Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping quantitative trait loci in crosses between outbred lines using least squares.

The use of genetic maps based upon molecular markers has allowed the dissection of some of the factors underlying quantitative variation in crosses between inbred lines. For many species crossing inbred lines is not a practical proposition, although crosses between genetically very different outbred lines are possible. Here we develop a least squares method for the analysis of crosses between outbred lines which simultaneously uses information from multiple linked markers. The method is suitable for crosses where the lines may be segregating at marker loci but can be assumed to be fixed for alternative alleles at the major quantitative trait loci (QTLs) affecting the traits under analysis (e.g., crosses between divergent selection lines or breeds with different selection histories). The simultaneous use of multiple markers from a linkage group increases the sensitivity of the test statistic, and thus the power for the detection of QTLs, compared to the use of single markers or markers flanking an interval. The gain is greater for more closely spaced markers and for markers of lower information content. Use of multiple markers can also remove the bias in the estimated position and effect of a QTL which may result when different markers in a linkage group vary in their heterozygosity in the F1 (and thus in their information content) and are considered only singly or a pair at a time. The method is relatively simple to apply so that more complex models can be fitted than is currently possible by maximum likelihood. Thus fixed effects of background genotype can be fitted simultaneously with the exploration of a single linkage group which will increase the power to detect QTLs by reducing the residual variance. More complex models with several QTLs in the same linkage group and two-locus interactions between QTLs can similarly be examined. Thus least squares provides a powerful tool to extend the range of crosses from which QTLs can be dissected whilst at the same time allowing flexible and realistic models to be explored.
Ovarian morphology in polycystic ovary syndrome: estimates from 2D and 3D ultrasound and magnetic resonance imaging and their correlation to anti-Müllerian hormone

Background Due to improved ultrasound scanners, new three-dimensional (3D) modalities, and novel Anti-Müllerian hormone (AMH)-assays, the ultrasound criteria for polycystic ovarian morphology are under debate and the appropriate thresholds are often requested. Purpose To quantify the differences in estimates of ovarian volume and antral follicle count (AFC) from two-dimensional (2D) and 3D transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). Material and Methods A cross-sectional study on 66 overweight women with polycystic ovary syndrome (PCOS) according to Rotterdam criteria. Ovarian volume and AFC were estimated from MRI, 2D TVUS, and 3D TVUS, and serum AMH levels were assessed. Bland–Altman statistics were used for comparison. Results Participants had a median age of 29 years (age range, 19–44 years) with a mean BMI of 32.7 kg/m2 (SD 4.5). Ovarian volume from 2D TVUS was 1.48 mL (95% confidence interval [CI], 0.94–2.03; P < 0.001) and 1.25 mL (95% CI, 0.62–1.87; P < 0.001) smaller than from 3D TVUS and MRI, respectively. AFC from 2D TVUS was 18% (95% CI, 13–23; P < 0.005) and 16% (95% CI, 6–25; P < 0.005) smaller than estimates from 3D TVUS and MRI, respectively. Correlations between AMH and AFC from 2D TVUS, 3D TVUS, and MRI were 0.67, 0.78, and 0.70, respectively (P < 0.001 for all). Conclusion In an overweight PCOS population, 2D TVUS underestimated ovarian volume and AFC as compared with 3D TVUS and MRI. Serum AMH correlated best with AFC from 3D TVUS, followed by MRI and 2D TVUS. The advantage of 3D TVUS might be of minor clinical importance when diagnosing PCOS, but useful when the actual AFC are of interest, e.g. in fertility counseling and research.
Comparison of application of 2013 ACC/AHA guideline and 2011 European Society of Cardiology guideline for the management of dyslipidemias for primary prevention in a Turkish cohort

