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)

Spatiotemporal control over the co-conformational switching in pH-responsive flavylium-based multistate pseudorotaxanes

A multistate molecular dyad containing flavylium and viologen units was synthesized and the pH dependent thermodynamics of the network completely characterized by a variety of spectroscopic techniques such as NMR, UV-vis and stopped-flow. The flavylium cation is only stable at acidic pH values. Above pH ≈ 5 the hydration of the flavylium leads to the formation of the hemiketal followed by ring-opening tautomerization to give the cis-chalcone. Finally, this last species isomerizes to give the trans-chalcone. For the present system only the flavylium cation and the trans-chalcone species could be detected as being thermodynamically stable. The hemiketal and the cis-chalcone are kinetic intermediates with negligible concentrations at the equilibrium. All stable species of the network were found to form 1 : 1 and 2 : 1 host : guest complexes with cucurbit[7]uril (CB7) with association constants in the ranges 10(5)-10(8) M(-1) and 10(3)-10(4) M(-1), respectively. The 1 : 1 complexes were particularly interesting to devise pH responsive bistable pseudorotaxanes: at basic pH values (≈12) the flavylium cation interconverts into the deprotonated trans-chalcone in a few minutes and under these conditions the CB7 wheel was found to be located around the viologen unit. A decrease in pH to values around 1 regenerates the flavylium cation in seconds and the macrocycle is translocated to the middle of the axle. On the other hand, if the pH is decreased to 6, the deprotonated trans-chalcone is neutralized to give a metastable species that evolves to the thermodynamically stable flavylium cation in ca. 20 hours. By taking advantage of the pH-dependent kinetics of the trans-chalcone/flavylium interconversion, spatiotemporal control of the molecular organization in pseudorotaxane systems can be achieved.

International comparative field evaluation of a traffic-responsive signal control strategy in three cities

The recently developed network-wide real-time signal control strategy TUC has been implemented in three traffic networks with quite different traffic and control infrastructure characteristics: Chania, Greece (23 junctions); Southampton, UK (53 junctions); and Munich, Germany (25 junctions), where it has been compared to the respective resident real-time signal control strategies TASS, SCOOT and BALANCE. After a short outline of TUC, the paper describes the three application networks; the application, demonstration and evaluation conditions; as well as the comparative evaluation results. The main conclusions drawn from this high-effort inter-European undertaking is that TUC is an easy-to-implement, inter-operable, low-cost real-time signal control strategy whose performance, after very limited fine-tuning, proved to be better or, at least, similar to the ones achieved by long-standing strategies that were in most cases very well fine-tuned over the years in the specific networks.

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 hypoxia-dependent 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.

A Rare Cause of Confusion: Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis

An 81-year-old female patient required numerous admissions for symptoms of confusion, visual hallucinations, myoclonus and seizures, which were treated as stroke, infections and viral encephalitis with some improvement after treatment but with recurrence that caused her to be readmitted to hospital. On the last admission, she was found to have very high antithyroid antibodies and a diagnosis of Hashimoto’s encephalopathy was made, with an overwhelming response to steroids.

Reduced graphene oxide wrapped Cu2O supported on C3N4: An efficient visible light responsive semiconductor photocatalyst

Herein, Cu 2O spheres were prepared and encapsulated with reduced graphene oxide (rGO). The Cu 2O–rGO–C3N4 composite covered the whole solar spectrum with significant absorption intensity. rGO wrapped Cu 2O loading caused a red shift in the absorption with respect to considering the absorption of bare C3N4. The photoluminescence study confirms that rGO exploited as an electron transport layer at the interface of Cu 2O and C3N4 heterojunction. Utmost, ∼2 fold synergistic effect was achieved with Cu 2O–rGO–C3N4 for the photocatalytic reduction of 4-nitrophenol to 4-aminophenol in comparison with Cu 2O–rGO and C3N4. The Cu 2O–rGO–C3N4 photocatalyst was reused for four times without loss in its activity.

