Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative N-glycoproteomics reveals altered glycosylation levels of various plasma proteins in bloodstream infected patients

Bloodstream infections are associated with high morbidity and mortality with rates varying from 10–25% and higher. Appropriate and timely onset of antibiotic therapy influences the prognosis of these patients. It requires the diagnostic accuracy which is not afforded by current gold standards such as blood culture. Moreover, the time from blood sampling to blood culture results is a key determinant of reducing mortality. No established biomarkers exist which can differentiate bloodstream infections from other systemic inflammatory conditions. This calls for studies on biomarkers potential of molecular profiling of plasma as it is affected most by the molecular changes accompanying bloodstream infections. N-glycosylation is a post-translational modification which is very sensitive to changes in physiology. Here we have performed targeted quantitative N-glycoproteomics from plasma samples of patients with confirmed positive blood culture together with age and sex matched febrile controls with negative blood culture reports. Three hundred and sixty eight potential N-glycopeptides were quantified by mass spectrometry and 149 were further selected for identification. Twenty four N-glycopeptides were identified with high confidence together with elucidation of the peptide sequence, N-glycosylation site, glycan composition and proposed glycan structures. Principal component analysis, orthogonal projections to latent structures-discriminant analysis (S-Plot) and self-organizing maps clustering among other statistical methods were employed to analyze the data. These methods gave us clear separation of the two patient classes. We propose high-confidence N-glycopeptides which have the power to separate the bloodstream infections from blood culture negative febrile patients and shed light on host response during bacteremia. Data are available via ProteomeXchange with identifier PXD009048.
Imaging of nonlocal hot-electron energy dissipation via shot noise

In modern microelectronic devices, hot electrons accelerate, scatter, and dissipate energy in nanoscale dimensions. Despite recent progress in nanothermometry, direct real-space mapping of hot-electron energy dissipation is challenging because existing techniques are restricted to probing the lattice rather than the electrons. We realize electronic nanothermometry by measuring local current fluctuations, or shot noise, associated with ultrafast hot-electron kinetic processes (~21 terahertz). Exploiting a scanning and contact-free tungsten tip as a local noise probe, we directly visualize hot-electron distributions before their thermal equilibration with the host gallium arsenide/aluminium gallium arsenide crystal lattice. With nanoconstriction devices, we reveal unexpected nonlocal energy dissipation at room temperature, which is reminiscent of ballistic transport of low-temperature quantum conductors.
Stochastic and deterministic models for age-structured populations with genetically variable traits

Understanding how stochastic and non-linear deterministic processes interact is a major challenge in population dynamics theory. After a short review, we introduce a stochastic individual- centered particle model to describe the evolution in continuous time of a population with (continuous) age and trait structures. The individuals reproduce asexually, age, interact and die. The 'trait' is an individual heritable property (d-dimensional vector) that may influence birth and death rates and interactions between individuals, and vary by mutation. In a large population limit, the random process converges to the solution of a Gurtin-McCamy type PDE. We show that the random model has a long time behavior that differs from its deterministic limit. However, the results on the limiting PDE and large deviation techniquesla Freidlin-Wentzell provide estimates of the extinction time and a better understanding of the long time behavior of the stochastic process. This has applications to the theory of adaptive dynamics used in evolutionary biology. We present simulations for two biological problems involving life-history trait evolution when body size is plastic and individual growth is taken into account. Resume. Nous illustrons ici certaines interactions entre processus probabilistes et deterministes en dynamique des populations. Apres une courte revue, nous introduisons un modele particulaire stochas- tique individu-centre pour decrire l'´evolution en temps continu d'une population structuree en age (con- tinu) et en trait. Les individus se reproduisent de facon asexuee, vieillissent, interagissent et meurent. Le trait est une propriete de l'individu mesuree par un vecteur de dimension d ; le trait est heritable et peut influencer les taux de naissance et de mort ainsi que les interactions entre individus. Par muta- tion, le trait peut varier entre parent et enfant. Dans une limite de grande population, notre processus aleatoire converge vers la solution d'une EDP du type Gurtin-McCamy. Nous montrons que le com- portement en temps long du processus aleatoire differe de celui de sa limite deterministe. Cependant, les deux types de modeles sont complementaires : les resultats sur l'EDP limite et des techniques de grandes deviationsla Freidlin-Wentzell, nous fournissent des estimees du temps d'extinction et une description precise du comportement en temps grand de notre processus aleatoire, avec des applica- tionsla theorie des "dynamiques adaptatives". Nous presentons ensuite sur des simulations deux problemes biologiques lies aux consequences de plasticite de la taille lorsque la croissance individuelle est prise en compte, ainsi qu'`a l'´evolution des strategies d'histoire de vie.
Exposure to Hexabromocyclododecanes (HBCDs) via Dust Ingestion, but Not Diet, Correlates with Concentrations in Human Serum: Preliminary Results

