bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the security management practices of humanitarian organizations
Authors: Bollettino Vincenzo
Published: February 2008

Humanitarian organisations operate in increasingly hostile environments. Although authoritative statistics are scarce, anecdotal evidence suggests that aid workers face life‐threatening risks that are exacerbated by the growing number of humanitarian organisations operating in the field, the diversity of their mandates, the lack of common professional security standards, and limited success in inter‐agency security coordination. Despite broad acceptance of the need for better security management and coordination, many humanitarian organisations remain ambivalent about devoting increased resources to security management and security coordination. A critical lack of basic empirical knowledge of the field security environment hampers efforts to enhance security management practices. The absence of a systematic means of sharing incident data undermines the capacity of the humanitarian community to address proactively security threats. In discussions about humanitarian staff safety and security, the least common denominator remains cumulative anecdotal evidence provided by the many security personnel working for humanitarian organisations in the feld.
Overview of deaths associated with natural events, United States, 1979–2004
Authors: Thacker Maria T.F. , Lee Robin , Sabogal Raquel I. , Henderson Alden
Published: February 2008

Analysis of the National Center for Health Statistics' Compressed Mortality File showed that between 1979 and 2004, natural events caused 21,491 deaths in the United States. During this 26‐year period, there were 10,827 cold‐related deaths and 5,279 heat‐related deaths. Extreme cold or heat accounted for 75 per cent of the total number of deaths attributed to natural events— more than all of deaths resulting from lightning, storms and foods, and earth movements, such as earthquakes and landslides. Cold‐related death rates were highest in the states of Alaska, Montana, New Mexico, and South Dakota, while heat‐related deaths were highest in the states of Arizona, Missouri, and Arkansas. These deaths occurred more often among the elderly and black men. Other deaths were attributed to lightning (1,906), storms and foods (2,741), and earth movements (738). Most deaths associated with natural events are preventable and society can take action to decrease the morbidity and mortality connected with them.
From Gift Relationships to Quasi‐markets: An Odyssey along the Policy Paths of Altruism and Egoism
Authors: Pinker Robert
Published: February 2008

Nearly forty years ago, the publication of ‘The Price of Blood’ (1968) and ‘The Gift Relationship’ (1970) added a new dimension of ideological conflict to the debate about the values, ends and means of social policy. The questions that Richard Titmuss posed in ‘The Gift Relationship’ are still discussed in current debates about the respective merits of unitary and pluralist models of welfare, the egoistic and altruistic motives that underpin them, and the rights and responsibilities intrinsic to the status of citizenship. The ways in which the content and focus of these debates have changed over the past forty years are here reviewed, taking Titmuss's ‘The Gift Relationship’, my own contributions in ‘Social Theory and Social Policy’ (1971) and ‘The Idea of Welfare’ (1979), and Julian Le Grand's ‘Motivation, Agency and Public Policy’ (2003) as the temporal and salient points of reference. A brief introduction describes how the academic debate became sharply polarized in the late 1960s and early 1970s, and how a key decision about the future development of this journal was taken at the same time.
Emigration from Zimbabwe: Migrant Perspectives
Authors: Bloch Alice
Published: February 2008

This article explores migration from Zimbabwe to the UK and South Africa and the experiences of the receiving countries from the perspective of the migrants. It provides a critical examination of the impact of structural barriers in both the UK and South Africa on the economic experiences of migrants. The effects of immigration status, due to the exclusion of asylum‐seekers in the UK and the presence of undocumented migrants in the UK and South Africa, is explored in relation to employment and remittance activities. The clear evidence of the deskilling taking place among the majority of Zimbabwean migrants – and its impact on remittances and other forms of transnational support – is also examined. The article concludes that any real commitment to alleviating global poverty on the part of the world's migrant receiving countries must include a re‐examination of barriers to employment, education and the use of skills, since these barriers not only have a short‐term impact on remittances to the sending country and fiscal capacity to contribute in the receiving country, but will also impact on longer‐term development should the migrants return to their country of origin.
Reasons and Inclusion: The Foundation of Deliberation
Authors: Schneiderhan Erik , Khan Shamus
Published: February 2008

This article provides two empirical evaluations of deliberation. Given that scholars of deliberation often argue for its importance without empirical support, we first examine whether there is a “deliberative difference”; if actors engaging in deliberation arrive at different decisions than those who think on their own or “just talk.” As we find a general convergence within deliberation scholarship around reasons and inclusion, the second test examines whether these two specific mechanisms are central to deliberation. The first evaluation looks at outcomes within a laboratory setting; the second at videotapes of decision-making processes within this setting. Our results show two things. First, in terms of outcomes, deliberation differs from other forms of interaction. Second, reasons and inclusion are central to the deliberative process. The more reasons provided within each group, the more likely participants were to change their position; similarly, the more inclusive groups were, the more likely participants were to change their position. We conclude by arguing that more work needs to be done, both in evaluating the deliberative difference and in disaggregating deliberation and examining its central explanatory mechanisms.
Effect of orthographic processes on letter position encoding
Authors: Pitchford N. J. , Ledgeway T. , Masterson J.
Published: February 2008

