Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

Significance Since the early days of neuroscience, the relative merit of structural vs. functional network accounts in explaining neurological deficits has been intensely debated. Using a large stroke cohort and a machine-learning approach, we show that visual memory and verbal memory deficits are better predicted by functional connectivity than by lesion location, and visual and motor deficits are better predicted by lesion location than functional connectivity. In addition, we show that disruption to a subset of cortical areas predicts general cognitive deficit (spanning multiple behavior domains). These results shed light on the complementary value of structural vs. functional accounts of stroke, and provide a physiological mechanism for general multidomain deficits seen after stroke. Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke.
Molecular mechanisms linking geranylgeranyl diphosphate synthase to cell survival and proliferation

Abstract Geranylgeranyl diphosphate is a 20-carbon isoprenoid phospholipid whose lipid moiety can be post-translationally incorporated into proteins to promote membrane association. The process of geranylgeranylation has been implicated in anti-proliferative effects of clinical agents that inhibit enzymes of the mevalonate pathway (i.e. statins and nitrogenous bisphosphonates) as well as experimental agents that deplete geranylgeranyl diphosphate. Inhibitors of geranylgeranyl diphosphate synthase are an attractive way to block geranylgeranylation because they possess a calcium-chelating substructure to allow localization to bone and take advantage of a unique position of the enzyme within the biosynthetic pathway. Here, we describe recent advances in geranylgeranyl diphosphate synthase expression and inhibitor development with a particular focus on the molecular mechanisms that link geranylgeranyl diphosphate to cell proliferation via geranylgeranylated small GTPases.
Innovation, Imitation, and Intellectual Property Rights

The debate between the North and the South about the enforcement of intellectual property rights in the South is examined within a dynamic general equilibrium framework in which the North innovates new products and the South imitates them. A welfare evaluation of a policy of tighter intellectual property rights is provided by decomposing a region's welfare change into four components: terms of trade, production composition, available product choice and intertemporal allocation of consumption spending. The paper provides a theoretical evaluation of each one of these components and their relative size. The analysis proceeds in stages. It begins with an exogenous rate of innovation in order to focus on the first two components. The last two components are added by endogenizing the rate of innovation. Finally, the paper considers the role of foreign direct investment.
Overexpression of eCLCA1 in Small Airways of Horses with Recurrent Airway Obstruction

The human hCLCA1 and murine mCLCA3 (chloride channels, calcium-activated) have recently been identified as promising therapeutic targets in asthma. Recurrent airway obstruction in horses is an important animal model of human asthma. Here, we have cloned and characterized the first equine CLCA family member, eCLCA1. The 913 amino acids eCLCA1 polypeptide forms a 120-kDa transmembrane glycoprotein that is processed to an 80-kDa protein in vivo. Three single nucleotide polymorphisms were detected in the eCLCA1 coding region in 14 horses, resulting in two amino acid changes (485H/R and 490V/L). However, no functional differences were recorded between the channel properties of the two variants in transfected HEK293 cells. The eCLCA1 protein was detected immunohistochemically in mucin-producing cells in the respiratory and intestinal tracts, cutaneous sweat glands, and renal mucous glands. Strong overexpression of eCLCA1 was observed in the airways of horses with recurrent airway obstruction using Northern blot hybridization, Western blotting, immunohistochemistry, and real-time quantitative RT-PCR. The results suggest that spontaneous or experimental recurrent airway obstruction in horses may serve as a model to study the role of CLCA homologs in chronic airway disease with overproduction of mucins.
Reconstructing the architecture of the ancestral amniote genome

MOTIVATION The ancestor of birds and mammals lived approximately 300 million years ago. Inferring its genome organization is key to understanding the differentiated evolution of these two lineages. However, detecting traces of its chromosomal organization in its extant descendants is difficult due to the accumulation of molecular evolution since birds and mammals lineages diverged. RESULTS We address several methodological issues for the detection and assembly of ancestral genomic features of ancient vertebrate genomes, which encompass adjacencies, contiguous segments, syntenies and double syntenies in the context of a whole genome duplication. Using generic, but stringent, methods for all these problems, some of them new, we analyze 15 vertebrate genomes, including 12 amniotes and 3 teleost fishes, and infer a high-resolution genome organization of the amniote ancestral genome, composed of 39 ancestral linkage groups at a resolution of 100 kb. We extensively discuss the validity and robustness of the method to variations of data and parameters. We introduce a support value for each of the groups, and show that 36 out of 39 have maximum support. CONCLUSIONS Single methodological principle cannot currently be used to infer the organization of the amniote ancestral genome, and we demonstrate that it is possible to gather several principles into a computational paleogenomics pipeline. This strategy offers a solid methodological base for the reconstruction of ancient vertebrate genomes. AVAILABILITY Source code, in C++ and Python, is available at http://www.cecm. sfu.ca/~cchauve/SUPP/AMNIOTE2010/ CONTACT cedric.chauve@sfu.ca SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Perianal Disease Predicts Changes in Crohn's Disease Phenotype—Results of a Population-Based Study of Inflammatory Bowel Disease Phenotype

