bluuebunny/crossref_metadata_2025 huggingface dataset:
High body mass index is not associated with atopy in schoolchildren living in rural and urban areas of Ghana
Authors: Larbi Irene A , Klipstein-Grobusch Kerstin , Amoah Abena S , Obeng Benedicta B , Wilson Michael D , Yazdanbakhsh Maria , Boakye Daniel A
Published: June 2011

Background

Factors which determine the development of atopy and the observed rural-urban gradient in its prevalence are not fully understood. High body mass index (BMI) has been associated with asthma and potentially atopy in industrialized countries. In developing countries, the transition from rural to urban areas has been associated with lifestyle changes and an increased prevalence of high BMI; however, the effect of high BMI on atopy remains unknown in this population. We therefore investigated the association between high BMI and atopy among schoolchildren living in rural and urban areas of Ghana.

Methods

Data on skin prick testing, anthropometric, parasitological, demographic and lifestyle information for 1,482 schoolchildren aged 6-15 years was collected. Atopy was defined as sensitization to at least one tested allergen whilst the Centres for Disease Control and Prevention (CDC, Atlanta) growth reference charts were used in defining high BMI as BMI ≥ the 85th percentile. Logistic regression was performed to investigate the association between high BMI and atopy whilst adjusting for potential confounding factors.

Results

The following prevalences were observed for high BMI [Rural: 16%, Urban: 10.8%, p < 0.001] and atopy [Rural: 25.1%, Urban: 17.8%, p < 0.001]. High BMI was not associated with atopy; but an inverse association was observed between underweight and atopy [OR: 0.57, 95% CI: 0.33-0.99]. Significant associations were also observed with male sex [Rural: OR: 1.49, 95% CI: 1.06-2.08; Urban: OR: 1.90, 95% CI: 1.30-2.79], and in the urban site with older age [OR: 1.76, 95% CI: 1.00-3.07], family history of asthma [OR: 1.58, 95% CI: 1.01-2.47] and occupational status of parent [OR: 0.33, 95% CI: 0.12-0.93]; whilst co-infection with intestinal parasites [OR: 2.47, 95% CI: 1.01-6.04] was associated with atopy in the rural site. After multivariate adjustment, male sex, older age and family history of asthma remained significant.

Conclusions

In Ghanaian schoolchildren, high BMI was not associated with atopy. Further studies are warranted to clarify the relationship between body weight and atopy in children subjected to rapid life-style changes associated with urbanization of their environments.
Personal genome testing: Test characteristics to clarify the discourse on ethical, legal and societal issues
Authors: Bunnik Eline M , Schermer Maartje HN , Janssens A Cecile JW
Published: June 2011

Background

As genetics technology proceeds, practices of genetic testing have become more heterogeneous: many different types of tests are finding their way to the public in different settings and for a variety of purposes. This diversification is relevant to the discourse on ethical, legal and societal issues (ELSI) surrounding genetic testing, which must evolve to encompass these differences. One important development is the rise of personal genome testing on the basis of genetic profiling: the testing of multiple genetic variants simultaneously for the prediction of common multifactorial diseases. Currently, an increasing number of companies are offering personal genome tests directly to consumers and are spurring ELSI-discussions, which stand in need of clarification. This paper presents a systematic approach to the ELSI-evaluation of personal genome testing for multifactorial diseases along the lines of its test characteristics.

Discussion

This paper addresses four test characteristics of personal genome testing: its being a non-targeted type of testing, its high analytical validity, low clinical validity and problematic clinical utility. These characteristics raise their own specific ELSI, for example: non-targeted genetic profiling poses serious problems for information provision and informed consent. Questions about the quantity and quality of the necessary information, as well as about moral responsibilities with regard to the provision of information are therefore becoming central themes within ELSI-discussions of personal genome testing. Further, the current low level of clinical validity of genetic profiles raises questions concerning societal risks and regulatory requirements, whereas simultaneously it causes traditional ELSI-issues of clinical genetics, such as psychological and health risks, discrimination, and stigmatization, to lose part of their relevance. Also, classic notions of clinical utility are challenged by the newer notion of 'personal utility.'

Consideration of test characteristics is essential to any valuable discourse on the ELSI of personal genome testing for multifactorial diseases. Four key characteristics of the test - targeted/non-targeted testing, analytical validity, clinical validity and clinical utility - together determine the applicability and the relevance of ELSI to specific tests. The paper identifies and discusses four areas of interest for the ELSI-debate on personal genome testing: informational problems, risks, regulatory issues, and the notion of personal utility.
The novel chemokine receptor CXCR7 regulates trans-endothelial migration of cancer cells
Authors: Zabel Brian A , Lewén Susanna , Berahovich Robert D , Jaén Juan C , Schall Thomas J
Published: June 2011

Background

Migration of metastatic tumor cells from the bloodstream into lymph nodes is thought to be facilitated by expression of the chemokine receptors CCR7, CXCR4 and, for B cell-derived tumors, CXCR5. Expression of their respective chemokine ligands (CCL19, CCL21, CXCL12 and CXCL13) by endothelial cells inside the lymph nodes facilitates the trans-endothelial migration (TEM) of these cells through high endothelial venules into the lymph node parenchyma. It is known that CXCR7, a second CXCL12 receptor, regulates TEM of CXCR4+CXCR7+ tumor cells towards a CXCL12 source. In this study, we set out to assess the potential stimulation by CXCL12 of tumor cell TEM towards other chemokines and whether CXCR7 might be able to regulate such effects.

