bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of learning style profile of team on quality of materials developed in collaborative learning processes
Authors: Erdem Mukaddes
Published: June 2009

The study described looks at the effects of learning style profile of teams on the quality of materials developed in a collaborative learning process. The study was carried out on collaborative teams of four or five university students, formed through learner preferences. Learning styles of the teams were determined using Kolb's Learning Styles Inventory. The learning style profiles of each team were found to vary, and each team had at least two students with different learning styles. At the end of the process, each team produced a printed material-developing manual. Evaluation was carried out by experts via analysis of the materials from the viewpoint of content adequacy, scientific accuracy, organization and originality, the specifications of which are also provided in the study. Statistical analyses indicated some significant differences between the teams regarding the product quality. Implications for practice in terms of team formation and possible effects on performance are given.
The genius of Rome: putting things together
Authors: Bal Mieke
Published: June 2009

The title of the 2001 exhibition ‘The Genius of Rome’, held in London and Rome, is ambiguous. The curatorial meaning is that the simultaneous presence of painters, patrons and other power brokers during two and a half decades made ‘the birth of the baroque’ possible. Through a thematic distribution, the exhibition attempts to convey the temporal and spatial convergence implied by the title. One can also take the title to refer to Rome not simply as a location, as a site where things happened to happen, but as a social, institutional and political unit with causal powers. Rome, then, not only houses people of genius; it itself has genius - that of the power brokers of church and state. A third connotation equally active in this exhibition is the individualizing, narrativizing one that leads up to Caravaggio. Through an analysis of the relationship between the title of the exhibition, the idea or concept of ‘baroque’ and the thematic arrangement of the paintings, the disciplinary distinction between art history, cultural history and visual culture studies is clarified. This article argues that the interdisciplinary study of visual culture is best served when visual culture allows itself to bleed over into cultural history, and the latter allows itself to become self-reflexive to the point of becoming what I have dubbed ‘preposterous’: an interdiscursive understanding of ‘baroque’ can de-center, and then, on different terms, re-center, those art works that help us, ourselves, to be ‘baroque’.
Of optimal views and other anxieties of attending to the beautiful and sublime
Authors: Miller William Ian
Published: June 2009

A meditation on how intrusions of self-consciousness alter, upset, or interrupt aesthetic experiences. The focus is on the impulse to identify optimum moments in sunsets, fall foliage, etc., and possible explanations for this urge to identify the optimum. Then follow, by various associations of ideas, discussions of the anxieties of the expert who fears he is no longer moved by great works, to the general anxieties of properly attending to great art in museums, primarily the anxiety of when you can declare yourself ‘released’ from further homage. The large theme is how full immersion into the aesthetic experience is threatened to be undone by some aspects of the aesthetic experience itself, and then if not by that, by other anxieties about playing our roles of appreciators of beauty properly.
This is not an opinion
Authors: Cohen Sande , Zelevansky Paul
Published: June 2009

This essay/assay interrogates the mixture of image/writing that is figured forth - objectified, mediatized, lodged in the brain - as the artifact called an opinion. Opinion is the medium that provides sense for ‘good’ and ‘common’ affirmations and negations. By means of opinions, connections are made that join subject and world - the opinion of the critic that ‘knows’ or can ‘sense’ the value of things, thereby making opinions normal, safe, and easily exchangeable. We contest that entire blockage - ‘ good and common sense’- by juxtaposing philosophy and art to opinion, arguing for a mode of criticism that is able to connect isolated instances of opinion with larger social frames. We argue that cultural criticism is often self-serving, and offer notions of philosophy and art that contest the solidity of opinion - philosophy and art conceived as excessive to opinion’s usual reductions.
Caught by images: on the role of visual imprints in Holocaust testimonies
Authors: van Alphen Ernst
Published: June 2009

The Holocaust has disrupted the conventional notions of seeing, of the visual domain in Western culture. Since the Enlightenment the observation of the visual world has had a privileged epistemological status: it is a precondition and guarantee for knowledge and understanding. Being an eye-witness of something implies almost automatic apprehension and comprehension of the observed situation or event. This link between seeing and comprehension, however, has been radically disrupted in the experiences of Holocaust victims. It will be argued here that it is because of this disruption that ‘to see’ and the description of visual imprints have such a central role in the testimonies of Holocaust survivors. But these eye-witnesses’ testimonies concern events that cannot be processed in the same manner as those recounted in the eye-witness accounts in police reports. In Holocaust testimonies the visual functions more like the unmodified return of what happened, instead of as a mode of access to or penetration into what happened. Readings of the work of Holocaust survivors Tadeusz Borowski and Charlotte Delbo will lead to a probing of vision that does not see, as an image of a memory that cannot relate.
The effects of fibrates on lipid metabolism and inflammation in type 2 diabetes
Authors: Chapman M John
Published: June 2009

