bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice
Authors: Rajanahally Saneal , Agno Julio E , Nalam Roopa L , Weinstein Michael B , Loveland Kate L , Matzuk Martin M , Li Qinglei
Published: June 2010

Background

Inhibin is a tumor-suppressor and activin antagonist. Inhibin-deficient mice develop gonadal tumors and a cachexia wasting syndrome due to enhanced activin signaling. Because activins signal through SMAD2 and SMAD3 in vitro and loss of SMAD3 attenuates ovarian tumor development in inhibin-deficient females, we sought to determine the role of SMAD2 in the development of ovarian tumors originating from the granulosa cell lineage.

Methods

Using an inhibin α null mouse model and a conditional knockout strategy, double conditional knockout mice of Smad2 and inhibin alpha were generated in the current study. The survival rate and development of gonadal tumors and the accompanying cachexia wasting syndrome were monitored.

Results

Nearly identical to the controls, the Smad2 and inhibin alpha double knockout mice succumbed to weight loss, aggressive tumor progression, and death. Furthermore, elevated activin levels and activin-induced pathologies in the liver and stomach characteristic of inhibin deficiency were also observed in these mice. Our results indicate that SMAD2 ablation does not protect inhibin-deficient females from the development of ovarian tumors or the cachexia wasting syndrome.

Conclusions

SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin.
Effects of vitrification on nuclear maturation, ultrastructural changes and gene expression of canine oocytes
Authors: Turathum Bongkoch , Saikhun Kulnasan , Sangsuwan Parisatcha , Kitiyanant Yindee
Published: June 2010

Background

Cryopreservation of oocytes, which is an interesting procedure to conserve female gametes, is an essential part of reproductive biotechnology. The objective of the present study was to investigate the effects of vitrification on nuclear maturation, ultrastructural changes and gene expression of canine oocytes.

Methods

Immature oocytes (germinal vesicles) isolated from ovaries of normal bitches (> 6 months of age) were either vitrified in open pulled straw (OPS) using 20% ethylene glycol (EG) and 20% dimethyl sulfoxide (DMSO) as vitrification solution or exposed to vitrification solution without subjected to liquid nitrogen. After warming, oocytes were investigated for nuclear maturation following in vitro maturation (IVM), ultrastructural changes using transmission electron microscopy (TEM) and gene expression using RT-PCR. Fresh immature oocytes were used as the control group.

Results

The rate of resumption of meiosis in vitrified-warmed oocytes (53.4%) was significantly (P < 0.05) lower than those of control (93.8%) and exposure (91.4%) groups. However, there were no statistically significant differences among groups in the rates of GV oocytes reaching the maturation stage (metaphase II, MII). The ultrastructural alterations revealed by TEM showed that cortical granules, mitochondria, lipid droplets and smooth endoplasmic reticulum (SER) were affected by vitrification procedures. RT-PCR analysis for gene expression revealed no differences in HSP70, Dnmt1, SOD1 and BAX genes among groups, whereas Bcl2 was strongly expressed in vitrified-warmed group when compared to the control.

Conclusion

Immature canine oocytes were successfully cryopreserved, resumed meiosis and developed to the MII stage. The information obtained in this study is crucial for the development of an effective method to cryopreserve canine oocytes for establishment of genetic banks of endangered canid species.
Objective cough frequency in Idiopathic Pulmonary Fibrosis
Authors: Key Angela L , Holt Kimberley , Hamilton Andrew , Smith Jaclyn A , Earis John E
Published: June 2010

Background

Cough is a common presenting symptom in patients with Idiopathic Pulmonary Fibrosis (IPF). This study measured cough rates in IPF patients and investigated the association between cough and measures of health related quality of life and subjective cough assessments. In addition, IPF cough rates were related to measures of physiological disease severity and compared to cough rates in health and other respiratory conditions.

Methods

Nineteen IPF patients, mean age 70.8 years ± 8.6, five female (26.3%) were studied. Subjects performed full pulmonary function testing, 24 hour ambulatory cough recordings, completed a cough related quality of life questionnaire (Leicester Cough Questionnaire) and subjectively scored cough severity with a visual analogue scale. Ambulatory cough recordings were manually counted and reported as number of coughs per hour.

Results

The 24hr cough rates were high (median 9.4, range 1.5-39.4), with day time rates much higher than night time (median 14.6, range 1.9-56.6 compared to 1.9, range 0-19.2, p = 0.003). Strong correlations were found between objective cough frequency and both the VAS (day r = 0.80, p < 0.001, night r = 0.71, p = 0.001) and LCQ (r = -0.80, p < 0.001), but not with measures of pulmonary function. Cough rates in IPF were higher than healthy subjects (p < 0.001) and asthma patients (p < 0.001) but similar to patients with chronic cough (p = 0.33).

