gebhart/patrepeval huggingface dataset:
Bare-Faced Curassow Lysozyme Carrying Amino Acid Substitutions at Subsites E and F Shows a Change in Activity against Chitooligosaccharide Caused by a Local Conformational Change (2004)

A new form of avian lysozyme, bare-faced curassow lysozyme (BCL), was purified and chemically sequenced. Of the 26 substitutions relative to chicken lysozyme, three, F34Y, T47S, and R114H, are of substrate-interacting residues in the E and F subsites, which would contribute to the acceptor binding for transglycosylation. T47S is a novel substitution in this lysozyme class. While other lysozymes also have substitutions at positions 114 and 34, they also contain numerous others, including ones in the other substrate binding sites, A-D. Furthermore, T47S lies on the left side, while F34Y and R114H are located on the right side of the E-F subsites. BCL therefore should allow comparison of the independent contributions of these sites to substrate binding and transglycosylation. The activity toward the N-acetylglucosamine pentamer revealed that the substitutions at the E-F sites reduced the binding free energies at the E-F sites and the rate constant for transglycosylation without the conformation change of other substrate binding sites on the protein. MD simulation analysis of BCL suggested that the substituted amino acids changed the local conformation of this lysozyme at the E-F sites.
Total Synthesis of Clerocidin via a Novel, Enantioselective Homoallenylboration Methodology (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTTotal Synthesis of Clerocidin via a Novel, Enantioselective Homoallenylboration MethodologyAlan X. Xiang, Donald A. Watson, Taotao Ling, and Emmanuel A. TheodorakisView Author Information Department of Chemistry and Biochemistry, University of CaliforniaSan Diego, 9500 Gilman Drive, La Jolla, California 92093-0358 Cite this: J. Org. Chem. 1998, 63, 20, 6774–6775Publication Date (Web):September 12, 1998Publication History Received9 July 1998Published online12 September 1998Published inissue 1 October 1998https://pubs.acs.org/doi/10.1021/jo981331lhttps://doi.org/10.1021/jo981331lrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1082Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alcohols,Aldehydes,Chemical synthesis,Enantioselective synthesis,Peptides and proteins Get e-Alerts
Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs (1993)

The objective of the present study was to characterize the role of adenosine in myocardial ischemic preconditioning in the canine heart. Preconditioning with 5 min of ischemia resulted in a marked reduction in infarct size after 60 min of left circumflex coronary artery occlusion and 5 h of reperfusion in barbital-anesthetized dogs compared with dogs that were not preconditioned (4.8 +/- 1.9 vs. 27.9 +/- 4.5%; P < 0.05). Pretreatment with either the nonselective adenosine receptor antagonist PD 115199 or the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked this protective effect, although in the absence of preconditioning neither of the antagonists affected infarct size. Intracoronary infusion of two different doses of adenosine or dipyridamole over a 5-min period before a prolonged 60-min occlusion period did not mimic preconditioning; however, intracoronary infusion of a combination of adenosine and dipyridamole produced a significant reduction in infarct size (13.6 +/- 4.1%), which was abolished by pretreatment with the ATP-dependent potassium (KATP) channel antagonist glibenclamide. These results suggest that activation of adenosine A1 receptors produces myocardial preconditioning in the canine heart by opening KATP channels.
Analyzing and Selecting Instructional Strategies and Tactics (2008)

“Formulation of instructional strategy to match subject matter and learner requirements” is an integral part of most instructional design models (Andrews & Goodson, 1980, p.5). Yet the meaning and purpose of instructional strategies in these design models vary considerably. An instructional strategy in traditional design models usually refers to the selection of instructional delivery vehicles (e.g., lecture, demonstration, computer-assisted instruction) and support activities (e.g., practice exercises, tutoring) (cf. Tracey, Flynn, <& Legere, 1970). Contrast those conceptions with the many instructional strategies described in elaboration theory (Reigeluth & Stein, 1983), such as sub-sumptive sequencing, internally consistent orienting structures, synthesizers, summarizers, and cognitive strategy activators. What is obvious from these disparate conceptions is that instructional designers do not share a consistent definition of instructional strategies. Many of the activities that are referred to as instructional strategies are not in fact strategies, but rather are presentation vehicles. In this article, we first define instructional strategies and tactics in the context of an iterative design model. Instructional strategies are then distinguished from instructional tactics, which are the implementation of strategies. We then list the range of instructional strategies and tactics that implement them. Finally, we provide a decision tree for assisting designers to select appropriate instructional tactics.
Identification of Accessory Genome Regions in Poultry Clostridium perfringens Isolates Carrying the netB Plasmid (2013)