Methods

The human Burkitt's lymphoma cell line NC-37, which expresses CXCR4, CXCR5, CXCR7 and CCR7, was selected as a model system. TEM of these cells through a human HUVEC endothelial cell monolayer was used as the main model system for these studies. Regulation of their TEM behavior by various concentrations of the various cognate chemokines for the above-mentioned receptors, placed in either the source or target wells of modified Boyden chamber migration plates, was assessed by quantifying the number of cells migrated under each experimental condition.

Results

Exposure of CXCR4+CXCR7+ cancer cells to CXCL12 greatly potentiated their TEM towards the chemokines CCL19 and CXCL13. This CXCL12-potentiated TEM was inhibited by the second CXCR7 chemokine ligand, CXCL11, as well as CXCR7-specific small molecule antagonists and antibodies. In contrast, the CXCR4 antagonist AMD3100 was less effective at inhibiting CXCL12-potentiated TEM. Thus, CXCR7 antagonists may be effective therapeutic agents for blocking CXCL12-mediated migration of CXCR4+CXCR7+ tumor cells into lymph nodes, regardless of whether the cancer cells follow a CXCL12 gradient or whether serum CXCL12 stimulates their migration towards CCR7 and CXCR5 chemokines in the lymph nodes.
Mechanics of lipid bilayer junctions affecting the size of a connecting lipid nanotube
Authors: Karlsson Roger , Kurczy Michael , Grzhibovskis Richards , Adams Kelly L , Ewing Andrew G , Cans Ann-Sofie , Voinova Marina V
Published: June 2011

In this study we report a physical analysis of the membrane mechanics affecting the size of the highly curved region of a lipid nanotube (LNT) that is either connected between a lipid bilayer vesicle and the tip of a glass microinjection pipette (tube-only) or between a lipid bilayer vesicle and a vesicle that is attached to the tip of a glass microinjection pipette (two-vesicle). For the tube-only configuration (TOC), a micropipette is used to pull a LNT into the interior of a surface-immobilized vesicle, where the length of the tube L is determined by the distance of the micropipette to the vesicle wall. For the two-vesicle configuration (TVC), a small vesicle is inflated at the tip of the micropipette tip and the length of the tube L is in this case determined by the distance between the two interconnected vesicles. An electrochemical method monitoring diffusion of electroactive molecules through the nanotube has been used to determine the radius of the nanotube R as a function of nanotube length L for the two configurations. The data show that the LNT connected in the TVC constricts to a smaller radius in comparison to the tube-only mode and that tube radius shrinks at shorter tube lengths. To explain these electrochemical data, we developed a theoretical model taking into account the free energy of the membrane regions of the vesicles, the LNT and the high curvature junctions. In particular, this model allows us to estimate the surface tension coefficients from R(L) measurements.
Human defensins 5 and 6 enhance HIV-1 infectivity through promoting HIV attachment
Authors: Rapista Aprille , Ding Jian , Benito Bernadette , Lo Yung-Tai , Neiditch Matthew B , Lu Wuyuan , Chang Theresa L
Published: June 2011

Background

Concurrent sexually transmitted infections (STIs) increase the likelihood of HIV transmission. The levels of defensins are frequently elevated in genital fluids from individuals with STIs. We have previously shown that human defensins 5 and 6 (HD5 and HD6) promote HIV entry and contribute toNeisseria gonorrhoeae-mediated enhancement of HIV infectivityin vitro. In this study, we dissect the molecular mechanism of the HIV enhancing effect of defensins.

Results

HD5 and HD6 primarily acted on the virion to promote HIV infection. Both HD5 and HD6 antagonized the anti-HIV activities of inhibitors of HIV entry (TAK 779) and fusion (T-20) when the inhibitors were present only during viral attachment; however, when these inhibitors were added back during viral infection they overrode the HIV enhancing effect of defensins. HD5 and HD6 enhanced HIV infectivity by promoting HIV attachment to target cells. Studies using fluorescent HIV containing Vpr-GFP indicated that these defensins enhanced HIV attachment by concentrating virus particles on the target cells. HD5 and HD6 blocked anti-HIV activities of soluble glycosaminoglycans including heparin, chondroitin sulfate, and dextran sulfate. However, heparin, at a high concentration, diminished the HIV enhancing effect of HD5, but not HD6. Additionally, the degree of the HIV enhancing effect of HD5, but not HD6, was increased in heparinase-treated cells. These results suggest that HD5 and haparin/heparan sulfate compete for binding to HIV.

