bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-verbal communication between Registered Nurses Intellectual Disability and people with an intellectual disability
Authors: Martin Anne-Marie , Connor-Fenelon Maureen O’ , Lyons Rosemary
Published: March 2012

This is the second of two articles presenting the findings of a qualitative study which explored the experiences of Registered Nurses Intellectual Disability (RNIDs) of communicating with people with an intellectual disability who communicate non-verbally. While Part 1 outlined the study background, context and methodology along with the overarching, multi-dimensional category of ‘familiarity/knowing the person’, the current article critically discusses the themes and subthemes encapsulated in this category. Each theme is considered in the light of current policies, strategies and philosophies shaping the provision of services to people with an intellectual disability in Ireland. The results suggest that the RNID is ideally located and key to supporting the implementation of these policies and strategies due to their highly developed and proficient skill set as well as experience of communicating with people with an intellectual disability who communicate non-verbally.
The tyrosine phosphatase SHP-1 dampens murine Th17 development
Authors: Mauldin Ileana S. , Tung Kenneth S. , Lorenz Ulrike M.
Published: March 2012

Th17 cells represent a subset of CD4+ T helper cells that secrete the proinflammatory cytokine IL-17. Th17 cells have been ascribed both a beneficial role in promoting clearance of pathogenic fungi and bacteria, and a pathogenic role in autoimmune diseases. Here we identify the tyrosine phosphatase SHP-1 as a critical regulator of Th17 development, using 3 complementary approaches. Impaired SHP-1 activity through genetic deletion of SHP-1, transgenic expression of an inducible dominant negative SHP-1, or pharmacologic inhibition of SHP-1 strongly promotes the development of Th17. Ex vivo Th17 skewing assays demonstrate that genetic or pharmacologic disruption of SHP-1 activity in T cells results in a hyper-response to stimulation via IL-6 and IL-21, 2 cytokines that promote Th17 development. Mechanistically, we find that SHP-1 decreases the overall cytokine-induced phosphorylation of STAT3 in primary CD4+ T cells. These data identify SHP-1 as a key modifier of IL-6–and IL-21–driven Th17 development via regulation of STAT3 signaling and suggest SHP-1 as a potential new therapeutic target for manipulating Th17 differentiation in vivo.
Proper desensitization of CXCR4 is required for lymphocyte development and peripheral compartmentalization in mice
Authors: Balabanian Karl , Brotin Emilie , Biajoux Vincent , Bouchet-Delbos Laurence , Lainey Elodie , Fenneteau Odile , Bonnet Dominique , Fiette Laurence , Emilie Dominique , Bachelerie Françoise
Published: March 2012

Desensitization controls G protein–dependent signaling of chemokine receptors. We investigate the physiologic implication of this process for CXCR4 in a mouse model harboring a heterozygous mutation of the Cxcr4 gene, which engenders a desensitization-resistant receptor. Such anomaly is linked to the warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome, a human rare combined immunodeficiency. Cxcr4+/mutant(1013) mice display leukocytes with enhanced responses to Cxcl12 and exhibit leukopenia as reported in patients. Treatment with CXCL12/CXCR4 antagonists transiently reverses blood anomalies, further demonstrating the causal role of the mutant receptor in the leukopenia. Strikingly, neutropenia occurs in a context of normal bone marrow architecture and granulocyte lineage maturation, indicating a minor role for Cxcr4-dependent signaling in those processes. In contrast, Cxcr4+/1013 mice show defective thymopoiesis and B-cell development, accounting for circulating lymphopenia. Concomitantly, mature T and B cells are abnormally compartmentalized in the periphery, with a reduction of primary follicles in the spleen and their absence in lymph nodes mirrored by an unfurling of the T-cell zone. These mice provide a model to decipher the role of CXCR4 desensitization in the homeostasis of B and T cells and to investigate which manifestations of patients with WHIM syndrome may be overcome by dampening the gain of CXCR4 function.
A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies
Authors: Sehn Laurie H. , Assouline Sarit E. , Stewart Douglas A. , Mangel Joy , Gascoyne Randy D. , Fine Gregg , Frances-Lasserre Susan , Carlile David J. , Crump Michael
Published: March 2012

