Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a Type 1 Peroxisomal Targeting Signal in a Viral Protein and Demonstration of Its Targeting to the Organelle

ABSTRACT Peroxisomes are unimembrane, respiratory organelles of the cell. Transport of cellular proteins to the peroxisomal matrix requires a type 1 peroxisomal targeting signal (PTS1) which essentially constitutes a tripeptide from the consensus sequence S/T/A/G/C/N-K/R/H-L/I/V/M/A/F/Y. Although PTS-containing proteins have been identified in eukaryotes, prokaryotes, and parasites, viral proteins with such signals have not been identified so far. We report here the first instance of a virus, the rotavirus, which causes infantile diarrhea worldwide, containing a functional C-terminal PTS1 in one of its proteins (VP4). Analysis of 153 rotavirus VP4-deduced amino acid sequences identified five groups of conserved C-terminal PTS1 tripeptide sequences (SKL, CKL, GKL, CRL, and CRI), of which CRL is represented in approximately 62% of the sequences. Infection of cells by a CRL-containing representative rotavirus (SA11 strain) and confocal immunofluorescence analysis revealed colocalization of VP4 with peroxisomal markers and morphological changes of peroxisomes. Further, transient cellular expression of green fluorescent protein (GFP)-fused VP4CRL resulted in transport of VP4 to peroxisomes, whereas the chimera lacking the PTS1 signal, GFP-VP4ΔCRL, resulted in diffuse cytoplasmic staining, suggesting a CRL-dependent targeting of the protein. The present study therefore demonstrates hitherto unreported organelle involvement, specifically of the peroxisomes, in rotaviral infections as demonstrated by using the SA11 strain of rotavirus and opens a new line of investigation toward understanding viral pathogenesis and disease mechanisms.
Abandonment of Antiretroviral Therapy among HIV-Positive Patients Attended at the Reference Center for HIV/AIDS in Vitória, Brazil

This study evaluates the risk factors for the abandonment of antiretroviral therapy (ART) among patients receiving care in an AIDS clinic in Vitória, Brazil. We conducted a case–control study of patients with AIDS attending a reference center for sexually transmitted disease (STD)/AIDS. A total of 62 patients, who abandoned therapy in 2008, and 188 HIV-infected patients answered an interview including demographic, social, and clinical characteristics. Risk factors associated with abandon in univariate analysis were entered into logistic regression models. A total of 250 patients were included in the study. Groups were similar regarding age, gender, and monthly income. In the final multivariate model, illicit drug use (adjusted odds ratio [AOR], 2.3; 95% confidence interval [CI], 1.03-5.07), previous abandon of medication (AOR 38.6; 95% CI 10.49-142.25), last CD4 count <200 cells/mm3 (AOR 1.5; 95% CI 1.03-2.10), and viral load higher than 1000 copies/mL (AOR 2.0 (95% CI 1.34-3.09) were independent predictors of abandonment of ART. In addition to the clinical indicators, behavioral factors remained important throughout the multivariate analysis in our study.
Practice‐related functional activation changes in a working memory task

The effects of practice on the functional anatomy of a visuospatial working memory (VSWM) task were studied using functional Magnetic Resonance Imaging (fMRI). Functional imaging was conducted as subjects completed a moderate (Experiment 1) or extensive (Experiment 2) amount of practice on a delayed‐match‐to‐sample task. While improvement in task performance was seen with practice, the task's dependence upon VSWM did not change. Activations in frontal (inferior, middle, and precentral gyri and superior frontal sulcus), parietal (intra‐parietal sulcus, inferior parietal lobule, and precuneus) and cingulate (anterior and posterior) regions were observed as were bilateral insular and occipital activations. With the exception of the posterior cingulate, practice produced activation decreases in these regions, thus providing little evidence for a re‐organization of the functional neuroanatomy. Fewer regions passing statistical criteria were observed at the end of practice relative to early in practice. Regions that were lost were mostly posterior (occipital and precuneus) but also included the left middle frontal gyrus, left precentral gyrus, and right insula suggesting that a more precise VSWM functional map can be observed once processes specific to encountering a novel task are removed. Little further activation changes were observed after extensive practice. These results suggest, minimally, that practice effects should be considered so as to avoid incorrectly attributing functional activation to a cognitive process of interest. Further, these data show that the dynamics of functional change can be tracked while a task is being learned and as an important cognitive process becomes more skilled. Microsc. Res. Tech. 51:54–63, 2000. © 2000 Wiley‐Liss, Inc.
Innovation in recessions : effects on firm performance

