Miracle-dz/UniFAR-FTUs huggingface dataset:
Ten questions about systems biology

Abstract In this paper we raise ‘ten questions’ broadly related to ‘omics’, the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist perspective about the contribution of genes and genetic variants to disease is a key reason ‘omics’ has failed to deliver the anticipated breakthroughs. We then point out the critical utility of key concepts from physiology like homeostasis, regulated systems and redundancy as major intellectual tools to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as ‘systems biology’ by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many common diseases. Finally, we attempt to integrate our critique of reductionism into a broader social framework about so‐called translational research in specific and the root causes of common diseases in general. Throughout we offer ideas and suggestions that might be incorporated into the current biomedical environment to advance the understanding of disease through the perspective of physiology in conjunction with epidemiology as opposed to bottom‐up reductionism alone.
Deep Multi-task Representation Learning: A Tensor Factorisation Approach

Most contemporary multi-task learning methods assume linear models. This setting is considered shallow in the era of deep learning. In this paper, we present a new deep multi-task representation learning framework that learns cross-task sharing structure at every layer in a deep network. Our approach is based on generalising the matrix factorisation techniques explicitly or implicitly used by many conventional MTL algorithms to tensor factorisation, to realise automatic learning of end-to-end knowledge sharing in deep networks. This is in contrast to existing deep learning approaches that need a user-defined multi-task sharing strategy. Our approach applies to both homogeneous and heterogeneous MTL. Experiments demonstrate the efficacy of our deep multi-task representation learning in terms of both higher accuracy and fewer design choices.
Methanol Assimilation in Methylobacterium extorquens AM1: Demonstration of All Enzymes and Their Regulation

Background Methylobacterium extorquens AM1 is an aerobic facultative methylotrophic α-proteobacterium that can use reduced one-carbon compounds such as methanol, but also multi-carbon substrates like acetate (C2) or succinate (C4) as sole carbon and energy source. The organism has gained interest as future biotechnological production platform based on methanol as feedstock. Methodology/Principal Findings We present a comprehensive study of all postulated enzymes for the assimilation of methanol and their regulation in response to the carbon source. Formaldehyde, which is derived from methanol oxidation, is assimilated via the serine cycle, which starts with glyoxylate and forms acetyl-CoA. Acetyl-CoA is assimilated via the proposed ethylmalonyl-CoA pathway, which thereby regenerates glyoxylate. To further the understanding of the central carbon metabolism we identified and quantified all enzymes of the pathways involved in methanol assimilation. We observed a strict differential regulation of their activity level depending on whether C1, C2 or C4 compounds are used. The enzymes, which are specifically required for the utilization of the individual substrates, were several-fold up-regulated and those not required were down-regulated. The enzymes of the ethylmalonyl-CoA pathway showed specific activities, which were higher than the calculated minimal values that can account for the observed growth rate. Yet, some enzymes of the serine cycle, notably its first and last enzymes serine hydroxymethyl transferase and malate thiokinase, exhibit much lower values and probably are rate limiting during methylotrophic growth. We identified the natural C1 carrying coenzyme as tetrahydropteroyl-tetraglutamate rather than tetrahydrofolate. Conclusion/Significance This study provides the first complete picture of the enzymes required for methanol assimilation, the regulation of their activity levels in response to the growth substrate, and the identification of potential growth limiting steps.
Isolation and Identification of Potential Phosphate Solubilizing Bacteria from the Rhizoplane of Oryza sativa L. cv. BR29 of Bangladesh

