bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial risk analysis of the association between attention‐deficit/hyperactivity disorder and psychoactive substance use disorder in female adolescents: a controlled study
Authors: Biederman Joseph , Petty Carter R. , Monuteaux Michael C. , Mick Eric , Clarke Allison , Ten Haagen Kristina , Faraone Stephen V.
Published: March 2009

Background:  A robust and bi‐directional comorbidity between attention‐deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD, alcohol or drug abuse, or dependence) has been consistently reported in the literature. However, this literature has been based almost exclusively on male only samples and, therefore, the findings may not generalize to females.

Methods:  First‐degree relatives from a large sample of pediatrically and psychiatrically referred girls with (123 probands, 403 relatives) and without ADHD (112 probands, 359 relatives) were comprehensively assessed by blind raters with structured diagnostic interviews. Familial risk analysis examined the risks in first‐degree relatives for ADHD and PSUD (alcohol or drug abuse or dependence) after stratifying probands by the presence and absence of these disorders.

Results:  ADHD in the proband significantly increased the risk for ADHD in relatives independently of the comorbidity with PSUD. PSUD in the proband was associated with a significantly increased risk for PSUD in relatives regardless of ADHD status. There was no evidence of co‐segregation or non‐random mating in the families of probands with ADHD and PSUD.

Conclusions:  Patterns of familial risk analysis suggest that the association between ADHD and PSUD in adolescent females is most consistent with the hypothesis that these disorders are independently transmitted, although the hypothesis of variable expressivity could not be ruled out. These findings are consistent with previously reported patterns of familial associations between ADHD and PSUD found in adolescent males. Longer follow‐up periods are needed to more fully clarify the relationship between ADHD and PSUD, as well as provide adequate power for separate analyses of alcohol and drug use.
Construct validity of the Capacity Profile in preschool children with cerebral palsy
Authors: MEESTER‐DELVER ANKE , BEELEN ANITA , KETELAAR MARJOLIJN , HADDERS‐ALGRA MIJNA , NOLLET FRANS , GORTER JAN WILLEM
Published: March 2009

The Capacity Profile (CAP) classifies additional care needs, subdivided into five domains of body functions (physical health, motor, sensory, mental, and voice/speech) of children with stable conditions. Construct validity of the CAP was established in 72 children (56 males, 16 females) with cerebral palsy (CP); median age 2 years 7 months, range 2 years 6 months to 3 years; 34 unilateral and 37 bilateral spastic‐type CP, one dyskinetic‐type CP. Gross Motor Function Classification System (GMFCS) classification was 24 in level I, eight in level II, 18 in level III, 14 in level IV, and eight in level V. All CAP domains were significantly associated (p<0.001) with the Functional Skills (rho=−0.42 to −0.85) and Caregiver Assistance scales (rho=−0.42 to −0.82) of the Dutch Paediatric Evaluation of Disability Inventory. The CAP‐motor domain and GMFCS were strongly correlated (rho=0.91, p<0.001). Stepwise regression analysis demonstrated that the CAP domains contributed 74% to mobility (CAP‐motor 66%, mental 6%, voice 2%); 75% to self‐care (CAP‐voice 61%, mental 12%, physical 2%); and 70% to social functionality (CAP‐mental 68%, voice 2%). CAP demonstrated good construct validity in young children with CP. The independent contribution of CAP domains to daily function underscores the importance of comprehensive assessment with regard to all domains of body functions in heterogeneous conditions like CP.
Cognitive visual dysfunctions in preterm children with periventricular leukomalacia
Authors: FAZZI ELISA , BOVA STEFANIA , GIOVENZANA ALESSIA , SIGNORINI SABRINA , UGGETTI CARLA , BIANCHI PAOLO
Published: March 2009

Aim  Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology.

Method  We studied 22 children born preterm (12 males, 10 females; mean age at examination 8y, range 6–15y; mean gestational age 30wks, range 28–36wks) with periventricular leukomalacia, spastic diplegia, normal intelligence (mean Full‐scale IQ 84; mean Verbal IQ 97; mean Performance IQ 74), and normal visual acuity, focusing on higher visual functions. Brain magnetic resonance images (MRI) were analysed to establish the presence of lesions along the primary optic pathway, in the occipitoparietal and occipitotemporal regions.

Results  Most children displayed an uneven cognitive profile, with deficits in visual object recognition, visual imagery, visual–spatial skills, and visual memory, and sparing of visual associative abilities, non‐verbal intelligence, and face and letter recognition. Conventional brain MRI did not document major alterations of parietal and temporal white matter, or cortical alteration of areas involved in visual associative functions.

Interpretation  We suggest a widespread involvement of higher visual processing systems, involving both the ventral and dorsal streams, in preterm children with periventricular leukomalacia. The lack of major alterations on conventional MRI does not exclude the possibility of malfunctioning of higher visual processing systems, expressing itself through discrete CVDs. Possible mechanisms underlying these neuropsychological deficits are discussed.
Clinical Risk Index for Babies score for the prediction of neurodevelopmental outcomes at 3 years of age in infants of very low birthweight
Authors: LODHA ABHAY , SAUVÉ REG , CHEN SOPHIE , TANG SELPHEE , CHRISTIANSON HEATHER
Published: March 2009

Aim  In this study, we evaluated the Clinical Risk Index for Babies ‐ revised (CRIB‐II) score as a predictor of long‐term neurodevelopmental outcomes in preterm infants at 36 months’ corrected age.

