bluuebunny/crossref_metadata_2025 huggingface dataset:
A Key Role for Matrix Metalloproteinases and Neutral Sphingomyelinase-2 in Transplant Vasculopathy Triggered by Anti-HLA Antibody
Authors: Galvani Sylvain , Trayssac Magali , Augé Nathalie , Thiers Jean-Claude , Calise Denis , Krell Hans-Willi , Sallusto Federico , Kamar Nassim , Rostaing Lionel , Thomsen Mogens , Nègre-Salvayre Anne , Salvayre Robert
Published: November 2011

Background—

Outcomes for organ transplantation are constantly improving because of advances in organ preservation, surgical techniques, immune clinical monitoring, and immunosuppressive treatment preventing acute transplant rejection. However, chronic rejection including transplant vasculopathy still limits long-term patient survival. Transplant vasculopathy is characterized by progressive neointimal hyperplasia leading to arterial stenosis and ischemic failure of the allograft. This work sought to decipher the manner in which the humoral immune response, mimicked by W6/32 anti-HLA antibody, contributes to transplant vasculopathy.

Methods and Results—

Studies were performed in vitro on cultured human smooth muscle cells, ex vivo on human arterial segments, and in vivo in a model consisting of human arterial segments grafted into severe combined immunodeficiency/beige mice injected weekly with anti-HLA antibodies. We report that anti-HLA antibodies are mitogenic for smooth muscle cells through a signaling mechanism implicating matrix metalloproteinases (MMPs) (membrane type 1 MMP and MMP2) and neutral sphingomyelinase-2. This mitogenic signaling and subsequent DNA synthesis are blocked in smooth muscle cells silenced for MMP2 or for neutral sphingomyelinase-2 by small interfering RNAs, in smooth muscle cells transfected with a vector coding for a dominant-negative form of membrane type 1 MMP, and after treatment by pharmacological inhibitors of MMPs (Ro28-2653) or neutral sphingomyelinase-2 (GW4869). In vivo, Ro28-2653 and GW4869 reduced the intimal thickening induced by anti-HLA antibodies in human mesenteric arteries grafted into severe combined immunodeficiency/beige mice.

Conclusions—

These data highlight a crucial role for MMP2 and neutral sphingomyelinase-2 in vasculopathy triggered by a humoral immune response and open new perspectives for preventing transplant vasculopathy with the use of MMP and neutral sphingomyelinase inhibitors, in addition to conventional immunosuppression.
Absence of SOCS3 in the Cardiomyocyte Increases Mortality in a gp130-Dependent Manner Accompanied by Contractile Dysfunction and Ventricular Arrhythmias
Authors: Yajima Toshitaka , Murofushi Yoshiteru , Zhou Hanbing , Park Stanley , Housman Jonathan , Zhong Zhao-Hua , Nakamura Michinari , Machida Mitsuyo , Hwang Kyung-Kuk , Gu Yusu , Dalton Nancy D. , Yajima Tomoko , Yasukawa Hideo , Peterson Kirk L. , Knowlton Kirk U.
Published: November 2011

Background—

Suppressor of cytokine signaling-3 (SOCS3) is a key negative-feedback regulator of the gp130 receptor that provides crucial signaling for cardiac hypertrophy and survival; however, an in vivo role of SOCS3 regulation on cardiac gp130 signaling remains obscure.

Methods and Results—

We generated cardiac-specific SOCS3 knockout (SOCS3 cKO) mice. These mice showed increased activation of gp130 downstream signaling targets (STAT3, ERK1/2, AKT, and p38) from 15 weeks of age and developed cardiac dysfunction from approximately 25 weeks of age with signs of heart failure. Surprisingly, SOCS3 cKO failing hearts had minimal histological abnormalities with intact myofibril ultrastructure. In addition, Ca
2+
transients were significantly increased in SOCS3 cKO failing hearts compared with wild-type hearts. We also found that Ser23/24 residues of troponin I were hypophosphorylated in SOCS3 cKO hearts before the manifestation of cardiac dysfunction. These data suggested the presence of abnormalities in myofilament Ca
2+
sensitivity in SOCS3 cKO mice. In addition to the contractile dysfunction, we found various ventricular arrhythmias in SOCS3 cKO nonfailing hearts accompanied by a sarcoplasmic reticulum Ca
2+
overload. To determine the contribution of gp130 signaling to the cardiac phenotype that occurs with SOCS3 deficiency, we generated cardiac-specific gp130 and SOCS3 double KO mice. Double KO mice lived significantly longer and had different histological abnormalities when compared with SOCS3 cKO mice, thus demonstrating the importance of gp130 signaling in the SOCS3 cKO cardiac phenotype.

