bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive process control using a moving radiant actuator
Authors: Zeng F , Ayalew B
Published: August 2011

This paper presents a predictive control framework for a class of industrial distributed-parameter processes employing moving radiant actuators. The use of a moving actuator provides additional control options, but it also requires more elaborate control strategies to ensure a desired level of quality for the target process. The proposed predictive control framework is based on a generic one-dimensional (1D) formulation that describes common characteristics of typical radiant source actuated processes. The developed control framework incorporates carefully reduced process models that capture the main features of the processes and a state/parameter estimator activated with a policy that considers the changing radiant input distribution accompanying the moving actuator. The developed model predictive control framework is then demonstrated on a 1D robotic ultraviolet paint curing process. The results show that the predictive control approach provides a better cure process performance than typical static optimization methods.
Dynamic capture of free-moving objects
Authors: Nagendran A , Crowther W , Richardson R C
Published: August 2011

A new stiffness control method is proposed for robotic systems to capture free-moving objects with minimum jerk. A bell-shaped stiffness curve is shown to minimize the jerk that occurs during capture tasks. The results verify that the method can be used to successfully decelerate objects over a predefined distance, while keeping the jerk experienced during the capture within limits. Shortcomings with the method are identified from the results, and an adaptive control scheme is proposed. An adaptive controller is designed to actively interact with the object to estimate the kinetic energy during the capture and scale the amount of force being applied accordingly. Simulation results confirm that the adaptive control scheme overcomes the shortcomings in previous methods.
Design of fractional order proportional–integral–derivative controller based on moment matching and characteristic ratio assignment method
Authors: Tabatabaei M , Haeri M
Published: August 2011

This paper presents a new analytical method to design fractional-order proportional–integral–derivative (PID) controllers. The control parameters are calculated so that the closed-loop system approximates a desired transfer function with transient response requirements. This function is determined based on the characteristic ratio assignment method. The control parameters are calculated by matching the first three moments of the closed-loop transfer function with the corresponding values of the desired system. Furthermore, to ensure closed-loop stability the proposed method is improved by using the shifted moments around the crossover frequency. Illustrative examples are given to show the performance of the proposed method.
Modelling and motion control of a double-pendulum driven cart
Authors: Liu Y , Yu H , Cang S
Published: August 2011

The significant advantage of ground mobile robots (GMRs) is their accessibility to areas that are inaccessible for humans. One difficulty of current GMR technology is that the external driving mechanisms, such as wheel, track, and leg, restrict its applications. In order to solve this limitation, the present paper proposes a novel driving mechanism using a novel GMR called the double-pendulum driven cart (DPDC). The DPDC, which employs only internal thrust and static friction, is capable of steering by two parallel pendulums mounted on the cart, and is able to implement planar elemental motions by designing the pendulum trajectory properly. The paper first studies the dynamic modelling and the motion control issues of the DPDC. A closed-loop controller using the partial feedback linearization technique is then designed for the tracking control of the parallel pendulums to guarantee accurate motion of the cart. Extensive simulation results verify the proposed model and the efficiency of the motion control strategy.
Evidence-Based Instruction Is Not Enough
Authors: Konrad Moira , Helf Shawnna , Joseph Laurice M.
Published: August 2011

Even evidence-based instructional methods may not be sufficient for closing achievement gaps. If teachers are not maximizing instructional time, achievement gaps are likely to widen over time; therefore, instruction need not only be effective but efficient as well. The purposes of this article are to (a) provide practitioners with a broad definition of instructional efficiency and (b) describe several considerations for increasing efficiency in the classroom. Suggestions are made for planning, delivering, and evaluating instruction.
Deviant Youth Groups in 30 Countries
Authors: Gatti Uberto , Haymoz Sandrine , Schadee Hans M. A.
Published: August 2011

In this study, the authors explored the link between deviant youth group (DYG) membership and antisocial behavior through a large student survey conducted by means of the same questionnaire in 62 cities in 30 countries. The sample ( N = 40,678) was made up of 7th-, 8th-, and 9th-grade students, both boys and girls, attending different types of schools. The definition of DYG that the authors used was the one drawn up by the Eurogang network: “Any durable, street-oriented youth group whose own identity includes involvement in illegal activity.” About 4.4% of youths were considered as DYG members according to this definition, with prevalence rates differing markedly among different countries, from less than 1% to more than 16%. In general, DYG membership implied a higher prevalence of delinquency, violence, and alcohol and drug use. Differences between DYG members and nonmembers were greater with regard to more serious antisocial behavior. Although the prevalence of DYG membership varies in different countries, the association between DYG membership and antisocial behavior is quite similar in the different national contexts.
Alliances, Conflicts, and Contradictions in Montreal’s Street Gang Landscape
Authors: Descormiers Karine , Morselli Carlo
Published: August 2011

This study proposes an analytical framework for examining the network of street gangs in Montreal. The objectives are twofold. One aim is to describe the core features of Montreal gangs. The second aim is to examine the structure of social relations between these gangs. These analyses allow us to assess whether the city’s gang landscape is structured around popularized rivalries between the Crips and the Bloods. Data for this research were gathered during focus group interviews involving 20 youth gang members residing in the Centre jeunesse de Montreal–Institut universitaire, the city’s main youth correctional institution. These gang members identified a total of 35 active gangs in Montreal. The network does reveal a relational setting that supports the popular Crips versus Bloods rivalry, with intercoalition conflicts and intracoalition alliances accounting for the vast majority of intergang relations. However, the study also revealed some important exceptions to this popular outlook. Such exceptions must be taken into consideration in order to arrive at a more complete and nuanced understanding of Montreal’s street gang landscape. The authors suspect that the conflicts and contradictions that emerge in the Montreal scene are also relevant for other major North American cities.
Leader Cultural Intelligence in Context
Authors: Groves Kevin S. , Feyerherm Ann E.
Published: August 2011

