bluuebunny/crossref_metadata_2025 huggingface dataset:
The Decline of Human Longevity in the Book of Jubilees
Authors: DeJong David N.
Published: May 2012

This article examines the decline in human longevity in the book of Jubilees, arguing that this motif's importance has been somewhat underappreciated by scholars. It examines three varied genres in Jubilees—death notices, an apocalypse, and an extended narrative—and demonstrates that an emphasis on declining human longevity thematically unifies these diverse additions to the stories of Genesis on which they are based. The decline in lifespan is connected both with the book's chronological system and its concern with covenantal obedience, specifically with respect to the commandment to honor one's parents.
Sustainability-oriented product modular design using kernel-based fuzzy c-means clustering and genetic algorithm
Authors: Yan Jihong , Feng Chunhua , Cheng Kai
Published: May 2012

With increasing sustainable development consciousness, sustainable design plays an important role, not only in the design phase, but also in the manufacturing process. Existing design methods, including life cycle design and environmental design, have not fully considered sustainability requirements. A modular design methodology is proposed for achieving sustainable design as well as fulfilling functional requirements. Factors related to function and sustainability of a product, such as material, manufacturability, component life, and so on, are defined as modular drivers. A design structure matrix, with great advantages on analyzing the correlation between product system elements, is employed to establish a correlation matrix between components. A kernel-based fuzzy c-means algorithm is used to integrate components of a product into different modules based on their correlation distance. Meanwhile, a genetic algorithm is employed to determine the optimal clustering number on account of its efficiency in coming up with the global solutions. In addition, an assessment model for product sustainability is established considering economic, social, and environmental factors. Finally, a reduction gear is used as a case study example to show the effectiveness of the proposed sustainability-oriented modular design method.
A Skew-t space-varying regression model for the spectral analysis of resting state brain activity
Authors: Ismail Salimah , Sun Wenqi , Nathoo Farouk S , Babul Arif , Moiseev Alexader , Beg Mirza Faisal , Virji-Babul Naznin
Published: May 2012

It is known that in many neurological disorders such as Down syndrome, main brain rhythms shift their frequencies slightly, and characterizing the spatial distribution of these shifts is of interest. This article reports on the development of a Skew-t mixed model for the spatial analysis of resting state brain activity in healthy controls and individuals with Down syndrome. Time series of oscillatory brain activity are recorded using magnetoencephalography, and spectral summaries are examined at multiple sensor locations across the scalp. We focus on the mean frequency of the power spectral density, and use space-varying regression to examine associations with age, gender and Down syndrome across several scalp regions. Spatial smoothing priors are incorporated based on a multivariate Markov random field, and the markedly non-Gaussian nature of the spectral response variable is accommodated by the use of a Skew-t distribution. A range of models representing different assumptions on the association structure and response distribution are examined, and we conduct model selection using the deviance information criterion. 1 Our analysis suggests region-specific differences between healthy controls and individuals with Down syndrome, particularly in the left and right temporal regions, and produces smoothed maps indicating the scalp topography of the estimated differences.
The Administrator as Superhero
Authors: Lewicki Roy J.
Published: May 2012

As a way to achieve better alignment of the ongoing teaching–research activity gap in business schools, David Balkin and Jeff Mello suggest that schools need to hire academic administrators with significantly developed management skills. The author responds to this recommendation with two concerns. First, many of the causes of the research–teaching gap are deeply embedded in the structure of the academic reward system and beyond the control of the academic administrator. Second, if academic administrators are to achieve what they propose, we need far better selection and training of these administrators.
Histopathological Characterization of a Cameron Lesion
Authors: Katz Jordan , Brar Sonia , Sidhu Jagmohan S.
Published: May 2012

Cameron lesions are linear erosions located at the neck of a hiatal hernia (HH) in patients with a large HH. The prevalence has been seen in up to 5% of patients with HH who undergo esophagogastroduodenoscopy, and they can be associated with overt gastrointestinal bleeding or anemia. These lesions occur due to vascular compression by the diaphragm in a large sliding HH. Histopathologic changes seen in the biopsy tissue of a Cameron lesion are due to ischemia, but this ischemia is reversible with treatment of HH. The existence of this entity and the histopathologic picture of a Cameron lesion is not well known to pathologists, and therefore, a microscopic picture of a Cameron lesion can be easily confused with ischemic gastritis. Ischemic gastritis is the result of atherosclerosis, usually seen in older people, unrelated to HH, and is not easily reversible. The authors received a gastric biopsy of a hiatal hernia without any associated clinical diagnosis of a Cameron lesion conveyed to the pathologist. This biopsy tissue showed ischemic changes in the gastric mucosa on microscopic examination. Diagnosis of ischemic gastritis was considered but ruled out after the case was discussed with the gastroenterologist. The correct diagnosis was made once the clinical diagnosis of HH with Cameron lesion (ie, a vertical red erosion) was made known to the pathologist. By reporting this case, the authors aim to increase awareness of Cameron lesion among pathologists so that they ask about the presence of a Cameron lesion before making the diagnosis of ischemic gastritis.
Defending a Paradigm by Patrolling a Boundary
Authors: Coddington Mark
Published: May 2012