Conclusions—

Our results demonstrate an important role of SOCS3 regulation on cardiac gp130 signaling in the pathogenesis of contractile dysfunction and ventricular arrhythmias.
Mechanisms of Premature Vascular Aging in Children With Hutchinson-Gilford Progeria Syndrome
Authors: Gerhard-Herman Marie , Smoot Leslie B. , Wake Nicole , Kieran Mark W. , Kleinman Monica E. , Miller David T. , Schwartzman Armin , Giobbie-Hurder Anita , Neuberg Donna , Gordon Leslie B.
Published: November 2011

Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and sex-matched controls in the intima-media (
P
<0.02), near adventitia (
P
<0.003), and deep adventitia (
P
<0.01), as was internal carotid artery mean flow velocity (
P
<0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrate that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in Hutchinson-Gilford progeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population.
Role of Uncoupled Endothelial Nitric Oxide Synthase in Abdominal Aortic Aneurysm Formation
Authors: Gao Ling , Siu Kin L. , Chalupsky Karel , Nguyen Andrew , Chen Peng , Weintraub Neal L. , Galis Zorina , Cai Hua
Published: November 2011

It has been shown that endothelial NO synthase (eNOS) uncoupling occurs in hypertension and atherosclerosis. However, its causal role in vascular pathogenesis has not been characterized previously. Here, we challenged eNOS preuncoupled hyperphenylalaninemia (hph)-1 mice (deficient in eNOS cofactor tetrahydrobiopterin biosynthetic enzyme GTPCHI) with angiotensin II (Ang II; 0.7 mg/kg per day, 14 days). Both wild-type and hph-1 groups developed hypertension similarly up to day 6 to 7. Thereafter, ≈14% of Ang II–infused (0.7 mg/kg per day) hph-1 mice (n=72) started to die suddenly of ruptured abdominal aortic aneurysm (AAA). Among the survivors, 65% developed AAA, resulting in a total morbidity rate of 79%. In contrast, none of the Ang II–infused wild-type mice died or developed AAA. Ang II progressively deteriorated eNOS uncoupling in hph-1 mice while augmenting tetrahydrobiopterin and nitric oxide (NO
·
) deficiencies. The abundance of the tetrahydrobiopterin salvage enzyme dihydrofolate reductase in the endothelium was decreased in hph-1 mice and further diminished by Ang II infusion. Intriguingly, restoration of dihydrofolate reductase expression by oral administration of folic acid or overexpression of dihydrofolate reductase completely prevented AAA formation in Ang II–infused hph-1 mice while attenuating progressive uncoupling of eNOS. Folic acid also attenuated vascular remodeling and inflammation characterized by medial elastin breakdown and augmented matrix metalloproteinase 2 activity and activation of matrix metalloproteinase 9, as well as macrophage infiltration. In conclusion, these data innovatively suggest a causal role of eNOS uncoupling/tetrahydrobiopterin deficiency in AAA formation. Therefore, oral folic acid administration, endothelium-targeted dihydrofolate reductase gene therapy, and perhaps other countermeasures directed against eNOS uncoupling could be used as new therapeutics for AAA.
Digital Economy Action: Composition by Participatory Piracy
Authors: Cornford Stephen
Published: November 2011

The author discusses the inspiration and design of an as-yet-unrealized composition in which participants serve in the roles of composer, performer and consumer all at the same time. Provoked by the passage of a law restricting sharing and distribution of music files, he explores the potential for file sharing as a compositional process.
The Initiation of Modern “Soft Snowball” and “Hard Snowball” Climates in CCSM3. Part II: Climate Dynamic Feedbacks
Authors: Yang Jun , Peltier W. Richard , Hu Yongyun
Published: November 2011

This study investigates the climate dynamic feedbacks during a transition from the present climate to the extremely cold climate of a “Snowball Earth” using the Community Climate System Model, version 3 (CCSM3). With the land–sea distribution fixed to modern, it is found that by reducing solar luminosity and/or carbon dioxide concentration: 1) the amount of atmospheric water vapor and its attendant greenhouse effect decrease with the logarithm of sea ice cover, thereby promoting the expansion of sea ice; 2) over the sea ice, the cloud radiative feedback is positive, thus enhancing sea ice advance; over the ocean, the cloud radiative feedback is first negative and then becomes positive as sea ice enters the tropics; and 3) the strength of the atmospheric Hadley cell and the wind-driven ocean circulation increases significantly in the Southern Hemisphere, inhibiting the expansion of sea ice into the tropics. Meanwhile, the North Atlantic Deep Water cell disappears and the Antarctic Bottom Water cell strengthens and expands to occupy almost the entire Atlantic basin. In the experiment with 6% less solar radiation and 70 ppmv CO2 compared to the control experiment with 100% solar radiation and 355 ppmv CO2 near the ice edge (28°S latitude), the changes of solar radiation, CO2 forcing, water vapor greenhouse effect, longwave cloud forcing at the top of the model, and atmospheric and oceanic energy transport are −22.4, −6.2, −54.4, +6.2, and +16.3 W m−2, respectively. Therefore, the major controlling factors in producing global ice cover are ice albedo feedback (Yang et al., Part I) and water vapor feedback.
Organization of Flash-Flood-Producing Precipitation in the Northeast United States
Authors: Jessup Stephen M. , Colucci Stephen J.
Published: November 2011

