bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical findings in patients with GLI2 mutations – phenotypic variability
Authors: Bertolacini CDP , Ribeiro‐Bicudo LA , Petrin A , Richieri‐Costa A , Murray JC
Published: December 2010

Bertolacini CDP, Ribeiro‐Bicudo LA, Petrin A, Richieri‐Costa A, Murray JC. Clinical findings in patients with GLI2 mutations – phenotypic variability.

Mutations in the human GLI2 gene were first reported in association with defective anterior pituitary formation, panhypopituitarism, and forebrain anomalies represented by typical holoprosencephaly (HPE) and holoprosencephaly‐like (HPE‐L) phenotypes and postaxial polydactyly. Subsequently, anophthalmia plus orbital anomalies, heminasal aplasia, branchial arch anomalies and polydactyly have also been incorporated into the general phenotype. Here we described six Brazilian patients with phenotypic manifestations that range from isolated cleft lip/palate with polydactyly, branchial arch anomalies to semi‐lobar holoprosencephaly. Novel sequence variants were found in the GLI2 gene in patients with marked involvement of the temporomandibular joint (TMJ), a new clinical finding observed with mutations of this gene. Clinical, molecular and genetic aspects are discussed.
Homozygous 10q23/PTEN deletion and its impact on outcome in glioblastoma: A prospective translational study on a uniformly treated cohort of adult patients
Authors: Srividya Mallavarapu R. , Thota Balaram , Shailaja Bangalore C. , Arivazhagan Arimappamagan , Thennarasu Kandavel , Chandramouli Bangalore A. , Hegde Alangar S. , Santosh Vani
Published: December 2010

Tumors from a prospective cohort of adult patients with newly diagnosed glioblastoma (n = 73), treated uniformly with radiochemotherapy, were examined for 10q23/PTEN deletion by fluorescence in situ hybridization (FISH). Statistical methods were employed to evaluate the degree of association between 10q23/PTEN deletion status and patient age. Survival analysis was performed using Kaplan‐Meier log‐rank test and multivariable Cox models to assess the prognostic value of 10q23/PTEN deletion. Interestingly, 10q23/PTEN homozygous deletion was frequent in patients >45 years of age (P = 0.034) and the median age of patients harboring PTEN homozygous deletions was significantly higher than those with the retained status (P = 0.019). 10q23/PTEN homozygous deletion was associated with shorter survival in the entire cohort as well in patients >45 years (P < 0.05), indicating that loss of 10q23/PTEN showed clinical importance in elderly patients. Our study highlights the independent prognostic/predictive value of 10q23/PTEN deletion status as identified by FISH, particularly in glioblastoma patients aged >45 years.
Does China Transfer Productivity Enhancing Technology to Sub‐Saharan Africa? Evidence from Manufacturing Firms*
Authors: Elu Juliet U. , Price Gregory N.
Published: December 2010

Abstract:  This paper considers whether trade between China and sub‐Saharan Africa results in productivity‐enhancing technology transfers to sub‐Saharan African manufacturing firms. As trade flows between countries potentially results in interactions that lead to technological improvements in the production of goods and services, we parameterize the level of total factor productivity for African manufacturing firms as a function of foreign direct investment flow, and for the country in which it operates, trade openness with China, and its interaction with foreign direct investment. With micro‐level data on manufacturing firms in five sub‐Saharan African countries, we estimate the parameters of firm‐level production functions between 1992 and 2004. Our parameter estimates reveal that across the firms and countries in our sample, there is no relationship between productivity‐enhancing foreign direct investment and trade with China. In addition, increasing trade openness with China has no effect on the growth rate of total factor productivity. To the extent that total factor productivity and its growth is a crucial determinant of economic growth and living standards in the long run, our results suggest that increasing trade openness with China is not a long‐run source of higher living standards for sub‐Saharan Africa.
The Future of African Trade with China under Alternative Trade Liberalization Schemes
Authors: Chemingui Mohamed A. , Bchir Mohamed H.
Published: December 2010

Abstract:  Evidence is gradually being built up in Africa on the full extent and rapidly growing role and interest of China in Africa. The global trade integration under the Doha Round, which is considered as the channel for fostering outward‐oriented development and generates economic and social benefits, is expected to effect more African trade with China. Our results show that with an agreement for the Doha Round, China will achieve its dominance on global trade faster than in the baseline scenario where no agreement is expected to be signed. In the long term, this impressive growth in Chinese exports to Africa is not a real value added, as China is already taking the place of the other major trade players both in African markets as well as in the markets of other regions and countries. In other words, China is expected to achieve in 10 years (2010–2020) what initially was expected to be achieved in 20 years in case of no agreement under the Doha Round, where a simple linear estimation on the evolution of Chinese exports is carried out. Our results also show that even in the case where China will offer more market access for African countries, the situation will not improve much for most of them. The reason is that Africa is still suffering from small productive capacities and a low level of diversification of its economy.
Impacts of the Rise of China on Developing Country Trade: Evidence from North Africa*
Authors: Brenton Paul , Walkenhorst Peter
Published: December 2010

