bluuebunny/crossref_metadata_2025 huggingface dataset:
Zyklophin, a systemically active selective kappa opioid receptor peptide antagonist with short duration of action
Authors: Aldrich Jane V. , Patkar Kshitij A. , McLaughlin Jay P.
Published: October 2009

The cyclic peptide zyklophin {[N-benzylTyr1,cyclo(D-Asp5,Dap8)-dynorphin A-(1–11)NH2, Patkar KA, et al. (2005)J Med Chem48: 4500–4503} is a selective peptide kappa opioid receptor (KOR) antagonist that shows activity following systemic administration. Systemic (1–3 mg/kg s.c.) as well as central (0.3–3 nmol intracerebroventricular, i.c.v.) administration of this peptide dose-dependently antagonizes the antinociception induced by the selective KOR agonist U50,488 in C57BL/6J mice tested in the 55 °C warm water tail withdrawal assay. Zyklophin administration had no effect on morphine- or SNC-80-mediated antinociception, suggesting that zyklophin selectively antagonizes KOR in vivo. Additionally, the antagonism of antinociception induced by centrally (i.c.v.) administered U50,488 following peripheral administration of zyklophin strongly suggests that the peptide crosses the blood-brain barrier to antagonize KOR in the CNS. Most importantly, the antagonist activity of zyklophin (3 mg/kg s.c.) lasts less than 12 h, which contrasts sharply with the exceptionally long duration of antagonism reported for the established small-molecule selective KOR antagonists such as nor-binaltorphimine (nor-BNI) that last weeks after a single administration. Systemically administered zyklophin (3 mg/kg s.c.) also prevented stress-induced reinstatement of cocaine-seeking behavior in a conditioned place preference assay. In conclusion, the peptide zyklophin is a KOR-selective antagonist that exhibits the desired shorter duration of action, and represents a significant advance in the development of KOR-selective antagonists.
Adenoviral transfer of HIF-1α enhances vascular responses to critical limb ischemia in diabetic mice
Authors: Sarkar Kakali , Fox-Talbot Karen , Steenbergen Charles , Bosch-Marcé Marta , Semenza Gregg L.
Published: October 2009

Diabetes is a major risk factor for ischemic disease. Treatment options for diabetic patients with peripheral arterial disease when revascularization is not possible are limited, resulting in a high incidence of limb amputation. We evaluated the therapeutic potential of AdCA5, an adenovirus encoding a constitutively active form of HIF-1α, in a diabetic model of critical limb ischemia. Diabetic
db
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and nondiabetic
db
/+ mice were subjected to unilateral femoral artery ligation. Limb perfusion, tissue viability, and motor function were more severely impaired in
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db
mice. Intramuscular injection of AdCA5 into the ischemic limb of
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db
mice increased the recovery of limb perfusion and function, reduced tissue necrosis, rescued the diabetes-associated impairment of circulating angiogenic cells, enhanced endothelial nitric oxide synthase activation, and increased vessel density and luminal area in the ischemic limb.
A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity
Authors: Hsu Lih-Yun , Tan Ying Xim , Xiao Zheng , Malissen Marie , Weiss Arthur
Published: October 2009

ZAP-70 is critical for T cell receptor (TCR) signaling. Tyrosine to phenylalanine mutations of Y315 and Y319 in ZAP-70 suggest these residues function to recruit downstream effector molecules, but mutagenesis and crystallization studies reveal that these residues also play an important role in autoinhibition ZAP-70. To address the importance of the scaffolding function, we generated a zap70 mutant mouse (YYAA mouse) with Y315 and Y319 both mutated to alanines. These YYAA mice reveal that the scaffolding function is important for normal development and function. Moreover, the YYAA mice have many similarities to a previously identified ZAP-70 mutant mouse, SKG, which harbors a distinct hypomorphic mutation. Both YYAA and SKG mice have impaired T cell development and hyporesponsiveness to TCR stimulation, markedly reduced numbers of thymic T regulatory cells and defective positive and negative selection. YYAA mice, like SKG mice, develop rheumatoid factor antibodies, but fail to develop autoimmune arthritis. Signaling differences that result from ZAP-70 mutations appear to skew the TCR repertoire in ways that differentially influence propensity to autoimmunity versus autoimmune disease susceptibility. By uncoupling the relative contribution from T regulatory cells and TCR repertoire during thymic selection, our data help to identify events that may be important, but alone are insufficient, for the development of autoimmune disease.
Runx proteins regulate Foxp3 expression
Authors: Bruno Ludovica , Mazzarella Luca , Hoogenkamp Maarten , Hertweck Arnulf , Cobb Bradley S. , Sauer Stephan , Hadjur Suzana , Leleu Marion , Naoe Yoshinori , Telfer Janice C. , Bonifer Constanze , Taniuchi Ichiro , Fisher Amanda G. , Merkenschlager Matthias
Published: October 2009

Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor β to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes.
Masking MALT1: the paracaspase's potential for cancer therapy
Authors: Vucic Domagoj , Dixit Vishva M.
Published: October 2009