Type 2 diabetes is associated with a cluster of cardiovascular risk factors that together promote macrovascular and microvascular disease. An atherogenic dyslipidaemia, characterised by an increase in serum triglyceride-rich lipoproteins, a decrease in plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased prevalence of small, dense low-density lipoprotein (LDL) particles (although LDL-C levels are normal or only modestly elevated), as well as chronic inflammation, play key roles in the pathogenesis of diabetes-related complications. As peroxisome proliferator-activated receptor a agonists, the fibrates exert an integrated action to favour normalisation of lipid metabolism, cholesterol homeostasis and reverse cholesterol transport, inflammation and haemostasis, suggesting potential efficacy in preventing vascular complications of diabetes. By synergistic therapeutic targeting of abnormalities in lipid metabolism and inflammation, fenofi-brate can promote anti-atherogenic effects at the arterial wall, as demonstrated in the Diabetes Atherosclerosis Intervention Study (DAIS), and reduction of total cardiovascular events, as shown in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.
Model calibration in the continual reassessment method
Authors: Lee Shing M , Ying Kuen Cheung
Published: June 2009

Background The continual reassessment method (CRM) is an adaptive model-based design used to estimate the maximum tolerated dose in dose finding clinical trials. A way to evaluate the sensitivity of a given CRM model including the functional form of the dose-toxicity curve, the prior distribution on the model parameter, and the initial guesses of toxicity probability at each dose is using indifference intervals. While the indifference interval technique provides a succinct summary of model sensitivity, there are infinitely many possible ways to specify the initial guesses of toxicity probability. In practice, these are generally specified by trial and error through extensive simulations.

Methods By using indifference intervals, the initial guesses used in the CRM can be selected by specifying a range of acceptable toxicity probabilities in addition to the target probability of toxicity. An algorithm is proposed for obtaining the indifference interval that maximizes the average percentage of correct selection across a set of scenarios of true probabilities of toxicity and providing a systematic approach for selecting initial guesses in a much less time-consuming manner than the trial-and-error method. The methods are compared in the context of two real CRM trials. Results For both trials, the initial guesses selected by the proposed algorithm had similar operating characteristics as measured by percentage of correct selection, average absolute difference between the true probability of the dose selected and the target probability of toxicity, percentage treated at each dose and overall percentage of toxicity compared to the initial guesses used during the conduct of the trials which were obtained by trial and error through a time-consuming calibration process. The average percentage of correct selection for the scenarios considered were 61.5 and 62.0% in the lymphoma trial, and 62.9 and 64.0% in the stroke trial for the trial-and-error method versus the proposed approach. Limitations We only present detailed results for the empiric dose toxicity curve, although the proposed methods are applicable for other dose—toxicity models such as the logistic.

Conclusions The proposed method provides a fast and systematic approach for selecting initial guesses of probabilities of toxicity used in the CRM that are competitive to those obtained by trial and error through a time-consuming process, thus, simplifying the model calibration process for the CRM.
Evaluating the benefit of event adjudication of cardiovascular outcomes in large simple RCTs
Authors: Pogue Janice , Walter Stephen D , Yusuf Salim
Published: June 2009

Background Event adjudication in randomized controlled trials is thought to be a necessary step to remove noise and potential bias from the results [1,2]. However, this hypothesis has not been widely evaluated. We conducted a meta-analysis of a series of cardiovascular outcomes trials and estimated the effect of adjudication on treatment estimates and on the number of outcomes included the trials.

Methods Data were retrieved from all cardiovascular outcomes trials conducted at the Population Health Research Institute (PHRI) between 1993 and 2006. These data included 10 trials with over 9000 events from 95 038 individuals. Differences in the log odds ratios between adjudicated and reported outcomes were analyzed and summarized using a ratio of odds ratios. Both masked and unmasked trials were included in this analysis.

Results There were no effects of event adjudication on the estimates of treatment effect for the primary outcomes, myocardial infarction (MI), stroke, or cardiovascular/vascular death. For the trial primary outcomes, the effect of adjudication vs. reported events was OR ratio = 1.00 [95% confidence interval (CI): 0.97—1.02]. There were also no significant differences in the number of outcomes included in the trials. Results were the same for masked and unmasked trials.

Limitations The number of unmasked trials were small, and this analysis was restricted to cardiovascular endpoints reported from trials managed by a single coordinating center, with similar sets of procedures. Individual patient data were not used for the analysis.

Conclusions This systematic meta-analysis failed to detect any effect of event adjudication on study conclusions and the numbers of events included in the final analyses were minimally changed. Given the considerable effort required to perform adjudication, there is a need to demonstrate that this process does indeed increase the sensitivity of trials. There is a need to conduct more systematic analyses of the effect of event adjudication in other trials to determine if this process is truly worthwhile.
Results of the Year 2000 Abdomen Task Survey of the American Registry of Diagnostic Medical Sonographers
Authors: Feld Rick I. , Reading Carl , Davies Dawn , Andrew Anne
Published: June 2009

