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•Exposure of MSCs to B-ALL cell lines triggers CAF formation.•The proximate trigger for CAF formation is ALL-derived mitochondrial dsRNA.

The optimal timing of anticoagulation for patients with acute ischaemic stoke with atrial fibrillation is uncertain. We investigated the efficacy and safety of early compared with delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischaemic stroke associated with atrial fibrillation.

Purpose: A growing body of evidence has pointed out diverse factors limiting carbon (C) sequestration in soils under conservation tillage. This suggests the need for site-specific evaluations for better understanding agricultural practice effects and deployment of sustainable agriculture. Methods: We used a long-term experiment (18 years) to explore 12 scenarios of corn production [conventional (CT), minimum (MT), and no-tillage (NT) combined with four cover crops] in a tropical sandy soil. The soil organic carbon (SOC), nitrogen (N) and C-pools with different turnover rates (active and passive) were measured over 60 cm depth. C-pools were determined under a gradient of C-oxidation. Results: Increments in SOC stocks in MT and NT were observed up to 40 cm depth, but it relied upon the cover crop choice. NT resulted in higher increments in the active-C pool (23%), while MT increased both the active (26%) and passive-C pools (78%) at 0–40 cm depth compared to CT. Higher N stocks were observed in conservation tillage systems than CT. Cover cropping did not influence SOC pools in superficial layers of CT. Conversely, it dictated the maximum C accrual over the soil profile (60 cm) of MT (53.9 Mg C ha− 1) and NT (47.8 Mg C ha− 1) systems. The combination of MT and leguminous species resulted in increments of up to 6 Mg C ha− 1in the active and passive-C pools when compared to CT. Conclusion: Our study demonstrates that higher soil C and N storage downward tropical sandy soils profile can be achieved by a long-term combination of reduced soil disturbance and cover crop choice. MT has the ability to increase both labile-C and stable-C pools, thereby potentially promoting biological activity and acting as a longer-term C sink simultaneously.

With the increasing prevalence of artificial intelligence (AI), a key question is how to adequately prepare the next generation of software engineers to build AI-intensive systems. This article presents our teaching experience for presenting the “Engineering of AI-intensive Systems” course to postgraduate students.

The modernization of monolithic legacy systems with microservices has been a trend in recent years. As part of this modernization, identifying microservice candidates starting from legacy code is challenging, as maintainers may consider many criteria simultaneously. Multi-objective search-based approaches represent a promising state-of-the-art solution to support this decision-making process. However, the rationale to adopt each microservice candidate automatically identified by these approaches is poorly investigated in industrial cases. Furthermore, studies with these approaches have not carefully investigated how maintainers reason and make decisions when designing microservice architectures from legacy systems. To address this gap, we conducted an on-site case study with maintainers of an industrial legacy system to investigate the usefulness of automatically generated microservice architectures. We analyze design decisions pointed out by the maintainers when reasoning about microservice candidates using several criteria at the same time. Our study is the first to assess a search-based approach involving actual maintainers conceiving microservice architectures in an industrial setting. Therefore, firstly, we considered individual evaluation of microservice candidates to understand the rationale for identifying a service. Secondly, we conducted a focus group study with maintainers with the goal of investigating design decisions at an architectural level. The results show that: (i) the automated approach is able to identify useful microservices; (ii) the criteria observed by previous studies are, in fact, considered by maintainers; and (iii) the maintainer profiles, i.e., the preferred granularity for microservice, highly affect design decisions. Finally, we observed the maintainers needed little effort in adjusting the automatically identified microservices to make them adoptable. In addition to indicating a promising potential of search-based approaches to generate microservice architectures, our findings highlight the need for: (i) interactive and/or customizable approaches that enable maintainers to include their preferences during the search process, and (ii) flexible or automated selection of criteria that fits the scenario in which the modernization is taking place.

Objective.Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII.