Drawing on the concepts of paradigm repair and professional boundary work, this study examined the way the New York Times and the Guardian portrayed the whistle-blowing group WikiLeaks as being beyond the bounds of professional journalism. Through a textual analysis of Times and Guardian content about WikiLeaks during 2010 and early 2011, the study found that the Times depicted WikiLeaks as outside journalism’s professional norms regarding institutionality, source-based reporting routines, and objectivity, while the Guardian did so only with institutionality. That value thus emerged as a supranational journalistic norm, while source-based reporting routines and objectivity were bound within national contexts.
SAP expression in invariant NKT cells is required for cognate help to support B-cell responses
Authors: Detre Cynthia , Keszei Marton , Garrido-Mesa Natividad , Kis-Toth Katalin , Castro Wilson , Agyemang Amma F. , Veerapen Natacha , Besra Gurdyal S. , Carroll Michael C. , Tsokos George C. , Wang Ninghai , Leadbetter Elizabeth A. , Terhorst Cox
Published: May 2012

One of the manifestations of X-linked lymphoproliferative disease (XLP) is progressive agammaglobulinemia, caused by the absence of a functional signaling lymphocyte activation molecule (SLAM)–associated protein (SAP) in T, invariant natural killer T (NKT) cells and NK cells. Here we report that α-galactosylceramide (αGalCer) activated NKT cells positively regulate antibody responses to haptenated protein antigens at multiple checkpoints, including germinal center formation and affinity maturation. Whereas NKT cell–dependent B cell responses were absent in SAP−/−.B6 mice that completely lack NKT cells, the small number of SAP-deficient NKT cells in SAP−/−.BALB/c mice adjuvated antibody production, but not the germinal center reaction. To test the hypothesis that SAP-deficient NKT cells can facilitate humoral immunity, SAP was deleted after development in SAPfl/fl.tgCreERT2.B6 mice. We find that NKT cell intrinsic expression of SAP is dispensable for noncognate helper functions, but is critical for providing cognate help to antigen-specific B cells. These results demonstrate that SLAM-family receptor-regulated cell-cell interactions are not limited to T-B cell conjugates. We conclude that in the absence of SAP, several routes of NKT cell–mediated antibody production are still accessible. The latter suggests that residual NKT cells in XLP patients might contribute to variations in dysgammaglobulinemia.
Epitope targeting and viral inoculum are determinants of Nef-mediated immune evasion of HIV-1 from cytotoxic T lymphocytes
Authors: Chen Diana Y. , Balamurugan Arumugam , Ng Hwee L. , Cumberland William G. , Yang Otto O.
Published: May 2012

The impact of HIV-1 Nef-mediated HLA-I down-regulation on CD8+ cytotoxic T lymphocytes (CTLs) varies by epitope, but the determining factors have not been elucidated. In the present study, we investigated the impact of Nef on the antiviral efficiency of HIV-1–specific CTLs targeting 17 different epitopes to define properties that determine susceptibility to Nef. The impact of Nef was not correlated with the presenting HLA-I type or functional avidity of CTLs, but instead was related directly to the kinetics of infected cell clearance. Whereas Gag-specific CTLs generally were less susceptible to Nef than those targeting other proteins, this was determined by the ability to eliminate infected cells before de novo synthesis of viral proteins, which was also observed for CTLs targeting a Nef epitope. This very early clearance of infected cells depended on virus inoculum, and the required inoculum varied by epitope. These results suggest that whereas Gag-specific CTLs are more likely to recognize infected cells before Nef-mediated HLA-I down-regulation, this varies depending on the specific epitope and virus inoculum. Reduced susceptibility to Nef therefore may contribute to the overall association of Gag-specific CTL responses to better immune control if a sufficient multiplicity of infection is attained in vivo, but this property is not unique to Gag.
How I treat newly diagnosed chronic phase CML
Authors: Cortes Jorge , Kantarjian Hagop
Published: May 2012

The progress made in the understanding of chronic myeloid leukemia (CML) since the recognition of a common chromosomal abnormality to the introduction of ever more effective tyrosine kinase inhibitors is unprecedented in cancer. The expected survival for patients diagnosed with CML today, if properly managed, is probably similar to that of the general population. When managing patients with CML the goal is to achieve the best long-term outcome and we should base the treatment decisions on the data available. The results from cytogenetic and molecular analyses have to be interpreted judiciously and all available treatment options integrated into the treatment plan properly. The availability of several treatment options in CML is an asset, but the temptation of rapid succession of treatment changes because of perceived suboptimal response or for adverse events that could be managed needs to be avoided. Any decision to change therapy needs to weigh the expected long-term outcome with the current option versus the true expectations with any new option, particularly as it relates to irre-versible outcomes, such as transformation to blast phase and death. In this manuscript, we discuss the treatment approach that has helped us manage successfully a large CML population.
Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution
Authors: Zeng Ming , Paiardini Mirko , Engram Jessica C. , Beilman Greg J. , Chipman Jeffrey G. , Schacker Timothy W. , Silvestri Guido , Haase Ashley T.
Published: May 2012

Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1–infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.
Overrepresentation of transcription factor families in the genesets underlying breast cancer subtypes
Authors: Joshi Himanshu , Nord Silje H , Frigessi Arnoldo , Børresen-Dale Anne-Lise , Kristensen Vessela N
Published: May 2012

Background

The human genome contains a large amount of cis-regulatory DNA elements responsible for directing both spatial and temporal gene-expression patterns. Previous studies have shown that based on their mRNA expression breast tumors could be divided into five subgroups (Luminal A, Luminal B, Basal, ErbB2+ and Normal-like), each with a distinct molecular portrait. Whole genome gene expression analysis of independent sets of breast tumors reveals repeatedly the robustness of this classification. Furthermore, breast tumors carrying a TP53 mutation show a distinct gene expression profile, which is in strong association to the distinct molecular portraits. The mRNA expression of 552 genes, which varied considerably among the different tumors, but little between two samples of the same tumor, has been shown to be sufficient to separate these tumor subgroups.

