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This paper presents a methodology based on the finite element method to simulate the flow of granular materials. Moreover, it allows proper estimation of dynamic pressure during silo discharge since this subject is still under discussion, especially for designing silos with an insert (an input element). A 2-D simulation of the discharge process of a cylindrical silo with cone and a central discharging orifice was performed. Two cases were studied, with and without using insert in silo. Numerical analysis was carried out with the help of the uncoupled arbitrary Lagrangian–Eulerian (ALE) approach. The resulting dynamic pressure distribution on the silo wall for each of the two cases was inferred numerically. The resulting values of pressure were compared with the results of the experimental study on a cylindrical metal silo to demonstrate the accuracy of the numerical model in determining the dynamic wall pressure, especially in the case of using an insert in silo during discharge.

This paper presents an experimental investigation of the discharge flow pressure in the vertical silo and the hopper due to the use of insert (top cone with trunk cone bottom). Using the Insert inside the silos is one of the proposed solutions to avoid the problems of having funnel flow pattern, which has a significant effect on the distribution of flow pressure exerted on the silo wall and the hopper. The experiments were performed on a metal cylinder prototype; corn was used as a granular material, and the wall and hopper pressure distribution was measured by a special pressure transducer. The experiments revealed an important result in the flow pressure due to the change in the location of the insert. The experiments were conducted in Damascus University laboratories.

Rapid technological progress in construction requires that more and more attention should be paid to human security issues. Threats occur both at the stage of building facilities and during their use. Some impacts are easy to identify during construction stage like shocks and vibrations, others are hidden from sight and direct sensing like the harmful effect of chemicals. In addition to accidents that happen on construction sites, there are still objective threats, which may occur throughout the lifetime of the facility. In addition to clearly perceptible ones such as earthquakes, hurricanes, fires, there are hidden threats as well: bacteriological contamination, radiation or chemical interactions that occur in time. This article points to the most common chemical hazards. Examples of chemical threats occurring in construction at the stages of design, construction and use of buildings will be given below.

Multilevel underground garages are often an ambitious geotechnical task in urban agglomeration. Lower levels of foundation slabs are often located below the groundwater level, which requires effective protection of the structure against groundwater invasion. The constructor’s task is to design slabs and walls so that no cracks will form to allow groundwater infiltration. In practice, this requires the development of a correct recipe for concrete; moreover, all factors affecting the total state of normal and tangential stresses as well as technologies allowing for correct execution of the facility must be considered. Additionally, long-term destructive factors ought to be taken into account. The article presents problems that arose during the use of an underground garage, which occurred as a result of failure to take into account at the design stage some rheological processes, as well as the assessment of the possibility of using the facility despite the damage.

The products covered by the common name polyurea were first developed and marketed in the United States in the 1980’s In the first period polyurea was used as a protective coating of polyurethane foam used for thermal insulation of roofs, and in the 1990s many other uses were quickly disseminated. In Europe this technology appeared in the second half of the nineties and the market for polyurea applications started to develop very dynamically in the recent years. Polyurea coatings, due to their extremely versatile physical properties such as watertightness, extremely high wear resistance, resistance to chemical and mechanical stresses, high elasticity and stretchability as well as resistance to freeze-thaw cycles, are increasingly popular, and more and more frequently used in the broadly understood construction. As a rule, the growing demand for technology fosters its development and enhances the knowledge of those who use it, so that it is used for its intended purpose, while maintaining security and enforcement procedures. However, in the absence of such knowledge, misconceptions about the use of polyurea spray coating technologies are emerging, both at the design stage and during the execution phase.

There are presented in this paper some problems connected with reinforced concrete shell objects operation in the aggressive environment and built in method of formworks. Reinforced concrete chimneys, cooling towers, silos and other shells were built for decades. Durability of cracked shells are one of the most important parameters during process of designing, construction and exploitation of shells. Some reasons of appearance of horizontal and vertical cracks as temperature, pressure of stored material, live loads e.g. dynamic character of wind, moisture, influence of construction joints, thermal insulation, chemistry active environmental etc. reduce the carrying capacity of the walls. Formworks, as is occurred recently, are the reason for technological joints with leaking connection, imperfections of flexible formworks slabs and as result can initiate cracks. Cracked surface of this constructions causes decreasing capacity and lower the state of reliability. Horizontal, vertical cracks can caused corrosion of concrete and steel bars, decreasing stiffness of contraction, increasing of deflection and carbonation of concrete cover. Local and global imperfactions of concrete shells are increasing according to greater number of cracks...

