gebhart/patrepeval huggingface dataset:
Accessibility in Calix[8]arene-Bound Gold Nanoparticles: Crucial Role of Induced-Fit Binding (2010)

Metal nanoparticles bound with polymeric and oligomeric ligands are commonly employed in areas where accessibility to the underlying metal is critical, such as in catalysis. Developing a fundamental understanding of molecular-scale factors that control accessibility to the metal surface in these systems enables approaches for ligand design. Here, we implement a comparative synthetic approach to investigate the role of an induced-fit binding mechanism on accessibility, which reduces to elucidating the correlation between ligand flexibility and accessibility. Four nm gold nanoparticles are bound with a calix[8]arene phosphine ligand in the comparative series 3a−c, and ligand molecular footprints of ∼230 Å2/calix[8]arene are measured on the gold surface using UV−vis spectroscopy of the surface plasmon resonance absorption band. Ligand flexibility in CDCl3 solution is characterized using variable-temperature 1H NMR spectroscopy, and results demonstrate 3c to be the most rigid of all three ligands. This is further reinforced by conformational analysis of 3a−c using molecular modeling calculations of the free ligand in the gas phase. Additional conformational analysis of bound 3a−c is modeled by using a constrained variant of the corresponding phosphine oxide 2a−c, in which the P═O bonds of the phosphine oxide are aligned, as they would be when bound to a surface underneath. Interestingly, the most rigid ligand in the bound state is 3a, a result that is in stark contrast to experiments in solution and simulations in the gas phase described above. The amount of accessible surface is measured using steady-state fluorescence of 2-naphthalenethiol (2NT) as a chemisorption probe. The most rigid ligand in the bound state (3a) synthesizes no accessible surface whereas the more flexible ligands in the bound state (both 3b and 3c) synthesize ∼0.5 2NT worth of accessible metal surface per calix[8]arene ligand, corresponding to 5−7% of the gold surface of the nanoparticle being accessible. These results demonstrate a correlation between accessibility and ligand flexibility in the bound state, and suggest an induced-fit binding mechanism in which a flexible bound ligand subtly changes shape in order to accommodate adsorption of an incoming molecule on the metal surface.
Interrelationships between Sex Hormone-Binding Globulin and 17β-Estradiol, Testosterone, 5α-Dihydrotestosterone, Thyroxine, and Triiodothyronine in Prepubertal and Pubertal Girls* (1980)

Sex hormone-binding globulin (SHBG), 17β-es-tradiol (E2), testosterone (T), 5α-dihydrotestosterone (DHT), T4,and T3 were measured in prepubertal (age, 1–8 yr; n = 44; group I) and pubertal (age, 9–16 yr; n = 56; group II) girls. The main results were as follows. 1) In group I, a higher mean (±SEM) value for SHBG was found (73.5 ± 2.82 nmol/1) compared to that in Group II (56.8 ± 3.37; P < 0.001). 2) Despite a significant increase of the androgens T and DHT withage in group I (rT age= 0.578; rDHT age = 0.544; P < 0.01 for each), no significant alteration of SHBG with age was present. 3) In group II, a significant decrease of SHBG with age occurred (r.SHBGage =–0.438; P < 0.05)along with the expected increases of E2(rE2 age= 0.691; P < 0.001), T (rT age= 0.765; P < 0.001), and DHT (rDHT age= 0.712; P < 0.001). 4) The analysis of the data by partial correlation coefficients supports the suggested role for androgens in the decline of SHBG during puberty in girls,(whereas correlations of SHBG with E2 or the thyroid hormones were insignificant.
Structural and Mutational Analysis of Affinity-Inert Contact Residues at the Growth Hormone−Receptor Interface (1996)

Mutational studies have shown that over two-thirds of the contact side chains at the human growth hormone (hGH)-receptor interface have little or no impact on binding affinity when converted to alanine [Cunningham, B. C., & Wells, J. A. (1993) J. Mol. Biol. 234, 554-563; Clackson, T., & Wells, J. A. (1995) Science 267. 383-386]. Herein, three of the most buried, yet functionally inert, residues on hGH (F25, Y42, and Q46) have been simultaneously mutated to alanine. Binding kinetics of the triple-alanine mutant shows that neither association nor dissociation rates are significantly affected and only slight, local disorder is seen in the crystal structure. However, large and compensating changes were observed in the enthalpy and entropy of binding as determined by isothermal titration calorimetry. The triple-alanine mutant bound with a more favorable enthalpy (delta H = -12.2 +/- 0.7 kcal/mol) and corresponding less favorable entropy [delta S = -2.3 +/- 2.4 cal/(mol.K)] compared to the wild-type interaction [delta H = -9.4 +/- 0.3 kcal/mol; delta S = 7.7 +/- 1.2 cal/(mol.K)]. Dissection of the triple-alanine mutant into the single F25A and double Y42A/Q46A mutant showed that the more favorable enthalpy was derived from the removal of the F25 side chain on helix-1 of the hormone. The delta Cp values for both the triple-alanine mutant [-927 +/- 10 cal/(mol.K)] and the individual mutants were significantly more negative than the delta Cp for the wild-type interaction [-767 +/- 34 cal/(mol.K)]. Such negative delta Cp values are consistent with the proposal that the hydrophobic effect is the primary contributor to the free energy of binding at this protein-protein interface. These results show that multiple-alanine mutations at contact residues may not affect binding kinetics, affinity, or global structure; however, they can produce local structural changes and can cause large compensating effects on the heat and entropy of binding. These studies emphasize that one cannot infer binding free energy from the existence of contacts alone and further support the notion that only a small set of contacts are crucial for the human growth hormone-receptor interaction.
[A clinical study on immediate implantation of particulate hydroxylapatite artificial bone after teeth extraction]. (2002)

