Synthesis, anti-Infammatory, Analgesic, Molecular Modeling and ADMET Studies of Novel Diclofenac Derivatives Containing Alanyl Moiety

The present work aims to synthesize novel diclofenac derivatives containing L-alanine moiety. The synthesized compounds docked into the active site to discover validated inhibitors of cyclooxygenases (COX-1 and COX-2). The calculations in-silico were predicted that, the compound with lowest energy of docked poses was interacted with residues of active site, perhaps could be making them possible selective inhibitors against (COX-2) and physiologically  active. The binding score of compound compared with reference drug, and show extensive interactions with the targets, which may consider it a suitable selective inhibitor against   (COX-2). Keywords: Alanine, Diclofenac, COX, DOCKING, ADMET

Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite

A regulated protein turnover machinery in the cell is essential for effective cellular homeostasis; any interference with this system induces cellular stress and alters the normal functioning of proteins important for cell survival. In this study, we show that persistent cellular stress and organelle dysfunction because of disruption of cellular homeostasis in human malaria parasite Plasmodium falciparum, leads to apoptosis-like cell death. Quantitative global proteomic analysis of the stressed parasites before onset of cell death, showed upregulation of a number of proteins involved in cellular homeostasis; protein network analyses identified upregulated metabolic pathways that may be associated with stress tolerance and pro-survival mechanism. However, persistent stress on parasites cause structural abnormalities in endoplasmic reticulum and mitochondria, subsequently a cascade of reactions are initiated in parasites including rise in cytosolic calcium levels, loss of mitochondrial membrane potential and activation of VAD-FMK-binding proteases. We further show that activation of VAD-FMK-binding proteases in the parasites leads to degradation of phylogenetically conserved protein, TSN (Tudor staphylococcal nuclease), a known target of metacaspases, as well as degradation of other components of spliceosomal complex. Loss of spliceosomal machinery impairs the mRNA splicing, leading to accumulation of unprocessed RNAs in the parasite and thus dysregulate vital cellular functions, which in turn leads to execution of apoptosis-like cell death. Our results establish one of the possible mechanisms of instigation of cell death by organelle stress in Plasmodium

Emotion Recognition for Affective Computing: Computer Vision and Machine Learning Approach

The purpose of affective computing is to develop reliable and intelligent models that computers can use to interact more naturally with humans. The critical requirements for such models are that they enable computers to recognise, understand and interpret the emotional states expressed by humans. The emotion recognition has been a research topic of interest for decades, not only in relation to developments in the affective computing field but also due to its other potential applications. A particularly challenging problem that has emerged from this body of work, however, is the task of recognising facial expressions and emotions from still images or videos in real-time. This thesis aimed to solve this challenging problem by developing new techniques involving computer vision, machine learning and different levels of information fusion. Firstly, an efficient and effective algorithm was developed to improve the performance of the Viola-Jones algorithm. The proposed method achieved significantly higher detection accuracy (95%) than the standard Viola-Jones method (90%) in face detection from thermal images, while also doubling the detection speed. Secondly, an automatic subsystem for detecting eyeglasses, Shallow-GlassNet, was proposed to address the facial occlusion problem by designing a shallow convolutional neural network capable of detecting eyeglasses rapidly and accurately. Thirdly, a novel neural network model for decision fusion was proposed in order to make use of multiple classifier systems, which can increase the classification accuracy by up to 10%. Finally, a high-speed approach to emotion recognition from videos, called One-Shot Only (OSO), was developed based on a novel spatio-temporal data fusion method for representing video frames. The OSO method tackled video classification as a single image classification problem, which not only made it extremely fast but also reduced the overfitting problem

Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan

<p>Abstract</p> <p>Background</p> <p>Placental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia.</p> <p>Methods</p> <p>A case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood presure≥140 mm Hg or diastolic blood pressure ≥ 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed.</p> <p>Results</p> <p>Twenty-eight (19.6%) vs. 16 (11.2%); <it>P </it>= 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, <it>P </it>= 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; <it>P </it>= 0.04) were significantly associated with pre-eclampsia.</p> <p>Conclusion</p> <p>Placental malaria was associated with pre-eclampsia. Further research is needed.</p

A comparison of derivatisation procedures for the detection of multiple analytes in systematic forensic toxicology

