bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the lumbosacral joint centre location from palpable anatomical landmarks
Authors: Murphy A J , Bull A M J , McGregor A H
Published: July 2011

The kinematics of the lumbar spine have previously been described by considering the bearing of the pelvis and lower back. However earlier studies have not described an intersegmental angle measured about a single point; which is necessary for investigation into movement, posture and balance, and lower back pain and injury. This study used computed tomography (CT) scans of 16 pelves to determine the location of palpable bony landmarks, and the junction of the fifth lumbar and first sacral vertebrae within a pelvis axis system. Data were used to derive equations which express the three-dimensional location of the lumbosacral joint centre as an offset from palpable surface landmarks. The magnitude of X, Y, Z offsets was controlled using individual pelvic geometry, and robustness and repeatability of the method was assessed. Regression equations provided the location of the lumbosacral junction to within 8.2 mm (±3.4 mm) of its true coordinate. Leave-one-out analyses calculated equation coefficients using 15 of the original pelves, with the 16th acting as a control; average errors increased by 6.7 per cent (±0.1 per cent). To the authors’ knowledge the current method is the most accurate non-invasive means of locating the lumbosacral junction and may be useful for constructing biomechanical models.
Psychodynamic Psychotherapy
Authors: Roseborough David J. , McLeod Jeffrey T. , Bradshaw William H.
Published: July 2011

This effectiveness study examined the course of treatment longitudinally and outcomes associated with psychodynamic psychotherapy for a sample of 1,050 people undertaking this treatment in a community setting, over the course of 4 years, at 3-month intervals, using the Outcome Questionnaire (OQ)-45.2. The authors used multilevel modeling to look at the nature of change over time and at potentially meaningful moderating variables. Results show a robust general improvement, though a more moderate one than described in recent meta-analyses including primarily prospective studies. The treatment was followed by broad improvements, over time, with a general trend and few notable interaction effects. The treatment involved little deterioration, particularly in the first year. Subgroup analysis suggested that (a) clients with more initial symptom severity showed greater improvement and a unique course of recovery with (b) clients who stayed over a year constituting a potentially unique subgroup.
Challenging the Biopsychosocial Model in a Chronic Constipation Clinic
Authors: Wainwright Megan , Russell Andrew J. , Yiannakou Yan
Published: July 2011

In this article we discuss the results of an ethnographic study of professionals’ and patients’ experiences within a specialist constipation clinic in England. Chronic constipation tends to be poorly understood and inadequately treated. Eleven patients were followed through their illness trajectory during a 5-month fieldwork period, involving 21 home interviews, clinic-based interviews, participant observation, and a focus group. Professionals were likewise observed and interviewed. The clinic could be broadly described as biopsychosocial in its approach. However, professionals expressed uncertainty about how best to provide biopsychosocial care and suggested that some patients were not “open” to psychosocial therapies or to discussing psychosocial aspects of their disease. Patients’ concerns were with being taken seriously, receiving treatment, and narrating intersections of life events, emotional well-being, and the bowels. We situate these findings within the discourse of “functional” disorders and discuss why implementing a biopsychosocial approach is problematic in this case.
Health Literacy as Controversy
Authors: Mackert Michael , Love Brad , Donovan-Kicken Erin , Uhle Katharine A.
Published: July 2011

Adults in the United States increasingly use the Internet for health information, and online discussions can provide insights into public perceptions of health issues. The purpose of this project was to investigate public perceptions of issues related to health literacy, within the context of a conversation about recommendations to the U.S. Food and Drug Administration, driven by concerns about acetaminophen-related liver injuries due in part to health literacy issues. The discussion took place July 2-8, 2009, on a technology/science blog and included 625 comments. Participants debated the risks and benefits of acetaminophen, and most believed responsibility for taking medication safely falls on consumers. Some were implicitly aware of issues related to health literacy and its relationship to patient outcomes; most felt improved education is all that is needed, whereas others acknowledged that health information is confusing—particularly for the elderly and sick. Recommendations for future research into public perceptions of health literacy are discussed.
Incidence and Cost of Serious Fall-Related Injuries in Nursing Homes
Authors: Quigley Patricia A. , Campbell Robert R. , Bulat Tatjana , Olney Ronald L. , Buerhaus Peter , Needleman Jack
Published: July 2011

