gebhart/patrepeval huggingface dataset:
Potential use of cholecalciferol polyethylene glycol succinate as a novel pharmaceutical additive (2007)

D-alpha-tocopheryl polyethylene glycol succinate (TPGS) has been utilized in numerous drug delivery formulations in recent years. Because of its amphiphilic structure, it can be used as emulsifier and vehicle for lipid-based drug delivery formulations. It is also an effective P-glycoprotein (P-gp) inhibitor. However, TPGS represents only one of the surfactants in the class of "Vitamin-PEG" conjugated surfactants. To design a new adjuvant or additive, a conjugate made of vitamin D (cholecalciferol) and PEG-cholecalciferol polyethylene glycol succinate (CPGS) was synthesized via a two-step reaction. We hypothesized that CPGS may exhibit similar characteristics to TPGS, and thus the physicochemical properties as well as the anticancer properties of CPGS were studied. The results demonstrated that CPGS reduced the particle size and increased the encapsulation efficiency of the PLGA nanoparticles, indicating that CPGS may also have the emulsifier function similar to TPGS. The drug release profiles showed that the nanoparticles with CPGS additive had a lower initial burst and more sustained release pattern. In vitro testing with Caco-2 cells showed that CPGS could increase the cytotoxicity of DOX-loaded PLGA nanoparticles. Based on the rhodamine accumulation study, the increased cytotoxicity is possibly due to the P-gp inhibition by CPGS. From current results, the use of CPGS as an adjuvant is promising and may enhance the efficacy of the overall drug delivery system.
Harnessing Localized Ridges for High‐Aspect‐Ratio Hierarchical Patterns with Dynamic Tunability and Multifunctionality (2013)

A simple method for fabricating high-aspect-ratio, hierarchical, and dynamically tunable surface patterns is invented by harnessing localized-ridge instabilities in gold nanofilms coated on elastomer substrates (a); a theoretical model to calculate the critical parameters (e.g., wavelength and amplitude) for designing the new patterns is developed (b); and novel applications of the patterns as super-hydrophobic coatings (c) and biomimetic cell-culture substrates (d) capable of on-demand tunability are demonstrated.
Facile Method for the Fabrication of Vertically Aligned ITO Nanopillars with Excellent Properties (2009)

Vertically aligned ITO film with high performance was successfully fabricated in atmospheric pressure using a direct deposition in flame (DDF) method. ITO films revealed a high transmittance with a low specific resistivity (high conductivity), which shows great promise for future optoelectronic device application.
Ubiquitin is part of the retrovirus budding machinery (2000)

Retroviruses contain relatively large amounts of ubiquitin, but the significance of this finding has been unknown. Here, we show that drugs that are known to reduce the level of free ubiquitin in the cell dramatically reduced the release of Rous sarcoma virus, an avian retrovirus. This effect was suppressed by overexpressing ubiquitin and also by directly fusing ubiquitin to the C terminus of Gag, the viral protein that directs budding and particle release. The block to budding was found to be at the plasma membrane, and electron microscopy revealed that the reduced level of ubiquitin results in a failure of mature virus particles to separate from each other and from the plasma membrane during budding. These data indicate that ubiquitin is actually part of the budding machinery.
Expression of prostacyclin-stimulating factor (PSF) in mononuclear cells of human peripheral blood and THP-1 derived macrophage-like cells, and effects of high glucose concentration (2005)

Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to development of diabetic angiopathies including that in atherosclerosis. We identified a bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis in cultured aortic ECs. Our previous studies demonstrated that PSF was predominantly expressed by arterial smooth muscle cells (SMCs) and ECs. We immunohistochemically showed that PSF existed in SMCs of human coronary arteries, and PSF staining was markedly reduced in coronary arterial SMCs of patients with type 2 diabetes and/or myocardial infarction. In the present study, we investigated the existence of PSF in human serum, and effects of glucose on serum PSF levels in patients with type 2 diabetes. Immunoblot analysis revealed the presence of PSF in serum, and showed that serum PSF protein concentration was significantly decreased in type 2 diabetic patients. Moreover, there was a significant negative correlation between serum PSF and HbA1c levels in these patients. Using immunohistochemistry, we also showed that PSF was present in serum and in macrophages (Mfs). PSF mRNA was found in Mfs using reverse transcription-polymerase chain reaction (RT-PCR). In addition, effects of high glucose conditions on PSF production in Mfs were examined by Western blotting, and we showed that PSF significantly decreased when Mfs were cultured in high glucose conditions. These results strongly suggested that decreased PSF production might result in decreased production of PGI_2 in atherosclerotic lesions, thus leading to development of diabetic macroangiopathy and atherosclerosis.
v-Src activates both protein kinase C-dependent and independent signaling pathways in murine fibroblasts. (1991)

