gebhart/patrepeval huggingface dataset:
Central role of the proteasome in senescence and survival of human fibroblasts: induction of a senescence-like phenotype upon its inhibition and resistance to stress upon its activation. (2003)

Normal human fibroblasts undergo a limited number of divisions in culture and progressively they reach a state of irreversible growth arrest, a process termed as replicative senescence. The proteasome is the major cellular proteolytic machinery, the function of which is impaired during replicative senescence. However, the exact causes of its malfunction in these conditions are unknown. Using WI38 fibroblasts as a model for cellular senescence we have observed reduced levels of proteasomal peptidase activities coupled with increased levels of both oxidized and ubiquitinated proteins in senescent cells. We have found the catalytic subunits of the 20 S complex and subunits of the 19 S regulatory complex to be down-regulated in senescent cells. This is accompanied by a decrease in the level of both 20 S and 26 S complexes. Partial inhibition of proteasomes in young cells caused by treatment with specific inhibitors induced a senescence-like phenotype, thus demonstrating the fundamental importance of the proteasome for retaining cellular maintenance and homeostasis. Stable overexpression of beta1 and beta5 subunits in WI38 established cell lines was shown to induce elevated expression levels of beta1 subunit in beta5 transfectants and vice versa. Transfectants possess increased proteasome activities and most importantly, increased capacity to cope better with various stresses. In summary these data demonstrate the central role of the proteasome during cellular senescence and survival as well as provide insights toward a better understanding of proteasome regulation.
A thin-film silicon solar cell and module (2005)

We have developed a new light-trapping scheme for a thin-film Si stacked module (Si HYBRID PULS module), where a (a-Si:H/transparent interlayer/microcrystalline Si) thin-film was integrated into a large-area solar cell module. An initial aperture efficiency of 131% has been achieved for a 910 455 mm Si HYBRID PLUS module, which was independently confirmed by AIST. This is the first report of the independently confirmed efficiency of a large-area thin-film Si module with an interlayer. The 19% increase of short-circuit current of this module was obtained by the introduction of a transparent interlayer that caused internal light-trapping. A minimodule was shown to exhibit a stabilized efficiency of 12%. Outdoor performance of a Si HYBRID (a-Si:H / micro-crystalline Si stacked) solar cell module has been investigated for over 4 years with two different kinds of module (top and bottom cell limited, respectively). The HYBRID modules limited by the top cell have exhibited a more efficient performance than the modules limited by the bottom cell, in natural sunlight at noon.
Semantic Photo Album Based on MPEG-4 Compatible Application Format (2007)

In this paper, we propose a promising photo album system that enables augmented use of digital photos over a wide range of multimedia devices and semantic consumption of photos as well. The proposed system contains an album engine to create metadata and a photo player to consume the photos. It operates based on a standardized application format to encode a group of photos and associated metadata. Experiments showed that the proposed system achieved reasonable albuming performance.
Differential effect of clozapine on weight: a controlled study (1996)

Weight gain is an important side effect of clozapine and is unrelated to the drug's differential antipsychotic efficacy.
Gene therapy with adeno-associated virus vector 5–human factor IX in adults with hemophilia B (2017)

Gene therapy for hemophilia B aims to ameliorate bleeding risk and provide endogenous factor IX (FIX) activity/synthesis through a single treatment, eliminating the requirement for FIX concentrate. AMT-060 combines an adeno-associated virus-5 (AAV5) vector with a liver-specific promoter driving expression of a codon-optimized wild-type human FIX gene. This multinational, open-label study included 10 adults with hemophilia B (FIX ≤2% of normal) and severe-bleeding phenotype. No participants tested positive for AAV5-neutralizing antibodies using a green-fluorescent protein-based assay, and all 10 were enrolled. A single dose of 5 × 10<sup>12</sup> or 2 × 10<sup>13</sup> genome copies of AMT-060/kilogram was administered to 5 participants each. In the low-dose cohort, mean endogenous FIX activity increased to 4.4 IU/dL. Annualized FIX use was reduced by 81%, and mean annualized spontaneous bleeding rate (ASBR) decreased from 9.8% to 4.6% (53%). In the higher-dose cohort, mean FIX activity increased to 6.9 IU/dL. Annualized FIX use decreased by 73%, and mean ASBR declined from 3.0 to 0.9 (70%). There was no reduction in traumatic bleeds. FIX activity was stable in both cohorts, and 8 of 9 participants receiving FIX at study entry stopped prophylaxis. Limited, asymptomatic, and transient alanine aminotransferase elevations in the low-dose (n = 1) and higher-dose (n = 2) cohorts were treated with prednisolone. No decrease in FIX activity or capsid-specific T-cell responses were detected during transaminase elevations. A single infusion of AMT-060 had a positive safety profile and resulted in stable and clinically important increases in FIX activity, a marked reduction in spontaneous bleeds and FIX concentrate use, without detectable cellular immune responses against capsids. This trial was registered at www.clinicaltrials.gov as #NCT02396342; EudraCT #2013-005579-42.
Exploring isonitrile-based click chemistry for ligation with biomolecules (2011)