This phase 1 study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by 2 years of maintenance. Cohorts of 3 to 6 patients received obinutuzumab (200-2000 mg) intravenously weekly for 4 weeks. Patients with a complete or partial response (or stable disease and clinical benefit) continued to receive obinutuzumab every 3 months, for a maximum of 8 doses. Twenty-two patients with relapsed CD20-positive non-Hodgkin lymphoma or chronic lymphocytic leukemia with an indication for treatment and no therapy of higher priority were enrolled. Patients received a median of 4 prior regimens; 86% had received at least 1 rituximab-containing regimen. No dose-limiting or unexpected AEs were observed. Infusion-related reactions were most common (all grades, 73%; grade 3/4, 18%), followed by infection (32%), pyrexia (23%), neutropenia (23%), headache (18%), and nausea (18%). At end of induction, 5 (23%) patients achieved partial responses and 12 (54%) had stable disease. Eight patients received maintenance; best overall response was 32% (6 partial responses/1 complete response). Obinutuzumab induction and maintenance therapy was well tolerated with promising efficacy in this heterogeneous, highly pretreated population and warrants further investigation. This study was registered at www.clinicaltrials.gov (identifier NCT00576758).
Combining automated peak tracking in SAR by NMR with structure-based backbone assignment from 15N-NOESY
Authors: Jang Richard , Gao Xin , Li Ming
Published: March 2012

Background

Chemical shift mapping is an important technique in NMR-based drug screening for identifying the atoms of a target protein that potentially bind to a drug molecule upon the molecule's introduction in increasing concentrations. The goal is to obtain a mapping of peaks with known residue assignment from the reference spectrum of the unbound protein to peaks with unknown assignment in the target spectrum of the bound protein. Although a series of perturbed spectra help to trace a path from reference peaks to target peaks, a one-to-one mapping generally is not possible, especially for large proteins, due to errors, such as noise peaks, missing peaks, missing but then reappearing, overlapped, and new peaks not associated with any peaks in the reference. Due to these difficulties, the mapping is typically done manually or semi-automatically, which is not efficient for high-throughput drug screening.

Results

We present PeakWalker, a novel peak walking algorithm for fast-exchange systems that models the errors explicitly and performs many-to-one mapping. On the proteins: hBclXL, UbcH5B, and histone H1, it achieves an average accuracy of over 95% with less than 1.5 residues predicted per target peak. Given these mappings as input, we present PeakAssigner, a novel combined structure-based backbone resonance and NOE assignment algorithm that uses just 15N-NOESY, while avoiding TOCSY experiments and 13C-labeling, to resolve the ambiguities for a one-to-one mapping. On the three proteins, it achieves an average accuracy of 94% or better.

Conclusions

Our mathematical programming approach for modeling chemical shift mapping as a graph problem, while modeling the errors directly, is potentially a time- and cost-effective first step for high-throughput drug screening based on limited NMR data and homologous 3D structures.
Win percentage: a novel measure for assessing the suitability of machine classifiers for biological problems
Authors: Parry R Mitchell , Phan John H , Wang May D
Published: March 2012

Background

Selecting an appropriate classifier for a particular biological application poses a difficult problem for researchers and practitioners alike. In particular, choosing a classifier depends heavily on the features selected. For high-throughput biomedical datasets, feature selection is often a preprocessing step that gives an unfair advantage to the classifiers built with the same modeling assumptions. In this paper, we seek classifiers that are suitable to a particular problem independent of feature selection. We propose a novel measure, called "win percentage", for assessing the suitability of machine classifiers to a particular problem. We define win percentage as the probability a classifier will perform better than its peers on a finite random sample of feature sets, giving each classifier equal opportunity to find suitable features.

Results

First, we illustrate the difficulty in evaluating classifiers after feature selection. We show that several classifiers can each perform statistically significantly better than their peers given the right feature set among the top 0.001% of all feature sets. We illustrate the utility of win percentage using synthetic data, and evaluate six classifiers in analyzing eight microarray datasets representing three diseases: breast cancer, multiple myeloma, and neuroblastoma. After initially using all Gaussian gene-pairs, we show that precise estimates of win percentage (within 1%) can be achieved using a smaller random sample of all feature pairs. We show that for these data no single classifier can be considered the best without knowing the feature set. Instead, win percentage captures the non-zero probability that each classifier will outperform its peers based on an empirical estimate of performance.

Conclusions

Fundamentally, we illustrate that the selection of the most suitable classifier (i.e., one that is more likely to perform better than its peers) not only depends on the dataset and application but also on the thoroughness of feature selection. In particular, win percentage provides a single measurement that could assist users in eliminating or selecting classifiers for their particular application.
Sensitive detection of pathway perturbations in cancers
Authors: Rivera Corban G , Tyler Brett M , Murali TM
Published: March 2012

Background

The normal functioning of a living cell is characterized by complex interaction networks involving many different types of molecules. Associations detected between diseases and perturbations in well-defined pathways within such interaction networks have the potential to illuminate the molecular mechanisms underlying disease progression and response to treatment.

Results

In this paper, we present a computational method that compares expression profiles of genes in cancer samples to samples from normal tissues in order to detect perturbations of pre-defined pathways in the cancer. In contrast to many previous methods, our scoring function approach explicitly takes into account the interactions between the gene products in a pathway. Moreover, we compute the sub-pathway that has the highest score, as opposed to merely computing the score for the entire pathway. We use a permutation test to assess the statistical significance of the most perturbed sub-pathway. We apply our method to 20 pathways in the Netpath database and to the Global Cancer Map of gene expression in 18 cancers. We demonstrate that our method yields more sensitive results than alternatives that do not consider interactions or measure the perturbation of a pathway as a whole. We perform a sensitivity analysis to show that our approach is robust to modest changes in the input data. Our method confirms numerous well-known connections between pathways and cancers.

