Miracle-dz/UniFAR-FTUs huggingface dataset:
Intensive aquaculture selects for increased virulence and interference competition in bacteria

Although increased disease severity driven by intensive farming practices is problematic in food production, the role of evolutionary change in disease is not well understood in these environments. Experiments on parasite evolution are traditionally conducted using laboratory models, often unrelated to economically important systems. We compared how the virulence, growth and competitive ability of a globally important fish pathogen, Flavobacterium columnare, change under intensive aquaculture. We characterized bacterial isolates from disease outbreaks at fish farms during 2003–2010, and compared F. columnare populations in inlet water and outlet water of a fish farm during the 2010 outbreak. Our data suggest that the farming environment may select for bacterial strains that have high virulence at both long and short time scales, and it seems that these strains have also evolved increased ability for interference competition. Our results are consistent with the suggestion that selection pressures at fish farms can cause rapid changes in pathogen populations, which are likely to have long-lasting evolutionary effects on pathogen virulence. A better understanding of these evolutionary effects will be vital in prevention and control of disease outbreaks to secure food production.
Local Linear Convergence of Forward-Backward under Partial Smoothness

In this paper, we consider the Forward-Backward proximal splitting algorithm to minimize the sum of two proper closed convex functions, one of which having a Lipschitz continuous gradient and the other being partly smooth relative to an active manifold M. We propose a generic framework under which we show that the Forward-Backward (i) correctly identifies the active manifold M in a finite number of iterations, and then (ii) enters a local linear convergence regime that we characterize precisely. This gives a grounded and unified explanation to the typical behaviour that has been observed numerically for many problems encompassed in our framework, including the Lasso, the group Lasso, the fused Lasso and the nuclear norm regularization to name a few. These results may have numerous applications including in signal/image processing processing, sparse recovery and machine learning.
Influence of Human Leukocyte Antigen on Susceptibility of Tropical Pulmonary Infectious Diseases and Clinical Implications

Human leukocyte antigen (HLA) is the most polymorphic genetic system in humans, with numerous alleles, and subsequently, various possible combinations [1]. These genes, the products of histocompatibility complex (MHC) [2] are located in the short arm of chromo‐ some 6 at band p 21.3 [2] and are divided into three classes, I, II and III [1]. HLA class I is responsible for coding the molecules HLA-A, -B and -C, present in almost all somatic cells with killing of viral infected targets by class I antigens restrict cytotoxic T-cell (CD8+) func‐ tion [2] while HLA class II genes code the molecules HLA-DR, -DQ and -DP [1] by presenta‐ tion of exogenous antigens to T-helper cells (CD4+) or antigen presenting cells (APC) [2]. This polymorphism contributes to the differences in susceptibility to diseases among geneti‐ cally distinct groups [1]. The molecules coded for by the HLA system are responsible for the antigen presentation [1]. The T lymphocytes that are linked to HLA molecules only recog‐ nize antigens by the antigen-specific cell surface receptor-antigens interaction [2], thus the HLA antigens [1] and MCH molecules [2] apparently participate in controlling susceptibility and resistance to various diseases. Some infectious diseases were considered as familial be‐ fore the finding of the causative microorganism and early twin studies indicated that there was a substantial host genetic influence on susceptibility to diseases such as polio and tuber‐ culosis (TB) [3]. At present, it has been confirmed that human genetic variation demon‐ strates a major influence on the course of diseases caused by several infectious microorganisms [3].
Echocardiographic Detection of Mitral Valve Prolapse: Exclusion of False Positive Diagnosis and Determination of Inheritance

An important potential source of error in the echocardiographic diagnosis of mitral valve prolapse has been identified — namely a systolic hammock-like pattern of the anterior and/or posterior mitral leaflet echoes, similar to that associated with true mitral valve prolapse, produced artifactually when the ultrasonic transducer is angulated inferiorly. Utilizing a modified, more specific technique we characterized the mode of inheritance and familial prevalence of this disorder. Among 74 subjects, composed of 57 first-degree relatives and 17 propositi with mitral valve prolapse, mitral valve prolapse was detected in 27 of 57 (47%) of the first-degree relatives. Fifty-three percent of female and 36% of male progeny of propositi were affected. Furthermore, familial transmission occurred from propositi to both sexes. Results of this study indicate that mitral valve prolapse is transmitted in an autosomal dominant mode with reduced male expressivity and a familial prevalence of 47% and that appropriate echocardiographic techniques must be employed to avoid a high incidence of false positive diagnosis.
On the construction and interpretation of fitness landscapes for HIV: a computational perspective

To identify vulnerable viral targets to incorporate into an immunogen, fitness landscapes for the viral proteome have been constructed. These landscapes describe the sum or synergistic replicative cost exacted on the virus for any combination of non-synonymous mutations. Here we attempt to assess the robustness of current computational methods for measuring the fitness cost of HIV polymorphisms in these landscapes. We also address in the following chapters assumptions and shortcomings that may underlie current landscape’s uneven ability to predict fitness effects. In the first chapter, I appraise the robustness of current frame-works that derive fitness costs from patient sequence data. In this chapter I also address the fields over-reliance on crosssectional data, justified by the assumptions that the viral populations can be 1) regarded as an ideal population at equilibrium and 2) are at large unmarred by host pressures. To explore how these problematic assumptions may undermine landscape construction, I assemble an alternate landscape, where fitness costs were directly measured from temporal population fluxes using a dynamical systems framework. This landscape paints a far different picture of the fitness topography. In the following chapter, I tackle another problematic aspect of current landscapes, their neglect of physicochemical detail. I demonstrate that this model contrivance, leads us to under or over estimating fitness costs at positions with highly divergent or similar physicochemical character. In response, I adapt a population genetics model to account for the functional impact of each residue mutation, and illustrate that it improves our ability to predict in vitro viral fitness. Finally, in the last chapter, we employ several different metrics of fitness to determine if the overall topography of the fitness landscape might shift over the course of early infection.
Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

OBJECTIVE The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI, deserve further study.
C-reactive protein and procalcitonin in the assessment of infection response to antibiotic therapy January 2009

With these limitations, researchers and clinicians look at the inflammatory cascade for a potential objective serum marker of infection. By definition a serum marker should be absent if the patient is not infected, appear concomitantly and ideally precede the clinical manifestations of infection, disappear with successful therapy or remain elevated if infection is refractory to treatment. Serial measurements of biomarkers, namely CRP and PCT, used in combination with the clinical examination are very useful in the monitoring of infection response to antibiotics.
Topical Antimicrobials in Wounds

Wounds are a major cause of morbidity especially diabetic foot wounds. Topical antimicrobials are frequently used in day to day practice mainly in management of wounds by various healthcare professionals ranging from general practitioner to specialist surgeons. However lot of controversies exists regarding the usage of antimicrobials. This article provides an insight on the usage of various commonly used topical antimicrobials including their mechanism of action and various side effects.
Reduced mRNA and protein expression of perilipin A and G0/G1 switch gene 2 (G0S2) in human adipose tissue in poorly controlled type 2 diabetes.

CONTEXT Increased lipolysis and free fatty acid (FFA) levels contribute significantly to the pathogenesis of chronic and acute insulin resistance in type 2 diabetes, but the underlying mechanisms are uncertain. OBJECTIVE Our objective was to test whether increased lipolysis and FFA levels induced by insulin withdrawal are accompanied by increased adipose tissue (AT) contents of adipose triglyceride lipase (ATGL) and/or altered intracellular ATGL regulation. DESIGN AND PARTICIPANTS Nine patients with type 2 diabetes were examined twice in a randomized crossover design after 16 h of 1) hyperglycemia/insulin withdrawal and 2) euglycemia/insulin infusion. Blood samples were drawn and a sc abdominal AT biopsy was obtained. SETTING The study was conducted at a university hospital research unit. RESULTS Circulating glucose (7.2 ± 0.3 vs. 11.2 ± 0.8 mmol/liter) and FFA (0.51 ± 0.05 vs. 0.65 ± 0.04 mmol/liter) were increased and insulin levels decreased after insulin withdrawal. AT ATGL protein tended to be increased (P = 0.075) after insulin withdrawal; by contrast, AT protein and mRNA content of perilipin A (Plin) and G(0)/G(1) switch gene 2 (G0S2), known negative regulators of ATGL activity, were decreased by 20-30% (all P values <0.03). All measured parameters related to hormone-sensitive lipase remained unaffected. CONCLUSIONS We found reduced mRNA and protein content of Plin and G0S2 and borderline increased ATGL protein in sc AT from poorly controlled type 2 diabetic subjects. This suggests that increased ATGL activity may contribute to the elevated lipolysis and circulating FFA levels in acute insulin withdrawal and metabolic dysregulation in type 2 diabetic patients and that this mechanism may be modifiable.
Precision autophagy directed by receptor regulators – emerging examples within the TRIM family

ABSTRACT Selective autophagy entails cooperation between target recognition and assembly of the autophagic apparatus. Target recognition is conducted by receptors that often recognize tags, such as ubiquitin and galectins, although examples of selective autophagy independent of these tags are emerging. It is less known how receptors cooperate with the upstream autophagic regulators, beyond the well-characterized association of receptors with Atg8 or its homologs, such as LC3B (encoded by MAP1LC3B), on autophagic membranes. The molecular details of the emerging role in autophagy of the family of proteins called TRIMs shed light on the coordination between cargo recognition and the assembly and activation of the principal autophagy regulators. In their autophagy roles, TRIMs act both as receptors and as platforms (‘receptor regulators’) for the assembly of the core autophagy regulators, such as ULK1 and Beclin 1 in their activated state. As autophagic receptors, TRIMs can directly recognize endogenous or exogenous targets, obviating a need for intermediary autophagic tags, such as ubiquitin and galectins. The receptor and regulatory features embodied within the same entity allow TRIMs to govern cargo degradation in a highly exact process termed ‘precision autophagy’. Summary: Precision autophagy represents direct recognition of targets by receptors, such as TRIMs, that simultaneously organize core autophagy proteins, coupling recognition to autophagosome formation.
Interannual Variability and Trends of Extratropical Ozone. Part I: Northern Hemisphere

The authors apply principal component analysis (PCA) to the extratropical total column ozone from the combined merged ozone data product and the European Centre for Medium-Range Weather Forecasts assimilated ozone from January 1979 to August 2002. The interannual variability (IAV) of extratropical O3 in the Northern Hemisphere (NH) is characterized by four main modes. Attributable to dominant dynamical effects, these four modes account for nearly 60% of the total ozone variance in the NH. The patterns of variability are distinctly different from those derived for total O3 in the tropics. To relate the derived patterns of O3 to atmospheric dynamics, similar decompositions are performed for the 30–100-hPa geopotential thickness. The results reveal intimate connections between the IAV of total ozone and the atmospheric circulation. The first two leading modes are nearly zonally symmetric and represent the connections to the annular modes and the quasi-biennial oscillation. The other two modes exhibit in-quadrature, wavenumber-1 structures that, when combined, describe the displacement of the polar vortices in response to planetary waves. In the NH, the extrema of these combined modes have preferred locations that suggest fixed topographical and land–sea thermal forcing of the involved planetary waves. Similar spatial patterns and trends in extratropical column ozone are simulated by the Goddard Earth Observation System chemistry–climate model (GEOS-CCM). The decreasing O3 trend is captured in the first mode. The largest trend occurs at the North Pole, with values 1 Dobson Unit (DU) yr 1 . There is almost no trend in tropical O3. The trends derived from PCA are confirmed using a completely independent method, empirical mode decomposition, for zonally averaged O3 data. The O3 trend is also captured by mode 1 in the GEOS-CCM, but the decrease is substantially larger than that in the real atmosphere.
Linkage, Mobility, and Selfishness in the MazF Family of Bacterial Toxins: A Snapshot of Bacterial Evolution

Prokaryotic MazF family toxins cooccur with cognate antitoxins having divergent DNA-binding folds and can be of chromosomal or plasmid origin. Sequence similarity search was carried out to identify the Toxin–Antitoxin (TA) operons of MazF family followed by sequence analysis and phylogenetic studies. The genomic DNA upstream of the TA operons was searched for the presence of regulatory motifs. The MazF family toxins showed a conserved hydrophobic pocket in a multibinding site and are present in pathogenic bacteria. The toxins of the MazF family are associated with four main types of cognate antitoxin partners and cluster as a subfamily on the branches of the phylogenetic tree. This indicates that transmission of the entire operon is the dominant mode of inheritance. The plasmid borne TA modules were interspersed between the chromosomal TA modules of the same subfamily, compatible with a frequent interchange of TA genes between the chromosome and the plasmid akin to that observed for antibiotic resistance gens. The split network of the MazF family toxins showed the AbrB-linked toxins as a hub of horizontal gene transfer. Distinct motifs are present in the upstream region of each subfamily. The presence of MazF family TA modules in pathogenic bacteria and identification of a conserved binding pocket are significant for the development of novel antibacterials to disrupt the TA interaction. However, the role of TAs in stress resistance needs to be established. Phylogenetic studies provide insight into the evolution of MazF family TAs and effect on the bacterial genome.
2 A Language-Based Approach to Categorical Analysis by Cameron Alexander Marlow