Mineral dissolution is an important process that occurs in both natural as well as anthropogenic processes. The kinetics of such dissolution processes are influenced not only by the characteristics of the solution but also by the characteristics of the minerals, such as crystal defects on the microscopic scale or macroscopic features such as the intersection of crystal planes to form edges and corners. Macroscopic features are known to increase the population of steps and kinks that may, in turn, affect the dissolution rate over time. Hence, this study presents a 3D empirical dissolution model aimed at examining the time-series evolution of macroscopic features together with the corresponding changes in the dissolution rate under far from equilibrium batch reactor conditions. The developed empirical model is based on the mineral geometry (surface topography and volume) derived from X-ray computed tomography (CT) measurements. The macroscopic features are identified using surface curvature which are then used to generate reactivity maps for dissolution model. As a study case, the dissolution of monomineralic galena (PbS) in ethaline and iodine as oxidizing agent is experimentally observed and then modelled. The model is then applied to seven particles of various shapes and sizes. The finding suggests that the surface reactivity increases over time as the particle shrinks and the macroscale steps and edges become dominant over the initial terraces. This implies that the persistent highly reactive surface sites defined by a particle’s geometry may play a dominant role in the overall particle dissolution in addition to the dissolution mechanisms typically studied on near atomic-flat surfaces. The model developed in this investigation offers the opportunity to be extended providing the possibility of simulating the dissolution of multi-mineral particles during batch dissolution experiments.

In the four years since he made his first music video, Nuno Gomes, 30, has lensed a staggering 145 more, collectively earning 5 billion-plus views on YouTube. The Venezuelan director [...]

Australian researchers estimate that the lifetime cost of treating HIV-infected patients in 1992-1993 ranged from $70,000 to $93,000. This is substantially less than the estimated cost in the US, which was $119,000 in one published study. However, the US study did not discount for future costs. When the US data are discounted, the lifetime cost is 17% lower, at $74,900. Costs in Australia may be higher because most Australians are covered by publicly funded health insurance, whereas many American patients may go untreated.

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AFTER FIVE DAYS OF THE INTENSE party marathon that takes over Brazil during Carnival, drag queen Pabllo Vittar is exhausted. The 23-year-old phenom, who kicked the internet into overdrive in [...]

X-ray computed micro tomography (CT) is the main 3D technique for imaging the internal microstructures of samples. Experimental planning is crucial to ensure the adequacy of CT results to answer specific scientific questions, optimizing the use of resources and maximizing the quality of results. Proper planning requires a certain level of expertise in the technique and the details of the specific scientific question to be answered. Notably, potential new CT users who have formulated a scientific question may not have the in-depth knowledge about CT necessary to make a first assessment of whether CT is suitable for their work.

Introduction: Cerebral blood flow (CBF) declines with age and abnormalities in CBF are associated with age-related cerebrovascular disease and neurodegeneration. Women have higher CBF than men, although this sex-difference diminishes to some extent with age in healthy subjects. The physiological drivers of these age/sex differences are uncertain, but might be secondary to age and sex-differences in haemoglobin (Hb) level. Hb levels are inversely correlated with CBF, are lower in women, and decline with age in men, but the interrelations between these factors have not been explored systematically either in healthy subjects or across the full age-range in patients with vascular risk factors. We aimed to determine the age-specific interrelations between sex, Hb, and CBF velocity in a large cohort of patients with cerebrovascular disease.Patients and methods: In patients with a recent transient ischaemic attack or minor stroke (Oxford Vascular Study) and no ipsilateral or contralateral stenosis of the carotid or intracranial arteries, we related peak-systolic velocity (PSV) and other parameters on transcranial Doppler ultrasound (TCD) of the middle cerebral artery to sex, age, Hb and vascular risk factors.Results: Of 958 eligible subjects (mean age/SD = 68.04/14.26, 53.2% male), younger women (age < 55 years) had higher CBF velocities than men (mean sex difference in PSV at age < 55 years = 16.31 cm/s; p< 0.001), but this difference declined with age (interaction p< 0.001), such that it was no longer significant at age 75–84 (∆PSV = 3.26 cm/s; p= 0.12) and was reversed at age ⩾ 85 (∆PSV = −7.42 cm/s; p= 0.05). These changes mirrored trends in levels of Hb, which were higher in men at age < 55 (∆Hb = 1.92 g/dL; p< 0.001), but steadily decreased with age in men but not in women (interaction p< 0.001), with no residual sex-difference at age ⩾ 85 (∆Hb = 0.12 g/dL; p= 0.70). There was an inverse correlation between Hb and PSV in both women and men (both p⩽ 0.01), and the sex-difference in PSV at age < 55 was substantially diminished after adjustment for Hb (∆PSV = 6.92; p= 0.036; ∆PSV = 5.92, p= 0.13 with further adjustment for end-tidal CO2). In contrast, the sex difference in PSV was unaffected by adjustment for systolic and diastolic blood pressure, heart rate, and vascular risk factors (history of hypertension, diabetes, hyperlipidaemia and smoking).Discussion: CBF velocity is strongly correlated with Hb level at all ages, and sex-differences in CBF velocity appear to be explained in major part by age-related sex-differences in Hb.