Method  CRIB‐II scores, which include birthweight, gestational age, sex, admission temperature, and base excess, were recorded prospectively on all infants weighing 1250g or less admitted to the neonatal intensive care unit (NICU). The sensitivity and specificity of CRIB‐II scores to predict poor outcomes were examined using receiver operating characteristic curves, and predictive accuracy was assessed using the area under the curve (AUC), based on the observed values entered on a continuous scale. Poor outcomes were defined as death or major neurodevelopmental disability (cerebral palsy, neurosensory hearing loss requiring amplification, legal blindness, severe seizure disorder, or cognitive score >2SD below the mean for adjusted age determined by clinical neurological examination and on the Wechsler Preschool and Primary Scale of Intelligence, Bayley Scales of Infant Development, or revised Leiter International Performance Scale).

Results  Of the 180 infants admitted to the NICU, 155 survived. Complete follow‐up data were available for 107 children. The male:female ratio was 50:57 (47–53%), median birthweight was 930g (range 511–1250g), and median gestational age was 27 weeks (range 23–32wks). Major neurodevelopmental impairment was observed in 11.2% of participants. In a regression model, the CRIB‐II score was significantly correlated with long‐term neurodevelopmental outcomes. It predicted major neurodevelopmental impairment (odds ratio [OR] 1.57, bootstrap 95% confidence interval [CI] 1.26–3.01; AUC 0.84) and poor outcome (OR 1.46; bootstrap 95% CI 1.31–1.71, AUC 0.82) at 36 months’ corrected age.

Interpretation  CRIB‐II scores of 13 or more in the first hour of life can reliably predict major neurodevelopmental impairment at 36 months’ corrected age (sensitivity 83%; specificity 84%).
Presence of α7 nicotinic acetylcholine receptors on dorsal root ganglion neurons proved using knockout mice and selective α‐neurotoxins in histochemistry
Authors: Shelukhina Irina V. , Kryukova Elena V. , Lips Katrin Susanne , Tsetlin Victor I. , Kummer Wolfgang
Published: March 2009

In complex tissues where multiple subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed, immunohistochemistry has been the most popular tool for investigation of nAChR subunit distribution. However, recent studies with nAChR subunit knockout mice demonstrated that a large panel of antibodies is unsuitable. Thus, we aimed to develop a histochemical method for selective labeling of α7 nAChR with neurotoxins, utilizing α7 nAChR‐transfected cells, dorsal root ganglia (DRG) and spinal cord from wild‐type and knockout mouse. The specificity of Alexa Fluor 488‐conjugated α‐bungarotoxin (Alexa‐αBgt) was demonstrated in binding to α7‐transfected cells inhibited by long‐chain α‐cobratoxin (CTX), but not short‐chain α‐neurotoxin II (NTII). In contrast, binding toTorpedomuscle‐type nAChRs and to motor end plates in mouse tongue sections was prevented by both CTX and NTII. In tissue sections of DRG, expressing all neuronal nAChR subunits, only CTX precluded Alexa‐αBgt labeling of neurons, with no staining for α7 nAChR knockout tissue. It proved that α7 nAChRs are the major αBgt‐binding sites in mouse DRG. Corresponding results were obtained for terminals in the spinal cord. Thus, we present a protocol utilizing Alexa‐αBgt and non‐labeled CTX/NTII that allows specific histochemical detection of α7 nAChR with a spatial resolution at the level of single axon terminals.
MigClim: Predicting plant distribution and dispersal in a changing climate
Authors: Engler Robin , Guisan Antoine
Published: March 2009

Aim  Many studies have forecasted the possible impact of climate change on plant distributions using models based on ecological niche theory, but most of them have ignored dispersal‐limitations, assuming dispersal to be either unlimited or null. Depending on the rate of climatic change, the landscape fragmentation and the dispersal capabilities of individual species, these assumptions are likely to prove inaccurate, leading to under‐ or overestimation of future species distributions and yielding large uncertainty between these two extremes. As a result, the concepts of ‘potentially suitable’ and ‘potentially colonizable’ habitat are expected to differ significantly. To quantify to what extent these two concepts can differ, we developed MigClim, a model simulating plant dispersal under climate change and landscape fragmentation scenarios. MigClim implements various parameters, such as dispersal distance, increase in reproductive potential over time, landscape fragmentation or long‐distance dispersal.

Location  Western Swiss Alps.

Methods  Using our MigClim model, several simulations were run for two virtual species by varying dispersal distance and other parameters. Each simulation covered the 100‐year period 2001–2100 and three different IPCC‐based temperature warming scenarios were considered. Results of dispersal‐limited projections were compared with unlimited and no‐dispersal projections.

