gebhart/patrepeval huggingface dataset:
Gold Catalysis (2006)

Catalysis by gold has rapidly become a hot topic in chemistry, with a new discovery being made almost every week. Gold is equally effective as a heterogeneous or a homogeneous catalyst and in this Review we attempt to marry these two facets to demonstrate this new found and general efficacy of gold. The latest discoveries are placed within a historical context, but the main thrust is to highlight the new catalytic possibilities that gold-catalyzed reactions currently offer the synthetic chemist, in particular in redox reactions and nucleophilic additions to pi systems. Indeed gold has proved to be an effective catalyst for many reactions for which a catalyst had not been previously identified, and many new discoveries are still expected.
Role of the forkhead protein FoxO1 in cell compensation to insulin resistance (2006)

Diabetes is associated with defective beta cell function and altered beta cell mass. The mechanisms regulating beta cell mass and its adaptation to insulin resistance are unknown. It is unclear whether compensatory beta cell hyperplasia is achieved via proliferation of existing beta cells or neogenesis from progenitor cells embedded in duct epithelia. We have used transgenic mice expressing a mutant form of the forkhead-O1 transcription factor (FoxO1) in both pancreatic ductal and endocrine beta cells to assess the contribution of these 2 compartments to islet expansion. We show that the mutant FoxO1 transgene prevents beta cell replication in 2 models of beta cell hyperplasia, 1 due to peripheral insulin resistance (Insulin receptor transgenic knockouts) and 1 due to ectopic local expression of IGF2 (Elastase-IGF2 transgenics), without affecting insulin secretion. In contrast, we failed to detect a specific effect of the FoxO1 transgene on the number of periductal beta cells. We propose that beta cell compensation to insulin resistance is a proliferative response of existing beta cells to growth factor signaling and requires FoxO1 nuclear exclusion.
A Frozen Analogue Approach to Aminopyridinylimidazoles Leading to Novel and Promising p38 MAP Kinase Inhibitors (2012)

In this study we report the design, synthesis, and biological evaluation of constrained aminopyridinylimidazoles as p38α MAP kinase inhibitors. The frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres as constrained structure analogues. The identification of the most potent bioisostere was followed by a further derivatization to address hydrophobic region II. In combination with C-2 modifications of the imidazole core, we were able to design highly active inhibitors on the p38α MAP kinase. The inhibitor design presented herein represents a promising and highly efficient advancement of recent stages of development in this class of p38 MAP kinase inhibitors. In combination with the highly flexible synthetic strategy, directions toward further investigations of complex C-5 modifications of diarylimidazoles are indicated.
Vibrio cholerae hybrid sex factor that contains ampicillin transposon Tn1 (1979)

The ampicillin resistance transposon Tn1 was translocated from the R plasmid RP4 to the Vibrio cholerae conjugative plasmid, P. The hybrid sex factor P::Tn1 was highly transmissible and expressed the biological activities of the P factor. In addition, P::Tn1 facilitated transfer of RP4 to V. cholerae recipients. Physical studies of P::Tn1 indicated that the Tn1 transposon was added to the otherwise unaltered P plasmid.
The typed access matrix model (2003)

The typed access matrix (TAM) model is defined by introducing the notion of strong typing into the Harrison, Ruzzo, and Ullman model (HRU) (M. H. Harrison et al., 1978). It is shown that monotonic TAM (MTAM) has decidable, but NP-hard, safety for its acyclic creation cases. It is further shown that ternary MTAM has polynomial time safety analysis for its acyclic cases, even though it is, in general, equivalent to MTAM. Ternary MTAM thus has strong safety properties. The expressive power of ternary MTAM has been shown to be equivalent to MTAM in general. The results establish that strong typing is crucial to achieving a useful demarcation between decidable and undecidable safety, and ternary monotonic commands are critical for tractable safety analysis.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Suppression of H2S Gas from Li2S-P2S5 Glass Electrolytes by the Addition of Li2O (2012)

Abstract not Available.
Prion protein NMR structure and species barrier for prion diseases (1997)