Table of Contents Abstract Introduction Case Report Discussion Conclusion References Abstract There are sparse data concerning redo surgery for failed odontoid screw fixation and posttraumatic spinal stenosis C1-2. Also, a [...]

This paper proposes a method for optimal classification of voice packets to enhance the quality of voice communications over priority-enabled networks when poor transmission conditions occur. Either high or low priority is assigned to each packet according to the relevance of its payload (voice segment) for the voice intelligibility. Then, in case of constrained networking conditions, by discarding first the voice packets of lower importance, the network always delivers those segments that most contribute to the perceptual quality. The proposed method is based on a dynamic programming optimisation algorithm that finds the optimal subset of m high priority voice segments in each utterance of size n > m. Such optimal subset minimizes the reconstruction distortion over all possible subsets with the same size m (i.e., the distortion incurred by a utterance reconstructed from only m segments). The simulation results show that the proposed method consistently achieves higher mean opinion scores (MOS) in comparison with non-selective packet drop under the same random network loss conditions, yielding better quality of experience (QoE) for the same packet loss rates (PLR). The priority classification algorithm is independent from error concealment methods and distortion metrics used in the optimisation process, which allows generalisation for diverse communication networks and applications.

Antimicrobial Resistance (AMR) is a serious problem for the humans since it threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. One way around this problem is to act on the virulence factors, produced by bacteria, which increase their infection effectiveness. In view of these facts, new coumarin derivatives were synthesized and evaluated for their anti-virulence biological activity towards Pseudomonas aeruginosa. The results suggest that coumarin derivatives with a secondary carbon at C-3 position reduces P. aeruginosa growth whereas compounds with one additional substituent have a significant effect over pyocyanin production (10k EC50 7 ± 2 μM; 10l EC50 42 ± 13 μM). Moreover, 10k reduces P. aeruginosa motility and biofilm formation, what is compatible with a quorum sensing related mechanism of action.

Patients with acute leukemia (AL) have a higher rate of congestive heart failure than patients with other cancers. AL may predispose to cardiac dysfunction before chemotherapy because of high cytokine release or direct leukemic myocardial infiltration. The aims of this study were to evaluate whether AL is associated with abnormalities of myocardial structure and function before chemotherapy and to identify possible risk factors associated with these myocardial changes.