Iterated responsive threshold search for the quadratic multiple knapsack problem

International audience

PUBLIC-PRIVATE PARTNERSHIP FOR RESPONSIVE EXTENSION EDUCATION: THE CASE OF SAFE AND UCC IN GHANA

Developing nations in Africa are not shielded from the pressures of a globalized competitive agricultural marketplace. With an appreciable bulk of her people deriving livelihoods from diverse agricultural enterprises, these nations must respond to important contemporary issues shaping global agriculture. Farmers from such nations, including Ghana, will be able to improve their participation in the competitive local, regional and global agricultural marketplace if the appropriate agricultural technologies and extension information support are available. To achieve this, a new breed of agricultural extension graduates who can respond to current and emerging challenges in agriculture and interface effectively with farmers must be produced through responsive extension education and training. While extension education can produce effective extensionists to hasten agricultural development, budgetary constraints make it difficult for most African governments to successfully and sustainably implement such educational programs. However, public-private partnership (PPP) initiatives offer a way out of this financial dilemma. Beginning in 1993, the Sasakawa Africa Fund for Extension Education (SAFE) worked with the University of Cape Coast (UCC) in Ghana to develop an innovative extension education program through a public private partnership. The program, comprising a BSc. and Diploma components, was designed to respond to the myriad of challenges facing higher agricultural extension education in Ghana. A key practical feature of the curricula is the “Supervised Enterprise Projects” (SEPS), which enable students to work with relevant stakeholders to identify and tackle agricultural problems in farming communities through experiential extension approaches and action research. The SAFE-UCC initiative fulfils important education goals such as: expanding and improving access; ensuring quality and relevance; ensuring funding and mobilizing resources for sustainability; building partnerships and linkages; and promoting international co-operation. The paper discusses the underlying conditions for a successful public private partnership in agricultural and extension education and sheds light on the impacts, lessons learned and challenges.

Designing Hydrogels that Transform their Shape in Response to Molecular Cues

There has been considerable interest in developing shape-changing soft materials for potential applications in drug delivery, microfluidics and biosensing. These shape- changing materials are inspired by the morphological changes exhibited by plants in nature, such as the Venus flytrap. One specific class of shape-change is that from a flat sheet to a folded structure (e.g., a tube). Such “self-folding” materials are usually composed of polymer hydrogels, and these typically fold in response to external stimuli such as pH and temperature. In order to develop these hydrogels for the previously described applications, it is necessary to expand the range of triggers. The focus of this dissertation is the advancement of shape-changing polymer hydrogels that are sensitive to uncommon cues such as specific biomolecules (enzymes), the substrates for such enzymes, or specific multivalent cations. First, we describe a hybrid gel that responds to the presence of low concentrations of a class of enzymes known as matrix metalloproteinases (MMPs). The hybrid gel was created by utilizing photolithographic techniques to combine two or more gels with distinct chemical composition into the same material. Certain portions of the hybrid gel are composed of a biopolymer derivative with crosslinkable groups. The hybrid gel is flat in water; however, in the presence of MMPs, the regions containing the biopolymer are degraded and the flat sheet folds to form a 3D structure. We demonstrate that hydrogels with different patterns can transform into different 3D structures such as tubes, helices and pancakes. Furthermore, this shape change can be made to occur at physiological concentrations of enzymes. Next, we report a gel with two layers that undergoes a shape change in the presence of glucose. The enzyme glucose oxidase (GOx) is immobilized in one of the layers. GOx catalyzes the conversion of glucose to gluconic acid. The production of gluconic acid decreases the local pH. The decrease in local pH causes one of the layers to swell. As a result, the flat sheet folds to form a tube. The tube unfolds to form a flat sheet when it is transferred to a solution with no glucose present. Therefore, this biomolecule- triggered shape transformation is reversible, meaning the glucose sensing gel is reusable. Furthermore, this shape change only occurs in the presence of glucose and it does not occur in the presence of other small sugars such as fructose. In our final study, we report the shape change of a gel with two layers in the presence of multivalent ions such as Ca2+ and Sr2+. The gel consists of a passive layer and an active layer. The passive layer is composed of dimethylyacrylamide (DMAA), which does not interact with multivalent ions. The active layer consists of DMAA and the biopolymer alginate. In the presence of Ca2+ ions, the alginate chains crosslink and the active layer shrinks. As a result, the gel converts from a flat sheet to a folded tube. What is particularly unusual is the direction of folding. In most cases, when flat rectangular gels fold, they do so about their short-side. However, our gels typically fold about their long-side. We hypothesize that non-homogeneous swelling determines the folding axis.

Porous self-protonating spiropyran-based NIPAAm gels with improved reswelling kinetics

The final publication is available at Springer via http://dx.doi.org/[10.1007/s10853-015-9458-2]

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.

Development of a responsive fisheries management system for the Portuguese crustacean bottom trawl fishery: Lessons learnt

A prototype for a Responsive Fisheries Management System (RFMS) was developed in the context of the European FP7 project EcoFishMan and tested on the Portuguese crustacean trawl fishery. Building on Results Based Management principles, RFMS involves the definition of specific and measurable objectives for a fishery by the relevant authorities but allows resource users the freedom to find ways to achieve the objectives and to provide adequate documentation. Taking into account the main goals of the new Common Fisheries Policy, such as sustainable utilization of the resources, end of discards and unwanted catches, a management plan for the Portuguese crustacean trawl fishery was developed in cooperation with the fishing industry, following the process and design laid out in the RFMS concept. The plan considers biological, social and economic goals and assigns a responsibility for increased data collection to the resource users. The performance of the plan with regard to selected indicators was evaluated through simulations. In this paper the process towards a RFMS is described and the lessons learnt from the interaction with stakeholders in the development of an alternative management plan are discussed. (C) 2014 Elsevier Ltd. All rights reserved.