Miracle-dz/UniFAR-FTUs huggingface dataset:
Tenebrionid secretions and a fungal benzoquinone oxidoreductase form competing components of an arms race between a host and pathogen

Significance Although entomopathogenic fungi and their invertebrate hosts share a >300 million year co-evolutionary history, little is known concerning the biochemical and genetic basis of insect defensive tactics and the countermeasures evolved and evolving by the pathogen to thwart these defenses. Our results provide a molecular mechanism to help explain why some insects are more resistant to broad host-range entomopathogenic fungi. We identify beetle cuticular secretions and a fungal detoxifying enzyme as components of an arms race between insects and the fungal pathogen, suggesting an evolving role for the quinone reductase enzyme as a specific virulence factor for host quinone detoxification. As races have winners and losers, this paper captures a snapshot where the host is leading the race. Entomopathogenic fungi and their insect hosts represent a model system for examining invertebrate-pathogen coevolutionary selection processes. Here we report the characterization of competing components of an arms race consisting of insect protective antimicrobial compounds and evolving fungal mechanisms of detoxification. The insect pathogenic fungus Beauveria bassiana has a remarkably wide host range; however, some insects are resistant to fungal infection. Among resistant insects is the tenebrionid beetle Tribolium castaneum that produces benzoquinone-containing defensive secretions. Reduced fungal germination and growth was seen in media containing T. castaneum dichloromethane extracts or synthetic benzoquinone. In response to benzoquinone exposure, the fungus expresses a 1,4-benzoquinone oxidoreductase, BbbqrA, induced >40-fold. Gene knockout mutants (ΔBbbqrA) showed increased growth inhibition, whereas B. bassiana overexpressing BbbqrA (Bb::BbbqrAO) displayed increased resistance to benzoquinone compared with wild type. Increased benzoquinone reductase activity was detected in wild-type cells exposed to benzoquinone and in the overexpression strain. Heterologous expression and purification of BbBqrA in Escherichia coli confirmed NAD(P)H-dependent benzoquinone reductase activity. The ΔBbbqrA strain showed decreased virulence toward T. castaneum, whereas overexpression of BbbqrA increased mortality versus T. castaneum. No change in virulence was seen for the ΔBbbqrA or Bb::BbbqrAO strains when tested against the greater wax moth Galleria mellonella or the beetle Sitophilus oryzae, neither of which produce significant amounts of cuticular quinones. The observation that artificial overexpression of BbbqrA results in increased virulence only toward quinone-secreting insects implies the lack of strong selection or current failure of B. bassiana to counteradapt to this particular host defense throughout evolution.
Expanding the lens of HIV services provision in Canada: results of a national survey of HIV health professionals

Abstract Those living with HIV may experience a range of disabilities, including body impairments, activity limitations, and social participation restrictions. The aim of this study was to examine HIV services provision in Canada by exploring practices, referrals, and service delivery challenges from the perspective of HIV health professionals (including nurses, physicians, social workers, pharmacists, psychologists, and dieticians), and to explore differences in referrals and perceived service delivery challenges by professional group, jurisdiction, community size, and practice in a Northern region. We conducted a nationwide mail survey with the population of selected HIV health professionals in Canada using the Dillman tailored design survey method. Of the 731 deliverable mailings, we received 462 (63%) responses, with 36% of eligible respondents completing the survey (n=214). The large majority (90%) of HIV professionals were located in metropolitan or urban communities and worked predominantly in hospital in-patient (42%), out-patient (50%), and HIV specialty clinic (46%) settings in one of the three provinces (Ontario, Quebec, and British Columbia) with the highest HIV prevalence. HIV health professionals referred primarily, and at relatively high levels, to AIDS service organizations (79%) and social workers (84%) to address participation restrictions and social issues; a lower percentage referred to rehabilitation professionals and other service providers to address impairments, activity limitations, or participation restrictions. Of respondents, 74% perceived barriers to care specific to HIV. Our results suggest that there is little difference in referral patterns by profession, jurisdiction, community size, or northern region of practice. There is a need for increased information and education of HIV health professionals that may refer to rehabilitation and other health services. In addition, new approaches are needed to coordinate multisectoral care and enhance the access and delivery of HIV rehabilitation health services to better meet the disablement needs of people living with HIV in Canada.
Implications of Protein Post‐Translational Modifications in IBD

Abstract: In recent years our understanding of the pathogenesis of inflammatory bowel disease (IBD) has greatly increased. Hallmarks of IBD include loss of intestinal barrier function, increased cytokine production, and failed resolution of tissue damage. Lasting treatments are still lacking and, therefore, a better understanding of the underlying molecular mechanisms is necessary to design novel therapeutic approaches. Apart from transcriptional and posttranscriptional regulation of relevant genes, mammals have evolved a complex and efficient series of mechanisms to rapidly modify newly made proteins for the purposes of signaling and adaptation. These posttranslational protein modifications include, among others, phosphorylation, hydroxylation, neddylation, and cytokine cleavage by the inflammasome. This review focuses on our current understanding of posttranslational protein modifications with a particular focus on their relevance to IBD pathogenesis. (Inflamm Bowel Dis 2012;)
Model for muscle regeneration around fibrotic lesions in recurrent strain injuries.