The structural basis of species specificity of transmissible spongiform encephalopathies, such as bovine spongiform encephalopathy or "mad cow disease" and Creutzfeldt-Jakob disease in humans, has been investigated using the refined NMR structure of the C-terminal domain of the mouse prion protein with residues 121-231. A database search for mammalian prion proteins yielded 23 different sequences for the fragment 124-226, which display a high degree of sequence identity and show relevant amino acid substitutions in only 18 of the 103 positions. Except for a unique isolated negative surface charge in the bovine protein, the amino acid differences are clustered in three distinct regions of the three-dimensional structure of the cellular form of the prion protein. Two of these regions represent potential species-dependent surface recognition sites for protein-protein interactions, which have independently been implicated from in vitro and in vivo studies of prion protein transformation. The third region consists of a cluster of interior hydrophobic side chains that may affect prion protein transformation at later stages, after initial conformational changes in the cellular protein.
Effects of Human Recombinant PEDF Protein and PEDF-Derived Peptide 34-mer on Choroidal Neovascularization (2010)

A functional region for the inhibition of vessel sprouting and CNV resides within the 34-mer region of PEDF. Furthermore, subconjunctival administration of optimal range dosages of rhuPEDF or 34-mer can suppress and regress rat CNV lesions, demonstrating that these agents reach the choroid/RPE complex as functionally active molecules.
A double‐blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis (2002)

Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side-effects than in a similar group of patients taking sulfasalazine, 3 g.
Cancer cell killing via ROS: To increase or decrease, that is the question (2008)

Reactive oxygen species (ROS) act as a second messenger in cell signaling and are essential for various biological processes in normal cells. Any aberrance in redox balance may relate to human pathogenesis including cancers. Since ROS are usually increased in cancer cells due to oncogene activation, relative lack of blood supply or other variances and ROS do involve in initiation, progression and metastasis of cancers, ROS are considered oncogenic. Ironically, ROS production is a mechanism shared by all non-surgical therapeutic approaches for cancers, including chemotherapy, radiotherapy and photodynamic therapy, due to their implication in triggering cell death, therefore ROS are also used to kill cancer cells. Because of the double-edged sword property of ROS in determining cell fate, both pro- or anti-oxidant therapies have been proposed for treatments of cancers. Based on either side, a number of drugs, agents and approaches are developed or in the progress of development, some of which have shown clinical promise. This review summarizes the current understanding on ROS-manipulation strategies in cancer treatment and underlying mechanisms. ROS-producing or -eliminating agents and the potential drugs in this aspect are categorized. An effort is made in particular to discuss the paradox in the rationales of two opposite ROS-manipulation strategies and the concerns for their use. Selectivity between tumor and non-tumor cells may depend on difference of their redox environments. A combinational set of cellular parameters including redox status, antioxidant enzymes expression, cell signaling and transcription factor activation profiles, namely "redox signaling signature", is waiting for being developed in order to choose ROS-elevating or ROS-depleting therapy specific to certain type of cancer cells. In clinical setting individualized choice of an optimal ROS-manipulation therapy may require accurate and convenient measurements for ROS as well as "redox signaling signature" for prediction of efficacy and systemic toxicity.
Database tool CPPsite: a curated database of cell penetrating peptides (2012)

Delivering drug molecules into the cell is one of the major challenges in the process of drug development. In past, cell penetrating peptides have been successfully used for delivering a wide variety of therapeutic molecules into various types of cells for the treatment of multiple diseases. These peptides have unique ability to gain access to the interior of almost any type of cell. Due to the huge therapeutic applications of CPPs, we have built a comprehensive database ‘CPPsite’, of cell penetrating peptides, where information is compiled from the literature and patents. CPPsite is a manually curated database of experimentally validated 843 CPPs. Each entry provides information of a peptide that includes ID, PubMed ID, peptide name, peptide sequence, chirality, origin, nature of peptide, sub-cellular localization, uptake efficiency, uptake mechanism, hydrophobicity, amino acid frequency and composition, etc. A wide range of user-friendly tools have been incorporated in this database like searching, browsing, analyzing, mapping tools. In addition, we have derived various types of information from these peptide sequences that include secondary/tertiary structure, amino acid composition and physicochemical properties of peptides. This database will be very useful for developing models for predicting effective cell penetrating peptides.
Detection of NF-κB Activity in Skeletal Muscle Cells by Electrophoretic Mobility Shift Analysis (2011)