Background: Fall-related injuries (FRIs) result in morbidity and mortality for patients, as well as unnecessary expense to health care institutions. Objectives: (a) Estimate the incidence of falls and FRIs with a nursing home as the source of admission in Veterans Administration (VA) and non-VA facilities. (b) Estimate the cost of hospitalizations for each level of FRI severity. Research Design: Retrospective analysis of falls and FRI resulting in a hospitalization whose source of admission was a VA nursing home. Data: Falls and FRIs were obtained from Minimum Data Set (MDS) reports (January 2007-June 2009). Costs were obtained from the VA Decision Support System reports and Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) reports (2000-2006). Measures: Incidence of falls, fracture incidence, number of hospitalizations for FRIs, and costs associated with hospitalization for by level of FRI severity. Results: Fall incidence was 10.6% in VA and 13.1% in CMS facilities. Fracture incidence was 0.9% in VHA and 1.65% in CMS facilities. Over a 3-year period, there were 2,400 admissions to VHA hospitals for FRI, with 55.4% hip fractures and10.1% intracranial injuries, with an average cost of US$23,723 per admission. Over a 9-year period, there were 141,308 admissions from nursing homes to non-VA hospitals for FRIs, with 38.8% hip fractures, 35.7% other fractures, and 11.1% intracranial injuries, with an average cost of US$31,507 per admission. Conclusions: Prevention program emphasis should shift away from a focus on preventing falls as a measure of quality care to decreasing FRIs. These findings support implementation of injury prevention programs for the elderly that reduces risk for injury as the primary outcome.
Multi-resonance capturing in a two-degree-of-freedom system under two different harmonic excitations
Authors: Pham Thanh Tung , Lamarque Claude-Henri , Savadkoohi Alireza Ture
Published: July 2011

In this paper we consider two coupled oscillators which exhibit energy transfer from master ‘linear’ degrees of freedom submitted to resonant external excitation with two different harmonics to a slave ‘nonlinear’ energy sink (NES). By endowing the idea of the relative mode, splitting harmonics and iterative techniques, we prove that control of the two one-to-one resonances of the system is possible simultaneously; moreover, the iterative technique gives us a better outlook over effects of the NES parameters on the overall behavior of the system. Then, analytical procedure for multi-resonance capture are explained and commented on. Finally, the obtained analytical results are compared with numerical evidence.
Free vibrations control of a cantilever beam using combined time delay feedback
Authors: Alhazza Khaled A , Majeed Majed A
Published: July 2011

A new multi-input single-output delay feedback controller is presented to reduce free vibrations of a cantilever beam. A linear model using the first mode is derived and used to analyze and characterize the damping produced by different delay-feedback controllers as a function of the controller's gains and delay. The stability regions and amount of damping produced by three different single delay feedback and the new combined delayed feedback are investigated. A three-dimensional figure for the new controller showing the stability regions as a function of the controller gains and delay is presented. The characteristic damping of the controller as predicted by the linear model is compared with that calculated using direct long-time integration of a three-mode nonlinear model. Optimal values of the controllers gains and delay are obtained, simulated, and compared. To validate the single mode approximation, numerical simulations are performed using three-mode full nonlinear model. The results obtained using multi-input delay-feedback controllers demonstrate an excellent improvement in mitigating the first-mode vibration.
Computationally efficient modeling of flexible robots using the transfer matrix method
Authors: Krauss Ryan W
Published: July 2011

An approach is presented for developing a computationally efficient model of robots with flexible links and joints. The approach uses the transfer matrix method, which allows continuous elements such as flexible links to be treated without spatial discretization. The small size of transfer matrices allows the analysis to be performed symbolically so that closed-form expressions can be found for the infinite-dimensional transfer functions between the robot inputs and sensor outputs. The approach is applied to a single-link robot where both the link and the joint are flexible. The computationally efficient model is used by an optimization routine to estimate unknown parameters of the robot model.
Developing an Internal Risk Audit Process in Home Health Care Organizations
Authors: Rowe Jimmy
Published: July 2011

To meet the New York State Office of the Medicaid Inspector General’s Compliance Standards and maintain certification, home health care organizations must now implement annual internal risk audits. This article explores what an internal risk audit is and how it can be used by providers to enhance their ability to meet effectiveness standards and achieve stated objectives. This exploration consists of understanding the definition of an internal risk audit, what is involved in risk assessment, what types of risk should be the focus of home health care, the role of the internal risk audit in supporting organizational operations, and how the board and senior management staff need to contribute to the internal risk audit. In order to implement an annual internal risk audit, it is also imperative to understand how the organizational culture can impact internal risk audit controls.
Beyond outbidding? Ethnic party strategies in Serbia
Authors: Zuber Christina Isabel
Published: July 2011