BACKGROUND:The Montreal classification system of inflammatory bowel disease (IBD) provides a framework for describing disease phenotype.OBJECTIVE:We aimed to describe changes in IBD phenotype using the Montreal system and determine predictors of phenotype change in a Caucasian population-based cohort.METHODS:Ninety-two percent of people with IBD in Canterbury, New Zealand were recruited. Clinical notes were reviewed to confirm diagnosis and phenotype. Determinants of phenotype change were analyzed using multivariate analysis.RESULTS:A total of 1,420 (715 Crohn's disease [CD], 668 ulcerative colitis [UC]) patients with IBD were included. Median follow-up was 6.5 and 10.9 yr for CD and UC, respectively. Disease location remained stable in 91% of those with CD. Seventy-three percent of CD patients had inflammatory disease at diagnosis with the proportion of patients with complicated disease increasing over time. Progression to complicated disease was more rapid in those with small bowel than colonic disease location, (P < 0.001). Perianal disease was a significant predictor of change in CD behavior (HR 1.62, P < 0.001). Younger UC patients were more likely to have extensive disease at diagnosis than older patients (P < 0.001). CONCLUSIONS:Although CD location remains relatively stable, behavior changes over time. Perianal disease is a strong predictor of developing more complicated CD. Proctitis is most common in UC patients at diagnosis although younger patients are more likely than older patients to have extensive disease. The Montreal classification provides a clinically useful framework for both researchers and clinicians.
Protection Against Esophageal Cancer in Rodents With Lyophilized Berries: Potential Mechanisms

Abstract: For several years, our laboratory has been evaluating the ability of lyophilized (freeze-dried) black raspberries (Rubus occidentalis, BRBs), blackberries (R. fructicosus, BBs), and strawberries (Fragaria ananasia, STRWs) to inhibit carcinogen-induced cancer in the rodent esophagus. To assure "standardized" berry preparations for study, each berry type is of the same cultivar, picked at about the same degree of ripeness, washed and frozen within 2–4 h of the time of picking, and freeze-dried under conditions that preserve the components in the berries. Some of the known chemopreventive agents in berries include vitamins A, C, and E and folic acid; calcium and selenium; β-carotene, α-carotene, and lutein; polyphenols such as ellagic acid, ferulic acid, p-coumaric acid, quercetin, and several anthocyanins; and phytosterols such as β-sitosterol, stigmasterol, and kaempferol. In initial bioassays, freeze-dried STRW, BRB, and BB powders were mixed into AIN-76A synthetic diet at concentrations of 5% and 10% and fed to Fischer 344 rats before, during, and after treatment with the esophageal carcinogen N-nitrosomethylbenzylamine (NMBA). At 25 wk of the bioassay, all three berry types were found to inhibit the number of esophageal tumors (papillomas) in NMBA-treated animals by 24-56% relative to NMBA controls. This inhibition correlated with reductions in the formation of the NMBA-induced O6-methylguanine adduct in esophageal DNA, suggesting that the berries influenced the metabolism of NMBA leading to reduced DNA damage. Studies are ongoing to determine the mechanisms by which berries influence NMBA metabolism and DNA adduct formation. BRBs and STRWs were also tested in a postinitiation scheme and were found to inhibit NMBA-induced esophageal tumorigenesis by 31–64% when administered in the diet following treatment of the animals with NMBA. Berries, therefore, inhibit tumor promotion and progression events as well as tumor initiation. In vivo mechanistic studies with BRBs indicate that they reduce the growth rate of premalignant esophageal cells, in part, through down-regulation of cyclooxygenase-2 leading to reduced prostaglandin production and of inducible nitric oxide synthase leading to reduced nitrate/nitrite levels in the esophagus. Based upon the preclinical data on rodents, we have initiated prevention trials in humans to determine if berries might exhibit chemopreventive effects in the esophagus.
Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts.

BACKGROUND Medication toxic effects and drug-related problems can have profound medical and safety consequences for older adults and economically affect the health care system. The purpose of this initiative was to revise and update the Beers criteria for potentially inappropriate medication use in adults 65 years and older in the United States. METHODS This study used a modified Delphi method, a set of procedures and methods for formulating a group judgment for a subject matter in which precise information is lacking. The criteria reviewed covered 2 types of statements: (1) medications or medication classes that should generally be avoided in persons 65 years or older because they are either ineffective or they pose unnecessarily high risk for older persons and a safer alternative is available and (2) medications that should not be used in older persons known to have specific medical conditions. RESULTS This study identified 48 individual medications or classes of medications to avoid in older adults and their potential concerns and 20 diseases/conditions and medications to be avoided in older adults with these conditions. Of these potentially inappropriate drugs, 66 were considered by the panel to have adverse outcomes of high severity. CONCLUSIONS This study is an important update of previously established criteria that have been widely used and cited. The application of the Beers criteria and other tools for identifying potentially inappropriate medication use will continue to enable providers to plan interventions for decreasing both drug-related costs and overall costs and thus minimize drug-related problems.
Insulin and intracellular calcium responsiveness to glucagon-like peptide-1 and pituitary adenylate cyclase-activating peptide by dispersed adult porcine islet cells.

BACKGROUND There is a great need to learn more about porcine islet physiology because porcine islets represent a promising source of xenogeneic tissue for beta-cell replacement therapy in humans. METHODS We evaluated the effects of two important physiological regulators of insulin secretion, glucagon-like peptide-1 (GLP-1) and pituitary adenylate cyclase-activating peptide (PACAP), on insulin release and intracellular calcium ([Ca++]i) by adult porcine islet cells. RESULTS Exposure to GLP-1 and PACAP significantly potentiated glucose-induced insulin release and improved the sensitivity to glucose as a secretagogue. About 70% of cells stimulated with 20 mmol/L glucose alone showed an increase in [Ca++]i, whereas the addition of GLP-1 and PACAP induced [Ca++]i increases in 86% and 93% of cells, respectively. CONCLUSIONS The good insulin and [Ca++]i responsiveness of porcine islet cells to both GLP-1 and PACAP provides an additional proof of their suitability for transplantation.
Migration, Financial Constraints, and Entrepreneurship: Evidence from Mexico

There has been evidence on the entrepreneurial behavior of migrants in receiving countries or after they return to home countries, but little research on the entrepreneurship of left-behind persons when migrants are still abroad. Using data from the Mexican Family Life Survey, this paper examines the effects of ongoing migration on the entrepreneurship of left-behind family members. Striking evidence shows that migration stimulates the entrepreneurship of left-behind members through improved financial status. The preferred estimates indicate that having migrant family members increases an individual’s rate of participation in entrepreneurship by at least 50% relative to the mean. The analysis also demonstrates the differential migration effects and differential motives pertinent to becoming new entrepreneurs by gender. These findings have profound implications for the empowerment of women and how public policies such as microcredit may promote entrepreneurship through the relaxation of financial constraints.
Comparison of Performance of Three Different Types of Respiratory Protection Devices

Respiratory protection is offered to American workers in a variety of ways to guard against potential inhalation hazards. Two of the most common ways are elastomeric N95 respirators and N95 filtering-facepiece respirators. Some in the health care industry feel that surgical masks provide an acceptable level of protection in certain situations against particular hazards. This study compared the performance of these types of respiratory protection during a simulated workplace test that measured both filter penetration and face-seal leakage. A panel of 25 test subjects with varying face sizes tested 15 models of elastomeric N95 respirators, 15 models of N95 filtering-facepiece respirators, and 6 models of surgical masks. Simulated workplace testing was conducted using a TSI PORTACOUNT Plus model 8020, and consisted of a series of seven exercises. Six simulated workplace tests were performed with redonning of the respirator/mask occurring between each test. The results of these tests produced a simulated workplace protection factor (SWPF). The geometric mean (GM) and the 5th percentile values of the SWPFs were computed by category of respiratory protection using the six overall SWPF values. The level of protection provided by each of the three respiratory protection types was compared. The GM and 5th percentile SWPF values without fit testing were used for the comparison, as surgical masks were not intended to be fit tested. The GM values were 36 for elastomeric N95 respirators, 21 for N95 filtering-facepiece respirators, and 3 for surgical masks. An analysis of variance demonstrated a statistically significant difference between all three. Elastomeric N95 respirators had the highest 5th percentile SWPF of 7. N95 filtering-facepiece respirators and surgical masks had 5th percentile SWPFs of 3 and 1, respectively. A Fisher Exact Test revealed that the 5th percentile SWPFs for all three types of respiratory protection were statistically different. In addition, both qualitative (Bitrex and saccharin) and quantitative (N95-Companion) fit testing were performed on the N95 filtering- and elastomeric-facepiece respirators. It was found that passing a fit test generally improves the protection afforded the wearer. Passing the Bitrex fit test resulted in 5th percentile SWPFs of 11.1 and 7.9 for elastomeric and filtering-facepiece respirators, respectively. After passing the saccharin tests, the elastomeric respirators provided a 5th percentile of 11.7, and the filtering-facepiece respirators provided a 5th percentile of 11.0. The 5th percentiles after passing the N95-Companion were 13.0 for the elastomeric respirators and 20.5 for the filtering-facepiece respirators. The data supports fit testing as an essential element of a complete respiratory protection program.
Developmental changes in subthreshold pace‐maker currents in chick embryonic heart cells.

