gebhart/patrepeval huggingface dataset:
Development and Validation of a Discriminating Dissolution Method for Atorvastatin Delayed-Release Nanoparticles Using a Flow-Through Cell: A Comparative Study Using USP Apparatus 4 and 1 (2016)

Atorvastatin, an HMG CoA reductase inhibitor, is widely used for the treatment of dyslipidemia and prevention of cardiovascular disease. It belongs to Class 2 of the Biopharmaceutics Classification System owing to its low solubility and high permeability. In vitro dissolution testing is an essential tool for the design of a dosage form. Appropriate selection of dissolution test conditions is essential since it will help establish an appropriate in vitro-in vivo correlation (IVIVC), which is imperative for a waiver of costly bioequivalence studies. Compounds belonging to BCS Class 2 are suitable for establishing a significant IVIVC. USP Apparatus 4 (flow-through cell) is an attractive alternative to conventional dissolution methods like Apparatus 1 and 2. The ability of the apparatus to maintain sink conditions over a longer period of time has proved useful in the development of dissolution methods for poorly soluble drugs, making the development of IVIVCs easier for such drugs. Nanoparticles of atorvastatin were formulated by an emulsion-solvent evaporation method to overcome its bioavailability problems. Development of a discriminatory dissolution method for the same was attempted using a flow-through cell (Apparatus 4) because dissolution performed using Apparatus 1 did not provide complete release of the drug within 60 min. Phosphate buffer pH 6.8 with 1.5% SLS was selected as the dissolution medium based on the results of the solubility studies. Various parameters such as flow rate and sample-loading method were optimized. The dissolution method was validated with respect to various parameters as per ICH guidelines.
Self Protection from Anti-Viral Responses – Ro52 Promotes Degradation of the Transcription Factor IRF7 Downstream of the Viral Toll-Like Receptors (2010)

Ro52 is a member of the TRIM family of single-protein E3 ligases and is also a target for autoantibody production in systemic lupus erythematosus and Sjögren's syndrome. We previously demonstrated a novel function of Ro52 in the ubiquitination and proteasomal degradation of IRF3 following TLR3/4 stimulation. We now present evidence that Ro52 has a similar role in regulating the stability and activity of IRF7. Endogenous immunoprecipitation of Ro52-bound proteins revealed that IRF7 associates with Ro52, an effect which increases following TLR7 and TLR9 stimulation, suggesting that Ro52 interacts with IRF7 post-pathogen recognition. Furthermore, we show that Ro52 ubiquitinates IRF7 in a dose-dependent manner, resulting in a decrease in total IRF7 expression and a subsequent decrease in IFN-alpha production. IRF7 stability was increased in bone marrow-derived macrophages from Ro52-deficient mice stimulated with imiquimod or CpG-B, consistent with a role for Ro52 in the negative regulation of IRF7 signalling. Taken together, these results suggest that Ro52-mediated ubiquitination promotes the degradation of IRF7 following TLR7 and TLR9 stimulation. As Ro52 is known to be IFN-inducible, this system constitutes a negative-feedback loop that acts to protect the host from the prolonged activation of the immune response.
Synthesis, Structure, Redox Properties, and Catalytic Activity of New Ruthenium Complexes Containing Neutral or Anionic and Facial or Meridional Ligands:  An Evaluation of Electronic and Geometrical Effects (2007)