A key feature of aggressive B cell lymphomas is constitutive NF-κB activation, which requires signals from the CARD11–BCL-10–MALT1 (CMB) complex. The unique enzymatic activity of MALT1 degrades one of its binding partners, BCL-10, as well as the NF-κB inhibitor A20. New data shows that targeting MALT1 protease activity may be a promising therapeutic strategy for treating aggressive B cell lymphomas.
Ethanol Production from Modified and Conventional Dry‐Grind Processes Using Different Corn Types
Authors: Khullar Esha , Sall Erik D. , Rausch Kent D. , Tumbleson M. E. , Singh Vijay
Published: October 2009

Different corn types were used to compare ethanol production from the conventional dry‐grind process to wet or dry fractionation processes. High oil, dent corn with high starch extractability, dent corn with low starch extractability and waxy corn were selected. In the conventional process, corn was ground using a hammer mill; water was added to produce slurry which was fermented. In the wet fractionation process, corn was soaked in water; germ and pericarp fiber were removed before fermentation. In the dry fractionation process, corn was tempered, degerminated, and passed through a roller mill. Germ and pericarp fiber were separated from the endosperm. Due to removal of germ and pericarp fiber in the fractionation methods, more corn was used in the wet (10%) and dry (15%) fractionation processes than in the conventional process. Water was added to endosperm and the resulting slurry was fermented. Oil, protein, and residual starch in germ were analyzed. Pericarp fiber was analyzed for residual starch and neutral detergent fiber (NDF) content. Analysis of variance and Fisher's least significant difference test were used to compare means of final ethanol concentrations as well as germ and pericarp fiber yields. The wet fractionation process had the highest final ethanol concentrations (15.7% v/v) compared with dry fractionation (15.0% v/v) and conventional process (14.1% v/v). Higher ethanol concentrations were observed in fractionation processes compared to the conventional process due to higher fermentable substrate per batch available as a result of germ and pericarp fiber removal. Germ and pericarp yields were 7.47 and 6.03% for the wet fractionation process and 7.19 and 6.22% for the dry fractionation process, respectively. Germ obtained from the wet fractionation process had higher oil content (34% db) compared with the dry fractionation method (11% db). Residual starch content in the germ fraction was 16% for wet fractionation and 44% for dry fractionation. Residual starch in the pericarp fiber fraction was lower for the wet fractionation process (19.9%) compared with dry fractionation (23.7%).
Effect of the Molecular Weight Distribution of Glutenin Protein from an Extra‐Strong Wheat Flour on Rheological and Breadmaking Properties Through Reconstitution Studies
Authors: Wang Wei , Khan Khalil
Published: October 2009

Ten glutenin fractions were separated by sequential extraction of wheat gluten protein with dilute hydrochloric acid from defatted glutenin‐rich wheat gluten of the Canadian hard red spring wheat (HRSW) cultivar Glenlea. The molecular weight distribution (MWD) of 10 different soluble glutenin fractions was examined by multistacking SDS‐PAGE under nonreduced conditions. Also, the subunit composition of the different glutenin fractions was determined by SDS‐PAGE under reduced conditions. The MWD of the fractions (especially HMW glutenins) varied from fraction to fraction. From early to later fractions, the MWD shifted from low to high. The early extracted fractions contained more LMW glutenin subunits (LMW‐GS) and less HMW glutenin subunits (HMW‐GS). The later extracted fractions and the residue fraction contained much more HMW‐GS (2*, 5, and 7 subunits) than the early extracted fractions. The trend in the amounts of 2*, 5, and 7 subunits in each fraction from low to high matched the extraction solvent sequence containing from lower to higher levels of HCl. The influence of glutenin protein fractions from the extra‐strong mixing cultivar, Glenlea, on the breadmaking quality of the weak HRSW, McVey, was assessed by enriching (by 1%) the McVey base flour with isolated glutenin protein fractions from Glenlea. The mixograph peak development times and loaf volumes of enriched flour were measured in an optimized baking test. The results indicated that the higher content in Glenlea glutenin of HMW‐GS with higher molecular weight, such as 2*, 5, and 7, seem to be the critical factor responsible for the strong mixing properties of Glenlea. Our results confirmed that subunit 7 occurred in the highest quantity of all the HMW‐GS. Therefore, it seems that the greater the content of larger molecular weight glutenin subunits, the larger the glutenin polymers and the stronger the flour.
Infrequent hypermethylation of the PTEN gene in Korean non‐small‐cell lung cancers
Authors: Kim Dong Sun , Lee Su Man , Yoon Ghil Suk , Choi Jin Eun , Park Jae Yong
Published: October 2009