Conclusions

This study confirms objectively that cough is a major, very distressing and disabling symptom in IPF patients. The strong correlations between objective cough counts and cough related quality of life measures suggest that in IPF patient's, perception of cough frequency is very accurate.
A case of mesothelial/monocytic incidental cardiac excrescence and literature review
Authors: Hu Zhong-Liang , Lü Hui , Yin Hong-Ling , Wen Ji-Fang , Jin Ou
Published: June 2010

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare entity which is an amalgam of mesothelial cells, histiocytes, and fibrin, often found occasionally during cardiac valve replacement. We report a case in a 25-year-old Chinese female with serous mitral stenosis and patent foramen ovale. Routine and immunohistochemical stains and ultrastructure examination revealed the vegetation was predominantly composed of histocytes with scattered mesothelial cells. In fact nodular histiocytic/mesothelial hyperplasia (NHMH) is a similar lesion to MICE. MICE and NHMH could be unified, and NHMH may be a better choice.
The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease
Authors: Fox Jonathan H , Connor Teal , Chopra Vanita , Dorsey Kate , Kama Jibrin A , Bleckmann Dorothee , Betschart Claudia , Hoyer Daniel , Frentzel Stefan , DiFiglia Marian , Paganetti Paolo , Hersch Steven M
Published: June 2010

Background

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD). In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD.

Results

Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels.

Conclusions

Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.
Reduced trabecular bone mineral density and cortical thickness accompanied by increased outer bone circumference in metacarpal bone of rheumatoid arthritis patients: a cross-sectional study
Authors: Aeberli Daniel , Eser Prisca , Bonel Harald , Widmer Jolanda , Caliezi Gion , Varisco Pierre-Alain , Möller Burkhard , Villiger Peter M
Published: June 2010

Introduction

The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT).

Methods

PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics.

Results

Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04).

Conclusions

Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone.
Recommendations for the intra-hospital transport of critically ill patients
Authors: Fanara Benoît , Manzon Cyril , Barbot Olivier , Desmettre Thibaut , Capellier Gilles
Published: June 2010

Introduction

This study was conducted to provide Intensive Care Units and Emergency Departments with a set of practical procedures (check-lists) for managing critically-ill adult patients in order to avoid complications during intra-hospital transport (IHT).

Methods

Digital research was carried out via the MEDLINE, EMBASE, CINAHL and HEALTHSTAR databases using the following key words: transferring, transport, intrahospital or intra-hospital, and critically ill patient. The reference bibliographies of each of the selected articles between 1998 and 2009 were also studied.

Results

This review focuses on the analysis and overcoming of IHT-related risks, the associated adverse events, and their nature and incidence. The suggested preventive measures are also reviewed. A check-list for quick execution of IHT is then put forward and justified.

Conclusions

Despite improvements in IHT practices, significant risks are still involved. Basic training, good clinical sense and a risk-benefit analysis are currently the only deciding factors. A critically ill patient, prepared and accompanied by an inexperienced team, is a risky combination. The development of adapted equipment and the widespread use of check-lists and proper training programmes would increase the safety of IHT and reduce the risks in the long-term. Further investigation is required in order to evaluate the protective role of such preventive measures.
Bacteria-induced phagocyte secondary necrosis as a pathogenicity mechanism
Authors: Silva Manuel T
Published: June 2010

Review discusses bacterial mechanism promoting immune evasion and release of tissue-damaging phagocyte molecules by induction of macrophage and neutrophil apoptotic secondary necrosis.

Triggering of phagocyte apoptosis is a major virulence mechanism used by some successful bacterial pathogens. A central issue in the apoptotic death context is that fully developed apoptosis results in necrotic cell autolysis (secondary necrosis) with release of harmful cell components. In multicellular animals, this occurs when apoptosing cells are not removed by scavengers, mainly macrophages. Secondary necrotic lysis of neutrophils and macrophages may occur in infection when extensive phagocyte apoptosis is induced by bacterial cytotoxins and removal of apoptosing phagocytes is defective because the apoptotic process exceeds the available scavenging capacity or targets macrophages directly. Induction of phagocyte secondary necrosis is an important pathogenic mechanism, as it combines the pathogen evasion from phagocyte antimicrobial activities and the release of highly cytotoxic molecules, particularly of neutrophil origin, such as neutrophil elastase. This pathogenicity mechanism therefore promotes the unrestricted multiplication of the pathogen and contributes directly to the pathology of several necrotizing infections, where extensive apoptosis and necrosis of macrophages and neutrophils are present. Here, examples of necrotizing infectious diseases, where phagocyte secondary necrosis is implicated, are reviewed.
Parent Opinions Regarding the Genetic Testing of Minors for BRCA1/2
Authors: Bradbury Angela R. , Patrick-Miller Linda , Egleston Brian , Sands Colleen Burke , Li Tianyu , Schmidheiser Helen , Feigon Maia , Ibe Comfort N. , Hlubocky Fay J. , Hope Kisha , Jackson Sarah , Corbman Melanie , Olopade Olufunmilayo I. , Daly Mary , Daugherty Christopher K.
Published: June 2010

