Elastohydrodynamic studies using thin film transducers

Imperial Users onl

c-FLIP, a master anti-apoptotic regulator

Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) is a master anti-apoptotic regulator and resistance factor that suppresses tumor necrosis factor-α (TNF-α), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, as well as apoptosis triggered by chemotherapy agents in malignant cells. c-FLIP is expressed as long (c-FLIP(L)), short (c-FLIP(S)), and c-FLIP(R) splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 and TRAIL receptor 5 (DR5) in a ligand-dependent and -independent fashion and forms an apoptosis inhibitory complex (AIC). This interaction in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. c-FLIP(L) and c-FLIP(S) are also known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective and pro-survival signaling proteins including Akt, ERK, and NF-kB. Upregulation of c-FLIP has been found in various tumor types, and its silencing has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIP(L) in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIP(L) and c-FLIP(S) splice variants have been found, and much effort is focused on developing other c-FLIP-targeted cancer therapies. This review focuses on (1) the anti-apoptotic role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and chemotherapy drug resistance, (2) the molecular mechanisms and factors that regulate c-FLIP expression, and (3) modulation of c-FLIP expression and function to eliminate cancer cells or increase the efficacy of anticancer agents. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later"

Reactivity of Dimethylplatinum (II) Complexes

This thesis describes a study of dimethylplatinum(II) and dimethylplatinum(IV) complexes containing bidentate nitrogen donor ligands. This work deals with oxidative addition, and reductive elimination chemistry, and it focuses on synthesis, characterization, and reaction mechanisms in studies of these complexes. The compound [PtMe2(bpe)], bpe = 1,2-bis(2-pyridyl)ethane, is easily oxidized to give octahedral organoplatinum(IV) complexes and the subsequent chemistry is profoundly influenced by the accompanying strain induced in the 7-membered Pt(bpe) chelate ring. On reaction of [PtMe2(bpe)] with HCl, the initial product [PtHClMe2(bpe)] undergoes reductive elimination of methane to form [PtClMe(bpe)]. In contrast, methyl iodide reacts with [PtMe2(bpe)] to give [PtIMe3(bpe)], and this decomposes by loss of the bpe ligand to give the cubane [(PtIMe3)4] and not by reductive elimination. Finally, a new class of platinum(IV) double cubane clusters was obtained on oxidation of complex [PtMe2(bpe)] with either hydrogen peroxide to give [Pt4(m-OH)4(m3-OH)2Me10], as a mixed complex with [PtMe2(CO3)(bpe)], or with oxygen in methanol to give [Pt4(m-OH)2(m-OMe)2(m3-OMe)2Me10]. The oxidation of the complex [PtMe2(bps)], bps = bis(2-pyridyl)-dimethylsilane, by oxygen, hydrogen peroxide or dibenzoyl peroxide in the presence of water or alcohol gives the complex cation, [PtMe3(k3-N,N,O-HOSiMe(2-C5H4N)2)]+, in a reaction involving easy cleavage of a methylsilicon bond. Treatment of the complex [PtMe2(bps)] with B(C6F5)3 in trifluoroethanol in air gives the complex [Me(bps)Pt-OSiMe(2-C5H4N)2PtMe3]+ [B(OCH2CF3)(C6F5)3]-. The unique binuclear platinum complex is formed via the competitive methyl platinum group cleavage from [PtMe2(bps)] by the acid H[B(OCH2CF3)(C6F5)3] to give the platinum(II) fragment and oxidation by air to give the platinum(IV) fragment. Combination of the two units then gives the binuclear complex which involves a very easy methylsilicon group cleavage reaction. The platinum(II) complexes containing five-membered heterocyclic imidazole ligands show high reactivity to a broad variety of alkyl halides, peroxides, and halogens forming stable platinum(IV) complexes. The dimethylplatinum(II) complex [PtMe2{(mim)2C=CH2}], (mim)2C=CH2= 1,1-bis(1-methylimidazole-2-yl)ethene reacts with dichloromethane to give the dimethylplatinum(IV) complex [PtCl(CH2Cl)Me2{(mim)2C=CH2}]. The product exists as a mixture of two isomers, the cis isomer as the kinetic product and the trans isomer as the thermodynamic product. The dimethylplatinum(II) complex [PtMe2(DECBP)], DECBP = 4,4’-diethoxycarbonyl-2-2’-bipyridine], undergoes easy oxidative addition to the corresponding platinum(IV) complexes. The reactions of the complex [PtMe2(DECBP)] with alkyl bromides RCH2Br, which have hydrogen bond donor or acceptor functional groups, result in the formation of stable platinum(IV) complexes. Those complexes self-assemble in the solid state to form supramolecular polymers via the intermolecular OH•••O=C, N-H•••Br, OH•••BrPt, interactions, with other predicted interactions such as the π-stacking, and the C(H)•••BrPt secondary weak interactions

