bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Landscape of the Pharmaceutical Management Education in India
Authors: Hasan Habib , Sharma Kavya , Zodpey Sanjay
Published: August 2012

Pharmaceutical management is a cross cutting domain across health care systems and the pharmaceutical industry. Also, higher education in pharmaceuticals lies at cross-roads between health and technical education. This has created enormous opportunities for developing synergistic and symbiotic relationships between academic institutions and the pharmaceutical industry for developing human resource trained in various domains of the pharmaceutical. However, there is limited information and data regarding educational institutions offering training in pharmaceuticals as well as supply of human resources trained in pharmaceuticals. This research article intends to fill the above mentioned research gap and stimulate discussion around various pertinent issues like regulation, accreditation and benchmarking of various educational programmes in pharmaceutical management.
Influence of Positive Affect on Physical Health and Psychological Well-Being: Examining the Mediating Role of Psychological Resilience
Authors: Nath Papri , Pradhan Rabindra Kumar
Published: August 2012

The present article examines the mediating role of psychological resilience in the relationship of positive affect with physical health and psychological well-being. The sample consists of 146 engineering, management and research students with an age range of 17–32 years (M = 22.93, SD = 3.67). Survey method was opted for data collection. Standard psychometric tools were used for collecting data on positive affect, psychological resilience, physical health, and psychological well-being. Positive affect was measured on the ‘Positive Negative Affectivity Scale’ (PANAS) constructed by Watson, Clark and Tellegen (1988). The ‘Ego Resiliency Scale’ by Block and Kremen (1996) was used to measure psychological resilience. Physical health and psychological well-being was assessed on the multi-dimensional health questionnaire proposed by Snell and Johnson (1997) and the psychological well-being scale by Ryff and Keyes (1995), respectively. The results revealed that psychological resilience significantly mediates between positive affect, and physical health and psychological well-being. The theoretical and practical implications of the study are discussed in the light of empirical findings.
Occupational Health Hazards: A Study of Bus Drivers
Authors: Bhatt Bindu , Seema M.S.
Published: August 2012

Health has always been closely linked with occupation. Sound health in relation to vocation and employment is the most important aspect of the very life of an individual who works and to the society as a whole. Occupational hazards natural in the work environment have become more prominent in the post-industrial societies. These include a wide range of health problems ranging from asthma, heart attack, high blood pressure, stress and other psychological disorders, with many more to list. Occupational health is therefore, an aspect seeking attention at the individual, group and community levels. The related study deals with ergonomics—a link between the worker and his working environment. This would have impact on the body and discomfort reflected in various parts of the body bringing about certain health problems.

The present article is an attempt to explore the health hazards among the bus drivers and conductors employed in State Road Transport Corporations. The attempt is directed at investigating risk factors at micro-level in a community of drivers and conductors. It not only establishes the link between health and work environment but also facilitates in assessing the adverse impacts that may be expected.
Knowledge Gaps, Belief Gaps, and Public Opinion about Health Care Reform
Authors: Hindman Douglas Blanks
Published: August 2012

This study tests hypotheses regarding the distribution of beliefs and knowledge about health care reform. The belief gap hypothesis suggests that in an era of political polarization, self-identification as a Democrat or Republican would be a better predictor of knowledge and beliefs about politically contested issues than would one’s educational level. Findings show that gaps in beliefs and knowledge regarding health care reform between Republicans and Democrats grew, and gaps based on educational levels disappeared.
‘We’re not programmed, we’re people’: Figuring the caring computer
Authors: Stoate Robin
Published: August 2012

This article intervenes in feminist theories concerning the politics of care, reading this contested notion through its representation in an ‘artificial’ relationship between a human clone and a computer in the science fiction film Moon (dir. Duncan Jones, 2009). Drawing on Joan Tronto’s work (1993), I delineate a conventional, vernacular conception of care, which puts in place problematic, prescriptive roles in caring relationships. Then, reading Moon through Donna Haraway’s theorisation of companion species (2008) and what she terms the ‘touching’ of material histories and contingencies, I show how these hierarchies may be unravelled. This figure of the caring computer represents a capacity for affective impact upon human subjects that is not normally ascribed to ‘emotionless’ technological subjects. It animates a disruption of the linear, instrumental relationships of power between humans and technologies by showing the ways in which ongoing processes of co-constitution are responsible for bringing each participant in the relationship into being. Care here is a manner of activating and making conspicuous those processes and can unravel, rather than prescribe, the roles which respective participants in such relationships are assigned.
Touching, unbelonging, and the absence of affect
Authors: Khanna Ranjana
Published: August 2012

