Effects of Cut-Off (Flood Relief) Channel Intersection on Bend Flow Characteristics

The characteristics of flow in a gentle wide channel bend at the intersection with a cut-off (flood relief) channel are studied. The studies are restricted to subcritical flows in bends with rigid boundaries and uniform rectangular cross sections. The object is to demonstrate how the intersection affects the water surface and velocities profiles in the channel bend. Two approaches are employed in the study namely; + Mathematical Approach + Experimental Approach The mathematical approach is divided into two stages. The first stage is concerned with the formulation of the flow in a gentle wide channel bend and the second stage with the formulation of the flow at the intersection with the flood channel. The flow entering the flood channel is treated as the flow spilling over a side weir with a broad crest. The conventional equations of motion are used to establish the model equations which are then solved numerically using a finite difference technique. For the experimental approach, a laboratory model was constructed in order to obtain physical data principally for the verification of the mathematical model. The analysis of the results follows two distinct lines: + Quantitative Analysis: where comparisons between the theoretical and experimental profiles are made for the bend flow with and without the introduction of the flood channel intersection. Principally for verification of the mathematical model results. + Qualitative Analysis: where qualitative comparisons between the flow profiles in both cases are made in order to show the influence of the intersection on the bend flow characteristics. The analysis shows that the suggested mathematical model can be used satisfactorily for high to medium flood channel bed levels. It is further shown that the bend characteristics continue to dominate the flow again for high to medium (weir) flood channel bed levels but that at medium to low (weir) channel bed levels, the local effects produced by the intersection predominate

Dimensionnement en fatigue des assemblages boulonnés à l’aide de critères de fatigue multiaxiale\ud \ud

Le principal objectif de ce travail de thèse est d’utiliser les critères de fatigue multiaxiale pour dimensionner les assemblages boulonnés. A partir d’une étude comparative des différents critères, nous en avons sélectionné deux : celui de SINES et celui de DANG VAN dont nous avons généralisé la formulation pour prendre en compte le domaine de l’endurance limitée. L’utilisation de ces critères nécessite la détermination de l’état de contrainte au fond du premier filet en prise, lieu privilégié de l’amorçage de la rupture des boulons. Nous avons donc réalisé des modèles éléments finis d’un boulon. Parallèlement, plusieurs campagnes d’essais fatigue ont été réalisées : les nombres de cycles à rupture obtenus couplés aux états de contrainte en fond de filet obtenus par simulation ont permis de caractériser le comportement en fatigue multiaxiale des boulons. Une fois cette caractérisation réalisée, l’usage de ces critères à été validé par un essai sur un assemblage de type bride. Puis, afin de s’affranchir de la phase modélisation EF, nous avons utilisé la règle de NEUBER et la méthode ESED pour déterminer l’état de contrainte en fond du premier filet en prise lors d’un chargement cyclique. Les essais de fatigue ont été faits sur deux types de boulons : des boulons roulés à froid puis trempés-revenus et des boulons trempés-revenus puis roulés à froid. Les performances améliorées de ces derniers a permis de bien mettre en évidence l’influence de la chronologie des opérations. Cette amélioration est à mettre sur le compte des contraintes résiduelles que nous avons essayé d’évaluer par modélisation du roulage.\ud The aim of this thesis is the use of multi-axial fatigue criterion in bolted assemblies design. From a comparative analysis of several criterion, we chose those of SINES and DANG VAN that we generalised to limited fatigue life. These criterion require the knowledge of the stress level in the screw at the bottom of its first thread in contact with the nut, where fatigue failure occurs. For this, we used a finite elements model of the bolt. On the other hand, several fatigue tests were undertaken; with the number of cycles to failure related to the stress level at the bottom of threads obtained by simulation, we characterised the multiaxial fatigue behaviour of the tested bolts. Then, the use of these criteria to industrial bolted joints was experimentally validated on a flanged type assembly. To overpass the finite elements model of the bolted joint, we used NEUBER’s generalised rule and ESED method to determine the stress level at the bottom of the first thread under a cyclic loading. The fatigue tests were carried on two types of bolts: cold rolled then heated-tempered bolts, and heated-tempered then cold rolled bolts. The improved performance on this last type of bolts has put in evidence the influence of chronology of the different manufacturing operations. This improvement is explained by the residual stresses induced by rolling that we tried to simulate