This thesis investigates how a firm’s innovation activities affect performance outcomes during recessions. The thesis uses a heteroskedasticity-robust multiple regression model to analyse a large sample of Norwegian firms with innovation data from 2006-2010 and performance data from 2008-2012. Innovation activities both prior to and during the recession and its performance effects were investigated, and provided very surprising results. Contrary to the positive innovation-performance link suggested by existing literature, the results show that innovators consistently underperform non-innovators on profitability measures. The more a firm innovates prior to or during the recession, the greater the underperformance compared to non-innovators. Type of innovation was also found to affect firm performance, though largely exhibiting the same negative performance link. This thesis also includes an attempt to explain this negative innovation-performance link using existing innovation and business cycle theory. In conclusion, this thesis provides an important limitation to the seeming societal and academic perception that innovation is always positive, and provides fertile ground for future research in the fields of strategy, business cycles, and innovation.
Sustainability management, strategy and reform in local government

ABSTRACT As discussions about sustainability management in local government evolve, public managers lack clear frameworks prescribing how sustainability should be integrated into the practice of management. Studies in public administration tend to emphasize the policy tools managers use for sustainable outcomes, rather than the management processes that can enhance sustainability through organizational change. Drawing on Laszlo and Zhexembayeva’s definition of ‘embedded sustainability,’ this essay suggests local government managers should focus on integrating sustainability into strategic planning processes in order to advance sustainability as a reform in local government. Public management scholars and local government professionals are urged to develop partnerships to support evidence-based decision-making in local government in order to investigate propositions about sustainability management.
Renal involvement in children with vesicoureteral reflux: Are prenatal detection and surgical approaches preventive?

Objective. Surgical correction of vesicoureteral reflux (VUR) and prolonged administration of antibiotics seem to lead to similar renal outcomes. However, it is not known whether prenatal recognition and the position of VUR modify the outcome in different ways. The purpose of this study was to investigate the effects of prenatal detection and different treatment methods on the outcome of unilateral refluxing renal units. Patients and methods. This retrospective study enrolled 119 children (mean age 2.8±3.5 years) with primary VUR. Kidney growth and renal function were measured with ultrasound and scintigraphy, respectively. To compare the ultrasound readings among patients of different ages the comparative-length index or index was calculated, as a percentage of the ratio of unilateral and the sum of bilateral renal length. Results. In unilateral refluxing renal units there was a reduction in both index and function, whereas not-refluxing was increased. In the follow-up, unilateral refluxing renal units had a worse index, whereas not-refluxing was better. Unexpectedly, surgical therapy of the left-refluxing renal unit led to a reduction in the index, whereas its function always stayed low in diagnosis but stable. The outcome of severely refluxing renal units was similar after both interventions. Prenatal and postnatal diagnosis did not seem to modify the renal result. Conclusions. Surgery showed similar renal outcomes to medical treatment. A kidney growth defect from high-grade VUR was detected in the diagnosis. Therefore, a congenitally damaged kidney does not ameliorate after each treatment. Finally, prenatal detection of VUR does not seem to modify the outcome of the kidney significantly.
Mutations in Replicative Stress Response Pathways Are Associated with S Phase-specific Defects in Nucleotide Excision Repair*

