bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical Equivalent Circuit of Multi-mode Flexible Beams with Piezoelectric Elements
Authors: Saghafi Mehdi , Meghdari Ali
Published: July 2007

Surface mounted piezoelectric sensors and actuators on elastic structures are often connected to electrical networks. The coupled equations of motion of the elastic structure with piezoelectric elements are already well known. However, due to complex behavior of some electrical elements in the electrical network, it is not an easy task to obtain the integrated equations of the whole system. A good remedy for this problem is to take advantage of an equivalent electrical circuit (EEC) representation of the mechanical part, leading the entire system to be represented as an electrical circuit. In this study, the authors propose a new method for constructing the EEC. This method is based upon the multimode analysis of vibrating structures. Utilizing modal analysis, the equations are converted to tridiagonal form which is shown to be appropriate for constructing the EEC. In contrast to previous works, no restrictive approximations are made in its development. This method can also be used in similar applications, such as power harvesting from vibrating structures.
A High-order Isotropic Continuum Damage Evolution Model
Authors: Thakkar Bhairav K. , Pandey P.C.
Published: July 2007

In this study, a continuum isotropic plastic damage evolution model has been derived in the framework of internal variable theory of thermodynamics. A new dissipation potential function has been suggested as a basis for developing the high-order damage evolution model based on continuum damage mechanics (CDM) theory. Subsequently, a high-order non-linear damage evolution model is derived. The damage model is based on the concept of effective stress and the principle of strain equivalence. The performance of the developed model is studied by comparing it with experimental data available in the literature for materials like aluminum, copper, spheroidized steel, and steel—XC38. The damage model is found to be versatile and is able to represent the experimental damage evolution patterns with a close agreement.
Situating Social Influence Processes: Dynamic, Multidirectional Flows of Influence Within Social Networks
Authors: Mason Winter A. , Conrey Frederica R. , Smith Eliot R.
Published: July 2007

Social psychologists have studied the psychological processes involved in persuasion, conformity, and other forms of social influence, but they have rarely modeled the ways influence processes play out when multiple sources and multiple targets of influence interact over time. However, workers in other fields from sociology and economics to cognitive science and physics have recognized the importance of social influence and have developed models of influence flow in populations and groups—generally without relying on detailed social psychological findings. This article reviews models of social influence from a number of fields, categorizing them using four conceptual dimensions to delineate the universe of possible models. The goal is to encourage interdisciplinary collaborations to build models that incorporate the detailed, microlevel understanding of influence processes derived from focused laboratory studies but contextualized in ways that recognize how multidirectional, dynamic influences are situated in people's social networks and relationships.
Selves Creating Stories Creating Selves: A Process Model of Self-Development
Authors: McLean Kate C. , Pasupathi Monisha , Pals Jennifer L.
Published: July 2007

This article is focused on the growing empirical emphasis on connections between narrative and self-development. The authors propose a process model of self-development in which storytelling is at the heart of both stability and change in the self. Specifically, we focus on how situated stories help develop and maintain the self with reciprocal impacts on enduring aspects of self, specifically self-concept and the life story. This article emphasizes the research that has shown how autobiographical stories affect the self and provides a direction for future work to maximize the potential of narrative approaches to studying processes of self-development.
Understanding the Role of the Self in Prime-to-Behavior Effects: The Active-Self Account
Authors: Wheeler S. Christian , DeMarree Kenneth G. , Petty Richard E.
Published: July 2007

In this article, the authors review research showing the different roles that the self-concept can play in affecting prime-to-behavior effects. As an organizing framework, an Active-Self account of stereotype, trait, and exemplar prime-to-behavior effects is presented. According to this view, such primes can influence people's behavior by creating changes in the active self-concept, either by invoking a biased subset of chronic self-content or by introducing new material into the active self-concept. The authors show how involvement of the active self-concept can increase, decrease, or reverse the effects of primes and describe how individual differences in responsiveness of the self to change and usage of the self in guiding behavior (e.g., self-monitoring) can moderate prime-to-behavior effects. The Active-Self account is proposed as an integrative framework that explains how the self is involved in prime-to-behavior effects and helps predict how changes in the self determine which motivational and behavioral representations will guide behavior.
Seven Principles of Goal Activation: A Systematic Approach to Distinguishing Goal Priming From Priming of Non-Goal Constructs
Authors: Förster Jens , Liberman Nira , Friedman Ronald S.
Published: July 2007