Conclusions

Our results indicate that integrating differential gene expression with the interaction structure in a pathway is a powerful approach for detecting links between a cancer and the pathways perturbed in it. Our results also suggest that even well-studied pathways may be perturbed only partially in any given cancer. Further analysis of cancer-specific sub-pathways may shed new light on the similarities and differences between cancers.
Quantitative genome re-sequencing defines multiple mutations conferring chloroquine resistance in rodent malaria
Authors: Kinga Modrzynska Katarzyna , Creasey Alison , Loewe Laurence , Cezard Timothee , Trindade Borges Sofia , Martinelli Axel , Rodrigues Louise , Cravo Pedro , Blaxter Mark , Carter Richard , Hunt Paul
Published: March 2012

Background

Drug resistance in the malaria parasite Plasmodium falciparum severely compromises the treatment and control of malaria. A knowledge of the critical mutations conferring resistance to particular drugs is important in understanding modes of drug action and mechanisms of resistances. They are required to design better therapies and limit drug resistance.

A mutation in the gene (pfcrt) encoding a membrane transporter has been identified as a principal determinant of chloroquine resistance in P. falciparum, but we lack a full account of higher level chloroquine resistance. Furthermore, the determinants of resistance in the other major human malaria parasite, P. vivax, are not known. To address these questions, we investigated the genetic basis of chloroquine resistance in an isogenic lineage of rodent malaria parasite P. chabaudi in which high level resistance to chloroquine has been progressively selected under laboratory conditions.

Results

Loci containing the critical genes were mapped by Linkage Group Selection, using a genetic cross between the high-level chloroquine-resistant mutant and a genetically distinct sensitive strain. A novel high-resolution quantitative whole-genome re-sequencing approach was used to reveal three regions of selection on chr11, chr03 and chr02 that appear progressively at increasing drug doses on three chromosomes. Whole-genome sequencing of the chloroquine-resistant parent identified just four point mutations in different genes on these chromosomes. Three mutations are located at the foci of the selection valleys and are therefore predicted to confer different levels of chloroquine resistance. The critical mutation conferring the first level of chloroquine resistance is found in aat1, a putative aminoacid transporter.

Conclusions

Quantitative trait loci conferring selectable phenotypes, such as drug resistance, can be mapped directly using progressive genome-wide linkage group selection. Quantitative genome-wide short-read genome resequencing can be used to reveal these signatures of drug selection at high resolution. The identities of three genes (and mutations within them) conferring different levels of chloroquine resistance generate insights regarding the genetic architecture and mechanisms of resistance to chloroquine and other drugs. Importantly, their orthologues may now be evaluated for critical or accessory roles in chloroquine resistance in human malarias P. vivax and P. falciparum.
Potential T cell epitopes of Mycobacterium tuberculosis that can instigate molecular mimicry against host: implications in autoimmune pathogenesis
Authors: Babu Chodisetti Sathi , Rai Pradeep K , Gowthaman Uthaman , Pahari Susanta , Agrewala Javed N
Published: March 2012

Background

Molecular mimicry between microbial antigens and host-proteins is one of the etiological enigmas for the occurrence of autoimmune diseases. T cells that recognize cross-reactive epitopes may trigger autoimmune reactions. Intriguingly, autoimmune diseases have been reported to be prevalent in tuberculosis endemic populations. Further, association of Mycobacterium tuberculosis (M. tuberculosis) has been implicated in different autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Although, in silico analyses have identified a number of M. tuberculosis specific vaccine candidates, the analysis on prospective cross-reactive epitopes, that may elicit autoimmune response, has not been yet attempted. Here, we have employed bioinformatics tools to determine T cell epitopes of homologous antigenic regions between M. tuberculosis and human proteomes.

Results

Employing bioinformatics tools, we have identified potentially cross-reactive T cell epitopes restricted to predominant class I and II alleles of human leukocyte antigens (HLA). These are similar to peptides of mycobacterial proteins and considerable numbers of them are promiscuous. Some of the identified antigens corroborated with established autoimmune diseases linked with mycobacterial infection.