Results

We analyzed in silico the transcriptional regulation of genes defining the subgroups at 3 different levels: 1. We studied the pathways in which the genes distinguishing the subgroups of breast cancer may be jointly involved including upstream regulators (1st and 2nd level of regulation) as well as downstream targets of these genes. 2. Then we analyzed the promoter areas of these genes (−500 bp to +100 bp relative to the transcription start site) for canonical transcription binding sites using Genomatix. 3. We looked for the actual expression levels of the identified TF and how they correlate with the overrepresentation of their TF binding sites in the separate groups. We report that promoter composition of the genes that most strongly predict the patient subgroups is distinct. The class-predictive genes showed a clearly different degree of overrepresentation of transcription factor families in their promoter sequences.

Conclusion

The study suggests that transcription factors responsible for the observed expression pattern in breast cancers may lead us to important biological pathways.
Programmed cell death in Saccharomyces cerevisiae is hampered by the deletion of GUP1 gene
Authors: Tulha Joana , Faria-Oliveira Fábio , Lucas Cândida , Ferreira Célia
Published: May 2012

Background

During the past years, yeast has been successfully established as a model to study mechanisms of programmed cell death regulation. Saccharomyces cerevisiae commits to cell death showing typical hallmarks of metazoan apoptosis, in response to different stimuli. Gup1p, an O-acyltransferase, is required for several cellular processes that are related to apoptosis development, such as rafts integrity and stability, lipid metabolism including GPI anchor correct remodeling, proper mitochondrial and vacuole function, bud site selection and actin dynamics. Therefore, we hypothesize that apoptotic process would be affected by GUP1 deletion.

Results

In the present work we used two known apoptosis inducing conditions, chronological aging and acetic acid, to assess several apoptotic markers in gup1∆ mutant strain. We found that this mutant presents a significantly reduced chronological lifespan as compared to Wt and it is also highly sensitive to acetic acid treatment. In addition, it presents extremely high levels of ROS. There were notorious differences on apoptotic markers between Wt and gup1∆ mutant strains, namely on the maintenance of plasma membrane integrity, on the phosphatidylserine externalization, on the depolarization of mitochondrial membrane and on the chromatin condensation. Those suggested that the mutant, under either condition, probably dies of necrosis and not from apoptosis.

Conclusions

To Gup1p has been assigned an important function on lipid rafts assembly/integrity, lipid metabolism and GPI anchor remodeling. Our results provide, for the first time, the connection of the integrity of yeast lipid rafts and apoptosis induction and/or signaling, giving new insights into the molecular mechanisms underlying this process in yeast.
Reduced-Calorie Dietary Weight Loss, Exercise, and Sex Hormones in Postmenopausal Women: Randomized Controlled Trial
Authors: Campbell Kristin L. , Foster-Schubert Karen E. , Alfano Catherine M. , Wang Chia-Chi , Wang Ching-Yun , Duggan Catherine R. , Mason Caitlin , Imayama Ikuyo , Kong Angela , Xiao Liren , Bain Carolyn E. , Blackburn George L. , Stanczyk Frank Z. , McTiernan Anne
Published: May 2012

Purpose

Estrogens and androgens are elevated in obesity and associated with increased postmenopausal breast cancer risk, but the effect of weight loss on these biomarkers is unknown. We evaluated the individual and combined effects of a reduced-calorie weight loss diet and exercise on serum sex hormones in overweight and obese postmenopausal women.

Patients and Methods

We conducted a single-blind, 12-month, randomized controlled trial from 2005 to 2009. Participants (age 50 to 75 years; body mass index > 25.0 kg/m2, exercising < 100 minutes/wk) were randomly assigned using a computer-generated sequence to (1) reduced-calorie weight loss diet (“diet”; n = 118), (2) moderate- to vigorous-intensity aerobic exercise (“exercise”; n = 117), (3) combined reduced-calorie weight loss diet and moderate- to vigorous-intensity aerobic exercise (“diet + exercise”; n = 117), or (4) control (n = 87). Outcomes were estrone concentration (primary) and estradiol, free estradiol, total testosterone, free testosterone, androstenedione, and sex hormone–binding globulin (SHBG) concentrations (secondary).

Results

Mean age and body mass index were 58 years and 30.9 kg/m2, respectively. Compared with controls, estrone decreased 9.6% (P = .001) with diet, 5.5% (P = .01) with exercise, and 11.1% (P < .001) with diet + exercise. Estradiol decreased 16.2% (P < .001) with diet, 4.9% (P = .10) with exercise, and 20.3% (P < .001) with diet + exercise. SHBG increased 22.4% (P < .001) with diet and 25.8% (P < .001) with diet + exercise. Free estradiol decreased 21.4% (P < .001) with diet and 26.0% (P < .001) with diet + exercise. Free testosterone decreased 10.0% (P < .001) with diet and 15.6% (P < .001) with diet + exercise. Greater weight loss produced stronger effects on estrogens and SHBG.

