gebhart/patrepeval huggingface dataset:
P3‐315: Inhibition of gamma‐secretase activity induces cell cycle defects and chromosome missegregation (2008)

Alzheimer's disease is the most common neurodegenerative disease in an aging population. The disease is characterized by the formation of cerebral cortical amyloid plaques and neurofibrillary tangles, ultimately leading to neuronal cell death and a progressive loss of memory and cognition. Presenilin-1 (PS1) is a component of the gamma-secretase complex, responsible for the C-terminal cleavage of the amyloid precursor protein (APP) into Abeta peptide, which is deposited as amyloid in the AD brain. In vitro and in vivo studies from our laboratory have demonstrated that familial Alzheimer's disease mutations in PS1 lead to chromosome mis-segregation and aneuploidy. A role for PS1 in cell division processes is substantiated by the localization of the protein to the centrosome and kinetechores and evidence that disruption of PS1 expression leads to tumor formation. In light of recent evidence suggesting that it is a loss of presenilin function that causes neurodegeneration and dementia in AD patients, we investigated the role of γ-secretase inhibitors (GSI) on cell cycle regulation and chromosome segregation. Human epithelial cells and normal or APP knockout mouse splenocytes were treated with GSIs or imatinib mesylate for 48 hours. Cell cycle progression was monitored by propidium iodide staining and flow cytometry analysis. Metaphase spreads were stained with Giemsa and counted using Metafer and Isis software. Treated cells were fixed and stained with anti-tubulin antibodies and Hoescht stain to analyze spindle pole formation. GSI-VI and GSI-XIV blocked the cell cycle in G0 and G2, respectively. GSI-IX and XXI-treated cells exhibited significant levels of aneuploidy with normal cell cycle progression. Mitotic spindle analysis revealed an abnormal microtubule array and lagging chromosomes with treatment of GSI-VI, -IX and -XXI. Treatment with GSI-IX or -XXI did not further augment abnormal chromosome numbers in APP knockout splenocytes, suggesting that APP is important for the aneugenic effects of the inhibitors. Furthermore, imatinib mesylate, which inhibits Abeta production without affecting Notch cleavage, also causes a significant increase in aneuploidy. These results suggest that inhibition of γ-secretase can result in cell cycle defects and chromosome mis-segregation in an APP dependent manner.
Ultrathin platinum nanowires grown on single-layered nickel hydroxide with high hydrogen evolution activity (2015)

Design and synthesis of effective electrocatalysts for hydrogen evolution reaction in alkaline environments is critical to reduce energy losses in alkaline water electrolysis. Here we report a hybrid nanomaterial comprising of one-dimensional ultrathin platinum nanowires grown on two-dimensional single-layered nickel hydroxide. Judicious surface chemistry to generate the fully exfoliated nickel hydroxide single layers is explored to be the key for controllable growth of ultrathin platinum nanowires with diameters of about 1.8 nm. Impressively, this hybrid nanomaterial exhibits superior electrocatalytic activity for hydrogen evolution reaction in alkaline solution, which outperforms currently reported catalysts, and the obviously improved catalytic stability. We believe that this work may lead towards the development of single-layered metal hydroxide-based hybrid materials for applications in catalysis and energy conversion.
Wireless Certificate Management Protocol Supporting Mobile Phones (2008)

PKI (Public Key Infrastructure) in wired internet is not suitable for the mobile phone because of the limitation of performance such as less memory and less powerful CPU. Therefore, we need to develop a wireless PKI that provides the similar security level as the wired PKI to support a mobile phone. Especially, certificate management is the start point of PKI. In this paper, we propose a lightweight and secure Wireless Certificate Management Protocol(CMP) that is executable to the mobile phone that has a constrained communication environment and limitation of performance, and show the implementation results of the scheme on the mobile phone. We minimize data sizes processed in mobile phone, and optimize protocols for the certificate management. This results in the reduced module sizes to be able to execute in mobile phone and shows as the same level as the wired CMP.
The 2.1 Å Structure of <i>Torpedo californica</i> Creatine Kinase Complexed with the ADP-Mg<sup>2+</sup>−NO<sub>3</sub><sup>-</sup>−Creatine Transition-State Analogue Complex<sup>,</sup> (2002)