This article argues that psychoanalytic notions of affect – including ideas of anxiety and melancholia, as well as deconstructive concepts of auto-affection – offer a feminist ethico-politics and a notion of affect as interface. Beyond the confines of the experiential and the positivist, both psychoanalysis and deconstruction provide insights into affect as a technology that understands the subject as porous. I consider works by Derek Jarman and Shirin Neshat to demonstrate the importance of the ethico-politics of affect as interface in contemporary cultural production. Both artists, in the process of considering the spectacular nature of notions of feminist and queer, use images of interface as a way of delimiting the spectacular nature of being and demonstrating the singularity of the event, the desire to fix through framing, and the parergonal nature of framing. The presence of the subject is questioned even as an auto-affection is suggestive of a spectral demand of the ethico-political. In the case of Jarman’s Blue, the denial of image as face in favour of the screen as interface is interrupted by sound and voice, which gesture toward representation as impossible but necessary. In the case of Neshat, the persistence of the photographic – the highly aesthetic self-portrait as mugshot – foregrounds face as interface, as one that questions presence through the insistence of a representational apparatus.
Prevalence and control of dyslipidaemia among diabetic patients with microalbuminuria in a Chinese hospital
Authors: Wang Shao-hua , Wang Lu , Zhou Yi , Guo Yi-jing , Yuan Yang , Li Feng-fei , Huang Yan , Xia Wen-qing
Published: August 2012

Background:

Accumulating evidence indicates that dyslipidaemia plays an important role in the progression of kidney disease in patients with diabetes. Hyperlipidaemia is a risk factor for microalbuminuria in patients with diabetes. Little information exists on the prevalence and control of dyslipidaemia among diabetic patients with microalbuminuria in China. The aims of this study were to investigate the prevalence and control of dyslipidaemia among diabetic patients with microalbuminuria in a Chinese hospital as well as factors affecting the disease.

Methods:

A total of 1060 type 2 diabetic inpatients were assigned to the with-microalbuminuria group ( n = 635) or the without-microalbuminuria group on the basis of urinary albumin-to-creatinine ratios (UACRs = 30–299 mg/g). Serum levels and the control of lipid profiles were assessed and classified according to the 2011 American Diabetes Association (ADA) guidelines, and low-density lipoprotein–cholesterol (LDL-C) was also assessed and classified according to Chinese intensified control criteria. Multiple regression analyses were performed to examine the factors affecting lipid variables.

Results:

Among patients with microalbuminuria, a significantly lower prevalence was found (33.1% vs. 58.6%; 35.3% vs. 52.5%, all p < 0.001) at target levels [LDL-C < 2.60 mmol/L or high-density lipoprotein–cholesterol (HDL-C) > 1.0 mmol/L for men and >1.3 mmol/L for women]. According to the intensified LDL-C goal (<2.07 mmol/L), a lower prevalence was found in male patients (15.5% vs. 32.7%, p < 0.001). Fewer patients with microalbuminuria were adherent to the therapy prescribed for dyslipidaemia (28.8% vs. 43.3%, p < 0.001). Even among patients who were on lipid-lowering treatment, the majority of individuals remained uncontrolled for all three lipid fractions [LDL-C, HDL-C and triglyceride (TG)] (82.5% vs. 69.0%, p = 0.003). Lipid and lipoprotein parameters were associated with gender and age.

Conclusion:

In China, diabetic patients with microalbuminuria displayed typical dyslipidaemias and were not adequately controlled. Intensified LDL-C and overall lipid-lowering clinical goals are potential precautions taken against diabetic nephropathy.
Neurodiversity
Authors: Mcgee Micki
Published: August 2012

The neurodiversity movement emerged as an extension of the disability rights movement to include the those individuals with neurological differences. Micki McGee posits that neurodiversity is also a response to the neoliberalism of the past three decades that has (1) shifted responsibility for individuals with neurological and cognitive challenges back to the family, and (2) fostered a crippling speed-up in our workplaces while simultaneously requiring new levels of sociability and flexibility that render more people debilitated or disabled. The article concludes that demands for the rights of neurologically diverse populations may challenge the very framework of liberal personhood.
Telling Stories about Rosa Parks
Authors: Schudson Michael
Published: August 2012

Rosa Parks has usually been portrayed as a highly principled but non-political person, not the long-time civil rights activist that she was. Sociologist Michael Schudson finds several factors that account for this, including efforts of civil rights movement participants to deflect criticism of the movement as instigated by outside agitators; participants’ efforts to explain their own actions to themselves; and their efforts not to present themselves immodestly as morally superior.
Marriage Goes to School
Authors: Avishai Orit , Heath Melanie , Randles Jennifer
Published: August 2012

In recent years, policy efforts to alleviate poverty have focused on marriage and relationship education. Orit Avishai’s, Melanie Heath’s,and Jennifer Randles’s research finds that efforts to address poverty via relationship skills training are misguided because this approach does not address the structural causes of poverty.
But Madame, We Are French Also
Authors: Beaman Jean
Published: August 2012

