REST is a hypoxia-responsive transcriptional repressor

Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxiadependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia.

Creating Responsive Information Systems with the Help of SSADM

In this paper, a program for a research is outlined. Firstly, the concept of responsive information systems is defined and then the notion of the capacity planning and software performance engineering is clarified. Secondly, the purpose of the proposed methodology of capacity planning, the interface to information systems analysis and development methodologies (SSADM), the advantage of knowledge-based approach is discussed. The interfaces to CASE tools more precisely to data dictionaries or repositories (IRDS) are examined in the context of a certain systems analysis and design methodology (e.g. SSADM).

The relationship of culturally responsive instruction and the reading comprehension and attitude of struggling urban adolescent readers

Culturally responsive instruction refers to the identification of relevant cultural aspects of students' lives and infusion of these into the curriculum. This instructional approach assumes that a culturally appropriate curriculum can potentially motivate, engage, and lead students to higher rates of achievement. This quasi-experimental study (N=44) investigated the relationship of culturally responsive instruction and the reading comprehension and attitude of struggling urban adolescent readers. The study incorporated the use of culturally responsive instruction using culturally relevant literature (CRL), the Bluford Series Novels, as authentic texts of instruction. Participants were seventh grade reading students at a Title I middle school in South Florida. After a baseline period, two different classes were taught for 8 weeks using different methods. One class formed the experimental group ( n=22) and the other class formed the comparison group (n =22). The CRI curriculum for the experimental group embraced the socio-cultural perspective through the use of small discussion groups in which students read and constructed meaning with peers through interaction with the Bluford Series Novels; gave written responses to multiple strategies according to SCRAP - Summarize, Connect, Reflect, Ask Questions, Predict; responded to literal and inferential questions, while at the same time validating their responses through evidence from the text. The Read XL (basal reader) curriculum of the comparison group utilized a traditional form of instruction which incorporated the reading of passages followed by responses to comprehension questions, and teacher-led whole group discussion. The main sources of data were collected from the Gates-MacGinitie Reading Tests, the Florida Assessments for Instruction in Reading (FAIR), and the Rhody Secondary Reading Attitude Assessment. Statistical analyses were performed using Repeated Measures ANOVAs. Findings from the study revealed that the experimental participants' reading attitudes and FAIR comprehension scores increased when compared to the comparison group. Overall, the results from the study revealed that culturally responsive instruction can potentially foster reading comprehension and a more positive attitude towards reading. However, a replication of this study in other settings with a larger, more randomized sample size and a greater ethnic variation is needed in order to make full generalizations.

The Roles of ‘Conventional’ and Demand-Responsive Bus Services

Purpose - The roles of ‘conventional’ (fixed-route and fixed-timetable) bus services is examined and compared to demand-responsive services, taking rural areas in England as the basis for comparison. It adopts a ‘rural’ definition of settlements under a population of 10,000. Design/methodology/approach - Evidence from the National Travel Survey, technical press reports and academic work is brought together to examine the overall picture. Findings - Inter-urban services between towns can provide a cost-effective way of serving rural areas where smaller settlements are suitably located. The cost structures of both fixed-route and demand-responsive services indicate that staff time and cost associated with vehicle provision are the main elements. Demand-responsive services may enable larger areas to be covered, to meet planning objectives of ensuring a minimum of level of service, but experience often shows high unit cost and public expenditure per passenger trip. Economic evaluation indicates user benefits per passenger trip of similar magnitude to existing average public expenditure per trip on fixed-route services. Considerable scope exists for improvements to conventional services through better marketing and service reliability. Practical implications - The main issue in England is the level of funding for rural services in general, and the importance attached to serving those without access to cars in such areas. Social implications - The boundary between fixed-route and demand-responsive operation may lie at relatively low population densities. Originality/value - The chapter uses statistical data, academic research and operator experience of enhanced conventional bus services to provide a synthesis of outcomes in rural areas.

An Infection-Responsive Approach to Reduce Bacterial Adhesion in Urinary Biomaterials

Infection is an inevitable consequence of chronic urinary catheterisation, with associated problems of recurrent catheter encrustation and blockage experienced by approximately 50% of all long-term catheterised patients. In this work we have exploited, for the first time, the reported pathogen-induced elevation of urine pH as a trigger for ‘intelligent’ antimicrobial release from novel hydrogel drug delivery systems of 2-hydroxyethyl methacrylate and vinyl-functionalised nalidixic acid derivatives, developed as candidate infection-resistant urinary catheter coatings. Demonstrating up to 20-fold faster rates of drug release at pH 10, representing infected urine pH, than at pH 7, and achieving reductions of up to 96.5% in in vitro bacterial adherence, our paradigm of pH-responsive drug delivery, which requires no external manipulation, therefore represents a promising development towards the prevention of catheter-associated urinary tract infections (CAUTIs) in vivo.

Stimuli-Responsive Microneedle Arrays For On-Demand Drug Delivery

Pulsatile, or “on-demand”, delivery systems have the capability to deliver a therapeutic molecule at the right time/site of action and in the right amount (1). Pulsatile delivery systems present multiple benefits over conventional dosage forms and provide higher patient compliance. The combination of stimuli-responsive materials with the drug delivery capabilities of hydrogel-forming MN arrays (2) opens an interesting area of research. In the present work we describe, a stimuli-responsive hydrogel-forming microneedle (MN) array that enable delivery of a clinically-relevant model drug (ibuprofen) upon application of UV radiation (Figure 1A). MN arrays were prepared using a micromolding technique using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) (Figure 1B). The arrays were loaded with up to 5% (w/w) ibuprofen included in a light-responsible conjugate (3,5-dimethoxybenzoin conjugate) (2). The presence of the conjugate inside the MN arrays was confirmed by Raman spectroscopy measurements. MN arrays were tested in vitro showing that they were able to deliver up to three doses of 50 mg of ibuprofen after application of an optical trigger (wavelength of 365 nm) over a long period of time (up to 160 hours) (Figure 1C and 1D). The work presented here is a probe of concept and a modified version of the system should be used as UV radiation is shown to be the major etiologic agent in the development of skin cancers. Consequently, for future applications of this technology an alternative design should be developed. Based on the previous research dealing with hydrogel forming MN arrays a suitable strategy will be to use hydrogel-forming MN arrays containing a backing layer made with the material described in this work as the drug reservoir (2). Finally, a porous layer of a material that blocks UV radiation should be included between the MN array and the drug reservoir. Therefore radiation can be applied to the system without reaching the skin surface. Therefore after modification, the system described here interesting properties as “on-demand” release system for prolonged periods of time. This technology has potential for use in “on-demand” delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.

Juliane Lamprecht: Rekonstruktiv-responsive Evaluation in der Praxis, Neue Perspektiven dokumentarischer Evaluationsforschung. Wiesbaden: VS Verlag für Sozialwissenschaften 2012 [Rezension]

Rezension von: Juliane Lamprecht: Rekonstruktiv-responsive Evaluation in der Praxis, Neue Perspektiven dokumentarischer Evaluationsforschung, Wiesbaden: VS Verlag für Sozialwissenschaften 2012 (305 S.; ISBN 978-3-5311-7985-8)