Necrotic enteritis (NE) is an economically important disease of poultry caused by certain Clostridium perfringens type A strains. NE pathogenesis involves the NetB toxin, which is encoded on a large conjugative plasmid within a 42-kb pathogenicity locus. Recent multilocus sequence type (MLST) studies have identified two predominant NE-associated clonal groups, suggesting that host genes are also involved in NE pathogenesis. We used microarray comparative genomic hybridization (CGH) to assess the gene content of 54 poultry isolates from birds that were healthy or that suffered from NE. A total of 400 genes were variably present among the poultry isolates and nine nonpoultry strains, many of which had putative functions related to nutrient uptake and metabolism and cell wall and capsule biosynthesis. The variable genes were organized into 142 genomic regions, 49 of which contained genes significantly associated with netB-positive isolates. These regions included three previously identified NE-associated loci as well as several apparent fitness-related loci, such as a carbohydrate ABC transporter, a ferric-iron siderophore uptake system, and an adhesion locus. Additional loci were related to plasmid maintenance. Cluster analysis of the CGH data grouped all of the netB-positive poultry isolates into two major groups, separated according to two prevalent clonal groups based on MLST analysis. This study identifies chromosomal loci associated with netB-positive poultry strains, suggesting that the chromosomal background can confer a selective advantage to NE-causing strains, possibly through mechanisms involving iron acquisition, carbohydrate metabolism, and plasmid maintenance.
A novel screening method to assess developability of antibody-like molecules (2015)

Monoclonal antibodies and antibody-like molecules represent a fast-growing class of bio-therapeutics that has rapidly transformed patient care in a variety of disease indications. The discovery of antibodies that bind to particular targets with high affinity is now a routine exercise and a variety of in vitro and in vivo techniques are available for this purpose. However, it is still challenging to identify antibodies that, in addition to having the desired biological effect, also express well, remain soluble at different pH levels, remain stable at high concentrations, can withstand high shear stress, and have minimal non-specific interactions. Many promising antibody programs have ultimately failed in development due to the problems associated with one of these factors. Here, we present a simple high-performance liquid chromatography (HPLC)-based screening method to assess these developability factors earlier in discovery process. This method is robust and requires only microgram quantities of proteins. Briefly, we show that for antibodies injected on a commercially available pre-packed Zenix HPLC column, the retention times are inversely related to their colloidal stability with antibodies prone to precipitation or aggregation retained longer on the column with broader peaks. By simply varying the salt content of running buffer, we were also able to estimate the nature of interactions between the antibodies and the column. We believe this approach should generally be applicable to assessment of the developability of other classes of bio-therapeutic molecules, and that the addition of this simple tool early in the discovery process will lead to selection of molecules with improved developability characteristics.
Methylprednisolone Causes Matrix Metalloproteinase–dependent Emphysema in Adult Rats (2003)

Abstract Previous investigations have shown that corticosteroids affect the development and maturation of the developing lung in utero and in neonatal animals. Systemic corticosteroids are routinely used for the treatment of acute exacerbations of chronic obstructive pulmonary disease, and inhaled corticosteroids are more frequently being prescribed for the long-term treatment of patients with chronic obstructive pulmonary disease. Because corticosteroids can affect matrix metalloproteinases and because the concept of protease/antiprotease imbalance is an important concept regarding the pathogenesis of emphysema, we examined the effects of chronic steroid treatment on lung structure in adult rats. Rats treated with 2 mg/kg of methylprednisolone daily for 1, 2, or 4 weeks had an increased mean linear intercept and a decrease of the surface–volume ratio when compared with age-matched control animals, and the animals showed increased matrix metalloproteinase-9 activity in their lungs on zymography. Rats treated concomitantly with methylprednisolone and a broad-spectrum matrix metalloproteinase inhibitor (GM6001) did not develop emphysema. We conclude that systemic treatment of adult rats with the antiinflammatory steroid methylprednisolone increases the activity of matrix metalloproteinases in the lung and causes emphysema.
Thin-Section CT Characteristics and Longitudinal CT Follow-up of Chemotherapy Induced Interstitial Pneumonitis (2016)

