Immune checkpoints in circulating and tumor-Infiltrating CD4 + T Cell Subsets in Colorectal cancer patients

Blockade of inhibitory immune checkpoints (ICs) is a promising therapeutic approach; however, it has shown limited success in some cancers including colorectal cancer (CRC). The tumor microenvironment (TME) is largely responsible for response to therapy, and its constituents may provide robust biomarkers for successful immunotherapeutic approaches. In this study, we performed phenotypical characterization and critical analyses of key inhibitory ICs and T regulatory cell (Treg)-related markers on CD4+ T cell subsets in CRC patients, and compared with normal colon tissues and peripheral blood from the same patients. We also investigated correlations between the levels of different CD4+ T cell subsets and the clinicopathologic features including disease stage and tumor budding. We found a significant increase in the levels of CD4+FoxP3+Helios+ T cells, which represent potentially highly immunosuppressive Tregs, in the CRC TME. Additionally, tumor-infiltrating CD4+ T cells upregulated programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), T cell immunoglobulin and mucin domain-3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3). We also characterized the expression of PD-1, CTLA-4, TIM-3, and LAG-3 on different CD4+FoxP3−/+Helios−/+ T cell subsets. Interestingly, we found that CTLA-4, TIM-3, and LAG-3 were mainly co-expressed on FoxP3+Helios+ Tregs in the TME. Additionally, FoxP3high Tregs expressed higher levels of Helios, CTLA-4 and TIM-3 than FoxP3low T cells. These results highlight the significance of Tregs in the CRC TME and suggest that Tregs may hamper response to IC blockade in CRC patients, but effects of different IC inhibition regimes on Treg levels or activity warrants further investigations. We also found that CD4+CTLA-4+ T cells in circulation are increased in patients with advanced disease stage. This study simultaneously provides important insights into the differential levels of CD4+ T cell subpopulations and IC expression in CRC TME, compared to periphery and associations with clinicopathologic features, which could be used as potential biomarkers for CRC progression and response to therapy

Parenting and Youth Sexual Risk in South Africa: The Role of Contextual Factors

Black South African youth are disproportionately affected by the HIV epidemic, and risky sexual behaviors increase youths’ vulnerability to HIV infection. U.S.-based research has highlighted several contextual factors that impact sexual risk, but these processes have not been examined in a South African context. In a sample of Black South African parent-youth dyads, this study examined relations among parenting, neighborhood quality, maternal social support, coparenting, and youth sexual risk. Hypotheses were evaluated using structural equation modeling. Results revealed that better neighborhood quality predicted less youth sexual risk via higher levels of positive parenting. Social support was positively related to parenting quality but did not interact with neighborhood quality to impact parenting. Coparenting did not moderate the relation between parenting and sexual risk. Results highlight the importance of family- and community-level processes for youth sexual risk in an understudied and high-risk sample. HIV prevention-interventions should be informed by these contextual factors

HIV Disclosure and Family Processes Among Mothers Living with HIV and Their Children: A Mixed-Methods Longitudinal Investigation

Despite recent reductions in HIV incidence in the U.S., African American and Latina women remain significantly overrepresented in HIV prevalence rates. Many women living with HIV are primary caregivers and are now living long enough to raise their children. Mothers living with HIV (MLH) face unique stressors, including elevated parenting stress, barriers to effective parenting, decisions related to disclosing their HIV status, and risk of child adjustment difficulties. Though studies have demonstrated cross-sectional relations among these family processes for MLH and their children, none have explored these processes transactionally across time. The current study was a longitudinal, mixed-methods examination of mothers’ HIV disclosure to children and its interplay with parenting quality, parenting stress, and child psychosocial adjustment. In the context of a randomized controlled trial evaluating an HIV disclosure intervention, a sample of 174 MLH and their children were recruited from two sites. Quantitative data were collected over four waves spanning 15 months. Qualitative data were collected with a subsample of 14 families in which disclosure had occurred. Two longitudinal structural equation modeling approaches—latent change score (LCS) modeling and cross-lagged panel analysis (CLPA)—were employed to examine relations among HIV disclosure, child adjustment, parenting, and parenting stress. Qualitative interviews were conducted to enrich the quantitative findings by further exploring families’ perspectives of these processes. Results of LCS models demonstrated that HIV disclosure led to subsequent improvements in parenting stress and children’s perceptions of parent-child communication and relationship quality. Changes in parenting stress inversely predicted changes in parental involvement. In the CLPA framework, several unidirectional and bidirectional relations were observed between mean levels of parenting stress and child adjustment, between child-reported parenting quality and child adjustment, and between child- and mother-reported parenting quality and parenting stress. Qualitative themes mirrored quantitative findings and provided explanation and contextualization for these findings. Results highlight the complex and multifaceted nature of the interplay among HIV disclosure, parenting practices, parenting stress, and child functioning. Findings suggest that MLH should be supported in disclosing their serostatus to their children to minimize parenting stress, bolster parenting skills, and promote positive outcomes for youth

