bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal programming of rat cortical collecting tubule sodium transport
Authors: Cheng Chih-Jen , Lozano German , Baum Michel
Published: December 2011

Prenatal insults have been shown to lead to elevated blood pressure in offspring when they are studied as adults. Prenatal administration of dexamethasone and dietary protein deprivation have demonstrated that there is an increase in transporter abundance for a number of nephron segments but not the subunits of the epithelial sodium channel (ENaC) in the cortical collecting duct. Recent studies have shown that aldosterone is elevated in offspring of protein-deprived mothers when studied as adults, but the physiological importance of the increase in serum aldosterone is unknown. As an indirect measure of ENaC activity, we compared the natriuretic response to benzamil in offspring of mothers who ate a low-protein diet (6%) with those who ate a normal diet (20%) for the last half of pregnancy. The natriuretic response to benzamil was greater in the 6% group (821.1 ± 161.0 μmol/24 h) compared with the 20% group (279.1 ± 137.0 μmol/24 h), consistent with greater ENaC activity in vivo ( P < 0.05). In this study, we also directly studied cortical collecting tubule function from adult rats using in vitro microperfusion. There was no difference in basal or vasopressin-stimulated osmotic water permeability. However, while cortical collecting ducts of adult offspring whose mothers ate a 20% protein diet had no sodium transport (−1.9 ± 3.1 pmol·mm−1·min−1), the offspring of rats that ate a 6% protein diet during the last half of pregnancy had a net sodium flux of 10.7 ± 2.6 pmol·mm−1·min−1( P = 0.01) in tubules perfused in vitro. Sodium transport was measured using ion-selective electrodes, a novel technique allowing measurement of sodium in nanoliter quantities of fluid. Thus we directly demonstrate that there is prenatal programming of cortical collecting duct sodium transport.
Finger Rehabilitation Support System Using a Multifingered Haptic Interface Controlled by a Surface Electromyogram
Authors: Hioki Masaaki , Kawasaki Haruhisa , Sakaeda Hirofumi , Nishimoto Yutaka , Mouri Tetsuya
Published: December 2011

This paper presents a new type of finger rehabilitation system using a multifingered haptic interface that is controlled by the patient though a surface electromyogram. We have developed the multifingered haptic interface robot: HIRO III that can give 3-directional forces to 5 fingertips. This robot can also be used as a rehabilitation device that can provide various fingertip exercises and measure various types of information. The sEMG works together with the HIRO III to consider the patient's intent. The proposed system is intended for patients having paralysis in the hand and fingers, and the motions will be provided as biofeedback to the fingertips with the device. In contrast to completely passive rehabilitation, the proposed system can provide active rehabilitation using sEMG. The experiment involved finger opening and closing with this system by ten able-bodied subjects. The results show that almost all subjects felt appropriate motion support from the device.
The Dynamics of Visual Art Dialogues: Experiences to Be Used in Hospital Settings with Visual Art Enrichment
Authors: Wikström Britt-Maj
Published: December 2011

Objectives. Given that hospitals have environmental enrichment with paintings and visual art arrangement, it would be meaningful to develop and document how hospital art could be used by health professionals.Methods. The study was undertaken at an art site in Sweden. During 1-hour sessions, participants () get together in an art gallery every second week five times.Results. According to the participants a new value was perceived. From qualitative analyses, three themes appear: raise association, mentally present, and door-opener. In addition 72% of the participants reported makes me happy and gives energy and inspiration, and 52% reported that dialogues increase inspiration, make you involved, and stimulate curiosity.Conclusion. The present study supported the view that visual art dialogue could be used by health care professionals in a structured manner and that meaningful art stimulation, related to a person’s experiences, could be of importance for the patients. Implementing art dialogues in hospital settings could be a fruitful working tool for nurses, a complementary manner of patient communication.
Toward an Understanding of the Madden-Julian Oscillation: With a Mesoscale-Convection-Resolving Model of 0.2 Degree Grid
Authors: Yamasaki Masanori
Published: December 2011