Activating the protein-tyrosine kinase activity of v-Src rapidly induced expression of the two 'primary response' genes, TIS10 and Egr-1, in Balb/c 3T3 cells. Depleting cells of protein kinase C (PKC) by prolonged exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA), blocked v-Src-induced TIS10 expression, but had no effect on v-Src-induced Egr-1 gene expression. In addition, the induction of TIS10 and Egr-1 by v-Src could be distinguished using protein kinase inhibitors. Thus, v-Src induced gene expression in murine fibroblasts via two distinguishable signaling pathways: one dependent upon PKC and another that is independent of PKC. Consistent with the use of PKC-mediated signaling pathway by v-Src in murine fibroblasts, we found that activating the kinase activity of v-Src led to increased phosphorylation of a major PKC substrate. Thus, data presented here suggest that v-Src-induced transformation involves the activation of multiple signalling pathways, one of which requires PKC.
Optimization of sidewall roughness in silica waveguides to reduce the propagation losses (2001)

Summary form only given. The propagation loss of silica waveguide is mainly due to the nonuniformities arising from the film deposition and etching process. Especially, scattering from the sidewall roughness (SWR) is the main cause of the propagation loss. Smooth sidewall offers lower propagation loss and reduced sensitivity to polarization. In this work SWR and etched profile of silica waveguides fabricated by dry etching were investigated. Fabrication techniques to form waveguides with vertical and smooth sidewall were suggested.
Density, Viscosity, and Surface Tension of Liquid Quinoline, Naphthalene, Biphenyl, Decafluorobiphenyl, and 1,2-Diphenylbenzene from 300 to 400 °C (1996)

The liquid density, liquid viscosity, and surface tension of quinoline, naphthalene, biphenyl, decafluorobiphenyl, and 1,2-diphenylbenzene were measured at saturation between 300 and 400 °C. The results were fit to temperature-dependent correlations. The critical temperature of decafluorobiphenyl was also determined.
Structural Requirements for Potent Versus Selective Cytotoxicity for Antimicrobial Dermaseptin S4 Derivatives (2002)

To better understand the structural requirements for selective cytotoxicity of antimicrobial peptides, seven dermaseptin S4 analogs were produced and investigated with respect to molecular organization in solution, binding properties to model phospholipid membranes, and cytotoxic properties. Native dermaseptin S4 displayed high aggregation in solution and high binding affinity. These properties correlated with high cytotoxicity. Yet, potency was progressively limited when facing cells whose plasma membrane was surrounded by increasingly complex barriers. Increasing the positive charge of the native peptide led to partial depolymerization that correlated with higher binding affinity and with virtually non-discriminative high cytotoxicity against all cell types. The C-terminal hydrophobic domain was found responsible for binding to membranes but not for their disruption. Truncations of the C terminus combined with increased positive charge of the N-terminal domain resulted in short peptides having similar binding affinity as the parent compound but displaying selective activity against microbes with reduced toxicity toward human red blood cells. Nuclear magnetic resonance-derived three-dimensional structures of three active derivatives enabled the delineation of a common amphipathic structure with a clear separation of two lobes of positive and negative electrostatic potential surfaces. Whereas the spatial positive electrostatic potential extended considerably beyond the peptide dimensions and was required for potency, selectivity was affected primarily by hydrophobicity. The usefulness of this approach for the design of potent and/or selective cytolytic peptides is discussed herein.
Catalytic Enantioselective Cyclopropanation of Olefins Using Carbenoid Chemistry (1997)

Use of metal complexes of chiral nonracemic ligands in asymmetric cyclopropanation reactions via homogeneous catalysis is one of the recent developments in synthetic organic chemistry. The extra carbon in the cyclopropane unit from the cyclopropanation of olefins comes from diazo esters or dihalomethanes. In this article we shall discuss the recent aspects of asymmetric intermolecular cyclopropanation reactions where decomposition of these compounds to carbenoid species takes place by organometallic complexes.
Efficient data structures for range-aggregate queries on trees (2009)

Graph-theoretic aggregation problems have been considered both in OLAP (grid graph) and XML (tree). This paper gives new results for MIN aggregation in a tree, where we want the MIN in a query subtree consisting of the nodes reachable from a node u along paths of length ≤ k (u and k are query parameters). The same problem is well solved when the aggregation is SUM rather than MIN, but the solutions rely on additive inverses for the + operator, and they fail for the MIN aggregation which is the topic of this paper. For the directed (rooted tree) case, we give an O(n) space, constant query time solution. For the undirected case, the space complexity is O(n log n) and the query time is O(log n).
Cutting the cord: student‐led discussion groups in higher education (1998)

