Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex Parameter Landscape for a Complex Neuron Model

The electrical activity of a neuron is strongly dependent on the ionic channels present in its membrane. Modifying the maximal conductances from these channels can have a dramatic impact on neuron behavior. But the effect of such modifications can also be cancelled out by compensatory mechanisms among different channels. We used an evolution strategy with a fitness function based on phase-plane analysis to obtain 20 very different computational models of the cerebellar Purkinje cell. All these models produced very similar outputs to current injections, including tiny details of the complex firing pattern. These models were not completely isolated in the parameter space, but neither did they belong to a large continuum of good models that would exist if weak compensations between channels were sufficient. The parameter landscape of good models can best be described as a set of loosely connected hyperplanes. Our method is efficient in finding good models in this complex landscape. Unraveling the landscape is an important step towards the understanding of functional homeostasis of neurons.
mirDIP 4.1—integrative database of human microRNA target predictions

Abstract MicroRNAs are important regulators of gene expression, achieved by binding to the gene to be regulated. Even with modern high-throughput technologies, it is laborious and expensive to detect all possible microRNA targets. For this reason, several computational microRNA–target prediction tools have been developed, each with its own strengths and limitations. Integration of different tools has been a successful approach to minimize the shortcomings of individual databases. Here, we present mirDIP v4.1, providing nearly 152 million human microRNA–target predictions, which were collected across 30 different resources. We also introduce an integrative score, which was statistically inferred from the obtained predictions, and was assigned to each unique microRNA–target interaction to provide a unified measure of confidence. We demonstrate that integrating predictions across multiple resources does not cumulate prediction bias toward biological processes or pathways. mirDIP v4.1 is freely available at http://ophid.utoronto. ca/mirDIP/.
Climate Predictions for Ludhiana District of Indian Punjab under RCP 4.5 and RCP 8.5

Climate change poses significant threats to global food security and water resources. In a present study, a Global Climate Model HAD GEM2-ES under RCPs 4.5 and 8.5 was used for climate prediction study. The study spanned 46 years of baseline (1970-2015) as well as two future periods’ mid-century (MC) (2020-2050) and end century EC (2060-2090). The results showed that the temperature would increase by 1.56°C and rainfall would decrease by 98 mm in MC (2020-2050); and 3.11°C and 90 mm in EC (2060-2090), respectively under RCP 4.5. In RCP 8.5 the increase in temperature and rainfall was 2.75°C and 153 mm, respectively in MC and the corresponding values in EC was 5.46°C and 251 mm, respectively.
Recombinant LPG3 Stimulates IFN-Γ and TNF-A Secretion by Human NK Cells

Background: Natural killer (NK) cells play an important role in early stages of innate immune responses against viral and tumoral attacks. Activation of NK cells by leishmaniasis results in secretion of cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, which enhances the phagocytosis and clearance of parasite. Lipophosphoglycan 3 (LPG3), the Leishmania homologous with GRP94 (glucose regulated protein 94), a member of HSP90 family, contributes to LPG assembly as the most abundant macromolecule on the surface of Leishmania promastigotes. Methods: We purified NK cells from healthy individuals (n=10) using magnetic-activated cell sorting (MACS) technology. Purified NK cells were co-incubated with different concentrations of recombinant LPG3 (rLPG3), and its N-terminal (NT) and C-terminal (CT) fragments. Finally, the production of IFN-γ and TNF-α by NK cells were measured by ELISA. Results: Recombinant LPG3 but not its fragments (CT and NT), can significantly enhance the production of TNF-α by NK cells (P<0.05). Moreover, rLPG3, CT, and NT fragments were markedly stimulated the secretion of IFN-γ by NK cells (P<0.001). Conclusion: The Leishmania LPG3 antigen can effectively activate NK cells, in vitro. Leishmania LPG3 participates in the innate immunity against leishmaniasis and thereby improves the effective parasite destruction. However, its efficiency should be tested in vivo.
Pathogenesis of Chytridiomycosis, a Cause of Catastrophic Amphibian Declines

