bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Shigella sonnei in Malaysia, an increasingly prevalent etiologic agent of local shigellosis cases
Authors: Koh Xiu Pei , Chiou Chien Shun , Ajam Noni , Watanabe Haruo , Ahmad Norazah , Thong Kwai Lin
Published: May 2012

Background

Shigellosis is a major public health concern worldwide, especially in developing countries. It is an acute intestinal infection caused by bacteria of the genus Shigella, with a minimum infective dose as low as 10–100 bacterial cells. Increasing prevalence of Shigella sonnei as the etiologic agent of shigellosis in Malaysia has been reported. As there is limited information on the genetic background of S. sonnei in Malaysia, this study aimed to characterize Malaysian S. sonnei and to evaluate the prospect of using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for subtyping of local S. sonnei.

Methods

Forty non-repeat clinical strains of S. sonnei isolated during the years 1997–2000, and 2007–2009 were studied. The strains were isolated from stools of patients in different hospitals from different regions in Malaysia. These epidemiologically unrelated strains were characterized using biotyping, antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE) and MLVA.

Results

The two biotypes identified in this study were biotype a (n = 29, 73%) and biotype g (n = 11, 27%). All the 40 strains were sensitive to kanamycin, ceftriaxone and ciprofloxacin. Highest resistance rate was observed for streptomycin (67.5%), followed by tetracycline (40%) and trimethoprim-sulfamethoxazole (37.5%). All the S. sonnei biotype g strains had a core resistance type of streptomycin - trimethoprim-sulfamethoxazole - tetracycline whereas the 29 biotype a strains were subtyped into eight resistotypes. All the strains were equally distinguishable by PFGE and MLVA. Overall, PFGE analysis indicated that S. sonnei biotype a strains were genetically more diverse than biotype g strains. Cluster analysis by MLVA was better in grouping the strains according to biotypes, was reflective of the epidemiological information and was equally discriminative as PFGE.

Conclusions

The S. sonnei strains circulating in Malaysia throughout the period studied were derived from different clones given their heterogeneous nature. MLVA based on seven selected VNTR loci was rapid, reproducible and highly discriminative and therefore may complement PFGE for routine subtyping of S. sonnei.
The German fibromyalgia consumer reports – a cross-sectional survey
Authors: Häuser Winfried , Jung Eva , Erbslöh-Möller Brigitte , Gesmann Mechthild , Kühn-Becker Hedi , Petermann Franz , Langhorst Jost , Thoma Reinhard , Weiss Thomas , Wolfe Frederick , Winkelmann Andreas
Published: May 2012

Background

Consumer surveys provide information on effectiveness and side effects of medical interventions in routine clinical care. A report of fibromyalgia syndrome (FMS) consumers has not been carried out in Europe.

Methods

The study was carried out from November 2010 to April 2011. Participants diagnosed with FMS rated the effectiveness and side effects of pharmacological and non-pharmacological FMS interventions on a 0 to 10 scale, with 10 being most efficacious (harmful). The questionnaire was distributed by the German League for people with Arthritis and Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care.

Results

1661 questionnaires (95% women, mean age 54 years, mean duration since FMS diagnosis 6.8 years) were analysed. The most frequently used therapies were self-management strategies, prescription pain medication and aerobic exercise. The highest average effectiveness was attributed to whole body and local warmth therapies, thermal bathes, FMS education and resting. The highest average side effects were attributed to strong opioids, local cold therapy, gamma-amino-butyric acid analogues (pregabalin and gabapentin), tramadol and opioid transdermal systems.

Conclusion

The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS, and challenges the strong recommendations for drug therapies given by FMS-guidelines.
Hepatitis B assays in serum, plasma and whole blood on filter paper
Authors: Mayer Theodor K , Vargas Roberto L , Knebel Ann E , Williams Scott A , Culver Sean P , Clark Daniel M , King Louise R
Published: May 2012

Background

Screening and determining the immune status of individuals for hepatitis B is usually done by detecting hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen-specific antibodies (HBsAb). In some countries with the highest viral burden, performing these assays is currently impractical. This paper explores the use of filter paper as a blood specimen transport medium.

Methods

Samples, chosen from routine clinical laboratory pool, were applied and dried onto filter paper. Eluates, from the paper samples, were analyzed as routine clinical specimens on ADVIA Centaur 5634® immunoassay analyzers using the standard HBsAg and HBsAb kits. Dried blood samples were subjected to a range of environmental conditions in order to assess stability.

Results

After drying and elution the assays showed linearity and precision comparable to clinical assays performed on fresh serum. Elutions at various times during a 149 day incubation period showed very little variability in the Index numbers. All analytes were temperature stable except for a decrease in the HBsAg signal at 42°C.