Results  Our simulations indicate that: (1) using realistic parameter values, the future potential distributions generated using MigClim can differ significantly (up to more than 95% difference in colonized surface) from those that ignore dispersal; (2) this divergence increases under more extreme climate warming scenarios and over longer time periods; and (3) the uncertainty associated with the warming scenario can be as large as the one related to dispersal parameters.

Main conclusions  Accounting for dispersal, even roughly, can importantly reduce uncertainty in projections of species distribution under climate change scenarios.
Of scales, networks and assemblages: the League of Nations apparatus and the scalar sovereignty of the Government of India
Authors: Legg Stephen
Published: March 2009

Whilst greatly valuing recent critiques of the vertical imaginary and reified ontology of scale theory, and of the unfettered flows of network theory, this paper argues against a human geography without scale. Rather, four propositions from the theoretical literature are used to provide a tool‐kit to analyse the practical negotiation of scalar politics, namely that: scales should be considered as effects, not frames or structures, of practice; networks must be considered in all their complexity and heterogeneity; networks can be interpreted as assemblages, the more re‐territorialising and re‐scaling of which can be analysed as apparatuses; and that state apparatuses work to create the impression that scales are ahistorical, hierarchical and possess exclusive relationships. These propositions are used to explore a period of history when the scalar constitution of the world was under intense debate. The interwar era saw the imperial scale clash with that of the international, both as ideological worldviews, and as a series of interacting institutions. The assemblages of internationalism and imperialism were embodied by apparatuses such as the League of Nations and the colonial Government of India respectively. Attempts by the League to encourage the abolition of tolerated brothels in an attempt to reduce the trafficking of women and children led to intense debates between the 1920s and 1930s over what constituted the legitimate domains of the international and the ‘domestic’. These explicitly scalar debates were the product of League networks that threatened the scalar sovereignty of the Raj, most directly through the travelling Commission of Enquiry into Traffic in Women and Children in the East in 1931.
Survivin is upregulated during liver regeneration in rats and humans and is associated with hepatocyte proliferation
Authors: Baba Hideo A. , Wohlschlaeger Jeremias , Schmitz Klaus J. , Nadalin Silvio , Lang Hauke , Benesch Alexandra , Gu Yanli , Biglarnia Ali‐R , Sotiropoulos Georgios C. , Takeda Atsushi , Takeda Nobuakira , Von Wnuck Lipinski Karen , Levkau Bodo
Published: March 2009

Background: Survivin regulates cell division and inhibits apoptosis. Liver regeneration is a complex process involving both proliferation and apoptosis. The role of survivin is not well elucidated and no data exist in humans.

Methods: Seventy per cent liver resection was used to investigate liver regeneration in rats. Survivin was identified by means of reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemistry. Proliferation and apoptosis were quantified. Liver biopsies from 33 patients who underwent living donor liver transplantation were used to study survivin immuno‐expression, proliferation and apoptosis within the first 17 days after transplantation. Seven healthy donors served as controls.

Results: Survivin transcript and protein were significantly upregulated in rat hepatocytes after 24–72 h during regeneration and showed a significant correlation with proliferation but not with apoptosis. In humans, survivin was nearly absent in donor and reperfused liver tissue but increased significantly 5–7 days after transplantation and correlated with proliferation but not with apoptosis.

Conclusions: Survivin is upregulated in human and rodent liver regeneration and correlates with proliferation, suggesting an association of survivin and cell division.
Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies
Authors: Tandon Puneeta , Garcia‐Tsao Guadalupe
Published: March 2009

Background: Although there are many studies of the predictors of death in hepatocellular carcinoma (HCC), most combine patients with and without cirrhosis and many combine those with compensated and decompensated cirrhosis.

Objective: To perform a systematic review of the literature evaluating the predictors of death in patients with cirrhosis and HCC and to evaluate whether the predictors differ between patients with compensated and decompensated cirrhosis.

Methods: Inclusion criteria: (i) publication in English, (ii) adult patients, (c) >80% of the patients had cirrhosis, (iv) follow‐up >6 months and (v) multivariable analysis. Quality was based on the accepted quality criteria for prognostic studies.

Results: Of the 1106 references obtained, 947 were excluded because they did not meet the inclusion criteria. A total of 23 968 patients were included in 72 studies (median, 177/study); 77% male, median age 64, 55% Child–Pugh class A. The most robust predictors of death were portal vein thrombosis, tumour size, α‐foetoprotein and Child–Pugh class. Sensitivity analysis using only 15 ‘good’ studies and 22 studies in which all patients had cirrhosis yielded the same variables. In the studies including mostly compensated or decompensated patients, the predictors were both liver and tumour related. However, these studies were few and the results were not robust.

Conclusions: This systematic review of 72 studies shows that the most robust predictors of death in patients with cirrhosis and HCC are tumour related and liver related. Future prognostic studies should include these predictors and should be performed in specific patient populations to determine whether specific prognostic indicators are more relevant at different stages of cirrhosis.
Urea Breath Test in Children: The United States Prospective, Multicenter Study
Authors: Elitsur Yoram , Tolia Vasundhara , Gilger Mark A. , Reeves‐Garcia Jesse , Schmidt‐Sommerfeld Eberhard , Opekun Antone R. , El‐Zimaity Hala , Graham David Y. , Enmei Kyoko
Published: March 2009

Background: The urea breath test (UBT) is generally considered the gold standard for the diagnosis of Helicobacter pylori infections in adults.