This paper describes results from numerical experiments which have been performed as the author's first step toward a better understanding of the Madden-Julian oscillation (MJO). This study uses the author's mesoscale-convection-resolving model that was developed in the 1980s to improve parametrization schemes of moist convection. Results from numerical experiments by changing the SST anomaly in the warm pool area indicate that the period of the MJO does not monotonously change with increasing SST anomaly. Between the two extreme cases (no anomaly and strong anomaly), there is a regime in which the period varies in a wide range from 20 to 60 days. In the case of no warm pool, eastward-propagating Kelvin waves are dominant, whereas in the case of a strong warm pool, it produces a quasi-stationary convective system (with pronounced time variation). In a certain regime between the two extreme cases, convective activities with two different properties are strongly interacted, and the period of oscillations becomes complicated. The properties and behaviors of large-scale convective system (LCS), synoptic-scale convective system (SCS), mesoscale convective system (MCS), and mesoscale convection (MC), which constitute the hierarchical structure of the MJO, are also examined. It is also shown that cloud clusters, which constitute the SCS (such as super cloud cluster SCC), consist of a few MCS, and a new MCS forms to the west of the existing MCS. The northwesterly and southwesterly low-level flows contribute to this feature. In view of recent emphasis of the importance of the relative humidity above the boundary layer, it is shown that the model can simulate convective processes that moisten the atmosphere, and the importance of latent instability (positive CAPE), which is a necessary condition for the wave-CISK, is emphasized.
Osteoid Osteoma of the Proximal Fibula: An Uncommon Location with the Indication for Open Surgery
Authors: Marquass Bastian , Hepp Pierre , Theopold Jan Dirk , von Dercks Nikolaus , Blattert Thomas R. , Josten Christoph
Published: December 2011

Purpose. This is a case report of a patient with an osteoid osteoma of the proximal fibula. The objective is to illustrate a rare tumor location that requires open surgery due to closeness of neurological structures.Methods. Clinical and roentgenographic findings, treatment, and histological appearance are presented.Results. Local pain and swelling of the proximal fibula with improvement under salicylates led to the diagnosis of an osteoid osteoma, what was confirmed with an MRI scan. Due to proximity to the common peroneal nerve, we decided for open surgery. During the operation, the nerve was seen to cross the tumor site making it necessary to retract it to expose the entire tumor. Histologically, typical features of osteoid osteoma with a rather well-defined nidus surrounded by sclerotic bone were seen. A complete removal was performed.Conclusion. Osteoid osteomas of the proximal fibula are rare. When planning surgery, the common peroneal nerve must be identified, and its further distal course should be taken into account to avoid iatrogenic damage to the nerve.
Nonlinear Elasto-Mammography for Characterization of Breast Tissue Properties
Authors: Wang Z. G. , Liu Y. , Wang G. , Sun L. Z.
Published: December 2011

Quantification of the mechanical behavior of normal and cancerous tissues has important implication in the diagnosis of breast tumor. The present work extends the authors' nonlinear elastography framework to incorporate the conventional X-ray mammography, where the projection of displacement information is acquired instead of full three-dimensional (3D) vector. The elastic parameters of normal and cancerous breast tissues are identified by minimizing the difference between the measurement and the corresponding computational prediction. An adjoint method is derived to calculate the gradient of the objective function. Simulations are conducted on a 3D breast phantom consisting of the fatty tissue, glandular tissue, and cancerous tumor, whose mechanical responses are hyperelastic in nature. The material parameters are identified with consideration of measurement error. The results demonstrate that the projective displacements acquired in X-ray mammography provide sufficient constitutive information of the tumor and prove the usability and robustness of the proposed method and algorithm.
A Case of Recurrent Transient Monocular Visual Loss after Receiving Sildenafil
Authors: Ghanem Asaad Ghanem
Published: December 2011

A 53-year-old man was attended to the Clinic Ophthalmic Center, Mansoura University, Egypt, with recurrent transient monocular visual loss after receiving sildenafil citrate (Viagra) for erectile dysfunction. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral nonarteritic anterior ischemic optic neuropathy (NAION). Physicians might look for arteriosclerotic risk factors and family history of NAION among predisposing risk factors before prescribing sildenafil erectile dysfunction drugs.
Ultrasonographic Guidance and Characterization of Cryoanalgesic Lesions in Treating a Case of Refractory Sural Neuroma
Authors: Rhame Ellen E. , DeBonet Alexander F. , Simopoulos Thomas T.
Published: December 2011

The recurrent pain of a neuroma following surgical excision and burial of nerve endings can be clinically challenging to manage. Cryoanalgesia in conjunction with ultrasound guidance was used successfully to manage this type of pain. Furthermore, ultrasound provided visualization of the cryolesions, as well as the relationships of the ice ball to the surrounding tissue. Following the completion of the freeze cycle, the tissue can be monitored for return to its usual morphology during the thaw period.
Homologue Pairing in Flies and Mammals: Gene Regulation When Two Are Involved
Authors: Apte Manasi S. , Meller Victoria H.
Published: December 2011

Chromosome pairing is usually discussed in the context of meiosis. Association of homologues in germ cells enables chromosome segregation and is necessary for fertility. A few organisms, such as flies, also pair their entire genomes in somatic cells. Most others, including mammals, display little homologue pairing outside of the germline. Experimental evidence from both flies and mammals suggests that communication between homologues contributes to normal genome regulation. This paper will contrast the role of pairing in transmitting information between homologues in flies and mammals. In mammals, somatic homologue pairing is tightly regulated, occurring at specific loci and in a developmentally regulated fashion. Inappropriate pairing, or loss of normal pairing, is associated with gene misregulation in some disease states. While homologue pairing in flies is capable of influencing gene expression, the significance of this for normal expression remains unknown. The sex chromosomes pose a particularly interesting situation, as females are able to pair X chromosomes, but males cannot. The contribution of homologue pairing to the biology of the X chromosome will also be discussed.
Water-Based Fe2O3 Nanofluid Characterization: Thermal Conductivity and Viscosity Measurements and Correlation
Authors: Colla L. , Fedele L. , Scattolini M. , Bobbo S.
Published: December 2011