Conclusions

The present study reveals many target proteins and their putative T cell epitopes that might have significant application in understanding the molecular basis of possible T cell autoimmune reactions during M. tuberculosis infections.
Multilocus microsatellite analysis of 'Candidatus Liberibacter asiaticus' associated with citrus Huanglongbing worldwide
Authors: Islam Md-Sajedul , Glynn Jonathan M , Bai Yang , Duan Yong-Ping , Coletta-Filho Helvecio D , Kuruba Gopal , Civerolo Edwin L , Lin Hong
Published: March 2012

Background

Huanglongbing (HLB) is one of the most destructive citrus diseases in the world. The disease is associated with the presence of a fastidious, phloem-limited α- proteobacterium, 'Candidatus Liberibacter asiaticus', 'Ca. Liberibacter africanus' or 'Ca. Liberibacter americanus'. HLB-associated Liberibacters have spread to North America and South America in recent years. While the causal agents of HLB have been putatively identified, information regarding the worldwide population structure and epidemiological relationships for 'Ca. L. asiaticus' is limited. The availability of the 'Ca. L. asiaticus' genome sequence has facilitated development of molecular markers from this bacterium. The objectives of this study were to develop microsatellite markers and conduct genetic analyses of 'Ca. L. asiaticus' from a worldwide collection. Two hundred eighty seven isolates from USA (Florida), Brazil, China, India, Cambodia, Vietnam, Taiwan, Thailand, and Japan were analyzed.

Results

A panel of seven polymorphic microsatellite markers was developed for 'Ca. L. asiaticus'. Microsatellite analyses across the samples showed that the genetic diversity of 'Ca. L. asiaticus' is higher in Asia than Americas. UPGMA and STRUCTURE analyses identified three major genetic groups worldwide. Isolates from India were genetically distinct. East-southeast Asian and Brazilian isolates were generally included in the same group; a few members of this group were found in Florida, but the majority of the isolates from Florida were clustered separately. eBURST analysis predicted three founder haplotypes, which may have given rise to three groups worldwide.

Conclusions

Our results identified three major genetic groups of 'Ca. L. asiaticus' worldwide. Isolates from Brazil showed similar genetic makeup with east-southeast Asian dominant group, suggesting the possibility of a common origin. However, most of the isolates recovered from Florida were clustered in a separate group. While the sources of the dominant 'Ca. L. asiaticus' in Florida were not clearly understood, the less-pervasive groups may have been introduced directly from Asia or via Brazil. Notably, the recent outbreak of HLB in Florida probably occurred through multiple introductions. Microsatellite markers developed in this study provide adequate discriminatory power for the identification and differentiation of closely-related isolates, as well as for genetic studies of 'Ca. L. asiaticus'.
The mediating role of psychological capital on the association between occupational stress and depressive symptoms among Chinese physicians: a cross-sectional study
Authors: Liu Li , Chang Ying , Fu Jialiang , Wang Jiana , Wang Lie
Published: March 2012

Background

Although occupational stress is an identified predictor of depressive symptoms, the mechanism behind the association is not well understood. The purpose of this study was to examine how psychological capital (PsyCap), a positive psychological state, mediates the association between occupational stress and depressive symptoms among Chinese physicians.

Methods

A cross-sectional survey was conducted in Liaoning Province, China, during September–October 2010. Self-administered questionnaires including items on depressive symptoms assessed by the Center for Epidemiologic Studies Depression Scale, occupational stress assessed by the effort–reward imbalance scale and PsyCap estimated by a 24-item Psychological Capital Questionnaire, together with age, gender, marital status and education were distributed to 1300 physicians employed in large general hospitals. The final sample consisted of 998 participants. Asymptotic and resampling strategies were used to examine how PsyCap mediates the association between occupational stress and depressive symptoms.

Results

Both the effort/reward ratio (ERR) and overcommitment were significantly associated with depressive symptoms among male and female physicians. There was a gender difference in the mediating role of PsyCap on the occupational stress–depressive symptoms association. For male physicians, PsyCap did not mediate the association between occupational stress and depressive symptoms. For female physicians, ERR and overcommitment were negatively associated with PsyCap, and PsyCap was negatively associated with depressive symptoms. As a result, PsyCap significantly mediated the associations of ERR and overcommitment with depressive symptoms. The proportion of PsyCap mediation was 19.07% for ERR, and 24.29% for overcommitment.

Conclusions

PsyCap could be a positive resource for combating depressive symptoms in Chinese physicians. In addition to reducing occupational stress, PsyCap development should be included in depression prevention and treatment strategies, especially for female physicians.
Pro-oxidant status and matrix metalloproteinases in apical lesions and gingival crevicular fluid as potential biomarkers for asymptomatic apical periodontitis and endodontic treatment response
Authors: Dezerega Andrea , Madrid Sonia , Mundi Verónica , Valenzuela María A , Garrido Mauricio , Paredes Rodolfo , García-Sesnich Jocelyn , Ortega Ana V , Gamonal Jorge , Hernández Marcela
Published: March 2012

Background

Oxidative stress and matrix metalloproteinases -9 and -2 are involved in periodontal breakdown, whereas gingival crevicular fluid has been reported to reflect apical status. The aim of this study was to characterize oxidant balance and activity levels of MMP -2 and -9 in apical lesions and healthy periodontal ligament; and second, to determine whether potential changes in oxidant balance were reflected in gingival crevicular fluid from asymptomatic apical periodontitis (AAP)-affected teeth at baseline and after endodontic treatment.