The authors' purpose was to evaluate the current practice of registered diagnostic medical sonographers, with specialty in abdomen, of the American Registry of Diagnostic Medical Sonographers (ARDMS).A randomized sample of 2350 registered diagnostic medical sonographers with specialty in abdomen were chosen from the ARDMS database to complete a task survey on the Internet.The survey consisted of a 235-item ques tionnaire with regard to demographics, education, and frequency of specific sonograms performed in daily practice.Compared with the 1994 survey, registrants have received more formal education and less on-the-job training. Traditional tasks remain the predominant responsibilities of registered diagnostic medical sonographers with specialty in abdomen, including liver, biliary system, gallbladder, kidney, and pancreas, but a small minority of sonographers also perform liver transplant, kidney transplant, trauma, and musculoskeletal sonograms, and use newer technologies, such as power Doppler and tissue harmonic sonography, as well as transrectal sonography.The authors conclude that the ARDMS abdomen examination reflects current practice, but future revisions should include a small percentage of items in these newer areas.
Pyomyositis
Authors: Holden Linda B.
Published: June 2009

The American College of Radiology considers ultrasound to be the most appropriate examination for the diagnosis of deep venous thrombosis (DVT).1,2 However, for patients with persistent calf pain, differential diagnoses must be considered. The most common are cellulitis, Baker's cyst, and superficial thrombophlebitis. Less common differential diagnoses include hematoma, muscle or bone tumor (mass lesion), muscle rupture, compartment syndrome, ischemic arterial disease, and a condition known as pyomyositis. Pyomyositis is the formation of a single abscess within the skeletal muscle that affects the large muscle groups such as the thighs and shoulders.3 If left untreated, pyomyositis is a potentially life-threatening infection. Most cases are reported in tropical climates; however, recent cases associated with human immunodeficiency virus (HIV) have been reported in more temperate climates.3-8
Gallstone Ileus
Authors: Wharton Peg , Kabat Mary Ann , Simkulet Jessica , Romeyn Antoinette
Published: June 2009

Gallstone ileus is a mechanical obstruction of the intestinal tract caused by gallstones. Usually, the responsible stone is solitary and large, 2 to 5 cm in diameter, and enters the bowel through a cholecystoduodenal fistula. Gallstone ileus is not a common occurrence. This condition can be difficult to diagnose, causing a delay in surgical treatment. Because of this delay, the mortality rate is high, 15% to 20%. When the diagnosis of gallstone ileus is made preoperatively, it is usually done radiographically. In this case, the diagnosis was made based on the ultrasound findings.
Ultrasound of the Carpal Tunnel and Median Nerve
Authors: Wilkinson Maureen , Grimmer Karen , Massy-Westropp Nicola
Published: June 2009

The authors describe a protocol for measuring the carpal tunnel and median nerve in a reproducible manner using ultrasound, as well as the variability of ultrasound measurements of the median nerve in the carpal tunnel on repeated testing. Measurements of the median nerve in the wrist and carpal tunnel and measurements of the carpal tunnel were taken on 23 wrists using high-resolution ultrasound following a specified protocol. These measurements were repeated a short time later to enable the initial measurements to be tested for reproducibility and stability. The same person obtained all measurements for the purposes of this study; thus, the results represent findings in an intraobserver variability study. Good correlation between the test and retest measurements was demonstrated, with r2 values between 0.72 and 0.98. Paired t test demonstrated no significant difference between the test and retest measurements. The study shows that repeated ultrasound measurements of the cross-sectional areas of the carpal tunnel, median nerve at the proximal edge of the carpal tunnel, distal to the carpal tunnel and at the level of the proximal wrist crease can all be satisfactorily reproduced when a strict ultrasound protocol is adhered to.
Sonography of Uterine Leiomyosarcoma
Authors: Smith Sharon K. , Riethman Joseph L. , Lomax Carter O.
Published: June 2009

A case of leiomyosarcoma (LMS) is presented. LMS is a potentially rapidly growing malignant uterine tumor that is thought to be indistinguishable from leiomyoma by ultrasound criteria. The authors present a case that shows extremely rapid rate of growth of an LMS and demonstrates its sonographic appearance.
Testicular Microlithiasis With Invading Neoplasm
Authors: Stuber Jennifer , Guidarelli Sharon , Budge John C.
Published: June 2009

A case of testicular microlithiasis with invading neoplasm is presented. Testicular microlithiasis is an uncommon condition in which calcifications are present in the testicle. Evidence shows that there is an association between testicular microlithiasis, germ cell neoplasms, and testicular tumors. Technical advances in high-resolution, real-time ultrasound and color flow Doppler allow sonographers to evaluate many scrotal diseases accurately.
Fetal Lingual Dermoid Cyst
Authors: Jones E. Diana
Published: June 2009

A case study of a fetal lingual dermoid cyst is presented. The cystic mass was seen protruding from the base of the tongue through the open fetal mouth. Teratomas, although usually benign, can result in a poor neonatal outcome if the respiratory tract is obstructed. The perinatal diagnosis of an oral mass will alert the obstetrician to the possible need to deliver at a tertiary-care center where a team of specialists can be available to aid in the establishment of the newborn's airway.
Trinity:
Authors: Bahner David Paul
Published: June 2009