Heavy precipitation and flash flooding have been extensively studied in the central United States, but less so in the Northeast. This study examines 187 warm-season flash flood events identified in Storm Data to better understand the structure of the precipitation systems that cause flash flooding in the Northeast. Based on the organization and movement of these systems on radar, the events are classified into one of four categories—back-building, linear, multiple, and other/size—and then further classified into subtypes for each category. Eight of these subtypes were not previously recognized in the literature. The back-building events were the most common, followed by the multiple, other/size, and linear types. The linear event types appear to produce flash flooding less commonly in the Northeast than in other regions. In general, the subtypes producing the highest precipitation estimates are those whose structures are most conducive to a long duration of sustained moderate to heavy rainfall. The event types were found to differ from those in the central United States in that the events were more often found to be more disorganized in the Northeast. One event type in particular, back-building with merging features, while not more disorganized than the previously recognized event types, offers promise for improved forecasting because its radar signature makes the duration of sustained heavy precipitation potentially easier to predict.
Listening to indigenous health workers
Authors: Walker David , Tennant Marc , Short Stephanie D
Published: November 2011

Objective: This research was undertaken to explore factors operating at the level of the clinic and the community which influence the development of the oral health role of Indigenous Health Workers. The research is a significant aspect of a wider study of the disconnect between the strong national policy support for the development of the oral health role of Indigenous Health Workers and the limited development of the role.

Design: Semi-structured interviews were conducted with Indigenous Health Workers to explore their perceptions of the priority of the development of an oral health role and to identify facilitators and barriers to sustainable role development.

Setting: The study was conducted in three remote Indigenous communities and two regional centres of the Cape York region in far north Australia.

Method: Interviews were conducted with 21 Indigenous Health Workers through five group interviews and eight individual interviews.

Results: The findings highlight the high priority given by Indigenous Health Workers to the development of their oral health role while also identifying significant barriers to the sustainable development of this role.

Conclusion: The identification of barriers to role development operating at the level of the clinic and the community helps to explain the disconnect between policy and practice in the development of the oral health role of these community health personnel.
The Otolaryngologist’s Cost in Treating Facial Trauma
Authors: McCusker Scott B. , Schmalbach Cecelia E.
Published: November 2011

Objectives

(1) To define practice patterns and perceptions of junior otolaryngologists treating maxillofacial/neck trauma. (2) To identify manners in which the American Academy of Otolaryngology—Head and Neck Surgery (AAO‐HNS) can meet future trauma needs.

Study Design

Cross‐sectional survey.

Setting

Academic and private otolaryngology practices.

Methods

A 26‐question survey was designed to identify demographics, practice patterns, perceptions, and areas for improvement in maxillofacial/neck trauma care. It was distributed anonymously to AAO‐HNS members completing residency from 2005 to 2009. Analysis included descriptive statistics and χ2 comparisons.

Results

Of 1343 otolaryngologists, 444 (33%) responded. A total of 85% of responding physicians treat maxillofacial/neck trauma, and 64% identify trauma as an ideal part of their practice. Sense of duty (54%), institutional requirements (33%), and enjoyment (32%) are the most common reasons for treating trauma. Major deterrents include patient noncompliance (60%) and lifestyle limitations (47%). Five respondents (3.1%) have been involved in a trauma‐related lawsuit. While insufficient reimbursement is a major deterrent to treating trauma (52%), only 36% would increase their volume if reimbursement improved. Increased educational opportunities represent the most common request to the AAO‐HNS (59%), followed by AAO‐HNS focus on improved reimbursement and tort reform (28%).