Conclusion

Weight loss significantly lowered serum estrogens and free testosterone, supporting weight loss for risk reduction through lowering exposure to breast cancer biomarkers.
Early- and Long-Term Outcome Data of Patients With Pseudomyxoma Peritonei From Appendiceal Origin Treated by a Strategy of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Authors: Chua Terence C. , Moran Brendan J. , Sugarbaker Paul H. , Levine Edward A. , Glehen Olivier , Gilly François N. , Baratti Dario , Deraco Marcello , Elias Dominique , Sardi Armando , Liauw Winston , Yan Tristan D. , Barrios Pedro , Gómez Portilla Alberto , de Hingh Ignace H.J.T. , Ceelen Wim P. , Pelz Joerg O. , Piso Pompiliu , González-Moreno Santiago , Van Der Speeten Kurt , Morris David L.
Published: May 2012

Purpose

Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study.

Patients and Methods

A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International.

Results

Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival.

Conclusion

The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.
Reach Out to Enhance Wellness Home-Based Diet-Exercise Intervention Promotes Reproducible and Sustainable Long-Term Improvements in Health Behaviors, Body Weight, and Physical Functioning in Older, Overweight/Obese Cancer Survivors
Authors: Demark-Wahnefried Wendy , Morey Miriam C. , Sloane Richard , Snyder Denise C. , Miller Paige E. , Hartman Terryl J. , Cohen Harvey J.
Published: May 2012

Purpose

Diet and exercise interventions have been tested in cancer survivors as a means to reduce late effects and comorbidity, but few have assessed adherence and health outcomes long term.

Methods

Between July 2005 and May 2007, the Reach Out to Enhance Wellness (RENEW) trial accrued 641 locoregionally staged, long-term (≥ 5 years from diagnosis) colorectal, breast, and prostate cancer survivors in the United States (21 states), Canada, and the United Kingdom. All participants were sedentary (< 150 minutes of physical activity [PA] a week), overweight or obese (body mass index, 25 to 40 kg/m2), and over age 65 years. The trial tested a diet-exercise intervention delivered via mailed print materials and telephone counseling. RENEW used a wait-list control, cross-over design (ie, participants received the year-long intervention immediately or after a 1-year delay), which allowed the opportunity to assess program efficacy (previously reported primary outcome), durability, and reproducibility (reported herein). Measures included diet quality (DQ), PA, BMI, and physical function (PF).

Results

No significant relapse was observed in the immediate-intervention arm for DQ, PA, and BMI; however, rates of functional decline increased when the intervention ceased. From year 1 to year 2, significant improvements were observed in the delayed-intervention arm; mean change scores in behaviors and BMI and PF slopes were as follows: DQ score, 5.2 (95% CI, 3.4 to 7.0); PA, 45.8 min/wk (95% CI, 26.9 to 64.6 min/wk); BMI, −0.56 (95% CI, −0.75 to −0.36); and Short Form-36 PF, −1.02 versus −5.52 (P < .001 for all measures). Overall, both arms experienced significant improvements in DQ, PA, and BMI from baseline to 2-year follow-up (P < .001).

Conclusion

Older cancer survivors respond favorably to lifestyle interventions and make durable changes in DQ and PA that contribute to sustained weight loss. These changes positively reorient functional decline trajectories during intervention delivery.
Patient and Physician Decision Styles and Breast Cancer Chemotherapy Use in Older Women: Cancer and Leukemia Group B Protocol 369901
Authors: Mandelblatt Jeanne S. , Faul Leigh Anne , Luta George , Makgoeng Solomon B. , Isaacs Claudine , Taylor Kathryn , Sheppard Vanessa B. , Tallarico Michelle , Barry William T. , Cohen Harvey J.
Published: May 2012

Purpose

Physician and patient decision styles may influence breast cancer care for patients ≥ 65 years (“older”) because there is uncertainty about chemotherapy benefits in this group. We evaluate associations between decision-making styles and actual treatment.

Methods

Data were collected from women treated outside of clinical trials for newly diagnosed stage I to III breast cancer (83% response) from January 2004 through April 2011 in 75 cooperative group sites. Physicians completed a one-time mailed survey (91% response), and clinical data were abstracted from charts. Patient decision style was measured on a five-point scale. Oncologists' preference for prescribing chemotherapy was based on standardized vignettes. Regression and multiple imputation were used to assess associations between chemotherapy and other variables.

Results

There were 1,174 women seen by 212 oncologists; 43% of women received chemotherapy. One-third of women preferred to make their own treatment decision. Patient and physician decision styles were independently associated with chemotherapy. Women who preferred less physician input had lower odds of chemotherapy than women who preferred more input (odds ratio [OR] = 0.79 per 1-point change; 95% CI, 0.65 to 0.97; P = .02) after considering covariates. Patients whose oncologists had a high chemotherapy preference had higher odds of receiving chemotherapy (OR = 2.65; 95% CI, 1.80 to 3.89; P < .001) than those who saw oncologists with a low preference.