Hypotension is a common endpoint to many disease processes and can be evaluated with ultrasonography at the bedside. This ultrasound protocol can be used to examine the key organs involved in maintaining a blood pressure and the areas within the torso where fluid can collect. Systematically investigating these areas can provide the health care team with key information concerning the hypotensive state. This protocol examines the torso from the geometric perspective of a cross (Trinity).
Prenatal Diagnosis of Bilateral Tibial Hypoplasia in Twins
Authors: Weiner Neal H.
Published: June 2009

The 1 in 1 million incidence of tibial hypoplasia makes it an uncommon condition, and diagnosis by ultrasound a rarity. Associated anomalies, such as clubfeet, can also be sonographically identified. Genetic counseling may be warranted by these findings. Treatment can vary depending on severity. Prenatal sonography and postnatal radiography can determine severity of this skeletal defect and assist in planning appropriate treatment for the best longterm results.
Congenital Abdominal Aortic Aneurysm and Hypertrophic Pyloric Stenosis in an Infant
Authors: Callahan Jodi , Drolshagen Leo , Cole Alisa , Duncan Nancy
Published: June 2009

Infantile abdominal aortic aneurysms are rare, usually detected incidentally, and associated with connective tissue disease or due to iatrogenic causes. The diagnosis should be considered when a large cystic mass (especially pulsatile) is found in a neonate and confirmed using color and duplex sonography. Undiagnosed aneurysms have a high mortality rate. Surgical treatment is warranted when the patient is stabilized and may result in a normal outcome, although future graft replacement may be necessary.
Dry sliding wear behaviour of plasma nitrocarburised AISI 304 stainless steel using response surface methodology
Authors: Kumari M. Mamatha , Natarajan S. , Alphonsa J. , Mukherjee S.
Published: June 2009

This paper deals with preparation of plasma nitrocarburised layers on austenitic stainless steel sample and subsequent assessment of its wear resistance. Plasma nitrocarburising was carried out on AISI 304 stainless steel samples at temperatures 400–450 and 560°C for 6 h using pulsed glow discharge plasma in a gas mixture of 78%H2, 20%N2 and 2%C2H2. Characterisation of the coating was carried out through hardness survey, XRD and optical microscopy. The sliding wear behaviour was studied using conventional pin-on-disc equipment. Experiments were designed using response surface methodology. The wear rate was studied as a function of applied load and sliding velocity to obtain empirical model. Worn surfaces were analysed using SEM. The wear mechanism of plasma nitrocarburised surface is found to be mild and dominated by oxidation and microabrasion, while in the uncoated, it is characterised by strong adhesion and severe plastic deformation.
Synaptotagmin-like protein 1 interacts with the GTPase-activating protein Rap1GAP2 and regulates dense granule secretion in platelets
Authors: Neumüller Olga , Hoffmeister Meike , Babica Jan , Prelle Carola , Gegenbauer Kristina , Smolenski Albert P.
Published: June 2009

The small guanine-nucleotide–binding protein Rap1 plays a key role in platelet aggregation and hemostasis, and we recently identified Rap1GAP2 as the only GTPase-activating protein of Rap1 in platelets. In search of Rap1GAP2-associated proteins, we performed yeast-2-hybrid screening and found synaptotagmin-like protein 1 (Slp1) as a new binding partner. We confirmed the interaction of Rap1GAP2 and Slp1 in transfected COS-1 and HeLa cells and at endogenous level in human platelets. Mapping studies showed that Rap1GAP2 binds through amino acids T524-K525-X-T527 within its C-terminus to the C2A domain of Slp1. Slp1 contains a Rab27-binding domain, and we demonstrate that Rap1GAP2, Slp1, and Rab27 form a trimeric complex in transfected cells and in platelets. Purified Slp1 dose-dependently decreased dense granule secretion in streptolysin-O–permeabilized platelets stimulated with calcium or guanosine 5′-O-[gamma-thio] triphosphate. The isolated C2A domain of Slp1 had a stimulatory effect on granule secretion and reversed the inhibitory effect of full-length Slp1. Purified Rap1GAP2 augmented dense granule secretion of permeabilized platelets, whereas deletion of the Slp1-binding TKXT motif abolished the effect of Rap1GAP2. We conclude that Slp1 inhibits dense granule secretion in platelets and that Rap1GAP2 modulates secretion by binding to Slp1.
Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the Pediatric Blood and Marrow Transplant Consortium Study ONC0313
Authors: Pulsipher Michael A. , Boucher Kenneth M. , Wall Donna , Frangoul Haydar , Duval Michel , Goyal Rakesh K. , Shaw Peter J. , Haight Ann E. , Grimley Michael , Grupp Stephan A. , Kletzel Morris , Kadota Richard
Published: June 2009