We show here that isonitriles can perform click reactions with tetrazines in aqueous media, making them promising candidates for ligation reactions in chemical biology and polymer chemistry. This is the first time that a [4+1] cycloaddition has been used as a biocompatible ligation reaction.
Purification, Substrate Range, and Metal Center of AtzC: the N -Isopropylammelide Aminohydrolase Involved in Bacterial Atrazine Metabolism (2002)

N-Isopropylammelide isopropylaminohydrolase, AtzC, the third enzyme in the atrazine degradation pathway in Pseudomonas sp. strain ADP, catalyzes the stoichiometric hydrolysis of N-isopropylammelide to cyanuric acid and isopropylamine. The atzC gene was cloned downstream of the tac promoter and expressed in Escherichia coli, where the expressed enzyme comprised 36% of the soluble protein. AtzC was purified to homogeneity by ammonium sulfate precipitation and phenyl column chromatography. It has a subunit size of 44,938 kDa and a holoenzyme molecular weight of 174,000. The K(m) and k(cat) values for AtzC with N-isopropylammelide were 406 micro M and 13.3 s(-1), respectively. AtzC hydrolyzed other N-substituted amino dihydroxy-s-triazines, and those with linear N-alkyl groups had higher k(cat) values than those with branched alkyl groups. Native AtzC contained 0.50 eq of Zn per subunit. The activity of metal-depleted AtzC was restored with Zn(II), Fe(II), Mn(II), Co(II), and Ni(II) salts. Cobalt-substituted AtzC had a visible absorbance band at 540 nm (Delta epsilon = 84 M(-1) cm(-1)) and exhibited an axial electron paramagnetic resonance (EPR) signal with the following effective values: g((x)) = 5.18, g((y)) = 3.93, and g((z)) = 2.24. Incubating cobalt-AtzC with the competitive inhibitor 5-azacytosine altered the effective EPR signal values to g((x)) = 5.11, g((y)) = 4.02, and g((z)) = 2.25 and increased the microwave power at half saturation at 10 K from 31 to 103 mW. Under the growth conditions examined, our data suggest that AtzC has a catalytically essential, five-coordinate Zn(II) metal center in the active site and specifically catalyzes the hydrolysis of intermediates generated during the metabolism of s-triazine herbicides.
Peptide growth factors protect against ischemia in culture by preventing nitric oxide toxicity (1993)

Reduction or elimination of nitric oxide (NO) production in cortical neurons by NO synthase (NOS) inhibitors during glutamate toxicity in vitro or during focal cerebral ischemia in vivo can prevent neuronal cell death. In contrast, growth factors can prevent neuronal degeneration induced by treatment with glutamate or potassium cyanide. We have determined whether NO mediates hippocampal cell death during anoxia in vitro and whether the peptide growth factors basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) can prevent hippocampal neuronal death during anoxia or NO exposure. Both bFGF and EGF increased hippocampal neuronal survival from about 35% in anoxic cultures to about 65% in treated cultures during an 8 hr period of anoxia. Inhibition of NOS by NG-monomethyl-L-arginine, a competitive inhibitor of NOS, rescued 65-70% of the neurons that would normally die during an 8 hr anoxic incubation, and this effect was reversed by L-arginine, a precursor for NO. Thus, hippocampal neuronal death following anoxia is, at least in part, mediated by NO. NO, generated by either nitroprusside or 3-morpholino-sydnonimine, was toxic to hippocampal neurons. Pretreatment of cultures with either bFGF (10 ng/ml) or EGF (10 ng/ml) prior to NO exposure increased survival from approximately 40% in untreated cultures to 80% in treated cultures, yet the effect of combining bFGF and EGF was not greater than treatment with either of the growth factors alone. Knowledge that the growth factors bFGF and EGF are neuroprotective against NO toxicity provides insights into the mechanisms of ischemic neuronal death that may direct future therapeutic modalities for cerebrovascular disease and neurodegenerative disorders.
Folate, Methionine, and Alcohol Intake and Risk of Colorectal Adenoma (1993)

These data support efforts to increase dietary folate in segments of the population having diets with low intakes of this nutrient.
Polarization-induced fading in fiber-optic sensor arrays (1995)