Background Hexabromocyclododecane (HBCD) is a high-production-volume chemical used as flame retardant in polystyrene insulation and textiles. Because it is not chemically bound to the polymer, HBCD can migrate into the environment, contaminating indoor dust and foodstuff. Objectives We examined for the first time the relationship between combined exposure to three HBCD isomers (∑HBCDs) via ingestion of food (duplicate diets) and indoor dust and HBCD concentrations in serum for 16 Belgian adults (20–25 years of age). We also determined the chiral signatures of HBCDs to advance understanding of source-to-human enantioselective degradation and/or metabolism. Methods Concentrations and chiral signatures of α-, β-, and γ-HBCD in duplicate diets, dust, and serum were measured by liquid chromatography/tandem mass spectrometry. Results Dietary intakes of ∑HBCDs were 1.2–20 ng/day (average, 7.2 ng/day), whereas those estimated under average (20 mg dust/day) and high (50 mg dust/day) dust ingestion scenarios were 1.1–15 ng/day (average intake, 3.2 ng/day) and 2.8–38 ng/day (average intake, 8.0 ng/day), respectively. Concentrations of ∑HBCDs measured in blood serum were < 0.5 to 11 ng/g lipid weight (lw) (average, 2.9 ng/g lw). γ-HBCD dominated in food, whereas α-HBCD dominated in dust and was the sole isomer in serum. Although exposure via dust ingestion correlated significantly (p < 0.01) with concentrations in serum, no such correlation was evident with dietary exposure (p > 0.1). Although no enantioselective enrichment was detected in either dust or diet, substantial enrichment of (−)α-HBCD was observed in serum. Conclusions Serum concentrations of HBCDs were correlated with the exposure via dust, but not via dietary ingestion. The enrichment of the (−)α-HBCD enantiomer in humans appears to be due to in vivo enantioselective metabolism/excretion rather than ingestion of dust or diet.
Role of skeletal muscle in plasma ion and acid-base regulation after NaHCO3 and KHCO3 loading in humans.

This paper examines the time course of changes in plasma electrolyte and acid-base composition in response to NaHCO3 and KHCO3 ingestion. It was hypothesized that skeletal muscle is involved in the correction of the ensuing plasma disturbance by exchanging ions, gasses, and fluids between cells and extracellular fluids. Five male subjects, with catheters in a brachial artery and antecubital vein, ingested 3.57 mmol/kg body mass NaHCO3 or KHCO3. While seated, blood samples were taken 30 min before ingestion of the solution, at 10-min intervals during the 60-min ingestion period, and periodically for 210 min after ingestion was complete. Blood was analyzed for gases, hematocrit, plasma ions, and total protein. With NaHCO3, arterial plasma Na+ concentration ([Na+]) increased from 143 ± 1 to 147 ± 1 (SE) meq/l, H+ concentration ([H+]) decreased by 6 ± 1 neq/l, and [Formula: see text] increased by 5 ± 1 mmHg. There was no detectable net Na+ uptake by tissues. An increased plasma strong ion difference ([SID]) accounted fully for the decrease in plasma [H+]. With KHCO3, K+ concentration increased from 4.25 ± 0.10 to 7.17 ± 0.13 meq/l, plasma volume decreased by 15.5 ± 2.3%, [H+] decreased by 4 ± 1 neq/l, and there was no change in[Formula: see text]. The decrease in [H+] in the KHCO3 trial primarily arose in response to the increased [SID]. Net K+ uptake by tissues accounted for 37 ± 5% of the ingested K+. In conclusion, ingestion of NaHCO3and KHCO3 produced markedly different fluid and ionic disturbances and associated regulatory responses by skeletal muscle. Accordingly, the physicochemical origins of the acid-base disturbances also differed between treatments. The tissues did not play a role in regulating plasma [Na+] after ingestion of NaHCO3. In contrast, the net influx of K+ to tissues played an important role in removing K+ from the extracellular compartment after ingestion of KHCO3.
Rapyuta: A Cloud Robotics Platform