Goals: To investigate the utility and accuracy of urea breath testing in children from the United States.

Methods: Children scheduled to undergo upper gastrointestinal endoscopy for various clinical symptoms underwent a 13C‐UBT using the US standard protocol for adults. Results were compared with rapid urease testing (RUT), culture, and histology. H. pylori positivity was defined according to the FDA, Division of Anti‐Infective Drug Products criteria, i.e. positive culture and/or positive RUT and histology. H. pylori negativity was defined as all tests negative. Results were evaluated by delta over baseline (DOB) and urea hydrolysis rate (UHR).

Results: A total of 176 children from five centers were evaluated; 48 were infected. Compared to the defined standard, the results with the UBT based on delta over baseline (DOB) cut‐off value (positive: ≥ 2.4‰) showed that the sensitivity and specificity of the UBT were 97.9% and 96.1%, respectively. Based on the UHR cut‐off value (positive: ≥ 10.0 µg/min), the sensitivity and specificity were 95.8% and 99.2%. In young children (2‐ to 5‐year olds), sensitivity and specificity of UHR method were higher than the DOB method (100% and 100% vs 100% and 82.4%, respectively).

Conclusion: The US standard 13C‐UBT proved to be both simple and accurate for the diagnosis of H. pylori infections in children. The UHR method to calculate of 13C‐UBT result provided excellent results for children of all ages.
The Prevalence, Characteristics of and Risk Factors for Eczema in Belgian Schoolchildren
Authors: Govaere Elke , Van Gysel Dirk , Verhamme Katia M.C. , Doli Erenik , Oranje Arnold P. , De Baets Frans
Published: March 2009

Abstract:  Childhood eczema is common in infants, but its nature and extent during later childhood remains unclear. In this cross‐sectional study we examined the prevalence and characteristics of eczema in an unbiased community population of 2,021 Belgian schoolchildren, aged 3.4 to 14.8 years with skin prick testing and parental questionnaires. Our study identified an eczema prevalence of 23.3% and a considerable allergic co‐morbidity, mainly in sensitized children. The reported prevalence of eczema in infancy was 18.5% and for current eczema 11.6%. The overall sensitization rate (33.2%) as well as sensitization rates for the individual allergens were significantly higher in children with “eczema ever.” Sensitization to Dermatophagoides pteronyssinus (19.6%), mixed grass pollen (15.1%), and cat (9.1%) were most common. Until the age of 6 years, boys with eczema were significantly more sensitized than girls (p = 0.007). Children with both eczema in infancy and current eczema show a tendency to be more sensitized than children with eczema in infancy only or current eczema only, but significance was only noted for a few individual allergens. Analysis of factors associated with eczema revealed a predominantly atopic profile characterized by family or personal history of allergy. Breastfeeding and environmental factors seemed to assume little relevance except for a protective effect of prematurity and having a dog at birth.
Clinical neurophysiology with special reference to the electroencephalogram
Authors: Zifkin Benjamin G. , Avanzini Giuliano
Published: March 2009

In the nineteenth and early twentieth centuries, many important discoveries in nervous system structure and function involved the electrical properties of nerve tissue. The application of these advances, as well as those in electronic amplification and recording, led to the discovery of the human electroencephalogram (EEG) by Hans Berger, a German psychiatrist. Originally received with skepticism, the EEG became a subject of intense interest, and after World War II, became a leading clinical and experimental tool in neurology. Today, it remains important especially in the study and treatment of epilepsy. Though the EEG has also given rise to more sophisticated applications, these remain based on Berger’s initial work, one of the great discoveries of medical history.
Service Provision for the Global Economy: The Evolving Indian Experience
Authors: Dossani Rafiq , Kenney Martin
Published: March 2009

Since 1995, the offshoring of services to India has rapidly evolved from a curiosity only studied by a few scholars to a phenomenon portending a major shift in the geography of global economic activity. The article examines the evolution of Indian global services provision quantitatively and qualitatively through the use of four case studies. The first case study examines the challenge that the Indian information technology systems integrators (ITSIs) pose to the formerly larger—but now roughly comparable in terms of employment—incumbent developed‐nation ITSIs. Because IT systems have become central to nearly every enterprise, the second case study illustrates the wide variety of enterprises that now have significant Indian offshore operations. The third case study describes the rapid growth of offshore integrated circuit design in India, a nation with now commercial‐scale integrated circuit production. The final case study describes the emergence of high‐opportunity entrepreneurial startups in India and the increasing number of Silicon Valley startups that very early in their lives or even as part of their business model have significant operations in India. The concluding discussion situates India within the global economy and speculates upon its future evolution.
The Services Transformation and Network Policy: The New Logic of Value Creation1
Authors: Kushida Kenji E. , Zysman John
Published: March 2009

There is currently a fundamental transformation of services, a transformation central to the growth of productivity and competition in the global economy. This transformation, a response to commodification generated by decomposition of production and intensified competition in global markets, is driven by developments in IT tools, the uses they are being put to, and the networks they run on. The service transformation is changing how firms add value, affecting the underlying economic activity in countries around the world.