As the world of higher education has become increasingly sensitive to employers’ needs so attention has focused on the development of skills and competences which will equip graduates to function effectively in the labour market. High on the list of graduates’ desired qualities are first, the ability to work in a team and second, the capacity for independent thought and action. At the same time, there has been a growing recognition that traditional methods of teaching (primarily tutorials and lectures) may be serving to perpetuate the opposite, namely dependency and passivity. With these issues in mind, the article outlines the experience of using leaderless group discussions and associated peer assessment as an integral part of an undergraduate degree programme. The practicalities of running the groups, the lessons which have been learnt over time, and the benefits for student learning are also discussed.
Key indicators of economic development in China and India: A comparative study (2012)

China and India are two neighbouring countries in Asia. India is geographically, the largest country in South Asia and seventh largest in the world. It has world's second largest population over one billion. Its total area is 32.9 lakh kms and present growth rate in GDP is 7.2% per annum. On the other hand, the People's Republic of China is located in Eastern Asia and is the third largest country in the world in terms of total area (96 lakh km). Both the economies have some similar characteristics. Their population size and its growth rate, GDP growth rate, place in global economy etc. stand almost on equal footing. Although the two countries went to war in 1962 due to some border dispute, they have since tried to normalise relations and in 1995 for the first time trade had exceeded US$1 billion between them. They have lately received a lot of international attention being viewed as emerging giant economies as they both play key roles at the international level. For example China has been a permanent member of the Security Council at the UN, while India who has leads the Non-Aligned Movement for years and is still vying for a similar position. Furthermore, India has been one of the founding members of the WTO and has played a prominent role as one of the developing nations whereas China has had to fight for decades to obtain its admission into this international organisation. While both China and India have an extended history of international trade going back centuries ago, both their economies were until recently highly protected and controlled to a large extent albeit that their political systems are very different. China is still a very unique case in the sense that while it has allowed its economy to be opened to Capitalists MNCs, it is still governed by the Communist Party with a strong leadership not giving away state power. Therefore, it is better to know about main features of both the economies. The aim of this paper is, to study two developing countries India and China w.r.t developments and regulations in economy in last two decades. Moreover this paper will cover the external sector prospects including FDI in two countries.
The Pathologic Significance of the Immunoglobulins Expressed by Chronic Lymphocytic Leukemia B-cells in the Development of Autoimmune Hemolytic Anemia (1998)

The increased number of CD5+ B-cells in some human autoimmune diseases, the frequent commitment of CD5+ B-cells to the production of natural autoantibodies, and the apparent involvement of these cells in the pathogenesis of the autoimmune hemolytic anemia (AIHA) in certain mouse models suggests a causal relationship between the CD5+ chronic lymphocytic leukemia (CLL) B-cell and the AIHA which frequently develops in this malignant disorder. In support of this conclusion is our recent finding that the VH region gene repertoire of the leukemic B-cells from CLL patients with AIHA is rather biased and characterised by the over-representation of the 51p1 VH gene. On the other hand, it appears relatively certain that the pathogenic anti-erythrocyte antibodies in CLL patients with AIHA are produced by remnant normal B-cells, and that the antibodies expressed by the leukemic CD5+ B-cells do not directly bind red blood cells (RBC). Of interest, the antibodies produced by the leukemic B-cells from CLL patients with AIHA might have in common rheumatoid factor (RF) activity. These data indicate that the antibodies produced by the leukemic B-cells from CLL patients with AIHA are not directly involved in red blood cell destruction, but may be involved in the induction or amplification of a polyclonal anti-RBC response. Finally, we discuss the possible clinical implications of our finding that CLL patients with leukemic cells expressing the 51p1 VH gene may be at a higher risk to develop autoimmune hemolytic anemia.
PROFILI DI ILLEGITTIMITÀ COSTITUZIONALE DI UNA MEDIAZIONECIVILE OBBLIGATORIA “PURCHESSIA” (2011)

L'obbligatorietà della mediazione civile introdotta con il d.lgs. 4 marzo 2010, n. 28 è costituzionalmente illegittima.
Semantics of interactive rotations (1987)

We first outline an overall design philosophy for rigid geometric manipulations, then examine a manipulation's characteristics: nesting, scope, pivot constraints, and axis, constraints. We show how a mnemonic notation helps us explain how a simple matrix operation can make manipulations (both rotations and translations) nested within rotations easy to control. Finally, we mention some practical considerations to increase calculation speed and control numerical error. An appendix collects formulas useful for working with rotations.
A multiscale methodology for the analysis of velocity anisotropy in organic-rich shale (2015)