In this paper, we present the design and implementation of Rapyuta, an open-source cloud robotics platform. Rapyuta helps robots to offload heavy computation by providing secured customizable computing environments in the cloud. The computing environments also allow the robots to easily access the RoboEarth knowledge repository. Furthermore, these computing environments are tightly interconnected, paving the way for deployment of robotic teams. We also describe three typical use cases, some benchmarking and performance results, and two proof-of-concept demonstrations. Note to Practitioners - Rapyuta allows to outsource some or all of a robot's onboard computational processes to a commercial data center. Its main difference to other, similar frameworks like the Google App Engine is that it is specifically tailored towards multiprocess high-bandwidth robotics applications/middlewares and provides a well-documented open-source implementation that can be modified to cover a large variety of robotic scenarios. Rapyuta supports the outsourcing of almost all of the current 3000+ ROS packages out of the box and is easily extensible to other robotic middleware. A pre-installed Amazon Machine Image (AMI) is provided that allows to launch Rapyuta in any of Amazon's data center within minutes. Once launched, robots can authenticate themselves to Rapyuta, create one or more secured computational environments in the cloud and launch the desired nodes/processes. The computing environments can also be arbitrarily connected to build parallel computing architectures on the fly. The WebSocket-based communication protocol, which provides synchronous and asynchronous communication mechanisms, allows not only ROS based robots, but also browsers and mobiles phones to connect to the ecosystem. Rapyuta's computing environments are private, secure, and optimized for data throughput. However, its performance is in large part determined by the latency and quality of the network connection and the performance of the data center. Optimizing performance under these constraints is typically highly application-specific. The paper illustrates an example of performance optimization in a collaborative real-time 3-D mapping application. Other target applications include collaborative 3-D mapping, task/grasp planning, object recognition, localization, and teleoperation, among others.
Postnatal maturation of carotid body and type I cell chemoreception in the rat.

The site of postnatal maturation of carotid body chemoreception is unclear. To test the hypothesis that maturation occurs synchronously in type I cells and the whole carotid body, the development of changes in the intracellular Ca2+ concentration responses to hypoxia, CO2, and combined challenges was studied with fluorescence microscopy in type I cells and compared with the development of carotid sinus nerve (CSN) responses recorded in vitro from term fetal to 3-wk animals. Type I cell responses to all challenges increased between 1 and 8 days and then remained constant, with no multiplicative O2-CO2interaction at any age. The CSN response to hypoxia also matured by 8 days, but CSN responses to CO2 did not change significantly with age. Multiplicative O2-CO2interaction occurred in the CSN response at 2-3 wk but not in younger groups. We conclude that type I cell maturation underlies maturation of the CSN response to hypoxia. However, because development of responses to CO2 and combined hypoxia-CO2 challenges differed between type I cells and the CSN, responses to these stimuli must mature at other, unidentified sites within the developing carotid body.
Superficial buffer barrier and preferentially directed release of Ca2+ in canine airway smooth muscle.