Based on participant observation and interviews in the Parisian metropolitan region, sociologist Jean Beaman discusses middle-class and upwardly-mobile children of North African immigrants in France, who despite their upward mobility feel just as marginalized as other children of immigrants.
Small Town, Big Totem
Authors: King Colby , Cazessus Matthew
Published: August 2012

The documentary “World’s Largest” explores how dozens of small towns throughout the United States build colossal and quirky sculptures celebrating local culture and place identity. Colby King and Matthew Cazessus provide a deeper look into these shrinking communities and explain how these sculptures work to maintain a sense of community and reaffirm local place identity in the face of dramatic demographic changes and economic uncertainty.
Immigrant Dreams
Authors: Radhakrishnan Smitha
Published: August 2012

Sociologist Smitha Radhakrishnan reviews the books The Managed Hand and The New Entrepreneurs. Each illustrates the opportunity and systematic discrimination faced by immigrant entrepreneurs in the United States. These works push us to reconsider the importance of minority business owners in continuing to make the American dream real for all of us.
Rethinking Sexual Violence
Authors: Whittier Nancy
Published: August 2012

Sociologist Nacy Whittier reviews the books Sex Panic and the Punitive State, At the Dark End of the Street, and Unspeakable. Each differently addresses sexual violence in relation to race, class, and criminalization.
Teaching a Hip-Hop Ecology
Authors: Cermak Michael J.
Published: August 2012

Sociologist Michael J. Cermak discusses what he learned while teaching environmental science with hip-hop in urban public high schools. This article provides an applied perspective of teaching at the crux of social justice and the environment.
When History Intervenes
Authors: Kimmel Michael
Published: August 2012

Sociologists tend to downplay the role of accidents, circumstance, serendipity, and luck. This essay describes three times that history derailed Michael Kimmel’s research agenda, and how he “recovered.”
Endovascular Treatment
Authors: Aburto-Murrieta Yolanda , Marquez-Romero Juan M. , Bonifacio-Delgadillo Dulce , López Iván , Hernández-Curiel B.
Published: August 2012

Cerebral vasospasm (CV) accounts significant morbimortality after aneurysmal subarachnoid hemorrhage. The objective of this study was to compare the clinical outcome of patients with CV treated by 2 endovascular procedures: intra-arterial nimodipine angioplasty (IANA) and balloon angioplasty (BA). Between 2008 and June 2011, we performed 22 IANA and 8 BA in 30 patients. The mean age was 44 years and 60% was female. In 17 patients, the treatment was clipping, whereas 13 underwent coil treatment. The CV was severe in 63%, moderate in 30%, and mild in 7%. Good outcome between 2 groups was similar ( P = .36). The clinical outcome according to the subgroups of CV severity and modality treatment was equivalent ( P = .22). Mortality at 3 months was 16% and 20% at 1 year. We did not find differences in the clinical outcome despite the fact that both techniques produce adequate angiographic resolution of CV.
Framing narratives: Opening sequences in contemporary American and British war films
Authors: Pötzsch Holger
Published: August 2012

This article analyses the function of opening sequences in war films. With reference to Erll’s studies on film and memory, the author suggests that, besides initiating processes of framing film worlds, opening sequences also activate a certain memory-making rhetoric that enables potential impacts on historical discourse and memory politics. He subdivides this last function into three rhetorical modes of cultural memory – an objectifying, subjective and reflexive approach. Subsequently, the author provides close readings of the opening sequences of various contemporary war films to exemplify and illustrate each function and rhetorical mode. In conclusion, the author connects a recent surge in films employing a subjective and reflexive rhetoric to changes in imaging technologies.
Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia
Authors: Robak Tadeusz , Windyga Jerzy , Trelinski Jacek , von Depka Prondzinski Mario , Giagounidis Aristoteles , Doyen Chantal , Janssens Ann , Álvarez-Román María Teresa , Jarque Isidro , Loscertales Javier , Rus Gloria Pérez , Hellmann Andrzej , Jêdrzejczak Wiesław Wiktor , Kuliczkowski Kazimierz , Golubovic Lana M. , Celeketic Dusica , Cucuianu Andrei , Gheorghita Emanuil , Lazaroiu Mihaela , Shpilberg Ofer , Attias Dina , Karyagina Elena , Svetlana Kalinina , Vilchevska Kateryna , Cooper Nichola , Talks Kate , Prabhu Mukhyaprana , Sripada Prasad , Bharadwaj T. P. R. , Næsted Henrik , Skartved Niels J. Ø. , Frandsen Torben P. , Flensburg Mimi F. , Andersen Peter S. , Petersen Jørgen
Published: August 2012