Primary sclerosing cholangitis (PSC) is an incurable, fibroinflammatory biliary disease for which there is no effective pharmacotherapy. We recently reported cholangiocyte senescence as an important phenotype in PSC while others showed that portal macrophages accumulate in PSC. Unfortunately, our ability to explore cholangiocyte senescence and macrophage accumulation has been hampered by limited in vitro models. Thus, our aim was to develop and characterize a three-dimensional (3D) model of normal and diseased bile ducts (cholangioids) starting with normal human cholangiocytes (NHC), senescent NHC (NHC-sen), and cholangiocytes from PSC patients. In 3D culture, NHCs formed spheroids of ~5000 cells with a central lumen of ~150 μm. By confocal microscopy and western blot, cholangioids retained expression of cholangiocyte proteins (cytokeratin 7/19) and markers of epithelial polarity (secretin receptor and GM130). Cholangioids are functionally active, and upon secretin stimulation, luminal size increased by ~80%. Cholangioids exposed to hydrogen peroxide exhibited cellular senescence and the senescence-associated secretory phenotype (SASP; increased IL-6, p21, SA‐β-Gal, yH2A.x and p16 expression). Furthermore, cholangioids derived from NHC-sen or PSC patients were smaller and had slower growth than the controls. When co-cultured with THP-1 macrophages, the number of macrophages associated with NHC-sen or PSC cholangioids was five- to seven-fold greater compared to co-culture with non-senescent NHC. We observed that NHC-sen and PSC cholangioids release greater number of extracellular vesicles (EVs) compared to controls. Moreover, conditioned media from NHC-sen cholangioids resulted in an ~2-fold increase in macrophage migration. In summary, we developed a method to generate normal and diseased cholangioids, characterized them morphologically and functionally, showed that they can be induced to senescence and SASP, and demonstrated both EV release and macrophage attraction. This novel model mimics several features of PSC, and thus will be useful for studying the pathogenesis of PSC and potentially identifying new therapeutic targets.

Primary sclerosing cholangitis (PSC) is an incurable, fibroinflammatory biliary disease for which there is no effective pharmacotherapy. We recently reported cholangiocyte senescence as an important phenotype in PSC while others showed that portal macrophages accumulate in PSC. Unfortunately, our ability to explore cholangiocyte senescence and macrophage accumulation has been hampered by limited in vitromodels. Thus, our aim was to develop and characterize a three-dimensional (3D) model of normal and diseased bile ducts (cholangioids) starting with normal human cholangiocytes (NHC), senescent NHC (NHC-sen), and cholangiocytes from PSC patients. In 3D culture, NHCs formed spheroids of ~5000 cells with a central lumen of ~150 μm. By confocal microscopy and western blot, cholangioids retained expression of cholangiocyte proteins (cytokeratin 7/19) and markers of epithelial polarity (secretin receptor and GM130). Cholangioids are functionally active, and upon secretin stimulation, luminal size increased by ~80%. Cholangioids exposed to hydrogen peroxide exhibited cellular senescence and the senescence-associated secretory phenotype (SASP; increased IL-6, p21, SA‐β-Gal, yH2A.x and p16 expression). Furthermore, cholangioids derived from NHC-sen or PSC patients were smaller and had slower growth than the controls. When co-cultured with THP-1 macrophages, the number of macrophages associated with NHC-sen or PSC cholangioids was five- to seven-fold greater compared to co-culture with non-senescent NHC. We observed that NHC-sen and PSC cholangioids release greater number of extracellular vesicles (EVs) compared to controls. Moreover, conditioned media from NHC-sen cholangioids resulted in an ~2-fold increase in macrophage migration. In summary, we developed a method to generate normal and diseased cholangioids, characterized them morphologically and functionally, showed that they can be induced to senescence and SASP, and demonstrated both EV release and macrophage attraction. This novel model mimics several features of PSC, and thus will be useful for studying the pathogenesis of PSC and potentially identifying new therapeutic targets.

Background: The mushroom Agaricus blazei has evoked considerable scientific and practical interest in several fields, especially those linked to its medicinal properties. This review aims to summarize and evaluate the past decade findings related to nutritional and therapeutic uses of A. blazei, with especial emphasis on the most recent discoveries regarding its chemical composition and clinical investigations. Methods: The specialized literature was searched for basic and clinical studies. The main isolated and identified compounds or fractions are described and confronted with their corresponding bioactivities. Results: Basic research of high quality using ex vivo and in vivo conditions are quite abundant in the specialized literature, but ony 17 clinical studies and two case reports were found. A great number of active molecules have been identified, and they can be divided into three categories, (1) hydrophilic small molecules (e.g., phenolics), (2) lipophilic or partially lipophilic small molecules (e.g., agarol) (3) and macromolecules (e.g., β-glucans). At least the following bioactivities can be considered as being supported by experimental evidence: antioxidant activity (in aging or disease), immunomodulation and cell signaling, anti-inflammatory activity, antiparasitic actions, antimicrobial activity, anticancer effects and tumor growth inhibiting effects, antimutagenic activity, hepatoprotection against chemical or viral infection and antidiabetic activity. Conclusion: The amount and quality of the evidence that has been accumulating during the last decade strongly speaks in favor of the health benefits of the ingestion of A.blazei or derived products. However, there are many uncertainties and limitations when attempts are made to extrapolate or to demonstrate their biological effects in the human organism in health or disease. Clearly, more clinical trials, using reliable statistical methods and standardized preparations are needed to establish the efficacy of A. blazei as a therapeutic agent.