The outbidding model of ethnic party competition predicts that ethnic parties adopt radical strategies to maximize support among voters of an ethnic group. In contrast, this article argues that ethnic parties have a wider range of strategies at their disposal. Integrating recent findings, ethnic party strategies are defined by the criteria of appeal and policy position as ‘static bidding‘, ‘ethnic underbidding‘, ‘ethnic outbidding‘, ‘lateral bidding‘, ‘lateral underbidding’ and ‘lateral outbidding‘. Empirically, a comparison of strategies adopted by ethnic parties competing for votes of the Hungarian and Bosniak minorities in Serbia shows variance of strategies within and across groups despite an environment conducive to outbidding and while holding institutional context factors constant. Factors causing this variance are explored through content analysis of 18 semi-structured interviews with ethnic party elites. An explanation that links strategies to parties' goals and the incentives of the structure of intra- and inter-ethnic competition is suggested for further research.
The Reluctance to Burden Others as a Value in End-of-life Decision Making: A Source of Inaccuracy in Substituted Judgment
Authors: Winter Laraine , Parks Susan M.
Published: July 2011

Most patients are decisionally incapacitated at the end of life, leaving final treatment decisions to proxies, whose substituted judgment is often inaccurate. We investigated the reluctance to burden others (RBO), a commonly cited patient value, as a possible source of proxy inaccuracy. In a sample of 202 elders and their proxies, elders responded to three burden-related questions and the Life-prolonging Treatment Preferences Questionnaire. Proxies used substituted judgment to respond to the same questions. Although RBO predicted treatment preferences for both elders and proxies, elders rated RBO significantly more important than did proxies. In addition, larger elder–proxy differences in RBO were associated with more inaccurate substituted judgment.
Surrogate fuels for premixed combustion in compression ignition engines
Authors: Kalghatgi G T , Hildingsson L , Harrison A J , Johansson B
Published: July 2011

Simple surrogate fuels are needed to model practical fuels, which are complex mixtures of hydrocarbons. The surrogate fuel should match the combustion and emissions behaviour of the target fuel as much as possible. This paper presents experimental results using a wide range of fuels in both the gasoline and diesel auto-ignition range, but of different volatilities and compositions, in a single cylinder diesel engine. Premixed combustion in a compression ignition engine is defined, in this paper, to occur when the injection event is clearly separated from the combustion and the engine-out smoke is very low – below 0.05 FSN (filter smoke number). Under such circumstances, if the combustion phasing is matched for two fuels at a given operating condition and injection timing, the emissions are also comparable regardless of the differences in composition and volatility. For the experimental conditions considered, combustion phasing at a given operating condition and injection timing depends only on the octane index (OI), OI =  (1-K)RON +  KMON, where RON and MON are research and motor octane numbers and K is an empirical constant that depends on operating conditions. A mixture of iso-octane, n-heptane and toluene can be found to match the RON and MON of any practical gasoline and will be a very good surrogate for the gasoline since it will have the same OI. If the compression ratio is greater than 14, practical diesel fuels, with DCN (derived cetane number) between 40 and 60, will have comparable ignition delays ton-heptane, which is an adequate surrogate for such fuels. However, premixed combustion can be attained only at much lower loads at a given speed with diesel fuels compared to gasolines.
Mapping Literary Britain: Tourist Guides to Literary Landscapes 1951-2007
Authors: Philips Deborah
Published: July 2011

The literary pilgrimage is a form of tourism that seeks out the landscapes and environments that shaped an author and their works. It is the illustrated literary guidebook to Britain (and often Ireland) that defines which authors and places are worthy of pilgrimage, draws these locations together, and points the literary tourist towards them. ‘Literary Britain’ is an object of the tourist gaze that has been constructed not only by tourist professionals, but also by literary critics and by writers. This article analyses a range of guidebooks to the literary landscapes of Britain from Bill Brandt’s Literary Landscapes published in 1951 to the current edition of The Oxford Illustrated Literary Guide to Great Britain and Ireland. The article argues that the hierarchy of both sites and authors remains remarkably unchanged; Literary Britain is seen in these collections as a place that turns its back on modernity and change. The selection of sites and authors is framed by nostalgia for the 19th century and for a pre-industrial rural world.
One Ring, Many Circles: The Hobbiton Tour Experience and a Spatial Approach to Media Power
Authors: Peaslee Robert Moses
Published: July 2011

This paper reports on fieldwork investigating the experience of visitors to the ‘Hobbiton’ film location site, a roughly 10-acre space in New Zealand co-opted for the production of The Lord of the Rings films. Based on participant observation of several tours of the attraction, as well as in-depth interviews with both visitors and guides, the data included herein engage with the draw of such a space, articulations of the visit experience, and the degree to which attitudes toward and behaviors within the space are indicative of an embodied assent to a particular kind of media power. In visiting the space, this paper suggests, actors respond to a repeating discursive structure that, by creating boundaries and sanctifying spaces, canalizes attitudes, behavior, and movement. Reified in the process is the normative centrality of media processes, people, and places.
The Role of Cultural Distance in Mediating the Host Gaze
Authors: Moufakkir O.
Published: July 2011