Rozrolimupab, a recombinant mixture of 25 fully human RhD-specific monoclonal antibodies, represents a new class of recombinant human antibody mixtures. In a phase 1 or 2 dose escalation study, RhD+ patients (61 subjects) with primary immune thrombocytopenia received a single intravenous dose of rozrolimupab ranging from 75 to 300 μg/kg. The primary outcome was the occurrence of adverse events. The principal secondary outcome was the effect on platelet levels 7 days after the treatment. The most common adverse events were headache and pyrexia, mostly mild, and reported in 20% and 13% of the patients, respectively, without dose relationship. Rozrolimupab caused an expected transient reduction of hemoglobin concentration in the majority of the patients. At the dose of 300 μg/kg platelet responses, defined as platelet count ≥ 30 × 109/L and an increase in platelet count by > 20 × 109/L from baseline were observed after 72 hours and persisted for at least 7 days in 8 of 13 patients (62%). Platelet responses were observed within 24 hours in 23% of patients and lasted for a median of 14 days. Rozrolimupab was well tolerated and elicited rapid platelet responses in patients with immune thrombocytopenia and may be a useful alternative to plasma-derived products. This trial is registered at www.clinicaltrials.gov as #NCT00718692.
Genomic variation in the vomeronasal receptor gene repertoires of inbred mice
Authors: Wynn Elizabeth H , Sánchez-Andrade Gabriela , Carss Keren J , Logan Darren W
Published: August 2012

Background

Vomeronasal receptors (VRs), expressed in sensory neurons of the vomeronasal organ, are thought to bind pheromones and mediate innate behaviours. The mouse reference genome has over 360 functional VRs arranged in highly homologous clusters, but the vast majority are of unknown function. Differences in these receptors within and between closely related species of mice are likely to underpin a range of behavioural responses. To investigate these differences, we interrogated the VR gene repertoire from 17 inbred strains of mice using massively parallel sequencing.

Results

Approximately half of the 6222 VR genes that we investigated could be successfully resolved, and those that were unambiguously mapped resulted in an extremely accurate dataset. Collectively VRs have over twice the coding sequence variation of the genome average; but we identify striking non-random distribution of these variants within and between genes, clusters, clades and functional classes of VRs. We show that functional VR gene repertoires differ considerably between different Mus subspecies and species, suggesting these receptors may play a role in mediating behavioural adaptations. Finally, we provide evidence that widely-used, highly inbred laboratory-derived strains have a greatly reduced, but not entirely redundant capacity for differential pheromone-mediated behaviours.

Conclusions

Together our results suggest that the unusually variable VR repertoires of mice have a significant role in encoding differences in olfactory-mediated responses and behaviours. Our dataset has expanded over nine fold the known number of mouse VR alleles, and will enable mechanistic analyses into the genetics of innate behavioural differences in mice.
Longitudinal in vitro surveillance of Plasmodium falciparum sensitivity to common anti-malarials in Thailand between 1994 and 2010
Authors: Parker Daniel , Lerdprom Rujira , Srisatjarak Wanna , Yan Guiyun , Sattabongkot Jetsumon , Wood James , Sirichaisinthop Jeeraphat , Cui Liwang
Published: August 2012

Background

Drug and multidrug-resistant Plasmodium falciparum malaria has existed in Thailand for several decades. Furthermore, Thailand serves as a sentinel for drug-resistant malaria within the Greater Mekong sub-region. However, the drug resistance situation is highly dynamic, changing quickly over time. Here parasite in vitro drug sensitivity is reported for artemisinin derivatives, mefloquine, chloroquine and quinine, across Thailand.

Methods

Blood was drawn from patients infected with P. falciparum in seven sentinel provinces along Thai international borders with Cambodia, Myanmar, Laos, and Malaysia. In vitro parasite sensitivity was tested using the World Health Organization’s microtest (mark III) (between 1994 and 2002) and the histidine-rich protein-2 (HRP2)-based enzyme-linked immunosorbent assay (in 2010). Following World Health Organization protocol, at least 30 isolates were collected for each province and year represented in this study. Where possible, t-tests were used to test for significant differences.

Results

There appears to be little variation across study sites with regard to parasite sensitivity to chloroquine. Quinine resistance appears to have been rising prior to 1997, but has subsequently decreased. Mefloquine sensitivity appears high across the provinces, especially along the north-western border with Myanmar and the eastern border with Cambodia. Finally, the data suggest that parasite sensitivity to artemisinin and its derivatives is significantly higher in provinces along the north-western border with Myanmar.