Purpose

Although not currently recommended, genetic testing of minors for adult hereditary cancer syndromes, along with risks and benefits, is still being debated. Thus, we evaluated parent opinions regarding BRCA1/2 testing of minors, in general, and hypothetically, for parents' own minor child.

Methods

Semistructured interviews were conducted to assess parent opinions regarding BRCA1/2 testing in minors, along with parent rationale for and factors associated with these opinions.

Results

In total, 246 parents at two academic cancer risk assessment programs who underwent BRCA1/2 testing completed the interview (60% response rate). In response to a dichotomous question, 37% of parents supported testing minors. Responses to an open-ended query suggest that 47% support testing minors in some or all circumstances. Parent negative BRCA1/2 test result (P = .02), parent male sex (P = .03), and minority race (P = .01) were independently associated with support of testing minors. In response to a dichotomous question, 44% of parents reported hypothetical interest in testing their own minor offspring. Responses to an open-ended query suggest that 55% would consider, hypothetically, testing their child in some or all circumstances. Parent negative test result (P = .01), less than a college education (P < .01), and older mean offspring age (P = .05) were associated with interest in testing one's own child.

Conclusion

Parents' opinions regarding BRCA1/2 testing of minors are divided. Given the lack of evidence supporting either the permission or restriction of BRCA1/2 testing in minors, further evaluation of the risks and benefits of providing genetic risk information and genetic testing to minors for adult-onset disease is needed to inform clinical practice and guidelines.
Oral Bisphosphonate Use and Breast Cancer Incidence in Postmenopausal Women
Authors: Chlebowski Rowan T. , Chen Zhao , Cauley Jane A. , Anderson Garnet , Rodabough Rebecca J. , McTiernan Anne , Lane Dorothy S. , Manson JoAnn E. , Snetselaar Linda , Yasmeen Shagufta , O'Sullivan Mary Jo , Safford Monika , Hendrix Susan L. , Wallace Robert B.
Published: June 2010

Purpose

Emerging clinical evidence suggests intravenous bisphosphonates may inhibit breast cancer while oral bisphosphonates have received limited evaluation regarding breast cancer influence.

Patients and Methods

The association between oral bisphosphonate use and invasive breast cancer was examined in postmenopausal women enrolled onto the Women's Health Initiative (WHI). We compared a published hip fracture prediction model, which did not incorporate bone mineral density (BMD), with total hip BMD in 10,418 WHI participants who had both determinations. To adjust for potential BMD difference based on bisphosphonate use, the hip fracture prediction score was included in multivariant analyses as a BMD surrogate.

Results

Of the 154,768 participants, 2,816 were oral bisphosphonate users at entry (90% alendronate, 10% etidronate). As calculated hip fracture risk score was significantly associated with both BMD (regression line = 0.79 to 0.0478 log predicted fracture; P < .001; r = 0.43) and breast cancer incidence (P = .03), this variable was incorporated into regression analyses to adjust for BMD difference between users and nonusers of bisphopshonate. After 7.8 mean years of follow-up (standard deviation, 1.7), invasive breast cancer incidence was lower in bisphosphonate users (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.88; P < .01) as was incidence of estrogen receptor (ER) –positive invasive cancers (HR, 0.70; 95% CI, 0.52 to 0.94, P = .02). A similar but not significant trend was seen for ER-negative invasive cancers. The incidence of ductal carcinoma in situ was higher in bisphosphonate users (HR, 1.58; 95% CI, 1.08 to 2.31; P = .02).