To describe the computed tomography (CT) features of chemotherapy-induced interstitial pneumonitis (CIIP) with longitudinal follow-up.The study was approved by the local ethics committee. One hundred consecutive patients with CIIP between May 2005 and March 2015 were retrospectively enrolled. The initial CT was reviewed by 2 independent chest radiologists and categorized into 1 of 4 CT patterns in accordance with the 2013 guidelines for idiopathic interstitial pneumonia: nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), hypersensitivity pneumonitis (HP) mimicking desquamative interstitial pneumonitis, and diffuse alveolar damage (DAD). We assessed semiquantitative analysis on a 5% scale to assess the extent of parenchymal abnormalities (emphysema, reticulation, ground-glass opacity, consolidation, honeycombing cyst) and their distribution on initial (n = 100), subsequent (n = 87), and second follow-up CT (n = 48). Interval changes in extent on follow-up CT were compared using paired t test. The clinic-radiologic factors were compared between Group 1 (NSIP and OP patterns) and Group 2 (HP and DAD patterns) using χ and independent t tests.The most common pattern of CIIP on the initial CT was HP (51%), followed by NSIP (23%), OP (20%), and DAD (6%). Diffuse ground-glass opacity was the most common pulmonary abnormality. The predominant distribution was bilateral (99%) and symmetric (82%), with no craniocaudal (60%) or axial (79%) dominance. Subsequent and second follow-up CTs showed decreased extent of total pulmonary abnormalities (P < 0.001, respectively). In comparison with Group 1 CIIP, Group 2 CIIP was more likely to be caused by molecularly targeted drugs (P = 0.030), appeared earlier (P = 0.034), and underwent more complete resolution (P < 0.001). Use of a CT pattern-recognition approach to CIIP is appropriate and practical in interpreting radiological findings.
Synthesis of deuterated N6-(o-hydroxybenzyl)adenosine-d3. (1980)

N6-(o-Hydroxybenzyl) adenosine-d4 was synthesized by dehalogenation of 2-chloro-6-(o-hydroxybenzylamino)-9-β-D-ribofuranosylpurine-d2 with deuterium gas in 0.3N-sodium deuter-oxide solution, which was obtained by condensation of 2, 6-dichloro-9-(2', 3', 5'-tri-O-acetyl-β-D-ribofuranosyl) purine and salicylamine-d2. The total extent of deuteration of d4 compound was 86.6%. The d4 compound was heated in water to yield N6-(o-hydroxybenzyl)adenosine-d3, whose total deuteration was 94.6%.
Identification of SNF1/AMP Kinase-related Kinase as an NF-κB-regulated Anti-apoptotic Kinase Involved in CD95-induced Motility and Invasiveness (2004)

The death receptor CD95 (APO-1/Fas) induces apoptosis in many tissues. However, in apoptosis-resistant tumor cells, stimulation of CD95 induces up-regulation of a defined number of mostly anti-apoptotic genes, resulting in increased motility and invasiveness of tumor cells. The majority of these genes are known NF-kappaB target genes. We have identified one of the CD95-regulated genes as the serine/threonine kinase (SNF1/AMP kinase-related kinase (SNARK)), which is induced in response to various forms of metabolic stress. We demonstrate that up-regulation of SNARK in response to CD95 ligand and tumor necrosis factor alpha depends on activation of NF-kappaB. Overexpression of SNARK rendered tumor cells more resistant, whereas a kinase-inactive mutant of SNARK sensitized cells to CD95-mediated apoptosis. Furthermore, small interfering RNA-mediated knockdown of SNARK increased the sensitivity of tumor cells to CD95 ligand- and TRAIL-induced apoptosis. Importantly, cells with reduced expression of SNARK also showed reduced motility and invasiveness in response to CD95 engagement. SNARK therefore represents an NF-kappaB-regulated anti-apoptotic gene that contributes to the tumor-promoting activity of CD95 in apoptosis-resistant tumor cells.
A Concise Guide to Intraoperative Monitoring (2000)

Covering both the applications and the related theory, A Concise Guide to Intraoperative Monitoring provides a general but comprehensive introduction to IOM. Unlike existing texts that typically report the results of specific studies, this book presents comprehensive coverage of the entire procedure, as well as the specific protocols used in hospit
Impact of Diffusivity to Carrier Recombination Rate in Nitride Semiconductors: From Bulk GaN to (In,Ga)N Quantum Wells (2013)

We combined light induced transient grating and free carrier absorption techniques to investigate temporal and spatial carrier dynamics in nitrides. Inverse correlation of diffusivity and nonradiative recombination rate in GaN epilayers was ascribed to carrier diffusive flow to the internal boundaries of hexagonal grains and recombination on dislocations there, while the similar dependence in InGaN quantum wells (QWs) was a consequence of carrier delocalization caused either by carrier injection or thermal escape. Numerical modeling of recombination rates in light emitting diode structures with In content up to 13% revealed increasing with excitation nonradiative recombination rate which is a consequence of higher overall carrier mobility at higher densities. We propose the injection-enhanced in-plane diffusivity as the most probable mechanism explaining the increase of non-radiative losses in high power light emitting diodes (LEDs).
Performance of high pressure Xe/TMA in GEMs for neutron and X-ray detection (2005)