Implantation of particulate hydroxylapatite artificial bone after teeth extraction could maintain the height of the alveolar ridge and reduce the complication of teeth extraction. It would be helpful for the following prosthetic restoration. The immediate implantation of artificial bone is therefore needed further study.
An Intron-Retaining Splice Variant of Human Cyclin A2, Expressed in Adult Differentiated Tissues, Induces a G1/S Cell Cycle Arrest In Vitro (2012)

This study has revealed that some highly differentiated human tissues express an intron-retaining cyclin A2 mRNA that induced a G1/S block in vitro. Contrary to full-length cyclin A2, which regulates cell proliferation, the A2V6 splice variant might play a role in regulating nondividing cell states such as terminal differentiation or senescence.
The Neuroprotective Effect of Rapamycin as a Modulator of the mTOR-NF-κB Axis during Retinal Inflammation (2016)

Our results propose the potential use of rapamycin as a neuroprotective therapy to suppress local activated mTOR levels, related inflammatory molecules, and the subsequent visual dysfunction during retinal inflammation.
Holographic optical switching using a ferroelectric liquid-crystal spatial light modulator (1993)

Holographic optical switching is demonstrated experimentally using a ferroelectric liquid crystal spatial light modulator. Each of 15 inputs can be switched to any of 23 output ports.
Complete localization of the intrachain disulphide bonds and the N-glycosylation points in the α-subunit of human platelet glycoprotein IIb (1989)

Glycoprotein IIb (GPIIb), one of the two molecular components of the inducible receptor for fibrinogen on the platelet surface, is formed from two subunits, GPIIb alpha (114 kDa) and GPIIb beta (22.5 kDa), joined by a single disulphide bond. CNBr cleavage of GPIIb, together with tryptic or endoproteinase Lys-C digestion of some of the isolated CNBr peptides, followed by amino acid and N-terminal sequence analysis of the isolated fragments, allowed us to locate unambiguously all the unknown disulphide bonds and the N-glycosylation points in platelet GPIIb. It could be established that each cysteine residue in GPIIb, beginning at alpha-Cys-56, is disulphide-bonded to its nearest neighbour in the amino acid sequence. Given the extensive structural similarity among the two-chain alpha-subunits of Arg-Gly-Asp adhesion receptors and the conservative positions of cysteine residues in their amino acid sequences, the intrachain and interchain disulphide-bond pattern found here in GPIIb will most probably be conserved in all two-chain alpha-subunits of these receptors. The N-linked glycosylation points found here in platelet GPIIb are the same as the five N-glycosylated asparagine residues suggested after cDNA sequencing of human erythroleukaemic-cell GPIIb [Poncz, Eisman, Heindenreich, Silver, Vilaire, Surrey, Schwartz & Bennett (1987) J. Biol. Chem. 262, 8476-8482]. Some of the general features of the structure of GPIIb, such as the existence of distinct domains in the alpha- and beta-subunits, as well as the identification of well-defined points in its external topography, are discussed.
Importance of gastrin in the pathogenesis and treatment of gastric tumors (2008)

In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffin cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia, such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.
Images of Nanobubbles on Hydrophobic Surfaces and Their Interactions (2001)

Imaging of hydrophobic surfaces in water with tapping mode atomic force microscopy reveals them to be covered with soft domains, apparently nanobubbles, that are close packed and irregular in cross section, have a radius of curvature of the order of 100 nm, and a height above the substrate of 20-30 nm. Complementary force measurements show features seen in previous measurements of the long-range hydrophobic attraction, including a jump into a soft contact and a prejump repulsion. The distance of the jump is correlated with the height of the images. The morphology of the nanobubbles and the time scale for their formation suggest the origin of their stability.
Ranking Attack Graphs (2006)