Creatine kinase (CK) catalyzes the reversible conversion of creatine and ATP to phosphocreatine and ADP, thereby helping maintain energy homeostasis in the cell. Here we report the first X-ray structure of CK bound to a transition-state analogue complex (CK-TSAC). Cocrystallization of the enzyme from Torpedo californica (TcCK) with ADP-Mg(2+), nitrate, and creatine yielded a homodimer, one monomer of which was liganded to a TSAC complex while the second monomer was bound to ADP-Mg(2+) alone. The structures of both monomers were determined to 2.1 A resolution. The creatine is located with the guanidino nitrogen cis to the methyl group positioned to perform in-line attack at the gamma-phosphate of ATP-Mg(2+), while the ADP-Mg(2+) is in a conformation similar to that found in the TSAC-bound structure of the homologue arginine kinase (AK). Three ligands to Mg(2+) are contributed by ADP and nitrate and three by ordered water molecules. The most striking difference between the substrate-bound and TSAC-bound structures is the movement of two loops, comprising residues 60-70 and residues 323-332. In the TSAC-bound structure, both loops move into the active site, resulting in the positioning of two hydrophobic residues (one from each loop), Ile69 and Val325, near the methyl group of creatine. This apparently provides a specificity pocket for optimal creatine binding as this interaction is missing in the AK structure. In addition, the active site of the transition-state analogue complex is completely occluded from solvent, unlike the ADP-Mg(2+)-bound monomer and the unliganded structures reported previously.
Increased 11β-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero (2006)

Rat offspring prenatally exposed to alcohol display features of metabolic syndrome characterized by a low birth weight, catch-up growth, dyslipidemia, and insulin-resistant diabetes with increased gluconeogenesis, during adult life. Gluconeogenesis is partly regulated by cyclic AMP- and glucocorticoid-dependent mechanisms. Glucocorticoid action at the receptor level depends on its circulating concentrations and is amplified at the prereceptor level by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which regenerates active glucocorticoids from inactive forms. To determine whether 11beta-HSD1 is dysregulated in this rat model, we examined the expression and enzyme activity of 11beta-HSD1 and its regulator enzyme hexose-6-phosphate dehydrogenase (H6PD) in the liver of postnatal day 7 (neonatal) and 3-mo-old (adult) rat offspring prenatally exposed to alcohol. Measurements of 11beta-HSD1 and H6PD were also performed in the omental fat of adult rat offspring. In both neonatal and adult rats, prenatal alcohol exposure resulted in increased tissue corticosterone concentrations, increased expression, and oxoreductase activity of 11beta-HSD1, and a parallel increase of H6PD expression. The data suggest that due to both transcriptional and posttranscriptional dysregulations, rats exposed to alcohol early in life have increased 11beta-HSD1 activity, which may explain insulin-resistant diabetes in these animals later in life.
Regulation of Seed Size by Hypomethylation of Maternal and Paternal Genomes (2006)

DNA methylation is an epigenetic modification of cytosine that is important for silencing gene transcription and transposons, gene imprinting, development, and seed viability. DNA METHYLTRANSFERASE1 (MET1) is the primary maintenance DNA methyltransferase in Arabidopsis (Arabidopsis thaliana). Reciprocal crosses between antisense MET1 transgenic and wild-type plants show that DNA hypomethylation has a parent-of-origin effect on seed size. However, due to the dominant nature of the antisense MET1 transgene, the parent with a hypomethylated genome, its gametophyte, and both the maternal and paternal genomes of the F(1) seed become hypomethylated. Thus, the distinct role played by hypomethylation at each generation is not known. To address this issue, we examined F(1) seed from reciprocal crosses using a loss-of-function recessive null allele, met1-6. Crosses between wild-type and homozygous met1-6 parents show that hypomethylated maternal and paternal genomes result in significantly larger and smaller F(1) seeds, respectively. Our analysis of crosses between wild-type and heterozygous MET1/met1-6 parents revealed that hypomethylation in the female or male gametophytic generation was sufficient to influence F(1) seed size. A recessive mutation in another gene that dramatically reduces DNA methylation, DECREASE IN DNA METHYLATION1, also causes parent-of-origin effects on F(1) seed size. By contrast, recessive mutations in genes that regulate a smaller subset of DNA methylation (CHROMOMETHYLASE3 and DOMAINS REARRANGED METHYLTRANSFERASES1 and 2) had little effect on seed size. Collectively, these results show that maternal and paternal genomes play distinct roles in the regulation of seed size in Arabidopsis.
Interaction between the <i>ADAM12</i> and <i>SH3MD1</i> genes may confer susceptibility to late‐onset Alzheimer's disease (2007)