GRAPHENE NANORIBBONS AND THEIR POLYMERIC NANOCOMPOSITES: CONTROLLED SYNTHESIS, CHARACTERIZATION AND APPLICATIONS

Carbon based materials are very promising as electrode materials energy generation and storage devices. They have been used for fuel cells, supercapacitors and solar cells. Among the carbon-based materials, graphene is very attractive due to its unique properties such as high electrical conductivity, good mechanical flexibility, large theoretical surface area (2630 m2/g), and high thermal and chemical stability. These unique properties make them very suitable for energy storage applications particularly for supercapacitors. The performance of the graphene as energy storage material could be further improved by growing them in nanoribbon form by unzipping carbon nanotubes. In this thesis, we report synthesis and characterization of graphene nanoribbons from multiwall carbon nanotubes (MWCNT). The synthesized graphene nanoribbons were structurally and electrochemically characterized. The shift of (002) peak in graphene nanoribbons compare to MWCNT confirms unzipping of MWCNT and its exfoliation. Other materials such as conducting polymers have been also used for energy applications. The performance of the conducting polymers such as polyaniline can be improved by making composites with graphene. We have found that nanocomposites of polyaniline with graphene nanoribbons (PA-GNR) have better performance for energy storage applications. The performance of the nanocomposites, polyaniline and graphene nanoribbons were electrochemically tested using cyclic voltammetry and galvanostatic charge-discharge methods. Cyclic voltammetry was performed at various scan rates to understand the charge transport mechanism. It was observed that the specific capacitance of the PA- GNR nanocomposites decreases with increasing scan rate. The overall charge storage capacity of the PA-GNR composites was higher than that of GNR. The higher charge storage capacity of the PA-GNR composites is due its enhance surface area and synergistic effect between polyaniline and graphene nanoribbons. A symmetric supercapacitor device was fabricated using PA-GNR composite. The effect of temperature on the charge storage capacity of the device was tested. It was observed that the charge storage capacity of the supercapacitor device increases with increase in temperature. The results suggest that graphene nanoribbons and composites of polyaniline with graphene nanoribbons could be used as an electrode material for supercapacitor applications

A Comparative Study of Heavy Metals and Trace Elements Concentration in Milk Samples Consumed in Iraq

في العمل الحالي  تم  قياس العناصر الرئيسية والنزرة لنماذج مختلفة من مسحوق الحليب المختار من الاسواق  العراقية باستخدام  تقنية فلورة  الأشعة السينية (XRF). كانت نتيجة القياسات تشير الى احتواء النماذج على تراكيز عالية من الصوديوم ،الفوسفور ،الكبريت ،الكلور، البوتاسيوم ،الكالسيوم والمغنيسيوم. وعلاوة على ذلك ، تم الكشف عن تراكيز منخفضة من الألمنيوم ،السيليكون ،الحديد ،البروم ،الموليبدينوم، اليود، الباريوم ،التيتانيوم ،المنغنيز ،الكوبالت ،الكروم ،النيكل ،النحاس ،الزنك والرصاص. تم أيضا استخدام تقنية التحليل بالتنشيط النيوتروني (NAA) وتقنية  Kjeldahlلتحديد تراكيز النيتروجين. وجد أن تركيز النيتروجين كان في حدود (1.96 - 3.23)٪ وهو ضمن الحدود المسموح بها. تم التحقق من تراكيز العناصر النزرة (النحاس، المنغنيز، الزنك، الرصاص) عن طريق استخدام تقنية مطيافية الامتصاص الذري (AAS) قورنت النتائج مع الحدود المسموح بها لمعايير منظمة الأغذية والزراعة ومنظمة الصحة العالمية.The measurements of major and trace elements in different brands of milk powder selected from the Iraqis market via the X-ray fluorescence (XRF) Technique have been studied in the present work. The result of the measurements reveals the high concentrations of sodium, phosphorus, sulfur, chlorine, potassium, calcium and magnesium. Furthermore, low concentrations of aluminum, silicon, iron, bromine, molybdenum, iodine, barium, titanium, manganese, cobalt, chrome, nickel, copper, zinc and lead were detected. Neutron activation analysis (NAA) and Kjeldahl technique were also employed to determine the concentrations of nitrogen. It was found that the nitrogen concentration was in the range of (1.96 - 3.23) % which is within the permissible limits. The concentrations of the trace elements (copper, manganese, zinc, lead) were verified via the atomic absorption spectrometer (AAS) technique. The results are compared with the authorized limit by the food and agriculture organization and the world health organization (FAO/WHO) standards