A majority of attacks on computer systems result from a combination of vulnerabilities exploited by an intruder to break into the system. An Attack Graph is a general formalism used to model security vulnerabilities of a system and all possible sequences of exploits which an intruder can use to achieve a specific goal. Attack Graphs can be constructed automatically using o#-the-shelf model-checking tools. However, for real systems, the size and complexity of Attack Graphs greatly exceeds human ability to visualize, understand and analyze. Therefore, it is useful to identify relevant portions of an Attack Graph. To achieve this, we propose a ranking scheme for the states of an Attack Graph. Rank of a state shows its importance based on factors like the probability of an intruder reaching that state. Given a Ranked Attack Graph, the system administrator can concentrate on relevant subgraphs to figure out how to start deploying security measures. We also define a metric of security of the system based on ranks which the system administrator can use to compare Attack Graphs and determine the e#ectiveness of various defense measures. We present two algorithms to rank states of an Attack Graph based on the probability of an attacker reaching those states. The first algorithm is similar to the PageRank algorithm used by Google to measure importance of web pages on the World Wide Web. It is flexible enough to model a variety of situations, e#ciently computable for large sized graphs and o#ers the possibility of approximations using graph partitioning. The second algorithm ranks individual states based on the reachability probability of an attacker in a random simulation. Finally, we give examples of an application of ranking techniques to multi-stage ...
Bicyclic imides with bridgehead nitrogen. Synthesis of an anti-Bredt bicyclic hydantoin (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBicyclic imides with bridgehead nitrogen. Synthesis of an anti-Bredt bicyclic hydantoinM. Shamim Akhtar, Wayne J. Brouillette, and D. Vincent WaterhousCite this: J. Org. Chem. 1990, 55, 18, 5222–5225Publication Date (Print):August 1, 1990Publication History Published online1 May 2002Published inissue 1 August 1990https://pubs.acs.org/doi/10.1021/jo00305a014https://doi.org/10.1021/jo00305a014research-articleACS PublicationsRequest reuse permissionsArticle Views418Altmetric-Citations18LEARN 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-Alertsclose Get e-Alerts
Quantification of CK20 gene and protein expression in colorectal cancer by RT‐PCR and immunohistochemistry reveals inter‐ and intratumour heterogeneity (2002)

Cytokeratin 20 (CK20) is an epithelial protein expressed almost exclusively in the gastrointestinal (GI) tract and is widely used as immunohistochemical marker for routine diagnosis. In contrast, CK20 gene expression is not an established marker for the classification of tumours and the detection of disseminated cancer cells in colorectal cancer. Recently, real-time reverse transcriptase polymerase chain reaction (RT-PCR) has provided the means for reproducible and quantitative investigation of molecular markers. This report directly compares CK20 mRNA and protein expression in serial sections of archival, formalin-fixed, paraffin-embedded (FFPE) colorectal adenocarcinomas. CK20 expression was detected by immunohistochemistry (IHC) in 60/63 (95.2%) cases, by conventional RT-PCR in 58/60 (96.7%) and by quantitative RT-PCR using the LightCycler (LightCycler is a trademark of a Member of the Roche Group) System in 29/32 (90.6%) microdissected cases, one case yielding variable results. Despite the high detection rate of all three techniques, marked heterogeneity of CK20 expression was seen between different cases and also within individual cases. CK20 expression profiles were not related to particular histopathological features of the tumours. A good correlation (r = 0.8964) was found between CK20 mRNA and protein expression by comparing quantitative RT-PCR with IHC in 32 cases. This was also true for selected heterogeneous tumour cells within individual cases. Both RT-PCR and IHC are therefore valuable tools for CK20 detection in colorectal adenocarcinoma, with real-time RT-PCR providing supplementary quantitative information. This suggests a promising supportive role for quantitative RT-PCR in molecular pathology.
Tetanus; the use of human hyperimmune globulin in treatment. (1963)

Twenty patients with tetanus were treated with human hyperimmune globulin. The mortality rate in the series was 30 per cent. No complications due to the use of this antitoxin were observed.
STRESS AND SYMPTOMATOLOGY IN PATIENTS WITH INTERSTITIAL CYSTITIS: A LABORATORY STRESS MODEL (2000)

These findings indicate that an acute stressor evokes increased symptoms of pain and urgency in patients with interstitial cystitis but not in controls. Findings are consistent with sympathetic effects on inflammatory processes in interstitial cystitis. However, further evaluation of the mechanisms underlying stress related interstitial cystitis symptom exacerbation is needed to provide a more comprehensive understanding of these phenomena.
Polymer capture by electro-osmotic flow of oppositely charged nanopores (2007)