Conclusions

HD5 and HD6 increased HIV infectivity by concentrating virus on the target cells. These defensins may have a negative effect on the efficacy of microbicides, especially in the setting of STIs.
The distinct binding properties between avian/human influenza A virus NS1 and Postsynaptic density protein-95 (PSD-95), and inhibition of nitric oxide production
Authors: Zhang Heng , Li Weizhong , Wang Gefei , Su Yun , Zhang Chi , Chen Xiaoxuan , Xu Yanxuan , Li Kangsheng
Published: June 2011

Background

The NS1 protein of influenza A virus is able to bind with many proteins that affect cellular signal transduction and protein synthesis in infected cells. The NS1 protein consists of approximately 230 amino acids and the last 4 amino acids of the NS1 C-terminal form a PDZ binding motif. Postsynaptic Density Protein-95 (PSD-95), which is mainly expressed in neurons, has 3 PDZ domains. We hypothesise that NS1 binds to PSD-95, and this binding is able to affect neuronal function.

Result

We conducted a yeast two-hybrid analysis, GST-pull down assays and co-immunoprecipitations to detect the interaction between NS1 and PSD-95. The results showed that NS1 of avian influenza virus H5N1 (A/chicken/Guangdong/1/2005) is able to bind to PSD-95, whereas NS1 of human influenza virus H1N1 (A/Shantou/169/2006) is unable to do so. The results also revealed that NS1 of H5N1 significantly reduces the production of nitric oxide (NO) in rat hippocampal neurons.

Conclusion

In summary, our study indicates that NS1 of influenza A virus can bind with neuronal PSD-95, and the avian H5N1 and human H1N1 influenza A viruses possess distinct binding properties.
An effective virus-based gene silencing method for functional genomics studies in common bean
Authors: Díaz-Camino Claudia , Annamalai Padmanaban , Sanchez Federico , Kachroo Aardra , Ghabrial Said A
Published: June 2011

Background

Common bean (Phaseolus vulgaris L.) is a crop of economic and nutritious importance in many parts of the world. The lack of genomic resources have impeded the advancement of common bean genomics and thereby crop improvement. Although concerted efforts from the "Phaseomics" consortium have resulted in the development of several genomic resources, functional studies have continued to lag due to the recalcitrance of this crop for genetic transformation.

Results

Here we describe the use of a bean pod mottle virus (BPMV)-based vector for silencing of endogenous genes in common bean as well as for protein expression. This BPMV-based vector was originally developed for use in soybean. It has been successfully employed for both protein expression and gene silencing in this species. We tested this vector for applications in common bean by targeting common bean genes encoding nodulin 22 and stearoyl-acyl carrier protein desaturase for silencing. Our results indicate that the BPMV vector can indeed be employed for reverse genetics studies of diverse biological processes in common bean. We also used the BPMV-based vector for expressing the green fluorescent protein (GFP) in common bean and demonstrate stable GFP expression in all common bean tissues where BPMV was detected.

Conclusions

The availability of this vector is an important advance for the common bean research community not only because it provides a rapid means for functional studies in common bean, but also because it does so without generating genetically modified plants. Here we describe the detailed methodology and provide essential guidelines for the use of this vector for both gene silencing and protein expression in common bean. The entire VIGS procedure can be completed in 4-5 weeks.
Cor triatriatum presenting as heart failure with reduced ejection fraction: a case report
Authors: Kokotsakis John , Anagnostakou Vania , Almpanis George , Paralikas Ioannis , Nenekidis Ioannis , Kratimenos Theodoros , Prapa Efi , Tragotsalou Nikolitsa , Lioulias Achilleas , Mazarakis Andreas
Published: June 2011

Cor triatriatum is a rare congenital cardiac malformation and it usually refers to the left atrium. We report an unusual case of cor triatriatum in a 33 - year old woman presented with congestive heart failure caused by left ventricular systolic dysfunction.
Application of seismic to mineral deposit exploration and evaluation
Authors: Gibson M. A. S.
Published: June 2011

Mineral deposits occur in different geological envi-ronments than oil and gas deposits, and are usually at very shallow depths (from surface outcrop, to hundreds of meters). Because of internal heterogeneities within most deposit types, extensive use of borehole sampling is required to satisfy resource and reserve reporting requirements. While borehole sampling can be designed to satisfy the geostatistical variability of a deposit, it is usually insufficient to adequately sample the structural continuity of deposits to a level required for accurate mine planning and production scheduling. For this reason, 2D and 3D seismic surveys are increasingly used in conjunction with borehole drilling and other geophysical methods such as aeromagnetic surveys to map the geological structure of known deposits. This paper will examine some challenges and results from Anglo American's use of seismic surveying in African coal and platinum deposits.
New insights into prospectivity of Liberia-Sierra Leone Basin because of improvements in seismic acquisition and processing
Authors: Conn Peter , Rodriguez Gary
Published: June 2011