An experimental investigation on water-based nanofluids containing iron oxide (Fe2O3) in concentrations ranging between 5 and 20% in mass is presented. The purpose of this study is to measure thermal conductivity and dynamic viscosity of these fluids, as a starting point to study the heat transfer capability. The stability of the nanofluids was verified by pH and Zeta potential measurements. A dynamic light scattering (DLS) technique was used to obtain the mean nanoparticle diameters. It was found that thermal conductivity of these nanofluids improved with temperature and particles concentration. The temperature and nanoparticle concentration effects on viscosity were analyzed, obtaining a significant increase with respect to water. All the fluids exhibited a Newtonian behaviour. The experimental values were compared with some theoretical models for both thermal conductivity and dynamic viscosity.
Potentiation of the Novel Topoisomerase I Inhibitor Indenoisoquinoline LMP-400 by the Cell Checkpoint and Chk1-Chk2 Inhibitor AZD7762
Authors: Aris Sheena M. , Pommier Yves
Published: December 2011

Novel topoisomerase I (Top1) inhibitors are in clinical development to circumvent the drawbacks of camptothecins (CPT). Here, we report molecular investigations into LMP-400, an indenoisoquinoline Top1 inhibitor in phase 1 clinical trial, by itself and in combination with the cell-cycle checkpoint inhibitor AZD7762. We examined drug effects on DNA replication and killing of cancer cells and found that LMP-400 showed synergistic antiproliferative activity when combined with AZD7762 in human colon carcinoma cells. Inhibition of S-phase progression and bromodeoxyuridine incorporation were similarly induced by LMP-400 and CPT and were abrogated by AZD7762. Replication studied by single DNA molecule analyses and immunofluorescence microscopy (molecular combing) showed rapid inhibition of fork progression in response to LMP-400 treatment with subsequent recapitulation after AZD7762 addition. AZD7762 inhibited both the activation/autophosphosphorylation of Chk1 and Chk2 at nanomolar concentrations in LMP-400–treated cells. This potent dual inhibition of Chk1 and Chk2 by AZD7762 was below the drug concentrations required to abrogate cell-cycle inhibition and produce synergism with LMP-400. Also, the synergism was independent of Chk2 both in Chk2-complemented cells and Chk2 knockout cells, suggesting additional mechanisms for cell-cycle abrogation by AZD7762. Together, our findings show a rationale for combining cell-cycle checkpoint inhibitors with the novel non-CPT indenoisoquinoline Top1 inhibitors. Cancer Res; 72(4); 979–89. ©2011 AACR.
MicroRNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer
Authors: Ikeda Yushi , Tanji Etsuko , Makino Naohiko , Kawata Sumio , Furukawa Toru
Published: December 2011

Aberrant expression of microRNAs (miRNA) is associated with phenotypes of various cancers, including pancreatic cancer. However, the mechanism of the aberrant expression is largely unknown. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in gene expression related to the malignant phenotype of pancreatic cancer. Hence, we studied the role of MAPK in the aberrant expression of miRNAs in pancreatic cancer cells. The alterations in expression of 183 miRNAs induced by activation or inactivation of MAPK were assayed in cultured pancreatic cancer cells and HEK293 cells by means of the quantitative real-time PCR method. We found that four miRNAs, namely, miR-7-3, miR-34a, miR-181d, and miR-193b, were preferentially associated with MAPK activity. Among these miRNAs, miR-7-3 was upregulated by active MAPK, whereas the others were downregulated. Promoter assays indicated that the promoter activities of the host genes of miR-7-3 and miR-34a were both downregulated by alteration in MAPK activity. Exogenous overexpression of the MAPK-associated miRNAs had the effect of inhibition of the proliferation of cultured pancreatic cancer cells; miR-193b was found to exhibit the most remarkable inhibition. A search for target genes of miR-193b led to identification of CCND1, NT5E, PLAU, STARD7, STMN1, and YWHAZ as the targets. Translational suppression of these genes by miR-193b was confirmed by reporter assay. These results indicate that activation of MAPK may play a significant role in aberrant expression of miRNAs and their associated phenotypes in pancreatic cancer. Mol Cancer Res; 10(2); 259–69. ©2011 AACR.
‘…Of real use to the people’
Authors: Nair Savithri Preetha
Published: December 2011