Methods

Patients with clinical diagnosis of AAP and healthy volunteers having indication of tooth extraction were recruited. Apical lesions and healthy periodontal ligaments, respectively, were homogenized or processed to obtain histological tissue sections. Matrix metalloproteinase -9 and -2 levels and/or activity were analyzed by Immunowestern blot, zymography and consecutive densitometric analysis, and their tissue localization was confirmed by immunohistochemistry. A second group of patients with AAP and indication of endodontic treatment was recruited. Gingival crevicular fluid was extracted from AAP-affected teeth at baseline, after endodontic treatment and healthy contralateral teeth. Total oxidant and antioxidant status were determined in homogenized tissue and GCF samples. Statistical analysis was performed using STATA v10 software with unpaired t test, Mann-Whitney test and Spearman's correlation.

Results

Activity of MMP-2 and MMP-9 along with oxidant status were higher in apical lesions (p < 0.05). Total oxidant status correlated positively with matrix metalloproteinase-2 and lesion size (p < 0.05). Gingival crevicular fluid showed significantly lower levels of total antioxidant status in diseased teeth at baseline compared to controls and endodontically-treated groups.

Conclusions

Apical lesions display an oxidant imbalance along with increased activity of matrix metalloproteinase-2 and -9 and might contribute to AAP progression. Oxidant imbalance can also be reflected in GCF from AAP-affected teeth and was restored to normal levels after conservative endodontic treatment. These mediators might be useful as potential biomarkers for chair-side complementary diagnostic of apical status in GCF.
Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase
Authors: Gårevik Nina , Skogastierna Cristine , Rane Anders , Ekström Lena
Published: March 2012

Background

Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR). There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR.

Methods

39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of Testoviron®--Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2).

Results

The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007). This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively.

Conclusion

Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.
Notes on the blood-feeding behavior of Aedes albopictus (Diptera: Culicidae) in Cameroon
Authors: Kamgang Basile , Nchoutpouen Elysée , Simard Frédéric , Paupy Christophe
Published: March 2012

Background

The invasive mosquitoAedes albopictusis often considered a poor vector of human pathogens, owing to its catholic feeding behavior. However, it was recently incriminated as a major vector in several Chikungunya epidemics, outside of its native range. Here we assessed two key elements of feeding behavior byAe. albopictusfemales in Yaoundé, Cameroon, Central Africa. Host preference was explored and the human-biting activity of females was monitored over 24 h to determine periods of maximum bite exposure.

Findings

Analysis of ingested blood in outdoor-resting females showed thatAe. albopictuspreferentially fed on humans rather than on available domestic animals (95% of the blood meals contained human blood). Our results further showed thatAe. albopictusis a day-biting species in Yaoundé, with a main peak of activity in the late afternoon.

Conclusion

This is the first report on the feeding behavior ofAe. albopictusin Central Africa. The species is highly aggressive to humans and might therefore be involved in human-human virus transmission in this setting.
Open science versus commercialization: a modern research conflict?
Authors: Caulfield Timothy , Harmon Shawn HE , Joly Yann
Published: March 2012

Background

Efforts to improve research outcomes have resulted in genomic researchers being confronted with complex and seemingly contradictory instructions about how to perform their tasks. Over the past decade, there has been increasing pressure on university researchers to commercialize their work. Concurrently, they are encouraged to collaborate, share data and disseminate new knowledge quickly (that is, to adopt an open science model) in order to foster scientific progress, meet humanitarian goals, and to maximize the impact of their research.

Discussion

We present selected guidelines from three countries (Canada, United States, and United Kingdom) situated at the forefront of genomics to illustrate this potential policy conflict. Examining the innovation ecosystem and the messages conveyed by the different policies surveyed, we further investigate the inconsistencies between open science and commercialization policies.

Commercialization and open science are not necessarily irreconcilable and could instead be envisioned as complementary elements of a more holistic innovation framework. Given the exploratory nature of our study, we wish to point out the need to gather additional evidence on the coexistence of open science and commercialization policies and on its impact, both positive and negative, on genomics academic research.
Marine resistivity tomography for coastal engineering applications in Greece
Authors: Apostolopoulos G.
Published: March 2012