The authors have addressed theoretically the hydrodynamic effect on the translocation of DNA through nanopores. They consider the cases of nanopore surface charge being opposite to the charge of the translocating polymer. The authors show that, because of the high electric field across the nanopore in DNA translocation experiments, electro-osmotic flow is able to create an absorbing region comparable to the size of the polymer around the nanopore. Within this capturing region, the velocity gradient of the fluid flow is high enough for the polymer to undergo coil-stretch transition. The stretched conformation reduces the entropic barrier of translocation. The diffusion limited translocation rate is found to be proportional to the applied voltage. In the authors' theory, many experimental variables (electric field, surface potential, pore radius, dielectric constant, temperature, and salt concentration) appear through a single universal parameter. They have made quantitative predictions on the size of the adsorption region near the pore for the polymer and on the rate of translocation.
Therapeutic Effect of Recombinant Mutated Interleukin 11 in the Mouse Model of Tuberculosis (2016)

Earlier we demonstrated that blocking of interleukin 11 (IL-11) by systemic administration of anti-IL-11 antibodies attenuates severity of Mycobacterium tuberculosis infection in mice. The substitution W147A in the IL-11 molecule creates the form of cytokine capable to disrupt gp130/IL11R signaling complex formation, thus serving as a high-affinity specific antagonist of IL-11-mediated signaling. We hypothesized that this mutant form of IL-11 may serve as an effective tool for inhibition of native IL-11 activity in vivo. We established the recombinant W147A mutant form of IL-11 in an optimized Escherichia coli expression system and administered it as the aerosol in the lungs of M. tuberculosis-susceptible I/St mice infected with M. tuberculosis Our results show that this therapeutic approach markedly inhibits tuberculous inflammation in lungs, increases the survival time of infected animals, and decreases expression of key inflammatory factors at the RNA and protein levels. These findings are a step toward clinical evaluation of the anti-IL-11 therapy for tuberculosis.
Animal models of arrhythmogenic cardiomyopathy (2009)

Arrhythmogenic cardiomyopathies are a heterogeneous group of pathological conditions that give rise to myocardial dysfunction with an increased risk for atrial or ventricular arrhythmias. Inherited defects in cardiomyocyte proteins in the sarcomeric contractile apparatus, the cytoskeleton and desmosomal cell-cell contact junctions are becoming recognized increasingly as major causes of sudden cardiac death in the general population. Animal models have been developed for the systematic dissection of the genetic pathways involved in the pathogenesis of arrhythmogenic cardiomyopathies. This review presents an overview of current animal models for arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) associated with cardiac arrhythmias and sudden cardiac death.
Optimizing the fabrication processes for manufacturing a hybrid hierarchical polyurethane–cell/hydrogel construct (2013)

It is essential to control the overall composition and internal architecture for complex organ manufacturing. In this study, several subprocesses were optimized to produce hybrid hierarchical polyurethane–cell/hydrogel constructs with an intrinsic network of grid and branched channels using a double-nozzle low-temperature deposition rapid prototyping system. The formation quality was mainly determined by the polymer concentration and composition. However, the cell viability was mainly determined by the formation time. Cell sensitivities to the inner nozzle diameter and extrusion flux were not significantly different within the given parameter ranges. The integrity of the two material systems can be varied by the formation routes and layer thickness. Under the optimal fabrication parameters, such as formation time within 20 min and gelatin:alginate:fibrinogen ratio of 2:1:1, a high cell survival rate of 80% was attained. The design and fabrication strategies used to create such a complex heterogeneous objects directly from a computer-aided design model represent a promising route for robotic hybrid hierarchical construct implementations, which would allow easy expansion of the subprocessing capabilities and scale up manufacturing capabilities.
Improved diagnostic classification of alcohol abusers by combining carbohydrate-deficient transferrin and gamma-glutamyltransferase. (2001)

The combined variable gamma-CDT is a powerful tool to discriminate alcohol abusers from social drinkers and is recommended for clinical use.
The Curse of Knowledge in Visual Data Communication (2019)

A viewer can extract many potential patterns from any set of visualized data values. But that means that two people can see different patterns in the same visualization, potentially leading to miscommunication. Here, we show that when people are primed to see one pattern in the data as visually salient, they believe that naïve viewers will experience the same visual salience. Participants were told one of multiple backstories about political events that affected public polling data, before viewing a graph that depicted those data. One pattern in the data was particularly visually salient to them given the backstory that they heard. They then predicted what naïve viewers would most visually salient on the visualization. They were strongly influenced by their own knowledge, despite explicit instructions to ignore it, predicting that others would find the same patterns to be most visually salient. This result reflects a psychological phenomenon known as the curse of knowledge, where an expert struggles to re-create the state of mind of a novice. The present findings show that the curse of knowledge also plagues the visual perception of data, explaining why people can fail to connect with audiences when they communicate patterns in data.