Conclusion

Most junior otolaryngologists treat maxillofacial/neck trauma on a monthly basis. A total of 64% identify trauma as a component of their ideal practice. They report being well to very well trained in all facets of trauma, with the exception of vascular and laryngotracheal injuries; but they desire additional education, such as courses and panels. Universal concerns include inadequate reimbursement, limited pool of treating physicians, and lack of practice guidelines.
How useful are catchment sediment budgets?
Authors: Parsons Anthony J.
Published: November 2011

Catchment sediment budgeting is an attempt to identify the sources, sinks and pathways of eroded material within catchments. However, the identification of these quantities is not straightforward, and the conceptual underpinnings of sediment budgets make unwarranted and untested assumptions about process stability. Many sediment budgets leave one or more quantities unmeasured and obtain estimates of them by subtraction (assuming budget closure). Consequently, errors in sediment budgets are often hidden and are not quantified. There has been an emphasis on suspended sediment, which, for management purposes, may not be useful. Sediment budgeting can act as a framework for a research agenda on catchment processes. What has been lacking from this agenda has been an adequate consideration of the time taken for sediment to travel via the various pathways to the catchment outlet. The storage term in such budgets has been used as a poor substitute for a thorough understanding of sediment velocity through catchments.
Anti-inflammatory and antioxidant effects of infliximab in a rat model of intestinal ischemia/reperfusion injury
Authors: Pergel Ahmet , Kanter Mehmet , Yucel Ahmet Fikret , Aydin Ibrahim , Erboga Mustafa , Guzel Ahmet
Published: November 2011

The aim of this study was to investigate the possible protective effects of infliximab on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group comprised 10 animals. Sham group animals underwent laparotomy without I/R injury. I/R groups after undergoing laparotomy, 1 hour of superior mesenteric artery ligation occurred, which was followed by 1 hour of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered intravenously. All animals were killed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no biochemical and histopathological changes have been reported regarding intestinal I/R injury in rats due to infliximab treatment. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased reduced superoxide dismutase and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Infliximab treatment significantly attenuated the severity of intestinal I/R injury, inhibiting I/R-induced apoptosis, and cell proliferation. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects on the experimental intestinal I/R model of rats.
Body Configuration Modulates the Usage of Local Cues to Direction in Biological-Motion Perception
Authors: Hirai Masahiro , Chang Dorita H. F. , Saunders Daniel R. , Troje Nikolaus F.
Published: November 2011

The presence of information in a visual display does not guarantee its use by the visual system. Studies of inversion effects in both face recognition and biological-motion perception have shown that the same information may be used by observers when it is presented in an upright display but not used when the display is inverted. In our study, we tested the inversion effect in scrambled biological-motion displays to investigate mechanisms that validate information contained in the local motion of a point-light walker. Using novel biological-motion stimuli that contained no configural cues to the direction in which a walker was facing, we found that manipulating the relative vertical location of the walker’s feet significantly affected observers’ performance on a direction-discrimination task. Our data demonstrate that, by themselves, local cues can almost unambiguously indicate the facing direction of the agent in biological-motion stimuli. Additionally, we document a noteworthy interaction between local and global information and offer a new explanation for the effect of local inversion in biological-motion perception.
Library and Information Science research areas: A content analysis of articles from the top 10 journals 2007–8
Authors: Aharony Noa
Published: November 2011

The current study seeks to describe and analyze journal research publications in the top 10 Library and Information Science journals from 2007–8. The paper presents a statistical descriptive analysis of authorship patterns (geographical distribution and affiliation) and keywords. Furthermore, it displays a thorough content analysis of keywords and abstracts extracted from 10 leading Information Science journals in 2007–8, using Zins’ (2007) classification scheme of Information Science. The main results suggest the tendency of authors towards collaboration in authorship. North American and European authors – from the core discipline of Librarianship and Information Science – can be considered as leaders in the top 10 LIS journals. Furthermore, there are three major cores of research in these journals: information technology, methodology and social information science. It is important that LIS researchers, professionals, teachers and students be keenly aware of the updated main spheres of research in top leading LIS journals.
Nondestructive health monitoring of cracked simply supported fiber-reinforced composite structures
Authors: Gaith Mohamed S.
Published: November 2011

A crack on a structural member introduces a local flexibility that is a function of crack depth. This flexibility changes the dynamic behavior of the system and its stability characteristics. A continuous cracked beam vibration theory is implemented for the lateral vibration of cracked Euler–Bernoulli beams with single-edge open cracks. In this study, the crack identification (health monitoring) for simply supported graphite/epoxy fiber-reinforced composite beams is considered. The effects of crack depth and location, fiber orientation, and fiber volume fraction on the flexibility and consequently on natural frequency and mode shapes for cracked fiber-reinforced composite beams are investigated.
Family Functioning of Child-Rearing Japanese Families on Family-Accompanied Work Assignments in Hong Kong
Authors: Hohashi Naohiro , Honda Junko
Published: November 2011

Although the number of employees on overseas assignments accompanied by their families has increased steadily, little is known about the effects of this experience on family functioning. Japanese families on family-accompanied assignments living in Hong Kong were compared with families living in Japan (consisting of 135 and 248 paired partners, respectively). Applying an ecological framework, family functioning was examined using the Feetham Family Functioning Survey–Japanese (FFFS-J). Japanese wives living in Hong Kong rated family functioning lower, particularly in the area of “relationship between family and family members.” Between paired marital partners living in Hong Kong, the level of satisfaction in the area of “relationship between family and society” was significantly lower for wives than for husbands. This study provides application of the family ecological framework in families in a multicultural environment and identifies potential areas for family assessment and intervention that may of interest to health care professionals who care for families living away from their home countries.
Spectral modeling of vibrating plates with general shape and general boundary conditions
Authors: Catania Giuseppe , Sorrentino Silvio
Published: November 2011