CpG islands (CGIs) hypermethylation is implicated in the pathogenesis of many cancers, including lung cancer. The phosphate and tension homolog (PTEN) is a tumor suppressor that controls a variety of biological processes including cell proliferation, growth, migration, and death. The defects in PTEN regulation have a profound impact on carcinogenesis. Herein, we have examined the methylation status of the human PTEN gene in 137 primary non‐small‐cell lung cancers (NSCLCs) by using a methylation‐specific PCR and correlated the results with clinicopathological features. Promoter methylation of the PTEN gene was observed in 5.1%, 2.9%, and 0.0% of three different CpG regions, which were localized at −1460 to −1263, −984 to −848, and −300 to −128 nucleotides upstream of the translation start site, respectively. Reverse transcription‐PCR and immunohistochemical analysis showed the methylation of the CGI region at −984 to −848 correlated more accurately with PTEN expression. In addition, no significant correlation was found between PTEN methylation and clinicopathological factors, including the survival rates. These findings suggest that promoter methylation is not an important mechanism for PTEN deregulation in NSCLCs from Koreans. (Cancer Sci 2010; 101: 568–572)
Plant community distribution and variation along the Awash river corridor in the main Ethiopian rift
Authors: Tikssa Mitiku , Bekele Tamrat , Kelbessa Ensermu
Published: October 2009

The vegetation along the Awash River (1200‐km long) in the main Ethiopian Rift, and its relationship with environmental factors was studied. Seven plant communities were described from the study area: (1) Acacia nilotica subsp. leiocarpa. – Carissa edulis type; (2) Acacia robusta subsp. usambarensis – Acokanthera schimperi type; (3) Celtis africana – Mimusops laurifolia type; (4) Acacia senegal – Acacia mellifera – Dobera glabra type; (5) Acacia nilotica subsp. indica – Ficus capreaefolia type; (6) Lannea schimperi–Glycine wightii type; and (7) Tamarix nilotica – Acacia hocki community type. It has been shown that the plant communities along the river follow an altitudinal gradient. The vegetation of the Awash River is mainly the result of the interactions between edaphic factors, the hydrology, altitude, slope and climate.
The influence of geographic and morphometric factors on the distribution of water bird species in small high altitude tropical man made reservoirs, Central Rift Valley, Kenya
Authors: Mwaura Francis
Published: October 2009

Variability in waterfowl characteristics among eight high altitude (2040–2640 m) small shallow (0.065–0.249 km2; 0.9–3.1 m) reservoirs in the escarpment zone along the central rift valley in Kenya between Naivasha and Nakuru towns were studied between 1998 and 2000. The aim of the study was to establish whether the geographic status of small reservoirs in terms of altitude and surface gradient can affect the characteristics of their birdlife in terms of bird counts and species numbers. The study also aimed at establishing whether reservoir bird counts and species number can be predicted by reservoir morphometric factors especially water depth, surface area, length of shoreline and area‐shoreline ratio. The other aim was to determine the influence of local environment especially distance from the nearest natural lakes, and house density on the birdlife. The findings showed that geographic location of the reservoirs in terms of altitude and landscape had a strong influence on birdlife whereby reservoirs in higher altitude and flat plateau landscape were found to support higher bird species and counts. Larger and deeper reservoirs were richer in water bird species but small and shallow reservoirs were superior in terms of both bird species and counts. Reservoirs with more coarse, irregular and highly erratic shorelines had higher species number than those with smooth and well‐rounded shorelines. The reservoir birdlife was found to be influenced by the number of farm houses near the waterbodies and also the distance from the nearby rift valley lakes. The results showed that both geographic and morphometric considerations are necessary in the establishment of new reservoirs especially for utilization in birdlife conservation and ecotourism.
‘I made some mistakes . . . but I love them dearly’ the views of parents of children in informal kinship care
Authors: Gleeson James P. , Seryak Claire M.
Published: October 2009

In‐depth semi‐structured interviews with 30 parents of children living with relatives in informal kinship care arrangements revealed the parents' views of the reasons for the informal kinship care arrangements, quality of their relationships with the children and their caregivers, their current and future roles in their children's lives, feelings experienced when with and away from the children, positive and negative aspects of kinship care, future goals and dreams for their children, and their assessments of their own strengths and challenges. Results of these interviews suggest several implications for social work practice and research.
Historical biogeography of an Indo‐Pacific passerine bird family (Pachycephalidae): different colonization patterns in the Indonesian and Melanesian archipelagos
Authors: Jønsson Knud A. , Bowie Rauri C. K. , Moyle Robert G. , Christidis Les , Norman Janette A. , Benz Brett W. , Fjeldså Jon
Published: October 2009

Aim  We use molecular‐based phylogenetic methods and ancestral area reconstructions to examine the systematic relationships and biogeographical history of the Indo‐Pacific passerine bird family Pachycephalidae (whistlers). Analysed within an explicit spatiotemporal framework, we elucidate distinct patterns of diversification across the Melanesian and Indonesian archipelagos and explore whether these results may be explained by regional palaeogeological events. We further assess the significance of upstream colonization and its role in species accumulation within the region.

Location  The Indo‐Pacific region, with an emphasis on the archipelagos on either side of the Australo‐Papuan continent.

Methods  We used three nuclear and two mitochondrial markers to construct a molecular phylogenetic hypothesis of the Pachycephalidae by analysing 35 of the 49 species known to belong to the family. The programs diva and MrBayes were used to reconstruct ancestral area relationships and to examine biogeographical relationships across the family, and beast was implemented to assess the timing of dispersal events.