Objective: Atherosclerotic cardiovascular disease is a major global cause of death. The common approach in primary prevention of cardiovascular disease is to identify patients at high risk for cardiovascular disease. This article analyzes and compares the application of 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline and the 2011 European Society of Cardiology (ESC) guideline for the management of dyslipidemias for primary prevention in Turkish population. Methods: The study included 833 patients (482 women and 351 men). Risk scores were calculated according to both guidelines and indications for statin treatment were determined according to sex and age group. Variables are presented as mean±SD or median with interquartile range for continuous data and as proportions for categorical data. Variables were analyzed by unpaired t-test, Mann-Whitney U test, chi-square or Fischer’s exact test as appropriate. Results: The ACC/AHA would suggest statin treatment in 415 patients out of 833 (49.5%), while ESC would recommend statin for 193 patients out of 833 (23.1%) (p<0.001). Statins would be recommended for 40.4% of women and 62.6% of men for primary prevention by the ACC/AHA, while this figure was 12% for women and 38.4% for men according to the ESC guideline (p<0.001 for both). Conclusion: When compared to the ESC guideline, the ACC/AHA guideline suggests augmented statin treatment for primary prevention in Turkish population.
Short telomere length, cancer survival, and cancer risk in 47102 individuals.

BACKGROUND Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer. METHODS We measured leukocyte telomere length in a prospective study of 47 102 Danish general population participants from the Copenhagen City Heart Study and the Copenhagen General Population Study. Participants were followed for up to 20 years for cancer diagnosis and death. Follow-up was 100% complete. All statistical tests were two-sided. RESULTS Telomere length decreased linearly with increasing age (P <.001). During follow-up, we observed 3142 first cancers and, among these individuals, 1730 deaths. Decreasing quartiles of telomere length were associated with decreasing survival after cancer (log-rank P <.001). Multivariable-adjusted hazard ratios of early death were 1.31 (95% confidence interval [CI] = 1.14 to 1.52) in individuals in the quartile and 1.43 (95% CI = 1.13 to 1.80) in individuals in the decile with the shortest telomeres vs the longest. Unadjusted hazard ratios of cancer risk were 1.74 (95% CI = 1.58 to 1.93) and 2.00 (95% CI = 1.70 to 2.35) in individuals in the quartile and decile with the shortest vs longest telomeres; however, multivariable adjustment changed these hazard ratios to 0.98 (95% CI = 0.88 to 1.08) and 0.95 (95% CI = 0.80 to 1.11), mainly because of age adjustment. CONCLUSIONS Short telomere length is associated with reduced survival after cancer but not with cancer risk. The latter contrasts with findings from recent meta-analyses.
Emerging therapeutic targets in bipolar mood disorder

Bipolar mood disorder is a chronic, severe and life-threatening psychiatric illness, whose underlying pathophysiology is still obscure. Lithium is the mainstay of treatment for this illness, with robust acute antimanic and long-term prophylactic effects. Over the past decade, valproate has been another medication shown to have possibly similar mood-stabilising properties to lithium, in double-blind controlled trials. Nonetheless, among patients suffering from bipolar disorder, a substantial percentage appears to respond poorly to currently available pharmacological therapies, including lithium, valproate, carbamazepine and other newer compounds, clearly demonstrating that there is a substantial need for improved therapeutic agents. Very significant effort has been made in the past several years to elucidate the cellular mechanisms by which lithium and valproate produce their therapeutic effects. The available evidence points to a modulatory action of these compounds over multiple neural biochemical pathways and most investigations have found relevant actions of mood stabilisers on intracellular signal transduction mechanisms. Moreover, it has been shown in recent years that lithium and valproate lead to long-term changes in neural plasticity, with eventual neurotrophic and neuroprotective effects. Although these actions are not fully understood, stimulation of transcription factors and effects on gene expression are potentially involved. The search for the mechanisms of action of well-established mood-stabilisers has helped to reveal promising molecular targets to test novel therapeutic approaches. This review will examine the current investigations on the diverse biochemical and molecular pathways regulated by either lithium or valproate and highlight the potential cellular targets for the development of novel mood stabilisers.
Effect of Light and p-Coumaric Acid on the Growth and Expression of Genes Related to Oxidative Stress in Brettanomyces bruxellensis LAMAP2480