The analysis and design of lightweight plate structures require efficient computational tools, because exact analytical solutions for vibrating plates are currently known only for some standard shapes in conjunction with a few basic boundary conditions. This paper deals with vibration analysis of Kirchhoff plates of general shape with non-standard boundary conditions, adopting a Rayleigh-Ritz approach. Three different coordinate mappings are considered, using different kinds of functions: 1) trigonometric and polynomial interpolation functions for mapping the shape of the plate, 2) trigonometric and polynomial interpolation functions for mapping a constraint domain of general shape, 3) products of linearly independent eigenfunctions evaluated from a standard beam in flexural vibration for describing the transverse displacement field of the plate. Flexural free vibration analysis of different shaped plates is then performed using the same approach: skew, trapezoid and triangular plates, plates with parabolic curved edges, sectors of circular plates, circular and elliptic annular plates. Purely elastic plates are considered, but the method may also be applied to the analysis of viscoelastic plates. The results are compared with those available in the literature and using standard finite element analysis.
“We Belong to Them”
Authors: Maier Shana L.
Published: November 2011

This research explores the transformation of rape crisis centers and whether directors, staff, interns, and volunteers see changes as beneficial or detrimental to rape crisis centers and the victims they serve. Data from 63 interviews with directors, staff, interns, and volunteers from six rape crisis centers located in four East Coast states indicate that although centers may have been formed for different reasons depending on when they opened, all have become more professional, rely less on volunteers, engage in more collaboration with other agencies, and have largely abandoned their traditional activism agenda. Traditional activism through political protests and membership in consciousness raising groups has been replaced by community education and outreach. Some of these changes are viewed as positive whereas others are viewed as negative.
Will You Tolerate This? The Impact of Affective Commitment on Complaint Intention and Postrecovery Behavior
Authors: Evanschitzky Heiner , Brock Christian , Blut Markus
Published: November 2011

Successful complaint management primarily depends on customers' willingness to voice their complaints and on companies' ability to adequately deal with these complaints. This article investigates the impact of one relationship characteristic in the complaint management process: affective commitment. Based on two studies, the authors investigate whether affective commitment moderates the impact of complaint barriers on complaint intention (a) and whether it moderates the link between complaint satisfaction and purchase behavior after the complaint (b). Results show that affectively committed customers exhibit higher complaint intention irrespective of the level of complaint barriers. Furthermore, affectively committed customers display little change in their postrecovery behavior, even after a service failure followed by an unsatisfactory recovery attempt. It seems that these customers are tolerant and want to help the provider improve their business. Affective commitment seems to amplify willingness to help the company by means of voicing dissatisfaction despite considerable efforts in doing so. Moreover, affective commitment buffers the negative effects of service failures on postrecovery behavior. Findings have important implications for managers. They highlight the necessity to measure customers' affective commitment. Based on that, tailored complaint systems can be designed, which help in achieving a more effective allocation of resources for customer recovery.
Fatigue-Related Gene Networks Identified in CD14+ Cells Isolated From HIV-Infected Patients—Part II
Authors: Voss Joachim G. , Dobra Adrian , Morse Caryn , Kovacs Joseph A. , Raju Raghavan , Danner Robert L. , Munson Peter J. , Logan Carolea , Rangel Zoila , Adelsberger Joseph W. , McLaughlin Mary , Adams Larry D. , Dalakas Marinos C.
Published: November 2011

Purpose:

In limited samples of valuable biological tissues, univariate ranking methods of microarray analyses often fail to show significant differences among expression profiles. In order to allow for hypothesis generation, novel statistical modeling systems can be greatly beneficial. The authors applied new statistical approaches to solve the issue of limited experimental data to generate new hypotheses in CD14+ cells of patients with HIV-related fatigue (HRF) and healthy controls.

Methodology:

We compared gene expression profiles of CD14+ cells of nucleoside reverse transcriptase inhibitor (NRTI)-treated HIV patients with low versus high fatigue to healthy controls ( n = 5 each). With novel Bayesian modeling procedures, the authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. Sparse association and liquid association networks further elucidated the possible biological pathways in which these genes are involved.

Relevance for nursing practice:

Genetic networks developed in a comprehensive Bayesian framework from small sample sizes allow nursing researchers to design future research approaches to address such issues as HRF.