Conclusions

Filter paper is an acceptable storage and transport medium for serum to be used in the detection of hepatitis B markers if atmospheric variability can be controlled. HBsAg, HBsAb and HBcAb are all stable for at least five months under storage conditions below room temperature. Drying specimens, particularly serum, on filter paper at remote locations, offers a reasonable solution to the problem of hepatitis surveillance in underdeveloped regions, although some attempt at temperature control might be desirable.
Optimization of fatty alcohol biosynthesis pathway for selectively enhanced production of C12/14 and C16/18 fatty alcohols in engineered Escherichia coli
Authors: Zheng Yan-Ning , Li Ling-Ling , Liu Qiang , Yang Jian-Ming , Wang Xiang-Wei , Liu Wei , Xu Xin , Liu Hui , Zhao Guang , Xian Mo
Published: May 2012

Background

With the increasing stress from oil price and environmental pollution, aroused attention has been paid to the microbial production of chemicals from renewable sources. The C12/14 and C16/18 alcohols are important feedstocks for the production of surfactants and detergents, which are widely used in the most respected consumer detergents, cleaning products and personal care products worldwide. Though bioproduction of fatty alcohols has been carried out in engineered E. coli, several key problems have not been solved in earlier studies, such as the quite low production of C16/18 alcohol, the lack of optimization of the fatty alcohol biosynthesis pathway, and the uncharacterized performance of the engineered strains in scaled-up system.

Results

We improved the fatty alcohol production by systematically optimizing the fatty alcohol biosynthesis pathway, mainly targeting three key steps from fatty acyl-acyl carrier proteins (ACPs) to fatty alcohols, which are sequentially catalyzed by thioesterase, acyl-coenzyme A (CoA) synthase and fatty acyl-CoA reductase. By coexpression of thioesterase gene BTE, acyl-CoA synthase gene fadD and fatty acyl-CoA reductase gene acr1, 210.1 mg/L C12/14 alcohol was obtained. A further optimization of expression level of BTE, fadD and acr1 increased the C12/14 alcohol production to 449.2 mg/L, accounting for 75.0% of the total fatty alcohol production (598.6 mg/L). In addition, by coexpression of thioesterase gene ‘tesA, acyl-CoA synthase gene fadD and fatty acyl-CoA reductase gene FAR, 101.5 mg/L C16/18 alcohol was obtained, with C16/18 alcohol accounting for 89.2% of the total fatty alcohol production.

Conclusions

To our knowledge, this is the first report on selective production of C12/14 and C16/18 alcohols by microbial fermentation. This work achieved high-specificity production of both C12/14 and C16/18 alcohols. The encouraging 598.6 mg/L of fatty alcohols represents the highest titer reported so far. In addition, the 101.5 mg/L 89.2% C16/18 alcohol suggests an important breakthrough in C16/18 alcohol production. A more detailed optimization of the expression level of fatty alcohol biosynthesis pathway may contribute to a further improvement of fatty alcohol production.
Optimal compressed sensing reconstructions of fMRI using 2D deterministic and stochastic sampling geometries
Authors: Jeromin Oliver , Pattichis Marios S , Calhoun Vince D
Published: May 2012

Background

Compressive sensing can provide a promising framework for accelerating fMRI image acquisition by allowing reconstructions from a limited number of frequency-domain samples. Unfortunately, the majority of compressive sensing studies are based on stochastic sampling geometries that cannot guarantee fast acquisitions that are needed for fMRI. The purpose of this study is to provide a comprehensive optimization framework that can be used to determine the optimal 2D stochastic or deterministic sampling geometry, as well as to provide optimal reconstruction parameter values for guaranteeing image quality in the reconstructed images.

Methods

We investigate the use of frequency-space (k-space) sampling based on: (i) 2D deterministic geometries of dyadic phase encoding (DPE) and spiral low pass (SLP) geometries, and (ii) 2D stochastic geometries based on random phase encoding (RPE) and random samples on a PDF (RSP). Overall, we consider over 36 frequency-sampling geometries at different sampling rates. For each geometry, we compute optimal reconstructions of single BOLD fMRI ON & OFF images, as well as BOLD fMRI activity maps based on the difference between the ON and OFF images. We also provide an optimization framework for determining the optimal parameters and sampling geometry prior to scanning.

Results

For each geometry, we show that reconstruction parameter optimization converged after just a few iterations. Parameter optimization led to significant image quality improvements. For activity detection, retaining only 20.3% of the samples using SLP gave a mean PSNR value of 57.58 dB. We also validated this result with the use of the Structural Similarity Index Matrix (SSIM) image quality metric. SSIM gave an excellent mean value of 0.9747 (max = 1). This indicates that excellent reconstruction results can be achieved. Median parameter values also gave excellent reconstruction results for the ON/OFF images using the SLP sampling geometry (mean SSIM > =0.93). Here, median parameter values were obtained using mean-SSIM optimization. This approach was also validated using leave-one-out.

Conclusions

We have found that compressive sensing parameter optimization can dramatically improve fMRI image reconstruction quality. Furthermore, 2D MRI scanning based on the SLP geometries consistently gave the best image reconstruction results. The implication of this result is that less complex sampling geometries will suffice over random sampling. We have also found that we can obtain stable parameter regions that can be used to achieve specific levels of image reconstruction quality when combined with specific k-space sampling geometries. Furthermore, median parameter values can be used to obtain excellent reconstruction results.
Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation
Authors: Fan Kai , Wu Xuefei , Fan Bin , Li Ning , Lin Yongzhong , Yao Yiwen , Ma Jianmei
Published: May 2012

Background

Cathepsin C (Cat C) functions as a central coordinator for activation of many serine proteases in inflammatory cells. It has been recognized that Cat C is responsible for neutrophil recruitment and production of chemokines and cytokines in many inflammatory diseases. However, Cat C expression and its functional role in the brain under normal conditions or in neuroinflammatory processes remain unclear. Our previous study showed that Cat C promoted the progress of brain demyelination in cuprizone-treated mice. The present study further investigated the Cat C expression and activity in lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro.

