gebhart/patrepeval huggingface dataset:
An Inventory to Assess Activities of Daily Living for Clinical Trials in Alzheimerʼs Disease (1997)

We developed a set of informant-based items describing performance of activities of daily living (ADL) by patients with Alzheimer's disease (AD) to identify which ADL are useful for assessment of patients in clinical trials. Evaluation of ADL is an important outcome measure in AD clinical trials. For clinical trial measurement, ADL should have broad applicability, good test-retest reliability, scaling to cover a range of performance, and sensitive to detect change in disease progression. A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer's Disease Cooperative Study Instrument protocol. Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months. Controls performed virtually all ADL items optimally at baseline and at 12 months. Among subjects with AD, 27 of the 45 ADL were widely applicable, i.e., performed at baseline or premorbidly by >90% of subjects; showed good test-retest reliability between baseline and 1 and 2 months; correlated with MMSE scores of AD patients cross-sectionally; and showed a decline in performance from baseline to 12 months in at least 20% of AD patients. ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE. The remaining 18 ADL included several that may be useful for trials that target specific populations, e.g., women with AD. Because change on specific items depends on baseline MMSE, ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial …
Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. (1995)

We have discovered that three longevity mutants of the nematode Caenorhabditis elegans also exhibit increased intrinsic thermotolerance (Itt) as young adults. Mutation of the age-1 gene causes not only 65% longer life expectancy but also Itt. The Itt phenotype cosegregates with age-1. Long-lived spe-26 and daf-2 mutants also exhibit Itt. We investigated the relationship between increased thermotolerance and increased life-span by developing conditions for environmental induction of thermotolerance. Such pretreatments at sublethal temperatures induce significant increases in thermotolerance and small but statistically highly significant increases in life expectancy, consistent with a causal connection between these two traits. Thus, when an animal's resistance to stress is increased, by either genetic or environmental manipulation, we also observe an increase in life expectancy. These results suggest that ability to respond to stress limits the life expectancy of C. elegans and might do so in other metazoa as well.
John Thornhill: Theologian of the church (2004)

This is written in tribute to Marist theologian, John Thornhill, in recognition of his contribution to theology and theological education in Australia. Specific references are made to John's article in the Journal, One Theologian's Personal Journey. It begins by outlining distinct habits of mind that inform John's approach to theology: philosophical realism; historical consciousness; and the original experience of the Gospel. This provides John with a theological template for interpreting the complex relationship between human history and divine revelation. Influences in John's theological project are then discussed under the self-explanatory headings of Marist, Vatican II, Ecumenism and Australian. Finally, it is proposed that John is first and foremost a theologian of the Church.
Cellular expression of tumor necrosis factor a and its receptors in human ischemic stroke. (2003)

We evaluated by immunocytochemistry cellular localization and time-dependent expression of tumor necrosis factor a (TNF-alpha) and its receptors p55 (TNF-RI) and p75 (TNF-R2) in human ischemic brains. We observed them in microglia, neurons, astrocytes, macrophages and blood vessels. Since TNF-alpha expression was very intense and prolonged in microglia, it probably constitutes the main cellular source of the cytokine following cerebral ischemia in humans. Constitutive expression of TNF-alpha receptors was observed in neurons and blood vessels while in other cells it was induced by ischemia. In macrophages, dominant immunolabeling for TNF-R2 was seen. In other cells, immunoreactions for both types of TNF-alpha receptors were similar but the pattern of immunostaining was different: homogenous for TNF-R1 and granular for TNF-R2. Beneficial and detrimental role of TNF-alpha in cerebral ischemia and supposed mechanisms of action are discussed.
Massively Parallel Hyperparameter Tuning (2018)

Modern learning models are characterized by large hyperparameter spaces. In order to adequately explore these large spaces, we must evaluate a large number of configurations, typically orders of magnitude more configurations than available parallel workers. Given the growing costs of model training, we would ideally like to perform this search in roughly the same wall-clock time needed to train a single model. In this work, we tackle this challenge by introducing ASHA, a simple and robust hyperparameter tuning algorithm with solid theoretical underpinnings that exploits parallelism and aggressive early-stopping. Our extensive empirical results show that ASHA slightly outperforms Fabolas and Population Based Tuning, state-of-the hyperparameter tuning methods; scales linearly with the number of workers in distributed settings; converges to a high quality configuration in half the time taken by Vizier (Google's internal hyperparameter tuning service) in an experiment with 500 workers; and beats the published result for a near state-of-the-art LSTM architecture in under 2x the time to train a single model.
Publisher's Note: “Curving monolithic silicon for nonplanar focal plane array applications” [Appl. Phys. Lett. 92, 091114 (2008)] (2008)