During the development of heart failure (HF), the changes of contraction timing pattern and temporal heterogeneity of segmental contraction happen early and may precede both symptomatic HF and the decrease in left ventricular ejection fraction (LVEF). In patients treated with anthracyclines, both symptomatic HF and the decrease of LVEF are detected once significant myocardial injury has occurred. The aim of the current study was to investigate whether changes in the timing of contraction can be detected early after anthracyclines therapy.

Dynamin-2 (Dyn2) is implicated in endocytosis of receptor tyrosine kinases, which contribute to hepatic stellate cell (HSC) activation and liver fibrosis. A point mutation converting lysine 44 of Dyn2 to alanine (Dyn2K44A) disrupts its GTPase activity. We hypothesized that Dyn2K44A expression in HSCs would decrease HSC activation and fibrogenesis in vivoby disrupting receptor tyrosine kinase endocytosis and signaling. Dyn2K44Afl/flmice were crossed with Collagen1-Cre(Col1Cre) mice to generate offspring with HSC selective expression of Dyn2K44A (Col1Cre/Dyn2K44Afl/fl). Contrary to our hypothesis, Col1Cre/Dyn2K44Afl/flmice showed increased hepatic fibrosis in response to liver injury. To elucidate mechanisms, we conducted in vitroexperiments with HSCs infected with adenoviral vectors encoding LacZ, Dyn2K44A, or Dyn2WT. HSC-expressing Dyn2K44A displayed increased mRNA and protein levels of sphingosine kinase-1 (SK1), an enzyme previously implicated in the pathogenesis of fibrosis. To study the functional effects of Dyn2K44A regulation of SK1, we examined effects of AKT signaling and migration in HSCs. Dyn2K44A promoted both AKT phosphorylation and HSC migration in an SK1-dependent manner. Genetic disruption of Dyn2 GTPase activity selectively in HSC enhances fibrogenesis, driven at least in part through up-regulation of the SK1 pathway and cell migration in HSCs.

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Kinins are important vasoactive peptides, but the role of the B1 receptor subtype in the vascular control is poorly understood. This study analyzed the nitric oxide (NO) release, L-arginine (L-Arg) uptake and the expression of the cationic amino acid transporter (CAT) -1 in endothelial cells obtained from B1 receptor knockout (B1-/-) and wild type (WT) mice. NO production was assessed through a fluorescent dye in living cells stimulated with acetylcholine. L-Arg uptake was determined indirectly in the culture medium by HPLC, in the presence or absence of the CAT-1 blocker N-ethylmaleimide (NEM). CAT-1 mRNA levels and protein expression were determined by qPCR and western blot, respectively. NO release was significantly reduced in B1-/- when compared to WT cells. This result was accompanied by a decreased rate in the L-Arg uptake by B1-/- cells. Incubation with NEM impaired the L-Arg uptake in WT, but had no effect in B1-/- cells. Protein expression and mRNA levels for CAT-1 were reduced in B1-/- in comparison to WT cells. These findings suggest an important role of the endothelial B1 receptor in the vascular control by interfering with CAT-1 expression, L-Arg uptake and NO release

A mathematical model of heat transfer and solidification for a continuous casting of round billets was developed. The water flux density of the secondary cooling zone was experimentally measured, using an apparatus in industrial scale with two types of nozzles, flat jet and full cone jet. The profiles of water distribution were applied on the mathematical model. The results showed that the water distribution is not uniform in both longitudinal and angular directions owing to the unevenness of the spray and to the curvature effect of the round billet. This non-uniformity causes important variation of the heat transfer coefficients and superficial temperature of the billet, especially in the first cooling zones, where the temperature is higher. The mathematical model was used to simulate a change of nozzle type in the first cooling zone. The results showed that the heat flux and superficial temperature variations were reduced with a full cone jet nozzle in comparison with the flat jet nozzles.