Croaking Frogs The global amphibian decline has been attributed, among other causes, to an amphibian skin disease chytridiomycosis caused by the fungus Batrachochytrium dendrobatidis. However, how this pathogen causes mortality has been unclear. Voyles et al. (p. 582) show that this superficial skin infection may lead to cardiac failure owing to changes caused by lowered ion transport through the skin and consequent electrolyte reduction in the blood. A fungal disease that is associated with frog mortality causes changes in electrolyte transport across the skin. The pathogen Batrachochytrium dendrobatidis (Bd), which causes the skin disease chytridiomycosis, is one of the few highly virulent fungi in vertebrates and has been implicated in worldwide amphibian declines. However, the mechanism by which Bd causes death has not been determined. We show that Bd infection is associated with pathophysiological changes that lead to mortality in green tree frogs (Litoria caerulea). In diseased individuals, electrolyte transport across the epidermis was inhibited by >50%, plasma sodium and potassium concentrations were respectively reduced by ~20% and ~50%, and asystolic cardiac arrest resulted in death. Because the skin is critical in maintaining amphibian homeostasis, disruption to cutaneous function may be the mechanism by which Bd produces morbidity and mortality across a wide range of phylogenetically distant amphibian taxa.
Whole-Genome Mapping of Agronomic and Metabolic Traits to Identify Novel Quantitative Trait Loci in Bread Wheat Grown in a Water-Limited Environment1[W][OA]

Comparison of the agronomic and metabolic trait variation between drought-sensitive and drought-tolerant wheat crosses uncovers novel correlations between agronomic traits and the levels of certain metabolites as well as important regions on the wheat genome that require further investigation. Drought is a major environmental constraint responsible for grain yield losses of bread wheat (Triticum aestivum) in many parts of the world. Progress in breeding to improve complex multigene traits, such as drought stress tolerance, has been limited by high sensitivity to environmental factors, low trait heritability, and the complexity and size of the hexaploid wheat genome. In order to obtain further insight into genetic factors that affect yield under drought, we measured the abundance of 205 metabolites in flag leaf tissue sampled from plants of 179 cv Excalibur/Kukri F1-derived doubled haploid lines of wheat grown in a field experiment that experienced terminal drought stress. Additionally, data on 29 agronomic traits that had been assessed in the same field experiment were used. A linear mixed model was used to partition and account for nongenetic and genetic sources of variation, and quantitative trait locus analysis was used to estimate the genomic positions and effects of individual quantitative trait loci. Comparison of the agronomic and metabolic trait variation uncovered novel correlations between some agronomic traits and the levels of certain primary metabolites, including metabolites with either positive or negative associations with plant maturity-related or grain yield-related traits. Our analyses demonstrate that specific regions of the wheat genome that affect agronomic traits also have distinct effects on specific combinations of metabolites. This approach proved valuable for identifying novel biomarkers for the performance of wheat under drought and could facilitate the identification of candidate genes involved in drought-related responses in bread wheat.
Intervention Effects on Adolescent Physical Activity in the Multicomponent SPACE Study: A Cluster Randomized Controlled Trial

Background Multicomponent school-based interventions have the potential to reduce the age-related decline in adolescents' physical activity (PA), yet there is not consistent evidence to guide non-curricular and school environment interventions. The aim of this study was to assess the effectiveness of a multicomponent environmental school-based intervention, designed to reduce the age-related decline in PA among adolescents. Methods A cluster randomized controlled trial was conducted with 7 intervention and 7 control schools. Baseline measurements were carried out in spring 2010 with 2 years of follow-up. A total of 1,348 students (11–13 years, in grade 5 and 6) enrolled in the study at baseline. The 14 schools included in the study were located in the Region of Southern Denmark. The intervention consisted of organizational and physical changes in the school environment with a total of 11 intervention components. The primary outcome measure was overall PA (cpm, counts per minute) and was supported by analyses of time spent in MVPA, and time spent sedentary. Furthermore, a secondary outcome measure was PA in school time and during recess. PA was measured using accelerometer (Actigraph GT3X). Results A total of 797 students completed the trial and had valid accelerometer data. No significant difference was found for overall PA with an adjusted difference of −19.1 cpm (95% CI: −93, 53) or for school time activity with an adjusted difference of 6 cpm (95% CI: −73, 85). A sensitivity analysis revealed a positive significant intervention effect of PA in recess with an adjusted difference of 95 cpm. Conclusions No evidence was found of the overall effect of a non-curricular multicomponent school-based intervention on PA among Danish adolescents. The intervention was positively associated with PA during school time and recess, however, with small estimates. Lack of effect on overall PA could be due to both program theory and different degrees of implementation. Trial Registration www.Controlled-Trials.com ISRCTN79122411
Can self-destructive killers be classified so easily?