Results  We constructed a molecular phylogenetic hypothesis for the Pachycephalidae and estimated divergence times and ancestral area relationships. Different colonization patterns are apparent for the Pachycephalidae in the Indonesian and the Melanesian archipelagos. The Indonesian archipelago was colonized numerous times, whereas one or two colonizations of the Melanesian archipelagos account for the entire diversity of that region. After initial colonization of the Melanesian archipelagos some whistler species recolonized Australia and may have commenced a second round of colonization into Melanesia.

Main conclusions  The contrasting dispersal patterns of whistlers in archipelagos on either side of the Australo‐Papuan continent are congruent with the arrangement and history of islands in each of the regions and demonstrate that knowledge of palaeogeography is important for an understanding of evolutionary patterns in archipelagos. We also highlight that recolonization of continents from islands may be more common than has previously been assumed.
Sex Differences in the Expression of Sex Steroid Receptor mRNA in the Quail Brain
Authors: Voigt C. , Ball G. F. , Balthazart J.
Published: October 2009

In Japanese quail, males will readily exhibit the full sequence of male‐typical sexual behaviors but females never show this response, even after ovariectomy and treatment with male‐typical concentrations of exogenous testosterone. Testosterone aromatisation plays a key‐limiting role in the activation of this behavior but the higher aromatase activity in the brain of males compared to females is not sufficient to explain the behavioural sex difference. The cellular and molecular bases of this prominent sex difference in the functional consequences of testosterone have not been identified so far. We hypothesised that the differential expression of sex steroid receptors in specific brain areas could mediate this behavioural sex difference. Therefore, using radioactive in situ hybridisation histochemistry, we quantified the expression of the mRNA coding for the androgen receptor (AR) and the oestrogen receptors (ER) of the α and β subtypes. All three receptors were expressed in an anatomically discrete manner in various nuclei of the hypothalamus and limbic system and, at usually lower densities, in a few other brain areas. In both sexes, the intensity of the hybridisation signal for all steroid receptors was highest in the medial preoptic nucleus (POM), a major site of testosterone action that is related to the activation of male sexual behaviour. Although no sex difference in the optical density of the AR hybridisation signal could be found in POM, the area covered by AR mRNA was significantly larger in males than in females, indicating a higher overall degree of AR expression in this region in males. By contrast, females tended to have significantly higher levels of AR expression than males in the lateral septum. ERα was more densely expressed in females than males throughout the medial preoptic and hypothalamic areas (including the POM and the medio‐basal hypothalamus), an area implicated in the control of female receptivity) and in the mesencephalic nucleus intercollicularis. ERβ was more densely expressed in the medio‐basal hypothalamus of females but a difference in the reverse direction (males > females) was observed in the nucleus taeniae of the amygdala. These data suggest that a differential expression of steroid receptors in specific brain areas could mediate at least certain aspects of the sex differences in behavioural responses to testosterone, although they do not appear to be sufficient to explain the complete lack of activation by testosterone of male‐typical copulatory behaviour in females.
Ascitic fluid infection in patients with hepatitis B virus‐related liver cirrhosis: Culture‐negative neutrocytic ascites versus spontaneous bacterial peritonitis
Authors: Kim Seung Up , Kim Do Young , Lee Chun Kyon , Park Jun Yong , Kim Sun Hye , Kim Hee Man , Choi Eun Hee , Kim Sinyoung , Han Kwang‐Hyub , Chon Chae Yoon , Ahn Sang Hoon
Published: October 2009

Background and Aim:  Ascitic fluid infection (AFI) consists of culture‐negative neutrocytic ascites (CNNA) and spontaneous bacterial peritonitis (SBP). The present study compared the clinical characteristics and prognosis of CNNA and SBP in hepatitis B virus (HBV)‐related cirrhotic patients.

Methods:  We analyzed 130 consecutive patients hospitalized due to the first episode of AFI between January 1998 and December 2007.

Results:  The mean age of the patients was 52.3 years (88 men, 42 women). Ninety‐three patients (71.5%) had CNNA and 37 patients (28.5%) had SBP; 117 patients (90.0%) died after a median survival period of 6.4 months. Patients with CNNA and SBP survived for a median period of 6.9 months and 5.4 months, respectively (P = 0.417). Patients with SBP showed higher in‐hospital mortality than those with CNNA (16.2 vs 4.3%; P = 0.031). Binary logistic regression analysis showed that culture positivity of ascitic fluid (CNNA vs SBP) was the only independent predictor of in‐hospital mortality (P = 0.042). In a Cox regression model for the 120 patients (92.3%) who survived the first episode of AFI, only the Child–Pugh score remained significant for survival (P = 0.007), whereas no association was observed for culture positivity of ascitic fluid (CNNA vs SBP) during the first episode of AFI (P = 0.752).

Conclusions:  Although in‐hospital mortality was higher in patients with SBP than CNNA, the clinical course of the two groups was similar after the first episode of AFI. Thus, liver transplantation should be considered, irrespective of culture positivity of ascitic fluid.
Rapid national survey of renal stones in New Zealand infants
Authors: Dickson Nigel , Kara Tonya , Tuohy Pat
Published: October 2009

Aim:  The aim of this study was to determine if there have been recent serious renal problems because of melamine among infants in New Zealand.