An electrophoretic mobility shift assay (EMSA) is a common and invaluable technique which can be utilized to study the affinity of proteins to a specific DNA or RNA sequence. These assays are performed in vitro with protein extracts isolated from either cultured cells or isolated tissues. Here, we describe the methodology used to isolate the cytoplasmic and nuclear protein extracts from both cultured cells and tissues and utilize the nuclear protein fraction to assess NF-κB DNA-binding activity by EMSA analysis.
Virulence Factors Associated with Escherichia coli Present in a Commercially Produced Competitive Exclusion Product (2002)

In this study, we assessed the pathogenic potential of Escherichia coli associated with a commercial competitive exclusion (CE) product by examining the phenotypic characteristics associated with E. coli virulent for humans and domestic animals. Most E. coli isolates were capable of proliferating in iron-deplete chicken sera. Interestingly, none of the E. coli isolates from the commercial CE product contained the bacterial adhesin Tsh characteristic of avian pathogenic E. coli associated with airsacculitis and colisepticemia. In terms of virulence potential for humans, most E. coli isolates (78%) were sensitive to killing by 12.5% human sera. Because of their sensitivity to human sera, the E. coli in the CE product are not likely to cause a serious systemic infection in humans and, therefore, do not present a risk of causing septicemia in humans. Because these isolates also lack the gene tsh, they are also less likely to cause systemic disease or airsacculitis in poultry than pathogenic strains commonly isolated from diseased birds.
Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? (2002)

We attempted to identify the specific structural features in sulfated galactans and sulfated fucans that confer anticoagulant activity. For this study we employed a variety of invertebrate polysaccharides with simple structures composed of well-defined units of oligosaccharides. Our results indicate that a 2-O-sulfated, 3-linked alpha-L-galactan, but not a alpha-L-fucan with a similar molecular size, is a potent thrombin inhibitor mediated by antithrombin or heparin cofactor II. The difference between the activities of these two polysaccharides is not very pronounced when factor Xa replaced thrombin. The occurrence of 2,4-di-O-sulfated units is an amplifying motif for 3-linked alpha-fucan-enhanced thrombin inhibition by antithrombin. If we replace antithrombin by heparin cofactor II, then the major structural requirement for the activity becomes single 4-O-sulfated fucose units. The presence of 2-O-sulfated fucose residues always had a deleterious effect on anticoagulant activity. Overall, our results indicate that the structural requirements for interaction of sulfated galactans and sulfated fucans with coagulation cofactors and their target proteases are stereospecific and not merely a consequence of their charge density and sulfate content.
A multicenter trial of the use of the proteolytic enzyme inhibitor aprotinin in colorectal surgery (1989)

Animal studies have demonstrated the value of the proteolytic enzyme inhibitor, aprotinin, in reducing collagen breakdown and improving the healing of experimental colonic anastomoses. A double-blind, multicenter, prospective trial has evaluated the use of aprotinin in the prevention of anastomotic leakage in patients. Two hundred sixteen patients undergoing colonic resection and anastomosis were studied. Patients were randomized to receive either aprotinin or placebo intravenously, peroperatively, and for the first three postoperative days. Anastomotic integrity was assessed clinically and by Hypaque enema on the tenth postoperative day. Although the use of aprotinin was not associated with a significant overall decrease in anastomotic leakage rates, in 95 patients undergoing anterior resection, leakage rates in those receiving aprotinin (clinical 10.8 percent; radiologic 32.4 percent) were lower than in those receiving placebo (17.2 percent and 43.1 percent, respectively). An apparent adverse association was noted, however, in patients undergoing left hemicolectomy or sigmoid colectomy who received aprotinin.
Lymph Stasis: Pathophysiology, Diagnosis and Treatment (2019)