The Contact Hypothesis suggests that contact between people of different cultural backgrounds may result in positive and negative outcomes. As people are more likely to develop social contact with their own national group, or those with a similar background, it was posited that Dutch hosts were more likely to develop positive social contact with German tourists than with East Asian tourists. Our in-depth interviews with Dutch tourism-related business participants suggested the opposite. Furthermore, it was found that stereotypes attributed to a culture travel with its people as tourists in different ways, depending on cultural distance. Cultural distance seems to mediate the host gaze in different ways, and new hypotheses have emerged calling for more research on tourism encounters in different geographical contexts.
Development of a triboluminescence-based sensor system for concrete structures
Authors: Olawale David O , Sullivan Garrett , Dickens Tarik , Tsalickis Steven , Okoli Okenwa I , Sobanjo John O , Wang Ben
Published: July 2011

The triboluminescence phenomenon has been proposed as a sensor system for detecting and monitoring damage in aerospace and civil infrastructure systems (CIS). While significant work is being done in developing such systems for aerospace structures, little or no work is being done in developing triboluminescence-based sensor systems for the critical and aging CIS. This article reports some findings in the work being done by the authors to develop such a sensor system for civil infrastructure applications. A ZnS:Mn-based cementitious patch that emits light when stressed or fractured was developed and its triboluminescence performance under loading characterized. The results show that a ZnS:Mn concentration level of 10% gives the best triboluminescence response without adversely affecting the compressive strength of the patch, while also minimizing the use of the expensive ZnS:Mn crystals. The triboluminescence response increased as the concentration of ZnS:Mn in the system increased. The highest triboluminescence response was obtained at a concentration level of 25% but resulted in significant reduction in the system’s compressive strength. Nonetheless, the presence of ZnS:Mn affects the hydration process by slowing down the conversion of the needle-shaped crystals of calcium sulfoaluminate hydrate (ettringites) into the monosulfate hydrate that makes concrete vulnerable to sulfate attack.
Examining the Retention of Nontraditional Latino(a) Students in a Career-Based Learning Community
Authors: Sandoval-Lucero Elena , Maes Johanna B. , Chopra Ritu V.
Published: July 2011

Learning communities are designed to increase student persistence and academic achievement and are a retention strategy to increase these outcomes for 1st-year college students. This article examines the educational outcomes for a learning community specifically designed for nontraditional Latina(o) students enrolled in a grant-funded program to become bilingual teachers. The learning community model was a grant objective. Student evaluations, retention, and graduation rates were analyzed to examine the effectiveness of the learning community.
A comparative analysis of the outcome of flexor tendon repair in the index and little fingers: does the little finger fare worse?
Authors: Orkar K. S. , Watts C. , Iwuagwu F. C.
Published: July 2011

The clinical and hand therapy notes of 180 patients who had single digit flexor tendon repairs in zones I and II from January 2000 to December 2004 were reviewed. Data from 60 index and 108 little fingers at 5 weeks, 8 weeks and 12 weeks follow-up visits were included. In zone I injuries, there was a statistically significant difference in flexion contracture (worse in the little fingers ) at all follow-up points. Although the range of motion and percentage of patients in the excellent category of the Strickland and Glogovac criteria were greater in the index finger group than the little finger for zone I and II injuries, these differences were not statistically significant. The rupture rate was also higher in the little finger group.
A review of non-linear structural control techniques
Authors: Wagg D J , Neild S A
Published: July 2011

In this articles the authors present a review of non-linear structural control techniques. This is an area of growing importance in a range of engineering applications, where non-linear behaviour is encountered. Structural control is usually divided into three main areas: (a) passive (b) semi-active, and (c) active control. This article follows this convention, and highlights in each section the relevant state of the art for non-linear systems, with additional references to related linear approaches.
Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain
Authors: Horowitz Netanel A. , Blevins Elizabeth A. , Miller Whitney M. , Perry Ashley R. , Talmage Kathryn E. , Mullins Eric S. , Flick Matthew J. , Queiroz Karla C. S. , Shi Kun , Spek C. Arnold , Conway Edward M. , Monia Brett P. , Weiler Hartmut , Degen Jay L. , Palumbo Joseph S.
Published: July 2011