We investigate whether orthographic processes influence the identification and encoding of letter position within letter strings. To minimise word‐specific effects, we adopt a visual letter search task that requires participants to identify a cued letter target among a random five‐letter string. Using this paradigm, previous studies have shown that letter targets to the left are identified faster than those to the right of centre and letter targets in the initial, medial and final positions are identified faster than those in neighbouring positions. While the medial letter advantage is likely to arise from greater visual acuity at the point of fixation, the mechanisms responsible for the left‐to‐right, and exterior, letter advantage have yet to be determined. We show that: (i) search functions for most letters reflect the directional scanning process required for reading English orthography; (ii) search times are significantly faster for letter targets that appear in the most, compared with the least, frequent position in written words; and (iii) search times correlate significantly with positional letter frequency, especially in the initial and final positions. We propose that a combination of low‐level visual, and higher‐level orthographic, processes modulate the encoding of letter identities and position in written word recognition.
Anti–tumour necrosis factor‐α therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study
Authors: Gisondi P , Cotena C , Tessari G , Girolomoni G
Published: February 2008

Background  Chronic plaque psoriasis is associated with overweight or obesity. Anti–tumour necrosis factor‐α (anti‐TNF‐α) treatments are now frequently used in psoriasis management. TNF‐α is deeply involved in body weight homeostasis, which may be affected by TNF‐α–targeted therapy.

Objective  To investigate whether anti‐TNF‐α treatments is associated with changes in body weight in patients with chronic plaque psoriasis.

Methods  We performed a retrospective controlled analysis comparing the variations in body weight and body mass index (BMI) in three closed cohorts of psoriatic patients during a 6‐month treatment with etanercept (N = 58), infliximab (N = 40) or methotrexate (N = 43).

Results  We observed a body weight increment of 1.5 ± 2.7 kg (mean ± SD; P = 0.0002) and 2.5 ± 3.3 kg (P = 0.004) in patients treated with etanercept and infliximab, respectively. In contrast, a non‐significant change (0.6 ± 1.4 kg; P = 0.4) was measured in patients treated with methotrexate. The BMI increased with 0.5 ± 0.5 (P = 0.01) and 0.8 ± 1 (P = 0.003) points in patients treated with etanercept and infliximab, respectively, whereas it did not change (< 0.2 ± 0.5; P = 0.06) in patients treated with methotrexate. About one fourth of patients experienced a 4‐ to 10‐kg weight gain. Differences in body weight variations among patients treated with anti‐TNF‐α therapies and methotrexate were statistically significant (P = 0.0005). We could not identify clinical parameters predicting this phenomenon.

Conclusions  Patients with psoriasis treated with long‐term anti‐TNF‐α therapies may manifest a body weight gain. This effect should be taken into account in the global approach to patients with psoriasis.
Clinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate‐to‐severe plaque psoriasis in Taiwan: results of an open‐label, single‐arm pilot study
Authors: Tsai TF , Liu MT , Liao YH , Licu D
Published: February 2008

Background  No clinical trial of efalizumab has been conducted in Asia.

Objective  To determine the efficacy and safety of efalizumab in Taiwanese patients with psoriasis.

Methods  This is an open‐label, single‐arm pilot study conducted at two centres. Patients were given 1 mg/kg efalizumab subcutaneously once a week for 12 weeks and were then followed up for a further 12 weeks.

Results  A total of 49 patients participated in the study. The median improvement in Psoriasis Area and Severity Index (PASI) during the treatment period was 19.6%, and a ≥ 50% improvement in PASI was seen in 20.4%. Rebound was seen in 17.8% of patients, and anti‐efalizumab antibodies were detected in 41% of patients. The most frequent adverse events were headache (34.7%), arthralgia/arthritis (28.6%), psoriasis events (new form/exacerbation; 26.5%) and pruritus (22.4%).

Conclusions  This small pilot study indicated that efalizumab was effective in improving psoriasis symptoms in Taiwanese patients, with no new safety issues identified.
Evidence‐based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgaris
Authors: Hædersdal M , Togsverd‐Bo K , Wulf HC
Published: February 2008

Background  There is a considerable need for effective and safe treatment for acne vulgaris.

Objective  In a systematic review with an evidence‐based approach to assess the effects of optical treatments for acne vulgaris.

Methods  Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library.

Results  A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad‐spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and one trial described adequate allocation concealment. Most trials were intraindividual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short‐term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, we conclude that optical treatments possess the potential to improve inflammatory acne on a short‐term basis with the most consistent outcomes for PDT [up to 68% improvement, aminolevulinic acid (ALA), methyl‐aminolevulinic acid (MAL) and red light]. IPL‐assisted PDT seems to be superior to IPL alone. Only two trials compare optical vs. conventional treatments, and further studies are needed. Side‐effects from optical treatments included pain, erythema, oedema, crusting, hyperpigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL.

