Design and development of a multi-layer memory system Final report, 28 Jan. 1966 - 27 Jan. 1967

Design and development of multilayer memory syste

Child Maltreatment, Non-Suicidal Self-Injury, and the Mediating Role of Self-Criticism

We examined the relation between child maltreatment and non-suicidal self-injury (NSSI). Participants were 86 adolescents who completed measures of child maltreatment, self-criticism, perceived criticism, depression, and NSSI. Analyses revealed significant, small-to-medium associations between specific forms of child maltreatment (physical neglect, emotional abuse, and sexual abuse) and the presence of a recent history of NSSI. Emotional and sexual abuse had the strongest relations with NSSI, and the data supported a theoretical model in which self-criticism mediates the relation between emotional abuse and engagement in NSSI. Specificity for the mediating role of self-criticism was demonstrated by ruling out alternative mediation models. Taken together, these results indicate that several different forms of childhood maltreatment are associated with NSSI and illuminate one mechanism through which maltreatment may be associated with NSSI. Future research is needed to test the temporal relation between maltreatment and NSSI and should aim to identify additional pathways to engagement in NSSI.Psycholog

Propagation of Avalanches in Mn12_{12}-acetate: Magnetic Deflagration

Local time-resolved measurements of fast reversal of the magnetization of single crystals of Mn12-acetate indicate that the magnetization avalanche spreads as a narrow interface that propagates through the crystal at a constant velocity that is roughly two orders of magnitude smaller than the speed of sound. We argue that this phenomenon is closely analogous to the propagation of a flame front (deflagration) through a flammable chemical substance.Comment: 5 pages, 5 figure

South Korea's automotive labour regime, Hyundai Motors’ global production network and trade‐based integration with the European Union

This article explores the interrelationship between global production networks(GPNs) and free trade agreements (FTAs) in the South Korean auto industry and its employment relations. It focuses on the production network of the Hyundai Motor Group (HMG) — the third biggest automobile manufacturer in the world — and the FTA between the EU and South Korea. This was the first of the EU’s ‘new generation’ FTAs, which among other things contained provisions designed to protect and promote labour standards. The article’s argument is twofold. First, that HMG’s production network and Korea’s political economy (of which HMG is a crucial part) limited the possibilities for the FTA’s labour provisions to take effect. Second, that the commercial provisions in this same FTA simultaneously eroded HMG’s domestic market and corporate profitability, leading to adverse consequences for auto workers in the more insecure and low-paid jobs. In making this argument, the article advances a multiscalar conceptualization of the labour regime as an analytical intermediary between GPNs and FTAs. It also provides one of the first empirical studies of the EU–South Korea FTA in terms of employment relations, drawing on 105 interviews with trade unions, employer associations, automobile companies and state officials across both parties

Geographically touring the eastern bloc: British geography, travel cultures and the Cold War

This paper considers the role of travel in the generation of geographical knowledge of the eastern bloc by British geographers. Based on oral history and surveys of published work, the paper examines the roles of three kinds of travel experience: individual private travels, tours via state tourist agencies, and tours by academic delegations. Examples are drawn from across the eastern bloc, including the USSR, Poland, Romania, East Germany and Albania. The relationship between travel and publication is addressed, notably within textbooks, and in the Geographical Magazine. The study argues for the extension of accounts of cultures of geographical travel, and seeks to supplement the existing historiography of Cold War geography