MST-312 induces G2/M cell cycle arrest and apoptosis in APL cells through inhibition of telomerase activity and suppression of NF-κB pathway

Telomerase-targeted therapy for cancer has received great attention because telomerase is expressed in almost all cancer cells but is inactive in most normal somatic cells. This study was aimed to investigate the effects of telomerase inhibitor MST-312, a chemically modified derivative of epigallocatechin gallate (EGCG), on acute promyelocytic leukemia (APL) cells. Our results showed that MST-312 exerted a dose-dependent short-term cytotoxic effect on APL cells, with G2/M cell cycle arrest. Moreover, MST-312 induced apoptosis of APL cells in caspase-mediated manner. Telomeric repeat amplification protocol (TRAP) assay revealed significant reduction in telomerase activity of APL cells following short-term exposure to MST-312. Interestingly, MST-312-induced telomerase inhibition was coupled with suppression of NF-κB activity as evidenced by inhibition of IκBα phosphorylation and its degradation and decreased NF-κB DNA binding activity. In addition, gene expression analysis showed downregulation of genes regulated by NF-κB, such as antiapoptotic (survivin, Bcl-2, Mcl-1), proliferative (c-Myc), and telomerase-related (hTERT) genes. Importantly, MST-312 did not show any apoptotic effect in normal human peripheral blood mononuclear cells (PBMCs). In conclusion, our data suggest that dual inhibition of telomerase activity and NF-κB pathway by MST-312 represents a novel treatment strategy for APL. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Nurses' Evaluation of Their Use and Mastery in Health Assessment Skills: Selected Iran's Hospitals

Background: Health assessment skills are of the most important skills which nurses require. The more precise assessment, the better results would be obtained and the quality of patient care would be improved. However, in Iran, few studies have investigated nurses’ assessment skills. Objectives: This study was aimed to assess nurses' evaluation of the learned skills of health assessment and their use. Materials and Methods: This cross-sectional study was conducted on 200 nurses in Isfahan province hospitals. Data was collected by a questionnaire including demographic data and 120 health assessment skills. Nurses scored their frequency of using and proficiency in skills. Statistical analysis was conducted by ANOVA, Tukey test and independent sample T-tests. Results: The highest level of using and proficiency in skills was related to taking history. Nurses received 87.25% of score in this field. The lowest level of application was in assessment of the urogenital system so that nurses received 16.37% of score in this area. Also the lowest proficiency was in assessment of the nervous system and nurses received 34.58% of score in this area. Conclusions: The level of nurses' proficiency in the health assessment skills was not satisfactory. Modifying the curriculum and cooperating of nurse managers and nursing schools can help to improve the situation

Measuring the Score Matching of the Pairwise Deoxyribonucleic Acid Sequencing using Neuro-Fuzzy

The proposed model for getting the score matching of the deoxyribonucleic acid (DNA) sequence is introduced; the Neuro-Fuzzy procedure is the strategy actualized in this paper; it is used the collection of biological information of the DNA sequence performing with global and local calculations so as to advance the ideal arrangement; we utilize the pairwise DNA sequence alignment to gauge the score of the likeness, which depend on information gathering from the pairwise DNA series to be embedded into the implicit framework; an adaptive neuro-fuzzy inference system model is reasonable for foreseeing the matching score through the preparation and testing in neural system and the induction fuzzy system in fuzzy logic that accomplishes the outcome in elite execution

Evaluation and improvement pedestrians characteristics for selection section of urban area

The pedestrians walking, crossing, environment and the influence of their movement with the traffic operations are the most important elements that must be taken into account in the design of roadways and intersections in the urban area. Thus the study seeks to evaluate the level of service (LOS) of sidewalks to identify the problems facing pedestrians in crossing and movements to suggest alternatives that would increase the safety, convenience, and efficiency of pedestrian’s movement within the study area, according to scientific methodology, based on the study of traffic analytical. The study has had been chosen two locations in the Baghdad capital, are Aden and Sana’a un signalized intersections. Data were collect for traffic volume and walking speed for pedestrians as well as sidewalk width. Rate of flow and effective walkway width within Peak Hour Volume ( PHV), with the aid of video technique method to cover engineering field survey and traffic, recorded data, due to workday (Monday, Tuesday, Wednesday), for the period from 20/11/2020 to30/03/2021. Data analysis was done by using the method of (highway capacity manual 2010) to determine (LOS) in the study area, rather than for roadside interview by designing a questionnaire form to identify the crosswalk users to get their opinions about the nature of the traffic facilities in the study area. The study concluded that (LOS) of pedestrians type (E&C) in Aden and Sana’a intersections respectively. The study conducted that when the excesses were eliminated from the walkway and provided buffer zones for pedestrians crossing. LOS will be increase to (B) and (C) respectively as well as the accident rate type vehicle pedestrians decrease by (20) percent, in the other hand marking and signing will be increase safety and convenience factors moreover provide appropriate time for vehicles and pedestrians crossing and movements