Conclusion

Oral bisphosphonate use was associated with significantly lower invasive breast cancer incidence, suggesting bisphosphonates may have inhibiting effects on breast cancer.
Phase III Trial Comparing Protracted Intravenous Fluorouracil Infusion Alone or With Yttrium-90 Resin Microspheres Radioembolization for Liver-Limited Metastatic Colorectal Cancer Refractory to Standard Chemotherapy
Authors: Hendlisz Alain , Eynde Marc Van den , Peeters Marc , Maleux Geert , Lambert Bieke , Vannoote Jaarke , Keukeleire Katrien De , Verslype Chris , Defreyne Luc , Cutsem Eric Van , Delatte Philippe , Delaunoit Thierry , Personeni Nicola , Paesmans Marianne , Laethem Jean-Luc Van , Flamen Patrick
Published: June 2010

Purpose

Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the β-emitting isotope yttrium-90 (90Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues.

Patients and Methods

We conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m2 days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m2 days 1 through 14 then 300 mg/m2 days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A.

Results

Forty-six patients were randomly assigned and 44 were eligible for analysis (arm A, n = 23; arm B, n = 21). Median follow-up was 24.8 months. Median TTLP was 2.1 and 5.5 months in arms A and B, respectively (hazard ratio [HR] = 0.38; 95% CI, 0.20 to 0.72; P = .003). Median time to tumor progression (TTP) was 2.1 and 4.5 months, respectively (HR = 0.51; 95% CI, 0.28 to 0.94; P = .03). Grade 3 or 4 toxicities were recorded in six patients after FU monotherapy and in one patient after radioembolization plus FU treatment (P = .10). Twenty-five of 44 patients received further treatment after progression, including 10 patients in arm A who received radioembolization. Median overall survival was 7.3 and 10.0 months in arms A and B, respectively (HR = 0.92; 95% CI, 0.47 to 1.78; P = .80).

Conclusion

Radioembolization with 90Y-resin microspheres plus FU is well tolerated and significantly improves TTLP and TTP compared with FU alone. This procedure is a valid therapeutic option for chemotherapy-refractory liver-limited mCRC.
Sm proteins specify germ cell fate by facilitatingoskarmRNA localization
Authors: Gonsalvez Graydon B. , Rajendra T. K. , Wen Ying , Praveen Kavita , Matera A. Gregory
Published: June 2010

Sm and Sm-like proteins are RNA-binding factors found in all three domains of life. Eukaryotic Sm proteins play essential roles in pre-mRNA splicing, forming the cores of spliceosomal small nuclear ribonucleoproteins (snRNPs). Recently, Sm proteins have been implicated in the specification of germ cells. However, a mechanistic understanding of their involvement in germline specification is lacking and a germline-specific RNA target has not been identified. We demonstrate that Drosophila SmB and SmD3 are specific components of the oskar messenger ribonucleoprotein (mRNP), proper localization of which is required for establishing germline fate and embryonic patterning. Importantly, oskar mRNA is delocalized in females harboring a hypomorphic mutation in SmD3, and embryos from mutant mothers are defective in germline specification. We conclude that Sm proteins function to establish the germline in Drosophila, at least in part by mediating oskar mRNA localization.
Modeling bistable cell-fate choices in theDrosophilaeye: qualitative and quantitative perspectives
Authors: Graham Thomas G. W. , Tabei S. M. Ali , Dinner Aaron R. , Rebay Ilaria
Published: June 2010

A major goal of developmental biology is to understand the molecular mechanisms whereby genetic signaling networks establish and maintain distinct cell types within multicellular organisms. Here, we review cell-fate decisions in the developing eye of Drosophila melanogaster and the experimental results that have revealed the topology of the underlying signaling circuitries. We then propose that switch-like network motifs based on positive feedback play a central role in cell-fate choice, and discuss how mathematical modeling can be used to understand and predict the bistable or multistable behavior of such networks.
Predicting embryonic patterning using mutual entropy fitness and in silico evolution
Authors: François Paul , Siggia Eric D.
Published: June 2010

During vertebrate embryogenesis, the expression of Hox genes that define anterior-posterior identity follows general rules: temporal colinearity and posterior prevalence. A mathematical measure for the quality or fitness of the embryonic pattern produced by a gene regulatory network is derived. Using this measure and in silico evolution we derive gene interaction networks for anterior-posterior (AP) patterning under two developmental paradigms. For patterning during growth (paradigm I), which is appropriate for vertebrates and short germ-band insects, the algorithm creates gene expression patterns reminiscent of Hox gene expression. The networks operate through a timer gene, the level of which measures developmental progression (a candidate is the widely conserved posterior morphogen Caudal). The timer gene provides a simple mechanism to coordinate patterning with growth rate. The timer, when expressed as a static spatial gradient, functions as a classical morphogen (paradigm II), providing a natural way to derive the AP patterning, as seen in long germ-band insects that express their Hox genes simultaneously, from the ancestral short germ-band system. Although the biochemistry of Hox regulation in higher vertebrates is complex, the actual spatiotemporal expression phenotype is not, and simple activation and repression by Hill functions suffices in our model. In silico evolution provides a quantitative demonstration that continuous positive selection can generate complex phenotypes from simple components by incremental evolution, as Darwin proposed.
Endothelial α5 and αv integrins cooperate in remodeling of the vasculature during development
Authors: van der Flier Arjan , Badu-Nkansah Kwabena , Whittaker Charles A. , Crowley Denise , Bronson Roderick T. , Lacy-Hulbert Adam , Hynes Richard O.
Published: June 2010