Countless studies have recently purported to demonstrate effects of goal priming; however, it is difficult to muster unambiguous support for the claims of these studies because of the lack of clear criteria for determining whether goals, as opposed to alternative varieties of mental representations, have indeed been activated. Therefore, the authors offer theoretical guidelines that may help distinguish between semantic, procedural, and goal priming. Seven principles that are hallmarks of self-regulatory processes are proposed: Goal-priming effects (a) involve value, (b) involve postattainment decrements in motivation, (c) involve gradients as a function of distance to the goal, (d) are proportional to the product of expectancy and value, (e) involve inhibition of conflicting goals, (f) involve self-control, and (g) are moderated by equifinality and multifinality. How these principles might help distinguish between automatic activation of goals and priming effects that do not involve goals is discussed.
Failure of allogeneic bone marrow transplantation to arrest disease activity in multiple sclerosis
Authors: Jeffery D.R.
Published: July 2007

Multiple sclerosis (MS) is thought to be an autoimmune disease in which activated T-cells initiate a macrophage mediated destruction of CNS myelin. Bone marrow transplantation (BMT) is currently being evaluated in the treatment of MS in patients with aggressive disease activity. Autologous BMT could potentially reset the immune response to myelin antigens leading to immune tolerance and decreased disease activity. Allogeneic transplantation could reconstitute the immune system potentially arresting the progression of autoimmune disease. The purpose of this paper is to report a patient with MS who underwent allogeneic BMT for chronic myelogenous leukemia (CML) and showed continued evidence of active demyelinating disease by clinical and radiologic criteria over a period of two years. While this is only a single case report with inherent limitations, it suggests that the immune mediated destruction of CNS myelin in MS may not be prevented or aborted by immune system reconstitution, and is consistent with the idea that immune mediated tissue destruction in MS could be targeted against an abnormal antigen. Multiple Sclerosis 2007; 13: 1071—1075. http://msj.sagepub.com
Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis
Authors: Watanabe S. , Misu T. , Miyazawa I. , Nakashima I. , Shiga Y. , Fujihara K. , Itoyama Y.
Published: July 2007

Neuromyelitis optica (NMO) is a relapsing neurologic disease characterized by severe optic neuritis and transverse myelitis. A disease-modifying therapy for NMO has not been established. We retrospectively analysed the effect of low-dose corticosteroid (CS) monotherapy on the annual relapse rate in nine patients with NMO. We divided the clinical course in each patient into two periods; the CS Period in which CS was administered, and the No CS Period in which CS was not administered. Periods related to other immunological therapies, such as high-dose methylprednisolone, immunosuppressants, interferon-beta, and plasma exchange, were excluded. As a result, the annual relapse rate during the CS Periods [median, 0.49 (range, 0—1.31)] was found to be significantly lower than that during the No CS Periods [1.48 (0.65—5.54)]. As for the dose of CS, relapses occurred significantly more frequently with `10 mg/day or less' than with `over 10 mg/day' (odds ratio: 8.75). The results of the present study suggest a beneficial effect of low-dose CS monotherapy in reducing relapses in NMO. Multiple Sclerosis 2007; 13: 968—974. http://msj.sagepub.com
A shortened version of PASAT-3 is feasible
Authors: Solari A. , Motta A. , Radice D. , Mendozzi L.
Published: July 2007

The Paced Auditory Serial Addition Test (PASAT), most used neuropsychological test in people with multiple sclerosis (pwMS), is available as PASAT-3 and more difficult PASAT-2. We determined PASAT performance in 105 pwMS and 105 matched controls and assessed the utility of a shortened PASAT-3 version. Qualitative and quantitative analyses were performed, the latter involving assessment of dyads (two consecutive correct responses) and singles (correct response between two omitted responses). Based on provisional results we then calculated the sensitivity of the first 20 items of PASAT-3 in relation to the full version. Mean PASAT-2 and 3 total score, dyads and singles differed significantly ( P ≤ 0.0002) in pwMS and controls, due to more omissions in pwMS, number and type of incorrect answers did not differ. Differences between pwMS and controls were highly significant for the first 50, 40, 30 and 20 responses of the PASAT-3. The sensitivity of the first 20 items of PASAT-3 was 87% (95% CI 0.70—1.00). PASAT-3 and PASAT-2 effectively discriminate pwMS from controls. Use of the first 20 items of PASAT-3 appears as a highly useful PASAT-3 version as it retains the discriminative value and sensitivity of the full version yet is quicker to administer and less demanding. Multiple Sclerosis 2007; 13: 1020—1025. http://msj.sagepub.com
Antidepressant use in multiple sclerosis: epidemiologic study of a large community sample
Authors: Cetin K. , Johnson K.L. , Ehde D.M. , Kuehn C.M. , Amtmann D. , Kraft G.H.
Published: July 2007