Abstract Lankford makes many useful points regarding the myths and shibboleths underlying our understanding of self-destructive killers and suicide bombers. He has collated an impressive data set on such offenders. However, his classification scheme is not built on sufficient evidence to support his proposed discrete categories of conventional, coerced, escapist, and indirect suicide terrorists. It would be straightforward to analyse the data, but it is unlikely that the resulting model would reflect that anticipated.
Leveraging delay slack in flip-flop and buffer insertion for power reduction

We show that the delay slack can be distributed optimally between flip-flops to reduce power in a pipelined interconnect, and such power reduction can be achieved by simultaneous flip-flop and buffer insertion satisfying latency and delay constraints specified at sinks. We develop a dynamic programming algorithm with effective pruning rules and pseudo polynomial time complexity with respect to the decimation and the length of a net. Experiments using a cluster of interconnect in a leading industrial high-performance design show that there exists plenty of useful slack for power reduction. Without jeopardizing the delay specification, as much as 17% of power can be saved for this cluster of interconnects.
Developing a framework for risk-based surveillance of tuberculosis in cattle: a case study of its application in Scotland – ERRATUM

REFERENCE 1. Bessell PR, Orton R, O’Hare A, Mellor DJ, Logue D and Kao RR. Developing a framework for risk-based surveillance of tuberculosis in cattle : a case study of its application in Scotland. Epidemiology and Infection. Published by Cambridge University Press, 26 April 2012. doi : 10.1017/S0950268812000635. Epidemiol. Infect. (2013), 141, 324. f Cambridge University Press 2012 doi:10.1017/S0950268812001288
Asymptomatic carotid stenosis: identifying patients at high enough risk to warrant endarterectomy or stenting.

See related article, p 702. In this issue of Stroke , Hirt1 reports that substantial progression of carotid stenosis predicted ipsilateral stroke or transient ischemic attack among patients randomized to medical therapy in the Asymptomatic Carotid Surgery Trial (ACST). 2 This might be regarded as another justification to perform carotid endarterectomy (CEA) or stenting (CAS) in some patients with asymptomatic carotid stenosis (ACS), and Hirt’s article may help in the selection for invasive treatment of those ACS patients at highest risk of having a stroke. However, the proportion of patients with progression by ≥2 grades (which carried a high enough risk to identify patients who might benefit from invasive intervention) was small. Among the 1469 patients in the study, there were events in only 50 (3.4%), among the 117 (8%) of patients with progression by ≥2 grades of stenosis. It must also be understood that the ACST trial was conducted before the widespread implementation of intensive medical therapy that has diminished the stroke risk picture markedly. The current situation in the United States is deplorable: as many as 95% of CEA and CAS procedures are being performed in patients with asymptomatic stenoses,3 and most of these patients are more likely to be harmed than helped by these interventions. This is being justified on the basis of historical stroke risks in the ACST2 and the Asymptomatic Carotid Surgery Trial.4 These risks …
A Phase 2a Study of Topical Perillyl Alcohol Cream for Chemoprevention of Skin Cancer