Integrin cell adhesion receptors and fibronectin, one of their extracellular matrix ligands, have been demonstrated to be important for angiogenesis using functional perturbation studies and complete knockout mouse models. Here, we report on the roles of the α5 and αv integrins, which are the major endothelial fibronectin receptors, in developmental angiogenesis. We generated an integrin α5-floxed mouse line and ablated α5 integrin in endothelial cells. Unexpectedly, endothelial-specific knockout of integrin α5 has no obvious effect on developmental angiogenesis. We provide evidence for genetic interaction between mutations in integrin α5 and αv and for overlapping functions and compensation between these integrins and perhaps others. Nonetheless, in embryos lacking both α5 and αv integrins in their endothelial cells, initial vasculogenesis and angiogenesis proceed normally, at least up to E11.5, including the formation of apparently normal embryonic vasculature and development of the branchial arches. However, in the absence of endothelial α5 and αv integrins, but not of either alone, there are extensive defects in remodeling of the great vessels and heart resulting in death at ~E14.5. We also found that fibronectin assembly is somewhat affected in integrin α5 knockout endothelial cells and markedly reduced in integrin α5/αv double-knockout endothelial cell lines. Therefore, neither α5 nor αv integrins are required in endothelial cells for initial vasculogenesis and angiogenesis, although they are required for remodeling of the heart and great vessels. These integrins on other cells, and/or other integrins on endothelial cells, might contribute to fibronectin assembly and vascular development.
Influence of Fat-Hippo and Notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia
Authors: Reddy B. V. V. G. , Rauskolb Cordelia , Irvine Kenneth D.
Published: June 2010

The Drosophila optic lobe develops from neuroepithelial cells, which function as symmetrically dividing neural progenitors. We describe here a role for the Fat-Hippo pathway in controlling the growth and differentiation of Drosophila optic neuroepithelia. Mutation of tumor suppressor genes within the pathway, or expression of activated Yorkie, promotes overgrowth of neuroepithelial cells and delays or blocks their differentiation; mutation of yorkie inhibits growth and accelerates differentiation. Neuroblasts and other neural cells, by contrast, appear unaffected by Yorkie activation. Neuroepithelial cells undergo a cell cycle arrest before converting to neuroblasts; this cell cycle arrest is regulated by Fat-Hippo signaling. Combinations of cell cycle regulators, including E2f1 and CyclinD, delay neuroepithelial differentiation, and Fat-Hippo signaling delays differentiation in part through E2f1. We also characterize roles for Jak-Stat and Notch signaling. Our studies establish that the progression of neuroepithelial cells to neuroblasts is regulated by Notch signaling, and suggest a model in which Fat-Hippo and Jak-Stat signaling influence differentiation by their acceleration of cell cycle progression and consequent impairment of Delta accumulation, thereby modulating Notch signaling. This characterization of Fat-Hippo signaling in neuroepithelial growth and differentiation also provides insights into the potential roles of Yes-associated protein in vertebrate neural development and medullablastoma.
Innovation Blindness: Culture, Frames, and Cross-Boundary Problem Construction in the Development of New Technology Concepts
Authors: Leonardi Paul M.
Published: June 2010

This paper has three goals. The first is to understand why members of one organizational department are blind to the reasons why members of another department do not share their ideas for a new technology—what I call a “technology concept.” The second is to understand what consequences this “innovation blindness” has for the development of technology concepts across organizational and occupational boundaries. The third is to uncover strategies organizations might use to successfully develop a new technological artifact from the technology concept even if innovators never understand the nature of their own blindness. To achieve these goals, I draw on research on organizational cultural toolkits to construct a framework suggesting that technology concepts frame cultural resources, which are then used to construct the very problems the technological artifact will be built to solve. From this perspective, culture does not directly shape technological artifacts. Rather, a technology concept activates culture as it draws frames around resources that will guide people's problem construction practices. By acting as a frame through which problems can be constructed, technology concepts play a key role in selecting the set of cultural resources that will be used to develop technological artifacts. I explore this framework through a qualitative study of computer simulation software in a major automotive engineering firm.
The Cultural Category of Cooperation: A Cultural Consensus Model Analysis for China and the United States
Authors: Keller Joshua , Loewenstein Jeffrey
Published: June 2010