ABSTRACT Changes in the sources of velocity anisotropy and their relative magnitude as maturation progresses in organic-rich shale are still incompletely characterized in the rock-physics literature. As a result of the increasing importance of organic-rich shale as unconventional reservoirs, a more thorough understanding of the elastic behavior of shale is needed. We have formulated a comprehensive, multiphysics, multiscale experimental methodology for the characterization of the intrinsic (syn-lithification) and extrinsic (postlithification) factors contributing to velocity anisotropy. Application of this methodology to unsaturated samples also enabled the characterization of the shale frame for fluid substitution modeling. The methodological framework was then tested on a set of five naturally matured organic-rich shale samples. In this experimental methodology, we combined classical rock-physics measurements, e.g., ultrasonic velocity and emergent high-resolution imaging techniques, such as X-ray diffraction (XRD), scanning electron microscopy, confocal laser scanning microscopy, and X-ray microtomography to better characterize the heterogeneous and microstructurally complex shale at all scales. The use of XRD-based lattice-preferred orientation measurements in conjunction with conventional ultrasonic velocity experiments confirmed that the degree of alignment of the mineral matrix governed the intrinsic anisotropy of organic-rich shale. The closure of soft, crack-like porosity, as identified from axial strain data, was identified as the extrinsic source governing the pressure sensitivity of velocity anisotropy. We determined, for the set of samples included in this study, that the intrinsic anisotropy was the dominant source of anisotropy at all confining pressures. Indeed, at low confining pressures, the opening of microcracks contributed no more than 30% of the total velocity anisotropy. Applying these results to saturated rocks at depth indicated that, for these shales, the extrinsic, crack-based sources, will contribute no more than 30% of the shale anisotropy in situ.
Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. (1997)

Paraoxonase was identified as a genetic risk factor for cardiovascular disease (CVD) in recent studies focusing on a polymorphism affecting position 191. A second polymorphism of the paraoxonase gene affects position 54 and involves a methionine (M allele) to leucine (L allele) change. It was investigated in diabetic patients (n = 408) with and without vascular disease. There were highly significant differences in plasma concentrations and activities of paraoxonase between genotypes defined by the 54 polymorphism: MMAA, MLAA, LLAA; protein, 65.3+/-18.0, 77.9+/-18.0, 93.5+/-26.0 microg/ml; P < 0.0001: activity (phenylacetate), 48.6+/-13.5, 64.1+/-14.5, 68.1+/-13.0 U/ml; P < 0.0001. The 191 variant had little impact on paraoxonase concentrations. Homozygosity for the L allele was an independent risk factor for CVD (odds ratio 1.98 (1.07-3.83); P = 0.031). A linkage disequilibrium (P < 0.0001) was apparent between the mutations giving rise to leucine and arginine at positions 54 and 191, respectively. The study underlines that susceptibility to CVD correlates with high activity paraoxonase alleles. The 54 polymorphism would appear to be of central importance to paraoxonase function by virtue of its association with modulated concentrations. The latter could explain the association between both the 54 and 191 polymorphisms and CVD.
Targeted manipulation of maize genes in vivo using chimeric RNA/DNA oligonucleotides (1999)

Site-specific heritable mutations in maize genes were engineered by introducing chimeric RNA/DNA oligonucleotides. Two independent targets within the endogenous maize acetohydroxyacid synthase gene sequence were modified in a site-specific fashion, thereby conferring resistance to either imidazolinone or sulfonylurea herbicides. Similarly, an engineered green fluorescence protein transgene was site-specifically modified in vivo. Expression of the introduced inactive green fluorescence protein was restored, and plants containing the modified transgene were regenerated. Progeny analysis indicated Mendelian transmission of the converted transgene. The efficiency of gene conversion mediated by chimeric oligonucleotides in maize was estimated as 10(-4), which is 1-3 orders of magnitude higher than frequencies reported for gene targeting by homologous recombination in plants. The heritable changes in maize genes engineered by this approach create opportunities for basic studies of plant gene function and agricultural trait manipulation and also provide a system for studying mismatch repair mechanisms in maize.
A randomized sequential trial of creatine in amyotrophic lateral sclerosis (2003)

Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double-blind, placebo-controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS. Between June 2000 and December 2001, 175 patients with probable, probable-laboratory supported, or definite ALS were randomly assigned to receive either creatine monohydrate or placebo 10 gm daily. A sequential trial design was used with death, persistent assisted ventilation, or tracheostomy as primary end points. Secondary outcome measurements were rate of decline of isometric arm muscle strength, forced vital capacity, functional status, and quality of life. The trial was stopped when the null hypothesis of indifference was accepted. Creatine did not affect survival (cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months, and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months), or the rate of decline of functional measurements. Creatine intake did not cause important adverse reactions. This placebo-controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS.