Miracle-dz/UniFAR-FTUs huggingface dataset:
Arabidopsis thaliana Yellow Stripe1-Like4 and Yellow Stripe1-Like6 localize to internal cellular membranes and are involved in metal ion homeostasis

Several members of the Yellow Stripe1-Like (YSL) family of transporter proteins are able to transport metal-nicotianamine (NA) complexes. Substantial progress has been made in understanding the roles of the Arabidopsis YSLs that are most closely related to the founding member of the family, ZmYS1 (e.g., AtYSL1, AtYSL2 and AtYSL3), but there is little information concerning members of the other two well-conserved YSL clades. Here, we provide evidence that AtYSL4 and AtYSL6, which are the only genes in Arabidopsis belong to YSL Group II, are localized to vacuole membranes and to internal membranes resembling endoplasmic reticulum. Both single and double mutants for YSL4 and YSL6 were rigorously analyzed, and have surprisingly mild phenotypes, in spite of the strong and wide-ranging expression of YSL6. However, in the presence of toxic levels of Mn and Ni, plants with mutations in YSL4 and YSL6 and plants overexpressing GFP-tagged YSL6 showed growth defects, indicating a role for these transporters in heavy metal stress responses.
Voriconazole-Induced Inhibition of the Fungicidal Activity of Amphotericin B in Candida Strains with Reduced Susceptibility to Voriconazole: an Effect Not Predicted by the MIC Value Alone

ABSTRACT An antagonistic effect of voriconazole on the fungicidal activity of sequential doses of amphotericin B has previously been demonstrated in Candida albicans strains susceptible to voriconazole. Because treatment failure and the need to switch to other antifungals are expected to occur more often in infections that are caused by resistant strains, it was of interest to study whether the antagonistic effect was still seen in Candida strains with reduced susceptibility to voriconazole. With the hypothesis that antagonism will not occur in voriconazole-resistant strains, C. albicans strains with characterized mechanisms of resistance against voriconazole, as well as Candida glabrata and Candida krusei strains with differences in their degrees of susceptibility to voriconazole were exposed to voriconazole or amphotericin B alone, to both drugs simultaneously, or to voriconazole followed by amphotericin B in an in vitro kinetic model. Amphotericin B administered alone or simultaneously with voriconazole resulted in fungicidal activity. When amphotericin B was administered after voriconazole, its activity was reduced (median reduction, 61%; range, 9 to 94%). Levels of voriconazole-dependent inhibition of amphotericin B activity differed significantly among the strains but were not correlated with the MIC values (correlation coefficient, −0.19; P = 0.65). Inhibition was found in C. albicans strains with increases in CDR1 and CDR2 expression but not in the strain with an increase in MDR1 expression. In summary, decreased susceptibility to voriconazole does not abolish voriconazole-dependent inhibition of the fungicidal activity of amphotericin B in voriconazole-resistant Candida strains. The degree of interaction could not be predicted by the MIC value alone.
Distance and ratio effects in the flanker task are due to different mechanisms

When participants must respond to a relevant central target and ignore irrelevant flanking stimuli the flanking stimuli produce a compatibility effect, with increased response speed and accuracy on compatible as compared to incompatible trials. This flanker effect is larger when compatible trials are more frequent than incompatible trials (the ratio effect). A potential explanation of this ratio effect is that the occurrence of frequent incompatible trials causes the focus of spatial attention to be set narrower than when there are frequent compatible trials. The present investigation tests this hypothesis by comparing the flanker effect with near and far flankers. The hypothesis predicts that the flanker distance should modulate the ratio effect more when incompatible trials are frequent than when compatible trials are frequent. The results, however, show the opposite pattern: Distance effects are larger in conditions with frequent compatible trials. Moreover, the effect of distance but not the ratio effect was eliminated when flanker distance remained fixed across blocks of trials, and also when participants had to attend to flanker stimuli in a go–no-go task. These results suggest that the ratio effect does not result from an adjustment of the focus of spatial attention.
Priors Engaged in Long-Latency Responses to Mechanical Perturbations Suggest a Rapid Update in State Estimation

In every motor task, our brain must handle external forces acting on the body. For example, riding a bike on cobblestones or skating on irregular surface requires us to appropriately respond to external perturbations. In these situations, motor predictions cannot help anticipate the motion of the body induced by external factors, and direct use of delayed sensory feedback will tend to generate instability. Here, we show that to solve this problem the motor system uses a rapid sensory prediction to correct the estimated state of the limb. We used a postural task with mechanical perturbations to address whether sensory predictions were engaged in upper-limb corrective movements. Subjects altered their initial motor response in ∼60 ms, depending on the expected perturbation profile, suggesting the use of an internal model, or prior, in this corrective process. Further, we found trial-to-trial changes in corrective responses indicating a rapid update of these perturbation priors. We used a computational model based on Kalman filtering to show that the response modulation was compatible with a rapid correction of the estimated state engaged in the feedback response. Such a process may allow us to handle external disturbances encountered in virtually every physical activity, which is likely an important feature of skilled motor behaviour.
Lyme Arthritis: Current Concepts and a Change in Paradigm

Lyme disease is the most common arthropod-borne infection in the United States, affecting approximately 23,000 individuals bitten by Borrelia burgdorferi -infected Ixodes ticks in 2005 ([30][1]). Infection with B. burgdorferi results in a multisystem disorder, manifesting as early as a week
Molecular dynamics of a κB DNA element: base flipping via cross-strand intercalative stacking in a microsecond-scale simulation

The sequence-dependent structural variability and conformational dynamics of DNA play pivotal roles in many biological milieus, such as in the site-specific binding of transcription factors to target regulatory elements. To better understand DNA structure, function, and dynamics in general, and protein···DNA recognition in the ‘κB’ family of genetic regulatory elements in particular, we performed molecular dynamics simulations of a 20-bp DNA encompassing a cognate κB site recognized by the proto-oncogenic ‘c-Rel’ subfamily of NF-κB transcription factors. Simulations of the κB DNA in explicit water were extended to microsecond duration, providing a broad, atomically detailed glimpse into the structural and dynamical behavior of double helical DNA over many timescales. Of particular note, novel (and structurally plausible) conformations of DNA developed only at the long times sampled in this simulation—including a peculiar state arising at ≈0.7 μs and characterized by cross-strand intercalative stacking of nucleotides within a longitudinally sheared base pair, followed (at ≈1 μs) by spontaneous base flipping of a neighboring thymine within the A-rich duplex. Results and predictions from the microsecond-scale simulation include implications for a dynamical NF-κB recognition motif, and are amenable to testing and further exploration via specific experimental approaches that are suggested herein.
Future scaling of processor-memory interfaces

Continuous evolution in process technology brings energy-efficiency and reliability challenges, which are harder for memory system designs since chip multiprocessors demand high bandwidth and capacity, global wires improve slowly, and more cells are susceptible to hard and soft errors. Recently, there are proposals aiming at better main-memory energy efficiency by dividing a memory rank into subsets. We holistically assess the effectiveness of rank subsetting in the context of system-wide performance, energy-efficiency, and reliability perspectives. We identify the impact of rank subsetting on memory power and processor performance analytically, then verify the analyses by simulating a chip-multiprocessor system using multithreaded and consolidated workloads. We extend the design of Multicore DIMM, one proposal embodying rank subsetting, for high-reliability systems and show that compared with conventional chipkill approaches, it can lead to much higher system-level energy efficiency and performance at the cost of additional DRAM devices.
p21-activated Kinase 1 Phosphorylates and Regulates 14-3-3 Binding to GEF-H1, a Microtubule-localized Rho Exchange Factor*

GEF-H1 is a guanine nucleotide exchange factor for Rho whose activity is regulated through a cycle of microtubule binding and release. Here we identify a region in the carboxyl terminus of GEF-H1 that is important for suppression of its guanine nucleotide exchange activity by microtubules. This portion of the protein includes a coiled-coil motif, a proline-rich motif that may interact with Src homology 3 domain-containing proteins, and a potential binding site for 14-3-3 proteins. We identify GEF-H1 as a binding target and substrate for p21-activated kinase 1 (PAK1), an effector of Rac and Cdc42 GTPases, using an affinity-based screen and localize a PAK1 phosphorylation site to the inhibitory carboxylterminal region of GEF-H1. We show that phosphorylation of GEF-H1 at Ser885 by PAK1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules. Phosphorylation of GEF-H1 by PAK may be involved in regulation of GEF-H1 activity and may serve to coordinate Rho-, Rac-, and Cdc42-mediated signaling pathways.
Impact of Exercise in Community-Dwelling Older Adults

Background Concern has been expressed that preventive measures in older people might increase frailty by increasing survival without improving health. We investigated the impact of exercise on the probabilities of health improvement, deterioration and death in community-dwelling older people. Methods and Principal Findings In the Canadian Study of Health and Aging, health status was measured by a frailty index based on the number of health deficits. Exercise was classified as either high or low/no exercise, using a validated, self-administered questionnaire. Health status and survival were re-assessed at 5 years. Of 6297 eligible participants, 5555 had complete data. Across all grades of frailty, death rates for both men and women aged over 75 who exercised were similar to their peers aged 65 to 75 who did not exercise. In addition, while all those who exercised had a greater chance of improving their health status, the greatest benefits were in those who were more frail (e.g. improvement or stability was observed in 34% of high exercisers versus 26% of low/no exercisers for those with 2 deficits compared with 40% of high exercisers versus 22% of low/no exercisers for those with 9 deficits at baseline). Conclusions In community-dwelling older people, exercise attenuated the impact of age on mortality across all grades of frailty. Exercise conferred its greatest benefits to improvements in health status in those who were more frail at baseline. The net effect of exercise should therefore be to improve health status at the population level.
Inferring Semantic Similarity from Distributional Evidence: an Analogy-based Approach to Word Sense Disambiguation

The paper describes an analogy-based measure of word-sense proximity grounded on distributional evidence in typical contexts, and illustrates a computational system which makes use of this measure for purposes of lexical disambiguation. Experimental results show that wordsense analogy based on contexts of use compares favourably with classical word-sense similarity defined in terms of thesaural proximity.
Use of Segregation Indices, Townsend Index, and Air Toxics Data to Assess Lifetime Cancer Risk Disparities in Metropolitan Charleston, South Carolina, USA

Background: Studies have demonstrated a relationship between segregation and level of education, occupational opportunities, and risk behaviors, yet a paucity of research has elucidated the association between racial residential segregation, socioeconomic deprivation, and lifetime cancer risk. Objectives: We examined estimated lifetime cancer risk from air toxics by racial composition, segregation, and deprivation in census tracts in Metropolitan Charleston. Methods: Segregation indices were used to measure the distribution of groups of people from different races within neighborhoods. The Townsend Index was used to measure economic deprivation in the study area. Poisson multivariate regressions were applied to assess the association of lifetime cancer risk with segregation indices and Townsend Index along with several sociodemographic measures. Results: Lifetime cancer risk from all pollution sources was 28 persons/million for half of the census tracts in Metropolitan Charleston. Isolation Index and Townsend Index both showed significant correlation with lifetime cancer risk from different sources. This significance still holds after adjusting for other sociodemographic measures in a Poisson regression, and these two indices have stronger effect on lifetime cancer risk compared to the effects of sociodemographic measures. Conclusions: We found that material deprivation, measured by the Townsend Index and segregation measured by the Isolation index, introduced high impact on lifetime cancer risk by air toxics at the census tract level.
High-Level Synthesis of Pipelined Circuits from Modular Queue-Based Specifications

SUMMARY This paper describes a novel approach to highlevel synthesis of complex pipelined circuits, including pipelined circuits with feedback. This approach combines a high-level, modular specification language with an efficient implementation. In our system, the designer specifies the circuit as a set of independent modules connected by conceptually unbounded queues. Our synthesis algorithm automatically transforms this modular, asynchronous specification into a tightly coupled, fully synchronous implementation in synthesizable Verilog.
Hemodialysis and peritoneal dialysis are associated with similar outcomes for end-stage renal disease treatment in Canada.

BACKGROUND There were 35 265 patients receiving renal replacement therapy in Canada at the end of 2007 with 11.0% of patients on peritoneal dialysis (PD) and 48.9% on hemodialysis (HD) and a remaining 40.1% living with a functioning kidney transplant. There are no contemporary studies examining PD survival relative to HD in Canada. The objective was to compare survival outcomes for incident patients starting on PD as compared to HD in Canada. METHODS Using data from the Canadian Organ Replacement Register, the Cox proportional hazards (PH) model was employed to study survival outcomes for patients initiating PD as compared to HD in Canada from 1991 to 2004 with follow-up to 31 December 2007. Comparisons of outcomes were made between three successive calendar periods: 1991-95, 1996-2000 and 2001-04 with the relative risk of death of incident patients calculated using an intent-to-treat (ITT) analysis with proportional and non-PH models using a piecewise exponential survival model to compare adjusted mortality rates. RESULTS In the ITT analysis, overall survival for the entire study period favored PD in the first 18 months and HD after 36 months. However, for the 2001-04 cohort, survival favored PD for the first 2 years and thereafter PD and HD were similar. Among female patients > 65 years with diabetes, PD had a 27% higher mortality rate. CONCLUSIONS Overall, HD and PD are associated with similar outcomes for end-stage renal disease treatment in Canada.
Complexity and Approximation Results for the Balance Optimization Subset Selection Model for Causal Inference in Observational Studies

Matching is widely used in the estimation of treatment effects in observational studies. However, the matching paradigm may be too restrictive in many cases because exact matches often do not exist in the available data. One mechanism for overcoming this issue is to relax the requirement of exact matching on some or all of the covariates (attributes that may affect the response to treatment) to a requirement of balance on the covariate distributions for the treatment and control groups. The balance optimization subset selection (BOSS) model can be used to identify a control group featuring optimal covariate balance. This paper explores the relationship between the matching and BOSS models and shows how BOSS subsumes matching. Complexity and approximation results are presented for the resulting models. Computational results demonstrate some of the important trade-offs between matching and BOSS. Data, as supplemental material, are available at http://dx.doi. org/10.1287/ijoc.2013. 0583. There is a video associated with this paper. Click here to view the Video Overview. To save the file, right click and choose “Save Link As” from the menu.
A Genomewide Analysis of the Cinnamyl Alcohol Dehydrogenase Family in Sorghum [Sorghum bicolor (L.) Moench] Identifies SbCAD2 as the Brown midrib6 Gene

The content and composition of the plant cell wall polymer lignin affect plant fitness, carbon sequestration potential, and agro-industrial processing. These characteristics, are heavily influenced by the supply of hydroxycinnamyl alcohol precursors synthesized by the enzyme cinnamyl alcohol dehydrogenase (CAD). In angiosperms, CAD is encoded by a multigene family consisting of members thought to have distinct roles in different stages of plant development. Due to the high sequence similarity among CAD genes, it has been challenging to identify and study the role of the individual genes without a genome sequence. Analysis of the recently released sorghum genome revealed the existence of 14 CAD-like genes at seven genomic locations. Comparisons with maize and rice revealed subtle differences in gene number, arrangement, and expression patterns. Sorghum CAD2 is the predominant CAD involved in lignification based on the phylogenetic relationship with CADs from other species and genetic evidence showing that a set of three allelic brown midrib (bmr) lignin mutants contained mutations in this gene. The impact of the mutations on the structure of the protein was assessed using molecular modeling based on X-ray crystallography data of the closely related Arabidopsis CAD5. The modeling revealed unique changes in structure consistent with the observed phenotypes of the mutants.
Why Defeating Insurgencies Is Hard: The Effect of Intelligence in Counterinsurgency Operations - A Best-Case Scenario

In insurgency situations, the government-organized force is confronted by a small guerrilla group that is dispersed in the general population with no or a very small signature. Effective counterinsurgency operations require good intelligence. Absent intelligence, not only might the insurgents escape unharmed and continue their violent actions, but collateral damage caused to the general population from poor targeting may generate adverse response against the government and create popular support for the insurgents, which may result in higher recruitment to the insurgency. We model the dynamic relations among intelligence, collateral casualties in the population, attrition, recruitment to the insurgency, and reinforcement to the government force. Even under best-case assumptions, we show that the government cannot totally eradicate the insurgency by force. The best it can do is contain it at a certain fixed level.
Test-retest and alternate forms reliability of the assisting hand assessment.

OBJECTIVE The Assisting Hand Assessment (AHA) has earlier demonstrated excellent validity and rater reliability. This study aimed to evaluate test-retest reliability of the AHA and alternate forms reliability between Small kids vs School kids AHA and the 2 board games in School kids AHA. DESIGN Test-retest and alternate forms reliability was evaluated by repeated testing with 2 weeks interval. SUBJECTS Fifty-five children with unilateral cerebral palsy, age range 2 years and 3 months to 11 years and 2 months. METHODS Intraclass correlation coefficients and smallest detectable difference were calculated. Common item and common person linking plots using Rasch analysis and Bland-Altman plots were created. RESULTS Intraclass correlation coefficients for test-retest was 0.99. Alternate forms intraclass correlation coefficients were 0.99 between Small kids and School kids AHA and 0.98 between board games. Smallest detectable difference was 3.89 points (sum scores). Items in common item linking plots and persons in common person linking plots were within 95% confidence intervals, indicating equivalence across test forms. CONCLUSION The AHA has excellent test-retest and alternate forms reliability. A change of 4 points or more between test occasions represents a significant change. Different forms of the AHA give equivalent results.
Model Rating Form An Investigation of the Factor Structure and Convergent and Discriminant Validity of the Five-Factor

The Five-Factor Model Rating Form (FFMRF) is a one-page measure designed to provide an efficient assessment of the higher order domains of the Five Factor Model (FFM) as well as the more specific, lower order facets proposed by McCrae and Costa. Although previous research has suggested that the FFMRF’s assessment of the lower order facets converge reasonably with other FFM measures, the structural validity of the domain-level assessment has not yet been evaluated. The current study employed an exploratory structural equation modeling framework to investigate the fit of a five-factor solution within a combined sample of 757 participants. This was a novel analysis using a combined sample drawn from three previously published studies and was composed primarily of undergraduates but also included a smaller clinical subsample. Results indicated that the FFMRF is well accommodated within a five-factor solution. Furthermore, the FFMRF domain scores evinced large correlations with domain scores from the NEO Personality Inventory–Revised. The results suggest that the FFMRF might hold promise as a choice for those seeking a brief measure that provides a valid assessment of both the broad and specific traits of the FFM.