PURPOSE The purpose of this study was to establish an in vivo model for muscle regeneration after strain injury in the presence of a fibrotic discontinuity. METHODS The musculus soleus of 5-wk-old male rats was exposed, completely lacerated, and sutured together with or without a collagen scaffold in between the muscle ends. The scaffold represents a fibrotic discontinuity in the muscle. Muscle healing was evaluated after 14 d by general histology and staining for myofibroblasts, satellite cells (activated), and inflammatory cells. RESULTS Around all wounds, satellite cells were activated. Inside the collagen scaffolds, satellite cells were absent, indicating that muscle regeneration was impaired. In the wounds without a collagen scaffold, the lacerated and the sutured myofibers contacted and had already started to regenerate, whereas this did not occur with an implanted scaffold. CONCLUSIONS A fibrotic discontinuity, such as an implanted collagen scaffold, delays muscle regeneration in skeletal muscle. This model is suitable to study skeletal muscle regeneration in the presence of a fibrotic lesion and to evaluate new treatment modalities for muscle strain injuries.
Polynomial size linear programs for non-bipartite matching problems and other problems in P

A perfect matching in an undirected graph G = (V,E) is a set of vertex disjoint edges from E that include all vertices in V . The perfect matching problem is to decide if G has such a matching. Recently Rothvoß proved the striking result that the Edmonds’ matching polytope has exponential extension complexity. Here we describe a perfect matching polytope that is different from Edmonds’ polytope and define a weaker notion of extended formulation. We show that the new polytope has a weak extended formulation (WEF) Q of polynomial size. For each graph G we can readily construct an objective function so that solving the resulting linear program over Q decides whether or not G has a perfect matching. With this construction, a straightforward O(n) implementation of Edmonds’ matching algorithm using O(n logn) bits of space would yield a WEF Q with O(n logn) inequalities and variables. The method described here can be easily adapted for other matching problems, or indeed, for any problem in P/poly which can be solved by a well defined circuit or algorithm. The main tool is a method that converts a given circuit, or algorithm written in our pseudocode, for a decision problem into a polytope. We also apply these results to obtain polynomial upper bounds on the non-negative rank of certain slack matrices related to membership testing of languages in P/Poly.
“Lovely Pie in the Sky Plans”: A Qualitative Study of Clinicians’ Perspectives on Guidelines for Managing Low Back Pain in Primary Care in England

Study Design. A qualitative study in south-west England primary care. Objective. To clarify the decision-making processes that result in the delivery of particular treatments to patients with low back pain (LBP) in primary care and to examine clinicians’ perspectives on the English National Institute for Health and Care Excellence (NICE) clinical guidelines for managing LBP in primary care. Summary of Background Data. Merely publishing clinical guidelines is known to be insufficient to ensure their implementation. Gaining an in-depth understanding of clinicians’ perspectives on specific clinical guidelines can suggest ways to improve the relevance of guidelines for clinical practice. Methods. We conducted semi-structured interviews with 53 purposively sampled clinicians. Participants were 16 general practitioners (GPs), 10 chiropractors, 8 acupuncturists, 8 physiotherapists, 7 osteopaths, and 4 nurses, from the public sector (20), private sector (21), or both (12). We used thematic analysis. Results. Official guidelines comprised just 1 of many inputs to clinical decision-making. Clinicians drew on personal experience and inter-professional networks and were constrained by organizational factors when deciding which treatment to prescribe, refer for, or deliver to an individual patient with LBP. Some found the guideline terminology—“non-specific LBP”—unfamiliar and of limited relevance to practice. They were frustrated by disparities between recommendations in the guidelines and the real-world situation of short consultation times, difficult-to-access specialist services, and sparse commissioning of guideline-recommended treatments. Conclusion. The NICE guidelines for managing LBP in primary care are one, relatively peripheral, influence on clinical decision-making among GPs, chiropractors, acupuncturists, physiotherapists, osteopaths, and nurses. When revised, these guidelines could be made more clinically relevant by: ensuring that guideline terminology reflects clinical practice terminology; dispelling the image of guidelines as rigid and prohibiting patient-centered care; providing opportunities for clinicians to engage in experiential learning about guideline-recommended complementary therapies; and commissioning guideline-recommended treatments for public sector patients. Level of Evidence: N/A.
Oczekiwania wobec lekarzy weterynarii jako odzwierciedlenie przemian świadomości ludzi