Conclusion

Physicians' and older patients' decision styles are each associated with breast cancer chemotherapy use. It will be important to re-evaluate the impact of decision styles when there is greater empirical evidence about the benefits and risks of chemotherapy in older patients.
UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit
Authors: Schneider Judsen , Skelton Rachel L. , Von Stetina Stephen E. , Middelkoop Teije C. , van Oudenaarden Alexander , Korswagen Hendrik C. , Miller David M.
Published: May 2012

Coordinated movement depends on the creation of synapses between specific neurons in the motor circuit. In C. elegans, this important decision is regulated by the UNC-4 homeodomain protein. unc-4 mutants are unable to execute backward locomotion because VA motor neurons are mis-wired with inputs normally reserved for their VB sisters. We have proposed that UNC-4 functions in VAs to block expression of VB genes. This model is substantiated by the finding that ectopic expression of the VB gene ceh-12 (encoding a homolog of the homeodomain protein HB9) in unc-4 mutants results in the mis-wiring of posterior VA motor neurons with VB-like connections. Here, we show that VA expression of CEH-12 depends on a nearby source of the Wnt protein EGL-20. Our results indicate that UNC-4 prevents VAs from responding to a local EGL-20 cue by disabling a canonical Wnt signaling cascade involving the Frizzled receptors MIG-1 and MOM-5. CEH-12 expression in VA motor neurons is also opposed by a separate pathway that includes the Wnt ligand LIN-44. This work has revealed a transcriptional mechanism for modulating the sensitivity of specific neurons to diffusible Wnt ligands and thereby defines distinct patterns of synaptic connectivity. The existence of comparable Wnt gradients in the vertebrate spinal cord could reflect similar roles for Wnt signaling in vertebrate motor circuit assembly.
Cellular retinoic acid-binding proteins are essential for hindbrain patterning and signal robustness in zebrafish
Authors: Cai Anna Q. , Radtke Kelly , Linville Angela , Lander Arthur D. , Nie Qing , Schilling Thomas F.
Published: May 2012

The vitamin A derivative retinoic acid (RA) is a morphogen that patterns the anterior-posterior axis of the vertebrate hindbrain. Cellular retinoic acid-binding proteins (Crabps) transport RA within cells to both its nuclear receptors (RARs) and degrading enzymes (Cyp26s). However, mice lacking Crabps are viable, suggesting that Crabp functions are redundant with those of other fatty acid-binding proteins. Here we show that Crabps in zebrafish are essential for posterior patterning of the hindbrain and that they provide a key feedback mechanism that makes signaling robust as they are able to compensate for changes in RA production. Of the four zebrafish Crabps, Crabp2a is uniquely RA inducible and depletion or overexpression of Crabp2a makes embryos hypersensitive to exogenous RA. Computational models confirm that Crabp2a improves robustness within a narrow concentration range that optimizes a ‘robustness index’, integrating spatial information along the RA morphogen gradient. Exploration of signaling parameters in our models suggests that the ability of Crabp2a to transport RA to Cyp26 enzymes for degradation is a major factor in promoting robustness. These results demonstrate a previously unrecognized requirement for Crabps in RA signaling and hindbrain development, as well as a novel mechanism for stabilizing morphogen gradients despite genetic or environmental fluctuations in morphogen availability.
Chemokine and Fgf signalling act as opposing guidance cues in formation of the lateral line primordium
Authors: Breau Marie A. , Wilson Duncan , Wilkinson David G. , Xu Qiling
Published: May 2012

The directional migration of many cell populations occurs as a coherent group. An amenable model is provided by the posterior lateral line in zebrafish, which is formed by a cohesive primordium that migrates from head to tail and deposits future neuromasts at intervals. We found that prior to the onset of migration, the compact state of the primordium is not fully established, as isolated cells with lateral line identity are present caudal to the main primordium. These isolated cells are retained in position such that they fuse with the migrating primordium as it advances, and later contribute to the leading zone and terminal neuromasts. We found that the isolated lateral line cells are positioned by two antagonistic cues: Fgf signalling attracts them towards the primordium, which counteracts Sdf1α/Cxcr4b-mediated caudal attraction. These findings reveal a novel chemotactic role for Fgf signalling in which it enables the coalescence of the lateral line primordium from an initial fuzzy pattern into a compact group of migrating cells.
Base-Catalyzed Asymmetric Diels–Alder Reaction of 3-Hydroxy-2-pyrone and Simple Aryl Vinyl Sulfoxide: Asymmetric Synthesis of Carbaketopyranoses
Authors: Okamura Hiroaki , Urabe Fumiya , Hamada Toshiyuki , Iwagawa Tetsuo
Published: May 2012

A highly stereoselective base-catalyzed asymmetric Diels–Alder reaction of 3-hydroxy-2-pyrone and simple aryl vinyl sulfoxide is reported. Furthermore, the synthetic utility of the resulting product was demonstrated by the efficient asymmetric synthesis of β-l-carbafructopyranose and β-l-carbapsicopyranose.
Optimization of a Histopathological Biomarker for Sphingomyelin Accumulation in Acid Sphingomyelinase Deficiency
Authors: Taksir Tatyana V. , Johnson Jennifer , Maloney Colleen L. , Yandl Emily , Griffiths Denise , Thurberg Beth L. , Ryan Susan
Published: May 2012