Brettanomyces bruxellensis is considered the most significant contaminant yeast in the wine industry since it causes a deterioration in the organoleptic properties of the wine and significant economic losses. This deterioration is due to the production of volatile phenols from hydroxycinnamic acids. These compounds possess antimicrobial properties; however, B. bruxellensis can resist this effect because it metabolizes them into less toxic ones. Recent studies have reported that B. bruxellensis grows under different stress conditions, including p-coumaric acid (pCA) but effective methods for its control have not been found yet. Since that in other yeasts, such as Saccharomyces cerevisiae, it has been described that light affects its growth, and we evaluated whether the light would have a similar effect on B. bruxellensis. The results show that at light intensities of 2,500 and 4,000 lux in the absence of pCA, B. bruxellensis LAMAP2480 does not grow in the culture medium; however, when the medium contains this acid, the yeast adapts to both factors of stress managing to grow. The expression of genes related to oxidative stress in B. bruxellensis LAMAP2480, such as SOD1, GCN4, and ESBP6, showed a higher relative expression when the yeast was exposed to 2,500 lux compared to 4,000 lux, agreeing with the growth curves. This suggests that a higher expression of the genes studied would be related to stress-protective effects by pCA.
Content-aware image resizing using perceptual seam carving with human attention model

In this paper, a new image resizing technique, perceptual seam carving, is proposed. With considering both face map and saliency map as human attention model in the energy function, it can keep important information in perceptual when the image is downsized. Moreover, a switching scheme between seam carving and resampling is also proposed to avoid excessively distorting the images. Experiments show that the proposed algorithm can generate more desirable resized images than cropping, resampling, and conventional seam carving techniques.
Comparison of cell viability and morphology of a human osteoblast-like cell line (SaOS-2) seeded on various bone substitute materials: An in vitro study

Background: Many studies have shown favorable results following the use of different bone graft materials. The aim of the present study was to evaluate the biocompatibility of four different bone graft materials regarding cell viability and morphology of Human osteoblast-like cells (SaOS-2) in vitro. Materials and Methods: The effects of Bio-Oss®, Tutodent®, Osteon®, and Cerasorb® were studied on the human osteoblast-like cell line to evaluate various parameters. Human osteoblast-like cells were seeded onto the mentioned bone substitute materials (BSMs). Cell differentiation; cell viability and alkaline phosphatase (ALP) activity of the seeded cells were evaluated by means of scanning electron microscopy, cell viability test and phase contrast microscopy Analysis of variance (ANOVA). Tamhane's post-hoc, Kruskal-Wallis Test, and Dunn's Test were used. The results were considered to be statistically significant at P<0.05. Results: The control group (SaOS-2 cells which were incubated in Dulbecco Modified Eagle Medium without any kind of bone graft materials) had the highest level of cell viability (P<0.001), followed by Tutodent®, Osteon®, Cerasorb®, and Bio-Oss®. There was no significant difference in MTT assay results between Tutodent® and the control group (P=0.032). All tested bone graft materials showed significantly higher ALP activity than the control (P<0.001). The Tutodent® group showed the best cell growth among all experimental groups, followed by the Osteon® group. The former had a higher spindle-like morphology with good attachment to the surface. Cells cultivated on the surfaces of the Cerasorb® and Bio-Oss® granules had more round morphologies. Conclusion: This in vitro study demonstrated that all tested BSMs can provide good cell differentiation but a lower rate of proliferation.
Costs and benefits of routine follow-up after curative treatment for endometrial cancer.

OBJECTIVE To examine the costs of routine outpatient follow-up after curative treatment of endometrial cancer, and to determine whether this leads to early detection of recurrence or survival. The impact of specific disease characteristics on survival is examined. DESIGN Retrospective chart review, and calculation of costs. SETTING Ottawa Regional Cancer Centre-Civic Division (ORCC-C). PATIENTS All 432 patients referred to the ORCC-C with endometrial cancer between 1982 and 1991 who received treatment with curative intent and who continued with routine follow-up. RESULTS Cancer recurred in 50 patients (11.57%). There was no statistically significant difference in overall survival between patients with symptomatic and asymptomatic recurrences, or between those with recurrences detected during routine follow-up visits or in the interval between routine visits. Of 4830 Papanicolaou (Pap) smears performed routinely, cancer was detected in 6 cases. The mean cost of the routine follow-up procedures for each patient with a recurrence was $19,200. CONCLUSION Intensive follow-up of women with endometrial cancer does not result in improved survival. A prospective randomized study is warranted to evaluate other potential benefits of follow-up, such as improved quality of life or decreased morbidity. There is no economic or clinical justification for the routine use of the Pap smear in the follow-up of patients with endometrial cancer. The potential benefits of routine follow-up in endometrial cancer and other types of cancer with favourable prognoses warrant critical evaluation.
A Capacity Scaling Law for Artificial Neural Networks