Abstract:  Despite the global financial and economic crisis, China has continued to experience strong export‐driven growth and, indeed, became the world's largest exporting country in 2009. This rise of China in international markets presents African countries with growing competition in their home and export markets, but also with new opportunities. This paper focuses on the impacts of these developments on countries in North Africa, which are directly affected by the prominence of Chinese manufacturing. In particular, the analysis addresses two policy questions: First, is competition from China leading to substantial displacement of resources that incur significant adjustment costs while moving to new activities, or are there opportunities to exploit finer patterns of specialization that entail less disruption? And second, will policies that mitigate the impact of competition from China limit the longer‐term capacity to exploit new opportunities in the global market? The findings from the empirical analysis suggest that policy makers can support North African producers in the increasingly fierce competition with China by reviewing the regulatory and incentives environment, reducing trade logistics costs, and broadening trade promotion efforts to non‐traditional markets.
Selective Identification, Quiet Distancing: Understanding the Working-Class Response to the Nordic Daycare Model
Authors: Stefansen Kari , Skogen Ketil
Published: December 2010

In Norway, our empirical case, enrolment of children under three years old in formal daycare has increased rapidly during the last 5–6 years, especially among the working class. This has happened despite working-class parents' traditional reluctance to use such childcare services for the youngest children. As a pedagogical project, formal daycare mirrors middle-class cultural traits that seem to clash with traditional working-class notions about young children's needs. Drawing on a longitudinal qualitative study, this paper explores this new element in working-class parenting. The analysis suggests that working-class parents' response to daycare unfolds as a dual process; it involves participation and identification as well as distancing and separation. This pattern of selective identification and distancing is interpreted as a type of boundary management that structures working-class childhoods in particular ways. To facilitate a discussion of the wider cultural context that working-class parents' response both reflects and potentially reproduces, we contrast it to middle-class parents' ways of relating to daycare. Koselleck's (2004) analytical concepts of ‘space of experience’ and ‘horizon of expectation’ are used to explore such linkages.
Olive Schreiner Globalising Social Inquiry: A Feminist Analytics of Globalization
Authors: Stanley Liz , Dampier Helen , Salter Andrea
Published: December 2010

Globalization theory sees the processes of change it is concerned with as distinctively new, with a feminist analytics part of the newness of the current period too, focusing on some of the specific gender dynamics involved. However, the work of the feminist writer and social theorist Olive Schreiner (1855–1920) challenges, indeed overturns, such assumptions. Similar structural economic and political circumstances to those now called globalization were the focus of Schreiner's theorising, with her work demonstrating that ‘it's been done before’ in the case of a feminist analytics of global social change. Also, Schreiner's feminist interrogation of global change refused any confinement to gender (although it encompassed it), because for her gender was always already interconnected with class, ‘race’ and an array of wider structural forces and changes. Schreiner's unfolding analysis of imperialism and the expansionist project in the period 1888 to 1913, and of war, peace and social movements in the period 1914 to 1920, are discussed, in particular by presenting new material from Schreiner's extant letters and exploring the significant ways these add to the analysis in her published work. Over 4000 Schreiner letters are extant, are being researched by the Olive Schreiner Letters Project ( www.oliveschreinerletters.ed.ac.uk ), and provide an unparalleled resource for exploring the emergent analysis of a key feminist theorist.
LIQUIDITY IN A BINOMIAL MARKET
Authors: Gökay Selim , Soner Halil Mete
Published: December 2010

We study the binomial version of the illiquid market model introduced by Çetin, Jarrow, and Protter for continuous time and develop efficient numerical methods for its analysis. In particular, we characterize the liquidity premium that results from the model. In Çetin, Jarrow, and Protter, the arbitrage free price of a European option traded in this illiquid market is equal to the classical value. However, the corresponding hedge does not exist and the price is obtained only in L2‐approximating sense. Çetin, Soner, and Touzi investigated the super‐replication problem using the same supply curve model but under some restrictions on the trading strategies. They showed that the super‐replicating cost differs from the Black–Scholes value of the claim, thus proving the existence of liquidity premium. In this paper, we study the super‐replication problem in discrete time but with no assumptions on the portfolio process. We recover the same liquidity premium as in the continuous‐time limit. This is an independent justification of the restrictions introduced in Çetin, Soner, and Touzi. Moreover, we also propose an algorithm to calculate the option’s price for a binomial market.
SKEWNESS‐AWARE ASSET ALLOCATION: A NEW THEORETICAL FRAMEWORK AND EMPIRICAL EVIDENCE
Authors: Low Cheekiat , Pachamanova Dessislava , Sim Melvyn
Published: December 2010

This paper presents a new measure of skewness, skewness‐aware deviation, that can be linked to prospective satisficing risk measures and tail risk measures such as Value‐at‐Risk. We show that this measure of skewness arises naturally also when one thinks of maximizing the certainty equivalent for an investor with a negative exponential utility function, thus bringing together the mean‐risk, expected utility, and prospective satisficing measures frameworks for an important class of investor preferences. We generalize the idea of variance and covariance in the new skewness‐aware asset pricing and allocation framework. We show via computational experiments that the proposed approach results in improved and intuitively appealing asset allocation when returns follow real‐world or simulated skewed distributions. We also suggest a skewness‐aware equivalent of the classical Capital Asset Pricing Model beta, and study its consistency with the observed behavior of the stocks traded at the NYSE between 1963 and 2006.
THE TRACKING ERROR RATE OF THE DELTA‐GAMMA HEDGING STRATEGY
Authors: Gobet Emmanuel , Makhlouf Azmi
Published: December 2010