Niemann-Pick disease (types A and B), or acid sphingomyelinase deficiency, is an inherited deficiency of acid sphingomyelinase, resulting in intralysosomal accumulation of sphingomyelin in cells throughout the body, particularly within those of the reticuloendothelial system. These cellular changes result in hepatosplenomegaly and pulmonary infiltrates in humans. A knockout mouse model mimics many elements of human ASMD and is useful for studying disease histopathology. However, traditional formalin-fixation and paraffin embedding of ASMD tissues dissolves sphingomyelin, resulting in tissues with a foamy cell appearance, making quantitative analysis of the substrate difficult. To optimize substrate fixation and staining, a modified osmium tetroxide and potassium dichromate postfixation method was developed to preserve sphingomyelin in epon-araldite embedded tissue and pulmonary cytology specimens. After processing, semi-thin sections were incubated with tannic acid solution followed by staining with toluidine blue/borax. This modified method provides excellent preservation and staining contrast of sphingomyelin with other cell structures. The resulting high-resolution light microscopy sections permit digital quantification of sphingomyelin in light microscopic fields. A lysenin affinity stain for sphingomyelin was also developed for use on these semi-thin epon sections. Finally, ultrathin serial sections can be cut from these same tissue blocks and stained for ultrastructural examination by electron microscopy.
Bildbasierte Regelung eines gliedelastischen Roboterarms mit einem RGB-D-Sensor
Authors: Malzahn Jörn , Phung Anh Son , Hoffmann Frank , Bertram Torsten
Published: May 2012

Der Beitrag befasst sich mit der bildbasierten Regelung eines mehrgliedrigen gliedelastischen Roboterarms unter Gravitationseinfluss anhand von RGB-D-Sensordaten. Der Fokus liegt auf der Mehrfachnutzung der in den zur Positionsregelung aufgenommenen Bildfolgen enthaltenen Bewegungsinformation auch zur Dämpfung der unerwünschten Armschwingungen. Es werden vier Ansätze zur Rekonstruktion der Schwingungsbewegung unter Verwendung der verfügbaren Tiefeninformation gegenübergestellt. Drei Ansätze zur Phasenkorrektur des bildbasiert am Endeffektor gewonnenen Schwingungssignals werden diskutiert. Die Validierung der bildbasierten Schwingungsdämpfung erfolgt im Experiment.
Online−6D-SLAM für RGB-D-Sensoren
Authors: Endres Felix , Hess Jürgen , Engelhard Nikolas , Sturm Jürgen , Burgard Wolfram
Published: May 2012

Zur Automatisierung komplexer Manipulationsaufgaben in dynamischen oder unbekannten Umgebungen benötigt die Steuerungssoftware eines autonomen Roboters eine Repräsentation des Arbeitsbereiches, mit der die Kollisionsfreiheit bei der Durchführung der Aufgabe gewährleistet werden kann. Dieser Beitrag beschreibt ein neues System zur Erstellung von 3D-Umgebungsrepräsentationen aus den RGB-D-Daten neuartiger Kameras, wie der Microsoft Kinect. Durch die Unabhängigkeit von weiterer Sensorik ist der Ansatz insbesondere zur Ergänzung von rein bildbasierten Regelungssystemen geeignet.
Schnelle 100-Prozent-Oberflächenkontrolle in der Produktion mit Zellularen Neuronalen Netzwerken
Authors: Strohm Peter , Blug Andreas , Carl Daniel , Höfler Heinrich
Published: May 2012

Kameras, die auf Zellularen Neuronalen Netzwerken basieren, können neue Anwendungsgebiete für die industrielle Bildverarbeitung erschließen, denn Rechenelemente lassen sich direkt in die elektronische Beschaltung von CMOS-Kamerapixeln integrieren. Insbesondere Regel- und Steuerungssysteme profitieren von der hohen Rechenleistung und den kurzen Latenzzeiten dieser neuartigen Kameratechnologie. Was damit jenseits konventioneller Bildverarbeitungssysteme möglich ist, wird anhand von drei konkreten Anwendungen gezeigt: beim Laserschweißen, bei der Laserablation und beim Drahtziehen.
Vision-based Control of Assistive Robot FRIEND: Practical Experiences and Design Conclusions
Authors: Gräser Axel , Kuzmicheva Olena , Ristic-Durrant Danijela , Natarajan Saravana K. , Fragkopoulos Christos
Published: May 2012

In this publication, we describe the evolution of control structures for vision-based control over several generations of the assistive robot FRIEND1. We also publish some evaluation results which were the basis of design decisions for the following system generation.
Visual Servoing für ein- und zweiarmige Manipulationsaufgaben bei humanoiden Robotern
Authors: Böge Christian , Vahrenkamp Nikolaus , Asfour Tamim , Dillmann Rüdiger
Published: May 2012