We derive the calculation of two critical numbers predicting the behavior of perceptron networks. First, we derive the calculation of what we call the lossless memory (LM) dimension. The LM dimension is a generalization of the Vapnik--Chervonenkis (VC) dimension that avoids structured data and therefore provides an upper bound for perfectly fitting almost any training data. Second, we derive what we call the MacKay (MK) dimension. This limit indicates a 50% chance of not being able to train a given function. Our derivations are performed by embedding a neural network into Shannon's communication model which allows to interpret the two points as capacities measured in bits. We present a proof and practical experiments that validate our upper bounds with repeatable experiments using different network configurations, diverse implementations, varying activation functions, and several learning algorithms. The bottom line is that the two capacity points scale strictly linear with the number of weights. Among other practical applications, our result allows to compare and benchmark different neural network implementations independent of a concrete learning task. Our results provide insight into the capabilities and limits of neural networks and generate valuable know how for experimental design decisions.
Chronic Moderate Hyperammonemia Impairs Active and Passive Avoidance Behavior and Conditional Discrimination Learning in Rats

The cerebral dysfunction associated with hepatic encephalopathy is generally considered to have hyperammonemia as one of its main causes. Hyperammonemia impairs the neuronal glutamate-nitric oxide-cyclic GMP pathway and the induction of NMDA receptor-dependent long-term potentiation in the hippocampus. We studied the performance of pre/neonatally and postnatally exposed rats to hyperammonemia on active avoidance, passive avoidance, and conditional discrimination tasks. Pre/neonatal hyperammonemia slowed learning of active avoidance behaviors and impaired memory for the passive avoidance task while postnatal hyperammonemia impaired learning on the conditional discrimination task. Hyperammonemia thus may produce cognitive disturbances that relate to the effects of ammonia on the neuronal glutamate-nitric oxide-cyclic GMP pathway.
Of Mice and MEN1: Insulinomas in a Conditional Mouse Knockout

ABSTRACT Patients with multiple endocrine neoplasia type 1 (MEN1) develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and endocrine pancreas, due to the inactivation of the MEN1 gene. A conditional mouse model was developed to evaluate the loss of the mouse homolog, Men1, in the pancreatic beta cell. Men1 in these mice contains exons 3 to 8 flanked by loxP sites, such that, when the mice are crossed to transgenic mice expressing cre from the rat insulin promoter (RIP-cre), exons 3 to 8 are deleted in beta cells. By 60 weeks of age, >80% of mice homozygous for the floxed Men1 gene and expressing RIP-cre develop multiple pancreatic islet adenomas. The formation of adenomas results in elevated serum insulin levels and decreased blood glucose levels. The delay in tumor appearance, even with early loss of both copies of Men1, implies that additional somatic events are required for adenoma formation in beta cells. Comparative genomic hybridization of beta cell tumor DNA from these mice reveals duplication of chromosome 11, potentially revealing regions of interest with respect to tumorigenesis.
Syllable-level prominence detection with acoustic evidence