This article introduces the notion of the services transformation, placing it in the historical context of production and competition, noting the advent of the Internet as a critical building block. Second, we consider national strategies for capturing value in this new era. The experiences of Japan and Korea, successful in deploying high‐speed IT networks, but facing unexpected challenges in using them to capture value, highlight several features of the services transformation.
A Melanesian Pygmalion: Masculine Creativity and Symbolic Castration in a Postcolonial Backwater
Authors: Lipset David
Published: March 2009

AbstractIn the early 1990s, a piece of folk theater was created by a Sepik male cult. A kind of Melanesian Pygmalion story, the new show brought a beautiful woman to life, a woman who answered the desire of which “her” creator had been deprived. Like Pygmalion's woman, “she” acknowledged her creator's emasculation while celebrating the enduring spectacle of “his” art. The new show exemplified that in the Sepik, some marginalized, or subaltern, men were imagining their gender around a void that I argue took the symbolic shape of the Lacanian signifier, a castrated phallus. Attachment to waning enchantments of, and entitlements afforded by, precapitalist masculinities, and the diffidence this attachment entailed about modernity, precipitated an ambivalent subject. Men longed for their signifying virility, mostly lost, but never really possessed in the first place, by inventing objects of desire. These objects simulated the continued presence of the symbol of their wounded masculinity, a symbol whose meanings were contradictory. The objects embodied disaffection and disconnection from modernity as well as a pleasure men took from what they created. “Woyon's Mother” was a mode of masculine creativity that constituted one‐half of an ambivalent answer to postcolonial modernity in Papua New Guinea. [creativity, masculinity, Lacan, postcolonial Papua New Guinea, Sepik, Murik]
Side by Side: Learning by Observing and Pitching In
Authors: Paradise Ruth , Rogoff Barbara
Published: March 2009

AbstractThis article examines cultural practices that support informal learning as children observe and pitch in with everyday activities that are integrated into family and community life. We discuss the social and cultural grounding of this learning tradition, drawing on research carried out in different parts of the world during more than 60 years. Children learn by watching, listening, and attending, often with great concentration, by taking purposeful initiative, and by contributing and collaborating. We try to correct the frequent misconception that this way of learning is essentially a nonverbal process by showing that speech is commonly used, but judiciously, in support of efficient communication rather than for “lessons.” This learning tradition is not in opposition to school learning; children with schooling experience learn this way when they belong and experience community. [informal learning, cultural practices, socialization, observation, family and community learning]
Heterogeneity of systemic inflammatory responses to periodontal therapy
Authors: Behle Jan H. , Sedaghatfar Michael H. , Demmer Ryan T. , Wolf Dana L. , Celenti Romanita , Kebschull Moritz , Belusko Paul B. , Herrera‐Abreu Miriam , Lalla Evanthia , Papapanou Panos N.
Published: March 2009

Aims: We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers.

Material and Methods: Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6‐week period. Blood samples were obtained at: 1‐week pre‐therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed the plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analysed using checkerboard hybridizations.

Results: At T3, PAI‐1, sE‐selectin, sVCAM‐1, MMP‐9, myeloperoxidase, and a composite summary inflammatory score (SIS) were significantly reduced. However, only sE‐selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced a marked reduction and a pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis.

Conclusions: Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further.
Regulation of interferon and Toll‐like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms
Authors: Hu Xiaoyu , Chakravarty Soumya D. , Ivashkiv Lionel B.
Published: March 2009

Summary: Activated macrophages and their inflammatory products play a key role in innate immunity and in pathogenesis of autoimmune/inflammatory diseases. Macrophage activation needs to be tightly regulated to rapidly mount responses to infectious challenges but to avoid toxicity associated with excessive activation. Rapid and potent macrophage activation is driven by cytokine‐mediated feedforward loops, while excessive activation is prevented by feedback inhibition. Here we discuss feedforward mechanisms that augment macrophage responses to Toll‐like receptor (TLR) ligands and cytokines that are mediated by signal transducer and activator of transcription 1 (STAT1) and induced by interferon‐γ (IFN‐γ). IFN‐γ also drives full macrophage activation by inactivating feedback inhibitory mechanisms, such as those mediated by interleukin‐10 (IL‐10), and STAT3. Priming of macrophages with IFN‐γ reprograms cellular responses to other cytokines, such as type I IFNs and IL‐10, with a shift toward pro‐inflammatory STAT1‐dominated responses. Similar but partially distinct priming effects are induced by other cytokines that activate STAT1, including type I IFNs and IL‐27. We propose a model whereby opposing feedforward and feedback inhibition loops crossregulate each other to fine tune macrophage activation. In addition, we discuss how dysregulation of the balance between feedforward and feedback inhibitory mechanisms can contribute to the pathogenesis of autoimmune and inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus.
OPTIMIZATION OF NEW FLOUR IMPROVER MIXING FORMULA BY SURFACE RESPONSE METHODOLOGY
Authors: GHORBEL RAOUDHA ELLOUZE , KAMOUN AMEL , NEIFAR MOHAMED , CHAABOUNI SEMIA ELLOUZE
Published: March 2009