Abstract Background A considerable amount of research has been conducted on clinical decision making (CDM) in short-term physical conditions. However, there is a lack of knowledge on CDM and its outcome in long-term illnesses, especially in care for people with severe mental illness. Methods/Design The study entitled "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR) is carried out in six European countries (Denmark, Germany, Hungary, Italy, Switzerland and UK). First, CEDAR establishes a methodology to assess CDM in people with severe mental illness. Specific instruments are developed (and psychometric properties established) to measure CDM style, key elements of CDM in routine care, as well as CDM involvement and satisfaction from patient and therapist perspectives. Second, these instruments are being put to use in a multi-national prospective observational study (bimonthly assessments during a one-year observation period; N = 560). This study investigates the immediate, short- and long-term effect of CDM on crucial dimensions of clinical outcome (symptom level, quality of life, needs) by taking into account significant variables moderating the relationship between CDM and outcome. Discussion The results of this study will make possible to delineate quality indicators of CDM, as well as to specify prime areas for further improvement. Ingredients of best practice in CDM in the routine care for people with severe mental illness will be extracted and recommendations formulated. With its explicit focus on the patient role in CDM, CEDAR will also contribute to strengthening the service user perspective. This project will substantially add to improving the practice of CDM in mental health care across Europe. Trial register ISRCTN75841675.

The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with the CON, the HFF diet increased the total cholic acid (CA) and the CA to chenodeoxycholic acid (CDCA) ratio in the liver, DI, and blood. CA and CDCA levels in the DI were negatively and positively correlated with ileal FGF19 expression, respectively, and blood levels of FGF19 decreased with an increasing ileal CA to CDCA ratio. Compared with the CON, the HFF diet increased the gene expression of hepatic 12-alpha-hydrolase, which catalyzes the synthesis of CA in the liver. Since CA species are weaker FXR ligands than CDCA, our results suggest that impairment of FXR-FGF19 signaling in NAFLD pigs is associated with a decrease in FXR agonism in the bile acid pool.

The objective of this study was to investigate the effect of dietary fatty acid (FA) saturation and carbon chain length on brain bile acid (BA) metabolism and neuronal number in a pig model of pediatric NAFLD. Thirty 20-day-old Iberian pigs, pair-housed in pens, were randomly assigned to receive one of three hypercaloric diets for 10 weeks: (1) lard-enriched (LAR; n = 5 pens), (2) olive-oil-enriched (OLI, n = 5), and (3) coconut-oil-enriched (COC; n = 5). Pig behavior and activity were analyzed throughout the study. All animals were euthanized on week 10 and frontal cortex (FC) samples were collected for immunohistochemistry, metabolomic, and transcriptomic analyses. Data were analyzed by multivariate and univariate statistics. No differences were observed in relative brain weight, neuronal number, or cognitive functioning between diets. Pig activity and FC levels of neuroprotective secondary BAs and betaine decreased in the COC and OLI groups compared with LAR, and paralleled the severity of NAFLD. In addition, OLI-fed pigs showed downregulation of genes involved in neurotransmission, synaptic transmission, and nervous tissue development. Similarly, COC-fed pigs showed upregulation of neurogenesis and myelin repair genes, which caused the accumulation of medium-chain acylcarnitines in brain tissue. In conclusion, our results indicate that secondary BA levels in the FCs of NAFLD pigs are affected by dietary FA composition and are associated with metabolic and transcriptomic markers of brain injury. Dietary interventions that aim to replace saturated FAs by medium-chain or monounsaturated FAs in high-fat hypercaloric diets may have a negative effect on brain health in NAFLD patients.