The marine resistivity tomography method can be useful for coastal engineering applications through the use of immersion cables, laid on the water bottom, thus achieving a deeper and more detailed detection of the formations underneath. Careful positioning of the profiles related to the available geologic, geomorphological, bathymetric, and drilling data and to the requirements of engineers, can give thicknesses of loose material as well as the bedrock relief. The formations and their interfaces are clearly defined either by calibration with available drilling data or by high resistivity changes which indicate discontinuities with resistivity values related to permeability and saline water presence. Two case studies are under examination. The first concerns the preservation of an old iron bridge in Lavrion Port with reinforcement and new foundations. Here, the geophysical investigation detects the formation on which the bridge was founded, as well as the loose material above it. The second case study concerns geophysical investigation asked by a construction company for the marine excavation work needed in the new Mesta port. Here, the geophysical measurements with the detected formations give valuable information with respect to the volume of material, equipment, time and cost of excavation as well as where the foundations will be laid for new constructions.
Evidence of a Role for Kisspeptin and Neurokinin B in Puberty of Female Sheep
Authors: Nestor Casey C , Briscoe Amanda M.S. , Davis Shay M. , Valent Miro , Goodman Robert L. , Hileman Stanley M.
Published: March 2012

Puberty onset in female sheep is marked by a decrease in estradiol-negative feedback, allowing for the increase in GnRH and LH pulses that heralds the first ovulation. Based on recent genetic studies in humans, two possible neuropeptides that could promote puberty onset are kisspeptin and neurokinin B (NKB). Our first experiment determined whether the NKB agonist, senktide, could stimulate LH secretion in prepubertal ewes. A second study used prepubertal and postpubertal ewes that were intact or ovariectomized (OVX) to test the hypothesis that expression of kisspeptin and NKB in the arcuate nucleus increased postpubertally. For comparison, kisspeptin and NKB expression in age-matched intact, and castrated males were also examined. In experiment 1, the percentage of ewes showing an LH pulse immediately after injection of senktide (100 μg, 60%; 500 μg, 100%) was greater than that for water-injected controls (experiment 1a, 25%; experiment 1b, 20%). In experiment 2, kisspeptin-positive cell numbers in the arcuate nucleus increased after puberty in intact females and were increased by OVX in prepubertal but not postpubertal ewes. Changes in kisspeptin cell numbers were paralleled by changes in kisspeptin-close contacts onto GnRH neurons in the medial preoptic area. NKB cell numbers did not differ significantly between intact prepubertal and postpubertal ewes but increased with OVX in both age groups. NKB fiber immunoreactivity was greater in postpubertal than in prepubertal intact ewes. In age-matched males, kisspeptin and NKB cell numbers increased with castration, but decreased with age. These results support the hypothesis that kisspeptin is a gatekeeper to female ovine puberty and raise the possibility that NKB may also play a role, albeit through different means.
Understanding the Sexome: Measuring and Reporting Sex Differences in Gene Systems
Authors: Arnold Arthur P. , Lusis Aldons J.
Published: March 2012

The current male bias in biomedical research should be eliminated. The large sex differences in incidence and progression of diseases mean that sex-biased factors are an untapped source of factors that protect from disease. Greater understanding will come from intensified study of the “sexome,” which is the sum of sex-biased effects on gene networks and cell systems. The global search for sites and mechanisms of sex-specific regulation in diverse tissues will provide unanticipated insights into physiological regulation and targets for novel therapies.
Autotrophic carbon budget in coral tissue: a new 13C-based model of photosynthate translocation
Authors: Tremblay Pascale , Grover Renaud , Maguer Jean François , Legendre Louis , Ferrier-Pagès Christine
Published: March 2012

Corals live in symbiosis with dinoflagellates of the genus Symbiodinum. These dinoflagellates translocate a large part of the photosynthetically fixed carbon to the host, which in turn uses it for its own needs. Assessing the carbon budget in coral tissue is a central question in reef studies that still vexes ecophysiologists. The amount of carbon fixed by the symbiotic association can be determined by measuring the rate of photosynthesis, but the amount of carbon translocated by the symbionts to the host and the fate of this carbon are more difficult to assess. In the present study, we propose a novel approach to calculate the budget of autotrophic carbon in the tissue of scleractinian corals, based on a new model and measurements made with the stable isotope 13C. Colonies of the scleractinian coral Stylophora pistillata were incubated in H13CO –3-enriched seawater, after which the fate of 13C was followed in the symbionts, the coral tissue and the released particulate organic carbon (i.e. mucus). Results obtained showed that after 15 min, ca. 60% of the carbon fixed was already translocated to the host, and after 48 h, this value reached 78%. However, ca. 48% of the photosynthetically fixed carbon was respired by the symbiotic association, and 28% was released as dissolved organic carbon. This is different from other coral species, where <1% of the total organic carbon released is from newly fixed carbon. Only 23% of the initially fixed carbon was retained in the symbionts and coral tissue after 48 h. Results show that our 13C-based model could successfully trace the carbon flow from the symbionts to the host, and the photosynthetically acquired carbon lost from the symbiotic association.
Evaporation dynamics of tarsal liquid footprints in flies (Calliphora vicina)and beetles (Coccinella septempunctata)
Authors: Peisker Henrik , Gorb Stanislav N.
Published: March 2012