In the present study, we search to improve the viscoelastic properties of wheat flour characterized by a low bread‐making quality. Six regulators were tested: broad bean flour, gluten, monodiglyceride (MDG), ascorbic acid, sodium alginate and a mixture of amylase and xylanase. A hybrid design was carried out in order to study the effect of these regulators on the alveographic properties of wheat flour dough. Two alveographic responses (W: deformation energy and P/L: elasticity‐to‐extensibility ratio) were studied and simultaneously optimized via the desirability functions. An optimal mixture, containing 13.17 g/kg of broad bean flour, 15.13 g/kg of gluten, 0.155 g/kg of ascorbic acid, 3.875 g/kg of MDG, 2.75 g/kg of sodium alginate and 0.3 g/kg of enzyme mixture, was obtained and tested in a Tunisian flour. It led to a dough characterized by a W = 274 × 10−4 J and P/L = 0.74 versus 191 × 10−4 J and 0.40, respectively, for the Tunisian flour without improvers.

PRACTICAL APPLICATIONS

In this work, we developed a new flour improver mixing formula intended to be used with wheat flour characterized by a low bread‐making quality. This improver mixture is in powder form and contains 13.17 g of broad bean flour, 15.13 g of gluten, 0.155 g of ascorbic acid, 3.875 g of monodiglyceride, 2.75 g of sodium alginate and 0.3 g of enzyme mixture per kilogram of wheat flour. The incorporation of this improver mixture in low bread‐making quality wheatflour leads to an increase of its deformation energy (W) of about 43% and produces large volume bread.
Devices and Desires: How Useful Is the ‘New’ New Economic Sociology for Understanding Market Attachment?
Authors: Mcfall Liz
Published: March 2009

This article explores the usefulness of recent economic sociology literature for understanding processes of market attachment. It focuses particularly on concepts like agencement and market devices proposed by authors like Michel Callon, Fabian Muniesa and Franck Cochoy and their application to mass consumer markets. The article addresses critical responses which have been levelled at this literature to argue that despite what some regard as an overly descriptive and apolitical banality, this may in fact be a prime and necessary virtue.
Omega‐3 Fatty Acids in Depression: A Review of Three Studies
Authors: Osher Yamima , Belmaker R. H.
Published: March 2009

We review three studies of omega‐3 fatty acids in the treatment of depression that were carried out by our research group at the Beer Sheva Mental Health Center. The first study examined eicosapentaenoic acid (EPA) versus placebo as an adjunct to antidepressant treatment in 20 unipolar patients with recurrent major depression. The second study used omega‐3 fatty acids in childhood major depression; 28 children aged 6–12 were randomized to omega‐3 fatty acids or placebo as pharmacologic monotherapy. The third study was an open‐label add‐on trial of EPA in bipolar depression. Twelve bipolar outpatients with depressive symptoms were treated with 1.5–2.0 g/day of EPA for up to 6 months. In the adult unipolar depression study, highly significant benefits were found by week 3 of EPA treatment compared with placebo. In the child study, an analysis of variance (ANOVA) showed highly significant effects of omega‐3 on each of the three rating scales. In the bipolar depression study, 8 of the 10 patients who completed at least 1 month of follow‐up achieved a 50% or greater reduction in Hamilton depression (Ham‐D) scores within 1 month. No significant side effects were reported in any of the studies. Omega‐3 fatty acids were shown to be more effective than placebo for depression in both adults and children in small controlled studies and in an open study of bipolar depression. (This review discusses three studies, all from our group, completed before the clinical trial registry was initiated.)
Pressure Drop in Rectangular Microchannels as Compared With Theory Based on Arbitrary Cross Section
Authors: Akbari Mohsen , Sinton David , Bahrami Majid
Published: March 2009

Pressure driven liquid flow through rectangular cross-section microchannels is investigated experimentally. Polydimethylsiloxane microchannels are fabricated using soft lithography. Pressure drop data are used to characterize the friction factor over a range of aspect ratios from 0.13 to 0.76 and Reynolds number from 1 to 35 with distilled water as working fluid. Results are compared with the general model developed to predict the fully developed pressure drop in arbitrary cross-section microchannels. Using available theories, effects of different losses, such as developing region, minor flow contraction and expansion, and streaming potential on the measured pressure drop, are investigated. Experimental results compare well with the theory based on the presure drop in channels of arbitrary cross section.
The Effects of Inlet Geometry and Gas-Liquid Mixing on Two-Phase Flow in Microchannels
Authors: Kawaji M. , Mori K. , Bolintineanu D.
Published: March 2009