Thrombomodulin (TM) is a predominantly endothelial transmembrane glycoprotein that modulates hemostatic function through a domain that controls thrombin-mediated proteolysis and an N-terminal lectin-like domain that controls inflammatory processes. To test the hypothesis that TM is a determinant of malignancy and dissect the importance of these functional domains in cancer biology, metastatic potential was evaluated in TMPro mice expressing a mutant form of TM with reduced thrombin affinity and TMLeD mice lacking the N-terminal lectin-like domain. Studies of TMPro mice revealed that TM is a powerful determinant of hematogenous metastasis. TMPro mice exhibited a strongly prometastatic phenotype relative to control mice that was found to result from increased survival of tumor cells newly localized to the lung rather than any alteration in tumor growth. The impact of the TMPro mutation on metastasis was dependent on both tumor cell-associated tissue factor and thrombin procoagulant function. In contrast, expression of a mutant form of TM lacking the lectin-like domain had no significant impact on metastasis. These studies directly demonstrate for the first time that TM-mediated regulation of tumor cell-driven procoagulant function strongly influences metastatic potential and suggest that endothelial cell-associated modulators of hemostasis may represent novel therapeutic targets in limiting tumor dissemination.
Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A
Authors: Preuss Klaus-Dieter , Pfreundschuh Michael , Fadle Natalie , Regitz Evi , Raudies Sybille , Murwaski Niels , Ahlgrimm Manfred , Bittenbring Joerg , Klotz Markus , Schäfer Karl-Herbert , Held Gerhard , Neumann Frank , Grass Sandra
Published: July 2011

Paratarg-7, a frequent autoantigenic target, and all other autoantigenic targets of human paraproteins molecularly defined to date are hyperphosphorylated in the respective patients compared with healthy controls, suggesting that hyperphosphorylation of autoantigenic paraprotein targets is a general mechanism underlying the pathogenesis of these paraproteins. We now show that hyperphosphorylation of paratarg-7 occurs because of an additional phosphorylation of Ser17, which is located within the paraprotein-binding epitope. Coimmunoprecipitation identified phosphokinase C ζ (PKCζ) as the kinase responsible for the phosphorylation of most, and phosphatase 2A (PP2A) as the phosphatase responsible for the dephosphorylation of all hyperphosphorylated autoantigenic targets of paraproteins. Single-nucleotide polymorphisms (SNPs) or mutations of PKCζ and PP2A were excluded. However, PP2A was inactivated by phosphorylation of its catalytic subunit at Y307. Stimulation of T cells from healthy carriers of wild-type paratarg-7 induced a partial and transient hyperphosphorylation between days 4 and 18, which was maintained by incubation with inhibitors of PP2A, again indicating that an inactivation of PP2A is responsible for the hyperphosphorylation of autoantigenic paraprotein targets. We conclude that the genetic defect underlying the dominantly inherited hyperphosphorylation of autoantigenic paraprotein targets is not in the PP2A itself, but in genes or proteins controlling PP2A activity by phosphorylation of its catalytic subunit.
Matrix metalloproteinase-19 inhibits growth of endothelial cells by generating angiostatin-like fragments from plasminogen
Authors: Brauer Rena , Beck Inken M , Roderfeld Martin , Roeb Elke , Sedlacek Radislav
Published: July 2011

Background

Angiogenesis is the process of forming new blood vessels from existing ones and requires degradation of the vascular basement membrane and remodeling of extracellular matrix (ECM) in order to allow endothelial cells to migrate and invade into the surrounding tissue. Matrix metalloproteinases (MMPs) are considered to play a central role in the remodeling of basement membranes and ECM. However, MMPs contribute to vascular remodeling not only by degrading ECM components. Specific MMPs enhance angiogenesis via several ways; they help pericytes to detach from vessels undergoing angiogenesis, release ECM-bound angiogenic growth factors, expose cryptic pro-angiogenic integrin binding sites in the ECM, generate promigratory ECM component fragments, and cleave endothelial cell-cell adhesions. MMPs can also negatively influence the angiogenic process through generating endogenous angiogenesis inhibitors by proteolytic cleavage. Angiostatin, a proteolytic fragment of plasminogen, is one of the most potent antagonists of angiogenesis that inhibits migration and proliferation of endothelial cells. Reports have shown that metalloelastase, pancreas elastase, plasmin reductase, and plasmin convert plasminogen to angiostatin.