Implication for practice:

The findings from this pilot study may take us one step closer to the development of useful biomarker targets for fatigue status. Specific and reliable tests are needed to diagnosis, monitor and treat fatigue and mitochondrial dysfunction.
Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis
Authors: Simpson Steve , Taylor Bruce , Dwyer Dominic E , Taylor Janette , Blizzard Leigh , Ponsonby Anne-Louise , Pittas Fotini , Dwyer Terence , van der Mei Ingrid
Published: November 2011

Background: Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however.

Methods: Prospective cohort of 198 persons with clinically definite MS, followed 2002–5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein–Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed-effects linear regression.

Results: For the 145 persons with relapsing–remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend ( p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males.

Discussion: These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing–remitting MS clinical course.
The Many Faces of International Adoption
Authors: Tessler Richard , Tuan Mia , Lee Shiao Jiannbin
Published: November 2011

Adoption is an old story with a new twist: international adoptions are reshaping American families and cultural landscape. In the long view, the authors believe international adoption is an immigration story that must be contextualized within research not only on individual adoptees, but within the waves of immigration that have altered American history.
Up Close and Communal
Authors: Hartmann Douglas , Page Letta
Published: November 2011

Photographer Wing Young Huie’s images of the everyday establish and emphasize the connections between the personal and the communal. This article uses a set of Huie’s landmark images to explore the photographer, subject, and viewer’s shared fascination with the reflected quotidian.
An experimental study on effects of post-heating parameters on resistance spot welding of SAPH440 steel
Authors: Jahandideh AR , Hamedi M , Mansourzadeh S A , Rahi A
Published: November 2011

The fracture mode of spot welded joints, made of SAPH440 steel sheets, is investigated. It was found that the weldment failure in the peel test of the joints occurred through the weld nugget. This is called an interfacial failure and is not acceptable because it is a sign of insufficient mechanical strength. Investigation showed that this kind of fracture is attributed to the brittleness of the nugget zone, caused by its martensitic microstructure due to the high cooling rate in the welding. For eliminating this defect, resistance spot welding procedures were augmented with post-heating stage. This approach is intended to reduce the cooling rate after welding and also to temper the weld nugget, generating a more ductile microstructure in the weld zone. The results of this research can be used for planning spot welding process and provides a guideline for analysing the results of hardness and peel test.
Formation and distribution of brittle structures in friction stir welding of aluminium and copper: influence of process parameters
Authors: Galvão I , Oliveira JC , Loureiro A , Rodrigues DM
Published: November 2011

Morphological, metallographic and structural analyses of aluminium–copper dissimilar welds produced under different friction stir welding conditions were conducted in order to analyse the mechanisms of intermetallic phases formation, its relation with welding conditions and its consequences in the weld structure and morphology. Under lower heat input conditions, only a thin intermetallic layer distributed along the aluminium/copper interface was depicted inside the nugget. Increasing the heat input promoted material mixing and formation of increasing amounts of intermetallic rich structures. The intermetallic phase content and the homogeneity of the mixed area increased with increasing heat input, evolving from structures containing Al, Cu, CuAl2 and Cu9Al4 to structures predominantly composed of Cu9Al4 and Cu(Al). In order to explain these results, the mechanisms of intermetallic phases formation are discussed, taking into account the process parameters and material flow mechanisms in friction stir welding. Important relations between intermetallic formation and weld surface morphology were also found.
Microstructure and mechanical properties of ZrB2–SiC ultrahigh temperature ceramic composite joint using TiZrNiCu filler metal
Authors: Li Z R , Wang ZZ , Wu G D , Feng JC
Published: November 2011

ZrB2–SiC ceramic composite was brazed by using TiZrNiCu active filler metal. The microstructure and interfacial phenomena of the joints were analysed by means of SEM, energy dispersive X-ray spectroscopy and X-ray diffraction. The joining effect was evaluated by shear strength. The results showed that the reaction products of the ZrB2–SiC ceramic composite joint were TiC, ZrC, Ti5Si3, Zr2Si, Zr(s,s) and (Ti, Zr)2 (Ni, Cu), and the microstructure was separately ZrB2–SiC/Zr(s,s)/Ti5Si3+Zr2Si+TiC+ZrC+(Ti,Zr)2(Ni,Cu)/Zr(s,s)/ZrB2–SiC. A conceptual interface evolution model was established to explain the interface evolution mechanism. The maximum shear strength of the brazed joints was 143·5 MPa at the brazing temperature T of 920°C and the holding time t of 10 min.
Effect of coaxial welding wire structure on arc instability in argon shielding gas
Authors: Nakamura T , Hiraoka K
Published: November 2011