This article throws light on the self-consciously modern attempt on the part of Raja Serfoji II (r. 1798–1832) of Tanjore, South India to establish a Devanagari press in 1802–07 for the dissemination of ‘useful knowledge’. Adopting a social constructivist approach, this article concerns itself with the locality, materiality and the historical contingency of knowledge production, thus opting for a highly detailed case study of the Tanjore press. It focuses on people, objects, knowledge, technologies and labour that flowed along short- and long-distance networks connecting the local and the global in the early nineteenth century, to produce the printed book in the ‘locality’ called Tanjore. The article argues that the superior and elegant Devanagari types cast for Serfoji were not simply ‘crafted out’ of a European template, but were the result of a five-year long typographical experiment funded and directed by the Tanjore court involving several kinds of expertise that cut across geographical and cultural boundaries. Serfoji’s celebration of the social and intellectual uses of this piece of European technology so early in the nineteenth century is indeed a remarkable historical episode, and a reflection of the nature of enlightened modernity he wished to articulate through the vernacular printed book.
Need for Cognition as an Antecedent of Individual Innovation Behavior
Authors: Wu Chia-Huei , Parker Sharon K. , de Jong Jeroen P. J.
Published: December 2011

The authors propose that need for cognition, an individual’s tendency to engage in and enjoy thinking, is associated with individual innovation behavior. Moreover, drawing on an interactionist perspective, the authors suggest that need for cognition becomes more important when individuals face lower job autonomy and time pressure in their work. This is because, when these job characteristics are low, there is no contextual driving force for individual innovation, so personality has a stronger influence. In a multisource study of 179 employees working in a Dutch research and consultancy organization, the authors’ expectations were largely supported. They found that need for cognition was positively associated with peer-rated innovation behavior, as were job autonomy and time pressure, even when controlling for openness to experience and proactive personality. Furthermore, the relationship between need for cognition and innovation behavior was strongest for individuals with low job autonomy and low time pressure and indeed was nonexistent at high levels of these contextual variables. This study, therefore, suggests that context can substitute for an individual’s need for cognition when it comes to individual innovation.
Normalization 2.0: A longitudinal analysis of German online campaigns in the national elections 2002–9
Authors: Schweitzer Eva Johanna
Published: December 2011

This article examines the functional, relational and discursive dimensions of the normalization thesis in one study, for both Web 1.0 and Web 2.0 features, in a longitudinal design. It is based on a quantitative content and structural analysis of German party websites in the national elections between 2002 and 2009. The results show that the normalization thesis holds true in all its dimensions over time and in the Web 2.0 era: parties still focus on the top-down elements of information provision and delivery while interactive options are scarce. The digital divide between parliamentary and non-parliamentary parties has narrowed over time, but remains visible for all online functions in 2009. Moreover, the gap is wider in Web 2.0 than in Web 1.0. Finally, German e-campaigns increasingly reflect those patterns of traditional election coverage that have been held accountable for rising political alienation among the public, i.e. strategic news and extensive negativism.
More Than Freud
Authors: Self Lauren , Shevell Michael
Published: December 2011

The Clarke University conferences were a seminal event in intellectual history most remembered for the lectures given by Freud on psychoanalytic theory and practice. Largely forgotten are the Child Welfare sessions that highlighted the nature/nurture debate that would foreshadow and frame social policy for the 20th century.
Power and energy management system for fuel cell unmanned aerial vehicle
Authors: Karunarathne L , Economou J T , Knowles K
Published: December 2011

In this article, a hybrid electric propulsion system which consists of a fuel cell (FC) and a battery is proposed for an unmanned aerial vehicle (UAV) propulsion application. Based on the UAV propulsion power requirements during take-off, climb, endurance, and maximum velocity, the hybrid electric power plant specifications are defined to respond to any propulsion power demand. A power and energy management system is introduced to control the hybrid system power flow while optimizing the FC system performances. The power and energy management system consists of three sections called, power management system, power electronic interface, and energy management system. The power management system decides the operating power of the each power source based on the propulsion power demand and the battery state of charge. The power electronic interface is an implementation protocol of the power management decisions through a unidirectional power converter and a bidirectional power converter which are connected to the FC, the battery, and the DC bus. Based on the FC current decided by the power management system, the energy management system controls the air supply system of the FC to maximize the FC system net power output. A referenced model is used to obtain the optimum inlet air pressure of the FC and a neuro-fuzzy-based adaptive control architecture adapts the FC air compressor power to the optimum value. The results show that the optimum compressor power configuration is superior than the constant power configuration.
Minimal modelling approach to describe turbulent rocket roll dynamics in a vertical wind tunnel
Authors: Hann C E , Snowdon M , Rao A , Winn O , Wongvanich N , Chen X
Published: December 2011