Depressive symptoms and disorders among individuals with multiple sclerosis (MS) are more common when compared to other chronic illnesses and the general population, but relatively little is known about the use of antidepressant medication in this population. In this cross-sectional study of 542 community-dwelling adults with MS, we examined the prevalence of antidepressant use and employed multivariate logistic regression modeling to identify factors significantly associated with antidepressant use. Thirty-five percent of the sample reported currently using at least one antidepressant medication. Gender, marital status, insurance status, fatigue, and use of disease modifying therapies were all significantly associated with antidepressant use. Just over half of the sample endorsed a clinically significant level of depressive symptoms, and the majority of this group was not currently taking an antidepressant. Conversely, 41% of those with depressive symptoms reported taking at least one antidepressant medication. More research is needed to better understand why people with MS and depressive symptoms use or do not use antidepressant medications and to further explore the possibility of an under-treatment of depressive disorder in this population. Rigorous studies testing the feasibility, acceptability, and efficacy of currently available therapies for depression in the MS population should also be conducted. Multiple Sclerosis 2007; 13: 1046—1053. http://msj.sagepub.com
Pregnancy in multiple sclerosis patients treated with immunomodulators prior to or during part of the pregnancy: a descriptive study in the Spanish population
Authors: De las Heras V. , De Andrés C. , Téllez N. , Tintoré M. ,   on behalf of the EMPATIE Study Group, Spain
Published: July 2007

Objectives To study the management of pregnancy in multiple sclerosis (MS) patients on immunomodulatory therapy (IMT) in routine clinical practice and to analyze pregnancy outcomes and the clinical course of MS around pregnancy.

Methods Retrospective, multicentric study in Spain in MS patients receiving IMT before conception and followed for at least three months post-partum.

Results A total of 1286 medical records were reviewed. Eighty-eight pregnancies were identified in 74 (6%) women, 66% of which were unexposed and 34% exposed pregnancies. In most cases, IMT was discontinued before conception and resumed shortly after delivery. Accidental exposure to IMT did not lead to higher rates of abortions ( P = 0.76) or malformations. The relapse rate was decreased during pregnancy (0.31 versus 0.61 in the pre-pregnancy year) and increased after delivery (0.87 on month 3), returning to pre-conception values on month 12. The median EDSS score was not increased during the study.

Conclusions Discontinuation of IMT before conception, and resumption shortly after delivery was the most frequent clinical practice procedure. Accidental exposure to IMT did not affect pregnancy outcomes or increased malformation rates. Pregnancy was associated with a reduced relapse rate. No factor was found to predict the risk of relapses during or after pregnancy. Multiple Sclerosis 2007; 13: 981—984. http://msj.sagepub.com
Estimation of the cost of MS in Europe: Extrapolations from a multinational cost study
Authors: Sobocki P. , Pugliatti M. , Lauer K. , Kobelt G.
Published: July 2007

The present study aims at estimating the total cost of MS in Europe based on actual cost data from nine countries and published epidemiological evidence. The epidemiological data are reported as 12 months prevalence estimates and cost data calculated as annual cost per patient at given levels of disease severity. Cost data are extrapolated to the rest of Europe based on a model, using economic indexes adjusting for price level differences in different sectors between countries. The aggregated annual cost estimates are presented in Euro for 2005. In 28 European countries with a population of 466 million, an estimated 380 000 individuals are affected by MS. The total annual cost of MS in Europe is estimated at 12.5 billion in year 2005, corresponding to a cost of 27 per European inhabitant. Direct costs represent slightly more than half of the total cost (6.0 billion). Informal care is estimated at 3.2 billion, and indirect costs due to morbidity at 3.2 billion. Thus, the largest component of costs is found outside the formal health care sector. Although our model appears to predict costs reasonably well, when comparing to previous national studies not included in the estimates, there are considerable uncertainties when extrapolating cost data across countries even within Europe. These weaknesses can only be overcome by collecting primary data. Multiple Sclerosis 2007; 13: 1054—1064. http://msj.sagepub.com
Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis
Authors: Glanz BI , Holland CM , Gauthier SA , Amunwa EL , Liptak Z. , Houtchens MK , Sperling RA , Khoury SJ , Guttmann CRG , Weiner HL
Published: July 2007