In the framework of development of a single-GEM detector for thermal neutron detection, with a position resolution of 1 mm, the charge multiplication in the GEM has been studied for different stopping gases at pressures up to 8 bar. The effect on the gain of addition of several bars of He to these gases has been determined. It has been found that a Penning mixture of Xe/TMA has the highest gain. At a pressure of 7 bar Xe+2.5% TMA a gain of 10 could still be obtained for a 50 /spl mu/m thick GEM with 80 /spl mu/m holes. A gain of 100 is possible in a mixture of 4 bar Xe, 2.5% TMA and 6 bar He, which makes the above mentioned position resolution possible. In addition it has been found that the Xe/TMA mixture scintillates around 300 nm in the multiplication process in the GEM. The light yield per secondary electron depends only slightly on the Xe pressure or the TMA concentration.
A cross-disciplinary approach to understanding neural stem cells in development and disease (2010)

The Company of Biologists recently launched a new series of workshops aimed at bringing together scientists with different backgrounds to discuss cutting edge research in emerging and cross-disciplinary areas of biology. The first workshop was held at Wilton Park, Sussex, UK, and the chosen theme was 'Neural Stem Cells in Development and Disease', which is indeed a hot topic, not only because of the potential use of neural stem cells in cell replacement therapies to treat neurodegenerative diseases, but also because alterations in their behaviour can, in certain cases, lie at the origin of brain tumours and other diseases.
Structural Realization with GGNNs (2021)

In this paper, we define an abstract task called structural realization that generates words given a prefix of words and a partial representation of a parse tree. We also present a method for solving instances of this task using a Gated Graph Neural Network (GGNN). We evaluate it with standard accuracy measures, as well as with respect to perplexity, in which its comparison to previous work on language modelling serves to quantify the information added to a lexical selection task by the presence of syntactic knowledge. That the addition of parsetree-internal nodes to this neural model should improve the model, with respect both to accuracy and to more conventional measures such as perplexity, may seem unsurprising, but previous attempts have not met with nearly as much success. We have also learned that transverse links through the parse tree compromise the model's accuracy at generating adjectival and nominal parts of speech.
Mid-Latitude Mobile Wideband HF- NVIS Channel Analysis: Part 1 (2017)

Abstract : High-frequency (HF) links (2 to 30 MHz) are an alternative to the cost and tactical fragility of commercial satellite communications (SATCOM) for beyond line-of-sight (LOS) links. However, standard HF systems operating over a 3-kHz bandwidth do not provide sufficient throughput for network applications. Simply increasing bandwidth does increase throughput provided the radios are properly designed for the time-varying wideband HF channel. The Wideband HF Channel is governed by the inonospheric variations caused by latitude, the night and day cycle, the direction and length of the haul, the seasons, and ionosphere disturbances. This report is the first of a series seeking a better understanding of each of these channel variations to aid in the design of wideband HF systems and the proper comparisons of different HF radios and waveforms. This report uses wideband mid-latitude HF channel soundings and 3-D ray-tracing simulations to develop a statistical model of a particular nearly vertical incidence skywave (NVIS) channel. The immediate application of this particular channel is for small-unit ground-mobile forces with vehicle-mounted antennas. Near-term extensions support mid-latitude short-haul (200 to 1500 km) and long-haul ship-to-ship and ship-to-shore wideband HF channels. Long-term payoffs for the warfighter will be a better HF radio design, leading to increase data rates, more stable networks, reduced power requirements, and improved low probability of detection (LPD).
Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders (2020)

Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Zai et al, 2012; Dwivedi et al, 2010) and BDNF regulates the expression of the dopamine D3 receptor.
Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia (2013)

Severe aplastic anemia (AA) is a bone marrow (BM) failure (BMF) disease frequently caused by aberrant immune destruction of blood progenitors. Although a Th1-mediated pathology is well described for AA, molecular mechanisms driving disease progression remain ill defined. The NOTCH signaling pathway mediates Th1 cell differentiation in the presence of polarizing cytokines, an action requiring enzymatic processing of NOTCH receptors by γ-secretase. Using a mouse model of AA, we demonstrate that expression of both intracellular NOTCH1(IC) and T-BET, a key transcription factor regulating Th1 cell differentiation, was increased in spleen and BM-infiltrating T cells during active disease. Conditionally deleting Notch1 or administering γ-secretase inhibitors (GSIs) in vivo attenuated disease and rescued mice from lethal BMF. In peripheral T cells from patients with untreated AA, NOTCH1(IC) was significantly elevated and bound to the TBX21 promoter, showing NOTCH1 directly regulates the gene encoding T-BET. Treating patient cells with GSIs in vitro lowered NOTCH1(IC) levels, decreased NOTCH1 detectable at the TBX21 promoter, and decreased T-BET expression, indicating that NOTCH1 signaling is responsive to GSIs during active disease. Collectively, these results identify NOTCH signaling as a primary driver of Th1-mediated pathogenesis in AA and may represent a novel target for therapeutic intervention.