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo

Targeted drug delivery to the endothelium has the potential to generate localized therapeutic effects at the blood- tissue interface. For some therapeutic cargoes, it is essential to maintain contact with the bloodstream to exert protective effects. The pharmacokinetics (PK) of endothelial surface- targeted affinity ligands and biotherapeutic cargo remain a largely unexplored area, despite obvious translational implications for this strategy. To bridge this gap, we site- specifically radiolabeled mono- (scFv) and bivalent (mAb) affinity ligands specific for the endothelial cell adhesion molecules, PECAM- 1 (CD31) and ICAM- 1 (CD54). Radiotracing revealed similar lung biodistribution at 30 minutes post- injection (79.3% ± 4.2% vs 80.4% ± 10.6% ID/g for αICAM and 58.9% ± 3.6% ID/g vs. 47.7% ± 5.8% ID/g for αPECAM mAb vs. scFv), but marked differences in organ residence time, with antibodies demonstrating an order of magnitude greater area under the lung concentration vs. time curve (AUCinf 1698 ± 352 vs. 53.3 ± 7.9 ID/g*hrs for αICAM and 1023 ± 507 vs. 114 ± 37 ID/g*hrs for αPECAM mAb vs scFv). A physiologically based pharmacokinetic model, fit to and validated using these data, indicated contributions from both superior binding characteristics and prolonged circulation time supporting multiple binding- detachment cycles. We tested the ability of each affinity ligand to deliver a prototypical surface cargo, thrombomodulin (TM), using one- to- one protein conjugates. Bivalent mAb- TM was superior to monovalent scFv- TM in both pulmonary targeting and lung residence time (AUCinf 141 ± 3.2 vs 12.4 ± 4.2 ID/g*hrs for ICAM and 188 ± 90 vs 34.7 ± 19.9 ID/g*hrs for PECAM), despite having similar blood PK, indicating that binding strength is more important parameter than the kinetics of binding. To maximize bivalent target engagement, we synthesized an oriented, end- to- end anti- ICAM mAb- TM conjugate and found that this therapeutic had the best lung residence time (AUCinf 253 ± 18 ID/g*hrs) of all TM modalities. These observations have implications not only for the delivery of TM, but also potentially all therapeutics targeted to the endothelial surface.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156501/3/fsb220760_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156501/2/fsb220760-sup-0001-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156501/1/fsb220760.pd

Identification of publicly available data sources to inform the conduct of Health Technology Assessment in India

Background: Health technology assessment (HTA) provides a globally-accepted and structured approach to synthesising evidence for cost and clinical effectiveness alongside ethical and equity considerations to inform evidence-based priorities. India is one of the most recent countries to formally commit to institutionalising HTA as an integral component of the heath resource allocation decision-making process. The effective conduct of HTA depends on the availability of reliable data. Methods: We draw from our experience of collecting, synthesizing, and analysing health-related datasets in India and internationally, to highlight the complex requirements for undertaking HTA, and explore the availability of such data in India. We first outlined each of the core data components required for the conduct of HTA, and their availability in India, drawing attention to where data can be accessed, and different ways in which researchers can overcome the challenges of missing or low quality data. Results: We grouped data into the following categories: clinical efficacy; cost; epidemiology; quality of life; service use/consumption; and equity. We identified numerous large local data sources containing epidemiological information. There was a marked absence of other locally-collected data necessary for informing HTA, particularly data relating to cost, service use, and quality of life. Conclusions: The introduction of HTA into the health policy space in India provides an opportunity to comprehensively assess the availability and quality of health data capture across the country. While epidemiological information is routinely collected across India, other data inputs necessary for HTA are not readily available. This poses a significant bottleneck to the efficient generation and deployment of HTA into the health decision space. Overcoming these data gaps by strengthening the routine collection of comprehensive and verifiable health data will have important implications not only for embedding economic analyses into the priority setting process, but for strengthening the health system as a whole

Towards ‘Onlife’ Education. How Technology is Forcing Us to Rethink Pedagogy

[EN] The objective of this chapter is twofold: on the one hand, to provide an explanation for the need we have today to rethink pedagogy based on new realities and the scenarios in which we live, also in education, generated by the technology of our time and, on the other hand, to point out the direction in which we can find a path that leads us to that reflection in the face of the inevitable convergence between technology and pedagogy in which we are today

The impact of emotional well-being on long-term recovery and survival in physical illness: a meta-analysis

This meta-analysis synthesized studies on emotional well-being as predictor of the prognosis of physical illness, while in addition evaluating the impact of putative moderators, namely constructs of well-being, health-related outcome, year of publication, follow-up time and methodological quality of the included studies. The search in reference lists and electronic databases (Medline and PsycInfo) identified 17 eligible studies examining the impact of general well-being, positive affect and life satisfaction on recovery and survival in physically ill patients. Meta-analytically combining these studies revealed a Likelihood Ratio of 1.14, indicating a small but significant effect. Higher levels of emotional well-being are beneficial for recovery and survival in physically ill patients. The findings show that emotional well-being predicts long-term prognosis of physical illness. This suggests that enhancement of emotional well-being may improve the prognosis of physical illness, which should be investigated by future research