The chemopreventive and antitumor properties of perillyl alcohol (POH) that were studied preclinically indicate that topical POH inhibits both UVB-induced murine skin carcinogenesis (squamous cell tumor models) and 7,12-dimethylbenz(a)anthracene–induced murine melanoma (transgenic models involving tyrosinase-driven Ras). A previous phase 1 clinical trial in participants with normal-appearing skin showed that topical POH cream was well tolerated at a dose of 0.76% (w/w). Here, we performed a 3-month, double-blind, randomized, placebo-controlled phase 2a trial of two different doses of topical POH in individuals with sun-damaged skin. Participants applied POH cream twice daily to each dorsal forearm. Baseline and end-of-study biopsies were taken from each participant to evaluate whether the topical application of POH was effective in reversing actinic damage as evidenced by normalization of quantitative skin histopathologic scores and change in nuclear chromatin pattern as measured by karyometric analysis. There was a borderline reduction in the histopathologic score of the lower-dose POH group compared with the placebo (P = 0.1), but this was not observed in the high-dose group. However, in the high-dose group, a statistically significant reduction in the proportion of nuclei deviating from normal was observed by the use of karyometric analysis (P < 0.01). There was no statistical significance shown in the lower-dose group. No changes were observed in p53 expression, cellular proliferation (by proliferating cell nuclear antigen expression), or apoptosis in either treatment group compared with the placebo group. These results suggest that whereas our karyometric analyses can detect a modest effect of POH in sun-damaged skin, improved delivery into the epidermis may be necessary. Cancer Prev Res; 3(2); 160–9
Loss of β1‐integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype

Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1‐integrin selectively in urothelium of mice using Cre‐LoxP targeted gene deletion. β1‐Integrin localized to basal/ intermediate urothelial cells by confocal microscopy. β1‐Integrin conditional‐knockout (β1‐cKO) mice lacking urothelial β1‐integrin exhibited down‐regulation and mislocalization of α3‐ and α5‐integrins by immunohistochemistry but, surprisingly, had normal morphology, permeability, and transepithelial resistance when compared with Cre‐negative littermate controls. β1‐cKO mice were incontinent, as judged by random urine leakage on filter paper (4‐fold higher spotting, P<0.01; 2.5‐fold higher urine area percentage, P<0.05). Urodynamic function assessed by cystometry revealed bladder overfilling with 80% longer intercontractile intervals (P<0.05) and detrusor hyperactivity (3‐fold more prevoid contractions, P<0.05), but smooth muscle contractility remained intact. ATP secretion into the lumen was elevated (49 vs. 22 nM, P<0.05), indicating abnormal filling‐induced purinergic signaling, and short‐circuit currents (measured in Ussing chambers) revealed 2‐fold higher stretch‐activated ion channel conductances in response to hydrostatic pressure of 1 cmH2O (P<0.05). We conclude that loss of integrin signaling from urothelium results in incontinence and overactive bladder due to abnormal mechanotransduction; more broadly, our findings indicate that urothelium itself directly modulates voiding. —Kanasaki, K. , Yu, W. , von Bodungen, M. , Larigakis, J. D. , Kanasaki, M. , Ayala de la Pena, F. , Kalluri, R. , Hill, W.G. Loss of β1‐integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype. FASEB J. 27, 1950–1961 (2013). www.fasebj. org
Variability driven gate sizing for binning yield optimization

Process variations result in a considerable spread in the frequency of the fabricated chips. In high performance applications, those chips that fail to meet the nominal frequency after fabrication are either discarded or sold at a loss which is typically proportional to the degree of timing violation. The latter is called binning. In this paper we present a gate sizing-based algorithm that optimally minimizes the binning yield-loss. We make the following contributions: 1) prove the binning yield function to be convex, 2) do not make any assumptions about the sources of variability, and their distribution model, 3) we integrate our strategy with statistical timing analysis tools (STA), without making any assumptions about how STA is done, 4) if the objective is to optimize the traditional yield (and not binning yield) our approach can still optimize the same to a very large extent. Comparison of our approach with sensitivity-based approaches under fabrication variability shows an improvement of on average 72% in the binning yield-loss with an area overhead of an average 6%, while achieving a 2.69 times speedup under a stringent timing constraint. Moreover we show that a worst-case deterministic approach fails to generate a solution for certain delay constraints. We also show that optimizing the binning yield-loss minimizes the traditional yield-loss with a 61% improvement from a sensitivity-based approach
Pituitary-Gonadal Relations in Female Children and Adolescents