This paper examines how the understanding of the prospectivity of the Liberia-Sierra Leone Basin has developed over the last 40 years largely due to improvements in seismic data over this period. A series of basins developed between major transform fault zones associated with the opening of the South Atlantic Ocean from the early Cretaceous onward. The Liberia-Sierra Leone Basin forms part of the West African Transform Margin that extends from Sierra Leone to Benin. Early hydrocarbon exploration (1972–1985) was targeted at shelfal structural synrift traps of Lower Cretaceous age. None of the wells drilled in this period was regarded as a discovery. In 2001, a new regional 2D seismic survey allowed a new play, deepwater Upper Cretaceous channel fans, to be identified. More recent 3D seismic using the latest data acquisition and processing technologies, including AVO, has enabled drillable prospects to be identified. Wells drilled in 2009–2010 offshore Sierra Leone have established that a working hydrocarbon system exists in this basin.
Biomarker Analyses and Final Overall Survival Results From a Phase III, Randomized, Open-Label, First-Line Study of Gefitinib Versus Carboplatin/Paclitaxel in Clinically Selected Patients With Advanced Non–Small-Cell Lung Cancer in Asia (IPASS)
Authors: Fukuoka Masahiro , Wu Yi-Long , Thongprasert Sumitra , Sunpaweravong Patrapim , Leong Swan-Swan , Sriuranpong Virote , Chao Tsu-Yi , Nakagawa Kazuhiko , Chu Da-Tong , Saijo Nagahiro , Duffield Emma L. , Rukazenkov Yuri , Speake Georgina , Jiang Haiyi , Armour Alison A. , To Ka-Fai , Yang James Chih-Hsin , Mok Tony S.K.
Published: June 2011

Purpose

The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status.

Patients and Methods

In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS.

Results

OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation–positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation–negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation–positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09).

Conclusion

EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR mutation–positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment.
Suppression of AMPK Activation via S485 Phosphorylation by IGF-I during Hyperglycemia Is Mediated by AKT Activation in Vascular Smooth Muscle Cells
Authors: Ning Junyu , Xi Gang , Clemmons David R.
Published: June 2011

As a metabolic sensor, the serine/threonine protein kinase AMP-activated protein kinase (AMPK) promotes the adaptation of cells to signals arising from nutrients, hormones, and growth factors. The ability of IGF-I to stimulate protein synthesis is suppressed by AMPK, therefore, these studies were undertaken to determine whether IGF-I modulates AMPK activity. IGF-I dose-dependently suppressed phosphorylation of AMPK T172, and it stimulated AMPK S485 phosphorylation in vascular smooth muscle cells (VSMC). To determine whether stimulation of AMPK S485 phosphorylation was mediating this response, VSMC were transduced with a mutant AMPKα (AMPK S485A). Expression of this altered form inhibited the ability of IGF-I to suppress AMPK T172 activation, which resulted in inhibition of IGF-I-stimulated phosphorylation of P70S6 kinase. In contrast, expression of an AMPK S485D mutant resulted in constitutive suppression of AMPK activity and was associated with increased IGF-I-stimulated P70S6K phosphorylation and protein synthesis. The addition of a specific AKT inhibitor or expression of an AKT1 short hairpin RNA inhibited AMPK S485 phosphorylation, and it attenuated the IGF-I-induced decrease in AMPK T172 phosphorylation. Exposure to high glucose concentrations suppressed AMPK activity and stimulated S485 phosphorylation, and IGF-I stimulated a further increase in S485 phosphorylation and AMPK T172 suppression. We conclude that AMPK S485 phosphorylation negatively regulates AMPK activity by modulating the T172 phosphorylation response to high glucose and IGF-I. IGF-I stimulates S485 phosphorylation through AKT1. The results suggest that AMPK plays an inhibitory role in modulating IGF-I-stimulated protein synthesis and that IGF-I must down-regulate AMPK activity to induce an optimal anabolic response.
“Gender” Trouble: Feminism in China under the Impact of Western Theory and the Spatialization of Identity
Authors: Spakowski Nicola
Published: June 2011