Conclusion  Evidence from controlled clinical trials indicates a short‐term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments.
Maneb potentiates paraquat neurotoxicity by inducing key Bcl‐2 family members
Authors: Fei Qingyan , Ethell Douglas W.
Published: February 2008

An important feature of Parkinson’s disease is the degeneration of dopaminergic neurons in theSubstantia Nigra pars compacta. Paraquat (PQ) and MPTP cause the selective degeneration of these neuronsin vivo, and combining PQ with maneb exacerbates that pathology. Elucidation of the cell death mechanisms involved is important to understand how multiple environmental toxins may contribute to sporadic Parkinson’s disease. We recently reported that PQ induces neuronal apoptosis through Bak activation, in contrast to MPP+, the toxic metabolite of MPTP, which relies on Bax and p53. Here we show that individually PQ and maneb activate Bak, but together they trigger Bax‐dependent cell death. Focusing on mechanisms responsible for this synergy, we found that maneb+PQ increased the expression of three strong Bak inhibitors, Bfl‐1, Bcl‐xL and Mcl‐1, and also induced Bax activators that included Bik and Bim. Those responses favor Bax‐dependent MOMP and apoptosis. SiRNA knockdown of Bax and Bak confirmed that individually PQ and maneb induce Bak‐dependent cell death, but together they block the Bak pathway and activate apoptosis through Bax.
Effects of Aripiprazole on Subjective and Physiological Responses to Alcohol
Authors: Kranzler Henry R. , Covault Jonathan , Pierucci‐Lagha Amira , Chan Grace , Douglas Kara , Arias Albert J. , Oncken Cheryl
Published: February 2008

Background:  Aripiprazole is an atypical antipsychotic with partial agonist activity at D2 receptors, which could reduce the reinforcing effects of alcohol. The present study examined whether aripiprazole modifies the behavioral and physiological effects of a moderate dose of alcohol in a group of social drinkers.

Methods:  Eighteen healthy subjects (9 men; mean age = 27.6 years) completed a double‐blind, within‐subject study with 3 experimental sessions in a randomized sequence, during which they received no medication, aripiprazole 2.5 mg, or aripiprazole 10 mg on the day prior to the laboratory session. During the session, subjects consumed alcohol that was served as three standardized drinks (i.e., a total of 0.8 g/kg for men and 0.7 g/kg for women). Breath alcohol concentration (BrAC), heart rate, blood pressure, static ataxia, and subjective effects were measured regularly throughout the laboratory sessions.

Results:  Alcohol consumption produced physiological and subjective responses that were consistent with the literature on its effects. Pre‐treatment with aripiprazole was generally well tolerated, with tiredness being the most commonly reported adverse event. The medication was associated with modest physiological effects. It also significantly and dose‐dependently increased the sedative effects of alcohol and, to a lesser degree, decreased the euphoric effects of alcohol.

Conclusions:  These findings require replication in a larger subject sample that includes heavy drinkers and in a study that employs a placebo session. Based on its capacity to increase the sedative effects and decrease the euphoric effects of alcohol, aripiprazole could be of value in the treatment of heavy drinking.
Public Administration as Pragmatic, Democratic, and Objective
Authors: Hildebrand David L.
Published: February 2008

In the foregoing essay, Patricia M. Shields argues that public administration and administrators should support a much greater incorporation of classical pragmatism than has been the case to date. This paper supports that conclusion by focusing on classical pragmatism’s central benefit to public administration: its ability to provide the field with a claim to objectivity that it badly needs, but which Shields barely mentions. It shows how objectivity is closely connected to a pragmatic conception of democracy, and how this conception of democracy is diametrically opposed to one built on a fact/value (or administration/politics) dichotomy.
Measuring Street Cleanliness: A Comparison of New York City’s Scorecard and Results from a Citizen Survey
Authors: Van Ryzin Gregg G. , Immerwahr Stephen , Altman Stan
Published: February 2008

Public administrators at the local level often rely on citizen surveys to measure the outcomes or accomplishments of their service delivery efforts. However, many remain skeptical about the value of survey‐based measures of local government performance, in large part because of the low empirical correlation between objective and subjective performance measures reported in the literature. Using data from New York City’s street cleanliness scorecard, a well‐established outcome measure, combined with responses from more than 4,000 respondents to a citizen survey, the authors find a clear and consistent correlation between the scorecard and citizen ratings of street cleanliness in their neighborhoods. Moreover, the street cleanliness scorecard is a much stronger predictor of citizen ratings than demographic factors, trust in government, or contextual effects. These results demonstrate that citizen judgments about government performance can correspond closely with more objectively measured outcomes—and that citizen surveys can provide valid and useful performance measures, at least for some local government services.
Factors Influencing the Use of Performance Data to Improve Municipal Services: Evidence from the North Carolina Benchmarking Project
Authors: Ammons David N. , Rivenbark William C.
Published: February 2008

