Assembly, trafficking and function of gamma-secretase

gamma-Secretase catalyzes the final cleavage of the beta-amyloid precursor protein to generate amyloid-beta peptide, the principal component of amyloid plaques in the brains of patients suffering from Alzheimer's disease. Here, we review the identification of gamma-secretase as a protease complex and its assembly and trafficking to its site(s) of cellular function. In reconstitution experiments, gamma-secretase was found to be composed of four integral membrane proteins, presenilin (PS), nicastrin (NCT), PEN-2 and APH-1 that are essential and sufficient for gamma-secretase activity. PS, which serves as a catalytic subunit of gamma-secretase, was identified as a prototypic member of novel aspartyl proteases of the GxGD type. In human cells, gamma-secretase could be further defined as a heterogeneous activity consisting of distinct complexes that are composed of PS1 or PS2 and APH-1a or APH-1b homologues together with NCT and PEN-2. Using green fluorescent protein as a reporter we localized PS and gamma-secretase activity at the plasma membrane and endosomes. Investigation of gamma-secretase complex assembly in knockdown and knockout cells of the individual subunits allowed us to develop a model of complex assembly in which NCT and APH-1 first stabilize PS before PEN-2 assembles as the last component. Furthermore, we could map domains in PS and PEN-2 that govern assembly and trafficking of the complex. Finally, Rer1 was identified as a PEN-2-binding protein that serves a role as an auxiliary factor for gamma-secretase complex assembly. Copyright (c) 2006 S. Karger AG, Basel

The Effect of Using Task-Based Approach on the Achievement of Iraqi EFL Learners in the Course of Translation

أن الهدف من هذه الدراسة هو معرفة  اثر استخدام المدخل المستند للمهام على تحصيل طلبة المرحلة الرابعة للكلية في كورس الترجمة.من اجل ذلك تم تبني الفرضية التالية "ليس هناك  فرق ذو دلالة إحصائية بين  تحصيل الطلبة الذين درسوا مادة   الترجمة باستخدام  (المدخل المستند للمهام) وأولئك الذين درسوا نفس المادة (بطريقة المحاضرة).           حددت الدراسة على طلبة المرحلة الرابعة في قسم اللغة الانكليزية/ كلية التربية الأساسية/الجامعة المستنصرية للفصل الدراسي الثاني للعام الدراسي 2016-2017. لتحقيق هدف الدراسة ومعرفة صدق الفرضية تم إجراء تجربة لمدة عشرة أسابيع  باستخدام التصميم التجريبي ذو الاختبار ألبعدي- مجموعة ضابطة. وعند الانتهاء من التجربة تم أجراء الاختبار ألبعدي على عينة البحث وقد بينت نتائج الاختباران درجات طلبة المجموعة التجريبية أعلى من درجات طلبة المجموع الضابطة, وهذا يعني بان  طريقة المدخل المستند للمهام توثر وبشكل ايجابي على تحصيل الطلبة في مادة الترجمة. واستنادا إلى نتائج الدراسة الحالية, تم وضع الاستنتاجات والتوصيات ,وكذلك قدمت بعض المقترحات لدراسات أخرى.The present study aims to investigate the effect of using the Task-Based Approach on the achievement of Iraqi EFL learners in the course of translation. To achieve the aim of the study, it is hypothesized that there is no statistically significant difference between the mean scores of the students who are taught translation using the Task-based approach) and that the students who are taught translation using the traditional methods. The study is intended to be carried out on the fourth-year students of the Dept. of English, College of Basic Education , Al-Mustansiryah University for the 2nd semester of the academic year  2016-2017. To fulfill the aim and verify the hypothesis of the study, a ten-week experiment was conducted using a control group random assignment, posttest design only. At the end of the experiment, the posttest has been administered to the study sample . The test results revealed that the students' scores in  the experimental group are higher than those in the control group, which means  that  task-based approach  has a positive impact on the students' achievement in translation.  In the light of the obtained results a number of   conclusions and recommendations are made , then some suggestions for further research are presented

Ionized Gas Kinematics At High Resolution. II. Discovery Of A Double Infrared Cluster In II Zw 40