INTRODUCTION. Lymphology and the Lymphatic System. STRUCTURE OF LYMPHATICS, LYMPH FORMATION AND FLOW. Structure of Initial and Collecting Lymphatic Vessels. Interstitial Edema-Preventing Mechanisms. Dynamics of Lymph Formation and Its Modification. Influence of Autonomic Nerves on Lymph Flow. Lymph Pressure and Flow in Limbs. Dermal Lymph and Lymphatics. Pulmonary Lymph and Lymphatics. Gastrointestinal Lymphatics. CHEMICAL AND CELLULAR COMPOSITION OF LYMPH. Chemistry of Lymph. Cells in Lymph. PATHOLOGICAL FACTORS AFFECTING LYMPH FLOW. Injury of Lymphatics. Lymphangitis. Lymph Stasis After Lymph Node Dissection. Lymphatic Spread of Cancer. Thoracic Duct: Conditions Affecting Function. Pathophysiology of Lymphatic Insufficiency and Principles of Treatment. CLINICAL PICTURE OF LYMPH STASIS IN LIMBS. Clinical Picture of Lymphedema. Histological and Ultrastructural Evaluation of the Crural Lymph Nodes in Primary Lymphedema of the Lower Limbs. Malformations of the Lymphatic System. DI AGNOSTIC PROCEDURES. Radionuclide Lymphography. Computerized Tomography, Xeroradiography, Lymphography and Xerolymphography in Diagnosis of Lymph Stasis. Indirect Lymphangiography. Volumetry of Limbs. Diagnosis of Lymphatic Invasion by Tumors. TREATMENT OF LYMPHEDEMA. Conservative Treatment of Lymphedema. Postmastectomy Lymphedema-Medical Therapy Using Intermittent Compression and a Pressure Gradient Prosthesis. Heating and Bandaging in the Treatment of Chronic Lymphedema of the Extremities. Pharmacological Treatment of Lymph Stasis. Surgical Lympho-Venous Anastomoses for Treatment of Lymphedema. A Technique of Lymphatic Vessel-Vein Anastomosis for the Treatment of Lymphedema of Limbs. Microsurgical Autologous Lymph-Vessel Grafting. The Autologous Vein Grafts in Reconstructive Microsurgery for Lymph Stasis. Drug Penetration to Peripheral Lymph in Man. Endolymphatic Therapy. Collection of Peripheral Lymph in Man.
E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins. (1996)

Ubiquitin-dependent proteolysis of the mitotic cyclins A and B is required for the completion of mitosis and entry into the next cell cycle. This process is catalyzed by the cyclosome, an approximately 22S particle that contains a cyclin-selective ubiquitin ligase activity, E3-C, that requires a cyclin-selective ubiquitin carrier protein (UBC) E2-C. Here we report the purification and cloning of E2-C from clam oocytes. The deduced amino acid sequence of E2-C indicates that it is a new UBC family member. Bacterially expressed recombinant E2-C is active in in vitro cyclin ubiquitination assays, where it exhibits the same substrate specificities seen with native E2-C. These results demonstrate that E2-C is not a homolog of UBC4 or UBC9, proteins previously suggested to be involved in cyclin ubiquitination, but is a new UBC family member with unique properties.
Real-Time Completion Optimization Of Multiple Laterals In Gas Shale Reservoirs: Integration of Geology, Log, Surface Seismic, and Microseismic Information (2011)

Abstract Multidisciplinary data integration combined with the deployment of proper technology is key to optimizing shale gas completions. This paper focuses on the real-time completion optimization of multiple laterals drilled from the same well pad in shale gas reservoirs. These laterals are spaced as closeas a few hundred feet laterally with varying vertical landing points. Though these laterals do expose more of the nanodarcy permeability shale rock and increase contact area through fracture stimulation—resulting in more efficient drainage—the challenge remains to optimize the stimulation treatment to maximize coverage around each designated lateral. The optimization process involves perforation and stage placement, sequential stimulation of these laterals, fluid and proppant schedules, treatment rates, and application of diversion technology when appropriate to achieve effective stimulation along these laterals and between the wells. In a comprehensive multiwell completion case history from the Barnett Shale, geologic, well, and surface seismic information was integrated with log measurements using Petrel reservoir modeling software. This integrated understanding was coupled with live microseismic data, enabling reliable real-time decisions during stimulation to optimize stimulation coverage and proppant placement around these laterals. Opportunities in making changes to original designs were seized when injectivity problems were encountered early in the treatment process. This approach was executed successfully to gain injectivity and, later, to increase the conductive fracture area, allowing the frac to be managed in real time. Observed fracture pressure responses and production from these pad wells validated the approach. Ultimately, an optimal horizontal stimulation was achieved by leveraging favorable rock properties to create a larger fracture surface contact area, thereby maximizing gas production potential and recovery. The integrated approach presented here can be applied to any single well or multilateral shale gaswells.
Comparative analysis of adenovirus fiber-cell interaction: adenovirus type 2 (Ad2) and Ad9 utilize the same cellular fiber receptor but use different binding strategies for attachment (1996)