Methods

C57BL/6 J mice were intraperitoneally injected with either 0.9% saline or lipopolysaccharide (LPS, 5 mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to analyze microglial activation, TNF-α, IL-1β, IL-6, iNOS mRNAs expressions and cellular localization of Cat C in the brain. Nitrite assay was used to examine microglial activation in vitro; RT-PCR and ELISA were used to determine the expression and release of Cat C. Cat C activity was analyzed by cellular Cat C assay kit. Data were evaluated for statistical significance with paired t test.

Results

Cat C was predominantly expressed in hippocampal CA2 neurons in C57BL/6 J mice under normal conditions. Six hours after LPS injection, Cat C expression was detected in cerebral cortical neurons; whereas, twenty-four hours later, Cat C expression was captured in activated microglial cells throughout the entire brain. The duration of induced Cat C expression in neurons and in microglial cells was ten days and three days, respectively. In vitro, LPS, IL-1β and IL-6 treatments increased microglial Cat C expression in a dose-dependent manner and upregulated Cat C secretion and its activity.

Conclusions

Taken together, these data indicate that LPS and proinflammatory cytokines IL-1β, IL-6 induce the expression, release and upregulate enzymatic activity of Cat C in microglial cells. Further investigation is required to determine the functional role of Cat C in the progression of neuroinflammation, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future.
Molecular diagnostics for congenital hearing loss including 15 deafness genes using a next generation sequencing platform
Authors: De Keulenaer Sarah , Hellemans Jan , Lefever Steve , Renard Jean-Pierre , De Schrijver Joachim , Van de Voorde Hendrik , Tabatabaiefar Mohammad Amin , Van Nieuwerburgh Filip , Flamez Daisy , Pattyn Filip , Scharlaken Bieke , Deforce Dieter , Bekaert Sofie , Van Criekinge Wim , Vandesompele Jo , Van Camp Guy , Coucke Paul
Published: May 2012

Background

Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. Identification of the genetic defects in patients is currently labor intensive and expensive. While screening with Sanger sequencing for GJB2 mutations is common, this is not the case for the other known deafness genes (> 60). Next generation sequencing technology (NGS) has the potential to be much more cost efficient. Published methods mainly use hybridization based target enrichment procedures that are time saving and efficient, but lead to loss in sensitivity. In this study we used a semi-automated PCR amplification and NGS in order to combine high sensitivity, speed and cost efficiency.

Results

In this proof of concept study, we screened 15 autosomal recessive deafness genes in 5 patients with congenital genetic deafness. 646 specific primer pairs for all exons and most of the UTR of the 15 selected genes were designed using primerXL. Using patient specific identifiers, all amplicons were pooled and analyzed using the Roche 454 NGS technology. Three of these patients are members of families in which a region of interest has previously been characterized by linkage studies. In these, we were able to identify two new mutations in CDH23 and OTOF. For another patient, the etiology of deafness was unclear, and no causal mutation was found. In a fifth patient, included as a positive control, we could confirm a known mutation in TMC1.

Conclusions

We have developed an assay that holds great promise as a tool for screening patients with familial autosomal recessive nonsyndromal hearing loss (ARNSHL). For the first time, an efficient, reliable and cost effective genetic test, based on PCR enrichment, for newborns with undiagnosed deafness is available.
Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1β production from human synovial fibroblasts
Authors: Migita Kiyoshi , Koga Tomohiro , Satomura Kenshi , Izumi Masahiro , Torigoshi Takafumi , Maeda Yumi , Izumi Yasumori , Jiuchi Yuka , Miyashita Taiichiro , Yamasaki Satoshi , Aiba Yoshihiro , Komori Atsumasa , Nakamura Minoru , Motokawa Satoru , Kawakami Atsushi , Nakamura Tadashi , Ishibashi Hiromi
Published: May 2012

Background

Monosodium urate (MSU) has been shown to promote inflammasome activation and interleukin-1β (IL-1β) secretion in monocyte/macrophages, but the cellular pathway and nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in synovial tissues, remain elusive. In this study, we investigated the effects of MSU on synovial fibroblasts to elucidate the process of MSU-mediated synovial inflammation.

Methods

Human synovial fibroblasts were stimulated with MSU in the presence or absence of serum amyloid A (SAA). The cellular supernatants were analyzed by immunoblotting using anti-IL-1β or anti-caspase-1 antibodies. IL-1β or NLRP3 mRNA expressions were analyzed by real-time PCR or reverse transcription-PCR (RT-PCR) method.

Results

Neither SAA nor MSU stimulation resulted in IL-1β or interleukin-1α (IL-1α) secretions and pro-IL-1β processing in synovial fibroblasts. However, in SAA-primed synovial fibroblasts, MSU stimulation resulted in the activation of caspase-1 and production of active IL-1β and IL-1α. The effect of SAA on IL-1β induction was impaired in cells by silencing NLRP3 using siRNA or treating with caspase-1 inhibitor. In addition, SAA induced the secretion of cathepsin B and NLRP3 mRNA expression in synovial fibroblasts.