Conclusions

Parasite sensitivity to anti-malarials in Thailand is highly variable over time and largely mirrors official drug use policy. The findings with regard to reduced sensitivity to artemisinin derivatives are supported by recent reports of reduced parasite clearance associated with artemisinin. This trend is alarming since artemisinin is considered the last defence against malaria. Continued surveillance in Thailand, along with increased collaboration and surveillance across the entire Greater Mekong sub-region, is clearly warranted.
Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity
Authors: Klawitter Marina , Quero Lilian , Klasen Juergen , Gloess Alexia N , Klopprogge Babette , Hausmann Oliver , Boos Norbert , Wuertz Karin
Published: August 2012

Background

As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time.

Methods

Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann WhitneyUtest with a significance level of p < 0.05 (two-tailed).

Results

Results indicate that the curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK.

Conclusions

Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory propertiesin vitrolead to analgesiain vivowill need to be confirmed in an appropriate animal model.
Single dose oral dexamethasone versus multi-dose prednisolone in the treatment of acute exacerbations of asthma in children who attend the emergency department: study protocol for a randomized controlled trial
Authors: Cronin John , Kennedy Una , McCoy Siobhan , an Fhailí Sinéad Nic , Crispino-O’Connell Gloria , Hayden John , Wakai Abel , Walsh Sean , O’Sullivan Ronan
Published: August 2012

Background

Asthma is a major cause of pediatric morbidity and mortality. In acute exacerbations of asthma, corticosteroids reduce relapses, subsequent hospital admission and the need for ß2-agonist therapy. Prednisolone is relatively short-acting with a half-life of 12 to 36 hours, thereby requiring daily dosing. Prolonged treatment course, vomiting and a bitter taste may reduce patient compliance with prednisolone. Dexamethasone is a long-acting corticosteroid with a half-life of 36 to 72 hours. It is used frequently in children with croup and bacterial meningitis, and is well absorbed orally. The purpose of this trial is to examine whether a single dose of oral dexamethasone (0.3 mg/kg) is clinically non-inferior to prednisolone (1 mg/kg/day for three days) in the treatment of exacerbations of asthma in children who attend the Emergency Department.

Methods/design

This is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16 years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05.

Discussion

This clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment.

Registration

ISRCTN26944158 and EudraCT Number 2010-022001-18
Guiametabolica.org: empowerment through internet tools in inherited metabolic diseases
Authors: Armayones Manuel , Vilaseca M Antònia , Cutillas Júlia , Fàbrega Jordi , Fernández Jorge Juan , García Mei , Egea Natàlia , Pousada Modesta , Gómez-Zuñiga Beni , Pérez-Payarols Jaume , Artuch Rafael , Palau Francesc , Serrano Mercedes
Published: August 2012

Web-based interventions are effective on the patient empowerment. Guiametabolica.org constitutes an interface for people involved in inherited metabolic diseases, trying to facilitate access to information and contact with professionals and other patients, offering a platform to develop support groups. Guiametabolica.org is widely considered for Spanish-speaking patients and caregivers with inherited metabolic diseases. Preliminary evaluations show changes in their habits, decrease in their senses of isolation and improvement regarding self-efficacy. Specific inherited metabolic diseases websites, especially participative websites, should be considered as a complement to more traditional clinical approaches. Their contribution lies in patient’s general well-being, without interfering with traditional care.
Flux variability scanning based on enforced objective flux for identifying gene amplification targets
Authors: Park Jong Myoung , Park Hye Min , Kim Won Jun , Kim Hyun Uk , Kim Tae Yong , Lee Sang Yup
Published: August 2012

Background

In order to reduce time and efforts to develop microbial strains with better capability of producing desired bioproducts, genome-scale metabolic simulations have proven useful in identifying gene knockout and amplification targets. Constraints-based flux analysis has successfully been employed for such simulation, but is limited in its ability to properly describe the complex nature of biological systems. Gene knockout simulations are relatively straightforward to implement, simply by constraining the flux values of the target reaction to zero, but the identification of reliable gene amplification targets is rather difficult. Here, we report a new algorithm which incorporates physiological data into a model to improve the model’s prediction capabilities and to capitalize on the relationships between genes and metabolic fluxes.

Results

We developed an algorithm, flux variability scanning based on enforced objective flux (FVSEOF) with grouping reaction (GR) constraints, in an effort to identify gene amplification targets by considering reactions that co-carry flux values based on physiological omics datavia“GR constraints”. This method scans changes in the variabilities of metabolic fluxes in response to an artificially enforced objective flux of product formation. The gene amplification targets predicted using this method were validated by comparing the predicted effects with the previous experimental results obtained for the production of shikimic acid and putrescine inEscherichia coli. Moreover, new gene amplification targets for further enhancing putrescine production were validated through experiments involving the overexpression of each identified targeted gene under condition-controlled batch cultivation.