إستراتيجية تطوير قطاع الصناعات الغذائية غير المنظم في سورية

  ستعرض هذه الدراسة ظاهرة القطاع الصناعي الغذائي غير المنظم , والتي تعتبر من أبرز القضايا الاقتصادية نظراً لانتشارها في كاف المناطق الجغرافية وعلى الرغم من أهمية هذا الموضوع لكن تبقى الدراسات التي تبحث في هذه في هذا الشأن قليلة جداً وهي غير كافية  لرفد اي خطة تهدف الى تنظيم وتنمية هذا القطاع . تبحث هذه الدراسة في  مفهوم القطاع غير المنظم بشكله العام وصولاً الى القطاع صناعات الغذائية غير المنظم ومكونات هذا القطاع ومخرجاته من أنشطة وخدمات والاسباب التي تحفز تواجد ونمو هذه الصناعات غير المنظمة وعلاقته بالمستوى الاقتصادي للأفراد  وما هي الخطوات الواجب اتخاذها لتنظيم هذه الصناعات . وتحليل مشاكله وإمكانات تنميته من خلال تأطيره وتقنينه بهدف تحسين أداء القطاع وتنظيمه، وتطوير الإنتاجية والجودة          

Immunotherapies for Neurodegenerative Diseases

The current treatments for neurodegenerative diseases are mostly symptomatic without affecting the underlying cause of disease. Emerging evidence supports a potential role for immunotherapy in the management of disease progression. Numerous reports raise the exciting prospect that either the immune system or its derivative components could be harnessed to fight the misfolded and aggregated proteins that accumulate in several neurodegenerative diseases. Passive and active vaccinations using monoclonal antibodies and specific antigens that induce adaptive immune responses are currently under evaluation for their potential use in the development of immunotherapies. In this review, we aim to shed light on prominent immunotherapeutic strategies being developed to fight neuroinflammation-induced neurodegeneration, with a focus on innovative immunotherapies such as vaccination therapy

Synthesis, crystal structure, DFT calculations, Hirshfeld surface analysis, energy frameworks, molecular dynamics and docking studies of novel isoxazolequinoxaline derivative (IZQ) as anti-cancer drug

Quinoxaline derivatives with the molecular formula C8H6N2] also named benzopyrazines, which are a valuable class of heterocyclic compounds useful for their numerous industrial and pharmaceutical applications. The new isoxazolquinoxalin (IZQ) 3-pheny1-14(3-(p-toly1)-4,5-dihydroisoxazol-5yl)methyl)quinoxalin-2(1H)- one (5) has been synthesized with good yield by stirring the compounds of 1-allyl-3-phenylquinoxalin-2(1H)-one (3, 3.8mmol), and (E)-4 methylbenzaldehydeoxime (4, 1.3mmol) in 20 ml of chloroform. The aqueous solution of sodium hypochlorite (10 ml of water bleach 12 degrees) was added drop wise using bromine funnel. The mixture was stirring at 0 degrees C temperature for 6 hours. Then it dried to obtain a crude product which on recrystallization with ethanol afforded the title compound (5) as colourless rectangular block shape crystals, and then confirmed by H NMR, LC-MS spectra. The structure of the compound has been confirmed by single crystal X-ray diffraction technique. The compound crystallizes in the monoclinic crystal system with the space group P2(1)/c. The unit cell constants; a =15.9437(6) angstrom, b =16.3936(6) angstrom, c =7.4913(3) angstrom, and beta =94.178(2)degrees. DFT calculations were carried out and HOMO-LUMO energy levels have been determined. In the structure, both Intermolecular and intramolecular hydrogen bonds of the type C-H center dot center dot center dot O were observed along with C-H center dot center dot center dot cg interactions. Hirshfeld surface studies were performed to understand the different interaction contacts of the molecule and the molecular packing strength of the crystal. Energy frameworks were constructed through different intermolecular interaction energies to investigate the stability of the compound and to know type of the dominate energy. Docking studies predicted anti-cancer activity of the title molecule against homo sapiens protein (pdb code:6HVH) and exhibited prominent interactions at active site region. (C) 2021 Elsevier B.V. All rights reserved