A total of 30 bacteria were isolated from the rhizoplane of rice cv. BR29 cultivated in Mymensingh, Bangladesh and from the seedlings obtained from surface-sterilized seeds of BR29. Upon screening, 6 isolates showed varying levels of phosphate solubilizing activity in both agar plate and broth assays using National Botanical Research Institute’s phosphate medium. The bacterial isolates were identified based on their phenotypic and 16S rRNA genes sequencing data as Acinetobacter sp. BR-12, Klebsiella sp. BR-15, Acinetobacter sp. BR-25, Enterobacter sp. BR-26, Microbacterium sp. BRS-1 and Pseudomonas sp. BRS-2. The BR-25 exhibited highest phosphate solubilizing activity followed by BR-15. They grew rapidly in the liquid medium at pH 5 and 7 but almost no growth occurred at pH 3. The pH value of the culture medium was decreased with bacterial growth suggesting that they might secrete organic acids to solubilize insoluble phosphorus. Scanning electron microscope analysis of two-week-old rice seedlings germinated from seeds previously inoculated with BR-25 and BR-15 revealed dense colonization at the root surfaces presumably using fimbriae on the bacterial cells.
Decreased beta‐adrenergic responsiveness following hypertrophy occurs only in cardiomyocytes that also re‐express beta‐myosin heavy chain

Cardiac hypertrophy is associated with a reduction in the contractile response to beta‐adrenergic stimulation, and with re‐expression of foetal genes such as beta‐myosin heavy chain (MHC). However, whether these two markers of pathology develop concordantly in the same individual cells or independently in different cells is not known.
ICU Professionals’ Experiences of Caring for Conscious Patients Receiving MVT

Over the last decade, caring for patients who are conscious while receiving mechanical ventilator treatment has become common in Scandinavian intensive care units. Therefore, this study aimed to describe anesthetists’, nurses’, and nursing assistants’ experiences of caring for such patients. Nine persons were interviewed. A hermeneutic method inspired by Gadamer’s philosophy was used to interpret and analyze the interview text. Staff members found it distressing to witness and be unable to alleviate suffering, leading to ethical conflicts, feelings of powerlessness, and betrayal of the promises made to the patient. They were frustrated about their inability to understand what the patients were trying to say and often turned to colleagues for help. When caring for conscious patients, it takes time to get to know them and establish communication and a trusting relationship.
Monotone Cellular Automata in a Random Environment

In this paper we study in complete generality the family of two-state, deterministic, monotone, local, homogeneous cellular automata in $\mathbb{Z}$d with random initial configurations. Formally, we are given a set $\mathcal{U}$ = {X1,. , Xm} of finite subsets of $\mathbb{Z}$d \ {0}, and an initial set A0 ⊂ $\mathbb{Z}$d of ‘infected’ sites, which we take to be random according to the product measure with density p. At time t ∈ $\mathbb{N}$, the set of infected sites At is the union of At-1 and the set of all x ∈ $\mathbb{Z}$d such that x + X ∈ At-1 for some X ∈ $\mathcal{U}$. Our model may alternatively be thought of as bootstrap percolation on $\mathbb{Z}$d with arbitrary update rules, and for this reason we call it $\mathcal{U}$-bootstrap percolation. In two dimensions, we give a classification of $\mathcal{U}$-bootstrap percolation models into three classes – supercritical, critical and subcritical – and we prove results about the phase transitions of all models belonging to the first two of these classes. More precisely, we show that the critical probability for percolation on ($\mathbb{Z}$/n$\mathbb{Z}$)2 is (log n)−Θ(1) for all models in the critical class, and that it is n−Θ(1) for all models in the supercritical class. The results in this paper are the first of any kind on bootstrap percolation considered in this level of generality, and in particular they are the first that make no assumptions of symmetry. It is the hope of the authors that this work will initiate a new, unified theory of bootstrap percolation on $\mathbb{Z}$d.
Colour pattern homology and evolution in Vanessa butterflies (Nymphalidae: Nymphalini): eyespot characters

Ocelli are serially repeated colour patterns on the wings of many butterflies. Eyespots are elaborate ocelli that function in predator avoidance and deterrence as well as in mate choice. A phylogenetic approach was used to study ocelli and eyespot evolution in Vanessa butterflies, a genus exhibiting diverse phenotypes among these serial homologs. Forty‐four morphological characters based on eyespot number, arrangement, shape and the number of elements in each eyespot were defined and scored. Ocelli from eight wing cells on the dorsal and ventral surfaces of the forewing and hindwing were evaluated. The evolution of these characters was traced over a phylogeny of Vanessa based on 7750 DNA base pairs from 10 genes. Our reconstruction predicts that the ancestral Vanessa had 5 serially arranged ocelli on all four wing surfaces. The ancestral state on the dorsal forewing and ventral hindwing was ocelli arranged in two heterogeneous groups. On the dorsal hindwing, the ancestral state was either homogenous or ocelli arranged in two heterogeneous groups. On the ventral forewing, we determined that the ancestral state was organized into three heterogeneous groups. In Vanessa, almost all ocelli are individuated and capable of independent evolution relative to other colour patterns except for the ocelli in cells −1 and 0 on the dorsal and ventral forewings, which appear to be constrained to evolve in parallel. The genus Vanessa is a good model system for the study of serial homology and the interaction of selective forces with developmental architecture to produce diversity in butterfly colour patterns.
Down-regulation of traditional oncomiRs in plasma of breast cancer patients

Deregulated expression of microRNAs has the oncogenic or tumor suppressor function in cancer. Since miRNAs in plasma are highly stable, their quantification could contribute to more precise cancer diagnosis, prognosis and therapy prediction. We have quantified expression of seven oncomiRs, namely miR-17/92 cluster (miR-17, miR-18a, miR-19a and miR-20a), miR-21, miR-27a and miR-155, in plasma of 137 breast cancer (BC) patients. We detected down-regulation of six miRNAs in patients with invasive BC compared to controls; however, only miR-20a and miR-27a down-regulations were statistically significant. Comparing miRNA expression between early and advanced stages of BC, we observed statistically significant decrease of miR-17 and miR-19a. We identified down-regulation of miR-17 and miR-20a in patients with clinical parameters of advanced BC (lymph node metastasis, tumor grade 3, circulating tumor cells, higher Ki-67-related proliferation, hormone receptor negativity and HER2 amplification), when compared to controls. Moreover, decreased level of miR-17 was found from low to high grade. Therefore, miR-17 could represent an indicator of advanced BC. Down-regulated miR-27a expression levels were observed in all clinical categories regardless of tumor progression. Hence, miR-27a could be used as a potential diagnostic marker for BC. Our data indicates that any changes in miRNA expression levels in BC patients in comparison to controls could be highly useful for cancer-associated pathology discrimination. Moreover, dynamics of miRNA expression changes could be used for BC progression monitoring.
The recent ascent of stock prices: can it be explained by earnings growth or other fundamentals?

An analysis of the current relationship between stock prices, dividends, earnings, and returns, aimed at examining the causes of the recent stock market surge. It reveals that the markets level cannot be explained by any single fundamental element of standard stock valuation models, but rather manifests optimism about future dividend growth (based on the present record growth in earnings) and a lower expected return (reflecting a diminished risk premium for holding equity).
Evaluation of the measurement properties of self-reported health-related work-functioning instruments among workers with common mental disorders.

OBJECTIVES During the past decade, common mental disorders (CMD) have emerged as a major public and occupational health problem in many countries. Several instruments have been developed to measure the influence of health on functioning at work. To select appropriate instruments for use in occupational health practice and research, the measurement properties (eg, reliability, validity, responsiveness) must be evaluated. The objective of this study is to appraise critically and compare the measurement properties of self-reported health-related work-functioning instruments among workers with CMD. METHODS A systematic review was performed searching three electronic databases. Papers were included that: (i) mainly focused on the development and/or evaluation of the measurement properties of a self-reported health-related work-functioning instrument; (ii) were conducted in a CMD population; and (iii) were fulltext original papers. Quality appraisal was performed using the consensus-based standards for the selection of health status measurement instruments (COSMIN) checklist. RESULTS Five papers evaluating measurement properties of five self-reported health-related work-functioning instruments in CMD populations were included. There is little evidence available for the measurement properties of the identified instruments in this population, mainly due to low methodological quality of the included studies. CONCLUSIONS The available evidence on measurement properties is based on studies of poor-to-fair methodological quality. Information on a number of measurement properties, such as measurement error, content validity, and cross-cultural validity is still lacking. Therefore, no evidence-based decisions and recommendations can be made for the use of health-related work functioning instruments. Studies of high methodological quality are needed to properly assess the existing instruments' measurement properties.
Elastofibroma of the Face: A Case Report