Conclusions

FVSEOF with GR constraints allows identification of gene amplification targets for metabolic engineering of microbial strains in order to enhance the production of desired bioproducts. The algorithm was validated through the experiments on the enhanced production of putrescine inE. coli, in addition to the comparison with the previously reported experimental data. The FVSEOF strategy with GR constraints will be generally useful for developing industrially important microbial strains having enhanced capabilities of producing chemicals of interest.
Direct integration of intensity-level data from Affymetrix and Illumina microarrays improves statistical power for robust reanalysis
Authors: Turnbull Arran K , Kitchen Robert R , Larionov Alexey A , Renshaw Lorna , Dixon J Michael , Sims Andrew H
Published: August 2012

Background

Affymetrix GeneChips and Illumina BeadArrays are the most widely used commercial single channel gene expression microarrays. Public data repositories are an extremely valuable resource, providing array-derived gene expression measurements from many thousands of experiments. Unfortunately many of these studies are underpowered and it is desirable to improve power by combining data from more than one study; we sought to determine whether platform-specific bias precludes direct integration of probe intensity signals for combined reanalysis.

Results

Using Affymetrix and Illumina data from the microarray quality control project, from our own clinical samples, and from additional publicly available datasets we evaluated several approaches to directly integrate intensity level expression data from the two platforms. After mapping probe sequences to Ensembl genes we demonstrate that, ComBat and cross platform normalisation (XPN), significantly outperform mean-centering and distance-weighted discrimination (DWD) in terms of minimising inter-platform variance. In particular we observed that DWD, a popular method used in a number of previous studies, removed systematic bias at the expense of genuine biological variability, potentially reducing legitimate biological differences from integrated datasets.

Conclusion

Normalised and batch-corrected intensity-level data from Affymetrix and Illumina microarrays can be directly combined to generate biologically meaningful results with improved statistical power for robust, integrated reanalysis.
A gene expression profile of stem cell pluripotentiality and differentiation is conserved across diverse solid and hematopoietic cancers
Authors: Palmer Nathan P , Schmid Patrick R , Berger Bonnie , Kohane Isaac S
Published: August 2012

Background

Understanding the fundamental mechanisms of tumorigenesis remains one of the most pressing problems in modern biology. To this end, stem-like cells with tumor-initiating potential have become a central focus in cancer research. While the cancer stem cell hypothesis presents a compelling model of self-renewal and partial differentiation, the relationship between tumor cells and normal stem cells remains unclear.

Results

We identify, in an unbiased fashion, mRNA transcription patterns associated with pluripotent stem cells. Using this profile, we derive a quantitative measure of stem cell-like gene expression activity. We show how this 189 gene signature stratifies a variety of stem cell, malignant and normal tissue samples by their relative plasticity and state of differentiation within Concordia, a diverse gene expression database consisting of 3,209 Affymetrix HGU133+ 2.0 microarray assays. Further, the orthologous murine signature correctly orders a time course of differentiating embryonic mouse stem cells. Finally, we demonstrate how this stem-like signature serves as a proxy for tumor grade in a variety of solid tumors, including brain, breast, lung and colon.

Conclusions

This core stemness gene expression signature represents a quantitative measure of stem cell-associated transcriptional activity. Broadly, the intensity of this signature correlates to the relative level of plasticity and differentiation across all of the human tissues analyzed. The fact that the intensity of this signature is also capable of differentiating histological grade for a variety of human malignancies suggests potential therapeutic and diagnostic implications.
Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion
Authors: Pereira Paulo N. G. , Dobreva Mariya P. , Maas Elke , Cornelis Frederique M. , Moya Iván M. , Umans Lieve , Verfaillie Catherine M. , Camus Anne , de Sousa Lopes Susana M. Chuva , Huylebroeck Danny , Zwijsen An
Published: August 2012

The strength and spatiotemporal activity of Nodal signaling is tightly controlled in early implantation mouse embryos, including by autoregulation and feedback loops, and involves secreted and intracellular antagonists. These control mechanisms, which are established at the extra-embryonic/embryonic interfaces, are essential for anterior-posterior patterning of the epiblast and correct positioning of the primitive streak. Formation of an ectopic primitive streak, or streak expansion, has previously been reported in mutants lacking antagonists that target Nodal signaling. Here, we demonstrate that loss-of-function of a major bone morphogenetic protein (BMP) effector, Smad5, results in formation of an ectopic primitive streak-like structure in mutant amnion accompanied by ectopic Nodal expression. This suggests that BMP/Smad5 signaling contributes to negative regulation of Nodal. In cultured cells, we find that BMP-activated Smad5 antagonizes Nodal signaling by interfering with the Nodal-Smad2/4-Foxh1 autoregulatory pathway through the formation of an unusual BMP4-induced Smad complex containing Smad2 and Smad5. Quantitative expression analysis supports that ectopic Nodal expression in the Smad5 mutant amnion is induced by the Nodal autoregulatory loop and a slow positive-feedback loop. The latter involves BMP4 signaling and also induction of ectopic Wnt3. Ectopic activation of these Nodal feedback loops in the Smad5 mutant amnion results in the eventual formation of an ectopic primitive streak-like structure. We conclude that antagonism of Nodal signaling by BMP/Smad5 signaling prevents primitive streak formation in the amnion of normal mouse embryos.
Principles and roles of mRNA localization in animal development
Authors: Medioni Caroline , Mowry Kimberly , Besse Florence
Published: August 2012