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

A Role of Therapy that Targets Immune Checkpoint Proteins for the Treatment of Melanoma Brain Metastasis, Liver, Breast, Pancreatic Cancer and Pancreatic Adenocarcinoma

Checkpoint inhibitors are a type of immune therapy used to treat different types of cancers. These drugs block different checkpoint proteins, for example, CTLA-4, PD-1, and PD-L1 inhibitors. They block proteins that stop the immune system from attacking the cancer cells.  Checkpoints are also described as a type of monoclonal antibody that antagonizes binding between B7 to CTLA-4 and PD-L1 to PD-1.  Immune checkpoint inhibitors are used to treat BARCA mutated triple-negative breast cancer (TNBCS) in patients who do not respond to chemotherapy, and also in the treatment of highly mutated and solid tumors such as brain tumors, liver, and pancreatic cancers. Immune checkpoint inhibitors exhibit an effect on solid tumors by suppressing CTLA-4, PD-1, and PDL-1. Anti-PD-1 is less toxic than anti-CTLA-4. For melanoma Brain metastasis immune checkpoint therapy is more effective and Combination therapy has great efficacy and less toxicity which improves overall survival rather than individual therapy liver cancer as hepatocellular carcinoma and cholangiocarcinoma used treatment with Genetics based therapy while using alternative immune checkpoint ligands, co-inhibitory (eg. LAG-3) or decreased t-cell infiltration causing therapy failure. Clinical studies for pancreatic cancer have not been completed yet and treating PDA needs more research as immune checkpoint inhibitors is a new treatment against  PDA. A new potent class of nivolumab, pembrolizumab, and ipilimumab have been FDA approved. For mutated tumors, Combination therapy between checkpoint inhibitors and chemotherapy has great efficacy and improves the city of life and overall survival, rather than individual therapy when using radiation or chemotherapy alone

Arhodomonas sp. strain Seminole and its genetic potential to degrade aromatic compounds under high-salinity conditions

Arhodomonas sp. strain Seminole was isolated from a crude oil-impacted brine soil and shown to degrade benzene, toluene, phenol, 4-hydroxybenzoic acid (4-HBA), protocatechuic acid (PCA), and phenylacetic acid (PAA) as the sole sources of carbon at high salinity. Seminole is a member of the genus Arhodomonas in the class Gammaproteobacteria, sharing 96% 16S rRNA gene sequence similarity with Arhodomonas aquaeolei HA-1. Analysis of the genome predicted a number of catabolic genes for the metabolism of benzene, toluene, 4-HBA, and PAA. The predicted pathways were corroborated by identification of enzymes present in the cytosolic proteomes of cells grown on aromatic compounds using liquid chromatography-mass spectrometry. Genome analysis predicted a cluster of 19 genes necessary for the breakdown of benzene or toluene to acetyl coenzyme A (acetyl-CoA) and pyruvate. Of these, 12 enzymes were identified in the proteome of toluene-grown cells compared to lactate-grown cells. Genomic analysis predicted 11 genes required for 4-HBA degradation to form the tricarboxylic acid (TCA) cycle intermediates. Of these, proteomic analysis of 4-HBA-grown cells identified 6 key enzymes involved in the 4-HBA degradation pathway. Similarly, 15 genes needed for the degradation of PAA to the TCA cycle intermediates were predicted. Of these, 9 enzymes of the PAA degradation pathway were identified only in PAA-grown cells and not in lactate-grown cells. Overall, we were able to reconstruct catabolic steps for the breakdown of a variety of aromatic compounds in an extreme halophile, strain Seminole. Such knowledge is important for understanding the role of Arhodomonas spp. in the natural attenuation of hydrocarbon-impacted hypersaline environments.Peer reviewedMicrobiology and Molecular GeneticsBiochemistry and Molecular Biolog