Results

We report here that MMP-19 processes human plasminogen in a characteristic cleavage pattern to generate three angiostatin-like fragments with a molecular weight of 35, 38, and 42 kDa. These fragments released by MMP-19 significantly inhibited the proliferation of HMEC cells by 27% (p = 0.01) and reduced formation of capillary-like structures by 45% (p = 0.05) compared with control cells. As it is known that angiostatin blocks hepatocyte growth factor (HGF)-induced pro-angiogenic signaling in endothelial cells due to structural similarities to HGF, we have analyzed if the plasminogen fragments generated by MMP-19 interfere with this pathway. As it involves the activation of c-met, the receptor of HGF, we could show that MMP-19-dependent processing of plasminogen decreases the phosphorylation of c-met.

Conclusion

Altogether, MMP-19 exhibits an anti-angiogenic effect on endothelial cells via generation of angiostatin-like fragments.
Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae)
Authors: Machado Tatiana C , Pansonato-Alves José C , Pucci Marcela B , Nogaroto Viviane , Almeida Mara C , Oliveira Claudio , Foresti Fausto , Bertollo Luiz AC , Moreira-Filho Orlando , Artoni Roberto F , Vicari Marcelo R
Published: July 2011

Background

The Characidium (a Neotropical fish group) have a conserved diploid number (2n = 50), but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR). In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography.

Results

A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR) amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location.

Conclusions

The results from dual-color fluorescence in situ hybridization (dual-color FISH) using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.
Identification of a human immunodominant T-cell epitope of mycobacterium tuberculosis antigen PPE44
Authors: Cuccu Barbara , Freer Giulia , Genovesi Alessandro , Garzelli Carlo , Rindi Laura
Published: July 2011

Background

Recently our group has identified a novel antigen ofMycobacterium tuberculosis, protein PPE44, belonging to the "PPE protein" family. Although its role in infection is largely unknown, PPE44-specific immune responses were detected in mice infected withM. tuberculosis; moreover, immunization of mice with PPE44 subunit vaccines resulted in protective efficacy comparable to the one afforded by BCG againstM. tuberculosis(Romanoet al., Vaccine 26, 6053-6063, 2008).

Results

In the present paper, we investigated anti-PPE44 T-lymphocyte responses during human infection by evaluating the frequency of PPE44-specific interferon (IFN)-γ-secreting cells by ELISpot and flow cytometry in a small cohort of healthy subjects that had proven positive to PPD (PPD+)in vitro, in patients with active tuberculosis, in subjects vaccinated with BCG and in unvaccinated, PPD-healthy controls. We showed IFN-γ+T cell immune responses to recombinant PPE44 in at least a very high proportion of PPD+individuals tested and, to a lower extent, in subjects vaccinated with BCG. By the use of a panel of overlapping synthetic 20-mer peptides spanning the PPE44 primary amino acid sequence, we identified a strong CD4+T-cell epitope, encompassed by peptide p1L (VDFGALPPEVNSARMYGGAG), in the NH2-terminus of the PPE44 molecule at the amino acid position 1-20. Conversely, our experiments did not provide evidence of a significant IFN-γ+CD4+T cell response to PPE44 or its immunodominant peptide p1L in most (7 out of 8) patients with active TB.

Conclusions

Our data suggest an important immunological role of PPE44 and its immunodominant epitope p1L that could be useful in the design of anti-tuberculosis vaccines and in the immunological diagnosis ofM. tuberculosisinfection.
Endotoxin-free purification for the isolation of Bovine Viral Diarrhoea Virus E2 protein from insoluble inclusion body aggregates
Authors: Cavallaro Antonino S , Mahony Donna , Commins Margaret , Mahony Timothy J , Mitter Neena
Published: July 2011

Background

Protein expression in Escherichia coli may result in the recombinant protein being expressed as insoluble inclusion bodies. In addition, proteins purified from E. coli contain endotoxins which need to be removed for in vivo applications. The structural protein, E2, from Bovine Viral Diarrhoea Virus (BVDV) is a major immunogenic determinant, and is an ideal candidate as a subunit vaccine. The E2 protein contains 17 cysteine residues creating difficulties in E. coli expression. In this report we outline a procedure for successfully producing soluble and endotoxin-free BVDV E2 protein from inclusion bodies (IB).

Results

The expression of a truncated form of BVDV-E2 protein (E2-T1) in E. coli resulted in predominantly aggregated insoluble IB. Solubilisation of E2-T1 with high purity and stability from IB aggregates was achieved using a strong reducing buffer containing 100 mM Dithiothreitol. Refolding by dialysis into 50 mM Tris (pH 7.0) containing 0.2% Igepal CA630 resulted in a soluble but aggregated protein solution. The novel application of a two-phase extraction of inclusion body preparations with Triton X-114 reduced endotoxin in solubilised E2-T1 to levels suitable for in vivo use without affecting protein yields. Dynamic light scattering analyses showed 37.5% of the protein was monomeric, the remaining comprised of soluble aggregates. Mice immunised with E2-T1 developed a high titre antibody response by ELISA. Western hybridisation analysis showed E2-T1 was recognised by sera from immunised mice and also by several BVDV-E2 polyclonal and monoclonal antibodies.