The nearby dwarf galaxy II Zw 40 hosts an intense starburst. At the center of the starburst is a bright compact radio and infrared source, thought to be a giant dense H II region containing approximate to 14,000 O stars. Radio continuum images suggest that the compact source is actually a collection of several smaller emission regions. We accordingly use the kinematics of the ionized gas to probe the structure of the radio-infrared emission region. With TEXES on the NASA-IRTF we measured the 10.5 mu m [S IV] emission line with effective spectral resolutions, including thermal broadening, of similar to 25 and similar to 3 km s(-1) and spatial resolution similar to 1 ''. The line profile shows two distinct, spatially coextensive, emission features. The stronger feature is at galactic velocity and has FWHM 47 km s(-1). The second feature is similar to 44 km s(-1) redward of the first and has FWHM 32 km s(-1). We argue that these are two giant embedded clusters, and estimate their masses to be approximate to 3 x 10(5) M-circle dot and approximate to 1.5 x 10(5) M-circle dot. The velocity shift is unexpectedly large for such a small spatial offset. We suggest that it may arise in a previously undetected kinematic feature remaining from the violent merger that formed the galaxy.University of Hawaii NNX-08AE38ANSF AST-0607312NASAAstronom

Issues and challenges in business intelligence case studies

Business Intelligence (BI) has embarked on decision-making setting. This has influenced many organizations from different industries that are located in diverse regions to implement BI. Critical Successful Factors (CSF) becomes the guideline for the implementer to adopt BI successfully. However, lack of BI knowledge and weak consideration of BI CSF led to the failure of BI implementation project. Several issues and challenges have been identified during the BI implementation. In addition, other researchers rarely discussed this subject. Thus, the objective of this paper is to recognize the issues and challenges on BI implementation. Through qualitative method, BI practices systematically described the purpose of BI execution on selected organizations, industries and regions. It has given the path towards the issues and challenges of BI implementation. The identified issues and challenges are defining the business goal, data management, limited funding, training and user acceptance as well as the lack of expertise issues. The findings categorized the issues and challenges into three dimensions of CSF for BI implementation, which are Organization, Process and Technology dimension. Limitation in this study requires future researchers to study in details of these issues and challenges including the solutions and the impact of BI implementation

Structured nursing follow-up: does it help in diabetes care?

BACKGROUND: In 1995 Clalit Health Services introduced a structured follow-up schedule, by primary care nurses, of diabetic patients. This was supplementary care, given in addition to the family physician’s follow-up care. This article aims to describe the performance of diabetes follow-up and diabetes control in patients with additional structured nursing follow-up care, compared to those patients followed only by their family physician. METHODS: We randomly selected 2,024 type 2 diabetic subjects aged 40–76 years. For each calendar year, from 2005–2007, patients who were “under physician follow-up only” were compared to those who received additional structured nursing follow-up care. MAIN OUTCOMES: Complete diabetes follow-up parameters including: HbA1c, LDL cholesterol, microalbumin, blood pressure measurements and fundus examination. RESULTS: The average age of study participants was 60.7 years, 52% were females and 38% were from low socioeconomic status (SES). In 2005, 39.5% of the diabetic patients received structured nursing follow-up, and the comparable figures for 2006 and 2007 were 42.1% 49.6%, respectively. The intervention subjects tended to be older, from lower SES, suffered from more chronic diseases and visited their family physician more frequently than the control patients. Patients in the study group were more likely to perform a complete diabetes follow-up plan: 52.8% vs. 21.5% (2005; p < 0.001) 55.5% vs. 30.3% (2006; p < 0.001), 52.3% vs. 35.7% (2007; p < 0.001). LDL cholesterol levels were lower in the study group only in 2005: 103.7 vs. 110.0 p < 0.001. CONCLUSION: Subjects with supplementary structured nursing follow-up care were more likely to perform complete diabetes follow-up protocol. Our results reinforce the importance of teamwork in diabetic care. Further study is required to identify strategies for channeling the use of the limited resources to the patients who stand to benefit the most

Affective Intimacies

The introduction of Affective intimacies lays out a novel terrain for rethinking intimacies through the lens of affect theories. The questions posed at the outset are set to promote an inquiry into the ways affect studies enrich contemporary theorisations of intimacy. Affective intimacies thus makes an effort to renew the prevailing scholarship and the imaginings of affective intimacies. By doing so, it points to an interdisciplinary lacuna and argues that the social sciences and humanities have yet to recognise affect and intimacy as conjoined processes. More specifically, it is suggested that instead of foregrounding affects and intimacies as pre-defined categories, scholarship would benefit from seeing affect and intimacy as entangled and meshed together. This line of inquiry includes encounters between humans as well as between human and non-human bodies. It thus provides key signposts for comprehending affective intimacies in new ways. The open-ended use of intimacy offers a situated analysis of affective intimacies. From this vantage point, proximity and closeness are not neutral practices but can be imbued with power. Rather than pointing to intimacy as an always positive and desirable closeness, the affective prism prompts us to consider new perspectives on the intimate as it is sensed, lived and entangled across human and non-human bodies. Lastly, the introduction closes with presenting the three sections of the book: the importance of re-imagining affective intimacies, the politics of affect and the queering of intimacies.</p