Insect tarsal adhesive structures secrete a thin layer of fluid into the contact area. It was previously reported that the presence of this fluid significantly increases adhesion on various substrata. Previous data obtained from representatives of different insect groups suggest a difference not only in the chemical composition of the fluid, but also in its physical properties. In the present study, we have measured for the first time changes in the droplet geometry over time and the evaporation rate of the fluid in flies (Calliphora vicina) and beetles (Coccinella septempunctata) by the use of atomic force microscopy. Flattened droplets of the beetle had lower evaporation rates than hemispherical footprints of the fly. Within 1 h, the droplet volume reduced to 21% of the initial volume for the fly, and to 65% for the beetle, suggesting a larger fraction of volatile compounds in the fly fluid. It was revealed that drop geometry changes significantly during evaporation and shows pinning effects for the fly footprints due to an assumed self-organizing oil layer on top of the water fraction of the micro-emulsion. The data obtained suggest that the adhesion strength in capillarity-based switchable adhesive systems must be time-dependent because of the specific evaporation rate of the adhesive fluid. These results are important for our understanding of the functional mechanism of insect adhesive systems and also for biomimetics of artificial capillarity-based adhesive systems.
Digesting blood of an auxiliary host in fleas: effect of phylogenetic distance from a principal host
Authors: Khokhlova Irina S. , Fielden Laura J. , Degen A. Allan , Krasnov Boris R.
Published: March 2012

Fleas are haematophagous ectoparasites that exhibit varying degrees of host specificity. Flea abundance is highest on principal hosts and lower on auxiliary hosts but may vary greatly among auxiliary hosts. We investigated the feeding and energy expenditure for digestion in two flea species Parapulex chephrenis and Xenopsylla ramesis on a principal host (Acomys cahirinus and Meriones crassus, respectively) and eight auxiliary host species. We predicted that fleas would perform better – that is (i) a higher proportion of fleas would take a blood meal, (ii) fleas would take larger blood meals and (iii) fleas would spend less energy on digestion – if they fed on (i) a principal host compared with an auxiliary host and (ii) an auxiliary host phylogenetically close to a principal host compared with an auxiliary host phylogenetically distant from a principal host. Energy costs of digestion were estimated using CO2 emission and represented energy cost during the first stage of blood digestion. Contrary to our predictions, fleas did not always perform better on a principal than on an auxiliary host or on auxiliary hosts phylogenetically closer to the principal host than on auxiliary hosts phylogenetically distant from a principal host. Variation in flea feeding performance may result from the interplay of several factors including co-occurrence between hosts and susceptibility of a host to flea attacks, the species-specific level of immunocompetence of a host and the level of host specificity of a flea. This study describes the first investigation into the metabolic expenditure of parasitism and its relationship to phylogenetic relationships amongst hosts.
A Branch-Price-and-Cut Algorithm for Single-Product Maritime Inventory Routing
Authors: Engineer Faramroze G. , Furman Kevin C. , Nemhauser George L. , Savelsbergh Martin W. P. , Song Jin-Hwa
Published: March 2012

A branch-price-and-cut algorithm is developed for a complex maritime inventory-routing problem with varying storage capacities and production/consumption rates at facilities. The resulting mixed-integer pricing problem is solved exactly and efficiently using a dynamic program that exploits certain “extremal” characteristics of the pricing problem. The formulation is tightened by using the problem's boundary conditions in preprocessing and to restrict the set of columns that are produced by the pricing problem. Branching schemes and cuts are introduced that can be implemented efficiently and that preserve the structure of the pricing problem. Some of the cuts are inspired by the capacity cuts known for the vehicle-routing problem, whereas others specifically target fractional solutions brought about by individual vessels “competing” for limited inventory at load ports and limited storage capacity at discharge ports. The branch-price-and-cut approach solves practically sized problems motivated by the operations of an oil company to optimality, and it provides reasonable bounds for larger instances.
Asymptotic Optimality of Balanced Routing
Authors: Chen Hong , Ye Heng-Qing
Published: March 2012

Consider a system with K parallel servers, each with its own waiting room. Upon arrival, a job is routed to the queue of one of the servers. Finding a routing policy that minimizes the total workload in the system is a known difficult problem in general. Even if the optimal policy is identified, the policy would require the full queue length information at the arrival of each job; for example, the join-the-shortest-queue policy (which is known to be optimal for identical servers with exponentially distributed service times) would require comparing the queue lengths of all the servers. In this paper, we consider a balanced routing policy that examines only a subset of c servers, with 1 ≤ c ≤ K: specifically, upon the arrival of a job, choose a subset of c servers with a probability proportional to their service rates, and then route the job to the one with the shortest queue among the c chosen servers. Under such a balanced policy, we derive the diffusion limits of the queue length processes and the workload processes. We note that the diffusion limits are the same for these processes regardless the choice of c, as long as c ≥ 2. We further show that the proposed balanced routing policy for any fixed c ≥ 2 is asymptotically optimal in the sense that it minimizes the workload over all time in the diffusion limit. In addition, the policy helps to distribute work among all the servers evenly.
On the Complexity of Nonoverlapping Multivariate Marginal Bounds for Probabilistic Combinatorial Optimization Problems
Authors: Doan Xuan Vinh , Natarajan Karthik
Published: March 2012