Unter dem Begriff “Visual Servoing” werden Ansätze zur visuell geregelten Ausführung z. B. von Roboterbewegungen zusammengefasst. Hierbei werden durch kontinuierliche Analyse von Kamerabildern Stellgrößen erzeugt, um beispielsweise einen Roboterarm anzusteuern. In diesem Artikel stellen wir das Visual-Servoing-System des humanoiden Roboters ARMAR-III vor, welches eine zuverlässige Ausführung von ein- und zweiarmigen Greif- und Manipulationsaufgaben ermöglicht. Durch den Closed-loop-Ansatz können Ungenauigkeiten in Aktorik und Sensorik ausgeglichen werden.
Eine Methode zur Erzeugung stochastischer Helligkeitsfelder durch homogene, einstufige Markoff-Ketten
Authors: Dubinin Dmitry , Geringer Viktor , Kochegurov Alexander
Published: May 2012

In diesem Beitrag wird eine Methode zur Erzeugung stochastischer Helligkeitsfelder durch homogene, einstufige Markoff-Ketten betrachtet. Die Feldeigenschaften sind untereinander von den “Palma”-Formeln bestimmt. Die Korrelationseigenschaften der erzeugten Zufallsfelder hängen jeweils nur von den Mosaikgitterstrukturen ab. Die ABC (Alphabet)-Auswahl, die eine Gitterform (Morphologie des Feldes) voraussetzt, wird manuell im Voraus vom Anwender bestimmt. Diese Methode ermöglicht es, verschiedene Typen der “Gitterformstrukturen” mit horizontalen, senkrechten und diagonalen Elementen bei einer 8-Nachbarschaft zu erzeugen.
Messabweichung der Stereo-PIV im Vergleich zu LDV und CFD anhand einer definiert gestörten Rohrströmung
Authors: Eichler Thomas , Tawackolian Karsten , Lederer Thomas
Published: May 2012

Stereoscopic Particle Image Velocimetry (SPIV) eignet sich als schnelles und präzises Messverfahren zur zeitlich und räumlich hochaufgelösten Ermittlung von 3D-Geschwindigkeitsverteilungen in Rohrleitungen. Die Methode wird mit dem bekannten Laser Doppler Velocimetry (LDV)-Messverfahren und Computational Fluid Dynamics (CFD)-Simulationen am Beispiel einer stark gestörten Strömung hinter einem Drallgenerator bewertet. Erstmalig können so SPIV-Messabweichungen bei der Volumenstrombestimmung von deutlicher kleiner als 2% an einem komplexen Strömungszustand nachgewiesen werden.
Office Work and Complaints of the Arms, Neck and Shoulders: The Role of Job Characteristics, Muscular Tension and Need for Recovery
Authors: Gawke Jason C. , Gorgievski Marjan J. , van der Linden Dimitri
Published: May 2012

Office Work and Complaints of the Arms, Neck and Shoulders: The Role of Job Characteristics, Muscular Tension and Need for Recovery: Jason C. GAWKE, et al. Department of Work and Organizational Psychology, Erasmus University Rotterdam, The Netherlands—

Objectives

This study investigated physical, psychological and social job characteristics as potential risk factors for complaints of the arms, neck and shoulders (CANS) and mediating effects of muscular tension and need for recovery.

Methods

Data were collected among 105 computer workers using questionnaires and electromyography (EMG), and were analyzed with linear regression analyses.

Results

Task interdependence, information processing and lower social support predicted more CANS. Physical job demands had no predictive power over and above psychological and social stressors. Both muscular tension and need for recovery partially mediated the job characteristics —CANS relationships.

Conclusions

Occupational health professionals should not neglect psychological and social job characteristics as potentially important predictors of CANS in specific occupational groups, such as office workers. Our findings imply that CANS interventions should not be restricted to ergonomic improvements, but should be accompanied by improvement of the job design from a psychological and social perspective and reactive intervention aimed at decreasing short‐term physical strain (muscular tension) and mental strain (need for recovery).
Effect of a Single Inhalation of Laninamivir Octanoate in Children With Influenza
Authors: Katsumi Yoshiki , Otabe Osamu , Matsui Fumihiro , Kidowaki Satoshi , Mibayashi Akiko , Tsuma Yusuke , Ito Hisato
Published: May 2012

OBJECTIVE:

The purpose of this study was to compare the efficiency and safety of a new neuraminidase inhibitor, laninamivir octanoate (LO), with zanamivir (ZN) in pediatric patients with influenza.

METHODS:

One hundred twelve pediatric patients ≤15 years, diagnosed with a rapid diagnostic test as having influenza from January to May 2011, were randomly assigned to the LO group or the ZN group, and their parents were asked to complete a questionnaire during the recovery at home. The LO group was instructed to inhale LO once (20 or 40 mg depending on age), and the ZN group was instructed to inhale ZN (20 mg) twice daily for 5 days.

RESULTS:

The LO group (n = 55) and the ZN group (n = 57) were well balanced. Finally, 44 patients in the LO group and 41 patients in the ZN group could be evaluated. Median times to fever resolution after initial treatment were 36 hours in the LO group and 37 hours in the ZN group. No differences were observed between the 2 groups with respect to the frequencies of asthmatic symptoms, pneumonia, gastrointestinal symptoms, or abnormal behaviors. Six younger children could not inhale LO well for technical reasons.