Cognitive dysfunction is common in patients with multiple sclerosis (MS), and has been associated with MRI measures of lesion burden and atrophy. Little is known about the prevalence of cognitive impairment in patients with early MS. The associations between cognitive impairment and MRI measures of disease severity early in the disease course are also unclear. This study used a brief battery of cognitive tests to determine the prevalence and pattern of cognitive impairment in patients with clinically isolated syndromes or newly diagnosed MS. The associations between cognitive impairment and MRI measures of disease severity early in the disease course were also examined. Ninety-two patients with clinically isolated syndromes or the diagnosis of MS within the last 3 years participating in the CLIMB study underwent a neurologic examination, neuropsychological evaluation and MRI at 1.5T. Forty-nine percent of patients were impaired on one or more cognitive measures. There were no significant correlations between cognitive scores and MRI measures of disease severity including total T2 lesion volume, normal appearing white matter volume, grey matter volume, and brain parenchymal fraction. These findings suggest that cognitive impairment may predate the appearance of gross structural abnormalities on MRI and serve as an early marker of disease activity in MS. Multiple Sclerosis 2007; 13: 1004—1010. http://msj.sagepub.com
Quality of life in multiple sclerosis: should clinicians trust proxy ratings?
Authors: Tripoliti E. , Campbell C. , Pring T. , Taylor-Goh S.
Published: July 2007

Purpose Measures of quality of life (QoL) are increasingly used to monitor psychological and social well being of clients with chronic illnesses. They are particularly useful in cases where an illness results in multiple disabilities. Where clients have difficulty completing the measure, others who know them may act as proxies. It is important, therefore to assess the accuracy of proxy scores. This study compared the QoL scores given by people with multiple sclerosis (PWMS) with proxy scores given by close relatives.

Method The Functional Assessment of Multiple Sclerosis (FAMS) quality of life instrument (Cella et al.) [1] was used. Forty PWMS completed the measure in face-to-face interviews with a speech and language therapist. Close relatives were asked to independently complete the measure on behalf of these clients.

Results The overall correlation between client and proxy scores was 0.62, which Sneeuw et al. [2] suggest indicates good agreement. As in previous studies with other groups of clients, proxies underestimated the scores of PWMS. Despite these findings, the results showed substantial disagreements for individual clients and their proxies and a relationship was found which suggests that proxies underestimate the scores of clients with better QoL and overestimate those with poorer QoL scores.

Conclusion The level of agreement found between client and proxy scores and the tendency for proxies to underestimate clients' scores are consistent with research with other client groups. The overestimation by proxies of clients who rate their QoL as poor needs further investigation. If confirmed it may complicate the estimation of client scores from those of proxies. We conclude that while proxy scores may be useful as a means of estimating the QoL of groups of clients in research studies they should be used cautiously in the prediction of the QoL of individual clients at the clinical level. Multiple Sclerosis 2007; 13: 1190—1194. http://msj.sagepub.com
Multidisciplinary fatigue management programme in multiple sclerosis: a randomized clinical trial
Authors: Kos D. , Duportail M. , D'hooghe MB , Nagels G. , Kerckhofs E.
Published: July 2007

Objective To establish the efficacy of a multidisciplinary fatigue management programme (MFMP) in MS.

Method Fifty-one subjects with MS were randomly allocated to group A, who only received the four weeks MFMP, or group B receiving a placebo intervention programme first and the MFMP after 6 months. In both groups, assessment was performed at baseline, 3 weeks and 6 months after the programmes and included Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), MS Self-Efficacy scale (MSSE), Mental Health Inventory (MHI) and Impact on Participation and Autonomy (IPA).

Results The MFIS showed a significant change over time ( F(4,152) = 3.346, P = 0.012), which was similar in both groups (time*group interaction: F(4,152) = 1.094, P = 0.361). A clinically relevant reduction of MFIS score of 10 points or more was found in 17% of individuals following the MFMP, compared to 44% after the placebo intervention programme ( P = 0.06). Compared to no intervention, a significant effect of the MFMP after 6 months ( P = 0.003) was found in five participants (31%). No significant changes in FSS, MSSE, MHI and IPA, in both groups, were found.

Conclusion Although an additional effect was found, the multidisciplinary fatigue management programme showed no efficacy in reducing the impact of fatigue compared to a placebo intervention programme. Multiple Sclerosis 2007; 13: 996—1003. http://msj.sagepub.com
Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis
Authors: Marrosu F. , Maleci A. , Cocco E. , Puligheddu M. , Barberini L. , Marrosu M.G.
Published: July 2007