Conclusions

Our data demonstrate that exposure of human synovial fibroblasts to SAA promotes MSU-mediated caspase-1 activation and IL-1β secretion in the absence of microbial stimulation. These findings provide insight into the molecular processes underlying the synovial inflammatory condition of gout.
Red cell distribution width improves the simplified acute physiology score for risk prediction in unselected critically ill patients
Authors: Hunziker Sabina , Celi Leo A , Lee Joon , Howell Michael D
Published: May 2012

Introduction

Recently, red cell distribution width (RDW), a measure of erythrocyte size variability, has been shown to be a prognostic marker in critical illness. The aim of this study was to investigate whether adding RDW has the potential to improve the prognostic performance of the simplified acute physiology score (SAPS) to predict short- and long-term mortality in an independent, large, and unselected population of intensive care unit (ICU) patients.

Methods

This observational cohort study includes 17,922 ICU patients with available RDW measurements from different types of ICUs. We modeled the association between RDW and mortality by using multivariable logistic regression, adjusting for demographic factors, comorbidities, hematocrit, and severity of illness by using the SAPS.

Results

ICU-, in-hospital-, and 1-year mortality rates in the 17,922 included patients were 7.6% (95% CI, 7.2 to 8.0), 11.2% (95% CI, 10.8 to 11.7), and 25.4% (95% CI, 24.8 to 26.1). RDW was significantly associated with in-hospital mortality (OR per 1% increase in RDW (95%CI)) (1.14 (1.08 to 1.19), P < 0.0001), ICU mortality (1.10 (1.06 to 1.15), P < 0.0001), and 1-year mortality (1.20 (95% CI, 1.14 to 1.26); P < 0.001). Adding RDW to SAPS significantly improved the AUC from 0.746 to 0.774 (P < 0.001) for in-hospital mortality and 0.793 to 0.805 (P < 0.001) for ICU mortality. Significant improvements in classification of SAPS were confirmed in reclassification analyses. Subgroups demonstrated robust results for gender, age categories, SAPS categories, anemia, hematocrit categories, and renal failure.

Conclusions

RDW is a promising independent short- and long-term prognostic marker in ICU patients and significantly improves risk stratification of SAPS. Further research is needed the better to understand the pathophysiology underlying these effects.
Efficient Laplace-domain modeling and inversion using an axis transformation technique
Authors: Ha Wansoo , Shin Changsoo
Published: May 2012

We tested an axis-transformation technique for modeling wave propagation in the Laplace domain using a finite-difference method. This technique enables us to use small grids near the surface and large grids at depth. Accordingly, we can reduce the number of grids and attain computational efficiency in modeling and inversion in the Laplace domain. We used a dispersion analysis and comparisons between modeled wavefields obtained on the regular and transformed axes. We demonstrated in a synthetic Laplace-domain inversion technique shows that this method is efficient and yields a result comparable to that of a Laplace-domain inversion using a regular grid. In a synthetic inversion example, the memory usage reduced to less than 33%, and the computation time reduced to 39% of those required for the regular grid case using a logarithmic transformation function.
Response to a Treatment Summary and Care Plan Among Adult Survivors of Pediatric and Young Adult Cancer
Authors: Spain Peter D. , Oeffinger Kevin C. , Candela Joanne , McCabe Mary , Ma Xiaomei , Tonorezos Emily S.
Published: May 2012

The authors found that a one-page treatment summary and care plan was accepted and retained by adult survivors of pediatric and young adult cancers, and did not result in undue worry or concern for most participants.
Trends in Neutropenia-Related Inpatient Events
Authors: Kozma Chris M. , Dickson Michael , Chia Victoria , Legg Jason , Barron Richard
Published: May 2012

Hospitalizations for neutropenic complications increased from 1989 to 1997 and then stabilized, whereas the number of hospitalizations with cancer diagnoses has remained steady since 1989.
Uptake of Oxaliplatin and Bevacizumab for Treatment of Node-Positive and Metastatic Colon Cancer
Authors: Neugut Alfred I. , Becker Daniel J. , Insel Beverly J. , Hershman Dawn L.
Published: May 2012

Uptake of new chemotherapy drugs for patients diagnosed with stages III and IV colon cancer in 2005 was rapid, and physician characteristics were consistently associated with this uptake.
Patient Out-of-Pocket Payments for Oral Oncolytics: Results From a 2009 US Claims Data Analysis
Authors: Raborn Martin L. , Pelletier Elise M. , Smith Daniel B. , Reyes Carolina M.
Published: May 2012

Out-of-pocket payments differ widely among oral oncolytic options. As cost for therapy becomes a greater part of treatment decisions, an understanding of patient out-of-pocket cost will be critical in informing choices.
Infused Chemotherapy Use in the Elderly After Patent Expiration
Authors: Conti Rena M. , Rosenthal Meredith B. , Polite Blase N. , Bach Peter B. , Shih Ya-Chen Tina
Published: May 2012