Methods:  New Zealand paediatricians were surveyed in October 2008 using the New Zealand Paediatric Surveillance Unit network.

Results:  Two cases of renal stones and none of unexplained renal failure in the previous 12 months were reported. Both cases of renal stones had an identifiable cause, and neither had features of melamine‐related stones.

Conclusion:  This survey confirmed the expectation that this was not a discernible problem of recent serious melamine‐associated renal damage in New Zealand. The method did however prove to be an effective way of undertaking a rapid determination of a possible recent serious health problem among children.
Brittle fracture evaluation of a fine grain cement mortar in combined tensile‐shear deformation
Authors: ALIHA M. R. M. , AYATOLLAHI M. R.
Published: October 2009

Different laboratory experiments are usually conducted to characterize the fracture behaviour and integrity properties of newly developed structural materials. However, the reported fracture tests data for an improved high strength cement mortar (HSCM) under combined tension‐shear loading are not in agreement with theoretical predictions obtained from well‐known fracture criteria. It is shown in this paper that the significant difference existing between the experimental and theoretical results is due to ignoring the effect of T‐stress on the processes of crack growth in the HSCM test specimens. A modified fracture model is then used to show that the theoretical predictions can be corroborated by the experimental results when the effect of T‐stress is taken into account.
A critical review of ontogenetic development in Terebellidae (Polychaeta)
Authors: Garraffoni André R. S. , Lana Paulo C.
Published: October 2009

Garraffoni, A.R.S. and Lana, P.C. 2009. A critical review of ontogenetic development in Terebellidae (Polychaeta). —Acta Zoologica (Stockholm) 91: 390–401.

This study reviews the ontogenetic variability of the head, the first segments and the uncini in Terebellidae, based on primary literature and development series of four terebellid species. We test hypotheses on character homologies and indicate informative characters for future phylogenetic analyses. The prostomium, identified as the region above the prototroch band of the larva, in addition to being the region of origin of the buccal tentacles, contains a series of nerves originating from the cerebrum. The peristomium, which contains the mouth, is innervated by the stomogastric nerve and consists of upper and lower lips and an internal pharynx. The loss of the first notochaetae and neurochaetae in the course of development is a recurrent pattern in terebellids. The claviform chaetae disappear with age and growth, and can be used to define the larval stage. Chaetogenesis shows that the long shaft‐shaped manubrium and posterior process develop from different regions. The uncini terminology ‘double rows’ was reinterpreted and renamed ‘inverted rows’, which better reflects the inversion of chaetal positions during ontogenetic development.
SEGREGATION IN ISTANBUL: PATTERNS AND PROCESSES
Authors: PINARCIOĞLU M. MELİH , IŞIK OĞUZ
Published: October 2009

In the 1990s, Istanbul regained its long‐forgotten role as a regional gateway between Asia and Europe. With the growing importance of the city in global flows, hypotheses concerning the global city and social/spatial polarisation were advanced for Istanbul, arguing that it could best be characterised as a ‘divided city’. This paper suggests that despite the city's growing integration with global dynamics, the degree of segregation is not on the rise but even registered a slight fall between 1990 and 2000. The distinct nature of social mobility that provided the poor with the opportunities for upward mobility generated an easily legible pattern of segregation. In the mid‐1990s these dynamics changed and the forces acting upon segregation became too diversified to be reduced to a single factor, generating unpredictable results in parts of the city. Our findings indicate that the mobility of the existing population and locational choices of newcomers work in opposite directions as far as their impacts on segregation are concerned, with the former increasing and the latter decreasing the existing levels of segregation.
HEDGING BY SEQUENTIAL REGRESSIONS REVISITED
Authors: Černý Aleš , Kallsen Jan
Published: October 2009

Almost 20 years ago Föllmer and Schweizer (1989) suggested a simple and influential scheme for the computation of hedging strategies in an incomplete market. Their approach of local risk minimization results in a sequence of one‐period least squares regressions running recursively backward in time. In the meantime, there have been significant developments in the global risk minimization theory for semimartingale price processes. In this paper we revisit hedging by sequential regression in the context of global risk minimization, in the light of recent results obtained by Černý and Kallsen (2007). A number of illustrative numerical examples are given.
ENHANCEMENT OF THE APPLICABILITY OF MARKOWITZ'S PORTFOLIO OPTIMIZATION BY UTILIZING RANDOM MATRIX THEORY
Authors: Bai Zhidong , Liu Huixia , Wong Wing‐Keung
Published: October 2009