Elastofibroma is a rare neoplasm that characteristically occurs in subscapular area in response to microtrauma. There are some reports of this tumor in other sites of the body but, up till now, there has been no report of elastofibroma in the face. A 20-year-old man presented with a slow growing painless mass in the face without any history of trauma. Histopathologic examination revealed a soft tissue mass composed of eosinophilic fibers admixed with aggregation of fat cells, capillary blood vessels, and fibroblasts. Elastic stain and Masson’s trichrome stain confirmed the nature of elastic and collagen fibers. It was a case of elastofibroma in the face.
Assessment of the Quality of Reporting of Randomised Controlled Trials in Otorhinolaryngologic Literature – Adherence to the CONSORT Statement

Background Randomised Controlled Trials (RCTs) are the preferred study design when comparing therapeutical interventions in medicine. To improve clarity, consistency and transparency of reporting RCTs, the Consolidated Standards of Reporting Trials (CONSORT) statement was developed. Objectives (1) To assess the quality of reports and abstracts of RCTs in otorhinolaryngologic literature by using CONSORT checklists, (2) to compare the quality of reports and abstracts of otorhinolaryngologic RCTs between the top 5 general medical journals and top 5 otorhinolaryngologic journals, and (3) to formulate recommendations for authors and editors of otorhinolaryngologic (‘ENT’) journals. Methods Based on 2012 ISI Web of Knowledge impact factors, the top 5 general medical and ENT journals were selected. On 25 June 2014, using a highly sensitive Cochrane RCT filter and ENT filter, possibly relevant articles since January 1st, 2010 were retrieved and relevant RCTs were selected. We assessed how many CONSORT items were reported adequately in reports and abstracts and compared the two journal types. Results Otorhinolaryngologic RCTs (n = 15) published in general medical journals reported a mean of 92.1% (95% confidence interval: 89.5%–94.7%) of CONSORT items adequately, whereas RCTs (n = 18) published in ENT journals reported a mean of 71.8% (66.7%–76.8%) adequately (p < 0.001). For abstracts, means of 70.0% (63.7%–76.3%) and 32.3% (26.6–38.0%) were found respectively (p < 0.001). Large differences for specific items exist between the two journal types. Conclusion The quality of reporting of RCTs in otorhinolaryngologic journals is suboptimal. RCTs published in general medical journals have a higher quality of reporting than RCTs published in ENT journals. We recommend authors to report their trial according to the CONSORT Statement and advise editors to endorse the CONSORT Statement and implement the CONSORT Statement in the editorial process to ensure more adequate reporting of RCTs and their abstracts.
Prioritization of Copy Number Variation Loci Associated with Autism from AutDB–An Integrative Multi-Study Genetic Database

Copy number variants (CNVs) are thought to play an important role in the predisposition to autism spectrum disorder (ASD). However, their relatively low frequency and widespread genomic distribution complicates their accurate characterization and utilization for clinical genetics purposes. Here we present a comprehensive analysis of multi-study, genome-wide CNV data from AutDB (http://mindspec.org/autdb.html), a genetic database that accommodates detailed annotations of published scientific reports of CNVs identified in ASD individuals. Overall, we evaluated 4,926 CNVs in 2,373 ASD subjects from 48 scientific reports, encompassing ∼2.12×109 bp of genomic data. Remarkable variation was seen in CNV size, with duplications being significantly larger than deletions, (P = 3×10−105; Wilcoxon rank sum test). Examination of the CNV burden across the genome revealed 11 loci with a significant excess of CNVs among ASD subjects (P<7×10−7). Altogether, these loci covered 15,610 kb of the genome and contained 166 genes. Remarkable variation was seen both in locus size (20 - 4950 kb), and gene content, with seven multigenic (≥3 genes) and four monogenic loci. CNV data from control populations was used to further refine the boundaries of these ASD susceptibility loci. Interestingly, our analysis indicates that 15q11.2-13.3, a genomic region prone to chromosomal rearrangements of various sizes, contains three distinct ASD susceptibility CNV loci that vary in their genomic boundaries, CNV types, inheritance patterns, and overlap with CNVs from control populations. In summary, our analysis of AutDB CNV data provides valuable insights into the genomic characteristics of ASD susceptibility CNV loci and could therefore be utilized in various clinical settings and facilitate future genetic research of this disorder.
Methods and Baseline Characteristics of Two Group-Randomized Trials With Multiracial and Multiethnic Working-class Samples