Computer aided photographic memory enhancement and speed reading (case study)

This work aimed to design and testing of a computer program – based eyeQ improvement, photographic memory enhancement, and speed reading to match the reading speed 150 – 250 word per minute (WPM) with the mind ability of processing and eye snap shooting 5000WPM . The package designed based on Visual Basic 6. The efficiency of the designed program was tested on a 10 persons with different levels of education and ages and the results show an increase in their reading speed of approximately 25% in the first month of training with noticeable enhancement in the memory as well as an increase in the ability to read for longer time without feeling nerves or boring, a nonlinear continuously increase in reading speed is assured after the first month with a hope of reaching a target of 3000WPM within 3 – 5 years of training and that is what is called photographic memory where most of the read data processed in right side of the mind, the smaller age, and higher level of education is an effective factor on the results

An improved neurogenetic model for recognition of 3D kinetic data of human extracted from the Vicon Robot system

في هذه الأيام ، انه من الضروري التمييز بين نوع السلوك البشري ، تلعب تقنيات الذكاء الاصطناعي دورًا كبيرًا في ذلك المجال. تم دمج خصائص خوارزمية الشبكة العصبية الاصطناعية (FANN) والخوارزمية الجينية لإنشاء آلية عمل مهمة تساعد في هذا المجال. حيث يمكن استخدام النظام المقترح للمهام الأساسية في الحياة ، مثل التحليل والأتمتة والتحكم والتعرف والمهام الأخرى. التقاطع والطفرة هما الآليتان الأساسيتان اللتان تستخدمهما الخوارزمية الجينية في النظام المقترح لاستبدال عملية الانتشار العكسي في ANN. بينما تركز تقنية الشبكة العصبية الاصطناعية المغذية على معالجة المدخلات ، يعتمد هذا العمل على عملية كسر خوارزمية الشبكة العصبية الاصطناعية المغذية. بالإضافة إلى ذلك ، يتم حساب النتيجة من كل ANN أثناء عملية التفكك ، والتي تعتمد على تقسيم خوارزمية الشبكة العصبية الاصطناعية إلى عدة شبكات ANN بناءً على عدد طبقات ANN ، وبالتالي ، كل طبقة في الشبكة العصبية الاصطناعية الأصلية يتم تقييمها. يتم اختيار أفضل الطبقات لمرحلة التقاطع بعد عملية الكسر ، بينما تمر الطبقات الأخرى بعملية الطفرة. ثم يتم تحديد مخرجات هذا الجيل من خلال دمج الشبكات العصبية الاصطناعية في شبكة ANN واحدة ؛ ثم يتم فحص النتيجة لمعرفة ما إذا كانت العملية تحتاج إلى إنشاء جيل جديد. ان أداء النظام جيدًا وأنتج نتائج دقيقة عند استخدامه مع البيانات المأخوذة من نظام Vicon Robot ، والذي تم تصميمه بشكل أساسي لتسجيل السلوكيات البشرية بناءً على بيانات ثلاثية الابعاد وتصنيفها على أنها طبيعية أو عدوانية.These days, it is crucial to discern between different types of human behavior, and artificial intelligence techniques play a big part in that.  The characteristics of the feedforward artificial neural network (FANN) algorithm and the genetic algorithm have been combined to create an important working mechanism that aids in this field. The proposed system can be used for essential tasks in life, such as analysis, automation, control, recognition, and other tasks. Crossover and mutation are the two primary mechanisms used by the genetic algorithm in the proposed system to replace the back propagation process in ANN. While the feedforward artificial neural network technique is focused on input processing, this should be based on the process of breaking the feedforward artificial neural network algorithm. Additionally, the result is computed from each ANN during the breaking up process, which is based on the breaking up of the artificial neural network algorithm into multiple ANNs based on the number of ANN layers, and therefore, each layer in the original artificial neural network algorithm is assessed. The best layers are chosen for the crossover phase after the breakage process, while the other layers go through the mutation process. The output of this generation is then determined by combining the artificial neural networks into a single ANN; the outcome is then checked to see if the process needs to create a new generation. The system performed well and produced accurate findings when it was used with data taken from the Vicon Robot system, which was primarily designed to record human behaviors based on three coordinates and classify them as either normal or aggressive