Vagus nerve stimulation (VNS), an adjunctive approach for the treatment of epilepsy, was performed in three multiple sclerosis (MS) patients displaying postural cerebellar tremor (PCT) and dysphagia. Following VNS, improvement of PCT and dysphagia was manifested over a period of two and three months, respectively. In view of the involvement of the main brainstem visceral component of the vagus, the nucleus tractus solitarius (NTS), in modulating central pattern generators (CPGs) linked to both olive complex pathway and swallowing, improvement is likely to be VNS related. The results obtained suggest an additional therapeutic application for VNS and may represent a novel form of treatment in patients with severe MS. Multiple Sclerosis 2007; 13: 1200—1202. http://msj.sagepub.com
Vocational rehabilitation services for people with multiple sclerosis: what patients want from clinicians and employers
Authors: Sweetland J. , Riazi A. , Cano S.J. , Playford E.D.
Published: July 2007

Background The NSF for Long-term Neurological Conditions highlights the need for vocational rehabilitation services. Although the barriers to work for people with MS (pwMS) have been clearly identified, there has been little research that identifies the type of support required.

Objective To identify what pwMS require from a vocational rehabilitation service in terms of content and service delivery.

Design of study Four focus groups of pwMS, currently in employment, were convened. These were audio-taped and content analysed using a constant comparison method.

Results People with MS identified two key needs; managing performance and managing expectations. Performance difficulties could be managed either by treating symptoms, by changing the environment, or by altering the demands of the job. PwMS highlighted the need for counselling to help them, and advocacy to help their employers have appropriate expectations.

Conclusion PwMS need support in the workplace in two distinct ways. First, by managing the interaction between the impairments caused by MS, the physical environment, and the demands imposed by the work. Second, by providing expert knowledge about the employment environment and the needs of employers, an awareness of the relevant legislation and counselling in supporting people to adapt, adjust and resolve complex issues. Multiple Sclerosis 2007; 13: 1183—1189. http://msj.sagepub.com
A Theoretical Exploration of Manager and Employee Social Identity, Cultural Values and Identity Conflict Management
Authors: Dalton Maxine , Chrobot-Mason Donna
Published: July 2007

As social identity conflicts based on ethnic origin, religion, caste, and so on, erupt around the globe, we investigate what may happen when these conflicts carry over into the workplace. In this article we explore possible employee responses to an organizational manager when the manager is attempting to prevent or reduce the intensity of social identity conflict in the workplace and the conflict is attributed to relatively non-fluid characteristics of social identity such as ethnicity, nationality, caste, or gender. We propose that employee responses to manager influence depend on: (1) whether the employee and manager are members of the same or different social identity groups, (2) whether the employees are members of the dominant or non-dominant group in the society at large, and (3) the shared influence of the embedded—autonomous cultural dimensions and the hierarchical—egalitarian cultural dimensions.
Which Is Easier, Adjusting to a Similar or to a Dissimilar Culture?
Authors: Selmer Jan
Published: July 2007

The intuitively paradoxical research proposition that it could be as difficult for business expatriates to adjust to a similar as to a dissimilar host culture is tested in this exploratory study. Based on data from a mail survey, a comparison of American business expatriates in Canada and Germany respectively did not reveal any difference in their extent of adjustment. Besides a significant between-group difference in cultural distance, confirming that the American expatriates perceived Canada as more culturally similar to America than Germany, no significant intergroup differences were detected for general adjustment, interaction adjustment, work adjustment and psychological adjustment. Neither was there a difference in the time-related variable; time to proficiency. Although highly tentative, the suggestion that the degree of cultural similarity/dissimilarity may be irrelevant as to how easily expatriates adjust is fundamental. Implications for theory, practice and future research of these findings are discussed in detail.
Paradigmapping Studies of Culture and Organization
Authors: Lowe Sid , Moore Fiona , Carr Adrian N.
Published: July 2007

This article argues that cross cultural management research is in a crisis of its own making. It is a captive of the delusion that nomothetic theory is progressing towards convergence of an ideal view. Within the context of this fallacy are competing perspectives and paradigms that appear incommensurable. The battle appears to be which paradigm will win. It is our contention that the battle is futile and unnecessary. We reveal how `paradigmapping' is useful in understanding the manner in which paradigms and incommensurability can be framed in discourse involving culture and organization. Through this work of Frijof Capra we seek to formulate a new perspective on paradigms. This view enables an informative account of where principal contributions can be located within the intellectual space of studies of culture and organizations. It reveals that all knowledge contributions are captive of one privileged view, tolerant of a second marginalized view and denigrative or ignorant of a third view. In other words, all knowledge is captive of blind prejudices. We offer an outline of strategic research options within the field and the potential for transcending potential problems of incommensurability. We conclude that `anything goes', as long as it involves what Capra has called `epistemic consciousness'; namely a realization of the prejudices inherent in our epistemologies, a determination to avoid single-paradigm myopia, and encouragement to employ bricolage in the context of local moralities, relationships and actionable outcomes.
Rethinking Organizational Commitment in Relation to Perceived Organizational Power and Perceived Employment Alternatives
Authors: Bar-Haim Aviad
Published: July 2007