We have analyzed the binding of adenovirus (Ad) serotypes from subgroups B, C, and D through fiber-virus and fiber-fiber cross-competition experiments. Since viruses in these distinct subgroups display markedly different tropisms, it was unexpected that the subgroup C viruses Ad2 and 5 and the subgroup D virus Ad9 cross-competed for the same cellular fiber receptor. The subgroup B serotype Ad3 recognized a receptor distinct from the Ad2, 5, and 9 fiber receptor. However, despite sharing the same fiber receptor, Ad2 and Ad9 displayed markedly different binding characteristics that appeared to result from direct Ad9 binding to cells via alpha(v)-integrins. Unlike Ad2, Ad9 binding to many cell lines was not abrogated by competition with the fiber 9 knob (F9K). Ad9 binding to fiber receptor-deficient cells was blocked by a monoclonal antibody to alpha(v)-integrins. In contrast, Ad9 binding to alpha(v)-deficient cells that express fiber receptor was blocked by F9K. Transfection of an alpha(v)-integrin-deficient cell line with a plasmid that expresses alpha(v)beta5 resulted in Ad9 binding that was not significantly blocked by F9K but was blocked with a combination of F9K and penton base. These results imply that the shorter length of fiber 9 (11 nm) relative to fiber 2 (37 nm) permits fiber-independent binding of Ad9 penton base to alpha(v)-integrins. The difference in fiber length may explain the different binding characteristics and tissue tropisms of each virus despite both utilizing the same fiber and penton base receptors.
Sequence alterations in temperature-sensitive M-protein mutants (complementation group III) of vesicular stomatitis virus (1985)

Sequences were determined of the coding regions of the M-protein genes of the Glasgow and Orsay strains of vesicular stomatitis virus (Indiana serotype) and of two group III (M-protein) mutants derived from each wild type. Synthetic primers were annealed with viral genomic RNA and extended with reverse transcriptase. The resulting high-molecular-weight cDNA was sequenced directly. Both Glasgow and Orsay wild types differed in 13 bases from a clone of the San Juan strain sequenced by J. K. Rose and C. J. Gallione (J. Virol. 39:519-528, 1981). Six of these base changes caused amino acid changes in each wild type, whereas seven were degenerate. The Orsay and Glasgow sequences resembled each other more closely than either resembled that of Rose and Gallione, differing in eight nucleotides and four amino acids. Each of the four mutants, however, differed from its parent wild type in only one or two point mutations. Every mutation caused a change either from or to a charged amino acid; the change for tsG31 was Lys (position 215) to Glu, the change for tsO23 was Gly (position 21) to Glu, the change for tsO89 was Ala (position 133) to Asp, the changes for tsG33 were Lys (position 204) to Thr and Glu (position 214) to Lys. The charge differences predicted from these amino acid changes was confirmed by nonequilibrium pH gradient electrophoresis for tsG31, tsG33, tsO23, and the two wild types. These mutations affect residues spanning nearly 85% of the linear sequence, although the mutants possess nearly identical phenotypic properties.
Towards a predictive model of electroporation-based therapies using pre-pulse electrical measurements (2012)

Electroporation-based therapies have been gaining momentum as minimally invasive techniques to facilitate transport of exogenous agents, or directly kill tumors and other undesirable tissue in a non-thermal manner. Typical procedures involve placing electrodes into or around the treatment area and delivering a series of short and intense electric pulses to the tissue/tumor. These pulses create defects in the cell membranes, inducing non-linear changes in the electric conductivity of the tissue. These dynamic conductivity changes redistribute the electric field, and thus the treatment volume. In this study, we develop a statistical model that can be used to determine the baseline conductivity of tissues prior to electroporation and is capable of predicting the non-linear current response with implications for treatment planning and outcome confirmation.