The role of reduced-intensity conditioning (RIC) regimens in pediatric cancer treatment is unclear. To define the efficacy of a busulfan/fludarabine/antithymocyte globulin RIC regimen in pediatric patients ineligible for myeloablative transplantation, we completed a trial at 23 institutions in the Pediatric Blood and Marrow Transplant Consortium. Forty-seven patients with hematologic malignancies were enrolled. Sustained engraftment occurred in 98%, 89%, and 90%, and full donor chimerism was achieved in 88%, 76%, and 78% of evaluable related bone marrow/peripheral blood stem cells (BM/PBSCs), unrelated BM/PBSCs, and unrelated cord blood recipients. With a median follow-up of 24 months (range, 11-53 months), 2-year event-free survival, overall survival (OS), transplantation-related mortality, and relapse were 40%, 45%, 11%, and 43%, respectively. Univariate analysis revealed an inferior outcome when patients had undergone previous total body irradiation (TBI)–containing myeloablative transplantation (2-year OS, 23% vs 63% vs 52%, previous TBI transplantation vs no TBI transplantation vs no transplantation, P = .02) and when patients not previously treated with TBI had detectable disease at the time of the RIC procedure (2-year OS, 0% vs 63%, detectable vs nondetectable disease, P = .01). Favorable outcomes can be achieved with RIC approaches in pediatric patients in remission who are ineligible for myeloablative transplantation. This study was registered at www.clinicaltrials.gov as #NCT00795132.
Power of QTL detection by either fixed or random models in half-sib designs
Authors: Kolbehdari Davood , Jansen Gerald B. , Schaeffer Lawrence R. , Allen Brian O.
Published: June 2009

The aim of this study was to compare the variance component approach for QTL linkage mapping in half-sib designs to the simple regression method. Empirical power was determined by Monte Carlo simulation in granddaughter designs. The factors studied (base values in parentheses) included the number of sires (5) and sons per sire (80), ratio of QTL variance to total genetic variance (λ = 0.1), marker spacing (10 cM), and QTL allele frequency (0.5). A single bi-allelic QTL and six equally spaced markers with six alleles each were simulated. Empirical power using the regression method was 0.80, 0.92 and 0.98 for 5, 10, and 20 sires, respectively, versus 0.88, 0.98 and 0.99 using the variance component method. Power was 0.74, 0.80, 0.93, and 0.95 using regression versus 0.77, 0.88, 0.94, and 0.97 using the variance component method for QTL variance ratios (λ) of 0.05, 0.1, 0.2, and 0.3, respectively. Power was 0.79, 0.85, 0.80 and 0.87 using regression versus 0.80, 0.86, 0.88, and 0.85 using the variance component method for QTL allele frequencies of 0.1, 0.3, 0.5, and 0.8, respectively. The log10 of type I error profiles were quite flat at close marker spacing (1 cM), confirming the inability to fine-map QTL by linkage analysis in half-sib designs. The variance component method showed slightly more potential than the regression method in QTL mapping.
The combined use of embryos and semen for cryogenic conservation of mammalian livestock genetic resources
Authors: Boettcher Paul J. , Stella Alessandra , Pizzi Flavia , Gandini Gustavo
Published: June 2009

The objective of this empirical simulation study was to evaluate the use of a combination of semen and embryos in the creation of gene banks for reconstruction of an extinct breed. Such an approach was compared for banks with varying proportions of embryos on the basis of the amount of the material to be stored, time for reconstruction, maintenance of genetic variability, and probability of failure during reconstruction. Four types of populations were simulated, based on reproductive rate: single offspring, twinning, enhanced reproduction, and litter bearing. Reconstruction was simulated for banks consisting of different combinations of semen and reduced numbers of embryos (expressed as a percentage of the material needed for a bank containing exclusively embryos and ranging from 10 to 90%). The use of a combination of semen and embryos increased the number of insemination cycles needed for reconstruction and the level of genetic relatedness in the reconstructed population. The risk for extinction was unacceptably high when a very low proportion of embryos (< 20%) was used. However, combining semen with embryos could decrease costs, allowing for the conservation of more breeds, and specific strategies for semen use could decrease the level of relationships in the reconstructed breed.
Ag85B DNA vaccine suppresses airway inflammation in a murine model of asthma
Authors: Wu Jian , Xu Jun , Cai Chuang , Gao Xinglin , Li Li , Zhong Nanshan
Published: June 2009

Background

In allergic asthma, Th2 lymphocytes are believed to play important roles in orchestrating airway eosinophilia and inflammation. Resetting the Th1/Th2 imbalance may have a therapeutic role in asthma. The mycobacterium tuberculosis 30-kilodalton major secretory protein (antigen 85B, Ag85B) can protect animals from M. tuberculosis infection by inducing a Th1-dominant response.

Methods

In this study, the Ag85B gene was cloned into pMG plasmids to yield the pMG-Ag85B plasmid. The expression of Ag85B gene in murine bronchial epithelia cells was detected by Western blotting and immunohistochemical staining after intranasal immunization with reconstructed pMG-Ag85B plasmids. The protective effect of pMG-Ag85B plasmids immunization in airway inflammation was evaluated by histological examination and bronchoalveolar lavage (BAL). IL-4 and IFN-γ levels in the BAL and supernatant from splenocyte culture were determined using ELISA kits.