Conclusion

We have developed a procedure using E. coli to produce soluble E2-T1 protein from IB, and due to their insoluble nature we utilised a novel approach using Triton X-114 to efficiently remove endotoxin. The resultant protein is immunogenic and detectable by BVDV-E2 specific antibodies indicating its usefulness for diagnostic applications and as a subunit vaccine. The optimised E. coli expression system for E2-T1 combined with methodologies for solubilisation, refolding and integrated endotoxin removal presented in this study should prove useful for other vaccine applications.
Scaling analysis for the investigation of slip mechanisms in nanofluids
Authors: Savithiri S , Pattamatta Arvind , Das Sarit K
Published: July 2011

The primary objective of this study is to investigate the effect of slip mechanisms in nanofluids through scaling analysis. The role of nanoparticle slip mechanisms in both water- and ethylene glycol-based nanofluids is analyzed by considering shape, size, concentration, and temperature of the nanoparticles. From the scaling analysis, it is found that all of the slip mechanisms are dominant in particles of cylindrical shape as compared to that of spherical and sheet particles. The magnitudes of slip mechanisms are found to be higher for particles of size between 10 and 80 nm. The Brownian force is found to dominate in smaller particles below 10 nm and also at smaller volume fraction. However, the drag force is found to dominate in smaller particles below 10 nm and at higher volume fraction. The effect of thermophoresis and Magnus forces is found to increase with the particle size and concentration. In terms of time scales, the Brownian and gravity forces act considerably over a longer duration than the other forces. For copper-water-based nanofluid, the effective contribution of slip mechanisms leads to a heat transfer augmentation which is approximately 36% over that of the base fluid. The drag and gravity forces tend to reduce the Nusselt number of the nanofluid while the other forces tend to enhance it.
Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family
Authors: Nasir Muhammad , Latif Amir , Ajmal Muhammad , Qamar Reem , Naeem Muhammad , Hameed Abdul
Published: July 2011

Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in theECM1gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family.

Methods

Genotyping of seven members of the family was performed by amplifying microsatellite markers, tightly linked to theECM1gene. To screen for mutations in theECM1gene, all of its exons and splice junctions were PCR amplified from genomic DNA and analyzed by SSCP and sequenced directly in an ABI 3130 genetic analyzer.

Results

The results revealed linkage of the LP family to theECM1locus. Sequence analysis of the coding exons and splice junctions of theECM1gene revealed a novel homozygous mutation (c.616C > T) in exon 6, predicted to replace glutamine with stop codon (p.Q206X) at amino acid position 206.

Conclusions

The finding of a novel mutation in Pakistani family extends the body of evidence that supports the importance ofECM1gene for the development of lipoid proteinosis.
Time and frequency domain analysis of heart rate variability in cattle affected by bovine spongiform encephalopathy
Authors: Konold Timm , Bone Gemma E , Simmons Marion M
Published: July 2011

Background

Heart rate variability (HRV) analysis is a method to assess the function of the autonomic nervous system. Brainstem nuclei that influence HRV are affected by vacuolar changes and accumulation of disease-associated prion protein (PrPd) in bovine spongiform encephalopathy (BSE) resulting in clinical signs suggestive of an increased parasympathetic tone. It was hypothesised that BSE in cattle causes changes in the autonomic nervous system; this was tested by comparing HRV indices derived from 1048 electrocardiograms, which were recorded from 51 naturally or experimentally infected cattle with BSE confirmed by postmortem tests, 321 clinical suspect cases or cattle inoculated with potentially infectious tissue without disease confirmation and 78 BSE-free control cattle.

Findings

Statistically significant differences were found for low or high frequency power, their normalised values and ratio when the last recording prior to cull or repeated recordings were compared but only between male and female cattle of the three groups and not between groups of the same gender, even though BSE cases of each gender appeared to be more nervous during the recording. The same findings were made for heart rate, deviation from the mean RR interval and vasovagal tonus index when repeated recordings were compared. BSE cases with severe vacuolar changes in the parasympathetic nucleus of the vagus nerve had a significantly lower low:high frequency power ratio but not a lower heart rate than BSE cases with mild vacuolation, whereas severity of vacuolar changes in the solitary tract nucleus or intensity of PrPdaccumulation in both nuclei did not appear to have any affect on either index. Abnormalities in the electrocardiogram were detected in 3% of the recordings irrespective of the BSE status; sinus arrhythmia was present in 93% of the remaining recordings.