Many local governments measure and report their performance, but the record of these governments in actually using performance measures to improve services is more modest. The authors of this study examine patterns of performance measurement use among a set of North Carolina cities and conclude that the types of measures on which officials rely, the willingness of officials to embrace comparison, and the degree to which measures are incorporated into key management systems distinguish cities that are more likely to use performance measures for service improvement from those less likely to do so.
Learning under Uncertainty: Networks in Crisis Management
Authors: Moynihan Donald P.
Published: February 2008

This article examines learning in networks dealing with conditions of high uncertainty. The author examines the case of a crisis response network dealing with an exotic animal disease outbreak. The article identifies the basic difficulties of learning under crisis conditions. The network had to learn most of the elements taken for granted in more mature structural forms—the nature of the structural framework in which it was working, how to adapt that framework, the role and actions appropriate for each individual, and how to deal with unanticipated problems. The network pursued this learning in a variety of ways, including virtual learning, learning forums, learning from the past, using information systems and learning from other network members. Most critically, the network used standard operating procedures to provide a form of network memory and a command and control structure to reduce the institutional and strategic uncertainty inherent in networks.
Steering Agencies with Short‐Term Authorizations
Authors: Hall Thad
Published: February 2008

After World War II, the U.S. Congress began a process of engaging in what David Rosenbloom refers to as Congress‐centered public administration. In this article, the author argues that the use of short‐term authorizations by Congress facilitates congressional oversight and co‐management of public programs. Using data from three case studies, the author shows that Congress is able to systematically, on a regularized basis, shape the overall goals, structures, and decision rules that govern agency activities. It can also promote research and analysis that will inform the reauthorization of a program by funding studies and requiring specific reports to be produced. The agencies are, in turn, able to implement the new legislative requirements over a given timeframe—typically four to six years—and do so in an environment that is relatively free from other congressional changes to the legislation underlying the program in question. During this time, the agency and Congress are able to determine what works and what does not work and to formulate changes that should be considered in the next reauthorization legislation.
The restructuring of the Spanish salted fish market
Authors: LINDKVIST KNUT BJØRN , GALLART‐JORNET LORENA , STABELL MAI CECILIE
Published: February 2008

This article discusses how cultural, technological and social factors contribute to the restructuring of the Spanish salted fish market and production systems. The analytical principles used are institutional, evolutionary socio‐economic theories on spatial, technological and social change. A major focus of the analysis is the use of production chain theory to analyze the Spanish salted fish market. The main issue is whether Spain, as a traditional salted fish consumer market, is more influenced by technology and supplier strategies than by cultural aspects and consumer traditions. The strategies of Icelandic salted fish suppliers, better preservation systems and new salting methods seem to have influenced the restructuring of the Spanish salted fish market more than cultural factors. Nevertheless, without the Spanish tradition of salted fish, the new light salted fillets and desalted products most likely would not have been accepted by consumers. In addition, the Icelandic influence proves the strength of national Icelandic production systems.
A Review of the Influence of Grain Boundary Geometry on the Electromagnetic Properties of Polycrystalline YBa2Cu3O7−x Films
Authors: Feldmann D. Matthew , Holesinger Terry G. , Feenstra Ron , Larbalestier David C.
Published: February 2008

Shortly after the discovery of high‐temperature superconducting (HTS) materials in the late 1980s, it was revealed that grain boundaries in these complex oxides are strong barriers to current flow. This fact has remained one of the most significant challenges to a viable HTS conductor, and necessitated the development of technologies capable of producing biaxially textured substrates in long lengths. Multiple studies have reported that the critical current density (Jc) across grain boundaries in the perovskite‐like superconductor YBa2Cu3O7−x (YBCO) falls off exponentially below the intragrain Jc beyond a critical misorientation angle θc of only ≈2°–3°. Here we review our recent work demonstrating that certain grain boundary geometries permit significant enhancements of Jc well beyond the conventional Jc(θ) limit, and also that the grain boundary structure in YBCO films is tied closely to the films' deposition technique. Pulsed laser deposition, a physical vapor deposition technique, results in a columnar grain structure and planar grain boundaries that exhibit the typical Jc(θ) dependence. Ex situ growth processes, where the YBCO film is converted from a previously deposited precursor, can result in laminar grain growth with highly meandered grain boundaries. These latter grain boundary structures are directly correlated to greatly improved Jc values over a wide range of applied magnetic fields. Consequently, very high Jc values are possible in polycrystalline HTS wire even when significant misorientations between grains are present.
Outcome Assessment in Emergency Medicine—A Beginning: Results of the Council of Emergency Medicine Residency Directors (CORD) Emergency Medicine Consensus Workgroup on Outcome Assessment
Authors: Hobgood Cherri , Promes Susan , Wang Ernest , Moriarity Risa , Goyal Deepi G.
Published: February 2008