Results

The Ag85B gene was successfully expressed in murine bronchial epithelia cells by intranasal immunization with reconstructed pMG-Ag85B plasmids. Using a murine model of asthma induced by ovalbumin (OVA), pMG-Ag85B immunization significantly inhibited cellular infiltration across the airway epithelium with a 37% decrease in the total number of cells (9.6 ± 2.6 × 105/ml vs. 15.2 ± 3.0 × 105/ml, p < 0.05) and a 74% decrease in the number of eosinophils (1.4 ± 0.2 × 105/ml vs. 5.4 ± 1.1 × 105/ml, p < 0.01) compared with the OVA-sensitized control group. There was no difference in the number of neutrophils in BAL fluid between the pMG-Ag85B group, the OVA-sensitized control group and the empty pMG group. IL-4 production was significantly decreased in the BAL fluid (32.0 ± 7.6 pg/ml vs. 130.8 ± 32.6 pg/ml, p < 0.01) and in the splenocyte supernatant (5.1 ± 1.6 pg/ml vs. 10.1 ± 2.3 pg/ml, p < 0.05) in the pMG-Ag85B group compared with the OVA-sensitized control group, while IFN-γ production was increased in the BAL fluid (137.9 ± 25.6 pg/ml vs. 68.4 ± 15.3 pg/ml, p < 0.05) and in the splenocyte supernatant (20.1 ± 5.4 pg/ml vs. 11.3 ± 3.2 pg/ml, p < 0.05).

Conclusion

In a murine model of asthma induced by OVA, intranasal immunization with pMG-Ag85B significantly reduced allergic airway inflammation with less eosinophil infiltration. This protective effect was associated with decreased IL-4 and increased IFN-γ production in the BAL fluid and in the supernatant of cultured splenocytes.
RetroTector online, a rational tool for analysis of retroviral elements in small and medium size vertebrate genomic sequences
Authors: Sperber Göran , Lövgren Anders , Eriksson Nils-Einar , Benachenhou Farid , Blomberg Jonas
Published: June 2009

Background

The rapid accumulation of genomic information in databases necessitates rapid and specific algorithms for extracting biologically meaningful information. More or less complete retroviral sequences, also called proviral or endogenous retroviral sequences; ERVs, constitutes at least 5% of vertebrate genomes. After infecting the host, these retroviruses have integrated in germ line cells, and have then been carried in genomes for at least several 100 million years. A better understanding of structure and function of these sequences can have profound biological and medical consequences.

Methods

RetroTector© (ReTe) is a platform-independent Java program for identification and characterization of proviral sequences in vertebrate genomes. The full ReTe requires a local installation with a MySQL database. Although not overly complicated, the installation may take some time. A "light" version of ReTe, (RetroTector online; ROL) which does not require specific installation procedures is provided, via the World Wide Web.

Results

ROL http://www.fysiologi.neuro.uu.se/jbgs/ was implemented under the Batchelor web interface (A Lövgren et al). It allows both GenBank accession number, file and FASTA cut-and-paste admission of sequences (5 to 10 000 kilobases). Up to ten submissions can be done simultaneously, allowing batch analysis of <= 100 Megabases. Jobs are shown in an IP-number specific list. Results are text files, and can be viewed with the program, RetroTectorViewer.jar (at the same site), which has the full graphical capabilities of the basic ReTe program. A detailed analysis of any retroviral sequences found in the submitted sequence is graphically presented, exportable in standard formats. With the current server, a complete analysis of a 1 Megabase sequence is complete in 10 minutes. It is possible to mask nonretroviral repetitive sequences in the submitted sequence, using host genome specific "brooms", which increase specificity.

Discussion

Proviral sequences can be hard to recognize, especially if the integration occurred many million years ago. Precise delineation of LTR, gag, pro, pol and env can be difficult, requiring manual work. ROL is a way of simplifying these tasks.

Conclusion

ROL provides 1. annotation and presentation of known retroviral sequences, 2. detection of proviral chains in unknown genomic sequences, with up to 100 Mbase per submission.
Identification of candidate structured RNAs in the marine organism 'Candidatus Pelagibacter ubique'
Authors: Meyer Michelle M , Ames Tyler D , Smith Daniel P , Weinberg Zasha , Schwalbach Michael S , Giovannoni Stephen J , Breaker Ronald R
Published: June 2009

Background

Metagenomic sequence data are proving to be a vast resource for the discovery of biological components. Yet analysis of this data to identify functional RNAs lags behind efforts to characterize protein diversity. The genome of 'Candidatus Pelagibacter ubique' HTCC 1062 is the closest match for approximately 20% of marine metagenomic sequence reads. It is also small, contains little non-coding DNA, and has strikingly low GC content.