First Page
Biological effects of 1alpha-hydroxy- and 1beta-(hydroxymethyl)-vitamin D compounds relevant for potential colorectal cancer therapy. (1999)

1alpha,25-dihydroxyvitamin D(3) and two synthetic analogs, 1alpha, 25-dihydroxy-16-ene-23-yne-vitamin D(3) (Ro 23-7553) and 1alpha, 25-dihydroxy-16-ene-24-oxo-vitamin D(3) (JK-1624-3), were tested for their ability to specifically inhibit growth and promote differentiation of human colon cancer cells in comparison with a series of 1beta-(hydroxymethyl) congeners of the natural hormone, such as 1beta-(hydroxymethyl)-3alpha,25(OH)(2)-16-ene,24-oxo-vitamin D(3) (JK-1624-2), 1beta-(hydroxymethyl)-3alpha, 25-dihydroxy-16-ene-26,27-dihomo vitamin D(3) (JK-1626-2), and 1beta-(hydroxymethyl)-3alpha,25-dihydroxy-22,24-diene-26,27- dihomo vitamin D(3) (MCW-EE). Western blot analysis revealed that reduction of cyclin D1 levels is a key mechanism by which the vitamin D compounds under investigation inhibit Caco-2 tumor cell growth. Both the 1alpha-hydroxy- as well as the 1beta-hydroxymethyl-type vitamin D compounds, which exhibit only low affinity for the vitamin D receptor, significantly reduced [(3)H]thymidine DNA labeling in confluent Caco-2 cell cultures. This suggests that high-affinity binding to the vitamin D receptor is not an absolute prerequisite for genomic action on tumor cell growth. Hybrid analogs JK-1624-2 and MCW-EE, although antimitotically active, were rather ineffective in promoting phenotypic differentiation of human colon cancer cells. However, because both compounds also do not promote osteoclast differentiation from hematopoetic bone marrow cells, they still could be used as antimitotic agents in cancer therapy, even at dose levels that, with other analogs, could cause hypercalcemia.
The Xanthomonas Hrp type III system secretes proteins from plant and mammalian bacterial pathogens (1999)

Studies of essential pathogenicity determinants in Gram-negative bacteria have revealed the conservation of type III protein secretion systems that allow delivery of virulence factors into host cells from plant and animal pathogens. Ten of 21 Hrp proteins of the plant pathogen Xanthomonas campestris pv. vesicatoria have been suggested to be part of a type III machinery. Here, we report the hrp-dependent secretion of two avirulence proteins, AvrBs3 and AvrRxv, by X. campestris pv. vesicatoria strains that constitutively express hrp genes. Secretion occurred without leakage of a cytoplasmic marker in minimal medium containing BSA, at pH 5.4. Secretion was strictly hrp-dependent because a mutant carrying a deletion in hrcV, a conserved hrp gene, did not secrete AvrBs3 and AvrRxv. Moreover, the Hrp system of X. campestris pv. vesicatoria was able to secrete proteins from two other plant pathogens: PopA, a protein secreted via the Hrp system in Ralstonia solanacearum, and AvrB, an avirulence protein from Pseudomonas syringae pv. glycinea. Interestingly, X. campestris pv. vesicatoria also secreted YopE, a type III-secreted cytotoxin of the mammalian pathogen Yersinia pseudotuberculosis in a hrp-dependent manner. YerA, a YopE-specific chaperone, was required for YopE stability but not for secretion in X. campestris pv. vesicatoria. Our results demonstrate the functional conservation of the type III system of X. campestris for secretion of proteins from both plant and mammalian pathogens and imply recognition of their respective secretion signals.
Similarity of atoms in molecules (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimilarity of atoms in moleculesJerzy Cioslowski and Asiri NanayakkaraCite this: J. Am. Chem. Soc. 1993, 115, 24, 11213–11215Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/ja00077a020https://doi.org/10.1021/ja00077a020research-articleACS PublicationsRequest reuse permissionsArticle Views167Altmetric-Citations46LEARN 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
Topical Sucralfate for Erosive Irritant Diaper Dermatitis (2000)

We present the case of a 42-year-old woman with spina bifida and paraplegia who was referred to us because of chronic discomfort related to erosions and ulcerations of her perineal area, buttocks, and upper posterior thighs (Figure 1).Twenty years previously she had an ileal diversion and urostomy resulting in chronic urethral discharge and diarrhea for 5 years.She required a diaper constantly and developed erosive dermatitis.Her discomfort had persisted for 5 years and failed to respond to 1% clotrimazole (Canesten; Bayer AG, Leverkusen, Germany) and a zinc oxide preparation (Sudocrem; Tosara Products Ltd, Dublin, Ireland).
Aberrant Elevation of Tyrosine‐specific Phosphorylation in Human Gastric Cancer Cells (1991)