Extract: Data are provided which concern daytime levels of circulating follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol and progesterone in healthy female children and adolescents. These findings are correlated with sexual and skeletal maturation. Serum estradiol and testosterone levels were low in childhood, but rose to adult levels coincident with the appearance of secondary sexual characteristics. Serum LH levels did not rise above prepubertal levels until these characteristics were already apparent. Serum FSH levels showed a biphasic pattern with age; widely scattered values, some into the adult range, were seen in infancy. Mean FSH levels then declined throughout childhood until the onset of clinical puberty at which time they increased again to adult levels. Serum progesterone concentrations remained low (below 150 ng/100 ml) until menarche. Levels of serum progresterone which suggested possible ovulation and corpus luteum formation (over 200 ng/100 ml) were found in 9 of 30 girls who were less than 3 years postmenarchal.Speculation: The finding of high serum FSH levels in female, but not in male, infants suggests that the infantile ovary may be relatively resistant to FSH stimulation. The decline in FSH levels during early childhood may represent increasing ovarian maturation, at least in terms of ability to secrete as yet unidentified gonadotropin-inhibiting feedback substance (or substances). The onset of female puberty appears to be heralded by increasing FSH secretion; although nocturnal LH release may be characteristic of early puberty, daytime elevation of this hormone is not seen until midpuberty. The surprising finding of luteal range serum progesterone levels in many early postmenarchal girls suggests that anovulatory cycles may not be characteristic of these years. The reported relative infertility of adolescent girls may relate to factors other than ovulation (such as a short corpus luteum life-span, defects in sperm capacitation, or impaired blastocyst implantation).
Object Tracking Based on Particle Filter and Scale Invariant Feature Transform

Particle filter is a popular stochastic tracker for object tracking. In this paper, we proposed a novel algorithm for object tracking based on particle filter and Scale Invariant Feature Transform (SIFT). The result of SIFT matching does not adopt to reweight the particles as previous methods, we adopts a hybrid schema to supplement the particle distribution of traditional factor sampling with importance sampling. Experiments show that the proposed algorithm yields a more robust tracking result.
Fluorescence Quantum Yields of Natural Organic Matter and Organic Compounds: Implications for the Fluorescence-based Interpretation of Organic Matter Composition

Absorbance and fluorescence spectroscopy are economical tools for tracing the supply, turnover and fate of dissolved organic matter (DOM). The colored and fluorescent fractions of DOM (CDOM and FDOM, respectively) are linked by the apparent fluorescence quantum yield (AQY) of DOM, which reflects the likelihood that chromophores emit fluorescence after absorbing light. Compared to the number of studies investigating CDOM and FDOM, few studies have systematically investigated AQY spectra for DOM, and linked them to fluorescence quantum yields (Φ) of organic compounds. To offer a standardized approach, a MATLAB toolbox for the determination of apparent quantum yields of DOM (aquaDOM), featuring two calculation approaches, was developed and used to derive AQYs for samples from the Norwegian Sea. Φ of the organic compounds varied between 0.00079 and 0.35, whereas the average AQY for DOM samples at 350 nm was 0.011 ± 0.003. The AQY at 350 nm increased with depth, while the AQY at 250 nm showed no trend. Laboratory tests indicated that Φ of compound mixtures are additive and represent an intermediate of the constituents. Additionally, the presence of non-fluorescent chromophores greatly suppressed calculated AQYs. Similar trends in the DOM AQY at 350 nm were observed in natural samples. We therefore hypothesize that fluorescence AQYs can indicate changes in the relative abundances of CDOM and FDOM. Additionally, the optical properties of 15 potential DOM constituents were determined and compared to more than 200 modeled spectra (PARAFAC components) in the OpenFluor database. Apparent matches, based on spectral similarity, were subsequently evaluated using molar fluorescence and absorbance. Five organic compounds were potential matches with PARAFAC components from 16 studies; however, the ability to confirm matches was limited due to multiple compounds exhibiting very similar spectra. This reiterates the fact that spectral similarity alone is insufficient evidence of the presence of particular compounds, and additional evidence is required.