In contemporary world the prestige of the profession of veterinarians increases significantly, mainly because of dynamic changes in perception of human – non‑human relations. Is the profession of veterinarian comparable to human medical doctor? The doctor of veterinary becomes not only medical expert, but also behaviorist and psychologist at the same time. Taking care of animals they enter close relationships with humans as well. Moreover‑ those relations reflect status of animal as the family member. On the other hand in some other contexts, veterinarian is expected to present very instrumental approach to animals (f.i. in industrial farming). This complex situation requires changes in educating perspective veterinarian specialists (both doctors and assistants). It becomes necessary to reflect on education system and ethics of veterinary sciences in present socio‑cultural context.
Hypercapnia: clinical relevance and mechanisms of action

Purpose of reviewMultiple clinical and laboratory studies have been conducted to illustrate the effects of hypercapnia in a range of injuries, and to understand the mechanisms underlying these effects. The aim of this review is to highlight and interpret information obtained from these recent reports and discuss how they may inform the clinical context. Recent findingsIn the last decade, several important articles have addressed key elements of how carbon dioxide interacts in critical illness states. Among them the most important insights relate to how hypercapnia affects critical illness and include the effects and mechanisms of carbon dioxide in pulmonary hypertension, infection, inflammation, diaphragm dysfunction, and cerebral ischemia. In addition, we discuss molecular insights that apply to multiple aspects of critical illness. SummaryExperiments involving hypercapnia have covered a wide range of illness models with varying degrees of success. It is becoming evident that deliberate hypercapnia in the clinical setting should seldom be used, except wherever necessitated to avoid ventilator-associated lung injury. A more complete understanding of the molecular mechanisms must be established.
DNA analysis of an early modern human from Tianyuan Cave, China

Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (∼30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia.
Improving Protocol State Fuzzing of SSH

With the scale and use of the Internet nowadays, it is crucial that we can eﬀectively test the correctness and security of systems that handle our personal data. In this thesis, we improve upon a previous work by Verleg. Verleg used protocol state fuzzing to test several implementations of the SSH protocol. By adapting a more formal methodology, we achieve higher conﬁdence in our results. We improve upon Verleg’s methodology in three ways: First, we expand the scope of our learned model, by learning a single model for the three layers of SSH. Then, we achieve a degree of conﬁdence in our model by using a more advanced testing algorithm. Finally, we increase conﬁdence in the analysis of model by performing formal model checking instead of manual inspection of results.
In vivo Drug Screening in Human Skin Using Femtosecond Laser Multiphoton Tomography

The novel femtosecond laser multiphoton imaging system DermaInspect forin vivotomography of human skin was used to study the diffusion and intradermal accumulation of topically applied cosmetic and pharmaceutical components. Near-infrared 80 MHz picojoule femtosecond laser pulses were employed to excite endogenous fluorophores and fluorescent components of a variety of ointments via a two-photon excitation process. In addition, collagen was imaged by second harmonic generation. A high submicron spatial resolution and 50 ps temporal resolution was achieved using galvoscan mirrors and piezodriven focusing optics together with a time-correlated single-photon counting module with a fast microchannel plate detector. Individual intratissue cells, intracellular mitochondria, melanosomes, and the morphology of the nuclei as well as extracellular matrix elements were clearly visualized due to NAD(P)H, melanin, elastin, and collagen imaging and the calculation of fluorescence lifetime images. Nanoparticles and intratissue drugs were detected by two-photon-excited fluorescence. In addition, hydration effects and UV effects were studied by monitoring modifications of cellular morphology and autofluorescence. The system was used to observe the diffusion through the stratum corneum and the accumulation and release of functionalized nanoparticles along hair shafts and epidermal ridges. The novel noninvasive 4-D multiphoton tomography tool provides high-resolution optical biopsies with subcellular resolution, and offers for the first time the possibility to study in situthe diffusion through the skin barrier, long-term pharmacokinetics, and cellular response to cosmetic and pharmaceutical products.
The evolution of cooperative breeding in birds: kinship, dispersal and life history