The neuropathology of Alzheimer's disease (AD) is characterized by intracellular neurofibrillary tangles and the extracellular deposition of beta-amyloid (Abeta) in senile plaques. Abeta has been shown to mediate neurodegenerative and inflammatory changes associated with amyloid plaques, although the pathological mechanism of Abeta remains largely unknown. Recent evidence suggests that the FISH adapter protein binds to, and potentially regulates, ADAM12 (a disintegrin and metalloprotease 12) to mediate a neurotoxic effect of Abeta. The ADAM12 gene lies on chromosome 10q26.3, and the gene encoding FISH, SH3MD1, lies within a region of linkage to late-onset AD (LOAD) on 10q25.1. This study investigates whether there is a relationship between variation in ADAM12 and SH3MD1 and susceptibility to LOAD in a sample of 1,051 AD cases and 1,269 matched controls. We observe significant interactions between variants in the two genes that may influence susceptibility to LOAD. The most significant statistical interaction is between rs3740473, a synonymous single nucleotide polymorphism (SNP) in SH3MD1 and rs11244787, an intronic SNP in ADAM12 (effect size = 2.1 for interaction term, P = 0.006).
Configuration space analysis of common cost functions in radiotherapy beam-weight optimization algorithms (2001)

The successful implementation of downhill search engines in radiotherapy optimization algorithms depends on the absence of local minima in the search space. Such techniques are much faster than stochastic optimization methods but may become trapped in local minima if they exist. A technique known as 'configuration space analysis' was applied to examine the search space of cost functions used in radiotherapy beam-weight optimization algorithms. A downhill-simplex beam-weight optimization algorithm was run repeatedly to produce a frequency distribution of final cost values. By plotting the frequency distribution as a function of final cost, the existence of local minima can be determined. Common cost functions such as the quadratic deviation of dose to the planning target volume (PTV), integral dose to organs-at-risk (OARs), dose-threshold and dose-volume constraints for OARs were studied. Combinations of the cost functions were also considered. The simple cost function terms such as the quadratic PTV dose and integral dose to OAR cost function terms are not susceptible to local minima. In contrast, dose-threshold and dose-volume OAR constraint cost function terms are able to produce local minima in the example case studied.
Kinetic properties of human placental aromatase. Application of an assay measuring 3H2O release from 1beta,2beta-3H-androgens. (1976)

The rapid and sensitive assay of 1beta,2beta-3H-androgen aromatization by measurement of 3H2O release (Thompson, E.A., Jr., and Siiteri, P.K. (1974) J. Biol. Chem. 249, 5364-5372) has been analyzed to determine its applicability to initial rate studies. It was found that aromatization is the sole reaction catalyzed by lyophilized placental microsomes that causes a loss of tritium from position 1 or 2 of androstenedione and testosterone. Tritium is, however, removed from position 2 of the estrogen products, presumably in 2-hydroxylation, but this does not invalidate use of the assay for initial rate measurements; it was therefore used to characterize the catalytic properties of aromatase. Aromatization by the freeze-dried preparation was stimulated by K+, EDTA, and dithiothreitol, and was maximally active at pH 7.5 TO 8.0. With incubation conditions optimized for these factors, the apparent Km for NADPH is approximately 1 muM. The maximum velocity of androstenedione aromatization exceeds that of testosterone, and the affinity of the substrate binding site is higher for the former substrate, the apparent Km values being 0.1 muM and 0.4 muM, respectively. Mutual competition experiments with the androgen substrates showed that each gives simple competitive inhibition of the other's aromatization; furthermore, the apparent Ki values for each are in close agreement with their respective Km values. Androst-1,4,6-triene-3,17-dione competitively inhibits the aromatization of both androstenedione and testosterone, the apparent Ki, in both cases being 0.2 muM. It is concluded that the two androgen substrates are aromatized at a single, identical site.
The transcriptional tissue specificity of the human pro<i>α</i>1(I) collagen gene is determined by a negative <i>cis</i>-regulatory element in the promoter (1992)