We analyze the convergence rate of the quadratic tracking error, when a Delta‐Gamma hedging strategy is used at N discrete times. The fractional regularity of the payoff function plays a crucial role in the choice of the trading dates, in order to achieve optimal rates of convergence.
ROBUST BOUNDS FOR FORWARD START OPTIONS
Authors: Hobson David , Neuberger Anthony
Published: December 2010

We consider the problem of finding a model‐free upper bound on the price of a forward start straddle with payoff . The bound depends on the prices of vanilla call and put options with maturities T1 and T2, but does not rely on any modeling assumptions concerning the dynamics of the underlying. The bound can be enforced by a super‐replicating strategy involving puts, calls, and a forward transaction. We find an upper bound, and a model which is consistent with T1 and T2 vanilla option prices for which the model‐based price of the straddle is equal to the upper bound. This proves that the bound is best possible. For lognormal marginals we show that the upper bound is at most 30% higher than the Black–Scholes price. The problem can be recast as finding the solution to a Skorokhod embedding problem with nontrivial initial law so as to maximize .
THE WHAT, HOW AND WHO OF HUMANITY BEFORE GOD: THEOLOGICAL ANTHROPOLOGY AND THE BIBLE IN THE TWENTY‐FIRST CENTURY
Authors: FORD DAVID F.
Published: December 2010

David Kelsey's Eccentric Existence. A Theological Anthropology is read in the context of the traditions of Christian theology, especially in Europe and North America, and of Kelsey's Yale colleagues. Its theocentric, scriptural and thoughtfully experimental contribution to theological anthropology from the perspectives of creation, consummation and reconciliation is analysed, appreciated and assessed. Implications of Kelsey's identification of three distinct plotlines in the Bible are explored. Questions are raised about the range of his Christian conversations, the limitations of his reliance on narrative, his neglect of significant parts of the Bible and Christian tradition, and his focus on the interaction with secular rather than religious dimensions of the contemporary world.
Exploring the experiences of people with intellectual disabilities when service users die
Authors: Ryan Karen , Guerin Suzanne , Dodd Philip , McEvoy John
Published: December 2010

Accessible summary

 People with intellectual disabilities are living for longer than ever before and are experiencing the deaths of their friends and other service users.

 This study describes the experiences of people with intellectual disabilities who have lived through the death of a friend or service user from the point of view of staff from intellectual disability and palliative care services.

 It is important to understand the experiences of people with intellectual disabilities to try and help people cope with the deaths of their friends.

 The study shows that it helps to include people with intellectual disabilities when their friends become unwell and to talk openly with them about what is happening.

Research is lacking on the effect of the deaths of fellow service users on people with intellectual disabilities. This qualitative study formed part of a project which aimed to describe the provision of palliative care to people with intellectual disabilities in Ireland and to assess the population’s palliative care needs. We report on findings from 16 focus groups held with staff in which participants described their perception of the experiences of people with intellectual disabilities when other service users die. Interviews were analysed using Framework Analysis. The findings highlight the emotional impact of the death of a friend on people with intellectual disabilities. Situations where staff facilitated the involvement of services users are described, and the study points to the benefits of this approach. Possible barriers to involvement are highlighted. The findings affirm the importance of ensuring that people with intellectual disabilities have a good understanding of the concept of death to alleviate the bereavement experience.
Heat perception and signalling in plants: a tortuous path to thermotolerance
Authors: Saidi Younousse , Finka Andrija , Goloubinoff Pierre
Published: December 2010

An accurate assessment of the rising ambient temperature by plant cells is crucial for the timely activation of various molecular defences before the appearance of heat damage. Recent findings have allowed a better understanding of the early cellular events that take place at the beginning of mild temperature rise, to timely express heat‐shock proteins (HSPs), which will, in turn, confer thermotolerance to the plant. Here, we discuss the key components of the heat signalling pathway and suggest a model in which a primary sensory role is carried out by the plasma membrane and various secondary messengers, such as Ca2+ ions, nitric oxide (NO) and hydrogen peroxide (H2O2). We also describe the role of downstream components, such as calmodulins, mitogen‐activated protein kinases and Hsp90, in the activation of heat‐shock transcription factors (HSFs). The data gathered for land plants suggest that, following temperature elevation, the heat signal is probably transduced by several pathways that will, however, coalesce into the final activation of HSFs, the expression of HSPs and the onset of cellular thermotolerance.
The flavonoid baicalein promotes NMDA receptor‐dependent long‐term potentiation and enhances memory
Authors: Wang Wei , Wang Fang , Yang Yuan‐Jian , Hu Zhuang‐Li , Long Li‐Hong , Fu Hui , Xie Na , Chen Jian‐Guo
Published: December 2010

BACKGROUND AND PURPOSE There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long‐term potentiation (LTP) in the hippocampal CA1 region and cognitive behavioural performance.

EXPERIMENTAL APPROACH Effects of baicalein on LTP in rat hippocampal slices were investigated by electrophysiological methods. Phosphorylation of Akt (at Ser473), the extracellular signal‐regulated kinase (ERK1/2) and the transcription factor cAMP response element‐binding protein (CREB) (at Ser133) were analysed by Western blot. Fear conditioning was used to determine whether baicalein could improve learning and memory in rats.