With the digitization of media, computers can be employed to help us with the process of classification, both by learning from our behavior to perform the task for us and by exposing new ways for us to think about our information. Given that most of our media comes in the form of electronic text, research in this area focuses on building automatic text classification systems. The standard representation employed by these systems, known as the bag-of-words approach to information retrieval, represents documents as collections of words. As a byproduct of this model, automatic classifiers have difficulty distinguishing between different meanings of a single word. This research presents a new computational model of electronic text, called a synchronic imprint, which uses structural information to contextualize the meaning of words. Every concept in the body of a text is described by its relationships with other concepts in the same text, allowing classification systems to distinguish between alternative meanings of the same word. This representation is applied to both the standard problem of text classification and also to the task of enabling people to better identify large bodies of text. The latter is achieved through the development of a visualization tool named flux that models synchronic imprints as a spring network. Thesis Advisor: Walter Bender Executive Director, MIT Media Laboratory The author gratefully thanks the Motorola Fellows Program for its support and input into the development of this research
Construction of Markov Partitions in PL1D Maps

A method is described for the construction of parameters' subspaces where Markov partitions can be found. The method is illustrated on the three-region piecewise linear 1-D (3PL1D) map, which is a popular approach for the chaos-based random number generator (RNG). For Markov partitions, the 3PL1D chaotic maps behave as Markov sources, and analytical calculation of its information entropy is possible, as demonstrated in this brief. From the knowledge of the stochastic transition matrix of the Markov source, one can exactly measure the appropriateness of the RNG in a given area. For classical RNGs, one typically relies on statistical tests as a quality indicator. Mathematical calculation of the quality of an RNG based on the 3PL1D chaotic maps makes the statistical tests useful only in the postimplementation phase as a verification of the hardware implementation.
High-Individuality Voice Conversion Based on Concatenative Speech Synthesis

Concatenative speech synthesis is a method that can make speech sound which has naturalness and high-individuality of a speaker by introducing a large speech corpus. Based on this method, in this paper, we propose a voice conversion method whose conversion speech has high-individuality and naturalness. The authors also have two subjective evaluation experiments for evaluating individuality and sound quality of conversion speech. From the results, following three facts have be confirmed: (a) the proposal method can convert the individuality of speakers well, (b) employing the framework of unit selection (especially join cost) of concatenative speech synthesis into conventional voice conversion improves the sound quality of conversion speech, and (c) the proposal method is robust against the difference of genders between a source speaker and a target speaker. Keywords—concatenative speech synthesis, join cost, speaker individuality, unit selection, voice conversion
Glycohemoglobin assays evaluated in a large-scale quality-control survey.

We report the results of a national quality-control survey on glycohemoglobin (GHb), monitored in France by the Société Française de Biologie Clinique on behalf of the authority of the "Agence du Médicament. " A sample of lyophilized hemolysate was sent to 3109 laboratories. Results were obtained from 2770 laboratories. HbA1C, HbA1, and total GHb were measured by 50%, 24%, and 26% of the participants, respectively. Of these measurements, 79% of the HbA1C results and 76% of the total GHb results, but only 48% of the HbA1 results, were within the +/- 20% limits of the indicated target values. Mean values for the hemolysate ranged from 8% to 11% for HbA1C, from 7% to 12% for HbA1, and from 11% to 13% for total GHb. The interlaboratory CVs ranged from 3% to 20%, according to method used. So, methods used for GHb assay, which are based on various principles, exhibit very different analytical performances. Nonetheless, this large-scale study indicates that some techniques can support transferability of results from laboratory to laboratory.