We examined cytosolic concentration of Ca2+([Ca2+]i) in canine airway smooth muscle using fura 2 fluorimetry (global changes in [Ca2+]i), membrane currents (subsarcolemmal [Ca2+]i), and contractions (deep cytosolic [Ca2+]i). Acetylcholine (10-4 M) elicited fluorimetric, electrophysiological, and mechanical responses. Caffeine (5 mM), ryanodine (0.1-30 μM), and 4-chloro-3-ethylphenol (0.1-0.3 mM), all of which trigger Ca2+-induced Ca2+ release, evoked Ca2+ transients and membrane currents but not contractions. The sarcoplasmic reticulum (SR) Ca2+-pump inhibitor cyclopiazonic acid (CPA; 10 μM) evoked Ca2+transients and contractions but not membrane currents. Caffeine occluded the response to CPA, whereas CPA occluded the response to acetylcholine. Finally, KCl contractions were augmented by CPA, ryanodine, or saturation of the SR and reduced when SR filling state was decreased before exposure to KCl. We conclude that 1) the SR forms a superficial buffer barrier dividing the cytosol into functionally distinct compartments in which [Ca2+]iis regulated independently; 2) Ca2+-induced Ca2+ release is preferentially directed toward the sarcolemma; and 3) there is no evidence for multiple, pharmacologically distinct Ca2+ pools.
Epidemiology, Treatment Efficacy, and Anxiety Aspects of Music Students Affected by Playing-Related Pain: A Retrospective Evaluation with Follow-up.

OBJECTIVES Playing-related pain (PRP) is a common problem among music students. We retrospectively assessed epidemiological factors that contributed to the manifestation of PRP and evaluated the efficacy of treatment methods used by affected music students. The long-term course of PRP symptoms was also examined, along with current (today) levels of trait anxieties. METHODS Demographic and epidemiological data of 186 music students who visited the musicians' outpatient clinic over a 5-year period were retrieved. Of these students, 122 had been diagnosed with PRP and were invited to participate (response rate 61.5%) in a follow-up online survey to: a) estimate the long-term course of their PRP symptoms, b) assess the efficacy of treatment methods they used, and c) assess their current trait anxiety (general and performance-related) using two standardized psychodiagnostic questionnaires. RESULTS Two-thirds of music students who sought medical care were affected by PRP, with most being affected during their first year of studies, and with 69% having acute rather than chronic pain. The sudden increase in practice time was the main triggering factor for PRP (but not for non-PRP-related problems). Concerning the course of PRP, almost all students recovered or improved significantly. Students reported that "active" treatment methods (e.g., physical activities) were more effective than "passive" methods (e.g., oral medications). Psychodiagnostic questionnaires indicated that about 40% of PRP-affected students currently had increased levels of trait anxieties (music and non-music related), possibly warranting further medical assistance. CONCLUSIONS PRP in music students occurs mainly at the beginning of their studies and has a good prognosis, although recovery may be lengthy. It is necessary to provide students with early information about PRP and about the multidimensional treatment framework that allows for individualized care of PRP in affected music students.
Icelandic inclusion, German hesitation and American fear: A cross-cultural comparison of mental-health stigma and the media

Aims: Quantitative survey research findings reveal that Western countries have lower rates of public stigma surrounding mental illness than other nations. However, qualitative media research across selected Western countries reports differences in stigmatising messages. Here, we take an in-depth look at country-level data exploring both similarities and differences in this stigma across three countries. Specifically, we use previous findings on global differences in public stigma and media to examine whether there is a correspondence between themes in newspaper reporting and variations in attitudes across seven stigma dimensions. Methods: The Stigma in Global Context – Mental Health Study provides nationally representative data from Iceland (N=1033; response rate=71%), Germany (N=1255; response rate=63.16%) and the USA (N=1425; response rate=67.31%). We limit analyses to respondents who received a vignette describing an individual meeting clinical criterion for schizophrenia or depression. Exploratory data analyses are used to examine overall patterns and cross-national differences. Results: Graphical analyses show patterned similarities, especially for more individuals endorsing social distance as contact becomes more intimate. However, results also corroborate cross-national differences documented in media research. More Americans endorse evaluations of dangerousness, to both self and others. Fewer Icelanders report exclusionary tendencies, whilst Germans report the most consistently moderate levels of stigma. Conclusions: While Western nations tend to report similar, lower levels of stigma globally, they each have unique areas of concern. Anti-stigma programs must take note of both similarities and differences to tailor their efforts to the local context.
Bioactive Glasses: Where Are We and Where Are We Going?