The instability of gas metal arc welding in pure Ar shielding gas is associated with the structure of the coaxial multilayer solid (CMS) wire. This wire has a coaxial double structure consisting of a different composition in its inner and outer parts. In this paper, four CMS wires were developed to investigate the influence of the wire structure on the welding behaviour. First, the wire melting behaviour was observed with a high speed video camera system. Then, the relation between the welding instability and the length of the column of liquid molten metal, which causes arc instability, was analysed. Next, a wire melting simulation of the CMS wire was carried out to discuss the effect of the wire structure on the melting behaviour. Finally, the welding stability was investigated at the V groove. An excellent bead shape was obtained, and stable welding was found to be possible using an appropriate wire structure.
BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells
Authors: Jämsä Anne , Belda Oscar , Edlund Michael , Lindström Erik
Published: November 2011

Background

Accumulation of amyloid β-peptide (Aβ) in the plaques is one of the major pathological features in Alzheimer's disease (AD). Sequential cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE-1) and γ-secretase results in the formation of Aβ peptides. Preventing Aβ formation is believed to attenuate AD progression and BACE-1 and γ-secretase are thus attractive targets for AD drug development.

Methods

Combining BACE-1 and γ-secretase inhibition on Aβ secretion from human neuroblastoma SH-SY5Y cells was evaluated in this study. Secreted Aβ40 and Aβ42 levels were measured from SH-SY5Y cells stably transfected with APPwt or APPswe genes. A selective BACE inhibitor and the γ-secretase inhibitor LY450139 (semagacestat) were used to inhibit respective secretase.

Results

LY450139 increased Aβ40 and Aβ42 secretion from SH-SY5Y APPwt cells at low concentrations (by 60% at 3 nM) followed by subsequent inhibition at higher concentrations (IC50 90 nM). Washout studies showed that the Aβ increase evoked by 3 nM LY450139 was not due to enhanced cleavage following substrate accumulation but rather to activation of Aβ formation. By contrast, LY450139 inhibited Aβ formation from SH-SY5Y APPswe in a monophasic manner (IC50 18 nM). The BACE inhibitor per se inhibited Aβ secretion from both SH-SY5Y APPwt and SH-SY5Y APPswe cells with IC50s ranging between 7 - 18 nM and also prevented the increased Aβ secretion evoked by 3 nM LY450139. Combining the BACE inhibitor with higher inhibitory concentrations of LY450139 failed to demonstrate any clear additive or synergistic effects.

Conclusion

BACE-1 inhibition attenuates the Aβ increase evoked by LY450139 while not providing any obvious synergistic effects on LY450139-mediated inhibition.
Chipster: user-friendly analysis software for microarray and other high-throughput data
Authors: Kallio M Aleksi , Tuimala Jarno T , Hupponen Taavi , Klemelä Petri , Gentile Massimiliano , Scheinin Ilari , Koski Mikko , Käki Janne , Korpelainen Eija I
Published: November 2011

Background

The growth of high-throughput technologies such as microarrays and next generation sequencing has been accompanied by active research in data analysis methodology, producing new analysis methods at a rapid pace. While most of the newly developed methods are freely available, their use requires substantial computational skills. In order to enable non-programming biologists to benefit from the method development in a timely manner, we have created the Chipster software.

Results

Chipster (http://chipster.csc.fi/) brings a powerful collection of data analysis methods within the reach of bioscientists via its intuitive graphical user interface. Users can analyze and integrate different data types such as gene expression, miRNA and aCGH. The analysis functionality is complemented with rich interactive visualizations, allowing users to select datapoints and create new gene lists based on these selections. Importantly, users can save the performed analysis steps as reusable, automatic workflows, which can also be shared with other users. Being a versatile and easily extendable platform, Chipster can be used for microarray, proteomics and sequencing data. In this article we describe its comprehensive collection of analysis and visualization tools for microarray data using three case studies.

Conclusions

Chipster is a user-friendly analysis software for high-throughput data. Its intuitive graphical user interface enables biologists to access a powerful collection of data analysis and integration tools, and to visualize data interactively. Users can collaborate by sharing analysis sessions and workflows. Chipster is open source, and the server installation package is freely available.
Cis-regulatory functions of overlapping HIF-1alpha/E-box/AP-1-like sequences of CD164
Authors: Tang Jingqun , Luo Zhaohui , Zhou Guangqian , Song Chao , Yu Fenglei , Xiang Juanjuan , Li Gang
Published: November 2011

Background

CD164 (also known as MGC-24v or endolyn) is a sialomucin which has been suggested to participate in regulating the proliferation, cell adhesion and differentiation of hematopoietic stem and progenitor cells. CD164 is also involved in the development of cancer. The functions of cis-regulatory elements of CD164 remain relatively unknown.