The transcriptional activity of plasmid pCOL-KT, in which human pro alpha 1 (I) collagen gene upstream sequences up to -804 and most of the first intron (+474 to +1440) drive expression of the chloramphenicol acetyltransferase (CAT) gene [Thompson, Simkevich, Holness, Kang & Raghow (1991) J. Biol. Chem. 266, 2549-2556], was tested in a number of mesenchymal and non-mesenchymal cells. We observed that pCOL-KT was readily expressed in fibroblasts of human (IMR-90 and HFL-1), murine (NIH 3T3) and avian (SL-29) origin and in a human rhabdomyosarcoma cell line (A204), but failed to be expressed in human erythroleukaemia (K562) and rat pheochromocytoma (PC12) cells, indicating that the regulatory elements required for appropriate tissue-specific expression of the human pro alpha 1 (I) collagen gene were present in pCOL-KT. To delineate the nature of cis-acting sequences which determine the tissue specificity of pro alpha 1 (I) collagen gene expression, functional consequences of deletions in the promoter and first intron of pCOL-KT were tested in various cell types by transient expression assays. Cis elements in the promoter-proximal and intronic sequences displayed either a positive or a negative influence depending on the cell type. Thus deletion of fragments using EcoRV (nt -625 to -442 deleted), XbaI (-804 to -331) or SstII (+670 to +1440) resulted in 2-10-fold decreased expression in A204 and HFL-1 cells. The negative influences of deletions in the promoter-proximal sequences was apparently considerably relieved by deleting sequences in the first intron, and the constructs containing the EcoRV/SstII or XbaI/SstII double deletions were expressed to a much greater extent than either of the single deletion constructs. In contrast, the XbaI* deletion (nt -804 to -609), either alone or in combination with the intronic deletion, resulted in very high expression in all cells regardless of their collagen phenotype; the XbaI*/(-SstII) construct, which contained the intronic SstII fragment (+670 to +1440) in the reverse orientation, was not expressed in either mesenchymal or nonmesenchymal cells. Based on these results, we conclude that orientation-dependent interactions between negatively acting 5'-upstream sequences and the first intron determine the mesenchymal cell specificity of human pro alpha 1 (I) collagen gene transcription.
Anaerobic Digestion Development (1991)

This chapter addresses conversion of the biodegradable fraction of municipal wastes to methane by anaerobic digestion. The scope is restricted to primary sludge and aquatic plants generated from treatment of domestic sewage and the organic fraction of municipal solid waste. Although many industries generate organic wastes which are suitable feedstocks for anaerobic digestion, they are generally treated on-site and the technology for their anaerobic treatment is so diverse that its discussion would be the subject of a separate book.
Aesthetic Image Classification for Autonomous Agents (2010)

Computational aesthetics is the study of applying machine learning techniques to identify aesthetically pleasing imagery. Prior work used online datasets scraped from large user communities like Flikr to get labeled data. However, online imagery represents results late in the media generation process, as the photographer has already framed the shot and then picked the best results to upload. Thus, this technique can only identify quality imagery once it has been taken. In contrast, automatically creating pleasing imagery requires understanding the imagery present earlier in the process. This paper applies computational aesthetics techniques to a novel dataset from earlier in that process in order to understand how the problem changes when an autonomous agent, like a robot or a real-time camera aid, creates pleasing imagery instead of simply identifying it.
The Blockchain and Kudos: A Distributed System for Educational Record, Reputation and Reward (2016)