As calls for improving the quality and cost efficiency of oncology increase, future empirical work is needed to examine the responsiveness of oncologists' treatment decision making to incentives among patients of all ages and insurance types.
Effect of Insurance Status on the Stage of Breast and Colorectal Cancers in a Safety-Net Hospital
Authors: Farkas Daniel T. , Greenbaum Arieh , Singhal Vinay , Cosgrove John M.
Published: May 2012

In a safety-net hospital, patients with Medicaid have rates of advanced-stage cancer similar to those of patients with other types of insurance; however, patients with no insurance have significantly higher rates of advanced disease.
Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Versus Intensity-Modulated Radiation Therapy: An Emerging Initial Radiation Treatment Option for Organ-Confined Prostate Cancer
Authors: Hodges Joseph C. , Lotan Yair , Boike Thomas P. , Benton Rhonda , Barrier Alyson , Timmerman Robert D.
Published: May 2012

Stereotactic body radiation therapy for low- to intermediate-risk prostate cancer has potential cost savings and may improve access to radiation, increase convenience, and boost quality of life.
Evidence Gaps in Advanced Cancer Care: Community-Based Clinicians' Perspectives and Priorities for Comparative Effectiveness Research
Authors: Lowry Sarah J. , Loggers Elizabeth T. , Bowles Erin J.A. , Wagner Edward H.
Published: May 2012

Comparative effectiveness research and pragmatic clinical trials are valued methods to address the limitations of traditional randomized trials, answer questions of cost-effectiveness or noninferiority, and inform data-driven dialogue and decision making by stakeholders.
Long Terminal Repeats Act as Androgen-Responsive Enhancers for the PSA-Kallikrein Locus
Authors: Lawrence Mitchell G. , Stephens Carson R. , Need Eleanor F. , Lai John , Buchanan Grant , Clements Judith A.
Published: May 2012

The androgen receptor (AR) signaling pathway is a common therapeutic target for prostate cancer, because it is critical for the survival of both hormone-responsive and castrate-resistant tumor cells. Most of the detailed understanding that we have of AR transcriptional activation has been gained by studying classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate-specific antigen) has been used as a prototypical AR target gene, because it is highly androgen responsive in prostate cancer cells. Three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation. Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes at the centromeric end of the kallikrein locus with enhancers that evolved from the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand-dependent recruitment of the AR to individual LTR-derived enhancers results in concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP prostate cancer cells. At the molecular level, a kallikrein-specific duplication within the LTR is required for maximal androgen responsiveness. Therefore, KLK3 represents a subset of target genes regulated by repetitive elements but is not typical of the whole spectrum of androgen-responsive transcripts. These data provide a novel and more detailed understanding of AR transcriptional activation and emphasize the importance of repetitive elements as functional regulatory units.
“Memories of Underdevelopment” after Area Studies
Authors: Harootunian Harry
Published: May 2012

The purpose of this article is to examine how the construction of a desire called area studies was founded on the privilege accorded to fixed spatial units such as the geographical area, culture region, and the directional localities west, east, south, and so forth. The model for such spatial regularities has been the nation-state form, itself a predominantly spatial figure, and its capacity for modernizing transformation leading to the establishment of modern rationalities such as the liberal democratic polity, capital accumulation, and the self-regulating market, which would constitute the sign of an unchanging modern structure. Even in the transmutation of area studies into identity studies, based on permanent ethnocultural determinations, the privilege of the spatial dominant still persists and prevails, announcing what appears as the “end of temporality.” In its place I offer the possibility of a “containment strategy” constituted of specific space/time relationships, recalling what M. M. Bakhtin named as “chronotope,” which restores time to any consideration of space and allows for the identification of changing conjunctural configurations prompted by momentary contingencies.
Arf6 negatively controls the rapid recycling of the β2AR
Authors: Macia E. , Partisani M. , Paleotti O. , Luton F. , Franco M.
Published: May 2012

β2-adrenergic receptor (β2AR), a member of the GPCR (G-Proteins Coupled Receptor) family, is internalized in a ligand- and β-arrestin-dependent manner into early endosomes, and subsequently recycled back to the plasma membrane. Here we report that β-arrestin promotes the activation of the small G protein Arf6, which regulates the recycling and degradation of β2AR. We demonstrate in vitro that the C-terminal region of β-arrestin1 interacted directly and simultaneously with Arf6GDP and its specific exchange factor EFA6, to promote Arf6 activation. Similarly, the ligand-mediated activation of β2AR leads to the formation of Arf6GTP in vivo in a β-arrestin-dependent manner. Expression of either EFA6 or an activated Arf6 mutant caused accumulation of β2AR in the degradation pathway. And this phenotype could be rescued by the expression of an activated mutant of Rab4, suggesting that Arf6 acts upstream of Rab4.

We propose a model in which Arf6 plays an essential role for the β2AR desensitization. The ligand-mediated stimulation of β2AR relocates β-arrestin to the plasma membrane, and triggers the activation of Arf6 by EFA6. The activated Arf6 leads to accumulation of β2AR to the degradation pathway, and negatively controls the Rab4-dependent fast recycling to prevent the re-sensitization of β2AR.
Efficient Cost Allocation
Authors: Ray Korok , Goldmanis Maris
Published: May 2012

Firms routinely allocate the costs of common corporate resources down to divisions. The main insight of this paper is that any efficient allocation rule must reflect the firm's underlying cost structure. We propose a new allocation rule (the polynomial rule), which achieves efficiency and approximate budget balance. Welfare losses due to linear allocation rules increase with firm size, so polynomial allocation rules dominate linear rules for larger firms.