Introduction Few papers address the methodological challenges in recruiting participants for studies of cancer prevention interventions designed for multiracial and multiethnic working-class populations. This paper reports the results of the sample selection and survey methods for two group-randomized intervention studies. Methods The two group-randomized intervention studies, Healthy Directions–Small Business (HD–SB) and Healthy Directions–Health Centers (HD–HC), included a worksite-based study in 26 small manufacturing businesses and a study in 10 outpatient health centers. We used selection and recruitment methods to obtain a multiracial and multiethnic working-class study sample. In 2000 and 2001, we assessed baseline measures of sociodemographic characteristics and behavioral outcomes by self-report. We then computed intraclass correlation coefficients (ICCs). Results Of the 1740 participants in the HD–SB study, 68% were non-Hispanic whites, and 76% had working-class occupations. In the HD–HC study, 59% of 2219 participants were non-Hispanic whites. Among those who worked, 51% had working-class occupations. Large percentages of both samples reported not meeting recommended guidelines for the target behaviors. For example, 86% of members of both samples consumed fewer than the recommended five servings of fruits and vegetables per day. The ICCs for the four target behaviors in HD–SB were between 0.006 and 0.02. In the HD–HC study, the ICCs ranged from 0.0004 to 0.003. Conclusion The two studies were successful in recruiting multiracial and multiethnic working-class participants. Researchers will find the estimates of the primary outcomes and their ICCs useful for planning future studies.
Phylogeography of the heavily poached African common pangolin (Pholidota, Manis tricuspis) reveals six cryptic lineages as traceable signatures of Pleistocene diversification

Knowledge on faunal diversification in African rainforests remains scarce. We used phylogeography to assess (i) the role of Pleistocene climatic oscillations in the diversification of the African common pangolin (Manis tricuspis) and (ii) the utility of our multilocus approach for taxonomic delineation and trade tracing of this heavily poached species. We sequenced 101 individuals for two mitochondrial DNA (mtDNA), two nuclear DNA and one Y‐borne gene fragments (totalizing 2602 bp). We used a time‐calibrated, Bayesian inference phylogenetic framework and conducted character‐based, genetic and phylogenetic delineation of species hypotheses within African common pangolins. We identified six geographic lineages partitioned into western Africa, Ghana, the Dahomey Gap, western central Africa, Gabon and central Africa, all diverging during the Middle to Late Pleistocene. MtDNA (cytochrome b + control region) was the sole locus to provide diagnostic characters for each of the six lineages. Tree‐based Bayesian delimitation methods using single‐ and multilocus approaches gave high support for ‘species’ level recognition of the six African common pangolin lineages. Although the diversification of African common pangolins occurred during Pleistocene cyclical glaciations, causative correlation with traditional rainforest refugia and riverine barriers in Africa was not straightforward. We conclude on the existence of six cryptic lineages within African common pangolins, which might be of major relevance for future conservation strategies. The high discriminative power of the mtDNA markers used in this study should allow an efficient molecular tracing of the regional origin of African common pangolin seizures.
A fault-tolerant control scheme for non-linear discrete-time systems: Application to the twin-rotor system

In this paper, an active FTC scheme is proposed. First, it is developed in the context of linear systems and then it is extended to non-linear systems with the differential mean value theorem. The key contribution of the proposed approach is an integrated FTC design procedure of the fault identification and fault-tolerant control schemes. Fault identification is based on the use of an observer. While, the FTC controller is implemented as a state feedback controller. This controller is designed such that it can stabilize the faulty plant using Lyapunov theory and LMIs. Finally, the last part of the paper shows application results regarding the Twin-Rotor MIMO System (TRMS) that confirm the high performance of the proposed approach.