This article is designed to serve as a guide for emergency medicine (EM) educators seeking to comply with the measurement and reporting requirements for Phase 3 of the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project. A consensus workshop held during the 2006 Council of Emergency Medicine Residency Directors (CORD) “Best Practices” conference identified specific measures for five of the six EM competencies—interpersonal communication skills, patient care, practice‐based learning, professionalism, and systems‐based practice (medical knowledge was excluded). The suggested measures described herein should allow for ease in data collection and applicability to multiple core competencies as program directors incorporate core competency outcome measurement into their EM residency training programs.
Delta2‐Specific Opioid Receptor Agonist and Hibernating Woodchuck Plasma Fraction Provide Ischemic Neuroprotection
Authors: Govindaswami Meera , Brown Stephan A. , Yu Jin , Zhu Hong , Bishop Paul D. , Kindy Mark S. , Oeltgen Peter R.
Published: February 2008

Objectives:  The authors present evidence that the δ opioid receptor agonist Deltorphin‐Dvariant (Delt‐Dvar) and hibernating woodchuck plasma (HWP), but not summer‐active woodchuck plasma (SAWP), can provide significant neuroprotection from focal ischemia in mice by a mechanism that relies in part on reducing nitric oxide (NO) release in ischemic tissue.

Methods:  Cerebral ischemia was produced in wild‐type and NO synthase–deficient (NOS–/–) mice by transient, 1‐hour middle cerebral artery occlusion (MCAO). Behavioral deficits were determined at 22 hours and infarct volume was assessed at 24 hours after MCAO. Mice were treated with saline or Delt‐Dvar at 2.0 and 4.0 mg/kg, or 200 μL of HWP or SAWP. NOS–/– mice were treated with either saline or Delt‐Dvar at 4.0 mg/kg. NO release was determined using an N9 microglial cell line pretreated with δ‐ or μ‐specific opioids and HWP or SAWP prior to activation with lipopolysaccharide and interferon‐γ. Nitrate in the medium was measured as an indicator of NO production.

Results:  Infusion of Delt‐Dvar or HWP (but not SAWP) decreased infarct volume and improved behavioral deficits following 1 hour of MCAO and 24 hours of reperfusion. In NOS–/– mice, endothelial NOS+/+ is required to provide Delt‐Dvar–induced neuroprotection. Delt‐Dvar and HWP dose‐dependently decreased NO release in cell culture, while SAWP and other δ‐ and μ‐specific opioids did not.

Conclusions:  Delt‐Dvar and HWP, but not SAWP, are effective neuroprotectant agents in a mouse model of transient MCAO. In cell culture, the mechanism of this ischemic neuroprotection may rely in part on their ability to block NO release.
Heterozygous disruption of Flk‐1 receptor leads to myocardial ischaemia reperfusion injury in mice: application of affymetrix gene chip analysis
Authors: Thirunavukkarasu M. , Addya S. , Juhasz B. , Pant R. , Zhan L. , Surrey S. , Maulik G. , Menon V. P. , Maulik N.
Published: February 2008

This study addresses an important clinical issue by identifying potential candidates of vascular endothelial growth factor (VEGF) signalling through the Flk‐1 receptor that trigger cardioprotective signals under ischaemic stress. Isolated working mouse hearts of both wild‐type (WT) and Flk‐1+/− were subjected to global ischaemia (I) for 30 min. followed by 2 hrs of reperfusion (R). Flk‐1+/− myocardium displayed almost 50% reduction in Flk‐1 mRNA as examined by quantitative real‐time RT‐PCR at the baseline level. Flk‐1+/− mouse hearts displayed reduction in left ventricular functional recovery throughout reperfusion (dp/dt 605 versus 884), after 2 hrs (P < 0.05). Coronary (1.9 versus 2.4 ml) and aortic flow (AF) (0.16 versus 1.2 ml) were reduced in Flk‐1+/− after 2 hrs of reperfusion. In addition, increased infarct size (38.4%versus 28.41%, P < 0.05) and apoptotic cardiomyocytes (495 versus 213) were observed in Flk‐1+/− knockout (KO) mice. We also examined whether ischaemic preconditioning (PC), a novel method to induce cardioprotection against ischaemia reperfusion injury, through stimulating the VEGF signalling pathway might function in Flk‐1+/− mice. We found that knocking down Flk‐1 resulted in significant reduction in the cardioprotective effect by PC compared to WT. Affymetrix gene chip analysis demonstrated down‐regulation of important genes after IR and preconditioning followed by ischaemia reperfusion in Flk‐1+/− mice compared to WT. To get insight into the underlying molecular pathways involved in ischaemic PC, we determined the distinct and overlapping biological processes using Ingenuity pathway analysis tool. Independent evidence at the mRNA level supporting the Affymetrix results were validated using real‐time RT‐PCR for selected down‐regulated genes, which are thought to play important roles in cardioprotection after ischaemic insult. In summary, our data indicated for the first time that ischaemic PC modifies genomic responses in heterozygous VEGFR‐2/Flk‐1 KO mice and abolishes its cardioprotective effect on ischaemic myocardium.
New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma
Authors: Wedel S. A. , Sparatore A. , Soldato P. D. , Al‐Batran S.‐E. , Atmaca A. , Juengel E. , Hudak L. , Jonas D. , Blaheta R. A.
Published: February 2008