We provide evidence that cooperation is a cultural category, and that what it means to cooperate is culturally conditioned. We use a cultural consensus model analysis to assess which types of situations people categorize as cooperation and whether these categorizations are consistent within and across China and the United States. The data support revisiting the role of cognition in mediating cooperative behavior and the means by which culture shapes behavior. The data also support broadening research attention to multiple aspects of cooperation within the same theory, generating new research on reciprocity, and rethinking how key behaviors, such as competition and helping, relate to cooperation.
PERSPECTIVE—Organizational Cognitive Neuroscience
Authors: Senior Carl , Lee Nick , Butler Michael
Published: June 2010

Organizational cognitive neuroscience (OCN) is the cognitive neuroscientific study of organizational behavior. OCN lets us start to understand the relationship between our organizational behavior and our brains and allows us to dissect specific social processes at the neurobiological level and apply a wider range of analysis to specific organizational research questions. The current paper examines the utility of OCN to address specific organizational research questions. A brief history and definition of the approach is first provided. Next, a discussion of the rationale for OCN as a research framework is provided, and then, finally, an overview of the range of techniques that the organizational researcher should (or should not) use is described.
Rational Decision Making as Performative Praxis: Explaining Rationality'sÉternel Retour
Authors: Cabantous Laure , Gond Jean-Pascal
Published: June 2010

Organizational theorists built their knowledge of decision making through a progressive critique of rational choice theory. Their positioning towards rationality, however, is at odds with the observation of rationality persistence in organizational life. This paper addresses this paradox. It proposes a new perspective on rationality that allows the theorizing of the production of rational decisions by organizations. To account for rationality's éternel retour, we approach rational decision making as performative praxis—a set of activities that contributes to turning rational choice theory into social reality. We develop a performative praxis framework that explains how theory, actors, and tools together produce rationality within organizations through three mechanisms: rationality conventionalization, rationality engineering, and rationality commodification. This framework offers new avenues of research on rational decision making and points to the factors that underlie the manufacture of rationality in organizations.
Reliable computation of scattering from metallic binary gratings using Fourier-based modal methods
Authors: Gundu Krishna Mohan , Mafi Arash
Published: June 2010

Convergence problems in modal methods for TM polarized fields are often attributed to the inaccuracies in computing the modes of a grating. We report that even in the absence of these inaccuracies convergence problems persist. These arise because of the truncation of the infinite set of linear equations resulting from matching the fields at the grating–substrate and grating–superstrate interfaces with a square matrix. We show that dramatic improvement in convergence can be achieved if the infinite set of linear equations is truncated with a rectangular matrix and by seeking a solution with minimum least squared error.
Resolution properties of nonlinear optical microscopy
Authors: Fukutake Naoki
Published: June 2010

We analyze the resolution properties of nonlinear optical microscopy systems that use nonlinear optical effects, such as multiphoton-excited fluorescence, second- and third-harmonic generation, coherent anti-Stokes Raman scattering, and stimulated-emission depletion. Image formation formulas are presented that unitedly describe the properties of the image observed, wherein coherent, incoherent, or mixed-coherent phenomena are utilized. We develop the formalism for the optical resolution of all types of nonlinear systems. The properties of image formation represented by the transmission cross-coefficient are different depending on the type of nonlinear systems.
Complex space source theory of partially coherent light wave
Authors: Seshadri S. R.
Published: June 2010

The complex space source theory is used to derive a general integral expression for the vector potential that generates the extended full Gaussian wave in terms of the input value of the vector potential of the corresponding paraxial beam. The vector potential and the fields are assumed to fluctuate on a time scale that is large compared to the wave period. The Poynting vector in the propagation direction averaged over a wave period is expressed in terms of the cross-spectral density of the fluctuating vector potential across the input plane. The Schell model is assumed for the cross-spectral density. The radiation intensity distribution and the power radiated are determined. The effect of spatial coherence on the radiation intensity distribution and the radiated power are investigated for different values of the physical parameters. Illustrative numerical results are provided to bring out the effect of spatial coherence on the propagation characteristics of the fluctuating light wave.
SPARC/Osteonectin Functions to Maintain Homeostasis of the Collagenous Extracellular Matrix in the Periodontal Ligament
Authors: Trombetta Jessica M. , Bradshaw Amy D. , Johnson Ralph H.
Published: June 2010