Nucleotide excision repair (NER) is a highly conserved pathway that removes helix-distorting DNA lesions induced by a plethora of mutagens, including UV light. Our laboratory previously demonstrated that human cells deficient in either ATM and Rad3-related (ATR) kinase or translesion DNA polymerase η (i.e. key proteins that promote the completion of DNA replication in response to UV-induced replicative stress) are characterized by profound inhibition of NER exclusively during S phase. Toward elucidating the mechanistic basis of this phenomenon, we developed a novel assay to quantify NER kinetics as a function of cell cycle in the model organism Saccharomyces cerevisiae. Using this assay, we demonstrate that in yeast, deficiency of the ATR homologue Mec1 or of any among several other proteins involved in the cellular response to replicative stress significantly abrogates NER uniquely during S phase. Moreover, initiation of DNA replication is required for manifestation of this defect, and S phase NER proficiency is correlated with the capacity of individual mutants to respond to replicative stress. Importantly, we demonstrate that partial depletion of Rfa1 recapitulates defective S phase-specific NER in wild type yeast; moreover, ectopic RPA1–3 overexpression rescues such deficiency in either ATR- or polymerase η-deficient human cells. Our results strongly suggest that reduction of NER capacity during periods of enhanced replicative stress, ostensibly caused by inordinate sequestration of RPA at stalled DNA replication forks, represents a conserved feature of the multifaceted eukaryotic DNA damage response.
Multiple imputation in the presence of high-dimensional data

Missing data are frequently encountered in biomedical, epidemiologic and social research. It is well known that a naive analysis without adequate handling of missing data may lead to bias and/or loss of efficiency. Partly due to its ease of use, multiple imputation has become increasingly popular in practice for handling missing data. However, it is unclear what is the best strategy to conduct multiple imputation in the presence of high-dimensional data. To answer this question, we investigate several approaches of using regularized regression and Bayesian lasso regression to impute missing values in the presence of high-dimensional data. We compare the performance of these methods through numerical studies, in which we also evaluate the impact of the dimension of the data, the size of the true active set for imputation, and the strength of correlation. Our numerical studies show that in the presence of high-dimensional data the standard multiple imputation approach performs poorly and the imputation approach using Bayesian lasso regression achieves, in most cases, better performance than the other imputation methods including the standard imputation approach using the correctly specified imputation model. Our results suggest that Bayesian lasso regression and its extensions are better suited for multiple imputation in the presence of high-dimensional data than the other regression methods.
Modulations of Temporal Perception by Consciously and Unconsciously Perceived Stimuli

Temporal processing is of fundamental importance to the understanding of orders and durations of events in daily life. While recent research found that the perception of event durations is modulated by the visibility of perceived stimuli, it is still not known whether consciously and unconsciously perceived stimuli modulate temporal perception of a following stimulus in a similar vein. We investigated this using a temporal-comparison task that requires duration judgments of a standard stimulus and a probe. A prime prior to the standard stimulus reduced the subjective duration of the standard stimulus when observers were aware of the prime, and this effect changed with the temporal distance between the prime and standard. In contrast, a prime increased the subjective duration of the following standard stimulus when observers were unaware of the presence of the prime. Our findings indicate that a temporally neighbouring transient stimulus produces essentially different effects on temporal perception of following events when it is consciously and unconsciously perceived, leading to compression and expansion of subjective time, respectively.
Nitrous oxide and methane emissions from cryptogamic covers

Cryptogamic covers, which comprise some of the oldest forms of terrestrial life on Earth (Lenton & Huntingford, ), have recently been found to fix large amounts of nitrogen and carbon dioxide from the atmosphere (Elbert et al., ). Here we show that they are also greenhouse gas sources with large nitrous oxide (N2O) and small methane (CH4) emissions. Whilst N2O emission rates varied with temperature, humidity, and N deposition, an almost constant ratio with respect to respiratory CO2 emissions was observed for numerous lichens and bryophytes. We employed this ratio together with respiration data to calculate global and regional N2O emissions. If our laboratory measurements are typical for lichens and bryophytes living on ground and plant surfaces and scaled on a global basis, we estimate a N2O source strength of 0.32–0.59 Tg year−1 for the global N2O emissions from cryptogamic covers. Thus, our emission estimate might account for 4–9% of the global N2O budget from natural terrestrial sources. In a wide range of arid and forested regions, cryptogamic covers appear to be the dominant source of N2O. We suggest that greenhouse gas emissions associated with this source might increase in the course of global change due to higher temperatures and enhanced nitrogen deposition.
Incorporating risk in a positive mathematical programming framework: a dual approach