Polycyclic aromatic hydrocarbons (PAHs) in air were measured in a municipality where sugarcane plantations are extensive, at three sites, one in the city center and two in rural localities. Twenty-four-hour sampling was done using PS1 PUF samplers from Andersen Instruments Inc., at least 1 day per month per site, from June 2009 to October 2009. The chemical analyses were performed by gas chromatography–mass spectrometry (GC/MS) for the 16 most toxic PAHs. The incremental lifetime cancer risk (ILTR) by inhalation was determined by the Monte Carlo method for the urban population using Crystal Ball software. The total concentration of the 16 PAHs at all sites varied from 6.2 to 65.7 ng m−3, with an average of 25.9 ± 18.2 ng m−3. The average concentrations per site were 14.1 ± 13.0 ng m−3at rural site B, 20.7 ± 11.5 ng m−3at rural site A, and 36.1 ± 22.7 ng m−3at the central site. The cancer risk for infants, children, and adults was approximately 14%, 25%, and 61% of the total IRLT, respectively. The mean (95% upper probability limit [95% UPL]) values were 1.2 × 10−7(2.2 × 10−7) for infants, 2.2 × 10−7(4.1 × 10−7) for children, and 8.9 × 10−7(1.1 × 10−6) for adults. Although the three most abundant PAHs found were phenanthrene, fluoranthene, and pyrene, the three most important contributions to the incremental risk of cancer came from benzo[a]pyrene, benzo[b]fluoranthene, and naphthalene. Compared with the risks in big cities such as São Paulo, this would be low, but not negligible. Analysis of ratios of PAHs according to the literature showed that vehicle exhaust and biomass burning, including sugarcane burning, seem to be the most important contributors to PAH concentrations in the central area of Araraquara City.Implications:The growth of biofuel use worldwide, especially ethanol, together with preharvesting burning practice, is cause of concern with regard to possible health effects, due to increased air pollution levels in cities in regions where sugarcane plantation and processing are intensive. This paper shows that the risk of cancer from PAH inhalation in an urban area surrounded by sugarcane agriculture was of the same order of magnitude as the tolerable risk value of 10−6. As other classical and hazardous pollutants are also present, care should be taken to keep pollution as low as possible to protect human health.

Workflows have been successfully applied to express the decomposition of complex scientific applications. This has motivated many initiatives that have been developing scientific workflow tools. However the existing tools still lack adequate support to important aspects namely, decoupling the enactment engine from workflow tasks specification, decentralizing the control of workflow activities, and allowing their tasks to run autonomous in distributed infrastructures, for instance on Clouds. Furthermore many workflow tools only support the execution of Direct Acyclic Graphs (DAG) without the concept of iterations, where activities are executed millions of iterations during long periods of time and supporting dynamic workflow reconfigurations after certain iteration. We present the AWARD (Autonomic Workflow Activities Reconfigurable and Dynamic) model of computation, based on the Process Networks model, where the workflow activities (AWA) are autonomic processes with independent control that can run in parallel on distributed infrastructures, e. g. on Clouds. Each AWA executes a Task developed as a Java class that implements a generic interface allowing end-users to code their applications without concerns for low-level details. The data-driven coordination of AWA interactions is based on a shared tuple space that also enables support to dynamic workflow reconfiguration and monitoring of the execution of workflows. We describe how AWARD supports dynamic reconfiguration and discuss typical workflow reconfiguration scenarios. For evaluation we describe experimental results of AWARD workflow executions in several application scenarios, mapped to a small dedicated cluster and the Amazon (Elastic Computing EC2) Cloud.

Introduction:Sterilisation using peracetic acid (PAA) has been advocated for orthodontic elastic bands. However, cane-loaded elastomeric ligatures can also become contaminated during processing, packaging, and manipulation before placement in the oral cavity and are therefore susceptible, and possible causes, of cross-contamination.