The synthesis of a family of new Ru complexes containing meridional or facial tridentate ligands with the general formula [RuII(T)(D)(X)]n+ [T = 2,2‘:6‘,2‘ ‘-terpyridine or tripyrazolylmethane; D = 4,4‘-dibenzyl-4,4‘,5,5‘-tetrahydro-2,2‘-bioxazole (S,S-box-C) or 2-[((1‘S)-1‘-(hydroxymethyl)-2‘-phenyl)ethylcarboxamide]-(4S)-4-benzyl-4,5-dihydrooxazole (S,S-box-O); X = Cl, H2O, MeCN or pyridine] has been described. All complexes have been spectroscopically characterized in solution through 1H NMR and UV−vis techniques. Furthermore, all of the chloro complexes presented here have also been characterized in the solid state through monocrystal X-ray diffraction analysis. The oxazolinic S,S-box-C ligands undergo a Ru-assisted hydrolysis reaction generating the corresponding amidate anionic oxazolinic ligands S,S-box-O, which are also strongly attached to the metal center and produce a strong σ-donation effect over the Ru metal center. The redox properties of all complexes have also been studied by means of cyclic voltammetry, strongly reflecting the nature of the ligands; both effects, geometrical (facial vs meridional) and electronic (neutral vs anionic), can be unveiled and rationalized. Finally, the reactivity of the Ru−OH2 complexes has been tested with regard to the epoxidation of trans-stilbene, and it has been shown that, in this particular case, the reactivity is practically not dependent on the redox potentials of the catalyst but, in sharp contrast, it is strongly dependent on the geometry of the tridentate ligands.
Plastic deformation of the intermetallic compound Al<sub>3</sub>Ti (1987)

Abstract Polycrystalline specimens of the intermetallic compound Al3Ti with the D022-type structure have been deformed under compression at 25–860°C. At temperatures below 620°C, specimens fracture with very small fracture strain since extremely localized deformation occurs and cracks are initiated in intensely deformed regions almost at yielding. At temperatures above 620°C, good compression ductility is observed. Yield stress starts decreasing rapidly with increasing temperature at around 330°C and becomes less temperature dependent above 630°C. The major mode of deformation of Al3Ti is twinning of the type (111)[112] which does not disturb the D022 symmetry of the lattice. However, at high temperatures, the four (111)[112]-type twinning systems are augmented by slip of the types [110], [100] and [010]. This would supply an explanation for the good compression ductility observed at temperatures above 620°C. Suggestions are made for further experimental work on alloying additions which may improve the ductility of Al3Ti.
Tissue factor promotes activation of coagulation and inflammation in a mouse model of sickle cell disease (2012)

Sickle cell disease (SCD) is associated with a complex vascular pathophysiology that includes activation of coagulation and inflammation. However, the crosstalk between these 2 systems in SCD has not been investigated. Here, we examined the role of tissue factor (TF) in the activation of coagulation and inflammation in 2 different mouse models of SCD (BERK and Townes). Leukocytes isolated from BERK mice expressed TF protein and had increased TF activity compared with control mice. We found that an inhibitory anti-TF antibody abrogated the activation of coagulation but had no effect on hemolysis or anemia. Importantly, inhibition of TF also attenuated inflammation and endothelial cell injury as demonstrated by reduced plasma levels of IL-6, serum amyloid P, and soluble vascular cell adhesion molecule-1. In addition, we found decreased levels of the chemokines MCP-1 and KC, as well as myeloperoxidase in the lungs of sickle cell mice treated with the anti-TF antibody. Finally, we found that endothelial cell-specific deletion of TF had no effect on coagulation but selectively attenuated plasma levels of IL-6. Our data indicate that different cellular sources of TF contribute to activation of coagulation, vascular inflammation, and endothelial cell injury. Furthermore, it appears that TF contributes to these processes without affecting intravascular hemolysis.
The syntheses of 6-<i>C</i>-alkyl derivatives of methyl α-isomaltoside for a study of the mechanism of hydrolysis by amyloglucosidase (2001)

