship on these emergent phenomena. In this introductory article, we describe features of SNSs and propose a comprehensive definition. We then present one perspective on the history of such sites, discussing key changes and developments. After briefly summarizing existing scholarship concerning SNSs, we discuss the articles in this special section and conclude with considerations for future research.
Intrinsic White-Light Emission from Layered Hybrid Perovskites (2014)

We report on the second family of layered perovskite white-light emitters with improved photoluminescence quantum efficiencies (PLQEs). Upon near-ultraviolet excitation, two new Pb-Cl and Pb-Br perovskites emit broadband "cold" and "warm" white light, respectively, with high color rendition. Emission from large, single crystals indicates an origin from the bulk material and not surface defect sites. The Pb-Br perovskite has a PLQE of 9%, which is undiminished after 3 months of continuous irradiation. Our mechanistic studies indicate that the emission has contributions from strong electron-phonon coupling in a deformable lattice and from a distribution of intrinsic trap states. These hybrids provide a tunable platform for combining the facile processability of organic materials with the structural definition of crystalline, inorganic solids.
A chimeric avian retrovirus containing the influenza virus hemagglutinin gene has an expanded host range (1992)

We have investigated what protein sequences are necessary for glycoprotein incorporation into Rous sarcoma virus (RSV) virions by utilizing the hemagglutinin (HA) protein of influenza virus. Two chimeric HA genes were constructed. In the first the coding sequence for the signal peptide of the RSV env gene product was fused in frame to the entire HA structural gene, and in the second the hydrophobic anchor and cytoplasmic domain sequences of the HA gene were also replaced with those from the RSV env gene. Both chimeric genes, expressed from a simian virus 40 expression vector in CV-1 cells, yielded functional HA proteins that were transported to the cell surface and were able to bind to erythrocytes. When the genes were expressed in combination with the RSV gag-pol gene region in QT6 cells by using a vaccinia virus-T7 expression/complementation system, virions that efficiently incorporated either chimeric protein were assembled. This result indicated that the presence of the RSV env membrane anchor and cytoplasmic sequences did not facilitate HA glycoprotein incorporation into virions. The presence of the RSV env signal sequence allowed the chimeric HA genes to be substituted into the RSV-derived BH-RCAN.HiSV viral genome in place of the RSV env gene. Both chimeric genomes yielded infectious virus that could infect human and avian cells with equal efficiency. These experiments demonstrate that a foreign glycoprotein, efficiently incorporated into virions lacking a native glycoprotein, can confer a broadened host range on the virus. Moreover, because the HA of influenza virus requires the acidic pH of the endosome in order to be activated, these results imply that foreign proteins can modify the normal route of entry of this avian retrovirus.
Urethral Reconstruction with a New Synthetic Absorbable Device (1992)

Four centimeters of the canine urethra was replaced by a graft consisting of a polyglactin fiber mesh tube, coated with polyhydroxybutyric acid. Microscopic examination 8-12 months later showed almost complete regeneration of the urethral epithelium and the adjacent connective tissue. The neo-urethra was patent and there were no anastomotic strictures, nor was there any inflammatory reaction around the urethra. The validity of this concept in humans remains to be proved.
The use of gene arrays and corresponding connectivity mapping (Cmap) to identify novel anti‐ageing ingredients (2015)

Based on RA mimicking gene array activity, potential use within skincare on molecular size, safety assessment and sourcing, we identified the natural amino acid, A-A-A as a potential candidate to treat ageing skin.