Conclusions

HRV analysis was not useful to distinguish BSE-positive from BSE-negative cattle grouped by gender, and HRV indices appeared to be mainly influenced by gender. There is agreement with earlier studies that vacuolar changes in the brainstem may be associated with an increased parasympathetic tone in BSE and that abnormalities in an electrocardiogram can be detected in cattle without evidence of heart disease.
Expression of aromatase and estrogen receptor alpha in chondrosarcoma, but no beneficial effect of inhibiting estrogen signaling both in vitro and in vivo
Authors: Meijer Danielle , Gelderblom Hans , Karperien Marcel , Cleton-Jansen Anne-Marie , Hogendoorn Pancras CW , Bovée Judith VMG
Published: July 2011

Background

Chondrosarcomas are malignant cartilage-forming tumors which are highly resistant to conventional chemotherapy and radiotherapy. Estrogen signaling is known to play an important role in proliferation and differentiation of chondrocytes and in growth plate regulation at puberty. Our experiments focus on unraveling the role of estrogen signaling in the regulation of neoplastic cartilage growth and on interference with estrogen signaling in chondrosarcomasin vitroandin vivo.

Methods

We investigated the protein expression of estrogen receptor alpha (ESR1), androgen receptor (AR), and aromatase in tumor specimens of various chondrosarcoma subtypes, and (primary) chondrosarcoma cultures. Dose-response curves were generated of conventional central chondrosarcoma cell lines cultured in the presence of 17β-estradiol, dihydrotestosterone, 4-androstene-3,17 dione, 4-hydroxytamoxifen, fulvestrant and aromatase inhibitors. In a pilot series, the effect of anastrozole (n = 4) or exemestane (n = 2) treatment in 6 chondrosarcoma patients with progressive disease was explored.

Results

We showed protein expression of ESR1 and aromatase in a large majority of all subtypes. Only a minority of the tumors showed few AR positive cells. The dose-response assays showed no effect of any of the compounds on proliferation of conventional chondrosarcomain vitro. The median progression-free survival of the patients treated with aromatase inhibitors did not significantly deviate from untreated patients.

Conclusions

The presence of ESR1 and aromatase in chondrosarcoma tumors and primary cultures supports a possible role of estrogen signaling in chondrosarcoma proliferation. However, ourin vitroand pilotin vivostudies have shown no effect of estrogen-signaling inhibition on tumor growth.
Mild hypoglycemia is independently associated with increased mortality in the critically ill
Authors: Krinsley James S , Schultz Marcus J , Spronk Peter E , Harmsen Robin E , van Braam Houckgeest Floris , van der Sluijs Johannes P , Mélot Christian , Preiser Jean Charles
Published: July 2011

Introduction

Severe hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear.

Methods

Prospectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint.

Results

We analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively.

Conclusions

Mild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality
Targeted enrichment beyond the consensus coding DNA sequence exome reveals exons with higher variant densities
Authors: Bainbridge Matthew N , Wang Min , Wu Yuanqing , Newsham Irene , Muzny Donna M , Jefferies John L , Albert Thomas J , Burgess Daniel L , Gibbs Richard A
Published: July 2011

Background

Enrichment of loci by DNA hybridization-capture, followed by high-throughput sequencing, is an important tool in modern genetics. Currently, the most common targets for enrichment are the protein coding exons represented by the consensus coding DNA sequence (CCDS). The CCDS, however, excludes many actual or computationally predicted coding exons present in other databases, such as RefSeq and Vega, and non-coding functional elements such as untranslated and regulatory regions. The number of variants per base pair (variant density) and our ability to interrogate regions outside of the CCDS regions is consequently less well understood.

Results

We examine capture sequence data from outside of the CCDS regions and find that extremes of GC content that are present in different subregions of the genome can reduce the local capture sequence coverage to less than 50% relative to the CCDS. This effect is due to biases inherent in both the Illumina and SOLiD sequencing platforms that are exacerbated by the capture process. Interestingly, for two subregion types, microRNA and predicted exons, the capture process yields higher than expected coverage when compared to whole genome sequencing. Lastly, we examine the variation present in non-CCDS regions and find that predicted exons, as well as exonic regions specific to RefSeq and Vega, show much higher variant densities than the CCDS.

Conclusions

We show that regions outside of the CCDS perform less efficiently in capture sequence experiments. Further, we show that the variant density in computationally predicted exons is more than 2.5-times higher than that observed in the CCDS.