The roll dynamics of a 5-kg, 1.3 -m high sounding rocket are analysed in a vertical wind tunnel. Significant turbulence in the tunnel makes the system identification of the effective inertia, damping, and asymmetry with respect to roll challenging. A novel method is developed, which decouples the disturbance from the rocket frame's intrinsic roll dynamics and allows accurate prediction of roll rate and angle. The parameter identification method is integral-based, and treats wind disturbances as equivalent to a movement in the actuator fins. The method is robust, requires minimal computation, and gave realistic disturbance distributions reflecting the randomness of the turbulent wind flow. Two models, one with constant damping and one with fin angle-dependant damping were considered. The mean absolute roll rate of the rocket frame observed in experiments was 16.4°/s and both models predicted the roll rate with a mean absolute error less than 0.10°/s with a standard deviation less than 0.08°/s. The roll angle (measured by an encoder), was tracked by the model with a mean absolute error less than 0.20° and a standard deviation less than 0.15°. These results prove the concept of this minimal modelling approach which will be extended to varying wind speed, and pitch, and yaw dynamics in the future.
Methemoglobinemia induced by rasburicase in a pediatric patient: A case report and literature review
Authors: Ng John S , Edwards Elisa M , Egelund Tosha A
Published: December 2011

Rasburicase is a recombinant urate oxidase enzyme indicated for tumor lysis syndrome (TLS), a potential life-threatening oncologic emergency that occurs most commonly during chemotherapy for hematological malignancies. As a result of the defects in the physiological antioxidant pathway, erythrocytes of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are not protected against the oxidating stress exerted by hydrogen peroxide generated with the administration of rasburicase. Therefore, rasburicase is contraindicated in patients with known G6PD deficiency and the manufacturer recommends screening all patients with high risk for G6PD deficiency before initiating rasburicase therapy. However, it is logistically difficult in clinical settings because of the high risk of morbidity and mortality associated with TLS if treatment is delayed and the long turnaround time of the G6PD deficiency screening. Therefore, administering rasburicase to patients developing TLS before confirming a patient’s G6PD status is practically inevitable. Methemoglobinemia, and/or hemolysis, may result from the oxidative stress. Descriptions of the clinical course should it happen are limited in the literature. There are eight reported cases of rasburicase-related methemoglobinemia, with or without hemolytic anemia, in the literature of which five are pediatric patients. Six reports (including three pediatric patients) had detailed descriptions of the event and management. The recent reports of methemoglobinemia observed in patients with probable G6PD activity further complicated the picture. We are reporting a 16-year-old patient diagnosed with Burkitt’s lymphoma who developed methemoglobinemia after receiving one dose of rasburicase. He was managed by transfusion and oxygen support. The patient recovered well and the observed methemoglobinemia was reversible.
Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
Authors: Langdon DW , Amato MP , Boringa J , Brochet B , Foley F , Fredrikson S , Hämäläinen P , Hartung H-P , Krupp L , Penner IK , Reder AT , Benedict RHB
Published: December 2011

Background: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures.

Objective: To recommend a brief cognitive assessment for multiple sclerosis (MS) that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use.

Methods: An expert committee of twelve members representing the main cultural groups that have so far contributed considerable data about MS cognitive dysfunction was convened. Following exhaustive literature review, peer-reviewed articles were selected to cover a broad spectrum of cultures and scales that targeted cognitive domains vulnerable to MS. Each was rated by two committee members and candidates scales were rated on psychometric qualities (reliability, validity, and sensitivity), international application, ease of administration, feasibility in the specified context, and acceptability to patients.

Results: The committee recommended the Symbol Digit Modalities Test, if only 5 minutes was available, with the addition of the California Verbal Learning Test – Second Edition and the Brief Visuospatial Memory Test – Revised learning trials if a further 10 minutes could be allocated for testing.

Conclusions: A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.
Improving substance abuse data systems to measure ‘waiting time to treatment’: Lessons learned from a quality improvement initiative
Authors: Hoffman Kim A , Quanbeck Andrew , Ford James H , Wrede Fritz , Wright Dagan , Lambert-Wacey Dawn , Chvojka Phil , Hanchett Andrew , McCarty Dennis
Published: December 2011

Robust data measurement systems assess health care performance and monitor population-level treatment trends. A key challenge in the assessment of substance abuse treatment is the development of systems to accurately monitor service delivery indicators. Wait time to treatment, as defined by the days between first request for service and first treatment, is an important measure of organizational process and delivery of care. The Network for the Improvement of Addiction Treatment emphasizes wait time as a primary outcome in their study of 201 addiction treatment agencies in the USA. This article describes the changes made in five state data systems to monitor wait times and outlines lessons learned that could be applied to other health data tracking systems.
Debunking Sarah Palin: Mainstream news coverage of ‘death panels’
Authors: Lawrence Regina G , Schafer Matthew L
Published: December 2011