Results

To aid the discovery of RNA motifs within the marine metagenome we exploited the genomic properties of 'Cand. P. ubique' by targeting our search to long intergenic regions (IGRs) with relatively high GC content. Analysis of known RNAs (rRNA, tRNA, riboswitches etc.) shows that structured RNAs are significantly enriched in such IGRs. To identify additional candidate structured RNAs, we examined other IGRs with similar characteristics from 'Cand. P. ubique' using comparative genomics approaches in conjunction with marine metagenomic data. Employing this strategy, we discovered four candidate structured RNAs including a new riboswitch class as well as three additional likely cis-regulatory elements that precede genes encoding ribosomal proteins S2 and S12, and the cytoplasmic protein component of the signal recognition particle. We also describe four additional potential RNA motifs with few or no examples occurring outside the metagenomic data.

Conclusion

This work begins the process of identifying functional RNA motifs present in the metagenomic data and illustrates how existing completed genomes may be used to aid in this task.
Validation of housekeeping genes for quantitative real-time PCR in in-vivo and in-vitro models of cerebral ischaemia
Authors: Gubern Carme , Hurtado Olivia , Rodríguez Rocío , Morales Jesús R , Romera Víctor G , Moro María A , Lizasoain Ignacio , Serena Joaquín , Mallolas Judith
Published: June 2009

Background

Studies of gene expression in experimental cerebral ischaemia models can contribute to understanding the pathophysiology of brain ischaemia and to identifying prognostic markers and potential therapeutic targets. The normalization of relative qRT-PCR data using a suitable reference gene is a crucial prerequisite for obtaining reliable conclusions. No validated housekeeping genes have been reported for the relative quantification of the mRNA expression profile activated in in-vitro ischaemic conditions, whereas for the in-vivo model different reference genes have been used.

The present study aims to determine the expression stability of ten housekeeping genes (Gapdh, β2m, Hprt, Ppia, Rpl13a, Oaz1, 18S rRNA, Gusb, Ywhaz and Sdha) to establish their suitability as control genes for in-vitro and in-vivo cerebral ischaemia models.

Results

The expression stability of the candidate reference genes was evaluated using the 2-ΔC'T method and ANOVA followed by Dunnett's test. For the in-vitro model using primary cultures of rat astrocytes, all genes analysed except for Rpl13a and Sdha were found to have significantly different levels of mRNA expression. These different levels were also found in the case of the in-vivo model of pMCAO in rats except for Hprt, Sdha and Ywhaz mRNA, where the expression did not vary. Sdha and Ywhaz were identified by geNorm and NormFinder as the two most stable genes.

Conclusion

We have validated endogenous control genes for qRT-PCR analysis of gene expression in in-vitro and in-vivo cerebral ischaemia models. For normalization purposes, Rpl13a and Sdha are found to be the most suitable genes for the in-vitro model and Sdha and Ywhaz for the in-vivo model. Genes previously used as housekeeping genes for the in-vivo model in the literature were not validated as good control genes in the present study, showing the need for careful evaluation for each new experimental setup.
Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model
Authors: Marques Ines J , Weiss Frank Ulrich , Vlecken Danielle H , Nitsche Claudia , Bakkers Jeroen , Lagendijk Anne K , Partecke Lars Ivo , Heidecke Claus-Dieter , Lerch Markus M , Bagowski Christoph P
Published: June 2009

Background

Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For primary human tumours we establish here a simple, fast, sensitive and cost-effective in vivo model to analyse tumour invasion and metastatic behaviour.

Methods

We fluorescently labelled small explants from gastrointestinal human tumours and investigated their metastatic behaviour after transplantation into zebrafish embryos and larvae. The transparency of the zebrafish embryos allows to follow invasion, migration and micrometastasis formation in real-time. High resolution imaging was achieved through laser scanning confocal microscopy of live zebrafish.

Results

In the transparent zebrafish embryos invasion, circulation of tumour cells in blood vessels, migration and micrometastasis formation can be followed in real-time. Xenografts of primary human tumours showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumour tissue was implanted. Furthermore, primary human tumour cells, when organotopically implanted in the zebrafish liver, demonstrated invasiveness and metastatic behaviour, whereas primary control cells remained in the liver. Pancreatic tumour cells showed no metastatic behaviour when injected into cloche mutant embryos, which lack a functional vasculature.

Conclusion

Our results show that the zebrafish is a useful in vivo animal model for rapid analysis of invasion and metastatic behaviour of primary human tumour specimen.
Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions
Authors: Garcia-Iglesias Trinidad , del Toro-Arreola Alicia , Albarran-Somoza Benibelks , del Toro-Arreola Susana , Sanchez-Hernandez Pedro E , Ramirez-Dueñas Maria Guadalupe , Balderas-Peña Luz Ma. Adriana , Bravo-Cuellar Alejandro , Ortiz-Lazareno Pablo C , Daneri-Navarro Adrian
Published: June 2009

Background

Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.

Methods

NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.

Results

We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.