The detachment of moral and affective motives from the actual behavior of loyalty and active commitment is recognized and expected in cross cultural research into organizational commitment. However, this separation is almost impossible to make from the perspective of western and managerially biased mainstream research into organizational commitment. Following the cross cultural perspective, the thesis of this article is that organizational commitment is not a state of mind but a behavior of choice. It is the unequivocal behavior of being obligated, regardless of individual goals, sentiments or moral values, particularly in the worst conditions, when organizations are unable to reward it. In a study of 361 respondents from four organized systems into the impact of perceived organizational power (POP) and perceived employment alternatives (PEA) on behavior of organizational commitment (OCb), it was found that OCb was dependent partially and in a non-linear manner on POP and PEA. However, the part that was not explained by these independent variables leaves ample room for a different possible explanation of OC b. For example, many people in this study chose active modes of positive commitment, in spite of having perceived employment alternatives and possessing only a small amount of perceived organizational power. This suggests that even during bad times for their employing organization, employees may not automatically rush to take advantage of their employment alternatives, but, on the contrary, may continue to contribute their knowledge, skills and abilities voluntarily, and not as tactics designed to protect their organizational assets. After all, pure commitment is an obligation to do something that is not necessarily agreeable or gainful. This lesson is well known in non-western cultures.
Id1, but not Id3, directs long-term repopulating hematopoietic stem-cell maintenance
Authors: Perry S. Scott , Zhao Ying , Nie Lei , Cochrane Shawn W. , Huang Zhong , Sun Xiao-Hong
Published: July 2007

E-proteins are widely expressed basic helix-loop-helix (HLH) transcription factors that regulate differentiation in many cell lineages, including lymphoid, muscle, and neuronal cells. E-protein function is controlled by HLH inhibitors such as Id and SCL/TAL1 proteins, which recently have been suggested to play a role in hematopoietic stem cell (HSC) differentiation. However, the precise stages when these proteins are expressed and their specific functions are not entirely clear. Using a knock-in mouse model where the sequence for the enhanced green fluorescent protein (GFP) was inserted downstream of the Id1 promoter, we were able to track Id1 expression on an individual cell basis and detected Id1 expression in long-term repopulating HSCs (LT-HSCs). Functional assays showed that the Id1/GFP+Lin−Sca1+c-kitHi population was highly enriched for LT-HSCs. Consistent with this expression pattern, Id1 deficiency led to a 2-fold reduction in the number of LT-HSCs defined as Lin−Sca1+c-kitHiCD48−CD150+. Primary bone marrow transplantation studies revealed that Id1 is dispensable for short-term engraftment. In contrast, both Id1−/− whole bone marrow and Lin−Sca1+c-kitHiThy1.1Lo-enriched HSCs, but not Id3−/− marrow, displayed impaired engraftment relative to wild-type controls in secondary transplantation assays. These findings suggest a unique role for Id1 in LT-HSC maintenance and hematopoietic development.
Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy
Authors: Drolet Renée , Simard Marc , Plante Julie , Laberge Philippe , Tremblay Yves
Published: July 2007

Background

During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2.

Methods

We obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol) and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium.

Results

High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium.

Conclusion

The spatial and temporal expression of 17beta-HSD2 in the placenta during pregnancy and the comparison of 17beta-HSD2 expression and steroid levels between placental villi and endometrium are compatible with a role in the modulation of active and inactive forms of estrogens. Our observations strongly support the hypothesis that 17beta-HSD2 acts as a barrier decreasing estradiol secretion rates in the foetal circulation.
Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection
Authors: White Ian R , Patel Keyur , Symonds William T , Dev Anouk , Griffin Philip , Tsokanas Nikos , Skehel Mark , Liu Chiang , Zekry Amany , Cutler Paul , Gattu Mahanandeeshwar , Rockey Don C , Berrey Michelle M , McHutchison John G
Published: July 2007

Background

Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis.

Methods

Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.

Results

Seven individual protein spots were identified as either significantly increased (α2-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α2-macroglobulin, are included in existing non-invasive serum marker panels.

Conclusion

Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.
Investigation of HIFU-induced anti-tumor immunity in a murine tumor model
Authors: Hu Zhenlin , Yang Xiao Yi , Liu Yunbo , Sankin Georgy N , Pua Eric C , Morse Michael A , Lyerly H Kim , Clay Timothy M , Zhong Pei
Published: July 2007

Background

High intensity focused ultrasound (HIFU) is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment.