Intracellular targeting of mRNAs has long been recognized as a means to produce proteins locally, but has only recently emerged as a prevalent mechanism used by a wide variety of polarized cell types. Localization of mRNA molecules within the cytoplasm provides a basis for cell polarization, thus underlying developmental processes such as asymmetric cell division, cell migration, neuronal maturation and embryonic patterning. In this review, we describe and discuss recent advances in our understanding of both the regulation and functions of RNA localization during animal development.
Slit2 and Robo3 modulate the migration of GnRH-secreting neurons
Authors: Cariboni Anna , Andrews William D. , Memi Fani , Ypsilanti Athena R. , Zelina Pavol , Chedotal Alain , Parnavelas John G.
Published: August 2012

Gonadotropin-releasing hormone (GnRH) neurons are born in the nasal placode and migrate along olfactory and vomeronasal axons to reach the forebrain and settle in the hypothalamus, where they control reproduction. The molecular cues that guide their migration have not been fully identified, but are thought to control either cell movement directly or the patterning of their axonal substrates. Using genetically altered mouse models we show that the migration of GnRH neurons is directly modulated by Slit2 and Robo3, members of the axon guidance Slit ligand and Robo receptor families. Mice lacking Slit2 or Robo3 have a reduced number of GnRH neurons in the forebrain, but a normal complement of their supporting axons, pointing to a direct role for these molecules in GnRH neuron migration.
Germline potential of parthenogenetic haploid mouse embryonic stem cells
Authors: Leeb Martin , Walker Rachael , Mansfield Bill , Nichols Jenny , Smith Austin , Wutz Anton
Published: August 2012

Haploid embryonic stem cells (ESCs) have recently been derived from parthenogenetic mouse embryos and offer new possibilities for genetic screens. The ability of haploid ESCs to give rise to a wide range of differentiated cell types in the embryo and in vitro has been demonstrated. However, it has remained unclear whether haploid ESCs can contribute to the germline. Here, we show that parthenogenetic haploid ESCs at high passage have robust germline competence enabling the production of transgenic mouse strains from genetically modified haploid ESCs. We also show that differentiation of haploid ESCs in the embryo correlates with the gain of a diploid karyotype and that diploidisation is the result of endoreduplication and not cell fusion. By contrast, we find that a haploid karyotype is maintained when differentiation to an extra-embryonic fate is forced by induction of Gata6.
Price Discovery in the U.S. Treasury Market: Automation vs. Intermediation
Authors: Man Kasing , Wang Junbo , Wu Chunchi
Published: August 2012

This paper examines the contribution to price discovery by electronic and voice-based trading systems in the U.S. Treasury market. Evidence shows that the electronic trading system has more price discovery and that trading automation increases the speed of incorporating information into prices. However, human trading generates significant price discovery, though its volume is low. The relative contribution of a trading system to price discovery depends on liquidity, volatility, volume, trade size, and order imbalance. The voice-based trading system contributes more to price discovery when trade size is large and liquidity is low. These findings provide important implications for the design of electronic markets for securities with different characteristics and trading environments.

This paper was accepted by Wei Xiong, finance.
Living in a Global World: Influence of Consumer Global Orientation on Attitudes toward Global Brands from Developed versus Emerging Countries
Authors: Guo Xiaoling
Published: August 2012

Despite increasing attention to consumers in developing markets, few studies explicitly explore the psychological mechanisms underlying their attitudes toward global brands from developed versus developing countries. The author proposes that global orientation, including global consumption orientation and global identity, are key factors accounting for the attitude variance. The results of Studies 1 and 2 in China show that consumers’ global orientation positively influences their attitudes toward global brands of developed-country origin. In addition, ethnocentrism negatively influences their attitudes toward these brands, but this effect diminishes for consumers with high global identity. Study 3 strengthens these findings by ruling out the alternative explanation that imports, not global brands, drive such results. Finally, Study 4 indicates that Indian consumers yield a similar pattern to Chinese consumers with regard to the global orientation effect, but the study reveals a relatively weak influence of ethnocentrism.
The Innovator's License: A Latitude to Deviate from Category Norms
Authors: Barone Michael J. , Jewell Robert D.
Published: August 2012