KEY RESULTS Baicalein enhanced the N‐methyl‐d‐aspartate glutamate receptor‐dependent LTP in a bell‐shaped concentration‐dependent manner. Addition of the lipoxygenase metabolites 12(S)‐HETE and 12(S)‐HPETE did not reverse these effects of baicalein. Baicalein treatment enhanced phosphorylation of Akt during induction of LTP with the same bell‐shaped dose–response curve. LTP potentiation induced by baicalein was blocked by inhibitors of phosphoinositide 3‐kinase. CREB phosphorylation was also increased in the CA1 region of baicalein‐treated slices. Baicalein‐treated rats performed significantly better than controls in a hippocampus‐dependent contextual fear conditioning task. Furthermore, baicalein treatment selectively increased the phosphorylation of Akt and CREB in the CA1 region of hippocampus, but not in the prefrontal cortex, after fear conditioning training.

CONCLUSIONS AND IMPLICATIONS Our results demonstrate that the flavonoid baicalein can facilitate memory, and therefore it might be useful in the treatment of patients with memory disorders.
Prolyl oligopeptidase induces angiogenesis both in vitro and in vivo in a novel regulatory manner
Authors: Myöhänen TT , Tenorio‐Laranga J , Jokinen B , Vázquez‐Sánchez R , Moreno‐Baylach MJ , García‐Horsman JA , Männistö PT
Published: December 2010

BACKGROUND AND PURPOSE A serine protease, prolyl oligopeptidase (POP) has been reported to be involved in the release of the pro‐angiogenic tetrapeptide acetyl‐N‐Ser‐Asp‐Lys‐Pro (Ac‐SDKP) from its precursor, 43‐mer thymosin β4 (Tβ4). Recently, it was shown that both POP activity and the levels of Ac‐SDKP are increased in malignant tumours. The aim of this study was to clarify the release of Ac‐SDKP, and test if POP and a POP inhibitor, 4‐phenyl‐butanoyl‐L‐prolyl‐2(S)‐cyanopyrrolidine (KYP‐2047), can affect angiogenesis.

EXPERIMENTAL APPROACH We used HPLC for bioanalytical and an enzyme immunoassay for pharmacological analysis. Angiogenesis of human umbilical vein endothelial cells was assessed in vitro using a ‘tube formation’ assay and in vivo using a Matrigel plug assay (BD Biosciences, San Jose, CA, USA) in adult male rats. Moreover, co‐localization of POP and blood vessels was studied.

KEY RESULTS We showed the sequential hydrolysis of Tβ4: the first‐step hydrolysis by proteases to <30‐mer peptides is followed by an action of POP. Unexpectedly, POP inhibited the first hydrolysis step, revealing a novel regulation system. POP with Tβ4 significantly induced, while KYP‐2047 effectively prevented, angiogenesis in both models compared with Tβ4 addition itself. POP and endothelial cells were abundantly co‐localized in vivo.

CONCLUSIONS AND IMPLICATIONS We have now revealed that POP is a second‐step enzyme in the release of Ac‐SDKP from Tβ4, and it has novel autoregulatory effect in the first step. Our results also advocate a role for Ac‐SDKP in angiogenesis, and suggest that POP has a pro‐angiogenic role via the release of Ac‐SDKP from its precursor Tβ4 and POP inhibitors can block this action.
Chemokine receptor CCR5: from AIDS to atherosclerosis
Authors: Jones KL , Maguire JJ , Davenport AP
Published: December 2010

There is increasing recognition of an important contribution of chemokines and their receptors in the pathology of atherosclerosis and related cardiovascular disease. The chemokine receptor CCR5 was initially known for its role as a co‐receptor for HIV infection of macrophages and is the target of the recently approved CCR5 antagonist maraviroc. However, evidence is now emerging supporting a role for CCR5 and its ligands CCL3 (MIP‐1α), CCL4 (MIP‐1β) and CCL5 (RANTES) in the initiation and progression of atherosclerosis. Specifically, the CCR5 deletion polymorphism CCR5delta32, which confers resistance to HIV infection, has been associated with a reduced risk of cardiovascular disease and both CCR5 antagonism and gene deletion reduce atherosclerosis in mouse models of the disease. Antagonism of CCL5 has also been shown to reduce atherosclerotic burden in these animal models. Crucially, CCR5 and its ligands CCL3, CCL4 and CCL5 have been identified in human and mouse vasculature and have been detected in human atherosclerotic plaque. Not unexpectedly, CC chemokines have also been linked to saphenous vein graft disease, which shares similarity to native vessel atherosclerosis. Distinct roles for chemokine–receptor systems in atherogenesis have been proposed, with CCR5 likely to be critical in recruitment of monocytes to developing plaques. With an increased burden of cardiovascular disease observed in HIV‐infected individuals, the potential cardiovascular‐protective effects of drugs that target the CCR5 receptor warrant greater attention. The availability of clinically validated antagonists such as maraviroc currently provides an advantage for targeting of CCR5 over other chemokine receptors.
The antipyretic effect of dipyrone is unrelated to inhibition of PGE2 synthesis in the hypothalamus
Authors: Malvar David do C , Soares Denis M , Fabrício Aline SC , Kanashiro Alexandre , Machado Renes R , Figueiredo Maria J , Rae Giles A , de Souza Glória EP
Published: December 2010

BACKGROUND AND PURPOSE Bacterial lipopolysaccharide (LPS) induces fever through two parallel pathways; one, prostaglandin (PG)‐dependent and the other, PG‐independent and involving endothelin‐1 (ET‐1). For a better understanding of the mechanisms by which dipyrone exerts antipyresis, we have investigated its effects on fever and changes in PGE2 content in plasma, CSF and hypothalamus induced by either LPS or ET‐1.