Over the past ten to fifteen years, feminism in China has been marked by three closely related characteristics. The first is the introduction of “Western” feminism with “gender” as the core of theory import. The second is the articulation of the “trouble” this import of Western theory has caused. Chinese feminist texts abound with terms such as trouble, difficulty, and clash, which are used to express worries about the consequences of this new orientation of feminism in China. They prove that the import of Western theory and the transition to “gender” as the basic category of analysis are not the logical and unquestionable developments some authors claim them to be. A third characteristic is the search for an identity for Chinese feminism in a global context. Chinese scholars, under the impact of Western theory, turn to spatial definitions of Chinese feminism vis-à-vis international feminism and adopt the notion of the “local” to define their place in the world. This essay highlights the “troubling” effects the import of “gender” has on feminist theory building in China and delineates the various and sometimes conflicting efforts Chinese feminists have made to restabilize feminist theory and identity. These include different translations and definitions of “gender,” diverging outlines of the history of Chinese feminism in a global context, various definitions of the “local,” differing visions of a regional “Asian” feminism, and more complex models that try to integrate conflicting perspectives. These responses demonstrate that contrary to its universalist claims, “gender” is a specific concept that finds support among particular groups of feminists only. This essay also tries to explain why Chinese feminists insist on the “local” as a site of theory building and identity formation even where they have acquired global horizons.
A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders
Authors: Mast Fred D. , Li Jing , Virk Maninder K. , Hughes Sarah C. , Simmonds Andrew J. , Rachubinski Richard A.
Published: June 2011

Human peroxisome biogenesis disorders are lethal genetic diseases in which abnormal peroxisome assembly compromises overall peroxisome and cellular function. Peroxisomes are ubiquitous membrane-bound organelles involved in several important biochemical processes, notably lipid metabolism and the use of reactive oxygen species for detoxification. Using cultured cells, we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins; required for peroxisome assembly and linked to peroxisome biogenesis disorders), and confirmed that at least 13 of them are required for normal peroxisome assembly. We also demonstrate the relevance of Drosophila as a genetic model for the early developmental defects associated with the human peroxisome biogenesis disorders. Mutation of the PEX1 gene is the most common cause of peroxisome biogenesis disorders and is one of the causes of the most severe form of the disease, Zellweger syndrome. Inherited mutations in Drosophila Pex1 correlate with reproducible defects during early development. Notably, Pex1 mutant larvae exhibit abnormalities that are analogous to those exhibited by Zellweger syndrome patients, including developmental delay, poor feeding, severe structural abnormalities in the peripheral and central nervous systems, and early death. Finally, microarray analysis defined several clusters of genes whose expression varied significantly between wild-type and mutant larvae, implicating peroxisomal function in neuronal development, innate immunity, lipid and protein metabolism, gamete formation, and meiosis.
Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase
Authors: Siller Saul S. , Broadie Kendal
Published: June 2011

Fragile X syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1) product (FMRP), is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP) inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1) null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ), clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP) in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity between the single dfmr1 mutants and controls. These results support minocycline as a promising potential FXS treatment and suggest that it might act via MMP inhibition. We conclude that FMRP and TIMP pathways interact in a reciprocal, bidirectional manner.
Reinventing Marketing to Manage the Environmental Imperative
Authors: Kotler Philip
Published: June 2011

Marketers in the past have based their strategies on the assumption of infinite resources and zero environmental impact. With the growing recognition of finite resources and high environmental costs, marketers need to reexamine their theory and practices. They need to revise their policies on product development, pricing, distribution, and branding. The recent financial meltdown has added another layer of concern as consumers adjust their lifestyles to a lower level of income and spending. Companies must balance more carefully their growth goals with the need to pursue sustainability. Increased attention will be paid to employing demarketing and social marketing thinking to meet the new challenges.
Getting a Grip on the Saddle: Chasms or Cycles?
Authors: Chandrasekaran Deepa , Tellis Gerard J.
Published: June 2011

The “saddle” is a sudden, sustained, and deep drop in sales of a new product, after a period of rapid growth following takeoff, followed by a gradual recovery to the former peak. The authors test for the generalizability of the saddle across products and countries and for three rival explanations: chasms in adopter segments, business cycles, and technological cycles. They model both boundary points of the saddle—start of the sales drop and recovery to the initial peak—using split-population models. Empirical analysis of historical sales data from ten products across 19 countries shows that the saddle is fairly pervasive. The onset of the saddle occurs in 148 product–country combinations. On average, the saddle occurs nine years after takeoff, at a mean penetration of 30%, and it lasts for eight years with a 29% drop in sales at its depth. The results support explanations of chasms and technological cycles for information/entertainment products and business cycles and technological cycles for kitchen/laundry products. The authors conclude with a discussion of the findings, contributions, and implications.
Stock Market Reaction to Unexpected Growth in Marketing Expenditure: Negative for Sales Force, Contingent on Spending Level for Advertising
Authors: Kim MinChung , McAlister Leigh M.
Published: June 2011