Methods

Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response.In vivodendritic cell activity was assessed along with the host's response to challenge tumor growth.

Results

Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio.

Conclusion

These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to dendritic cell activation. Because DC activation was more pronounced when tumor cells were mechanically lysed by focused ultrasound treatment, mechanical HIFU in particular may be employed as a potential strategy in combination with subsequent thermal ablations for increasing the efficacy of HIFU cancer treatment by enhancing the host's anti-tumor immunity.
A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study
Authors: Gaïni Shahin , Koldkjær Ole G , Møller Holger J , Pedersen Court , Pedersen Svend S
Published: July 2007

Introduction

High-mobility group box-1 protein (HMGB1) has been known as a chromosomal protein for many years. HMGB1 has recently been shown to be a proinflammatory cytokine with a role in the immunopathogenesis of sepsis. Lipopolysaccharide-binding protein (LBP) has a central role in the innate immune response when the host is challenged by bacterial pathogens. Procalcitonin (PCT) has been suggested as a marker of severe bacterial infections and sepsis. The aim of the present study was to investigate levels of HMGB1, LBP and PCT in a well-characterised sepsis cohort. The study plan included analysis of the levels of the inflammatory markers in relation to the severity of infection, to the prognosis and to the ability to identify patients with bacteraemia.

Methods

Patients suspected of having severe infections and admitted to a department of internal medicine were included in a prospective manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score and mortality on day 28 were recorded. Plasma and serum were sampled within 24 hours after admission. Levels of all studied markers (HMGB1, LBP, PCT, IL-6, C-reactive protein, white blood cell count and neutrophils) were measured with commercially available laboratory techniques.

Results

A total of 185 adult patients were included in the study; 154 patients fulfilled our definition of infection. Levels of HMGB1, LBP and PCT were higher in infected patients compared with a healthy control group (P < 0.0001). Levels of HMGB1, LBP and PCT were higher in the severe sepsis group compared with the sepsis group (P < 0.01). No differences were observed in levels of the inflammatory markers in fatal cases compared with survivors. Levels of all studied markers were higher in bacteraemic patients compared with nonbacteraemic patients (P < 0.05). PCT performed best in a receiver–operator curve analysis discriminating between bacteraemic and nonbacteraemic patients (P < 0.05). HMGB1 correlated to LBP, IL-6, C-reactive protein, white blood cell count and neutrophils (P < 0.001). LBP correlated to PCT, IL-6 and C-reactive protein (P < 0.001).

Conclusion

Levels of HMGB1, PCT and LBP were higher in infected patients compared with those in healthy controls, and levels were higher in severe sepsis patients compared with those in sepsis patients. Levels of all studied inflammatory markers (HMGB1, LBP, PCT, IL-6) and infection markers (C-reactive protein, white blood cell count, neutrophils) were elevated among bacteraemic patients. PCT performed best as a diagnostic test marker for bacteraemia.
A high utility integrated map of the pig genome
Authors: Humphray Sean J , Scott Carol E , Clark Richard , Marron Brandy , Bender Clare , Camm Nick , Davis Jayne , Jenks Andrew , Noon Angela , Patel Manish , Sehra Harminder , Yang Fengtang , Rogatcheva Margarita B , Milan Denis , Chardon Patrick , Rohrer Gary , Nonneman Dan , de Jong Pieter , Meyers Stacey N , Archibald Alan , Beever Jonathan E , Schook Lawrence B , Rogers Jane
Published: July 2007

Background

The domestic pig is being increasingly exploited as a system for modeling human disease. It also has substantial economic importance for meat-based protein production. Physical clone maps have underpinned large-scale genomic sequencing and enabled focused cloning efforts for many genomes. Comparative genetic maps indicate that there is more structural similarity between pig and human than, for example, mouse and human, and we have used this close relationship between human and pig as a way of facilitating map construction.

Results

Here we report the construction of the most highly continuous bacterial artificial chromosome (BAC) map of any mammalian genome, for the pig (Sus scrofa domestica) genome. The map provides a template for the generation and assembly of high-quality anchored sequence across the genome. The physical map integrates previous landmark maps with restriction fingerprints and BAC end sequences from over 260,000 BACs derived from 4 BAC libraries and takes advantage of alignments to the human genome to improve the continuity and local ordering of the clone contigs. We estimate that over 98% of the euchromatin of the 18 pig autosomes and the X chromosome along with localized coverage on Y is represented in 172 contigs, with chromosome 13 (218 Mb) represented by a single contig. The map is accessible through pre-Ensembl, where links to marker and sequence data can be found.