EXPERIMENTAL APPROACH Rats were given (i.p.) dipyrone (120 mg·kg−1) or indomethacin (2 mg·kg−1) 30 min before injection of LPS (5 µg·kg−1, i.v.) or ET‐1 (1 pmol, i.c.v.). Rectal temperature was measured by tele‐thermometry. PGE2 levels were determined in the plasma, CSF and hypothalamus by elisa.

KEY RESULTS LPS or ET‐1 induced fever and increased CSF and hypothalamic PGE2 levels. Two hours after LPS, indomethacin reduced CSF and hypothalamic PGE2 but did not inhibit fever, while at 3 h it reduced all three parameters. Three hours after ET‐1, indomethacin inhibited the increase in CSF and hypothalamic PGE2 levels but did not affect fever. Dipyrone abolished both the fever and the increased CSF PGE2 levels induced by LPS or ET‐1 but did not affect the increased hypothalamic PGE2 levels. Dipyrone also reduced the increase in the venous plasma PGE2 concentration induced by LPS.

CONCLUSIONS AND IMPLICATIONS These findings confirm that PGE2 does not play a relevant role in ET‐1‐induced fever. They also demonstrate for the first time that the antipyretic effect of dipyrone was not mechanistically linked to the inhibition of hypothalamic PGE2 synthesis.
The Legitimacy Challenges for New Modes of Governance: Trustworthy Responsiveness
Authors: Føllesdal Andreas
Published: December 2010

Two typical features of new modes of governance (NMG) are of particular concern: (1) the delegation of regulatory activities to independent regulatory authorities at the national and the European level; and (2) regulatory networks outside the legislative arenas, with both private and public actors. These features tend to make the NMG less democratically accountable. Yet some hold that NMG can confer legitimacy on the European Union, especially because they secure ‘output’ more effectively than democratic arrangements, even though they lack any ‘input’ from voters. This article challenges these normative claims: the alleged benefits of NMG may be less than often claimed, while democratic accountability measures are less of a challenge to effectiveness and credibility, properly conceived.
New Modes of Governance and Democratic Accountability
Authors: Héritier Adrienne , Lehmkuhl Dirk
Published: December 2010

This article raises the question of the link between new modes of governance and democratic accountability. Our definition of new modes of governance as modes refers to public policy-making that includes private actors and/or public policy-making by public actors that takes place outside legislative arenas, and which focuses on delimited sectoral or functional areas. We identify three different ways in which new modes of governance can be subjected to democratic control: parliamentary control, multi-stakeholder involvement and control through the public sphere and civil society at large. Building on a number of the illustrative insights from various empirical projects, we find that, in our cases at least, new modes of governance did not have a negative effect on existing patterns of democratic accountability. At the same time, neither multi-stakeholder policies nor the participation of civil society guarantee democratic accountability in the strict sense. We provide some evidence to the effect that, if institutionally linked to democratically elected governmental bodies – meaning, in this context, the European Parliament – it is more likely that negative externalities deriving from public policy-making in functionally segmented arenas of the European Union's multilevel polity will be dealt with in a more systematic way.
Effect of percutaneous transluminal angioplasty on tissue oxygenation in ischemic diabetic feet
Authors: Kim Hong‐Ryul , Han Seung‐Kyu , Rha Seung‐Woon , Kim Hyun‐Surk , Kim Woo‐Kyung
Published: December 2010

Percutaneous transluminal angioplasty (PTA) has been performed as an alternative to bypass surgery for improving tissue oxygenation in ischemic diabetic feet because the former is less invasive than the latter. The purpose of this study was to evaluate the effect of PTA on tissue oxygenation in ischemic diabetic feet. This study included 29 ischemic diabetic feet, as determined by a transcutaneous oxygen pressure (TcPO2)<30 mmHg. The PTA was carried out in 29 limbs. The PTA procedure was considered successful, acceptable, and failed when residual stenosis was<30%, between 30 and 50%, and>50%, respectively. For evaluation of tissue oxygenation, the foot TcPO2 was measured before PTA and weekly for 6 weeks after PTA. Immediately after PTA, 26 feet were evaluated as being successful and the remaining three as acceptable. Before PTA, the average foot TcPO2 was 12.7±8.9 mmHg. The TcPO2 values were increased to 43.6±24.1, 51.0±22.6, 58.3±23.0, 61.3±24.2, 59.0±22.2, and 53.8±21.0 mmHg 1, 2, 3, 4, 5, and 6 weeks after PTA, respectively (p<0.01). The PTA procedure significantly increases tissue oxygenation in ischemic diabetic feet. The maximal level of tissue oxygenation was measured on the fourth week following PTA.
Bioactive peptides derived from vascular endothelial cell extracellular matrices promote microvascular morphogenesis and wound healing in vitro
Authors: Demidova‐Rice Tatiana N. , Geevarghese Anita , Herman Ira M.
Published: December 2010