The epimeric (6aR)- and (6aS)-C-alkyl (methyl, ethyl and isopropyl) derivatives of methyl α-isomaltoside (1) were synthesized in order to examine the effects of introducing alkyl groups of increasing bulk on the rate of catalysis for the hydrolysis of the interunit α-glycosidic bond by the enzyme amyloglucosidase, EC 3.2.1.3, commonly termed glucoamylase (AMG). It was previously established that methyl (6aR)-C-methyl α-isomaltoside is hydrolysed about 2 times faster than methyl α-isomaltoside and about 8 times faster than its S-isomer. The kinetics for the hydrolyses of the ethyl and isopropyl analogs were also recently published. As was expected from molecular model calculations, all the R-epimers are good substrates. A rationale is presented for the catalysis based on conventional mechanistic theories that includes the assistance for the decomposition of the activated complex to products by the presence of a hydrogen bond, which connects the 4a-hydroxyl group to the tryptophane and arginine units. It is proposed that activation of the initially formed complex to the transition state is assisted by the energy released as a result of both of the displacement of perturbed water molecules of hydration at the surfaces of both the polyamphiphilic substrate and the combining site and the establishment of intermolecular hydrogen bonds, i.e., micro-thermodynamics. The dissipation of the heat to the bulk solution is impeded by a shell of aromatic amino acids that surround the combining site. Such shields are known to be located around the combining sites of lectins and carbohydrate specific antibodies and are considered necessary to prevent the disruption of the intermolecular hydrogen bonds, which are of key importance for the stability of the complex. These features together with the exquisite stereoelectronic dispositions of the reacting molecules within the combining site offer a rationalization for the catalysis at ambient temperatures and near neutral pH. The syntheses involved the addition of alkyl Grignard reagents to methyl 6-aldehydo-α-D-glucopyranoside. The addition favoured formation of the S-epimers by over 90%. Useful amounts of the active R-isomers were obtained by epimerization of the chiral centers using conventional methods. Glycosylation of the resulting alcohols under conditions for bromide-ion catalysis, provided methyl (6aS)- and (6aR)-C-alkyl-hepta-O-benzyl-α-isomaltosides. Catalytic hydrogenolysis of the benzyl groups afforded the desired disaccharides. 1 H NMR studies established the absolute configurations and provided evidence for conformational preferences.Key words: amyloglucosidase (AMG), exo-anomeric effect, 6-C-alkyl-α-D-glucopyranosides and isomaltosides, mechanism of enzyme catalysis.
Controlling Linguistic Style Aspects in Neural Language Generation (2017)

Most work on neural natural language generation (NNLG) focus on controlling the content of the generated text. We experiment with controlling several stylistic aspects of the generated text, in addition to its content. The method is based on conditioned RNN language model, where the desired content as well as the stylistic parameters serve as conditioning contexts. We demonstrate the approach on the movie reviews domain and show that it is successful in generating coherent sentences corresponding to the required linguistic style and content.
Association of a Soybean Raffinose Synthase Gene with Low Raffinose and Stachyose Seed Phenotype (2010)

Oligosaccharides are an important component of soybean [Glycine max (L.) Merr.] meal in terms of metabolizable energy for monogastric animals. Sucrose, raffi nose, and stachyose are the three main oligosaccharides present in soybean meal. Of the three, only sucrose is nutritionally useful. When raffi nose and stachyose are fermented by microbes present in the gut, the results are fl atulence and discomfort, which ultimately lead to poor weight gain. The long term objective of this research is ultimately to increase the nutritional value of soybean meal by elevating the metabolizable energy at the expense of raffi nose and stachyose through the manipulation of soybean raffi nose synthase, the key enzyme for raffi nose and stachyose biosynthesis. The objectives of this work were to develop molecular genetic information about soybean raffi nose synthases and to evaluate the candidate raffi nose synthase genes in a soybean germplasm accession (PI 200508) that contains low levels of raffi nose and stachyose. Our results indicate the soybean genome contains at least two expressed genes similar to other characterized raffi nose synthases. A novel allele of one of these putative soybean raffi nose synthase genes was discovered from the PI 200508 that completely associates with the low raffi nose and stachyose phenotype. Molecular marker assays specifi c for the PI 200508 allele were developed to allow direct selection for the low raffi nose and low stachyose phenotype. T ODAY, SOYBEAN [Glycine max (L.) Merr.] represents one of the most important economic crops in the United States. It is considered similar to corn (zea mays L.) in acreage and second only to corn in value (Sleper and Poehlman, 2006). Th e oil, protein, and carbohydrate composition of the soybean seed generally controls its use. Seeds of soybean cultivars in the United States have an average composition of 20% oil, 40% protein, and 15% soluble carbohydrates in dry weights of cotyledons of
Fluorescent Chemosensor for Chloroalkanes (2008)