The statistics of polarization-induced visibility fading is studied for fiber-optic interferometric (Michelson or Mach-Zehnder) sensor arrays made of either regular single-mode fibers or polarization-maintaining fibers. Performance is measured in terms of the probability to observe visibilities, all of which exceed a given value, for all members of the array. Very poor performance is obtained for arrays made of nonpolarization maintaining fibers, unless the input state of polarization is dynamically controlled to optimize the visibility of the worst sensor of the array. While the use of the more costly polarization-maintaining fibers could, in principle, solve this polarization-related fading problem, finite extinction ratios of couplers and splices make the performance of such arrays comparable to that of nonpolarization maintaining arrays with optimally controlled input-polarization.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
MARA: a novel approach for highly multiplexed locus-specific SNP genotyping using high-density DNA oligonucleotide arrays (2004)

We have developed a locus-specific DNA target preparation method for highly multiplexed single nucleotide polymorphism (SNP) genotyping called MARA (Multiplexed Anchored Runoff Amplification). The approach uses a single primer per SNP in conjunction with restriction enzyme digested, adapter-ligated human genomic DNA. Each primer is composed of common sequence at the 5' end followed by locus-specific sequence at the 3' end. Following a primary reaction in which locus-specific products are generated, a secondary universal amplification is carried out using a generic primer pair corresponding to the oligonucleotide and genomic DNA adapter sequences. Allele discrimination is achieved by hybridization to high-density DNA oligonucleotide arrays. Initial multiplex reactions containing either 250 primers or 750 primers across nine DNA samples demonstrated an average sample call rate of approximately 95% for 250- and 750-plex MARA. We have also evaluated >1000- and 4000-primer plex MARA to genotype SNPs from human chromosome 21. We have identified a subset of SNPs corresponding to a primer conversion rate of approximately 75%, which show an average call rate over 95% and concordance >99% across seven DNA samples. Thus, MARA may potentially improve the throughput of SNP genotyping when coupled with allele discrimination on high-density arrays by allowing levels of multiplexing during target generation that far exceed the capacity of traditional multiplex PCR.
A secure extensible container for hybrid mobile applications (2013)

An agile, lightweight, but secure extensible hybrid application container and deployment mechanism for mobile devices has the potential to provide improved cross platform support, reduced development lifecycle time and a consistent application security model within large organizations. We demonstrate how such an architecture can provide a set of security and mobile device management interfaces to lightweight applications written in a high level markup and scripting language and also how these applications can be provisioned via push or pull mechanisms to an Enterprise user's device. The use of such a container for hybrid applications widens the potential support and development resource within an organization to employees possessing readily available skill sets, this permits mission critical applications to be developed in a much shorter time frame than with native mobile application deployment methods.
Nucleoside phosphorothioates (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleoside phosphorothioatesFritz EcksteinCite this: J. Am. Chem. Soc. 1970, 92, 15, 4718–4723Publication Date (Print):July 1, 1970Publication History Published online1 May 2002Published inissue 1 July 1970https://pubs.acs.org/doi/10.1021/ja00718a039https://doi.org/10.1021/ja00718a039research-articleACS PublicationsRequest reuse permissionsArticle Views516Altmetric-Citations71LEARN 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
Prognostic value of baroreflex sensitivity testing after acute myocardial infarction. (1992)

Disordered autonomic function as measured by depressed baroreflex sensitivity or reduced heart rate variability was associated with an increase incidence of arrhythmic events in post-infarction patients. Baroreflex testing can be safely performed in the immediate post-infarction period.
Bone marrow‐derived cells expand memory CD8+ T cells in response to viral infections of the lung and skin (2006)

While naive CD8(+) T cells have been shown to require bone marrow-derived dendritic cells (DC) to initiate immunity, such a requirement for memory CD8(+) T cells has had limited assessment. By generating bone marrow chimeras that express the appropriate antigen-presenting molecules on either radiation-sensitive bone marrow-derived or radiation-resistant non-bone marrow-derived compartments, we showed that both primary and secondary immune responses to influenza virus infection of the lung were initiated in the draining LN. This required cells of bone marrow origin, most likely DC, for optimal expansion within the secondary lymphoid compartment. This was similarly the case with HSV-1 infection of the skin. As Langerhans cells are radioresistant, unlike other DC populations, these studies also demonstrate that the radiosensitive DC responsible for secondary expansion of HSV-specific memory are not Langerhans cells.
Introduction: On Conflict and Difference in Nineteenth-Century Literature (2010)