Phosphotyrosine-containing proteins in various human cancer cell lines were studied by immunoblotting with anti-phosphotyrosine antibody. Of 29 cell lines derived from oral epidermoid cancer, esophageal cancer, gastric cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma and malignant melanoma, 3 of the 6 gastric cancer cells showed aberrant elevation of tyrosine-specific phosphorylation. On the other hand, both esophageal cancer cells and colon cancer cells, which were reported to have amplified epidermal growth factor receptor and activated p60v-src kinase, respectively, showed no apparent elevation of tyrosine-specific phosphorylation, and their profiles of phosphorylation were similar to that of normal human fibroblasts. Two gastric cancer cells, NUGC-4 and MKN-45, showed similar profiles of phosphorylation but their responses to growth factors differed from each other. Tyrosine phosphorylation in NUGC-4 was strongly activated by treatment with epidermal growth factor and quickly reduced by the acid treatment which is effective in removing growth factors from cellular surface receptors. On the contrary, phosphorylation in MKN-45 did not respond to either growth factor or acid treatment. These results suggest that NUGC-4 and MKN-45 have tyrosine kinases which are activated by different mechanisms but share similar substrates.
Identification of a Chromosome 11q23.2-q24 Locus for Familial Aortic Aneurysm Disease, a Genetically Heterogeneous Disorder (2001)

FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.
Evolutionary diversification of Pseudomonas aeruginosa in an artificial sputum model (2017)

We observed considerable within-population phenotypic diversity in P. aeruginosa populations evolving in the artificial sputum medium biofilm model. Replicate populations evolved both in the presence and absence of phages converged upon similar sets of phenotypes. The evolved phenotypes, including antimicrobial resistance, were similar to those observed amongst clinical isolates from cystic fibrosis infections.
Host Immune Responses to Chronic Adenovirus Infections in Human and Nonhuman Primates (2008)

Recent studies indicate that great apes and macaques chronically shed adenoviruses in the stool. Shedding of adenovirus in the stool of humans is less prevalent, although virus genomes persist in gut-associated lymphoid tissue in the majority of individual samples. Chimpanzees have high levels of broadly reactive neutralizing antibodies to adenoviruses in serum, with very low frequencies of adenovirus-specific T cells in peripheral blood. A similar situation exists in macaques; sampling of guts from macaques demonstrated adenovirus-specific T cells in lamina propria. Humans show intermediate levels of serum neutralizing antibodies, with adenovirus-specific T cells in peripheral blood of all individuals sampled and about 20% of samples from the gut, suggesting a potential role of T cells in better controlling virus replication in the gut. The overall structure of the E3 locus, which is involved in modulating the host's response to infection, is degenerate in humans compared to that in apes, which may contribute to diminished evasion of host immunity. The impact of adenovirus persistence and immune responses should be considered when using adenoviral vectors in gene therapy and genetic vaccines.
Distributed Differential Oscillators for Global Clock Networks (2006)

This paper presents a distributed differential oscillator global clock network where the clock capacitance is rendered resonant with a set of on-chip spiral inductors. The clock amplitude and clock phase are both uniform across the entire global distribution, making this design scalable and compatible with existing local clocking methodologies. The resonant network, combined with phase averaging of the distributed oscillator, provides high immunity to process-, voltage-, and temperature-variation-induced timing uncertainty. Measurement results from a prototype design implemented in a 0.18-mum CMOS technology show almost an order of magnitude less jitter and power than a traditional tree-driven grid global clock distribution. On-chip measurement circuits are used to characterize the jitter on the test chip, while a simulation model is used to examine skew and higher-order resonances in the resonant clock network
Measurements of wound edge microvascular blood flow during negative pressure wound therapy using thermodiffusion and transcutaneous and invasive laser Doppler velocimetry (2011)