Because firms do not publicly report marketing expenditures, most studies of the link between firm value and marketing consider advertising (which is publicly reported for many firms) a proxy for marketing. The authors extend those studies in two ways. First, they broaden the proxy for marketing by considering both advertising and sales force. Second, they offer an explanation for the fact that some studies linking advertising to firm value find a positive relationship, whereas others find a negative relationship. The accounting literature suggests that the link to firm value for both unexpected growth in sales force expenditures and unexpected growth in advertising expenditures should be negative. The authors confirm the hypothesized accounting relationship for sales force expenditures but find a contingent relationship for advertising expenditures. Firm value and unexpected growth in advertising expenditures are negatively related for firms that advertise below the advertising response threshold, but they are positively related for firms that advertise above that threshold. Perhaps because this contingent relationship is difficult for analysts to learn through observation of the stock market, analysts ignore value-relevant advertising expenditure information when they forecast firm value.
The Impact of Incomplete Typeface Logos on Perceptions of the Firm
Authors: Hagtvedt Henrik
Published: June 2011

This research investigates the influence of incomplete typeface logos on consumer perceptions of the firm. In these logos, parts of the characters in the company name are intentionally missing or blanked out, giving rise to a form of perceptual ambiguity. Three studies demonstrate that although incomplete typeface logos have an unfavorable influence on perceived firm trustworthiness, they have a favorable influence on perceived firm innovativeness. The former influence is tied to the logo's perceived clarity, while the latter influence is tied to its perceived interestingness. Furthermore, incomplete typeface logos have an unfavorable influence on overall attitude toward the firm, but only for consumers with a prevention, rather than promotion, focus. These findings suggest that firms should avoid incomplete typeface logos if perceptions of trustworthiness are critical or if consumers are likely to have a prevention focus. However, such logos may be successfully employed with promotion-focused consumers, and they may be used as a tool to position a firm as innovative.
Introduction to the Kroll Zirconium Medal Papers Book
Authors: Adamson Ronald B.
Published: June 2011

The WILLIAM J. KROLL ZIRCONIUM MEDAL was established to recognize outstanding achievement in the scientific, technological or commercial aspects of zirconium production and utilization, and to encourage future efforts, studies and research. Once regarded as a rare metallurgical curiosity, this exotic metal has been proven to possess exceptional properties, which made it suitable for use in nuclear reactors, and to possess exceptional resistance to corrosion in most media.
Zirconium Technology—Twenty Years of Evolution
Authors: Lustman B.
Published: June 2011

Progress since 1955 in the technology of zirconium and its alloys is reviewed primarily from an applications viewpoint. A number of favorable features have been uncovered as their use broadened as well as problem areas which required accommodation in design or lifetime. Zirconium technology has reached its present stage of development as a result of world-wide contributions. The original paper was published by ASTM International in STP 681, Zirconium in the Nuclear Industry (Fourth Conference), 1979, pp. 5–18.
Mechanistic Modeling of Zircaloy Deformation and Fracture in Fuel Element Analysis
Authors: Nichols F. A.
Published: June 2011

A review is given of the comprehensive model developed in the 1960s at the Bettis Atomic Power Laboratory to explain the creep of Zircaloy during neutron irradiation and applied to fuel to element analysis and design. The in-pile softening observed at low stresses was hypothesized to be due to a combination of the growth-directed Roberts-Cottrell yielding creep originally proposed for α-uranium and the formation of point defect loops preferentially on certain planes in response to the applied stress, with the second process being of relatively greater importance. The in-pile hardening observed at high stresses (or strain-rates) was proposed to be due to the cutting by dislocations of radiation-produced obstacles. In this stress (strain-rates) region, in-pile behavior was proposed to be identical to post-irradiation behavior. At intermediate stresses (strain-rates) a mechanism of radiation-enhanced climb around obstacles was suggested as being rate-controlling. As the stress is decreased, the climb process becomes easier, and the rate was then predicted to be controlled by glide at a flow-stress characteristic of unirradiated, annealed material, where radiation-enhanced diffusion enabled climbing around the normal strain-hardening obstacles. At still lower stresses, this glide process became negligibly slow compared with the growth-connected creep mechanism that was presumed to operate independently. The overall scheme was shown to be in good agreement with all the in-pile data then available and implemented into the computer analysis of fuel element behavior. The original paper was published by ASTM International in STP 939, Zirconium in the Nuclear Industry: Seventh International Symposium, 1987, pp. 5–22.
Forty-One Years with Zirconium
Authors: Mishima Yoshitsugu
Published: June 2011

Reprinted from Journal of Nuclear Science and Technology, Vol. 27, Y. Mishima, “Forty-One Years with Zirconium” pp. 285–292, 1990 with permission from The Atomic Energy Society of Japan.
The Irradiation Creep and Growth Phenomena
Authors: Fidleris V.
Published: June 2011