Conclusion

Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.
Equivalent benefit of mTORC1 blockade and combined PI3K-mTOR blockade in a mouse model of tuberous sclerosis
Authors: Pollizzi Kristen , Malinowska-Kolodziej Izabela , Stumm Michael , Lane Heidi , Kwiatkowski David
Published: June 2009

Background

Tuberous sclerosis (TSC) is a hamartoma syndrome in which renal and lung tumors cause the greatest morbidity. Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1 and suppression of AKT. Recent studies indicate that inhibition of mTORC1 with RAD001 (everolimus) leads to rebound activation of AKT, which could protect tumors from drug-induced cell death. Here we examine the potential benefit of inhibition of both mTOR and AKT signaling in a mouse model of TSC, using a dual pan class I PI3K/mTOR catalytic small molecule inhibitor NVP-BEZ235.

Results

Using ENU to enhance Tsc2
+- kidney tumor development, both RAD001 (10 mg/kg PO 5 d/week) and NVP-BEZ235 (45 mg/kg PO QD) had equivalent effects in suppressing tumor development during a 4 week treatment period, with a 99% reduction in tumor cell mass. Marked reduction in activation of mTORC1, induction of cell cycle arrest, and absence of apoptotic cell death was seen in mice treated with either drug. However, when either was discontinued, there was prompt recovery of tumor growth, with extensive proliferation.

Conclusion

Both mTORC1 blockade alone and combined PI3K-mTOR blockade lead to suppression of tumor development but not tumor elimination in this TSC model.
A pneumatic power harvesting ankle-foot orthosis to prevent foot-drop
Authors: Chin Robin , Hsiao-Wecksler Elizabeth T , Loth Eric , Kogler Géza , Manwaring Scott D , Tyson Serena N , Shorter K Alex , Gilmer Joel N
Published: June 2009

Background

A self-contained, self-controlled, pneumatic power harvesting ankle-foot orthosis (PhAFO) to manage foot-drop was developed and tested. Foot-drop is due to a disruption of the motor control pathway and may occur in numerous pathologies such as stroke, spinal cord injury, multiple sclerosis, and cerebral palsy. The objectives for the prototype PhAFO are to provide toe clearance during swing, permit free ankle motion during stance, and harvest the needed power with an underfoot bellow pump pressurized during the stance phase of walking.

Methods

The PhAFO was constructed from a two-part (tibia and foot) carbon composite structure with an articulating ankle joint. Ankle motion control was accomplished through a cam-follower locking mechanism actuated via a pneumatic circuit connected to the bellow pump and embedded in the foam sole. Biomechanical performance of the prototype orthosis was assessed during multiple trials of treadmill walking of an able-bodied control subject (n = 1). Motion capture and pressure measurements were used to investigate the effect of the PhAFO on lower limb joint behavior and the capacity of the bellow pump to repeatedly generate the required pneumatic pressure for toe clearance.

Results

Toe clearance during swing was successfully achieved during all trials; average clearance 44 ± 5 mm. Free ankle motion was observed during stance and plantarflexion was blocked during swing. In addition, the bellow component repeatedly generated an average of 169 kPa per step of pressure during ten minutes of walking.

Conclusion

This study demonstrated that fluid power could be harvested with a pneumatic circuit built into an AFO, and used to operate an actuated cam-lock mechanism that controls ankle-foot motion at specific periods of the gait cycle.
Differential radio-sensitivities of human chromosomes 1 and 2 in one donor in interphase- and metaphase-spreads after 60Co γ-irradiation
Authors: Pathak Rupak , Ramakumar Adarsh , Subramanian Uma , Prasanna Pataje GS
Published: June 2009

Background

Radiation-induced chromosome aberrations lead to a plethora of detrimental effects at cellular level. Chromosome aberrations provide broad spectrum of information ranging from probability of malignant transformation to assessment of absorbed dose. Studies mapping differences in radiation sensitivities between human chromosomes are seldom undertaken. Consequently, health risk assessment based on radio-sensitivities of individual chromosomes may be erroneous. Our efforts in this article, attempt to demonstrate differences in radio-sensitivities of human chromosome-1 and/or -2, both in interphase and metaphase spreads.

Methods

Upon blood collection, dosimetry and irradiation were performed. Lymphocytes were isolated after whole-blood irradiation with 60Co γ-rays in the dose range of 0–5 Gy for both interphase, and metaphase aberration studies. Induction of premature chromosome condensation in interphase cells was accomplished using a phosphatase inhibitor, calyculin-A. Metaphase spreads were harvested from short-term peripheral blood lymphocyte cultures following colcemid arrest and using an automated metaphase harvester and spreader. Aberration analysis in both interphase and metaphase spreads were done using FISH.

Results

In interphase, aberrant cell and aberration frequency involving chromosome 1 and/or 2 increased linearly with radiation dose. In metaphase, aberrations increased in a linear-quadratic manner with dose. Our studies ascertain that chromosome-2 is more radio-sensitive than chromosome-1 in both interphase and metaphase stages, albeit the DNA content of chromosome-2 is lesser than chromosome-1 by almost 10 million base pairs.

Conclusion

Differences in radio-sensitivities of chromosomes have implications in genetic damage, chromosome organization, and chromosome function. Designing research experiments based on our vital findings may bring benefit to radiation-induced risk assessment, therapeutics and development of chromosome specific biomarkers.