The traditional estimated return for the Markowitz mean‐variance optimization has been demonstrated to seriously depart from its theoretic optimal return. We prove that this phenomenon is natural and the estimated optimal return is always  times larger than its theoretic counterpart, where  with y as the ratio of the dimension to sample size. Thereafter, we develop new bootstrap‐corrected estimations for the optimal return and its asset allocation and prove that these bootstrap‐corrected estimates are proportionally consistent with their theoretic counterparts. Our theoretical results are further confirmed by our simulations, which show that the essence of the portfolio analysis problem could be adequately captured by our proposed approach. This greatly enhances the practical uses of the Markowitz mean‐variance optimization procedure.
LOCAL RISK MINIMIZATION FOR DEFAULTABLE MARKETS
Authors: Biagini Francesca , Cretarola Alessandra
Published: October 2009

We study the local risk minimization approach for defaultable markets in a general setting where the asset price dynamics and the default time may influence each other. We find the Föllmer‐Schweizer decomposition in this general setting and compute it explicitly in two particular cases, when default time depends on the risky asset's behavior and when only a dependence of discounted asset price on default time is occurring.
ONE‐PARAMETER FAMILIES OF DISTORTION RISK MEASURES
Authors: Tsukahara Hideatsu
Published: October 2009

This paper introduces parametric families of distortion risk measures, investigates their properties, and discusses their use in risk management. Their derivation is based on Kusuoka's representation theorem of law invariant and comonotonically additive coherent risk measures. Our approach is to narrow down a tractable class of risk measures by requiring their comparability with the traditional expected shortfall. We make numerical comparison among them and propose a method of estimating the value of the distortion risk measures based on data. Their use and interpretation in risk management will also be discussed.
Learning and sharing in a Chinese high‐technology cluster: a study of inter‐firm and intra‐firm knowledge flows between R&D employees
Authors: Ramirez Matias , Li Xibao
Published: October 2009

This paper highlights a new emerging division of labour among Chinese Research and Development (R&D) workers in Beijing's Zhongguancun Science Park, which emphasises learning through external networks. Such learning relies on the ability to develop common practices and ‘translate’ external knowledge to the firm. The discussion highlights the significant costs that can be associated with developing and establishing such skills and the underlying practices that can support this process.
Problems with the Human Rights Act 1998 and How to Remedy Them: Is a Bill of Rights the Answer?
Authors: Amos Merris
Published: October 2009

Recently there has been much discussion of the prospect of replacing, or supplementing, the Human Rights Act 1998 (HRA) with a British bill of rights. The Government, opposition Conservative Party and others have published detailed plans and research reports. Whilst there has been some limited examination of the alleged failures of the HRA in providing effective legal protection for human rights, the debate has not been accompanied by a thorough examination of these types of problems with the HRA, free from political criticisms. Drawing on research concerning aspects of the HRA carried out over the past ten years, it is possible to identify concrete problems which have prevented the HRA from meeting the objectives originally set for it. But given the limitations of the present debate, future plans do not adequately address many of these problems making it uncertain how effective any new bill of rights will actually be.
On the Margins or Moving into the Mainstream? Higher Education in Further Education in England
Authors: Scott Peter
Published: October 2009

As many students are now enrolled on higher education programmes in further education today as the total of all higher education students – whether in universities, advanced further education or teacher training – at the time of the Robbins Report in 1963 when the advance towards mass higher education first got under way. These programmes make a vital contribution to the diversity and, in particular, the accessibility and flexibility of higher education provision in England in 2009. Yet higher education in further education receives limited, and dwindling, policy attention. It is sometimes treated as a marginal, and even anomalous, provision. Yet the realisation of a truly lifelong learning system will depend crucially on the local delivery of higher education that is perhaps better tailored to social demand and economic imperatives.
Urban sustainability and governance: issues for the twenty‐first century
Authors: Lieberherr‐Gardiol Françoise
Published: October 2009

The notion of urban sustainability that emerged at the end of the 1980s falls within the scope of sustainable development, a concept that arose in reaction to the model of technological and economic growth that triumphed after World War II. It comes into play as an attempt to link and put into perspective economic effectiveness, social equity and ecological balance. The sustainability approach focuses on how urban societies organise their space, their way of life and transportation, their technologies of production and consumption, as well as their governance and dynamics. Applied to cities, sustainable development can be defined in terms of concrete objectives: efforts to combat wasted energy, space and natural resources, and to reduce pollution, the problems of sanitation and the degradation of the environment. To the extent that governance is established and maintained with regard to the decision‐making powers of public authorities faced with demands by divergent but equally legitimate interest groups, the responsibilities of citizens and the involvement of private stakeholders, sustainable innovations will succeed. The International Platform on Sustainable Urban Development, put in place by S‐DEV Geneva 05, makes it possible to illustrate the problem by presenting the priority issues in sustainability, along with experiments undertaken by cities that were invited to present their innovations in renewable energy, soft mobility, green planning, systematic recycling, appropriate sanitation, urban agriculture and participatory governance.
On the road: fifty years later
Authors: Griffey Adam
Published: October 2009

This essay concerns itself with issues surrounding the 50th anniversary of the initial publication of Jack Kerouac's novel On the road. Attention is paid to aspects of the novel's publication history, diverse commemorative events planned for this anniversary, and problems arising from Kerouac's own difficult relationship with the very counterculture that he is thought to have engendered. Kerouac's role as a prophetic voice in American fiction is set against his equally powerful position as a cultural icon and literary celebrity.
The semantic dimension in AIDS policy changes in France
Authors: Eun Jaeho
Published: October 2009