1. Small re‐aggregates of cells dissociated from the ventricles of 12‐or 17‐day‐old chick embryonic hearts have beating properties in low potassium tissue culture medium which differ from re‐aggregates prepared from 7‐day‐old hearts; 12‐day preparations either beat with a slower rate than comparable‐size 7‐day preparations or they are quiescent; 17‐day preparations usually do not beat. 2. A two‐micro‐electrode voltage‐clamp technique was used to analyse the membrane currents in these preparations in the ‐120 to ‐40 mV potential range. 3. A potassium ion membrane current was measured in 12‐day and 17‐day preparations which was qualitatively similar to the potassium ion current measured in 7‐day preparations (Clay & Shrier, 1981). It differed in that its amplitude was diminished in the ratio 1:0.2:0.03 over the 7‐, 12‐ and 17‐day sequence. Furthermore, its maximum time constant was 2 sec at both 12 and 17 days, as compared to 1 sec at 7 days, and its membrane potential range of activation was ‐80 to ‐70 mV at 12 and 17 days, as compared to ‐90 to ‐60 mV at 7 days. 4. The background current also changed with development, becoming less inward over the 7‐, 12‐ and 17‐day sequence. The voltage dependence of this change suggested that it was caused by a developmental decrease of the background sodium current. 5. The change in the background component is primarily responsible for the loss of automaticity over the 7‐, 12‐, and 17‐day sequence.
Diagnostic sensitivity of predicted F‐wave latency by age, height, and MCV

Objectives– The aim was to investigate whether minimum F‐wave latency (Fmin) predicted by a multiple regression equation utilizing age, height, and motor nerve conduction velocity (MCV) (3‐factor method) was clinically useful to detect Fmin abnormality in diabetic polyneuropathy (DP) and lumbosacral monoradiculopathy (RAD). Materials and methods– Thirty‐one DP patients (ulnar, tibial, and peroneal nerves) and 66 RAD patients (peroneal nerve) were investigated. The specificity and sensitivity of the 3‐factor method were compared to those obtained by a univariate (height) regression method (1‐factor method) and another multivariate (height and age) regression method (2‐factor method). Results– In general satisfactory specificity was obtained with all three methods. In DP patients the tibial 3‐factor method showed statistically lower sensitivity than the other two methods. There were no significant differences in diagnostic sensitivity among the three methods in two other nerves of the DP patients and the peroneal nerve of the RAD patients. Conclusion– The 3‐factor method was useful to estimate Fmin in normal subjects, but it was of little value in increasing the diagnostic sensitivity in DP and RAD patients. The 2‐factor method was more appropriate for detecting DP.
Would wider adoption of reproducible research be beneficial for empirical software engineering research?

Researchers have identiﬁed problems with the validity of software engineering research ﬁndings. In particular, it is often impossible to reproduce data analyses, due to lack of raw data, or sufﬁcient summary statistics, or undeﬁned analysis procedures. The aim of this paper is to raise awareness of the problems caused by unreproducible research in software engineering and to discuss the concept of reproducible research (RR) as a mechanism to address these problems. RR is the idea that the outcome of research is both a paper and its computational environment. We report some recent studies that have cast doubts on the reliability of research outcomes in software engineering. Then we discuss the use of RR as a means of addressing these problems. We discuss the use of RR in software engineering research and present the methodology we have used to adopt RR principles. We report a small working example of how to create reproducible research. We summarise advantages of and problems with adopting RR methods. We conclude that RR supports good scientiﬁc practice and would help to address some of the problems found in empirical software engineering research.
Welfare and Optimal Trading Frequency in Dynamic Double Auctions

This paper studies the welfare consequence of increasing trading speed in financial markets. We build and solve a dynamic trading model, in which traders receive private information of asset value over time and trade strategically with demand schedules in a sequence of double auctions. A stationary linear equilibrium and its efficiency properties are characterized explicitly in closed form. Infrequent trading (few double auctions per unit of time) leads to a larger market depth in each trading period, but frequent trading allows more immediate asset re-allocation after new information arrives. Under natural conditions, the socially optimal trading frequency coincides with information arrival frequency for scheduled information releases, but can (far) exceed information arrival frequency for stochastic information arrivals. If traders have heterogeneous trading speeds, fast traders prefer the highest feasible trading frequency, whereas slow traders tend to prefer a strictly lower frequency.
How Quickly is News Incorporated in Fiscal Forecasts

This paper tests for the existence of information rigidities in private sector budget-balance forecasts in a multi-country context for a sample of G7 countries between 1993 and 2012. We find evidence of information rigidities in fiscal forecast as private forecasters fail to adjust their budget balance forecasts quick enough in response not only to domestic news, but also to news from abroad.