Accurate prominence annotation beneﬁts many spoken language understanding tasks as well as speech synthesis. In this work, we conduct a thorough study using acoustic prosodic cues for prominence detection in speech. This study is different from previous work in several aspects. In addition to the widely used prosodic features, such as pitch, energy, and duration, we introduce the use of cepstral features. Furthermore, we evaluate the effect of different features, speaker dependency and variation, different classiﬁers, and contextual information. Our experiments on the Boston University Radio News Corpus show that although the cepstral features alone do not perform well, when combined with prosodic features they yield some performance gain and, more importantly, can reduce much of the speaker variation in this task. We ﬁnd that the previous context is more informative than the following context, and their combination achieves the best performance. The ﬁnal result using selected features with context information is signiﬁcantly better than that in previous work.
Product–Service Innovation and Performance: The Role of Collaborative Partnerships and R&D Intensity

Treating the intersection of the strategic partnerships, R&D intensity and servitisation literatures, this study explores empirically whether external collaborative service development and provision and industrial R&D intensity help to unpack the complex relation between product–service innovation (servitisation) and performance. We argue that manufacturing firms implementing services benefit from strategic partnerships with Knowledge-Intensive Business Service (KIBS) firms. KIBS partnering provides opportunities for downsizing, externalising risks and sharing knowledge. Additionally, manufacturers in R&D-intensive industries are more likely to benefit from implementing service provision than firms in other sectors because of industry dynamics and reduced customer uncertainty. The study surveys executives in 370 large manufacturers worldwide. Results reinforce the importance of concentric strategic partnerships to successful product–service innovation in high R&D industries.
Asthma-Like Symptoms are Increased in the Metabolic Syndrome

Background. The prevalence of obesity and asthma has been increasing during the last several decades. Obesity has been reported to be associated with asthma. Obesity, especially abdominal obesity, is the main component of the metabolic syndrome. Objectives. We thus hypothesized that metabolic syndrome is an important contributing factor for the development of asthma-like symptoms. Methods. The Korean Health and Genome Study started in 2001 as an ongoing population-based study of Korean adults 40 to 69 years of age. The prevalence of asthma-like symptoms in the previous 12 months was obtained by a questionnaire, and spirometric testing was conducted. Results. Among the 10,038 participants, the data from 9,942 individuals (4,716 men and 5,226 women) was available. Asthma-like symptoms (wheeze [p = 0.0006], resting dyspnea [p = 0.0062], and post-exercise dyspnea [p < 0.0001]) were increased in the subjects of the metabolic syndrome group. Subjects with asthma-like symptoms had a decreased lung function compared to subjects without asthma-like symptoms. Among the components of the metabolic syndrome, abdominal obesity and hypertension were the risk factors for asthma-like symptoms. Conclusions. Metabolic syndrome is associated with asthma-like symptoms. Among the components of metabolic syndrome, abdominal obesity and hypertension are the risk factors for asthma-like symptoms.
Plastic responses of bryozoans to ocean acidification

ABSTRACT Phenotypic plasticity has the potential to allow organisms to respond rapidly to global environmental change, but the range and effectiveness of these responses are poorly understood across taxa and growth strategies. Colonial organisms might be particularly resilient to environmental stressors, as organizational modularity and successive asexual generations can allow for distinctively flexible responses in the aggregate form. We performed laboratory experiments to examine the effects of increasing dissolved carbon dioxide (CO2) (i.e. ocean acidification) on the colonial bryozoan Celleporella cornuta sampled from two source populations within a coastal upwelling region of the northern California coast. Bryozoan colonies were remarkably plastic under these CO2 treatments. Colonies raised under high CO2 grew more quickly, investing less in reproduction and producing lighter skeletons when compared with genetically identical clones raised under current surface atmosphere CO2 values. Bryozoans held under high CO2 conditions also changed the Mg/Ca ratio of skeletal calcite and increased the expression of organic coverings in new growth, which may serve as protection against acidified water. We also observed strong differences between source populations in reproductive investment and organic covering reaction norms, consistent with adaptive responses to persistent spatial variation in local oceanographic conditions. Our results demonstrate that phenotypic plasticity and energetic trade-offs can mediate biological responses to global environmental change, and highlight the broad range of strategies available to colonial organisms. Summary: Colonies of the bryozoan Celleporella cornuta exhibit unique resilience to future ocean acidification. This is achieved through plastic shifts in reproductive investment, calcification and skeletal composition.