Traditional studies of policy change do not examine directly the source of far‐reaching changes that can commonly be observed in empirical life. The definitional approach is a promising alternative area of research. It can be used to shed light on what is known as the punctuated equilibrium mechanism, meaning a two‐speed pace of policy change: alternating between lengthy periods of incremental change and relatively brief periods of dramatic change. From this perspective, the degrees of policy change are closely related to semantic levels of problem definitions. The greater the enveloping character of the legitimate definition, the more generalised and even radical the change is felt to be. Conversely, as the definitional level diminishes, so the change becomes more local. Indeed, the pace of change is dependent on the pace of the emergence and acceptance of a new legitimate definition. The greater the legitimacy encountered by the new definition, the more rapid the change in policy. Conversely, if the new legitimate definition is adopted only slowly then policies too change only gradually.
Evolution of urban policy and slum clearance in Morocco: successes and transformations of “social contracting”
Authors: Navez‐Bouchanine Françoise
Published: October 2009

This article uses as a frame of reference the attempts to reform urban policies undertaken in Morocco in the 1990s and attempts to explain how new modes of governance, which are more democratic and more concerned by the social effects of urban interventions, can be implemented, the possibilities and difficulties encountered during their implementation, and the various kinds of “limits” or obstacles that impede the generalisation of their positive effects. In particular, this article emphasises the frequently excessive tensions and gaps between the various partners and the projects conceived, as well as the constraints that hinder the improvement of living conditions in cities today.
Did Recent Experience of a Financial Crisis Help in Coping with the Current Financial Turmoil? The Case of the Nordic Countries
Authors: MAYES DAVID G.
Published: October 2009

This article considers the lessons learned from the Nordic crises of the 1980s and 1990s and how far problems incurred during the present crisis stem from a failure to act on those lessons. Iceland, which was little affected on the first occasion, has had the worst crisis of any country round the world while Finland, which was worst affected last time, has come through almost unscathed. The ways of avoiding problems caused by having cross‐border banks, a feature that did not exist on the previous occasion, were known but it has taken a second crisis to get governments to act.
Die Krise but not La Crise? The Financial Crisis and the Transformation of German and French Banking Systems
Authors: HARDIE IAIN , HOWARTH DAVID
Published: October 2009

This article explores what the financial crisis shows about changes in the German and French banking systems, the two largest in continental Europe. In particular, we highlight processes of financialization – defined here as the increased trading of risk. We focus on an apparent contradiction: why did the supposedly more protectionist and conservative German banking system suffer much higher losses than the more liberalized French system? This article also examines the responses of German and French banks and governments to the crisis and speculates how far these responses might limit future financialization and shape national banking systems.
The normative development of emotion regulation strategy use in children and adolescents: a 2‐year follow‐up study
Authors: Gullone Eleonora , Hughes Elizabeth K. , King Neville J. , Tonge Bruce
Published: October 2009

Background:  Emotion regulation involves intrinsic and extrinsic processes responsible for managing one’s emotions toward goal accomplishment. Research on emotion regulation has predominantly focused on early developmental periods and the majority of emotion regulation research examining the pre‐adult years has lacked a comprehensive theoretical framework. The current study examined the use of two strategies of emotion regulation during childhood and adolescents, as conceptualised within Gross’s (1998) process‐oriented model.

Methods:  To determine the use, norms and development of the Expressive Suppression and Cognitive Reappraisal strategies, the Emotion Regulation Questionnaire for Children and Adolescents (ERQ‐CA) was administered to 1,128 participants aged between 9 and 15 years. Three data collection phases, each one year apart, enabled investigation of developmental patterns in the use of the two strategies.

Results:  As predicted, Suppression use was found to be lower for older participants compared to their younger peers, and over time participants reported less use of this strategy. Older participants also scored lower on Reappraisal but stability over time was found. Also as expected, males reported more Suppression use compared to females.

Conclusions:  By documenting the development and norms for Cognitive Reappraisal and Expressive Suppression in a community sample of children and adolescents, the current study makes a significant contribution to our understanding of these two ER strategies during these developmental periods.
Inactivation of cytochrome c oxidase by mutant SOD1s in mouse motoneuronal NSC‐34 cells is independent from copper availability but is because of nitric oxide
Authors: Arciello Mario , Capo Concetta Rosa , Cozzolino Mauro , Ferri Alberto , Nencini Monica , Carrì Maria Teresa , Rossi Luisa
Published: October 2009