In this study we develop a new methodological proposal to incorporate risk into a farm-level positive mathematical programming (PMP) model. We estimate simultaneously the farm nonlinear cost function and a farmer-specific coefficient of absolute risk aversion as well as the resource shadow prices. The model is applied to a sample of representative arable crop farms from the Emilia-Romagna region in Italy. The estimation results confirm the calibration ability of the model and reveal the values of the individual risk aversion coefficients. We use the model to simulate different scenarios of crop price volatility, in order to explore the potential risk management role of an agri-environmental scheme.
Factors affecting mirror behaviour in western lowland gorillas,Gorilla gorilla


To date, it has proven difficult to demonstrate mirror self-recognition in gorillas. However, gorillas display pronounced gaze aversion that may prevent them from spending a sufficient amount of time exploring their mirror images to understand that they are the source of their reflections. It has also been suggested that the presence of observers may inhibit gorillas from engaging in mark-directed behaviours. To overcome the problem of gaze aversion, we used an angled-mirror apparatus developed by Anderson & Roeder (1989, Primates, 30, 581-587) that prevented two gorillas at the National Zoological Park from making direct eye contact with their reflections. To counter the observer inhibition hypothesis, we conducted mark tests on these animals using video cameras. Despite addressing these and other concerns in a series of four experiments, the gorillas did not show compelling evidence of self-recognition, even after over 4 years of mirror exposure. Copyright 1999 The Association for the Study of Animal Behaviour.
Disruption of MAP kinase activation and nuclear factor binding to the IL‐12 p40 promoter in HIV‐infected myeloid cells

Progressive immunodeficiency in HIV infection is paralleled by a decrease in IL‐12 production, a cytokine crucial for cellular immune function. Here we examine the molecular mechanisms by which HIV infection suppresses IL‐12 p40 expression. HIV infection of THP‐1 myeloid cells resulted in decreased LPS‐induced nuclear factor binding to the NF‐κB, AP‐1, and Sp1 sites of the IL‐12 p40 promoter. By site‐directed mutagenesis we determined that each of these sites was necessary for transcriptional activation of the IL‐12 p40 promoter. Binding of NF‐κB p50, c‐Rel, p65, Sp1, Sp3, c‐Fos, and c‐Jun proteins to their cognate nuclear factor binding sites was somewhat impaired by HV infection, although a role for other as yet unidentified factors cannot be dismissed. The cellular levels of these transcription factors were unaffected by HIV infection, with the exception of a decrease in expression of NF‐κB p65, consistent with the observed decrease in its binding to the IL‐12 p40 promoter following HIV infection. Analysis of regulation of upstream LPS‐induced MAP kinases demonstrated impaired phosphorylation of JNK and p38 MAPK, and suppressed phosphorylation and degradation of IκBα following HIV infection. These results suggest that alterations in nuclear factor binding to numerous sites in the IL‐12 p40 promoter, together may contribute to the suppression in IL‐12 p40 transcription previously reported. These effects on nuclear factor binding may be a direct effect of HIV infection on the IL‐12 p40 promoter, or may occur indirectly as a consequence of altered MAP kinase activation.
Juvenile rheumatoid arthritis in a Canadian First Nations (aboriginal) population: onset subtypes and HLA associations.