Two structurally related macrocyclic amines with naphthalene groups are shown to act as fluorescent dosimeters for reactive chloroalkanes, including the common industrial solvent dichloromethane. The macrocyclic structures contain two NH residues which greatly accelerate N-alkylation by activating the chloride leaving group. The chemical reaction increases fluorescence intensity by promoting excimer emission and attenuating the quenching induced by photoinduced electron transfer (PET).
The Immunopathogenesis of Cutaneous T-Cell Lymphoma (1993)

For the past 20 years, mycosis fungoides and the Sézary syndrome have been recognized as heterogeneous forms of cutaneous T-cell lymphoma (CTCL).<sup>1</sup>The former condition typically evolves slowly through progressive phases of localized cutaneous involvement with plaques and tumors with progression to extracutaneous involvement, generally over a period of years. Malignant cells are usually not detected within the blood in early stages of mycosis fungoides. In contrast, the Sézary syndrome presents with diffuse skin involvement (erythroderma), generalized lymphadenopathy, and the presence of circulating malignant lymphocytes. Thus, the Sézary syndrome is considered to be an advanced form of CTCL characterized by widespread dissemination of the malignant lymphocytes. The neoplastic cells, originally identified in the peripheral blood by Sézary and termed<i>monstrous</i>cells, have maintained the eponym of<i>Sézary cell</i>since that time.<sup>2</sup>A hallmark of these cells is the presence of a hyperchromatic nucleus, which, on refined light microscopy and electron microscopy, exhibits deeply
DeepIoT: Compressing Deep Neural Network Structures for Sensing Systems with a Compressor-Critic Framework (2017)

Recent advances in deep learning motivate the use of deep neutral networks in sensing applications, but their excessive resource needs on constrained embedded devices remain an important impediment. A recently explored solution space lies in compressing (approximating or simplifying) deep neural networks in some manner before use on the device. We propose a new compression solution, called DeepIoT, that makes two key contributions in that space. First, unlike current solutions geared for compressing specific types of neural networks, DeepIoT presents a unified approach that compresses all commonly used deep learning structures for sensing applications, including fully-connected, convolutional, and recurrent neural networks, as well as their combinations. Second, unlike solutions that either sparsify weight matrices or assume linear structure within weight matrices, DeepIoT compresses neural network structures into smaller dense matrices by finding the minimum number of non-redundant hidden elements, such as filters and dimensions required by each layer, while keeping the performance of sensing applications the same. Importantly, it does so using an approach that obtains a global view of parameter redundancies, which is shown to produce superior compression. We conduct experiments with five different sensing-related tasks on Intel Edison devices. DeepIoT outperforms all compared baseline algorithms with respect to execution time and energy consumption by a significant margin. It reduces the size of deep neural networks by 90% to 98.9%. It is thus able to shorten execution time by 71.4% to 94.5%, and decrease energy consumption by 72.2% to 95.7%. These improvements are achieved without loss of accuracy. The results underscore the potential of DeepIoT for advancing the exploitation of deep neural networks on resource-constrained embedded devices.
Gleason grading: past, present and future (2011)

In 1966 Donald Gleason developed his grading and scoring system for prostatic adenocarcinoma. This classification was refined in 1974 and gained almost universal acceptance, being classified as a category 1 prognostic parameter by the College of American Pathologists. Modifications to the classification were recommended at a conference convened by the International Society of Urological Pathology (ISUP) in 2005. This modified classification has resulted in a significant upgrading of tumours, although some studies have shown a greater concordance between needle biopsy and radical prostatectomy scores when compared to classical Gleason (CG) grading. The ISUP consensus conference recommended that for needle biopsies higher tertiary patterns should be incorporated into the final Gleason score, and this has been correlated with biochemical failure, tumour volume and mortality. Recently the validity of including cribriform glands as a component of Gleason pattern 3 has been questioned and it has been recommended that all tumours showing cribriform architecture should be classified as Gleason pattern 4. The recommendations arising from the 2005 Consensus Conference were largely unsupported by validating data, yet this new grading system has achieved widespread usage. It is unfortunate that recent suggestions for further modification are similarly lacking in supporting evidence. In view of this it is recommended that the Modified Gleason Scoring Classification should continue to be utilized in its original (2005) format and that any future alterations should be implemented only when mandated by tumour-related outcome studies.
Two-dimensional ordering of the DNA base guanine observed by scanning tunneling microscopy. (1991)