Firms often look for ways to improve the return on investment they earn from costly innovation strategies. The authors investigate a previously unexplored benefit of innovation that occurs when a brand's reputation as a provider of valued new offerings allows it to earn innovation credit, a form of customer-based brand equity. Innovation credit provides brands with the license or latitude to use strategies that violate category norms without the penalty (in the form of impaired attitudes) that consumers are shown to levy on less innovative brands. Consistent with the proposed theoretical framework, three studies demonstrate that innovative brands are granted the license to employ nonnormative strategies without sanction. In addition to providing evidence regarding the inferential mechanism underlying this licensing effect, Study 3 shows that, under certain conditions, innovative brands not only escape the penalty associated with using atypical strategies but are actually rewarded for utilizing such approaches. The authors provide theoretical and managerial implications of these findings and suggestions for further research in this emerging area of innovation research.
How Doppelgänger Brand Images Influence the Market Creation Process: Longitudinal Insights from the Rise of Botox Cosmetic
Authors: Giesler Markus
Published: August 2012

Using actor-network theory from sociology, the author explores the creation of new markets as a brand-mediated legitimation process. Findings from an eight-year longitudinal investigation of the Botox Cosmetic brand suggest that the meanings of a new cosmetic self-enhancement technology evolve over the course of contestations between brand images promoted by the innovator and doppelgänger brand images promoted by other stakeholders. Each contestation addresses an enduring contradiction between nature and technology. A four-step brand image revitalization process is offered that can be applied either by managers interested in fostering an innovation's congruence with prevailing social norms and ideals or by other stakeholders (e.g., activists, competitors) interested in undermining its marketing success. The findings integrate previously disparate research streams on branding and market creation and provide managers with the conceptual tools for sustaining a branded innovation's legitimacy over time.
Creating Major Innovations with Customers: Insights from Small and Young Technology Firms
Authors: Coviello Nicole E. , Joseph Richard M.
Published: August 2012

The marketing literature typically argues that customers cannot easily be involved with, and contribute to, the creation of major innovation (MI). This article finds otherwise. The authors use an inductive process method to study how six MIs were developed for business-to-business markets by small and young technology firms. Three of the MIs were successful, and three failed. The firms with MI success are distinguished by a nonconventional new product development process that includes five iterative and overlapping activities and up to ten different customer roles. These activities and roles are captured in a multifaceted taxonomy of customer participation. The analysis also uncovers three capabilities relevant to the development of successful MI—capabilities that are effectual rather than adaptive in nature. These findings and the propositions derived from them offer a more complete understanding of customer participation, new product development across contexts, and marketing capabilities.
Employees’ Decision Making in the Face of Customers’ Fuzzy Return Requests
Authors: Wang Sijun , Beatty Sharon E. , Liu Jeanny
Published: August 2012

Frontline service employees frequently encounter customers’ fuzzy requests, defined as requests that are slightly or somewhat outside company policy but not completely unacceptable or detrimental to the company. Employees’ compliance decisions can profoundly affect customers, organizations, and employees themselves. However, the complex decision process in which service employees engage is largely unexplored. The authors draw from script and motivated reasoning theories, as well as qualitative interviews, to model employees’ responses to customers’ fuzzy requests in a retail setting. The results, which are based on a national survey of retail employees, indicate that employees with higher customer orientation and higher conflict avoidance tend to handle fuzzy return requests in a friendlier, more effortful manner, especially when customers demonstrate an affiliative style. In contrast, when customers display a dominant style, employees engage in motivated reasoning and perceive the request to be less legitimate, reducing their likelihood of complying. In addition, the employees’ perceived flexibility influences their compliance decisions, but punishment expectations do not. The authors conclude with some managerial implications, including better identification of these requests and more training of employees to handle them appropriately.
Principles and Principals: Do Customer Stewardship and Agency Control Compete or Complement When Shaping Frontline Employee Behavior?
Authors: Schepers Jeroen , Falk Tomas , de Ruyter Ko , de Jong Ad , Hammerschmidt Maik
Published: August 2012

This article introduces customer stewardship control (CSC) to the marketing field. This concept represents a frontline employee's felt ownership of and moral responsibility for customers’ overall welfare. In two studies, the authors show that CSC is a more encompassing construct than customer orientation, which reflects a frontline employee's focus on meeting customers’ needs. They provide evidence that the former is more potent in shaping in- and extra-role employee behaviors. Moreover, they highlight how CSC operates in conjunction with an organization's agency control system: Stewardship's positive influence on in- and extra-role behavior is weaker in the presence of high agency control. They offer actionable advice about how to solve the resulting managerial control dilemma. Finally, the authors show that CSC depends on drivers that reside at the individual level (employee relatedness), the team level (team competence), or both levels of aggregation (employee and team autonomy). These findings show how to effectively design a frontline employee's work environment to ensure optimal frontline performance.