Data analytics applications handle large data sets subject to multiple processing phases, some of which can execute in parallel on clusters, grids or clouds. Such applications can benefit from using MapReduce model, only requiring the end-user to define the application algorithms for input data processing and the map and reduce functions, but this poses a need to install/configure specific frameworks such as Apache Hadoop or Elastic MapReduce in Amazon Cloud. In order to provide more flexibility in defining and adjusting the application configurations, as well as in the specification of the composition of the application phases and their orchestration, the authors describe an approach for supporting MapReduce stages as sub-workflows in the AWARD framework (Autonomic Workflow Activities Reconfigurable and Dynamic). The authors discuss how a text mining application is represented as a complex workflow with multiple phases, where individual workflow nodes support MapReduce computations. Access to intermediate data produced during the MapReduce computations is supported by a data sharing abstraction. The authors describe two implementations of this abstraction, one based on a shared tuple space and another based on an in-memory distributed key/value store. The authors describe the implementation of the framework, a set of developed tools, and our experimentation with the execution of the text mining algorithm over multiple Amazon EC2 (Elastic Compute Cloud) instances, and report on the speed-up and size-up results obtained up to 20 EC2 instances and for different corpus sizes, up to 97 million words.

Glioblastoma (GBM) is considered incurable due to its resistance to current cancer treatments. So far, all clinically available alternatives for treating GBM are limited, evoking the development of novel treatment strategies that can more effectively manage these tumors. Extensive effort is being dedicated to characterize the molecular basis of GBM resistance to chemotherapy and to explore novel therapeutic procedures that may improve overall survival. Cytolysins are toxins that form pores in target cell membranes, modifying ion homeostasis and leading to cell death. These pore-forming toxins might be used, therefore, to enhance the efficiency of conventional chemotherapeutic drugs, facilitating their entrance into the cell. In this study, we show that a non-cytotoxic concentration of equinatoxin II (EqTx-II), a pore-forming toxin from the sea anemone Actinia equina, potentiates the cytotoxicity induced by temozolomide (TMZ), a first-line GBM treatment, and by etoposide (VP-16), a second- or third-line GBM treatment. We also suggest that this effect is selective to GBM cells and occurs via PI3K/Akt pathway inhibition. Finally, Magnetic resonance imaging (MRI) revealed that a non-cytotoxic concentration of EqTx-II potentiates the VP-16-induced inhibition of GBM growth in vivo. These combined therapies constitute a new and potentially valuable tool for GBM treatment, leading to the requirement of lower concentrations of chemotherapeutic drugs and possibly reducing, therefore, the adverse effects of chemotherapy.

Follicular atresia is a key event in the selection of the ovulatory follicles and occurs during all developmental stages. The aims of the study were to evaluate the follicular population as well as the rates of follicular recruitment and atresia in different strains of mice. Ovaries were obtained from four strains of mice: G1/Swiss, G2/F1 Swiss×C57BL/6, G3/inbred strain C57BL/6, and G4/F1 C57BL/6×Swiss. All mice used in the study were 60 days old. Ovaries collected from the mice were fixed and processed for histological analysis. The G2 ovaries were also used to examine immunolocalization of active caspase-3. The pimordial follicle population was smaller in G3 mice than in G1, G2 and G4 groups (7 565±1 845 vs. 17 180±3 159, 14 785±3 319 and 13 325±2 685, respectively; p<0.05). The rate of follicular recruitment in G3, however, was higher than in the other groups (29.2% vs. 18.2%, 17.3% and 13.0% in G1, G2 and G4, respectively; p<0.05), resulting in a similar (p0.05) number of antral follicles among groups. The small follicular pool in G3 mice was also associated with a lower rate of follicular atresia (11.4% vs. 17.2%, 16.7% and 13.6% for G3, G1, G2 and G4, respectively; p<0.05). The number of follicles stained with active caspase-3 was higher (p<0.05) during the final stage of preantral folliculogenesis than in other stages of follicular development suggesting that apoptosis in mice occurs earlier in comparison to large animals. Thus, it was concluded that differences in follicle reservoir among mice strains are compensated by an increased rate of follicular recruitment and a decreased rate of follicular atresia; and atresia occurs in mice mainly at the end of the preantral stage of folliculogenesis.