This paper was accepted by Mary E. Barth, accounting.
Measuring the Informative and Persuasive Roles of Detailing on Prescribing Decisions
Authors: Ching Andrew T. , Ishihara Masakazu
Published: May 2012

In the pharmaceutical industry, measuring the importance of informative and persuasive roles of detailing is crucial for both drug manufacturers and policy makers. However, little progress has been made in disentangling these two roles of detailing in empirical research. In this paper, we provide a new identification strategy to address this problem. Our key identification assumptions are that the informative component of detailing is chemical specific and the persuasive component is brand specific. Our strategy is to focus on markets where some drug manufacturers engage in a comarketing agreement, under which two or more companies market the same chemical using their own brand names. With our identification assumptions, the variation in the relative market shares of these two brands, together with their brand specific detailing efforts, would allow us to measure the persuasive component of detailing. The variation in the market shares of chemicals, and the detailing efforts summed across brands made of the same chemical, would allow us to measure the informative component of detailing. Using the data for angiotensin-converting enzyme inhibitor with diuretic in Canada, we find evidence that our identification strategy can help disentangle these two effects. Although both effects are statistically significant, we find that the persuasive function of detailing plays a very minor role in determining the demand at the chemical level—the informative role of detailing is mainly responsible for the diffusion patterns of chemicals. In contrast, the persuasive role of detailing plays a crucial role in determining the demand for brands that comarket the same chemical.

This paper was accepted by Pradeep Chintagunta, marketing.
A Generalized Norton–Bass Model for Multigeneration Diffusion
Authors: Jiang Zhengrui , Jain Dipak C.
Published: May 2012

The Norton–Bass (NB) model is often credited as the pioneering multigeneration diffusion model in marketing. However, as acknowledged by the authors, when counting the number of adopters who substitute an old product generation with a new generation, the NB model does not differentiate those who have already adopted the old generation from those who have not. In this study, we develop a generalized Norton–Bass (GNB) model that separates the two different types of substitutions. The GNB model provides closed-form expressions for both the number of units in use and the adoption rate, and offers greater flexibility in parameter estimation, forecasting, and revenue projection. An appealing aspect of the GNB model is that it uses exactly the same set of parameters as the NB model and is mathematically consistent with the later. Empirical results show that the GNB model delivers better overall performance than previous models both in terms of model fit and forecasting performance. The analyses also show that differentiating leapfrogging and switching adoptions based on the GNB model can help gain additional insights into the process of multigeneration diffusion. Furthermore, we demonstrate that the GNB model can incorporate the effect of marketing mix variables on the speed of diffusion for all product generations.

This paper was accepted by Pradeep Chintagunta, marketing.
Student Resistance to Schooling: Disconnections With Education in Rural Appalachia
Authors: Hendrickson Katie A.
Published: May 2012

This study investigates student reasons for resisting engagement with school in a rural Appalachian area. The concept of student resistance to school is considered within a White, working-class student population. Through classroom observations, students displaying resistant behaviors were selected to participate in interviews. Coding of interview data and comparisons with observation data resulted in three main themes: family values and expectations, quality and relevance of education, and misunderstandings between teachers and students. These themes underscore the various tensions experienced by students whose schools encourage higher education and abstract concepts, but whose parents encourage values of family and vocational work. Thus, the students do not value the education provided by the school, leading to disengagement and misunderstandings with teachers. The article includes implications and recommendations for schools to reverse the negative perception of resistance and use student resistance as a conversation for critical change.
"In the Art of My Profession": Adrian Boot and Dutch Water Management in Colonial Mexico City
Authors: López John F.
Published: May 2012

En 1614 el ingeniero holandés Adrian Boot llegó a la Ciudad de México para apoyar a Enrico Martínez con "el desagüe"—un proyecto para llevar el agua de los lagos que rodeaban la ciudad hacia el Golfo de México que tenía la intención de prevenir inundaciones. Sin embargo, Boot rechazó el proyecto de Martínez. En este ensayo explico las razones que tuvo para hacerlo, y discuto su proyecto alterno basado en la regulación de las aguas lacustres a través de la reutilización de tecnología hidráulica de su tierra natal. Mantener las aguas, sin duda, era más acorde con el entorno ambiental y social de la isla en la que se había fundado México.
Along the Waterfront: Alejandro Malaspina, Fernando Brambila, and the Invention of the Buenos Aires Cityscape, 1789-1809
Authors: Bockelman Brian
Published: May 2012