Methods

In this study, we investigated the function of cis-regulatory elements within the promoter of CD164. We fused the 5'-flanking region of CD164 to a luciferase reporter vector. The minimal promoter region was confirmed by luciferase reporter assay. Using in silico analysis, we found the presence of one HIF-1alpha (HIF-1A) motif (5_-RCGTG-3_) overlapping E-box (CACGTG) and two AP-1-like binding sites (CGCTGTCCC, GTCTGTTG), one of which is also overlapped with HIF-1alpha sequence. Dual-luciferase assay was performed to examine the transcriptional activity of AP-1 and HIF-1alpha of CD164 promoter. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to measure CD164 expression. Chromatin Immunoprecipitation was used to confirm the binding of HIF-1alpha and CD164.

Results

Co-transfection of c-jun, HIF-1alpha and minimal promoter region construct demonstrated that c-jun and HIF-1alpha bound the CD164 promoter and promoted CD164 expression. Hypoxia treatment also led to the up-regulation of CD164 expression. The mutation of overlapping sequences resulted in the reduced expression of CD164 induced by HIF-1alpha. Chromatin Immunoprecipitation demonstrated that the HIF-1alpha bound the minimal promoter region.

Conclusions

Determination of the optimal promoter region and transcription factors governing CD164 expression is useful in understanding CD164 functions. These results suggest that cis-regulatory elements of CD164 overlapping HIF-1alpha/E-box/AP-1-like sequences may play important regulatory roles.
Long-term medical utilization following ventilator-associated pneumonia in acute stroke and traumatic brain injury patients: a case-control study
Authors: Yang Chih-Chieh , Shih Nai-Ching , Chang Wen-Chiung , Huang San-Kuei , Chien Ching-Wen
Published: November 2011

Background

The economic burden of ventilator-associated pneumonia (VAP) during the index hospitalization has been confirmed in previous studies. However, the long-term economic impact is still unclear. The aim of this study is to examine the effect of VAP on medical utilization in the long term.

Methods

This is a retrospective case-control study. Study subjects were patients experiencing their first traumatic brain injury, acute hemorrhagic stroke, or acute ischemic stroke during 2004. All subjects underwent endotracheal intubation in the emergency room (ER) on the day of admission or the day before admission, were transferred to the intensive care unit (ICU) and were mechanically ventilated for 48 hours or more. A total of 943 patients who developed VAP were included as the case group, and each was matched with two control patients without VAP by age ( ± 2 years), gender, diagnosis, date of admission ( ± 1 month) and hospital size, resulting in a total of 2,802 patients in the study. Using robust regression and Poisson regression models we examined the effect of VAP on medical utilization including hospitalization expenses, outpatient expenses, total medical expenses, number of ER visits, number of readmissions, number of hospitalization days and number of ICU days, during the index hospitalization and during the following 2-year period.

Results

Patients in the VAP group had higher hospitalization expenses, longer length of stay in hospital and in ICU, and a greater number of readmissions than the control group patients.

Conclusions

VAP has a significant impact on medical expenses and utilization, both during the index hospitalization during which VAP developed and in the longer term.
Fruit and vegetables intake among elderly Iranians: a theory-based interventional study using the five-a-day program
Authors: Salehi Leili , Mohammad Kazem , Montazeri Ali
Published: November 2011

Background

The benefit of FV intake in old age is well documented. However, there is evidence that old people do not consume enough FV. The purpose of this study was to evaluate the effectiveness of a tailored nutrition intervention that aimed to increase the FV intake among elderly Iranians aged 60 and over.

Methods

This quasi-experimental study was performed among a community-based sample of elderly in Tehran, Iran in year 2008 to 2009. Data were collected at baseline and 4 weeks follow-up. At baseline face-to-face interviews were conducted using a structured questionnaire including items on demographic information, stages of change, self-efficacy, decisional balance, daily servings of FV intake. Follow-up data were collected after implementing the intervention.

Results

In all 400 elderly were entered into the study (200 individuals in intervention group and 200 in control group). The mean age of participants was 64.06 ± 4.48 years and overall two-third of participants were female. At baseline total FV intake was not differed between two groups but it was significantly increased in the intervention group at posttest assessment (mean serving/day in intervention group 3.08 ± 1.35 vs. 1.79 ± 1.08 in control group; P = 0.001). Further analysis also indicated that elderly in intervention group had higher FV intake, perceived benefits and self-efficacy, and lower perceived barriers. Compared with control group, greater proportions of elderly in intervention group moved from pre-contemplation to contemplation/preparation and action/maintenance stages (P < 0.0001), and from contemplation/preparation to action/maintenance stages (P = 0.004) from pretest to posttest assessments.

Conclusion

This study suggests that the Transtheoretical Model is a useful model that can be applied to dietary behavior change, more specifically FV consumption among elderly population in Iran and perhaps elsewhere with similar conditions.