Given a combinatorial optimization problem with an arbitrary partition of the set of random objective coefficients, we evaluate the tightest-possible bound on the expected optimal value for joint distributions consistent with the given multivariate marginals of the subsets in the partition. For univariate marginals, this bound was first proposed by Meilijson and Nadas [Meilijson, I., A. Nadas. 1979. Convex majorization with an application to the length of critical path. J. Appl. Probab. 16(3) 671–677]. We generalize the bound to nonoverlapping multivariate marginals using multiple-choice integer programming. New instances of polynomial-time computable bounds are identified for discrete distributions. For the problem of selecting up to M items out of a set of N items of maximum total weight, the multivariate marginal bound is shown to be computable in polynomial time, when the size of each subset in the partition is O(log N). For an activity-on-arc PERT network, the partition is naturally defined by subsets of incoming arcs into nodes. The multivariate marginal bound on expected project duration is shown to be computable in time polynomial in the maximum number of scenarios for any subset and the size of the network. As an application, a polynomial-time solvable two-stage stochastic program for project crashing is identified. An important feature of the bound developed in this paper is that it is exactly achievable by a joint distribution, unlike many of the existing bounds.
Consistency of Multidimensional Convex Regression
Authors: Lim Eunji , Glynn Peter W.
Published: March 2012

Convex regression is concerned with computing the best fit of a convex function to a data set of n observations in which the independent variable is (possibly) multidimensional. Such regression problems arise in operations research, economics, and other disciplines in which imposing a convexity constraint on the regression function is natural. This paper studies a least-squares estimator that is computable as the solution of a quadratic program and establishes that it converges almost surely to the “true” function as n → ∞ under modest technical assumptions. In addition to this multidimensional consistency result, we identify the behavior of the estimator when the model is misspecified (so that the “true” function is nonconvex), and we extend the consistency result to settings in which the function must be both convex and nondecreasing (as is needed for consumer preference utility functions).
Price of Correlations in Stochastic Optimization
Authors: Agrawal Shipra , Ding Yichuan , Saberi Amin , Ye Yinyu
Published: March 2012

When decisions are made in the presence of high-dimensional stochastic data, handling joint distribution of correlated random variables can present a formidable task, both in terms of sampling and estimation as well as algorithmic complexity. A common heuristic is to estimate only marginal distributions and substitute joint distribution by independent (product) distribution. In this paper, we study possible loss incurred on ignoring correlations through a distributionally robust stochastic programming model, and we quantify that loss as price of correlations (POC). Using techniques of cost sharing from game theory, we identify a wide class of problems for which POC has a small upper bound. To our interest, this class will include many stochastic convex programs, uncapacitated facility location, Steiner tree, and submodular functions, suggesting that the intuitive approach of assuming independent distribution acceptably approximates the robust model for these stochastic optimization problems. Additionally, we demonstrate hardness of bounding POC via examples of subadditive and supermodular functions that have large POC. We find that our results are also useful for solving many deterministic optimization problems like welfare maximization, k-dimensional matching, and transportation problems, under certain conditions.
The EU-Korea Free Trade Agreement: Making of a "Deep" Free Trade Agreement
Authors: Das Dilip K.
Published: March 2012

Korea a dynamic newly-industrialized economy, and the EU, the largest economic block have negotiated an FTA. It came in force on July 1, 2011. Before the FTA was formed, the two were important trading partners of each other. Korea has enjoyed a trade surplus in merchandise trade vis-à-vis the EU. An overwhelmingly large proportion of EU-Korea trade is in manufacturing products. The EU took has had a surplus in trade in services vis-à-vis Korea. The FTA protocol has specified lowering of tariffs and NTBs in a phased manner over a transition period. The FTA had sector-focused negations. Technological standards and environmental considerations are a part of the FTA protocol. It has a comprehensive coverage and in trade economics parlance known as a “deep” regional integration arrangement.

The impact of the FTA on the two partner economies would be positive but small. The empirical analyses predictably concluded that of the two, the FTA will benefit Korean economy relatively more in terms of welfare gains, while the EU economy will only gain modestly. An important fact that will influence the welfare gains is that the magnitude of the EU trade with Korea; it is only 2 percent to 2.5 percent of total extra-EU trade. Sectoral impact of the FTA will be important for both the EU and Korea and this article elucidates which sectors will benefit more than others. To protect domestic producers and markets from sudden surge in imports, there is a provision of a bilateral safeguard clause in the FTA.