OBJECTIVE To determine onset subtypes and HLA associations of juvenile rheumatoid arthritis (JRA) in a First Nations (aboriginal) population; to determine whether population frequencies of HLA antigens may explain the distribution of subtypes of JRA in this population. METHODS All patients were children from Manitoba and Northwestern Ontario seen in a single pediatric rheumatology clinic between 1975 and 1996. Patients were identified from a clinic registry. Controls were adults of Algonkian Cree and Ojibway heritage. Class I and II major histocompatibility (HLA) typing was performed for First Nations patients and controls. RESULTS There were a total of 74 First Nations patients with JRA. The relative frequency of rheumatoid factor (RF) positive polyarticular JRA was higher and that of pauciarticular JRA was lower in First Nations compared with Caucasian patients (42 versus 3% and 22 versus 58%, respectively; p = 0.00000). HLA-DRB1*04 (63%), 08 (43%), and 1402 (25%) were the most common DRB1 antigens among controls. The main subtypes of DRB1*04 were 0404 (33% of controls) and 0407 (23%). HLA typing was performed for 39 First Nations patients; 27 were Cree or Ojibway, 4 were from other tribes, and 8 were part First Nations. Among Cree and Ojibway, 59% of controls and 63% of patients with RF positive polyarticular JRA (n = 16) had HLA-DRB1 antigens bearing the rheumatoid arthritis (RA) shared epitope (OR 1.16, 95% CI: 0.38, 3.48). The OR for polyarticular RF positive JRA in those with DRB1*0802 and 0901 were 0.15, 95% CI: 0.02; and 1.24 and 5.83, 95% CI: 1.58, 28.38, respectively. CONCLUSION There was a high frequency of the RA shared epitope represented by both HLA-DRB1*0404 and 1402 in this Algonkian population. This high frequency may explain the high frequency of RF positive polyarticular JRA. DRB1*0802 may be protective, whereas DRB1*0901 may increase the risk for this subtype of JRA.
The health risks of occupational stress in islamic industrial workers during the Ramadan fasting period.

During Ramadan, Moslems are required strictly to avoid fluids and nourishment from dawn to sunset. Heat stress during such abstinence represents a substantial health hazard. In the Federal Republic of Germany (FRG) where numerous Moslems, particularly of Turkish origin, perform heat work and other heavy labour, we observed moderate to severe health disturbances in such labourers during Ramadan, e.g.: tachycardia, severe headaches, dizziness, nausea, vomiting and circulatory collapse. The severe dehydration of these workers was demonstrated by substantial increases in their hematocrit, serum protein, urea, creatinine, uric acid and electrolyte imbalance. Because of the evidence of the substantial health hazard to Islamic workers in such situations, we have strongly urged employers to refrain from assigning Islamic workers to heat work or heavy daytime work during Ramadan; we have therefore limited systematic studies of health problems during Ramadan to persons performing only moderate work. Even under these conditions signs of dehydration were found in the 32 labourers monitored. Some of these labourers also had to interrupt their observance of Ramadan due to health problems, e.g.: acute gout due to serum uric acid increase, or circulatory insufficiency. In light of the observed potentially harmful pathophysiological effects, the danger of dehydration of Islamic workers due to heat work during Ramadan should be taken very seriously. (ABSTRACT TRUNCATED AT 250 WORDS)
Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy.

PURPOSE To assess the biologic activity of celecoxib, a selective cyclooxygenase-2 inhibitor, in men with recurrent prostate cancer using change in prostate-specific antigen (PSA) doubling time (PSADT) as the primary outcome variable. PATIENTS AND METHODS Participants had histologically confirmed prostate cancer, no recent hormone therapy, rising serum PSA after radical prostatectomy and/or radiation therapy, and no radiographic evidence of metastases. Patients were randomly assigned to celecoxib (400 mg by mouth twice daily) or placebo. Treatment continued until disease progression or until adverse effects stopped treatment. A positive outcome was defined as post-treatment PSADT of more than 200% baseline PSADT with no new metastases. RESULTS The study was terminated early after information about the cardiovascular safety of celecoxib prompted review of ongoing clinical studies. Before discontinuation of the study, 78 men were assigned randomly to either celecoxib or placebo. Eight (20%) of 40 men in the placebo group and 15 (40%) of 38 men in the celecoxib group had post-treatment PSADT of more than 200% of baseline PSADT with no new metastases (P = .08). Mean PSA velocity increased by 3.0% for the placebo group and decreased by 3.4% for the celecoxib group (P = .02). CONCLUSION Although the primary efficacy objective was not met, this study provides some evidence for biologic activity of celecoxib in prostate cancer. Compared with placebo, celecoxib significantly decreased mean PSA velocity and tended to increase the proportion of men who doubled their PSADT.