Three different derivatisation procedures were evaluated for their general applicability to systematic toxicological analysis (STA) involving (a) acylation with pentafluoropropionyl anhydride (PFPA) and pentafluoropropanol (PFP-OH), (b) acylation/esterification (methylation) with pentafluoropropionyl anhydride (PFPA) and a novel methylating agent trimethylsilyldiazomethane (TMS-diazomethane), used as a chromatographic derivatisation reagent for the first time in this study, and (c) silylation with tertiary-butyldimethylsilyl-trifluoroacetamide (MTBSTFA). Model compounds were selected for the evaluation process including a primary amine (amphetamine), a secondary amine (methamphetamine), alicyclic and aromatic hydroxy compounds (morphine, tetrahydrocannabinol), and carboxylic acids (benzoylecgonine, 11-nor tetrahydrocannabinol-9-carboxylic acid). For method (a) derivatisation was successful for all of the test compounds and mass spectra were obtained for each of them. For method (b), the novel methylating agent trimethylsilyl-diazomethane was used to convert carboxylic acids into the corresponding methyl esters. This reaction was found to proceed rapidly and quantitatively at room temperature and holds potential for future use in toxicology to replace diazomethane, a hazardous and toxic material. Method (c) gave derivatives with all test compounds except the secondary amine, methamphetamine, and the alcohol, morphine. The gas chromatographic behaviour of these derivatives was good and the mass spectra had prominent ions suitable for GC-MS-SIM. The extraction of multiple drugs from blood was evaluated using the novel polymeric SPE sorbent Strata-X. The same test compounds were used to assess the extraction step in terms of recovery and variation (within day and between days). The extracts were analysed by GC-MS-SIM using each of the three types of derivative. Recoveries of the test compounds were in the range of 50-100 percent depending on the analyte and its concentration in blood. All calibration curves were linear and had correlation coefficients higher than 0.99. Within day variations and between day variations were in the range of 2-22% relative standard deviation. Limits of detection and quantitation were measured for the model compounds and were found to be in the ranges of 0.4-7.3 ng/ml and 1.1-24.4 ng/ml respectively. The full method, combining extraction with each of the derivatisation reactions was finally evaluated for the presence of interferences with real case blood samples. The three derivatisation procedures were evaluated using four test compounds comprising diazepam plus its three metabolites nordiazepam, temazepam and oxazepam. The hydroxylated metabolites (temazepam and oxazepam) formed derivatives readily with all three reagent mixtures but nordiazepam (secondary aromatic amine) did not react except with MTBSTFA. Based on the work of this study it is concluded that a method is possible for STA based on a polymeric sorbent, to give a general extract, followed by a generalised derivatisation procedure such as acylation, with PFPA/PFP-OH prior to GC-MS.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Studying and Modeling The Effects of Quartz Addition and Heat Treatment on Corrosion Properties of Ceramic Coating

In this work, a new glass-ceramic coating has been developed and applied, as a single coat without prior chemical treatment of the surface, by using the dipping technique on metal substrate. the coating are designed for application on varies grades of low alloy steel, the selected substrate was low carbon low alloyed steel with (0.2)%C. Various heat treatments at temperatures ( 500,550, and 600˚C ) at different times (60 & 120)min and with quartz addition in the range (0-15)% were used to obtain a glass-ceramics that have the optimum coating properties. These coating have been characterized by x-ray diffraction analyses and the results showed presence of a number of microcrystalline phases which are formed during the heat treatments. The results of corrosion resistance tests indicated that the acid resistance was greatly improved by addition of quartz into enamel frit but at same times decreased the alkali corrosion resistance, while the heat treatments improved both acid and alkali resistance for all cases, this is attributed to the formation of complex network from crystalline phases. The results also indicated that the heat treatment at 600˚C for 120min with 15% quartz addition brought the optimum values for acid resistance property which are improved by 86.66%, while the optimum values for alkali resistance property was brought with free quartz added samples which were treated at 600˚C for 120min. Mathematical modeling is implemented and regression equations are obtained by using ( SPSS ) software to predict the experimental data for acid and alkali corrosion rate. Comparing the predicted and measured values gives high prediction accuracy. The accuracy of prediction has been (82.58%, and 96.7%) for acid and alkali resistance properties respectively

Humoral immune factor changes in group of patients with Non-muscle invasive bladder cancer treated with intravesical therapy.