The ‘blockchain’ is the core mechanism for the Bitcoin digital payment system. It embraces a set of inter-related technologies: the blockchain itself as a distributed record of digital events, the distributed consensus method to agree whether a new block is legitimate, automated smart contracts, and the data structure associated with each block. We propose a permanent distributed record of intellectual effort and associated reputational reward, based on the blockchain that instantiates and democratises educational reputation beyond the academic community. We are undertaking initial trials of a private blockchain or storing educational records, drawing also on our previous research into reputation management for educational systems.
Biocatalytic oxidation of cellobiose in an hydrated ionic liquid (2008)

Extraction of electrons from cellobiose is realised by cellobiose dehydrogenase (CDH) in hydrated choline dihydrogen phosphate (dhp). Both inter- and intra-electron transfer of CDH were observed in the hydrated choline dhp suggesting a potential candidate of a non-aqueous solvent for enzymatic treatment of depolymerised biomass.
Characterization of <i>pilQ</i>, a new gene required for the biogenesis of type 4 fimbriae in <i>Pseudomonas aeruginosa</i> (1993)

Type 4 fimbriae are produced by a variety of pathogens, in which they appear to function in adhesion to epithelial cells, and in a form of surface translocation called twitching motility. Using transposon mutagenesis of Pseudomonas aeruginosa, we have identified a new locus required for fimbrial assembly. This locus contains the gene pilQ which encodes a 77 kDa protein with an N-terminal hydrophobic signal sequence characteristic of secretory proteins. pilQ mutants lack the spreading colony morphology characteristic of twitching motility, are devoid of fimbriae, and are resistant to the fimbrial-specific bacteriophage PO4. The pilQ gene was mapped to Spel fragment 2, which is located at 0-5 minutes on the P. aeruginosa PAO1 chromosome, and thus it is not closely linked to the previously characterized pilA-D, pilS,R or pilT genes. The pilQ region also contains ponA, aroK and aroB-like genes in an organization very similar to that of corresponding genes in Escherichia coli and Haemophilus influenzae. The predicted amino acid sequence of PilQ shows homology to the PulD protein of Klebsiella oxytoca and related outer membrane proteins which have been found in association with diverse functions in other species including protein secretion, DNA uptake and assembly of filamentous phage. PilQ had the highest overall homology to an outer membrane antigen from Neisseria gonorrhoeae, encoded by omc, that may fulfil the same role in type 4 fimbrial assembly in this species.
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women (2004)

S ignificant advances in our knowledge about interventions to prevent cardiovascular disease (CVD) have occurred since publication of the first female-specific recommendations for preventive cardiology in 1999. 1 Despite researchbased gains in the treatment of CVD, it remains the leading killer of women in the United States and in most developed areas of the world. [2] 3] In the United States alone, more than one half million women die of CVD each year, exceeding the number of deaths in men and the next 7 causes of death in women combined. This translates into approximately 1 death every minute. 2 Coronary heart disease (CHD) accounts for the majority of CVD deaths in women, disproportionately afflicts racial and ethnic minorities, and is a prime target for prevention. [1] 2] Because CHD is often fatal, and because nearly two thirds of women who die suddenly have no previously recognized symptoms, it is essential to prevent CHD. 2 Other forms of atherosclerotic/thrombotic CVD, such as cerebrovascular disease and peripheral arterial disease, are critically important in women. Strategies known to reduce the burden of CHD may have substantial benefits for the prevention of noncoronary atherosclerosis, although they have been studied less extensively in some of these settings.
Reflection removal using disparity and gradient-sparsity via smoothing algorithm (2015)

The purpose of this paper is to introduce a new method for removing reflections from multi-view images taken through a transparent medium, such as pane glass. Our method utilizes an optimization approach based on the probabilistic model of relative smoothness algorithm, which exploits gradient value to separate the image into two sub-layers. As this algorithm has certain limitations on removing reflections, we improve upon it by imposing a gradient-sparsity constraint. This allows the type of reflection captured within a camera's focal length to be effectively removed. We also introduce another constraint on a disparity map which smooths specific areas of reflection layer while simultaneously preserves the sharpness of the main object. These two major contributions are proven to be sufficient in producing high-quality images. Our algorithm demonstrates good results compared with other existing methods as most of the reflection spots have been removed, and the computational time of our system is arguably fast.