Guanine, one of the four DNA bases, has been observed by tunneling microscopy to form a two-dimensional ordered structure on two crystalline substrates, graphite and MoS2. The two-dimensional lattice formed by guanine is nearly identical on the two surfaces, and heteroepitaxy appears to be the growth mechanism in both cases. Although the resolution of molecular details is superior for the graphite substrate, the simpler results on MoS2 are not only easier to interpret but also facilitate the understanding of the more complex images on graphite. We propose that the interfacial structure is composed of linear chains of hydrogen-bonded molecules aligned into a closely packed two-dimensional array.
Mouth Lesions in Iron-Deficient Anemia: Relationship to Candida albicans in Saliva and to Impairment of Lymphocyte Transformation (1975)

The atrophic glossitis and angular chilosis in patients with iron-deficient anemia are associated with infection of the mouth by Candida albicans. Saliva from these patients contained more Candida and supported the growth of Candida better than did saliva from a control group. The possibility that growth of Candida may be due to impaired lymphocyte function was investigated by measuring transformation of lymphocytes stimulated with phytohemagglutinin. Transformation was depressed in iron-deficient subjects and returned to normal after correction of their iron status. The lymphocyte count in the peripheral blood was also depressed and corrected by additional iron. Impaired lymphocyte function did not explain the mouth lesions and growth of Candida in saliva since lymphocyte transformation was equally depressed in patients with and without mouth lesions. A local factor, such as an effect of lack of iron on the resident vacterial flora of the mouth, may be important.
Moving Toward Sustainability (2008)

The world today relies primarily on petroleum to fuel more than 800 million passenger cars, trucks, and buses.[...]
Development and Validation of A 48-Target Analytical Method for High-throughput Monitoring of Genetically Modified Organisms (2015)

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection.
Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. (1999)

Progranulin is a 593-amino acid glycoprotein, the mRNA of which is expressed by many epithelial cells both in vitro and in vivo, but the biological significance of this expression is unclear. In this study, we demonstrate that overexpression of the progranulin gene in SW-13 adrenal carcinoma cells and MDCK nontransformed renal epithelia results in the transfection-specific secretion of progranulin, acquired clonogenicity in semisolid agar, and increased mitosis in monolayer culture, whereas diminution of progranulin gene expression impairs growth of these cells. Purified recombinant progranulin reproduces the effects of forced progranulin expression, being clonogenic in soft agar and mitogenic in monolayer culture to SW-13 and MDCK cells and other epithelia of various origins such as GPC16 colonic epithelium and A549 lung carcinoma cells. Progranulin overproduction in SW-13 cells markedly increases its tumorigenicity in nude mice, demonstrating that it can regulate epithelial proliferation in vivo. We propose that the rate of growth for some epithelia, such as SW-13 and MDCK, is proportional to the level of intrinsic progranulin gene expression, and that elevated progranulin gene expression confers a transformed phenotype on epithelial cells including anchorage independence in vitro and growth as tumors in nude mice.
Irritable bowel syndrome (1985)

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AVP: a highly efficient real-time protocol for multimedia communications on Internet (2002)

A new transport protocol called Audio-Video Protocol (AVP) for highly efficient multimedia communications on the Internet is presented in this paper. While providing similar real-time delivery functions of RTP/RTCP AVP adopts a novel audio-based synchronization scheme. This synchronization scheme has two advantages. One is that there is no need to include a timestamp in each transmitted packet so that the AVP header is small for highly efficient transmission. The other is that AVP can achieve lower end-to-end message delay by putting multiple audio frames or mixed audio-video frames in the same AVP packet to reduce the packet rate. Furthermore, AVP provides different QoS by assigning different priority numbers to the packers. Simulation results are presented to show the good performance of AVP in real-time video-audio delivery.