The effects of gas-liquid inlet geometry and mixing method on adiabatic gas-liquid two-phase flow in a microchannel of 100 μm diameter have been investigated using a T-junction inlet with the same internal diameter as the microchannel. Two-phase flow patterns, void fraction, and friction pressure drop data obtained with the T-junction inlet were found to be significantly different from those obtained previously with a reducer inlet. For the T-junction inlet, the two-phase flow patterns in the microchannel were predominantly intermittent flows with short gas and liquid plugs/slugs flowing with nearly equal velocities. The void fraction data then conformed nearly to that of a homogeneous flow model, and the two-phase friction multiplier data could be described by the Lockhart–Martinelli correlation applicable to larger channels. However, when a reducer inlet was used previously and the diameter of the inlet section was much larger than that of the microchannel, an intermittent flow of long gas slugs separated by long liquid slugs became prevalent and the void fraction decreased to values far below the homogeneous void fraction. The differences in the two-phase flow characteristics between a T-junction inlet and reducer inlet were attributed to the differences in the gas bubble/slug generation mechanisms.
ADHESION STRENGTH OF TiN COATINGS AT VARIOUS ION ETCHING DEPOSITED ON TOOL STEELS USING CATHODIC ARC PVD TECHNIQUE
Authors: ALI MUBARAK , HAMZAH ESAH , ALI NOUMAN
Published: March 2009

Titanium nitride ( TiN ) widely used as hard coating material was coated on tool steels, namely on high-speed steel (HSS) and D2 tool steel by physical vapor deposition method. The goal of this study was to examine the effect of ion etching with and without titanium ( Ti ) and chromium ( Cr ) on the adhesion strength of TiN coatings deposited on tool steels. From the scratch tester, it was observed that by increasing Ti ion etching showed an increase in adhesion strength of the deposited coatings. The coatings deposited with Cr ion etching showed poor adhesion compared with the coatings deposited with Ti ion etching. Scratch test measurements showed that the coating deposited with titanium ion etching for 16 min is the most stable coating and maintained even at the critical load of 66 N. The curve obtained via penetration depth along the scratch trace is linear in the case of HSS, whereas is slightly flexible in the case of D2 tool steel. The coatings deposited on HSS exhibit better adhesion compared with those on D2 tool steel.
INFLUENCE OF Al MONOLAYERS ON THE PROPERTIES OF AlN LAYERS ON Si (111)
Authors: CHUAH L. S. , HASSAN Z. , ABU HASSAN H.
Published: March 2009

High-quality aluminum nitride ( AlN ) layers with full width at half maximum (FWHM) values of 11 arcmin were grown by plasma-assisted molecular-beam epitaxy on Si (111) substrates. AlN nucleation layers are being investigated for the growth of GaN on Si . Growth using AlN buffer layers leads to Al -polar films, with surfaces strongly dependent on the flux conditions used. Flat surfaces can be obtained by growing as Al -rich as possible, although Al droplets tend to form. Before starting the AlN growth, a few monolayers of Al are deposited on the substrate to avoid the formation of Si 3 N 4. X-ray diffraction (XRD) techniques were employed to determine the surface and structural quality of the layers. XRD revealed that monocrystalline AlN was obtained. Best AlN films were obtained at high substrate temperatures (875°C) and III/V ratios close to stoichiometry.
GraphClust: A Method for Clustering Database of Graphs
Authors: Reforgiato Diego , Gutierrez Rodrigo , Shasha Dennis
Published: March 2009

Any application that represents data as sets of graphs may benefit from the discovery of relationships among those graphs. To do this in an unsupervised fashion requires the ability to find graphs that are similar to one another. That is the purpose of GraphClust. The GraphClust algorithm proceeds in three phases, often building on other tools:

(1) it finds highly connected substructures in each graph;

(2) it uses those substructures to represent each graph as a feature vector; and

(3) it clusters these feature vectors using a standard distance measure. We validate the cluster quality by using the Silhouette method. In addition to clustering graphs, GraphClust uses SVD decomposition to find frequently co-occurring connected substructures. The main novelty of GraphClust compared to previous methods is that it is application-independent and scalable to many large graphs.
Stimulus-Specific and Stimulus-Nonspecific Firing Synchrony and Its Modulation by Sensory Adaptation in the Whisker-to-Barrel Pathway
Authors: Khatri Vivek , Bruno Randy M. , Simons Daniel J.
Published: March 2009

The stimulus-evoked response of a cortical neuron depends on both details of the afferent signal and the momentary state of the larger network in which it is embedded. Consequently, identical sensory stimuli evoke highly variable responses. Using simultaneous recordings of thalamic barreloid and/or cortical barrel neurons in the rat whisker-to-barrel pathway, we determined the extent to which the responses of pairs of cells covary on a trial-by-trial basis. In the thalamus and cortical layer IV, a substantial component of trial-to-trial variability is independent of the specific parameters of the stimulus, probed here using deflection angle. These stimulus-nonspecific effects resulted in greater-than-chance similarities in trial-averaged angular tuning among simultaneously recorded pairs of barrel neurons. Such effects were not observed among simultaneously recorded thalamic and cortical barrel neurons, suggesting strong intracortical mechanisms of synchronization. Sensory adaptation produced by prior whisker deflections reduced response magnitudes and enhanced the joint angular tuning of simultaneously recorded neurons. Adaptation also decorrelated stimulus-evoked responses, rendering trial-by-trial responses of neuron pairs less similar to each other. Adaptation-induced decorrelation coupled with sharpened joint tuning could enhance the saliency of cells within thalamus or cortex that continue to fire synchronously during ongoing tactile stimulation associated with active touch.
RasV12-Mediated Down-regulation of CCAAT/Enhancer Binding Protein β in Immortalized Fibroblasts Requires Loss of p19Arf and Facilitates Bypass of Oncogene-Induced Senescence
Authors: Sebastian Thomas , Johnson Peter F.
Published: March 2009