Background: Bladder cancer (BC) one of the most common urologic cancer characterized by the highest recurrence rate, many types belong to BC, but most common of them worldwide are transitional cell carcinoma(TCC) which constitute about 90-95% cases, squamous cell carcinoma (SCC) and adenocarcinomas Objective: This study was designed to evaluate parameters of humoral immunity in Non-muscle invasive (superficial or early) bladder cancer patients in Iraq that may provide a new insight into the future of immunotherapies development and BC management. Materials and methods: Fifty-nine volunteer's patients ranged from 24 to 83years old, and 30 control individuals ranged from 51-80 years old, who attended and admitted to Hospital of Gazi AL-Harery in medical city of Baghdad, and Al-Emamain Al-Khadhemain Teaching hospital was recruited in this investigation. The sera of study groups were subjected to serological test to estimate the levels of (IgA, IgG, IgM and C3) by Single radial immunodiffusion (sRID) assay and Enzyme-Linked immunosorbent assay (ELISA) was used to estimate the serum levels of IL-10. Results: The ages ranged from 24 to 83years (females: 26 to 72years, males: 38 to 83years) with male to female ratio 4.9:1 and ages of controls ranged from 51 to 80years (females: 54 to 70years, males: 51 to 80years) with male to female ratio 2.75:1, the mean ages of cases and controls groups were (61.65±11.04) , current study showed significance dropping in C3 levels in patients control and Mitomycin C groups compared with apparently healthy, levels of IgM showed significant elevation in BCG group compared with apparently healthy group while patients control and mitomycin C groups showed insignificant elevation of IgM. Levels of IgG showed significant elevation in patients control and mitomycin C groups compared with apparently healthy group while in BCG group showed no differences. Serum levels of IL-10 showed no differences between apparently healthy group and each of patient's groups, also showed no differences within patient's groups Conclusions: Bladder cancer is a common urologic malignancy in male than female patients enrolled in this study. Intravesical BCG or Mitomycin C leading to effective anti-bladder cancer immunity in the majority of Patients الخلفية: سرطان المثانة   واحدة من أكثر سرطان المسالك البولية شيوعا تتميز أعلى معدل تكرار، العديد من الأنواع تنتمي إلى  سرطان المثانة ، ولكن الأكثر شيوعا منهم في جميع أنحاء العالم هي سرطان الخلايا الانتقالية   التي تشكل حوالي 90-95٪  من الحالات.   الهدف: تم تصميم هذه الدراسة لتقييم المعلمات من المناعة الخلطية   في  مرضى سرطان المثانة في العراق التي قد توفر نظرة جديدة في مستقبل    العلاج المناعي لهذا المرض .  المواد والأساليب: تراوح عدد المرضى المتطوعين الذين تتراوح أعمارهم بين 24 و 83 سنة، و 30 فردا من الأشخاص الذين تتراوح أعمارهم بين 51 و 80 عاما، والذين حضروا إلى مستشفى غازي الحريري في مدينة بغداد الطبية، و مدينة الامامين الكاظمين   . تم اختبار مصل الدم من مجموعات الدراسة لاختبار المصلية لتقدير مستويات (IgA, IgG, IgM and C3 ) من خلال فحص المناعي الشعاعي واحد   وبواسطة  فحص (إليسا)      النتائج: تراوحت الأعمار من 24 إلى 83 سنة (الإناث: 26 إلى 72 سنة، ذكور: 38 إلى 83 سنة) مع نسبة الذكور إلى الإناث 4.9: 1 وأعمار الضوابط تراوحت بين 51 إلى 80 سنة (الإناث: 54 إلى 70 سنة، ذكور: 51 إلى (61.65 ± 11.04)، وأظهرت الدراسة الحالية انخفاض معنوي في مستويات C3 في السيطرة على المرضى ومجموعات ميتوميسين C مقارنة بمستويات سليمة على ما يبدو من  IgM أظهرت ارتفاع كبير في مجموعة  IgGمقارنة مع مجموعة   صحية بينما أظهرت الدراسة  السيطرة على المرضى والمجموعات ميتوميسين C ارتفاع كبير من IgM. وأظهرت مستويات  IgG ارتفاع ملحوظ في السيطرة على المرضى والمجموعات ميتوميسين C مقارنة مع مجموعة على ما يبدو صحي   أظهرت مستويات مصل الدم من  IL10 عدم وجود فروق بين المجموعة الصحية على ما يبدو وكل من مجموعات المريض، كما أظهرت أي اختلافات داخل مجموعات المريض الاستنتاجات: سرطان المثانة هو الأورام الخبيثة المسالك البولية شيوعا في الذكور من الإناث المرضى المسجلين في هذه الدراسة.  BCG أو ميتوميسين C   يؤدي إلى فعالية المناعة المضادة لسرطان المثانة في غالبية المرض

Confocal laser scanning, scanning electron, and transmission electron microscopy investigation ofEnterococcus faecalisbiofilm degradation using passive and active sodium hypochlorite irrigation within a simulated root canal model

Root canal irrigation is an important adjunct to control microbial infection. The aim of this study was to investigate the effect of 2.5% (wt/vol) sodium hypochlorite (NaOCl) agitation on the removal, killing, and degradation of Enterococcus faecalis biofilm. A total of 45 root canal models were manufactured using 3D printing with each model comprising an 18 mm length simulated root canal of apical size 30 and taper 0.06. E. faecalis biofilms were grown on the apical 3 mm of the models for 10 days. A total of 60 s of 9 ml of 2.5% NaOCl irrigation using syringe and needle was performed, the irrigant was either left stagnant in the canal or agitated using manual (Gutta-percha), sonic, and ultrasonic methods for 30 s. Following irrigation, the residual biofilms were observed using confocal laser scanning, scanning electron, and transmission electron microscopy. The data were analyzed using one-way ANOVA with Dunnett post hoc tests at a level of significance p ≤ .05. Consequence of root canal irrigation indicate that the reduction in the amount of biofilm achieved with the active irrigation groups (manual, sonic, and ultrasonic) was significantly greater when compared with the passive and untreated groups (p < .05). Collectively, finding indicate that passive irrigation exhibited more residual biofilm on the model surface than irrigant agitated by manual or automated (sonic, ultrasonic) methods. Total biofilm degradation and nonviable cells were associated with the ultrasonic group