Studies in our laboratory indicate that collagenase from Clostridium histolyticum promotes endothelial cell and keratinocyte responses to injury in vitro and wound healing in vivo. We postulate that matrix degradation by Clostridial collagenase creates bioactive fragments that can stimulate cellular responses to injury and angiogenesis. To test this hypothesis, we performed limited digestion of defined capillary‐endothelial‐derived extracellular matrices using purified human or bacterial collagenases. Immunoprecipitation with antibodies recognizing collagens I, II, III, IV, and V, followed by mass spectrometry reveals the presence of unique fragments in bacterial, but not human‐enzyme‐digested matrix. Results show that there are several bioactive peptides liberated from Clostridial collagenase‐treated matrices, which facilitate endothelial responses to injury, and accelerate microvascular remodeling in vitro. Fragments of collagen IV, fibrillin‐1, tenascin X, and a novel peptide created by combining specific amino acids contained within fibrillin 1 and tenascin X each have profound proangiogenic properties. The peptides used at 10–100 nM increase rates of microvascular endothelial cell proliferation by up to 47% and in vitro angiogenesis by 200% when compared with serum‐stimulated controls. Current studies are aimed at revealing the molecular mechanisms regulating peptide‐induced wound healing while extending these in vitro observations using animal modeling.
Akt‐mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation
Authors: Paterno Josemaria , Vial Ivan N. , Wong Victor W. , Rustad Kristine C. , Sorkin Michael , Shi Yubin , Bhatt Kirit A. , Thangarajah Hariharan , Glotzbach Jason P. , Gurtner Geoffrey C.
Published: December 2010

Although numerous factors are implicated in skin fibrosis, the exact pathophysiology of hypertrophic scarring remains unknown. We recently demonstrated that mechanical force initiates hypertrophic scar formation in a murine model, potentially enhancing cellular survival through Akt. Here, we specifically examined Akt‐mediated mechanotransduction in fibroblasts using both strain culture systems and our murine scar model. In vitro, static strain increased fibroblast motility, an effect blocked by wortmannin (a phosphoinositide‐3‐kinase/Akt inhibitor). We also demonstrated that high‐frequency cyclic strain was more effective at inducing Akt phosphorylation than low frequency or static strain. In vivo, Akt phosphorylation was induced by mechanical loading of dermal fibroblasts in both unwounded and wounded murine skin. Mechanically loaded scars also exhibited strong expression of α‐smooth muscle actin, a putative marker of pathologic scar formation. In vivo inhibition of Akt increased apoptosis but did not significantly abrogate hypertrophic scar development. These data suggest that although Akt signaling is activated in fibroblasts during mechanical loading of skin, this is not the critical pathway in hypertrophic scar formation. Future studies are needed to fully elucidate the critical mechanotransduction components and pathways which activate skin fibrosis.
Combination of stromal cell‐derived factor‐1 and collagen–glycosaminoglycan scaffold delays contraction and accelerates reepithelialization of dermal wounds in wild‐type mice
Authors: Sarkar Aparajita , Tatlidede Soner , Scherer Saja Sandra , Orgill Dennis P. , Berthiaume François
Published: December 2010

While dermal substitutes can mitigate scarring and wound contraction, a significant drawback of current dermal replacement technologies is the apparent delay in vascular ingrowth compared with conventional skin grafts. Herein, we examined the effect of the chemokine stromal cell‐derived factor‐1 (SDF‐1) on the performance of a porous collagen–glycosaminoglycan dermal analog in excisional wounds in mice. C57BL/6 mice with 1 cm × 1 cm dorsal full‐thickness wounds were covered with a collagen–glycosaminoglycan scaffold, followed by four daily topical applications of 1 μg SDF‐1 or phosphate‐buffered saline vehicle. Some animals were also pretreated with five daily doses of 300 mg/kg granulocyte colony‐stimulating factor. Animals treated with SDF‐1 and no granulocyte colony‐stimulating factor reepithelialized 36% faster than vehicle controls (16 vs. 25 days), and exhibited less wound contraction on postwounding day 18 (∼35% greater wound area) plus three‐fold longer neoepidermis formed than controls. Conversely, granulocyte colony‐stimulating factor promoted contraction and no epidermal regeneration. Early (postwounding Day 3) inflammatory cell infiltration in the SDF‐1‐treated group was 86% less, while the fraction of proliferating cells (positive Ki67 staining) was 32% more, when compared with controls. These results suggest that SDF‐1 simultaneously delays contraction and promotes reepithelialization and may improve the wound‐healing performance of skin substitutes.
A role for Notch signaling in corneal wound healing
Authors: Ma Aihua , Zhao Bojun , Boulton Mike , Albon Julie
Published: December 2010

To identify the role of the Notch signaling pathway in corneal wound healing, rat corneas receiving either epithelial or stromal wounds were placed in organ culture for up to 3 and 14 days, respectively. Localization of Notch receptors—Notch1, Notch2, and their ligands—Delta1, Jagged1 was determined by immunofluorescence. Wounds were treated with a γ‐secretase inhibitor to suppress Notch signaling or recombinant Jagged1 to enhance Notch signaling and morphological changes in the epithelium and stroma were recorded. The expressions of markers of cell proliferation (Ki67) and epithelial differentiation (cytokeratin 3) were assessed by immunohistology. Notch1 and Notch2 were localized to suprabasal epithelial cells in normal corneas. During corneal wound healing, both Notch receptors were detected in suprabasal and superficial epithelial layers. Delta1 and Jagged1 were observed throughout all corneal epithelial cell layers and occasional keratocytes of the stroma in normal and wounded corneas. γ‐secretase inhibition of Notch resulted in increased epithelial cell layers, with recombinant Jagged1 activation of Notch leading to a reduction in epithelial cell layers during corneal wound healing. Correspondingly, the activation of Notch resulted in a decreased cytokeratin 3 expression in the corneal epithelium, with no effect on cellular expression of Ki67. Notch signaling pathway suppressed corneal epithelial differentiation during corneal wound healing, but had no effect on epithelial cell proliferation.
Congenital Plaque‐Type Glomuvenous Malformations Associated with Fetal Pleural Effusion and Ascites
Authors: Goujon Elisa , Cordoro Kelly M. , Barat Muriel , Rousseau Thierry , Brouillard Pascal , Vikkula Miikka , Frieden Ilona J. , Vabres Pierre
Published: December 2010