Este artículo trata de ampliar nuestro conocimiento de como el arte visual ha contribuido a la nueva ola de imperialismo científico y representación geográfica avanzado por la España borbónica a través de sus numerosas expediciones ultramarinas al final del siglo XVIII, enfocando especialmente el viaje extensivo del Malaspina de 1789-1794 y dos cuadros de paisajes urbanos de Buenos Aires, atribuidos al miembro del equipo, el artista Fernando Brambila (1763-1834). Esto estudio intenta mostrar como la representación de esta ciudad capitalina viceregia de bajo perfíl fue condicionada no solamente por dictados científicos sino por la topografía extraña de la línea costanera del Río de la Plata y una cultura visual europea más amplia que incluía las convenciones artísticas evolucionandas de representar el espacio urbano y un interés creciente por los detalles de sitios distantes. El artículo usa este acercamiento para explicar la génesis de las dos vistas de Brambila y los motivos estéticos y prácticos por qué un cuadro, que mirando la ciudad a lo largo de su costa ribareña, se hizo el más conocido como imagen de Buenos Aires dl principio de siglo diecinueve, mientras el otro fue en gran parte olvidado.
The Contested Spaces of the Subterranean: Colonial Governmentality, Mining, and the Mita in Early Spanish Peru
Authors: Scott Heidi V.
Published: May 2012

Este artículo examina las "racionalidades espaciales" (Huxley 2007) que influyeron en los debates coloniales sobre el trabajo forzado en las minas del Perú. El artículo desarrolla la idea propuesta por Huxley que las cualidades causativas de ciertos espacios desempeñan un papel importante en la formación de racionalidades gubernmentales, y considera cómo las percepciones coloniales de ambientes subterráneos estaban conectadas con ideas sobre las características de los indios y los derechos y responsabilidades que, según los europeos, tenían como vasallos de la corona española. El análisis se centra primero en la época toledana y después en tres textos del siglo diecisiete que prestan atención a la cuestión de la minería y la mita.
The Ties That (Un)Bind: Fathers, Daughters, and Pietas in Ovid's Metamorphoses
Authors: Prince Meredith
Published: May 2012

This article examines the father-daughter relationship, in the context of pietas , in the Metamorphoses . Ovid uses this relationship to explore pietas ' potential for promoting conflicting claims and the consequences of its breakdown. He questions the nature of paternal power and filial loyalty and stresses the potential for both sides to undermine the bond, convert pietas into scelus , or destroy the relationship. Ovid thus criticizes pietas and, through stories of rebellious and independent daughters and cruel and exploitative fathers, alludes to the negative effects of Augustus' moral legislation and Augustus' own role as pater patriae .
Plutarch and Saint Basil as Readers of Greek Literature
Authors: Beneker Jeffrey
Published: May 2012

Basil's Address to Young Men on How to Read Greek Literature is often read as an imitation of Plutarch's How to Study Poetry . Exploring the authors' connections more generally, I suggest that Basil has relied on Plutarch's approach in both the Moralia and the Lives to make the central argument of his essay, which is a justification for the reading of pagan literature in a Christian context. Basil follows Plutarch in his moralizing interpretations of historical anecdotes and in turning to Plato's Republic for philosophical support, but he also adapts Plutarch's approach to fit the social, religious, and political climate of his times.
The End of Manhattan: How the Gas Centrifuge Changed the Quest for Nuclear Weapons
Authors: Kemp R. Scott
Published: May 2012

The gas centrifuge revolutionized uranium processing for nuclear power, but it also enabled countries to make nuclear weapons more easily. It is widely known that the Manhattan Project failed to make a viable centrifuge; the first successful machines were produced in the 1950s by German prisoners of war in the Soviet Union. Little has been written about what it took to perfect the device or why it became the proliferation machine it is today. This article traces its development by exploring the role of technological change, tacit knowledge, and secrecy. This history argues that, contrary to popular understanding, constructing basic centrifuges has never been cutting-edge or resource-intensive. This breaks with the Manhattan Project mythology that nuclear weapons require techno-industrial greatness. Consequently, technology-based nonproliferation policies flowing from such thinking were arguably misinformed; it is likely that nuclear proliferation has been, or will be, controlled more by motivations than by technological constraints.
Socialist Housing in the Eastern Bloc: Lynne Attwood, Gender and Housing in Soviet Russia Kimberly Elman Zarecor, Manufacturing a Socialist Modernity
Authors: De Vos Els
Published: May 2012

This essay reviews

Gender and Housing in Soviet Russia: Private Life in a Public Sphere

(Pittsburgh: 2011) by Lynne Attwood and

Manufacturing A Socialist Modernity: Housing in Czechoslovakia, 1945–1960

(Manchester and New York: 2010) by Kimberly Elman Zarecor. The two books contribute to a deep inside analysis of socialist housing. They do this from different perspectives and with different scopes. While Zarecor’s study is driven by a fascination with the emergence of (prefabricated) architecture under the socialist regime in an Eastern European country, Attwood mainly shows how Soviet citizens experienced their housing from within. Both publications contribute to the understanding of the meaning of housing in the Eastern Bloc, and both show how living and housing were treated in a stepmotherly way, despite the importance of housing in the socialist ideology.
“Improving” the Decoration of Furniture: Imitation and Mechanization in the Marquetry Process in Britain and America, 1850–1900
Authors: Edwards Clive
Published: May 2012