A summary of known experimental results on in-reactor creep and irradiation growth is presented in terms of behavioural trends. The information is drawn primarily from observations in experimental and power reactors on various zirconium alloys and concentrates on new discoveries since the time of the last Conference on Fundamental Mechanisms of Radiation Induced Creep and Growth, Chalk River 1979. It covers the dependence of creep and growth on test conditions (neutron flux and fluence, temperature and stress) and material variables (composition, texture, cold-work, grain size and microstructure), together with irradiation-induced changes in density and microstructure. A brief account is given of the acceleration of growth in certain zirconium alloys at high fluences (growth breakaway) as well as evidence for breakaway creep. The role of internal stresses from thermo-mechanical treatments on irradiation growth behaviour is discussed. Reprinted from Journal of Nuclear Materials, Vol 159, Fidleris, V., “The Irradiation Creep and Growth Phenomena” pp. 22–42, 1988, with permission from Elsevier.
In-Reactor Deformation of Zirconium Alloy Components
Authors: Holt R. A.
Published: June 2011

This paper briefly reviews work by the author identifying and describing in-reactor deformation mechanisms of materials and structures used in nuclear reactors, in particular, Zircaloy-2, Zircaloy-4, and Zr-2.5Nb, and the CANDU fuel channel (comprising Zr alloy pressure tubes, calandria tubes, and spacers). The discussion is set in the context of contemporary findings of other workers in the international community The following themes are highlighed: The contributions of creep and growth to deformation; c-component dislocations and the fluence dependence of irradiation growth; anisotrophy of irradiation growth; deformation equations and pressure tube-to-calandria tube contact in CANDU reactors; low temperature flux (damage rate) dependence of deformation rates. The first developments were reported in 1976 at the third conference in this series and there are ongoing developments in all areas. The linear low temperature flux dependence of creep and growth rates is yet to be satisfactorily explained. The original paper was published by ASTM International in the Journal of ASTM International, June 2008.
Microstructure Evolution in Zr Alloys during Irradiation: Dose, Dose Rate, and Impurity Dependence
Authors: Griffiths M.
Published: June 2011

The performance of zirconium alloys in BWR, PWR, and PHWR nuclear reactors is dependent on the microstructure. Accordingly, the characterization of the microstructure is an integral part of any study conducted to develop models for in-reactor performance. Although the as-fabricated microstructure (texture, grain size, dislocation density, and phase or precipitate distribution) determines the basic physical properties of a given component, there are changes that occur during irradiation that can have a significant effect on these properties. Microstructures that illustrate specific features of the radiation damage that forms in Zr alloys will be illustrated and discussed in terms of the dose, dose rate, and impurity factors that are applicable. The original paper was published by ASTM International in the Journal of ASTM International, December 2007.
Latein als Medium für das Russisch-französische Wörterbuch von Antioch Kantemir
Authors: Otten Fred
Published: June 2011

The “century of the encyclopaedias and dictionaries” (Siècle de l’Encyclopédie) in France will have induced Antioch Kantemir (in 1738–1744 in Paris as Russian diplomat) to compile the first known “Russian-French dictionary”. As his main sources – Polikarpov (1704) and Weismann (1731) – provided Russian and Latin equivalents (as well as Greek or German vocabulary), but not the French words, a remarkable specific feature of the Kantemir-dictionary becomes apparent: for the French semantization process of Russian headwords often the Latin equivalent was used by means of consultation of Latin-French encyclopaedias or French dictionaries listing also the Latin words (even Lémery’s Latin-French specialised dictionary). Those dictionaries prove a Russian-Latin-French transfer, even though the step from Latin to French is not listed in Kantemir’s dictionary.
Transpositionen ins Glück? Jáchym Topols Kurzroman „Anděl“
Authors: Gölz Christine
Published: June 2011

The novel “Anděl / Angel Station” delivers an another example of the unusual writing style of the Czech author Jáchym Topol after “Sestra / City Sister Silver”. In his early narratives the author deals with the harrowing times after 1991 not only thematically, but also on a structural and linguistic level. This troubling thriller, driven by the search for happiness in threatening static times, unfolds into an allegory – and proclaims a story of salvation both psychedelic and from an “unreliable” perspective. The paper shows how this allegory is produced through a specific poetic of transpositions, by examples of displacement figures on the spatio-temporal level, on the level of motifs and the specific development of the story. In doing so, a glance is cast on the changes that are made through translation (drawing on the example of the German translation) and by transferring the novel to other media (here, above all, the resulting film).
Buchbesprechung
Authors: Fieguth Rolf
Published: June 2011

Reinhard Ibler (Hg.), Der russische Gedichtzyklus: Ein Handbuch. Heidelberg: Universitätsverlag Winter, 2006, 356 S., Personenverzeichnis, ISBN 3-8253-5253-6
Changes in the Htp-dj-nsw Formula in the Late Middle Kingdom and the Second Intermediate Period
Authors: Ilin-Tomich Alexander
Published: June 2011

The paper focuses on the formal criteria to date the inscriptions currently attributed to the “Late Middle Kingdom” more precisely. This time-span is divided into three periods: the late Twelfth dynasty (Senwosret III to Neferusobek), the Thirteenth dynasty and the Second Intermediate Period. On the basis of a study of the offering formulas on 479 datable monuments, the existing dating criteria are reviewed and new approaches are established.