Abstract:  Glomuvenous malformations are hereditary vascular anomalies, usually without extracutaneous involvement. We report two cases of extensive thoracic plaque‐type glomuvenous malformation in newborns who had previously been diagnosed in utero with pleural effusion and ascites, suggesting a pathogenic link between the two conditions.
Congenital Cutaneous Angioleiomyoma
Authors: OROZCO‐COVARRUBIAS LUZ , CARRASCO‐DAZA DANIEL , JULIAN‐GONZALEZ ROLANDO , SAEZ‐DE‐OCARIS MARIMAR , DURAN‐MCKINSTER CAROLA , PALACIOS‐LOPEZ CAROLINA , RUIZ‐MALDONADO RAMON
Published: December 2010

Abstract:  Congenital cutaneous angioleiomyoma is an extremely rare benign smooth muscle tumor. We present a case of a firm, painful subcutaneous mass noticed at birth on the left leg that on surgical excision proved to be an angioleiomyoma. Prognosis is good, and recurrences are uncommon. To our knowledge, this is the second report of a congenital angioleiomyoma.
Storage characteristics of cord blood progenitor cells: report of a multicenter study by the cellular therapies team of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Authors: Pamphilon Derwood , Curnow Elinor , Belfield Helen , Reems Jo‐Anna , McMannis John , Lecchi Lucilla , Szczepiorkowski Zbigniew , McKenna David
Published: December 2010

BACKGROUND: Most hematopoietic progenitor cell (HPC) products are infused or processed shortly after collection, but in some cases this may be delayed for up to 48 hours. A number of variables such as temperature and cell concentration are of critical importance for the integrity of HPCs during this time.

STUDY DESIGN AND METHODS: We evaluated critical variables using cord blood HPC units that were divided equally and stored at 4°C versus room temperature (RT) for up to 96 hours. Total nucleated cell (TNC) and mononuclear cell (MNC) counts, viable CD34+ cell counts, and CD45+ cell viability as well as colony‐forming unit–granulocyte‐macrophage (CFU‐GM) present over time at each temperature were determined.

RESULTS: Overall, the data indicate that with the exception of viable CD34+ cells, there was a significant decrease in each variable measured for 72 to 96 hours and, with the exception of viable CD34+ cells and CFU‐GM, the reductions were significantly greater in RT units than 4°C units. There was an increase in viable CD34+ count for units where TNC count was greater than 8.5 × 109/L, compared with units where TNC count was less than 8.5 × 109/L, that was different for each storage temperature.

CONCLUSIONS: Cord blood HPC collections maintained at 4°C retained higher TNC counts, MNC counts, and CD45+ cell viability over a 72‐ to 96‐hour storage period.
Investigation of heparin‐related hypotensive adverse events during photopheresis: utility of a patient care database
Authors: McPherson Richard A. , Buckler Aileen G. , Sanford Kimberly W. , Roseff Susan D.
Published: December 2010

BACKGROUND:Extracorporeal photopheresis (ECP) is a procedure in which leukocytes are harvested from a patient's whole blood, treated with a DNA binding dye and ultraviolet light to inactivate lymphocytes, and then returned into the patient's circulation. In January 2008, we observed moderately severe anaphylactoid reactions in eight of 16 patients undergoing ECP.

CASE STUDY:Each affected individual exhibited hypotension of sudden onset, usually with tachycardia, during the return of heparin‐anticoagulated blood at the end of the first cycle of collection of leukocytes. A systematic investigation of possible contributing factors revealed that all reactions were associated with administration of a single new lot of heparin.

RESULTS:Changing to a different manufacturer of heparin eliminated the occurrence of further such hypotensive reactions during ECP. Although the symptoms were initially attributed to vasovagal reactions or dehydration, their temporal association with exposure to a new lot of heparin suggested a procedure‐related phenomenon. Of particular note, was the finding that of the eight patients who had reactions at any time, six had initial exposures without reactions, suggesting a process of sensitization.

CONCLUSION:This study demonstrated the value of a patient database listing lot numbers of all medications and components used in each routine ECP procedure for facilitating rapid determination of common patient exposures, making it easier to determine the cause of adverse events, in this case, a particular lot of heparin responsible for the hypotensive adverse events.
Assessing the functional importance of large‐bodied invertebrates in experimental headwater streams
Authors: Lecerf Antoine , Richardson John S.
Published: December 2010