Expression of secreted protein acidic and rich in cysteine (SPARC)/osteonectin, a collagen-binding matricellular protein, is frequently associated with tissues with high rates of collagen turnover, such as bone. In the oral cavity, expression of SPARC/osteonectin has been localized to the periodontal ligament (PDL), a collagen-rich tissue with high rates of collagen turnover. The PDL is critical for tooth position within the alveolar bone and for absorbing forces generated by chewing. To characterize the function of SPARC/osteonectin in PDL, SPARC/osteonectin expression in murine PDL was evaluated by immunochemistry at 1, 4, 6, and >18 months. Highest levels of SPARC/osteonectin were detected at 1 and >18 months, with decreased levels associated with adult (4–6 months) PDL. To determine whether the absence of SPARC/osteonectin expression influenced cellular and fibrillar collagen content in PDL, PDL of SPARC-null mice was evaluated using histological stains and compared with that of wild-type (WT). Our results demonstrated decreased numbers of nuclei in PDL of SPARC-null mice at 1 month. In addition, decreased collagen volume fractions were found at 1 and >18 months and decreases in thick collagen fiber volume fraction were detected at 4, 6, and >18 months in SPARC-null PDL. The greatest differences in cell number and in collagen content between SPARC-null and WT PDL coincided with ages at which levels of SPARC/osteonectin expression were highest in WT PDL, at 1 and >18 months. These results support the hypothesis that SPARC/osteonectin is critical in the control of tissue collagen content and indicate that SPARC/osteonectin is necessary for PDL homeostasis.
Localization of Carboxyl Ester Lipase in Human Pituitary Gland and Pituitary Adenomas
Authors: La Rosa Stefano , Vigetti Davide , Placidi Claudia , Finzi Giovanna , Uccella Silvia , Clerici Moira , Bartolini Barbara , Carnevali Ileana , Losa Marco , Capella Carlo
Published: June 2010

Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.
Cellular Localization of Sphingosine-1-phosphate Receptor 1 Expression in the Human Central Nervous System
Authors: Nishimura Hirotake , Akiyama Takashi , Irei Isao , Hamazaki Shuji , Sadahira Yoshito
Published: June 2010

Sphingosine-1-phosphate (S1P), a potent lipid mediator, transduces intracellular signals through the activation of S1P receptors (S1PRs). Although S1PRs have been shown to play an important role in the central nervous system (CNS), accurate localization and the function of S1PR1 in the human CNS are still unclear. In this study, we investigated the localization of S1PR1 in the human CNS of postmortem samples, using a rabbit polyclonal antibody, the specificity of which had been well defined. Immunohistochemical investigation of paraffin-embedded sections revealed diffuse granular staining of the gray matter. The signals of the gray matter were much stronger than those of the white matter. The immunohistochemical expression levels correlated well with the results of quantitative real-time RT-PCR-based analysis and Western blotting. Studies using double immunostaining and immunoelectron microscopy revealed that the antigen was strongly expressed in the membrane of the astrocytic foot processes of glia limitans and astrocytes with radial cytoplasm, but not distributed in neurons. In neurological disorders, hypertrophic astrocytes with strong expression of glial fibrillary acidic protein exhibited significantly decreased expression of S1PR1 in contrast to its strong expression in astrocytes forming fibrillary gliosis. These results indicate that S1PR1 is localized in astrocytes, and its expression level may change during the processes that occur after brain damage.
Zur Interpretation adnominaler Genitive bei nominalisierten Infinitiven im Deutschen
Authors: Bücking Sebastian
Published: June 2010

The argumental status of verbal participants in event nominalizations is still under debate. Investigating syntactic and semantic properties of referentially interpreted genitive noun phrases related to German nominalized infinitives (= NI), cf.das Stören der Mannschaft(‘the disturbing the team-gen’), I will argue in favor of different interpretative mechanisms at stake: whereas themes retain their argumental status in the nominal domain, agents are not lambda-bound in the argument structure of NI. Instead, the corresponding participant is a modifier whose agentive interpretation is motivated merely conceptually.