Bioactive glasses caused a revolution in healthcare and paved the way for modern biomaterial-driven regenerative medicine. The first 45S5 glass composition, invented by Larry Hench fifty years ago, was able to bond to living bone and to stimulate osteogenesis through the release of biologically-active ions. 45S5-based glass products have been successfully implanted in millions of patients worldwide, mainly to repair bone and dental defects and, over the years, many other bioactive glass compositions have been proposed for innovative biomedical applications, such as soft tissue repair and drug delivery. The full potential of bioactive glasses seems still yet to be fulfilled, and many of today’s achievements were unthinkable when research began. As a result, the research involving bioactive glasses is highly stimulating and requires a cross-disciplinary collaboration among glass chemists, bioengineers, and clinicians. The present article provides a picture of the current clinical applications of bioactive glasses, and depicts six relevant challenges deserving to be tackled in the near future. We hope that this work can be useful to both early-stage researchers, who are moving with their first steps in the world of bioactive glasses, and experienced scientists, to stimulate discussion about future research and discover new applications for glass in medicine.
Lgr5+ intestinal stem cells reside in an unlicensed G1 phase

During late mitosis and the early G1 phase, the origins of replication are licensed by binding to double hexamers of MCM2–7. In this study, we investigated how licensing and proliferative commitment are coupled in the epithelium of the small intestine. We developed a method for identifying cells in intact tissue containing DNA-bound MCM2–7. Interphase cells above the transit-amplifying compartment had no DNA-bound MCM2–7, but still expressed the MCM2–7 protein, suggesting that licensing is inhibited immediately upon differentiation. Strikingly, we found most proliferative Lgr5+ stem cells are in an unlicensed state. This suggests that the elongated cell–cycle of intestinal stem cells is caused by an increased G1 length, characterized by dormant periods with unlicensed origins. Significantly, the unlicensed state is lost in Apc-mutant epithelium, which lacks a functional restriction point, causing licensing immediately upon G1 entry. We propose that the unlicensed G1 phase of intestinal stem cells creates a temporal window when proliferative fate decisions can be made.
Regional differences in effects of E-4031 within the sinoatrial node.

Effects of block of the rapid delayed rectifier K+current ( I K,r) by E-4031 on the electrical activity of small ball-like tissue preparations from different regions of the rabbit sinoatrial node were measured. The effects of partial block of I K,r by 0.1 μM E-4031 varied in different regions of the node. In tissue from the center of the node spontaneous activity was generally abolished, whereas in tissue from the periphery spontaneous activity persisted, although the action potential was prolonged, the maximum diastolic potential was decreased, and the spontaneous activity slowed. After partial block of I K,r, the electrical activity of peripheral tissue was more like that of central tissue under normal conditions. One possible explanation of these findings is that the density of I K,r is greater in the periphery of the node; this would explain the greater resistance of peripheral tissue to I K,r block and help explain why, under normal conditions, the maximum diastolic potential is more negative, the action potential is shorter, and pacemaking is faster in the periphery.
Recent Insights into the Paradoxical Effect of Echinocandins

Echinocandin antifungals represent one of the most important drug classes for the treatment of invasive fungal infections. The mode of action of the echinocandins relies on inhibition of the β-1,3-glucan synthase, an enzyme essentially required for the synthesis of the major fungal cell wall carbohydrate β-1,3-glucan. Depending on the species, echinocandins may exert fungicidal or fungistatic activity. Apparently independent of this differential activity, a surprising in vitro phenomenon called the “paradoxical effect” can be observed. The paradoxical effect is characterized by the ability of certain fungal isolates to reconstitute growth in the presence of higher echinocandin concentrations, while being fully susceptible at lower concentrations. The nature of the paradoxical effect is not fully understood and has been the focus of multiple studies in the last two decades. Here we concisely review the current literature and propose an updated model for the paradoxical effect, taking into account recent advances in the field.