Recent theoretical advances in food web ecology emphasize the importance of body size disparities among species for the structure, stability and functions of ecosystems. Experimental confirmations of the functional importance of large species, independent of their trophic position, are scarce. We specifically examine the multiple ecological roles of large invertebrates from two distinct trophic levels in headwater streams. We experimentally manipulated the presence of large predatory invertebrates (two Perlid stoneflies) or detritivores (a limnephilid caddisfly and aPteronarcysstonefly) in a two‐by‐two design in stream channels open to immigration/emigration of smaller biota. We assessed treatment effects on the trophic structure of the benthic invertebrate community, dynamics of basal resources (benthic algae and leaf litter of cedar and alder), and stability of litter decomposition rates against an experimental pulse perturbation (fine sediment input). The presence of the large invertebrates was associated with a ten‐fold decrease in the biomass of invertebrate filterers whereas other trophic groups were unaffected by the large species. The biomass of benthic algae was lower and the rate of mass loss of alder litter was higher in channels lacking the large predators, thus revealing trophic cascades operating along both algal‐based and detritus‐based food chains. The large predators had no detectable effect on the decomposition of cedar whereas both cedar and alder disappeared faster in the presence of the large detritivores. Furthermore, the large predators and large detritivores interactively influenced the decomposition of the cedar–alder mixture through a litter diversity effect and the variability of the rate of alder decomposition after a pulse of fine sediment. Because the large invertebrates affected multiple ecosystem properties, and as their absence was not rapidly compensated for by small immigrant species, our findings support the notion that large species could be critically important in controlling ecosystem structure and functioning.
Expression Profiling of Cassava Storage Roots Reveals an Active Process of Glycolysis/GluconeogenesisF
Authors: Yang Jun , An Dong , Zhang Peng
Published: December 2010

Mechanisms related to the development of cassava storage roots and starch accumulation remain largely unknown. To evaluate genome‐wide expression patterns during tuberization, a 60 mer oligonucleotide microarray representing 20 840 cassava genes was designed to identify differentially expressed transcripts in fibrous roots, developing storage roots and mature storage roots. Using a random variance model and the traditional twofold change method for statistical analysis, 912 and 3 386 upregulated and downregulated genes related to the three developmental phases were identified. Among 25 significantly changed pathways identified, glycolysis/gluconeogenesis was the most evident one. Rate‐limiting enzymes were identified from each individual pathway, for example, enolase, L‐lactate dehydrogenase and aldehyde dehydrogenase for glycolysis/gluconeogenesis, and ADP‐glucose pyrophosphorylase, starch branching enzyme and glucan phosphorylase for sucrose and starch metabolism. This study revealed that dynamic changes in at least 16% of the total transcripts, including transcription factors, oxidoreductases/transferases/hydrolases, hormone‐related genes, and effectors of homeostasis. The reliability of these differentially expressed genes was verified by quantitative real‐time reverse transcription‐polymerase chain reaction. These studies should facilitate our understanding of the storage root formation and cassava improvement.
γ-rays and the far-infrared–radio continuum correlation reveal a powerful Galactic Centre wind
Authors: Crocker R. M. , Jones D. I. , Aharonian F. , Law C. J. , Melia F. , Ott J.
Published: December 2010

We consider the thermal and non-thermal emission from the inner 200 pc of the Galaxy. The radiation from this almost starburst-like region is ultimately driven dominantly by ongoing massive star formation. We show that this region's radio continuum (RC) emission is in relative deficit with respect to the expectation afforded by the far-infrared–radio continuum correlation (FRC). Likewise we show that the region's γ-ray emission falls short of that expected given its star formation and resultant supernova rates. These facts are compellingly explained by positing that a powerful (400–1200 km s−1) wind is launched from the region. This wind probably plays a number of important roles including advecting positrons into the Galactic bulge thus explaining the observed ∼kpc extension of the 511 keV positron annihilation signal around the GC. We also show that the large-scale GC magnetic field falls in the range ∼100–300 μG and that – in the time they remain in the region – GC cosmic rays do not penetrate into the region's densest molecular material.
Tails of the unexpected: the interaction of an isothermal shell with a cloud
Authors: Pittard J. M.
Published: December 2010

A new mechanism for the formation of cometary tails behind dense clouds or globules is discussed. Numerical hydrodynamical models show that when a dense shell of swept-up matter overruns a cloud, material in the shell is focused behind the cloud to form a tail. This mode of tail formation is completely distinct from other methods, which involve either the removal of material from the cloud or shadowing from a strong, nearby source of ionization. This mechanism is relevant to the cometary tails seen in planetary nebulae and to the interaction of superbubble shells with dense clouds.
Removal of River‐Stage Fluctuations from Well Response Using Multiple Regression
Authors: Spane Frank A. , Mackley Rob D.
Published: December 2010

Many contaminated unconfined aquifers are located in proximity to river systems. In groundwater studies, the physical presence of a river is commonly represented as a transient‐head boundary that imposes hydrologic responses within the intersected unconfined aquifer. The periodic fluctuation of river‐stage height at the boundary produces associated responses within the adjacent aquifer system, the magnitude of which is a function of the existing well, aquifer, boundary conditions, and characteristics of river‐stage fluctuations. The presence of well responses induced by the river stage can significantly limit characterization and monitoring of remedial activities within the stress‐impacted area. This article demonstrates the use of a time‐domain, multiple‐regression, convolution (superposition) method to develop well/aquifer river response function (RRF) relationships. Following RRF development, a multiple‐regression deconvolution correction approach can be applied to remove river‐stage effects from well water‐level responses. Corrected well responses can then be analyzed to improve local aquifer characterization activities in support of optimizing remedial actions, assessing the area‐of‐influence of remediation activities, and determining mean groundwater flow and contaminant flux to the river system.