An early date of the king Awibre Hor proposed by S. Aufrère is also disputed.
Miszelle
Authors: Bojowald Stefan
Published: June 2011

In this article the “Eye-determinativ” after the “bxn”-stone is studied once again. The aim is to show, that it could be influenced by the radix “bAX” with three different meanings related to the eye.
Japan's Involvement in Asia-Centered Regional Forums in the Context of Relations with China and the United States
Authors: Chung Chien-Peng
Published: June 2011

Against China's attempts at cultivating multilateral forums to augment and institutionalize its influence in Central, Northeast, and Southeast Asia, Japan's major foreign policy challenge now is how to secure its own interests in these forums while balancing its relations with China and the United States.
Dogtooth: The Family Syndrome
Authors: Fisher Mark
Published: June 2011

An analysis of Yorgos Lanthimos's Dogtooth, in which parents create a totally insular, weirdly theatrical, and sometimes brutal world for their children. To what extent does this blackly comic, almost Dadaist horror show show reveal wider truths about what Badiou calls today's “pathogenic” families?
Crowd, Mob, and Nation in Boris Godunov: What Did Musorgsky Think, and Does It Matter?
Authors: Taruskin Richard
Published: June 2011

When Musorgsky revised his opera Boris Godunov in 1871–72 as a condition for its eventual performance in 1874, he made many changes that went far beyond what the Imperial Theaters demanded of him. Among these changes was the composition of a crowd scene outside Moscow, in which the rebellious populace hails the Pretender, to replace a crowd scene at Red Square in which a submissive, hungry crowd begs Boris for bread. The original scene came, like the rest of the libretto, directly from Pushkin's eponymous play. The new scene reflected a new view of the historical events, and Musorgsky wrote his own text for it. The two scenes are ideologically at odds, particularly as regards their view of the Russian nation in relation to the Russian people. Moreover, the two scenes share the episode of the Holy Fool and the thieving boys, which Musorgsky transferred from the one score to the other. Obviously, Musorgsky regarded them as incompatible within a single production and thought he had made conflating them impossible. And yet, at the Bolshoy Theater, beginning in 1927, the two scenes have indeed been played that way, inconsistencies and redundancies be damned. The Bolshoy production of 1939 (which became widely known and influential through recordings and film) might be written off, the way we tend to write off the art of the Stalinist era, as a politically motivated anomaly. But many other productions and most recordings since 1948 have included both scenes without any such evident motivation, indicating that the Bolshoy production is now regarded as canonical. Is the historiographical contradiction involving the theme of the conference at which this article was first presented (“Opera and Nation,” Budapest 2010) to be regarded as a blemish? If not, what considerations can be seen to outweigh it? Can Musorgsky's political ideas be deduced from the work in which we assume they are embodied? And if they can be, should they be regarded as an aspect of the work that performers need respect?
The Panama-California Exposition, San Diego, 1915: The Olmsted Brothers' Ecological Park Typology
Authors: O'Hara Christine Edstrom
Published: June 2011

During the last weeks of his practice, Frederick Law Olmsted, Sr., wrote that the future of his firm depended on developing an appropriate landscape style for the arid West. Christine Edstrom O'Hara tells how his sons' firm, Olmsted Brothers, set out to reach that goal in their unbuilt proposal for the 1915 San Diego Panama-California Exposition, in what is now Balboa Park. The Panama-California Exposition, San Diego, 1915: The Olmsted Brothers' Ecological Park Typology is the story of their innovative embrace of regionalist aesthetics and a respect for local ecology, topography, and weather. The ideals of their design, however, were not taken up by their clients. The Olmsted firm was fired, and the fairgrounds that welcomed visitors to San Diego in 1915 had architecture that was more appropriate to large cities and a landscape better suited to a wet climate.
"In the Nature of a Clinic": The Design of Early Public Housing in St. Louis
Authors: Heathcott Joseph
Published: June 2011

Several important episodes in the early history of mass housing in America are the subject of "In the Nature of a Clinic": The Design of Early Public Housing in St. Louis. In the late 1920s housing and reform advocates coalesced out of the strong St. Louis settlement house to push for slum clearance and large-scale home building for the working class. Their first achievement, Joseph Heathcott reports, was Neighborhood Gardens, completed in 1934 with funding from the Public Works Administration. Modern in architectural design and segregated in social plan, the project established a model for the larger undertakings inspired by the landmark 1937 Housing Act. By World War II, housing advocates and officials in St. Louis had created prototypes of a new urban form that would shape postwar activities, including the notorious Pruitt-Igoe.