The effects of negative pressure wound therapy (NPWT) on wound edge microvascular blood flow are not clear. The aim of the present study was therefore to further elucidate the effects of NPWT on periwound blood flow in a porcine peripheral wound model using different blood flow measurement techniques. NPWT at -20, -40, -80, and -125 mmHg was applied to a peripheral porcine wound (n = 8). Thermodiffusion, transcutaneous, and invasive laser Doppler velocimetry were used to measure the blood perfusion 0.5, 1.0, and 2.5 cm from the wound edge. Thermodiffusion (an invasive measurement technique) generally showed a decrease in perfusion close to the wound edge (0.5 cm), and an increase further from the edge (2.5 cm). Invasive laser Doppler velocimetry showed a similar response pattern, with a decrease in blood flow 0.5 cm from the wound edge and an increase further away. However, 1.0 cm from the wound edge blood flow decreased with high pressure levels and increased with low pressure levels. A different response pattern was seen with transcutaneous laser Doppler velocimetry, showing an increase in blood flow regardless of the distance from the wound edge (0.5, 1.0, and 2.5 cm). During NPWT, both increases and decreases in blood flow can be seen in the periwound tissue depending on the distance from the wound edge and the pressure level. The pattern of response depends partly on the measurement technique used. The combination of hypoperfusion and hyperperfusion caused by NPWT may accelerate wound healing.
Neutrophils and Protease/Antiprotease Imbalance (1999)

An imbalance between neutrophil proteases and the surrounding antiproteases is critical in the normal functioning of the neutrophil. Enzyme activity is of importance in cell migration and may play a role in some beneficial aspects of host defense. However, when persistent or excessive this imbalance can be detrimental and (even in the absence of antiprotease deficiency) central to most of the pathogenic processes in COPD. Understanding of these complex relationships that alter a beneficial host defense response to a destructive one will be critical in the development of long-term therapeutic strategies. Stockley RA. Neutrophils and protease/antiprotease imbalance.
Structure of free fumarase C fromEscherichia coli (2005)

Previous crystal structures of fumarase C from Escherichia coli have noted two occupied dicarboxylate-binding sites termed the active site and the B site. Here, the first known fumarase C structure is reported in which both sites are unoccupied by bound ligand. This so-called ;free' crystal form shows conservation of the active-site water in a similar orientation to that reported in other fumarase C crystal structures. More importantly, a shift of His129 has been observed at the B site. This new crystallographic information suggests the use of water as a permanent member of the active site and the use of an imidazole-imidazolium conversion to control access at the allosteric B site.
Reaction of phenanthrenequinone with ammonium acetate (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReaction of phenanthrenequinone with ammonium acetateIvan LantosCite this: J. Org. Chem. 1975, 40, 11, 1641–1642Publication Date (Print):May 1, 1975Publication History Published online1 May 2002Published inissue 1 May 1975https://pubs.acs.org/doi/10.1021/jo00899a028https://doi.org/10.1021/jo00899a028research-articleACS PublicationsRequest reuse permissionsArticle Views251Altmetric-Citations11LEARN 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
Hedgehog‐EGFR cooperation response genes determine the oncogenic phenotype of basal cell carcinoma and tumour‐initiating pancreatic cancer cells (2012)

Inhibition of Hedgehog (HH)/GLI signalling in cancer is a promising therapeutic approach. Interactions between HH/GLI and other oncogenic pathways affect the strength and tumourigenicity of HH/GLI. Cooperation of HH/GLI with epidermal growth factor receptor (EGFR) signalling promotes transformation and cancer cell proliferation in vitro. However, the in vivo relevance of HH-EGFR signal integration and the critical downstream mediators are largely undefined. In this report we show that genetic and pharmacologic inhibition of EGFR signalling reduces tumour growth in mouse models of HH/GLI driven basal cell carcinoma (BCC). We describe HH-EGFR cooperation response genes including SOX2, SOX9, JUN, CXCR4 and FGF19 that are synergistically activated by HH-EGFR signal integration and required for in vivo growth of BCC cells and tumour-initiating pancreatic cancer cells. The data validate EGFR signalling as drug target in HH/GLI driven cancers and shed light on the molecular processes controlled by HH-EGFR signal cooperation, providing new therapeutic strategies based on combined targeting of HH-EGFR signalling and selected downstream target genes.
Structure and Function of a Squalene Cyclase (1997)

The crystal structure of squalene-hopene cyclase from Alicyclobacillus acidocaldarius was determined at 2.9 angstrom resolution. The mechanism and sequence of this cyclase are closely related to those of 2,3-oxidosqualene cyclases that catalyze the cyclization step in cholesterol biosynthesis. The structure reveals a membrane protein with membrane-binding characteristics similar to those of prostaglandin-H2 synthase, the only other reported protein of this type. The active site of the enzyme is located in a large central cavity that is of suitable size to bind squalene in its required conformation and that is lined by aromatic residues. The structure supports a mechanism in which the acid starting the reaction by protonating a carbon-carbon double bond is an aspartate that is coupled to a histidine. Numerous surface alpha helices are connected by characteristic QW-motifs (Q is glutamine and W is tryptophan) that tighten the protein structure, possibly for absorbing the reaction energy without structural damage.