The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) is involved in cellular responses to oncogenic and physiologic Ras signals. C/EBPβ is required for premature senescence of primary mouse fibroblasts induced by expression of H-RasV12, demonstrating its role in oncogene-induced senescence. Here, we have investigated the mechanisms by which Ras inhibits proliferation of normal cells but transforms immortalized cells. We show that oncogenic Ras down-regulates C/EBPβ expression in NIH 3T3 cells, which are immortalized by a deletion of the CDKN2A locus and, therefore, lack the p16Ink4a and p19Arf tumor suppressors. RasV12-induced silencing of C/EBPβ occurred at the mRNA level and involved both the Raf–mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase–ERK and phosphatidylinositol 3-kinase signaling pathways. Oncogenic Ras decreased C/EBPβ expression in Ink4a/Arf−/− mouse embryo fibroblasts (MEF) but increased C/EBPβ levels in wild-type MEFs. C/EBPβ down-regulation in NIH 3T3 cells was reversed by expression of p19Arf, but not of p53 or p16Ink4a, highlighting a critical role for p19Arf in sustaining C/EBPβ levels. Ectopic expression of p34 C/EBPβ (LAP) inhibited RasV12-mediated transformation of NIH 3T3 cells, suppressed their tumorigenicity in nude mice, and reactivated expression of the proapoptotic Fas receptor, which is also down-regulated by Ras. Our findings indicate that Cebpb gene silencing eliminates a growth inhibitory transcription factor that would otherwise restrain oncogenesis. We propose that C/EBPβ is part of a p53-independent, p19Arf-mediated network that enforces Ras-induced cell cycle arrest and tumor suppression in primary fibroblasts. [Cancer Res 2009;69(6):2588–98]
The Potential Role of Systemic Buffers in Reducing Intratumoral Extracellular pH and Acid-Mediated Invasion
Authors: Silva Ariosto S. , Yunes Jose A. , Gillies Robert J. , Gatenby Robert A.
Published: March 2009

A number of studies have shown that the extracellular pH (pHe) in cancers is typically lower than that in normal tissue and that an acidic pHe promotes invasive tumor growth in primary and metastatic cancers. Here, we investigate the hypothesis that increased systemic concentrations of pH buffers reduce intratumoral and peritumoral acidosis and, as a result, inhibit malignant growth. Computer simulations are used to quantify the ability of systemic pH buffers to increase the acidic pHe of tumors in vivo and investigate the chemical specifications of an optimal buffer for such purpose. We show that increased serum concentrations of the sodium bicarbonate (NaHCO3) can be achieved by ingesting amounts that have been used in published clinical trials. Furthermore, we find that consequent reduction of tumor acid concentrations significantly reduces tumor growth and invasion without altering the pH of blood or normal tissues. The simulations also show that the critical parameter governing buffer effectiveness is its pKa. This indicates that NaHCO3, with a pKa of 6.1, is not an ideal intratumoral buffer and that greater intratumoral pHe changes could be obtained using a buffer with a pKa of ∼7. The simulations support the hypothesis that systemic pH buffers can be used to increase the tumor pHe and inhibit tumor invasion. [Cancer Res 2009;69(6):2677–84]
CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection
Authors: Pavelko Kevin D. , Hansen Michael J. , Pease Larry R.
Published: March 2009

Vaccine strategies for cancer immunotherapy have focused on peptide ligands with high affinity for MHC class I. Largely, these vaccines have not been therapeutic. We have examined the peptide specificity of a strongly protective T-cell response that eradicates established B16 melanoma and find that the recognized epitope is generated by a low-affinity MHC class I ligand from tyrosinase-related protein 1 (TRP1). Cytotoxic T-cell responses are induced against TRP1222-229 by several vaccination schemes using a Toll-like receptor agonist, T regulatory cell depletion, or the immune modulator B7-DCXAb to drive immunity. TRP1222 CTL are generated from multiple antigen sources, including antigens expressed by tumors growing in situ, tumor cell lysates, and peptide vaccines. The key finding in this study is that protection from freshly implanted or established B16 tumors is primarily mediated by TRP1222-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gp100. This finding challenges the assumption that the optimal peptide antigens for cancer vaccines are high-affinity MHC ligands. We propose that when administered appropriately, native low-affinity MHC ligands are optimal inducers of immunotherapeutic CTL. [Cancer Res 2009;69(7):3114–20]