Evidence for the proposed asymmetric analysis comes from two sources: it will be shown that the alleged agentive genitive contributes a possessive relation not identical to the verbal agentive interpretation. The conceptual preference for an identification with the verbal agent will be accounted for by abductive reasoning thereby explaining the modifier's argument-like behavior. In addition, as data on NI from different sources reveal, the genitive interpretation is mainly conditioned by lexical properties of the base verb. In particular, it will be shown that a postnominal agentive interpretation is bound to configurations where the theme is independently predicted optional. These findings follow from the proposed asymmetry.
Ikonizität und Indexikalität im gebärdensprachlichen Lexikon – Zur Typologie sprachlicher Zeichen
Authors: Kutscher Silvia
Published: June 2010

The paper deals with the iconic and indexical relations of lexical signs in German Sign Language (DGS). It is argued that the theory of signs as established by Charles S. Peirce is particular fruitful with respect to the description and classification of signs in the visual-gestural modality, but also needs some additional discussion on the nature of the relation between sign and reference object. As will be demonstrated, motivated signs in German Sign Language are more complex with respect to indexicality and iconicity as is recognized in contemporary research. Accordingly, the paper discusses the necessity to modify the typology of linguistic signs with respect to sign languages. It will be demonstrated that there has to be established a class of schematic signs within the group of hypoicons. Secondly, it is argued that DGS has a class of motivated but non-iconic signs, which show a designative-indexical relation which relates to the spoken or written form of a word of the oral contact language German. In sum, a modified typology of lexical signs is established which not only includes the sign types symbol, index and (image)icon but also the new types schematic icon and indicator (‘Hinweis’).
Resources Employed by Health Researchers to Ensure Ethical Research Practice
Authors: Guillemin Marilys , Gillam Lynn , Rosenthal Doreen , Bolitho Annie
Published: June 2010

There is little empirical evidence about what resources health researchers use in order to make decisions about the ethical conduct of human research. Undertaking an empirical examination of how researchers understand research ethics and how they address ethical issues in research practice can lead to a richer understanding of how researchers approach research ethics. Our findings are based on interviews with 54 Australian health researchers. We conclude that, despite the considerable time devoted to ethics review, ethics committees and research guidelines were not seen as valuable resources for researchers undertaking research in the field. Although researchers did not perceive ethics committees as a resource when faced with ethical issues in the field, they nevertheless perceived the process of ethics review as beneficial to them; this allowed them to clarify their research, make decisions about the ethical conduct of the research, as well as offering them a sense of protection when undertaking research. In the actual undertaking of research practice, it was their past professional experience and personal values that researchers considered most useful resources when encountering ethical problems.
Are We Asking the Right Questions? A Review of Canadian REB Practices in Relation to Community-Based Participatory Research
Authors: Guta Adrian , Wilson Michael G. , Flicker Sarah , Travers Robb , Mason Catherine , Wenyeve Gloria , O'Campo Patricia
Published: June 2010

Access barriers to effective ethics review continue to be a significant challenge for researchers and community-based organizations undertaking community-based participatory research (CBPR). This article reports on findings from a content analysis of select (Behavioural, Biomedical, Social Sciences, Humanities) research ethics boards (REBs) in the Canadian research context (n = 86). Existing ethics review documentation was evaluated using 30 CBPR related criteria for their sensitivity to relevant approaches, processes, and outcomes. A linear regression was conducted to determine whether specific organizational characteristics have an impact on the CBPR sensitivity: (1) region of Canada, (2) type of institution (university or a healthcare organization), (3) primary institutional language (English or French) and (4) national ranking with respect to research intensiveness. While only research intensiveness proved statistically significant (p = .001), we recognize REB protocol forms may not actually reflect how CBPR is reviewed. Despite using a single guiding ethical framework, REBs across Canada employ a variety of techniques to review research studies. We report on these differences and varying levels of sensitivity to CBPR. Finally, we highlight best practices and make recommendations for integrating CBPR principles into existing ethics review.
Parental Permission and Perceived Research Benefits in Adolescent STI Research
Authors: Ott Mary A. , Rosenberger Joshua G. , Fortenberry J. Dennis
Published: June 2010

An understanding of why parents provide consent for adolescent participation in research on sensitive topics can inform and improve the ethical conduct and review of such research. As part of a longitudinal study of sexually transmitted infections (STIs) in lower-income adolescents, we asked 134 parents why they permitted their daughter to participate, analyzing responses using qualitative methods. Over half described participation benefits, providing reasons such as the study being generally good for their daughters, sex education, someone to talk to, and STI testing. Other reasons included positive interactions and familiarity with research and clinical staff, friend or family member participation, and adolescent autonomy in making the decision to participate. If parents perceived their daughter to be “at risk” in some way, such as for STI or pregnancy, they were more likely to cite participation benefits. These data can be used to make such research more sensitive to family and community needs.