J. Neurochem. (2010) 112, 183–192.

The copper‐enzyme cytochrome c oxidase (Cytox) has been indicated as a primary molecular target of mutant copper, zinc superoxide dismutase (SOD1) in familial amyotrophic lateral sclerosis (fALS); however, the mechanism underlying its inactivation is still unclear. As the toxicity of mutant SOD1s could arise from their selective recruitment to mitochondria, it is conceivable that they might compete with Cytox for the mitochondrial copper pool causing Cytox inactivation. To investigate this issue, we used mouse motoneuronal neuroblastoma × spinal cord cell line‐34, stably transfected for the inducible expression of low amounts of wild‐type or mutant (G93A, H46R, and H80R) human SOD1s and compared the effects observed on Cytox with those obtained by copper depletion. We demonstrated that all mutants analyzed induced cell death and decreased the Cytox activity, but not the protein content of the Cytox subunit II, at difference with copper depletion that also affected subunit II protein. Copper supplementation did not counteract mutant hSOD1s toxicity. Otherwise, the treatment of neuroblastoma × spinal cord cell line‐34 expressing G93A, H46R, or H80R hSOD1 mutants, and showing constitutive expression of iNOS and nNOS, with either a NO scavenger, or NOS inhibitors prevented the inhibition of Cytox activity and rescued cell viability. These results support the involvement of NO in mutant SOD1s‐induced Cytox damage, and mitochondrial toxicity.
Further pharmacological characterization of 5‐HT2Creceptor agonist‐induced inhibition of 5‐HT neuronal activity in the dorsal raphe nucleusin vivo
Authors: Quérée P , Peters S , Sharp T
Published: October 2009

Background and purpose: Recent experiments using non‐selective 5‐hydroxytryptamine (5‐HT)2Creceptor agonists including WAY 161503 suggested that midbrain 5‐HT neurones are under the inhibitory control of 5‐HT2Creceptors, acting via neighbouring gamma‐aminobutyric acid (GABA) neurones. The present study extended this pharmacological characterization by comparing the actions of WAY 161503 with the 5‐HT2Creceptor agonists, Ro 60‐0275 and 1‐(3‐chlorophenyl) piperazine (mCPP), as well as the non‐selective 5‐HT agonist lysergic acid diethylamide (LSD) and the 5‐HT releasing agent 3,4‐methylenedioxymethamphetamine (MDMA).

Experimental approach: 5‐HT neuronal activity was measured in the dorsal raphe nucleus (DRN) using extracellular recordings in anaesthetized rats. The activity of DRN GABA neurones was assessed using double‐label immunohistochemical measurements of Fos and glutamate decarboxylase (GAD).

Key results: Ro 60‐0175, like WAY 161503, inhibited 5‐HT neurone firing, and the 5‐HT2Cantagonist SB 242084 reversed this effect. mCPP also inhibited 5‐HT neurone firing (∼60% neurones) in a SB 242084‐reversible manner. LSD inhibited 5‐HT neurone firing; however, this effect was not altered by either SB 242084 or the 5‐HT2A/Creceptor antagonist ritanserin but was reversed by the 5‐HT1Areceptor antagonist WAY 100635. Similarly, MDMA inhibited 5‐HT neurone firing in a manner reversible by WAY 100635, but not SB 242084 or ritanserin. Finally, both Ro 60‐0275 and mCPP, like WAY 161503, increased Fos expression in GAD‐positive DRN neurones.

Conclusions and implications: These data strengthen the hypothesis that midbrain 5‐HT neurones are under the inhibitory control of 5‐HT2Creceptors, and suggest that the 5‐HT2Cagonists Ro 60‐0175, mCPP and WAY 161503, but not LSD or MDMA, are useful probes of the mechanism(s) involved.
Inhibition of nitric oxide‐activated guanylyl cyclase by calmodulin antagonists
Authors: James LR , Griffiths CH , Garthwaite J , Bellamy TC
Published: October 2009

Background and purpose: Nitric oxide (NO) controls numerous physiological processes by activation of its receptor, guanylyl cyclase (sGC), leading to the accumulation of 3′‐5′ cyclic guanosine monophosphate (cGMP). Ca2+‐calmodulin (CaM) regulates both NO synthesis by NO synthase and cGMP hydrolysis by phosphodiesterase‐1. We report that, unexpectedly, the CaM antagonists, calmidazolium, phenoxybenzamine and trifluoperazine, also inhibited cGMP accumulation in cerebellar cells evoked by an exogenous NO donor, with IC50values of 11, 80 and 180 µM respectively. Here we sought to elucidate the underlying mechanism(s).

Experimental approach: We used cerebellar cell suspensions to determine the influence of CaM antagonists on all steps of the NO‐cGMP pathway. Homogenized tissue and purified enzyme were used to test effects of calmidazolium on sGC activity.

Key results: Inhibition of cGMP accumulation in the cells did not depend on changes in intracellular Ca2+concentration. Degradation of cGMP and inactivation of NO were both inhibited by the CaM antagonists, ruling out increased loss of cGMP or NO as explanations. Instead, calmidazolium directly inhibited purified sGC (IC50= 10 µM). The inhibition was not in competition with NO, nor did it arise from displacement of the haem moiety from sGC. Calmidazolium decreased enzymeVmaxandKm, indicating that it acts in an uncompetitive manner.

Conclusions and implications: The disruption of every stage of NO signal transduction by common CaM antagonists, unrelated to CaM antagonism, cautions against their utility as pharmacological tools. More positively, the compounds exemplify a novel class of sGC inhibitors that, with improved selectivity, may be therapeutically valuable.