The anti‐epileptic drug valproic acid is also under trial as an anti‐cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti‐neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA‐derivatives (ACS2, ACS33) on pre‐clinical prostate cancer models. PC3 and DU‐145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up‐regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU‐145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti‐tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer.
The ubiquitin‐proteasome system in Alzheimer's disease
Authors: Oddo Salvatore
Published: February 2008

Introduction

Biology of the UPS

The involvement of the UPS in AD pathogenesis

The UPS as a link between Aβ and tau interaction

Conclusions

Accumulation of proteins is a recurring event in many neurodegenerative diseases, including Alzheimer's disease (AD).Evidence has suggested that protein accumulation may result from a dysfunction in the ubiquitin proteasome system (UPS). Indeed, there is clear genetic and biochemical evidence of an involvement of the ubiquitin proteasome system in AD. This review summarizes the data supporting an involvement of the UPS in the pathogenesis of AD, focusing on the data showing the relationship between Aβ and tau, the two hallmark lesions of AD, and the UPS.
Delayed development of interstitial cells of Cajal in the ileum of a human case of gastroschisis
Authors: Midrio Paola , Vannucchi Maria Giuliana , Pieri Laura , Alaggio Rita , Faussone‐Pellegrini Maria Simonetta
Published: February 2008

The Interstitial Cells of Cajal (ICC) are responsible for rhythmic electrical activity. A paralytic ileus is present in gastroschisis (GS), a malformation due to a defective closure of the abdominal wall through which part of the intestine herniates during pregnancy. In experimental GS, ICC morphological immaturity was shown in the rat foetus at‐term but it could not be demonstrated whether differentiation is accomplished post‐natally. For this purpose we morphologically investigated ICC, as well as enteric neurons and smooth muscle cells, in a case of human GS at birth and 1 month later when peristaltic activity had initiated. A 36 weeks gestation female was born by c/section with prenatal diagnosis of GS and possible volvulus of the herniated intestine. At birth, the necrotic intestine was resected and both ileostomy and colostomy were performed. The intestine continuity was restored after 4 weeks. Intestinal specimens, taken during both operations at the level of the proximal stoma, were immunostained with c‐kit, neuron‐specific‐enolase and α‐smooth‐muscle‐actin antibodies and some processed for electron microscopy. ICC were present at the myenteric plexus only. At birth, these cells were rare and ultrastructurally immature; 1 month later, when partial enteral feeding was tolerated, they formed rows or groups and many of them were ultrastructurally differentiated. Neurons and smooth muscle cells, immature at birth, had developed after 1 month. Therefore, ICC differentiation, as well as that of neurons and smooth muscle cells, is delayed at birth and this might explain the paralytic ileus in GS. One month later, differentiation quickly proceeded at all cellular levels paralleling the increasing tolerance of enteral nutrition.
Biomarker candidates for cardiovascular disease and bone metabolism disorders in chronic kidney disease: a systems biology perspective
Authors: Perco Paul , Wilflingseder Julia , Bernthaler Andreas , Wiesinger Martin , Rudnicki Michael , Wimmer Barbara , Mayer Bernd , Oberbauer Rainer
Published: February 2008

Introduction

Kidney disease and cardiovascular risk

Kidney disease and bone metabolism disorders

Data integration and systems biology analyses

Conclusion and outlook

Patients with chronic kidney disease (CKD) show a panel of partially de‐regulated serum markers indicative for bone metabolism disorders and cardiovascular diseases (CVDs). This review provides an overview of currently reported biomarker candidates at the interface of kidney disease, bone metabolism disorders and CVDs, and gives details on their functional interplay on the level of protein–protein interaction data. We retrieved 13 publications from 1999 to 2006 reporting 31 genes associated with CVDs, and 46 genes associated with bone metabolism disorders in patients with CKD. We identified these genes to be functionally involved in signal transduction processes, cell communication, immunity and defence, as well as skeletal development. On the basis of the given set of 77 genes further 276 interacting proteins were identified using reference data on known protein interactions. Their functional interplay was estimated by linking properties reflected by gene expression data characterizing CKD, gene ontology terms as provided by the gene ontology consortium and transcription factor binding site profiles. Highly connected sub‐networks of proteins associated with CKD, CVDs or bone metabolism disorders were detected involving proteins like collagens (COL1A1, COL1A2), fibronectin, transforming growth factor‐β1, or components of fibrinogen (FG‐α, FG‐β, FG‐γ). A systems biology approach provides a methodological framework for linking singular biomarker candidates towards deriving functional dependencies among clinically interlinked diseases.
Apolipoprotein E genotype and risk for development of cataract and age‐related macular degeneration
Authors: Utheim Øygunn A. , Ritland Jon Ståle , Utheim Tor P. , Espeseth Thomas , Lydersen Stian , Rootwelt Helge , Semb Svein Ove , Elsås Tor
Published: February 2008

Purpose:  To study whether apolipoprotein E (APOE) genotypes are associated with risk for developing cataract and age‐related macular degeneration (AMD).