This collection explores Victorian patterns of engagement with concepts of ‘difference’ and ‘conflict’. In some respects, these terms may be defined in terms of antagonism. Benjamin Disraeli’s identification of one of the most prominent sites of division in the nineteenth century quickly became the dominant binary of the ‘Condition of England’ novel in the 1840s and 1850s, but it is just one reflection of the profound conflicts that characterized the Victorian period. From Disraeli’s ‘THE RICH AND THE POOR’ to Matthew Arnold’s ignorant armies clashing by night in ‘Dover Beach’ (1867) via Elizabeth Gaskell’s North and South (1855) and Alfred Tennyson’s doubting belief in In Memoriam (1850), the literature of the Victorian period now seems to us to bristle with intellectual, cultural and social oppositions. Dissonance generated by forces of faith and doubt and the educative powers of science and religion, the divide between men and women, the apparent competition between loyalty to nature and industry, not to mention the party-based politics, class conflicts generated by the volatile economic situation, and the military battlefields necessary to the growth and maintenance of an empire — these features of modernity formed the lives and the writings of the Victorians. The inventiveness of the age was not built on consensus, but on conflict.
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib (2006)

The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents.
The role of malate in plant homeostasis (2009)

Malate is a central metabolite of the plant cell with important roles in plant physiology and metabolism. Here, we summarize the most recent advances in our understanding of malate homeostasis in central metabolism, guard cell functioning, and root exudation.
Abnormal Fear Response and Aggressive Behavior in Mutant Mice Deficient for α-Calcium-Calmodulin Kinase II (1994)

Mice deficient for the gene encoding alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII knockout mice) provide a promising tool to link behavioral and cellular abnormalities with a specific molecular lesion. The heterozygous mouse exhibited a well-circumscribed syndrome of behavioral abnormalities, consisting primarily of a decreased fear response and an increase in defensive aggression, in the absence of any measured cognitive deficits. Unlike the heterozygote, the homozygote displayed abnormal behavior in all paradigms tested. At the cellular level, both extracellular and whole-cell patch clamp recordings indicated that serotonin release in putative serotonergic neurons of the dorsal raphe was reduced. Thus, alpha-CaMKII knockout mice, in particular the heterozygote, may provide a model for studying the molecular and cellular basis underlying emotional disorders involving fear and aggression.
Cationic Mucic Acid Polymer-Based siRNA Delivery Systems (2015)

Nanoparticle (NP) delivery systems for small interfering RNA (siRNA) that have good systemic circulation and high nucleic acid content are highly desired for translation into clinical use. Here, a family of cationic mucic acid-containing polymers is synthesized and shown to assemble with siRNA to form NPs. A cationic mucic acid polymer (cMAP) containing alternating mucic acid and charged monomers is synthesized. When combined with siRNA, cMAP forms NPs that require steric stabilization by poly(ethylene glycol) (PEG) that is attached to the NP surface via a 5-nitrophenylboronic acid linkage (5-nitrophenylboronic acid–PEGm (5-nPBA–PEGm)) to diols on mucic acid in the cMAP in order to inhibit aggregation in biological fluids. As an alternative, cMAP is covalently conjugated with PEG via two methods. First, a copolymer is prepared with alternating cMAP–PEG units that can form loops of PEG on the surface of the formulated siRNA-containing NPs. Second, an mPEG–cMAP–PEGm triblock polymer is synthesized that could lead to a PEG brush configuration on the surface of the formulated siRNA-containing NPs. The copolymer and triblock polymer are able to form stable siRNA-containing NPs without and with the addition of 5-nPBA–PEGm. Five formulations, (i) cMAP with 5-nPBA–PEGm, (ii) cMAP–PEG copolymer both (a) with and (b) without 5-nPBA–PEGm, and (iii) mPEG–cMAP–PEGm triblock polymer both (a) with and (b) without 5-nPBA–PEGm, are used to produce NPs in the 30–40 nm size range, and their circulation times are evaluated in mice using tail vein injections. The mPEG–cMAP–PEGm triblock polymer provides the siRNA-containing NP with the longest circulation time (5–10% of the formulation remains in circulation at 60 min postdosing), even when a portion of the excess cationic components used in the formulation is filtered away prior to injection. A NP formulation using the mPEG–cMAP–PEGm triblock polymer that is free of excess components could contain as much as ca. 30 wt % siRNA.
The COSINE and Internet X.500 Schema (1991)

The COSINE and
The Inaugural Selway Lecture: The Machine of Justice - Who Is Driving It? (2007)

John Doyle's speech delivered at the University of Adelaide Law School, Adelaide, 29 March 2006 is presented which canvasses some aspects of the functioning of the judicial system in South Australia, and comments on changes that are occurring. This article discusses the process of change within the judicial system, and within the judiciary. Who or what drives or produces change? How is it managed? Does the process of change have any implications for the principle of judicial independence? Who is accountable for change, or for the lack of it? The article also focuses on the management of efficiencies within the system for the administration of justice. How does one strike the balance between justice and efficiency? How does one measure efficiency? What is being done to measure efficiency in Australia?