The generation of large metabolomic data sets has created a high demand for software that can fit statistical models to one-metabolite-at-a-time on hundreds of metabolites. We provide the %polynova_2way macro in SAS to identify metabolites differentially expressed in study designs with a two-way factorial treatment and hierarchical design structure. For each metabolite, the macro calculates the least squares means using a linear mixed model with fixed and random effects, runs a 2-way ANOVA, corrects the P-values for the number of metabolites using the false discovery rate or Bonferroni procedure, and calculate the P-value for the least squares mean differences for each metabolite. Finally, the %polynova_2way macro outputs a table in excel format that combines all the results to facilitate the identification of significant metabolites for each factor. The macro code is freely available in the Supporting Information., Competing Interests: The authors have declared that no competing interests exist.

Chemotherapy-induced peripheral neuropathy (CIPN), a debilitating major side effect of cancer treatment, is characterized by pain and sensory loss in hand and feet. Platinum-based chemotherapeutics like cisplatin frequently induce CIPN. The molecular mechanism underlying these neurotoxic symptoms is incompletely understood and there are no preventive or curative interventions. We hypothesized that cisplatin acts as a cellular stressor that triggers p53 accumulation at mitochondria, leading to mitochondrial dysfunction and CIPN. To test this hypothesis, we examined the effect of the small molecule pifithrin-μ (PFT-μ), an inhibitor of p53 mitochondrial association on CIPN and the associated mitochondrial dysfunction. We show here for the first time that in vivo cisplatin rapidly increases mitochondrial accumulation of p53 in dorsal root ganglia (DRG), spinal cord, and peripheral nerve without evidence for apoptosis. Cisplatin-treatment also reduced mitochondrial membrane potential and lead to abnormal mitochondrial morphology and impaired mitochondrial function in DRG neurons. Pre-treatment with PFT-μ prevented the early cisplatin-induced increase in mitochondrial p53 and the reduction in mitochondrial membrane potential. Inhibition of the early mitochondrial p53 accumulation by PFT-μ also prevented the abnormalities in mitochondrial morphology and mitochondrial bioenergetics (reduced oxygen consumption rate, maximum respiratory capacity, and adenosine triphosphate synthesis) that develop in DRG and peripheral nerve after cisplatin-treatment. Functionally, inhibition of mitochondrial p53 accumulation prevented the hallmarks of CIPN including mechanical allodynia, peripheral sensory loss (numbness) as quantified by an adhesive-removal task, and loss of intra-epidermal nerve fibers. In conclusion, PFT-μ is a potential neuroprotective agent that prevents cisplatin-induced mitochondrial dysfunction in DRG and peripheral nerves thereby protecting against CIPN through blockade of the early cisplatin-induced increase in mitochondrial p53. Notably, there is accumulating evidence that PFT-μ has anti-tumor activities and could therefore be an attractive candidate to prevent CIPN while promoting tumor cell death.

Cognitive impairment, termed chemobrain, is a common neurotoxicity associated with chemotherapy treatment, affecting an estimated 78% of patients. Prompted by the hypothesis that neuronal mitochondrial dysfunction underlies chemotherapy-induced cognitive impairment (CICI), we explored the efficacy of administering the small-molecule pifithrin (PFT)-μ, an inhibitor of mitochondrial p53 accumulation, in preventing CICI. Male C57BL/6J mice injected with cisplatin ± PFT-μ for two 5-day cycles were assessed for cognitive function using novel object/place recognition and alternation in a Y-maze. Cisplatin impaired performance in the novel object/place recognition and Y-maze tests. PFT-μ treatment prevented CICI and associated cisplatin-induced changes in coherency of myelin basic protein fibers in the cingular cortex and loss of doublecortin + cells in the subventricular zone and hippocampal dentate gyrus. Mechanistically, cisplatin decreased spare respirator capacity of brain synaptosomes and caused abnormal mitochondrial morphology, which was counteracted by PFT-μ administration. Notably, increased mitochondrial p53 did not lead to cerebral caspase-3 activation or cytochrome-c release. Furthermore, PFT-μ administration did not impair the anticancer efficacy of cisplatin and radiotherapy in tumor-bearing mice. Our results supported the hypothesis that neuronal mitochondrial dysfunction induced by mitochondrial p53 accumulation is an underlying cause of CICI and that PFT-μ may offer a tractable therapeutic strategy to limit this common side-effect of many types of chemotherapy. Cancer Res; 77(3); 742-52. ©2016 AACR., Competing Interests: The authors report no conflicts of interest in this work., (©2016 American Association for Cancer Research.)