On 7 August 2009, Sarah Palin posted two words to her Facebook page that would come to define a summer of discord around health care reform. This study examines how traditional media reported on the ‘death panels’ claim that was immediately debunked by several fact-checking organizations. Our content analysis of over 700 newspaper and television stories shows that, to a significant degree, journalists stepped outside the bounds of procedural objectivity to label the ‘death panels’ claim as false, often without attribution. Many stories, however, simultaneously covered the claim in typical ‘he said/she said’ fashion, thus perhaps extending some legitimacy to the claim. Our study illustrates the challenges to fact-based public deliberation in the contemporary media environment, and suggests that competing practices of objectivity undercut the ability of mainstream media to help the public separate truth from fiction.
A default Bayesian approach for regression on extremes
Authors: Cabras Stefano , Castellanos María Eugenia , Gamerman Dani
Published: December 2011

A default Bayesian approach to predict extreme events in the presence of explanatory variables is presented. In the prediction model, covariates are introduced, using a non-homogenous Poisson-Generalized Pareto Distribution (GPD) point process, which allows for variation in the tail behaviour. The prior distribution proposed is based on a Jeffreys’ rule for regression parameters, extending the results previously obtained for an independent and identically distributed random sample drawn from the GPD. Special attention is given to mean return levels as an important summarizer. Inference is performed approximately via Markov chain Monte Carlo methods and the posterior distribution turns out to be relatively easy to be computed. The model is applied to two real datasets from meteorological applications.
A method to identify important dynamical states in boolean models of regulatory networks: application to regulation of stomata closure by ABA in A. thaliana
Authors: Bugs Cristhian A , Librelotto Giovani R , Mombach José CM
Published: December 2011

Background

We introduce a method to analyze the states of regulatory Boolean models that identifies important network states and their biological influence on the global network dynamics. It consists in (1) finding the states of the network that are most frequently visited and (2) the identification of variable and frozen nodes of the network. The method, along with a simulation that includes random features, is applied to the study of stomata closure by abscisic acid (ABA) in A. thaliana proposed by Albert and coworkers.

Results

We find that for the case of study, that the dynamics of wild and mutant networks have just two states that are highly visited in their space of states and about a third of all nodes of the wild network are variable while the rest remain frozen in True or False states. This high number of frozen elements explains the low cardinality of the space of states of the wild network. Similar results are observed in the mutant networks. The application of the method allowed us to explain how wild and mutants behave dynamically in the SS and determined an essential feature of the activation of the closure node (representing stomata closure), i.e. its synchronization with the AnionEm node (representing anion efflux at the plasma membrane). The dynamics of this synchronization explains the efficiency reached by the wild and each of the mutant networks.

Conclusions

For the biological problem analyzed, our method allows determining how wild and mutant networks differ ‘phenotypically’. It shows that the different efficiencies of stomata closure reached among the simulated wild and mutant networks follow from a dynamical behavior of two nodes that are always synchronized. Additionally, we predict that the involvement of the anion efflux at the plasma membrane is crucial for the plant response to ABA.

Availability

The algorithm used in the simulations is available upon request.
A singular value decomposition approach for improved taxonomic classification of biological sequences
Authors: Santos Anderson R , Santos Marcos A , Baumbach Jan , McCulloch John A , Oliveira Guilherme C , Silva Artur , Miyoshi Anderson , Azevedo Vasco
Published: December 2011

Background

Singular value decomposition (SVD) is a powerful technique for information retrieval; it helps uncover relationships between elements that are notprima facierelated. SVD was initially developed to reduce the time needed for information retrieval and analysis of very large data sets in the complex internet environment. Since information retrieval from large-scale genome and proteome data sets has a similar level of complexity, SVD-based methods could also facilitate data analysis in this research area.

Results

We found that SVD applied to amino acid sequences demonstrates relationships and provides a basis for producing clusters and cladograms, demonstrating evolutionary relatedness of species that correlates well with Linnaean taxonomy. The choice of a reasonable number of singular values is crucial for SVD-based studies. We found that fewer singular values are needed to produce biologically significant clusters when SVD is employed. Subsequently, we developed a method to determine the lowest number of singular values and fewest clusters needed to guarantee biological significance; this system was developed and validated by comparison with Linnaean taxonomic classification.

Conclusions

By using SVD, we can reduce uncertainty concerning the appropriate rank value necessary to perform accurate information retrieval analyses. In tests, clusters that we developed with SVD perfectly matched what was expected based on Linnaean taxonomy.
Amino acids biosynthesis and nitrogen assimilation pathways: a great genomic deletion during eukaryotes evolution
Authors: Guedes RLM , Prosdocimi F , Fernandes GR , Moura LK , Ribeiro HAL , Ortega JM
Published: December 2011

Background

Besides being building blocks for proteins, amino acids are also key metabolic intermediates in living cells. Surprisingly a variety of organisms are incapable of synthesizing some of them, thus named Essential Amino Acids (EAAs). How certain ancestral organisms successfully competed for survival after losing key genes involved in amino acids anabolism remains an open question. Comparative genomics searches on current protein databases including sequences from both complete and incomplete genomes among diverse taxonomic groups help us to understand amino acids auxotrophy distribution.