Conclusion

The map will enable immediate electronic positional cloning of genes, benefiting the pig research community and further facilitating use of the pig as an alternative animal model for human disease. The clone map and BAC end sequence data can also help to support the assembly of maps and genome sequences of other artiodactyls.
Histone Deacetylase Inhibitors Regulate Retinoic Acid Receptor β Expression in Neuroblastoma Cells by Both Transcriptional and Posttranscriptional Mechanisms
Authors: De los Santos Maxy , Zambrano Alberto , Sánchez-Pacheco Aurora , Aranda Ana
Published: July 2007

The retinoic acid receptor β (RARβ) is a retinoic acid (RA)-inducible tumor suppressor, which plays an important role in the arrest of neuroblastoma cell growth. Using human neuroblastoma SH-SY5Y cells, we have examined the regulation of RARβ expression by histone deacetylase inhibitors (HDACi), considered to be promising agents in anticancer therapy. Our results show that HDACi cooperated with RA to increase RARβ mRNA levels and to activate the RARβ2 promoter in transient transfection assays. Chromatin immunoprecipitation assays showed that the basal RARβ2 promoter that contains the RA response element was refractory to acetylation by both HDACi and RA. In addition, HDACi caused a transient increase in acetylation of a downstream RARβ2 region, even though global histones remain hyperacetylated after a prolonged treatment with the inhibitors. RA potentiated this response and maintained acetylation for a longer period. Despite the cooperation of RA with HDACi to increase transcription of the RARβ gene, these inhibitors caused a paradoxical reduction of the cellular levels of the RARβ protein in cells treated with the retinoid. This reduction is secondary to a change in the protein half-life that is decreased by the HDACi due to increased ubiquitin-independent proteasomal degradation. These results show that HDACi regulate expression of the tumor suppressor gene RARβ by both transcriptional and posttranscriptional mechanisms and might then modulate sensitivity to the retinoid in neuroblastoma cells.
The membrane targeting and spatial activation of Src, Yes and Fyn is influenced by palmitoylation and distinct RhoB/RhoD endosome requirements
Authors: Sandilands Emma , Brunton Valerie G. , Frame Margaret C.
Published: July 2007

Src activation is a tightly regulated process which requires RhoB endosome-associated actin assembly and transit to the cell periphery. We show here that although two other ubiquitous Src family kinases (SFKs) Yes and Fyn also require intact actin filaments for peripheral membrane targeting, they display distinct spatial activation and endosomal requirements. Unlike Src, both Yes and Fyn are constitutively membrane-localized to some extent, and Fyn is present in RhoD-positive endosomes whereas Yes does not visibly colocalize with either of the endosomal markers RhoB or RhoD. By modulating amino acid acceptor sites for palmitoylation in Src, Yes and Fyn, we show that Src S3C/S6C, which is palmitoylated (unlike wild-type Src) behaves in a manner more similar to Fyn, by predominantly colocalizing with RhoD endosomes, and the targeting of both Fyn and Src S3C/S6C is inhibited by siRNA-mediated knockdown of RhoD. Moreover, Fyn C3S/C6S, which is no longer palmitoylated, behaves much more like Src by colocalizing with RhoB endosomes and by requiring RhoB for activation and membrane translocation. These data imply that distinct modes of spatial activation and membrane delivery, at least partly under the control of specific acylation attachment sequences and endosome sub-type requirements, define distinct properties of the three ubiquitously expressed SFKs.
The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons
Authors: Sone Masamitsu , Hayashi Tetsutaro , Tarui Hiroshi , Agata Kiyokazu , Takeichi Masatoshi , Nakagawa Shinichi
Published: July 2007

Recent transcriptome analyses have revealed that a large body of noncoding regions of mammalian genomes are actually transcribed into RNAs. Our understanding of the molecular features of these noncoding RNAs is far from complete. We have identified a novel mRNA-like noncoding gene, named Gomafu, which is expressed in a distinct set of neurons in the mouse nervous system. Interestingly, spliced mature Gomafu RNA is localized to the nucleus despite its mRNA-like characteristics, which usually act as potent export signals to the cytoplasm. Within the nucleus, Gomafu RNA is detected as numerous spots that do not colocalize with known nuclear domain markers. Gomafu RNA is extremely insoluble and remains intact after nuclear matrix preparation. Furthermore, heterokaryon assays revealed that Gomafu RNA does not shuttle between the nucleus and cytoplasm, but is retained in the nucleus after its transcription. We propose that Gomafu RNA represents a novel family of mRNA-like noncoding RNA that constitutes a cell-type-specific component of the nuclear matrix.