Dosimetric And Geometric Accuracy Of Image Guided Intensity Modulated Radiotherapy (IG-IMRT) In Head And Neck Cancer Patients

Advances in radiotherapy technology has made it possible to deliver highly conformal Intensity Modulated Radiotherapy (IMRT) beam to treat patient with improved setup accuracy using Image Guided Radiotherapy (IGRT). This retrospective study investigates the accuracy of IG-IMRT treatment for 25 head and neck cancer (HNC) patients in Advanced Medical & Dental Institute (AMDI), Universiti Sains Malaysia. An ionisation chamber array detector has been characterised and used for patient specific IMRT QA. The characterisation study shows the doses measured using ionisation chamber array detector were within 2% compared with the doses calculated from the treatment planning system (TPS). All 25 IMRT treatment obtained percentage pass rate ≥95% when 3%/3 mm gamma criteria were used. The geometrical accuracy of the treatment was also analysed based on setup errors measured using kV cone beam CT based-IGRT. A total of 231 pre-treatment CBCT imaging were acquired prior to treatment and compared to the reference CT. PTV margin of ≥3 mm in RL direction, SI direction and AP direction is required if no setup correction was performed. Offline setup protocols; NAL and eNAL were simulated on the setup errors recorded. The eNAL protocol recorded the smallest setup error in all three directions; which were 1.59 mm for RL direction, 2.13 mm for SI direction and 1.61 mm for AP direction. The impact of setup errors on dose distributions was also assessed on six HNC patients

Synthesis and Characterization of Naphthalenediimide-Functionalized Flavin Derivatives

Two acceptor–acceptor dyads have been synthesized featuring a flavin moiety and a naphthalenediimide (NDI) unit. The NDI unit is linked to the flavin through a short spacer group via either the N(3) or N(10) positions of the flavin. We have investigated the UV-Vis and redox properties of these multi-electron accepting systems which indicate that these materials display the collective properties of their component systems. Fluorescence spectroscopy measurements have revealed that their emission properties are dominated by the flavin unit

Strengthen Privacy by Policy Generation & Secure Access on Content Sharing Sites

Creating privacy controls for social networks that are both expressive and usable is a major challenge. Lack of user understanding of privacy settings can lead to unwanted disclosure of private information and, in some cases, to material harm. In light of these incidents, the need of tools to help users control access to their shared content is apparent. Toward addressing this need, we propose a Policy Hardening system to help users compose privacy settings for not only their images but securing each and every type of uploaded file. Dynamic groups are generated with particular policies of each group for secure access of files. We examine the role of social context, file content, and policies as possible indicators of users� privacy preferences. We propose a policy framework where user can upload all kind of files and provide different policies with different users

On the ubiquity of molecular anions in the dense interstellar medium

Results are presented from a survey for molecular anions in seven nearby Galactic star-forming cores and molecular clouds. The hydrocarbon anion C6H- is detected in all seven target sources, including four sources where no anions have been previously detected: L1172, L1389, L1495B and TMC-1C. The C6H-/C6H column density ratio is greater than about 1.0% in every source, with a mean value of 3.0% (and standard deviation 0.92%). Combined with previous detections, our results show that anions are ubiquitous in dense clouds wherever C6H is present. The C6H-/C6H ratio is found to show a positive correlation with molecular hydrogen number density, and with the apparent age of the cloud. We also report the first detection of C4H- in TMC-1 (at 4.8-sigma confidence), and derive an anion-to-neutral ratio C4H-/C4H = (1.2 +- 0.4) x 10^-5 (= 0.0012 +- 0.0004%). Such a low value compared with C6H- highlights the need for a revised radiative electron attachment rate for C4H. Chemical model calculations show that the observed C4H- could be produced as a result of reactions of oxygen atoms with C5H- and C6H-

Automated prototyping tool-kit (APT)

Automated prototyping tool-kit (APT) is an integrated set of software tools that generate source programs directly from real-time requirements. The APT system uses a fifth-generation prototyping language to model the communication structure, timing constraints, I/O control, and data buffering that comprise the requirements for an embedded software system. The language supports the specification of hard real-time systems with reusable components from domain specific component libraries. APT has been used successfully as a research tool in prototyping large war-fighter control systems (e.g. the command-and-control station, cruise missile flight control system, patriot missile defense systems) and demonstrated its capability to support the development of large complex embedded software. © 2002 Elsevier Science Inc. All rights reserved