Results

Here, we applied a methodology based on clustering of homologous genes to seed sequences from autotrophic organisms Saccharomyces cerevisiae (yeast) and Arabidopsis thaliana (plant). Thus we depict evidences of presence/absence of EAA biosynthetic and nitrogen assimilation enzymes at phyla level. Results show broad loss of the phenotype of EAAs biosynthesis in several groups of eukaryotes, followed by multiple secondary gene losses. A subsequent inability for nitrogen assimilation is observed in derived metazoans.

Conclusions

A Great Deletion model is proposed here as a broad phenomenon generating the phenotype of amino acids essentiality followed, in metazoans, by organic nitrogen dependency. This phenomenon is probably associated to a relaxed selective pressure conferred by heterotrophy and, taking advantage of available homologous clustering tools, a complete and updated picture of it is provided.
Preimplantation development regulatory pathway construction through a text-mining approach
Authors: Donnard Elisa , Barbosa-Silva Adriano , Guedes Rafael LM , Fernandes Gabriel R , Velloso Henrique , Kohn Matthew J , Andrade-Navarro Miguel A , Ortega J Miguel
Published: December 2011

Background

The integration of sequencing and gene interaction data and subsequent generation of pathways and networks contained in databases such as KEGG Pathway is essential for the comprehension of complex biological processes. We noticed the absence of a chart or pathway describing the well-studied preimplantation development stages; furthermore, not all genes involved in the process have entries in KEGG Orthology, important information for knowledge application with relation to other organisms.

Results

In this work we sought to develop the regulatory pathway for the preimplantation development stage using text-mining tools such as Medline Ranker and PESCADOR to reveal biointeractions among the genes involved in this process. The genes present in the resulting pathway were also used as seeds for software developed by our group called SeedServer to create clusters of homologous genes. These homologues allowed the determination of the last common ancestor for each gene and revealed that the preimplantation development pathway consists of a conserved ancient core of genes with the addition of modern elements.

Conclusions

The generation of regulatory pathways through text-mining tools allows the integration of data generated by several studies for a more complete visualization of complex biological processes. Using the genes in this pathway as “seeds” for the generation of clusters of homologues, the pathway can be visualized for other organisms. The clustering of homologous genes together with determination of the ancestry leads to a better understanding of the evolution of such process.
Effect of the explicit flexibility of the InhA enzyme from Mycobacterium tuberculosis in molecular docking simulations
Authors: Cohen Elisangela ML , Machado Karina S , Cohen Marcelo , Norberto de Souza Osmar
Published: December 2011

Background

Protein/receptor explicit flexibility has recently become an important feature of molecular docking simulations. Taking the flexibility into account brings the docking simulation closer to the receptors’ real behaviour in its natural environment. Several approaches have been developed to address this problem. Among them, modelling the full flexibility as an ensemble of snapshots derived from a molecular dynamics simulation (MD) of the receptor has proved very promising. Despite its potential, however, only a few studies have employed this method to probe its effect in molecular docking simulations. We hereby use ensembles of snapshots obtained from three different MD simulations of the InhA enzyme from M. tuberculosis (Mtb), the wild-type (InhA_wt), InhA_I16T, and InhA_I21V mutants to model their explicit flexibility, and to systematically explore their effect in docking simulations with three different InhA inhibitors, namely, ethionamide (ETH), triclosan (TCL), and pentacyano(isoniazid)ferrate(II) (PIF).

Results

The use of fully-flexible receptor (FFR) models of InhA_wt, InhA_I16T, and InhA_I21V mutants in docking simulation with the inhibitors ETH, TCL, and PIF revealed significant differences in the way they interact as compared to the rigid, InhA crystal structure (PDB ID: 1ENY). In the latter, only up to five receptor residues interact with the three different ligands. Conversely, in the FFR models this number grows up to an astonishing 80 different residues. The comparison between the rigid crystal structure and the FFR models showed that the inclusion of explicit flexibility, despite the limitations of the FFR models employed in this study, accounts in a substantial manner to the induced fit expected when a protein/receptor and ligand approach each other to interact in the most favourable manner.