CONCLUSIONS:

Our data suggest that the efficiency and safety of LO are the same as those of ZN in pediatric patients with influenza but that LO may be more convenient than ZN because it requires only a single inhalation. However, younger patients may not inhale LO efficiently.
Cardiovascular Risk Factors in Children and Young Adults Born to Preeclamptic Pregnancies: A Systematic Review
Authors: Davis Esther Frances , Lazdam Merzaka , Lewandowski Adam James , Worton Stephanie Anne , Kelly Brenda , Kenworthy Yvonne , Adwani Satish , Wilkinson Andrew R. , McCormick Kenny , Sargent Ian , Redman Christopher , Leeson Paul
Published: May 2012

BACKGROUND AND OBJECTIVE:

Preeclampsia is an independent cardiovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardiovascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero.

METHODS:

We performed a systematic review and meta-analysis on studies reporting traditional cardiovascular risk factors in those exposed to preeclampsia compared to controls. Information was extracted on the classic cardiovascular risk factors, including blood pressure, lipid profile, glucose metabolism, and BMI from articles published between 1948 and August 2011 in Medline and Embase.

RESULTS:

Eighteen studies provided cumulated data on 45 249 individuals. In utero exposure to preeclampsia was associated with a 2.39 mm Hg (95% confidence interval: 1.74–3.05; P < .0001) higher systolic and a 1.35 mm Hg (95% confidence interval: 0.90–1.80; P < .00001) higher diastolic blood pressure during childhood and young adulthood. BMI was increased by 0.62 kg/m2 (P < .00001). Associations were similar in children and adolescents, for different genders, and with variation in birth weight. There was insufficient evidence to identify consistent variation in lipid profile or glucose metabolism.

CONCLUSIONS:

Young offspring of pregnancies complicated by preeclampsia already have increased blood pressure and BMI, a finding that may need to be considered in future primary prevention strategies for cardiovascular disease.
Fabrication of Metallic Nanocomponents by Forging of Ni3Al-Nanoparticles.
Authors: Andreas Landefeld , Joachim Rösler
Published: May 2012

The trend to manufacture components reduced in size at the micro- and nano-scale is obvious and is becoming more and more the state of art in designing actuators, sensors and chips. In recent years, nanoscale fabrication has developed considerably, but the fabrication of freestanding nanosize components is still a great challenge. The fabrication of metallic nanocomponents utilizing three basic steps is demonstrated here. First, metallic alloys are used as factories to produce a metallic raw stock of nano-objects/nanoparticles in large numbers. These objects are then isolated from the powder containing thousands of such objects inside a scanning electron microscope using manipulators, and placed on a micro-anvil or a die. Finally, the shape of the individual nano-object is changed by nanoforging using a microhammer to get specific geometries such as discs and more complex components such as gears and wheels in the near future. The almost cubic particles are essentially defect-free, therefore, provide very high strength (σ>2500MPa) in combination with excellent formability (|ϕ|>1,6). There are two approaches for forming these small particles. Upset forging is used to forge small discs (height<100nm) and to shape the nanoparticle in specific areas. Press forging into nano-dies is used to forge more complex structures. In this way free-standing, high-strength, metallic nanoobjects may be shaped into components with dimensions in the 100 nm range. By assembling such nano-components, high-performance microsystems can be fabricated, which are truly in the micrometre scale (the size ratio of a system to its component is typically 10:1).
Hierarchical Metallic and Ceramic Nanostructures Produced via a Hybrid Approach Combining Laser Interference Ablation and Block Co-Polymer Phase Separation
Authors: Alabi Taiwo R. , Yuan Dajun , Das Suman
Published: May 2012

We report on the formation of hierarchical nanostructures of Au, Pt, Fe2O3 and PdO2 using a hybrid technique combining laser interference patterning (LIP) and block copolymer phase separation (BCPS). By varying the loading time of the block copolymer with metallic salts and the laser interference technique, different types of hierarchical square, triangular, linear and circular arrays can be formed. Such a robust method can be applied to other metallic and ceramic materials and has potential for use in the large-scale production of nano-catalysts, photonics, optoelectronics, MEMS devices and bio-sensors.
Nanofabrication with the Helium Ion Microscope
Authors: Boden Stuart A. , Moktadir Zakaria , Alkhalil Feras M. , Mizuta Hiroshi , Rutt Harvey N. , Bagnall Darren M.
Published: May 2012

Although initially developed as an imaging tool, the helium ion microscope (HIM) is finding applications in nanofabrication as its focused ion beam is capable of highly-localized material modification. In this study, an external pattern generator is used to explore the capabilities of the HIM for localized milling of a ∼7 nm thick layer of silicon-on-insulator, with atomic force microscopy (AFM) used to characterize the resulting patterns. The dose and patterned area size are varied and milling to depths >7 nm is demonstrated. At high doses and large areas, protuberances form, primarily due to sub-surface swelling caused by the implanted helium. The results suggest this technique could enable the rapid prototyping of next-generation nanoelectronic devices in thin silicon.
Thermal conductivity of sands
Authors: HAIGH S.K.
Published: May 2012

The thermal properties of soils are important in a variety of applications, including the thermal performance of buried pipelines and geothermal heat pumps. A variety of methods exist for the prediction of thermal conductivity based on empirical fits to databases of soil thermal conductivities. In this paper an analytical model will be developed based on unidirectional heat flow through a three-phase soil element. The performance of this model will be validated against a database of 155 test measurements from the published literature. A variety of alternative prediction methods will be tested against this dataset, with the model derived here being shown to be at least as good as the best empirical model while retaining a physical origin.