The evolution of cooperation among animals has posed a major problem for evolutionary biologists, and despite decades of research into avian cooperative breeding systems, many questions about the evolution of their societies remain unresolved. A review of the kin structure of avian societies shows that a large majority live in kin-based groups. This is consistent with the proposed evolutionary routes to cooperative breeding via delayed dispersal leading to family formation, or limited dispersal leading to kin neighbourhoods. Hypotheses proposed to explain the evolution of cooperative breeding systems have focused on the role of population viscosity, induced by ecological/demographic constraints or benefits of philopatry, in generating this kin structure. However, comparative analyses have failed to generate robust predictions about the nature of those constraints, nor differentiated between the viscosity of social and non-social populations, except at a coarse level. I consider deficiencies in our understanding of how avian dispersal strategies differ between social and non-social species, and suggest that research has focused too narrowly on population viscosity and that a broader perspective that encompasses life history and demographic processes may provide fresh insights into the evolution of avian societies.
Velocity observer-based iterative learning control for robot manipulators

This article addresses the problem of designing an iterative learning control for trajectory tracking of rigid robot manipulators subject to external disturbances, and performing repetitive tasks, without using the velocity measurement. For solving this problem, a velocity observer having an iterative form is proposed to reconstruct the velocity signal in the control laws. Under assumptions that the disturbances are repetitive and the velocities are bounded, it has been shown that the whole control system (robot plus controller plus observer) is asymptotically stable and the observation error is globally asymptotically stable, over the whole finite time-interval when the iteration number tends to infinity. This proof is based upon the use of a Lyapunov-like positive definite sequence, which is shown to be monotonically decreasing under the proposed observer–controller schemes.
Extracellular Signal-regulated Kinase (ERK) Activation Is Required for GP Ibα-dependent Endothelial Cell Migration

Summary The GP Ib complex can participate in endothelial cell (EC) migration on von Willebrand factor (vWF) or the mixed matrix of vWF and type I collagen (vWF/collagen). In this study, viper venom proteins alboaggregin (albo) A or B blocked GP Ibα, and echistatin inhibited αvβ3 binding. Albo A, B and echistatin inhibited EC migration on vWF and vWF/collagen. Albo B or the anti-GP Ibα monoclonal antibody (mAb) 1b1 did not affect the migration of smooth muscle cells or fibroblasts, which lack GP Ib. EC also migrate on albo A- or albo B-coated dishes. PD98059, which blocks ERK activation, abolished EC migration on vWF, vWF/collagen, collagen or albo B. Soluble albo A or 1b1 dramatically inhibited ERK activation during EC migration on vWF or albo B. Echistatin inhibited ERK activation on vWF and vitronectin (VN), but not albo B. Thus, in addition to αvβ3, EC GP Ibα initiates ERK activation, and regulates ERK-induced EC migration on vWF.
An Analysis of Prognostic Factors in Pancreatic Neuroendocrine Tumors

Background: Pancreatic neuroendocrine tumors (PNETs) generally behave indolently. However, some manifest an aggressive clinical course with poor prognosis. It is not clear whether this is due to intrinsic tumor aggressiveness, dedifferentiation, or simply silent progressive tumor accumulation that then triggers complications. This study analysed the features of PNETs to gain further insight into their biology. Methods: A retrospective clinicopathologic review of 74 PNETs using Kaplan-Meier and Cox proportional hazard analyses. Results: Median overall survival was 117 months; 5 year survivals were 92% where the PNETs were resected versus 35% for those not resected (p<0.001). Liver metastases developed in 33/74 (18/33 synchronous metastases; 15/33 metachronous). There was a significant difference in Ki67 grade between metastatic and non-metastatic tumors (p<0.001). However, there was considerable overlap of grades between synchronous and metachronous tumor groups with 5/10 (50%) of synchronous PNETs being well-differentiated. Most patients with metachronous metastases (10/15; 67%) showed non-progressive disease whereas the majority with synchronous metastases (15/18; 83%) manifested progressive disease (p=0.01). On Cox analysis, synchronous metastases and inoperability were significant predictors of survival whereas Ki67 grade and T/N stage were not. Conclusion: Aggressive PNETs were associated with synchronous metastases and inoperability. By multivariate analysis, the strongest adverse prognostic factor was synchronous metastases and this was related to the poor outcome over and above what was indicated by the Ki67 grade on univariate analysis. While it is not entirely clear whether the presence of synchronous metastases reflects intrinsic tumor aggressiveness or simply disease in the later stages of its natural history, our findings suggest that they reflect intrinsic aggressiveness de novo. However larger studies with more statistical power are required to further substantiate this. While cell proliferation markers such as Ki67 have greatly improved our grading and understanding of PNETs, molecular studies of events involved in the metastatic cascade could also be meritorious in elucidating disease biology.