Conclusions

Protein/receptor explicit flexibility, or FFR models, represented as an ensemble of MD simulation snapshots, can lead to a more realistic representation of the induced fit effect expected in the encounter and proper docking of receptors to ligands. The FFR models of InhA explicitly characterizes the overall movements of the amino acid residues in helices, strands, loops, and turns, allowing the ligand to properly accommodate itself in the receptor’s binding site. Utilization of the intrinsic flexibility of Mtb’s InhA enzyme and its mutants in virtual screening via molecular docking simulation may provide a novel platform to guide the rational or dynamical-structure-based drug design of novel inhibitors for Mtb’s InhA. We have produced a short video sequence of each ligand (ETH, TCL and PIF) docked to the FFR models of InhA_wt. These videos are available at http://www.inf.pucrs.br/~osmarns/LABIO/Videos_Cohen_et_al_19_07_2011.htm.
Association between Helicobacter pylori cagA-related genes and clinical outcomes in Colombia and Japan
Authors: Watada Masahide , Shiota Seiji , Matsunari Osamu , Suzuki Rumiko , Murakami Kazunari , Fujioka Toshio , Yamaoka Yoshio
Published: December 2011

Background

Specific genotypes of several virulence factors of Helicobacter pylori (eg, cagA-positive, vacA s1, oipA "on" and babA-positive) have been reported to be predictors of severe clinical outcomes. Importantly, the presence of these genotypes correlates with each other. We hypothesized that novel virulence genes correlate with the presence of cagA. Therefore, we aimed to find novel candidate virulence genes that correlate with cagA and examined the association of these genes with clinical outcomes in Colombian and Japanese populations.

Methods

cagA-associated genes were selected based on previous H. pylori genome microarray data. A total of 343 strains (174 from Colombia and 169 from Japan) were examined for the status of cagA, vacA, and candidate genes by polymerase chain reaction and dot blot.

Results

Microarray data showed that 9 genes were significantly correlated with the presence of cagA. Among the 9 genes, the functions of 4 were known, and we selected these 4 genes as candidate genes (hp0967, jhp0045, jhp0046, and jhp0951). The prevalences of cagA, vacA s1/m1 genotype, and hp0967 were significantly higher in Japan than Colombia, whereas those of jhp0045 and jhp0046 were more prevalent in Colombia than Japan. The prevalences of jhp0045 and jhp0046 in cagA-positive cases of gastric cancer were significantly higher than those from gastritis in Colombia (P = 0.015 and 0.047, respectively). In contrast, the prevalence of 4 candidate genes was independent of clinical outcomes in Japan.

Conclusions

jhp0045 and jhp0046 might be novel markers for predicting gastric cancer in cagA-positive cases in Colombia, but not in Japan.
Myogenic progenitors contribute to open but not closed fracture repair
Authors: Liu Renjing , Birke Oliver , Morse Alyson , Peacock Lauren , Mikulec Kathy , Little David G , Schindeler Aaron
Published: December 2011

Background

Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.

Methods

We employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a human alkaline phosphatase (hAP) reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.

Results

In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP+ cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP+ cells detected in the open fracture callus. At early stages of repair, many hAP+ cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP+ cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP+ staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.

Conclusions

These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery.

Please see related article: http://www.biomedcentral.com/1741-7015/9/136
Proximity of public elementary schools to major roads in Canadian urban areas
Authors: Amram Ofer , Abernethy Rebecca , Brauer Michael , Davies Hugh , Allen Ryan W
Published: December 2011

Background

Epidemiologic studies have linked exposure to traffic-generated air and noise pollution with a wide range of adverse health effects in children. Children spend a large portion of time at school, and both air pollution and noise are elevated in close proximity to roads, so school location may be an important determinant of exposure. No studies have yet examined the proximity of schools to major roads in Canadian cities.

Methods

Data on public elementary schools in Canada's 10 most populous cities were obtained from online databases. School addresses were geocoded and proximity to the nearest major road, defined using a standardized national road classification scheme, was calculated for each school. Based on measurements of nitrogen oxide concentrations, ultrafine particle counts, and noise levels in three Canadian cities we conservatively defined distances < 75 m from major roads as the zone of primary interest. Census data at the city and neighborhood levels were used to evaluate relationships between school proximity to major roads, urban density, and indicators of socioeconomic status.

Results

Addresses were obtained for 1,556 public elementary schools, 95% of which were successfully geocoded. Across all 10 cities, 16.3% of schools were located within 75 m of a major road, with wide variability between cities. Schools in neighborhoods with higher median income were less likely to be near major roads (OR per $20,000 increase: 0.81; 95% CI: 0.65, 1.00), while schools in densely populated neighborhoods were more frequently close to major roads (OR per 1,000 dwellings/km2: 1.07; 95% CI: 1.00, 1.16). Over 22% of schools in the lowest neighborhood income quintile were close to major roads, compared to 13% of schools in the highest income quintile.

Conclusions

A substantial fraction of students at public elementary schools in Canada, particularly students attending schools in low income neighborhoods, may be exposed to elevated levels of air pollution and noise while at school. As a result, the locations of schools may negatively impact the healthy development and academic performance of a large number of Canadian children.