Dietary antioxidant compounds, due to their pivotal role in the modulation of cellular redox mechanisms, are gaining attention of researchers in the field of brain aging and related degenerative diseases. In this perspective, green tea (GT) can be an excellent resource, as it contains large amounts of brain-accessible polyphenols. Many of these compounds are monomeric catechins, which have been shown to exert antioxidant effects, acting directly as radical scavengers or metal-chelators. In the current article, we review the general properties of GT, the direct antioxidant action of its polyphenols and the fine modulation of signaling systems related to survival and antioxidant defenses in the central nervous system of aging rats. The effects in the glutathione system and the activation of several transcription factors including cyclic AMP response element-binding (CREB) protein, levels of the brain-derived neurotrophic factor (BDNF) and the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) are given in detail. We discuss also the beneficial action of catechins in learning and memory with a particular focus on the hippocampal formation. We conclude that GT polyphenols can have a promising role in the reversal of age-related loss of neuronal plasticity and recovery after neuronal lesions associated with aging.

Characterisation of residual stress state was performed in 4 mm low carbon steel plates laser welded in keyhole and conduction mode. Residual stress characterisation was carried out at the ENGIN-X strain scanner at ISIS (Oxford, UK). It was shown that although the maximum magnitude of tensile residual stress is similar in welded specimens manufactured under different welding modes, the distribution profile is quite distinguished. The conduction welding mode resulted in a larger tensile stress domain as compared to the keyhole mode in the longitudinal direction. This also resulted in a different magnitude of balancing compressive residual stress field. Understanding of such different stress profiles is important for application of such advanced welding processes in joining of design efficient structural material.

Background: Pancreatic ductal adenocarcinoma initiation is most frequently caused by Kras mutations. Results: Here, we apply biological, biochemical, and network biology methods to validate GEMM-derived cell models using inducible KrasG12Dexpression. We describe the time-dependent, chromatin remodeling program that impacts function during early oncogenic signaling. We find that the KrasG12D-induced transcriptional response is dominated by downregulated expression concordant with layers of epigenetic events. More open chromatin characterizes the ATAC-seq profile associated with a smaller group of upregulated genes and epigenetic marks. RRBS demonstrates that promoter hypermethylation does not account for the silencing of the extensive gene promoter network. Moreover, ChIP-Seq reveals that heterochromatin reorganization plays little role in this early transcriptional program. Notably, both gene activation and silencing primarily depend on the marking of genes with a combination of H3K27ac, H3K4me3, and H3K36me3. Indeed, integrated modeling of all these datasets shows that KrasG12Dregulates its transcriptional program primarily through unique super-enhancers and enhancers, and marking specific gene promoters and bodies. We also report chromatin remodeling across genomic areas that, although not contributing directly to cis-gene transcription, are likely important for KrasG12Dfunctions. Conclusions: In summary, we report a comprehensive, time-dependent, and coordinated early epigenomic program for KrasG12Din pancreatic cells, which is mechanistically relevant to understanding chromatin remodeling events underlying transcriptional outcomes needed for the function of this oncogene.

Multiple fractures of the axis are rare and present challenging patterns of instability in cervical spine surgery. Once a surgeon is faced with a combination of fractures in the axis vertebra, including stable and unstable components, a sound treatment concept must be worked out to achieve primary stability, early mobilization, and superior outcome. We demonstrate an operative technique for the stabilization of a 4-part fracture of the axis. Utilizing anterior odontoid screw fixation and C2-3 arthrodesis, an unstable traumatic spondylolisthesis with fracture of the odontoid type IIA, and lateral mass of C2 was successfully stabilized at once. The technique enabled early postoperative mobilization of our patient, who, after 1 year, showed a favorable outcome with a pain-free range of motion. The basic thoughts guiding to treatment options in multiple fractures of the axis are discussed and our therapy concept is presented.