Methods:  A sample of 88 healthy adults (50–75 years) genotyped for polymorphisms of APOE underwent an eye examination which included visual acuity (VA) testing, slit‐lamp cataract evaluation, optical coherence tomography (OCT) and fundus photography, the last of which was analysed and graded for macular pathology at the Reading Centre, Moorfields Eye Hospital, London. Two‐by‐two cross tables were analysed using the Fisher–Boschloo unconditional full multinomial test. Two‐sample t‐tests were used for comparing means of scale variables.

Results:  Thirty‐two participants were diagnosed with cataract or had undergone cataract surgery in one or both eyes, and 56 participants demonstrated no signs of cataract. We found that APOE4 carriers were less likely to have cataract than non‐APOE4 carriers (p = 0.039). No correlation between APOE genotypes and morphologic changes in the macular region was revealed. However, APOE3 carriers disclosed significantly higher average macular thickness in both eyes than non‐APOE3 carriers (p = 0.012), and APOE3 carriers also had significantly better VA than non‐APOE3 carriers (p = 0.041).

Conclusions:  We found no association between AMD and APOE polymorphism in a population of 96 individuals aged 50−75 years. A weak negative association between APOE4 and cataract was uncovered in the same population. Apolipoprotein E3 may be a protective factor against the loss of nerve fibres in the macular region.
Ultrasound biomicroscopy of zonular anatomy in clinically unilateral exfoliation syndrome
Authors: Sbeity Zaher , Dorairaj Syril K. , Reddy Swathi , Tello Celso , Liebmann Jeffrey M. , Ritch Robert
Published: February 2008

Purpose:  To evaluate the ability of ultrasound biomicroscopy (UBM) to detect abnormalities in the zonular apparatus in unaffected eyes of patients with clinically unilateral exfoliation syndrome (XFS) using a standardized grading system.

Methods:  The affected and unaffected eyes of 17 patients with clinically unilateral XFS and 17 eyes of 17 control subjects underwent UBM. Radial sections detailing the lens and zonules at 12:00, 1:30, 3:00, 4:30, 6:00, 7:30, 9:00 and 10:30 clock hours were obtained. The images were graded by a masked, experienced UBM observer using a standardized scoring system based on the zonular appearance (0, none; 1 and 2, uneven or disrupted zonules with or without patchy deposits; 3, diffuse granulation, thick zonules or both; 4, total zonular disruption). Affected meridians were compared by the Friedman test, while distributions of unaffected and affected eyes were compared using the Student t‐test.

Results:  In the control group, 15/17 eyes showed normal zonules; the remaining two eyes showed grade 1 changes in some meridians. The mean grade score was 0.33 [standard deviation (SD) 0.84]. Eyes with XFS had a higher score than control eyes, with a mean score of 14.35 (SD 7.14, P < 0.001, Student t‐test). In clinically unaffected fellow eyes, the mean score was 10.53 (SD 7.44), and was less than that of XFS eyes (P = 0.008, Student t‐test). Twelve XFS eyes (71%) and six unaffected fellow eyes (35%) had grade 3 or 4 in at least one meridian (P = 0.07, Friedman test).

Conclusion:  Bilateral zonular involvement is present in subjects with clinically unilateral XFS. These zonular changes may be extensive in fellow eyes without clinically evident exfoliation material. UBM assessment of zonular status in fellow eyes prior to cataract extraction may aid in surgical planning.
The dihydropyridine isradipine inhibits the murine but not the bovine a‐wave response of the electroretinogram
Authors: Banat Mohammed , Lüke Matthias , Siapich Siarhei A. , Hescheler Jürgen , Weiergräber Marco , Schneider Toni
Published: February 2008

Purpose:  In order to record light‐evoked responses from photoreceptor cells and the higher neuronal retinal network, the isolated vertebrate retina represents a sensitive tool for basic research of retinal function and for testing the toxicity of ocular therapeutics. In the past, this in vitro technique was optimized for frog and bovine retina; it should be transferred now to the isolated murine retina because the model could allow for functional testing of genes involved in retinal signalling using wild‐type and gene‐inactivated mice. Thus, alterations in the electroretinogram (ERG) may reveal differences in retinal information processing because of the inactivation of a specific gene.

Methods:   We used a superfused vertebrate retina assay to test bovine and murine retina.

Results:  In order to evaluate the sensitivity of the ERG recording technique from the isolated murine retina, we first determined the light intensity response and the stability of the a‐wave amplitude during ERG recording, which did not differ between the species. However, testing the dihydropyridine sensitivity of the a‐wave, we found that the murine a‐wave was highly sensitive towards racemic isradipine (8–25 nM) but the bovine retina a‐wave was not. A similar species‐dependent difference was observed for mibefradil (10 μM).