In the 1980s, the application of the laser to cut veneers for marquetry was arguably the first major successful development for improving the process since the nineteenth century. Despite attempts to advance what had been an essentially hand-crafted technique, successful economic applications remained elusive. This article analyzes attempts made since the mid nineteenth-century to apply technologies to “improve” the marquetry process in Britain and America. Inventors intended to increase opportunities for manufacturers to supply decorative furniture for a growing market. Speed of production and the possibility of supplying furniture with greater decoration reflected a desire to address both the economic and consumption agendas. I describe how inventors proposed attempts to mechanize or imitate marquetry often through patented processes, and then consider their success. I argue that applying technologies as knowledge, practice, and material resource to craft works raises a number of issues particularly when there is an element of “art” involved.
The Education Iron Triangle
Authors: West Martin R. , Henderson Michael , Peterson Paul E.
Published: May 2012

Do teachers and the public disagree on education reform? We use data from a nationally representative survey conducted in 2011 to identify the extent of the differences between the opinion of teachers and the general public on a wide range of education policies. The overall cleavage between teachers and the general public is wider than the cleavages between other relevant groups, including that between Democrats and Republicans. At least with respect to patterns of opinion on education reform, school politics is largely a conflict between producers within the system and consumers outside it – a classic iron triangle theme.
Political Science as a Vocation: An Appreciation of the Life and the Work of James Q. Wilson
Authors: Melnick R. Shep
Published: May 2012

James Q. Wilson produced a remarkably varied, influential, and profound body of scholarly work on American politics. The first part of this tribute provides an overview of his contribution to our understanding of city politics, crime and policing, voluntary organizations, bureaucracy, and the development of those character traits upon which democratic government depends. The second part of the essay describes key features of Wilson’s approach to studying politics, features notably and lamentably absent from most political science today.
Analysis of Gamma-Ray Dosimetry Experiments in the Zero Power MINERVE Facility
Authors: Amharrak H. , Di Salvo J. , Lyoussi A. , Roche A. , Masson-Fauchier M. , Bosq J. C. , Carette M.
Published: May 2012

The objective of this study is to develop nuclear heating measurement methods in zero power experimental reactors. These developments contribute to the qualification of photonics calculation schemes for the assessment of gamma heating in the future Jules Horowitz Material Testing Reactor. This paper presents the analysis of thermoluminescent detector (TLD) experiments in the UO2 core of the MINERVE Research Reactor at the French Alternative Energies and Atomic Energy Commission center in Cadarache. The experimental sources of uncertainty in the gamma dose have been reduced by improving the measurement conditions and the repeatability of the calibration step for each individual TLD. The interpretation of these measurements needs to take into account the calculation of cavity correction factors related to calibration and irradiation configurations, as well as neutron correction calculations. These calculations are based on Monte Carlo simulations of neutron-gamma and gamma-electron transport coupled particles. The comparison between calculated and measured integral gamma-ray absorbed doses in the aluminum material surrounding the TLD shows that calculations slightly overestimate the measurement, with a calculated versus experimental ratio equal to 1.04 ± 5.7 % (k = 2).
Uncertainty-Accounted Calculational–Experimental Approach for Improved Conservative Evaluations of VVER RPV Radiation Loading Parameters
Authors: Borodkin P. G. , Borodkin G. I. , Khrennikov N. N.
Published: May 2012

The approach of improved uncertainty-accounted conservative evaluation of vodo-vodyanoi energetichesky reactor (VVER) (reactor-) pressure-vessel (RPV) radiation loading parameters has been proposed. This approach is based on the calculational–experimental procedure, which takes into account C/E ratio, depending on over- or underestimation, and uncertainties of measured and calculated results. An application of elaborated approach to the full-scale ex-vessel neutron dosimetry experiments on Russian VVERs combined with neutron-transport calculations has been demonstrated in the paper.
New Measurements and the Associated Unfolding Methodologies to Characterize the Caliban Pulsed Reactor Cavity Neutron Spectrum by the Foil Activation Method
Authors: Jacquet X. , Casoli P. , Authier N. , Rousseau G. , Barsu C.
Published: May 2012

Caliban is a cylindrical metallic core reactor mainly composed of uranium 235. It is operated by the Criticality and Neutron Science Research Laboratory located at the French Atomic Energy Commission research center in Valduc. As with other fast burst reactors, Caliban is used extensively for determining the responses of electronic parts or other objects and materials to neutron-induced displacements. Therefore, Caliban’s irradiation characteristics, and especially its central cavity neutron spectrum, have to be very accurately evaluated. The foil activation method has been used in the past by the Criticality and Neutron Science Research Laboratory to evaluate the neutron spectrum of the different facilities it operated, and in particular to characterize the Caliban cavity spectrum. In order to strengthen and to improve our knowledge of the Caliban cavity neutron spectrum and to reduce the uncertainties associated with the available evaluations, new measurements have been performed on the reactor and interpreted by the foil activation method. A sensor set has been selected to sample adequately the studied spectrum. Experimental measured reaction rates have been compared to the results from UMG spectrum unfolding software and to values obtained with the activation code Fispact. Experimental and simulation results are overall in good agreement, although gaps exist for some sensors. UMG software has also been used to rebuild the Caliban cavity neutron spectrum from activation measurements. For this purpose, a default spectrum is needed, and one has been calculated with the Monte-Carlo transport code Tripoli 4 using the benchmarked Caliban description.