Conclusion:  Murine and bovine retina differ with respect to transretinal signalling. At the level of photoreceptor cells, the ERG/a‐wave is modulated by isradipine‐sensitive voltage‐gated Ca2+ channels, which trigger feedback signalling to photoreceptors.
New insights into evolution of crustacean hyperglycaemic hormone in decapods – first characterization in Anomura
Authors: Montagné Nicolas , Soyez Daniel , Gallois Dominique , Ollivaux Céline , Toullec Jean‐Yves
Published: February 2008

The neuropeptides of the crustacean hyperglycaemic hormone (CHH) family are encoded by a multigene family and are involved in a wide spectrum of essential functions. In order to characterize CHH family peptides in one of the last groups of decapods not yet investigated, CHH was studied in two anomurans: the hermit crab Pagurus bernhardus and the squat lobster Galathea strigosa. Using RT‐PCR and 3′ and 5′ RACE methods, a preproCHH cDNA was cloned from the major neuroendocrine organs (X‐organs) of these two species. Hormone precursors deduced from these cDNAs in P. bernhardus and G. strigosa are composed of signal peptides of 29 and 31 amino acids, respectively, and CHH precursor‐related peptides (CPRPs) of 50 and 40 amino acids, respectively, followed by a mature hormone of 72 amino acids. The presence of these predicted CHHs and their related CPRPs was confirmed by performing MALDI‐TOF mass spectrometry on sinus glands, the main neurohaemal organs of decapods. These analyses also suggest the presence, in sinus glands of both species, of a peptide related to the moult‐inhibiting hormone (MIH), another member of the CHH family. Accordingly, immunostaining of the X‐organ/sinus gland complex of P. bernhardus with heterologous anti‐CHH and anti‐MIH sera showed the presence of distinct cells producing CHH and MIH‐like proteins. A phylogenetic analysis of CHHs, including anomuran sequences, based on maximum‐likelihood methods, was performed. The phylogenetic position of this taxon, as a sister group to Brachyura, is in agreement with previously reported results, and confirms the utility of CHH as a molecular model for understanding inter‐taxa relationships. Finally, the paraphyly of penaeid CHHs and the structural diversity of CPRPs are discussed.
The effect of small molecules in modulating the chaperone activity of αB‐crystallin against ordered and disordered protein aggregation
Authors: Ecroyd Heath , Carver John A.
Published: February 2008

Protein aggregation can proceed via disordered or ordered mechanisms, with the latter being associated with amyloid fibril formation, which has been linked to a number of debilitating conditions including Alzheimer’s, Parkinson’s and Creutzfeldt‐Jakob diseases. Small heat‐shock proteins (sHsps), such as αB‐crystallin, act as chaperones to prevent protein aggregation and are thought to play a key role in the prevention of protein‐misfolding diseases. In this study, we have explored the potential for small molecules such as arginine and guanidine to affect the chaperone activity of αB‐crystallin against disordered (amorphous) and ordered (amyloid fibril) forms of protein aggregation. The effect of these additives is highly dependent upon the target protein undergoing aggregation. Importantly, our results show that the chaperone action of αB‐crystallin against aggregation of the disease‐related amyloid fibril forming protein α‐synucleinA53T is enhanced in the presence of arginine and similar positively charged compounds (such as lysine and guanidine). Thus, our results suggest that target protein identity plays a critical role in governing the effect of small molecules on the chaperone action of sHsps. Significantly, small molecules that regulate the activity of sHsps may provide a mechanism to protect cells from the toxic protein aggregation that is associated with some protein‐misfolding diseases.
The luminosity–halo mass relation for brightest cluster galaxies
Authors: Brough S. , Couch W. J. , Collins C. A. , Jarrett T. , Burke D. J. , Mann R. G.
Published: February 2008

We examine the central galaxy luminosity–host halo mass relation for 54 brightest group galaxies (BGGs) and 92 brightest cluster galaxies (BCGs) at z < 0.1 and present the first measurement of this relation for a sample of known BCGs at . At z < 0.1 we find LK∝M0.24±0.08200 for the BCGs and the early-type BGGs in groups with extended X-ray emission and LK∝M0.11±0.10200 for the BCGs alone. At 0.1 < z < 0.8 we find LK∝M0.28±0.11200. We conclude that there is no evidence for evolution in this relationship between z < 0.1 and z < 0.8: BCG growth appears to still be limited by the time-scale for dynamical friction at these earlier times, not proceeding according to the predictions of present semi-analytic models.
Accretion rates and beaming in ultraluminous X-ray sources
Authors: King A. R.
Published: February 2008

I show that extreme beaming factors b are not needed to explain ultraluminous X-ray sources (ULXs) as stellar-mass binaries. For neutron-star accretors, one typically requires b∼ 0.13, and for black holes almost no beaming (b∼ 0.8). The main reason for the high apparent luminosity is the logarithmic increase in the limiting luminosity for super-Eddington accretion. The required accretion rates are explicable in terms of thermal-time-scale mass transfer from donor stars of mass 6–10 M⊙, or possibly transient outbursts. Beaming factors ≲0.1 would be needed to explain luminosities significantly above 1040L40 erg s−1, but these requirements are relaxed somewhat if the accreting matter has low hydrogen content.