Despite clear calls from industry to better understand cross-cultural leadership competencies, academic research on leader cultural intelligence (CQ) is remarkably sparse. To date, very few empirical studies have examined the unique contribution of leader CQ to leadership performance outcomes beyond the effects of competing leadership competencies. Data from 99 culturally diverse organizational leaders and 321 of their followers demonstrated that leader CQ predicted follower perceptions of leader performance and team performance in contexts where work teams were characterized by significant ethnic and nationality diversity. Furthermore, leader CQ predicted follower perceptions of leader performance and team performance on culturally diverse work teams beyond the effects of leader emotional intelligence and other leadership competencies. Implications for cultural intelligence theory, future research directions, and management practice are discussed.
Conflict Management for Government and Businesses to Share Effective Practices in China
Authors: Wong Alfred , Wei Lu , Tjosvold Dean
Published: August 2011

Governments and businesses are increasingly forming partnerships to further common purposes and learn from each other. However, they are apt to have considerable conflict as they have diverse interests and perspectives. Findings from 119 pairs of government officials and business managers support the theorizing that the cooperative approach to conflict, but not the competitive approach, contributes to successful government–business partnerships in China. Specifically, structural equation analyses support the model that the cooperative approach to conflict fosters interorganizational trust and the sharing of effective practices that in turn result in effective partnerships and industry development.
Practising engagement: Infusing communication with empathy and compassion in medical students’ clinical encounters
Authors: Warmington Sally
Published: August 2011

Patients commonly experience some physicians’ ways of interacting with them as detached and indicating a lack of concern for their welfare. This is likely to add to the distress experienced by a person seeking healing, as well as interfering with the exchange of information required for good medical care. Despite contemporary medical schools’ focus on clinical communication, and on training for ‘patient-centred’ practice, problems with the relations between doctors and patients are still widely acknowledged. The importance of demonstrating empathy, compassion and caring has been highlighted in the literature. In this article I draw on a clinical narrative to elucidate my interpretation of engagement, which entails practices of attentiveness, respectful dialogue and commitment. I propose that practising engagement may help medical students and doctors to infuse their clinical encounters with empathy and compassion, with the aim of providing care that is experienced as being more humane. This practice has the potential to contribute to innovative pedagogical approaches to clinical communication.
Estimation of Low-Level Radiation Dose from Some Building Materials Using Gamma Spectroscopy
Authors: Gupta Monika , Chauhan R.P.
Published: August 2011

The study of the radiation hazards from building materials is of interest in many countries. So, it becomes necessary to study the natural radioactivity in different materials to assess the dose for the population to know the health risks and to have a baseline for future changes in the environmental radioactivity due to human activities. The present study assesses the level of terrestrial gamma radiation and associated dose rates from the naturally occurring radionuclides 226Ra, 232Th and 40K in building materials collected from the Northeastern part of Haryana state of India using gamma ray spectrometry. Places are in the vicinity of Shivalik range of Himalayas. The activity of radium, thorium and potassium in various soil samples varied from 27 ± 1.2 to 51 ± 1.5 Bq/kg, 42 ± 1.5 to77 ± 2.3 Bq/kg and 277 ± 3.2 to 584 ± 6.1 Bq/kg and in various building materials varied from 14 ± 0.4 to 87 ± 7.7 Bq/kg, 6 ± 0.3 to 24 ± 1.1 Bq/kg and 26 ± 0.4 to 245 ± 3.7 Bq/kg, respectively. The values of absorbed annual effective doses (indoors and outdoors) were found to vary in various soil samples from 50 to 95 nGyh−1, 0.24 to 0.46 mSv and 0.06 to 0.12 mSv and in various building materials found to vary from 11 to 57 nGyh−1, 0.05 to 0.28 mSv and 0.01 to 0.07 mSv, respectively.
Online multimedia news in print media: A lack of vision in Slovenia
Authors: Vobič Igor
Published: August 2011

Using the case of two Slovenian print media as an example, this article examines how online multimedia news has been adopted, what role different newsroom organization models play in online multimedia news production, and what multimedia news formats have emerged on news websites of Slovenian print media organizations. In the last decade, different multimedia news content has been emerging rapidly within news websites of print media organizations with online production organized differently and multimedia news formatted distinctly. A review of scholarly debates and research in media and journalism studies reveals that the particular institutionally structured features of online news production, and the technical and organizational attributes which influence what gets represented in the medium and the manner in which it is done have not yet emerged. Furthermore, on the basis of news format analysis, participant observation, and problem-centered interviews, the article concludes that there is a lack of vision in furthering the evolution of online production organization and news formats in Slovenian print media arena, which signals the present marginal significance of online multimedia news.
The Press Union at the end of empire: Anglo-Australian perspectives, 1946–65
Authors: Cryle Denis
Published: August 2011

This article provides an overview of the post-war contexts in which the Empire Press Union (EPU) became the Commonwealth Press Union and offers an assessment of its changing leadership and regular five-yearly conferences over the period 1946 to 1965. In particular, it examines the extent to which its pre-war hierarchies and British influence were sustained or modified with the decline of empire and the advent of international bodies such as the United Nations. It assesses the impact over two critical decades of the politics of decolonization and the changing roles of both the Australian and British sections of the organization within the new information order. How did these post-war changes and the power blocks which emerged affect the Press Union and its member countries and shape the ethos of the newly named Commonwealth Press Union thereafter? The article argues that the issues of press freedom and censorship are central to understanding the changing character of the organization and its emerging international profile by the mid-1960s. At a time when the United Nations proclaimed freedom of information to be a fundamental human right, the Press Union’s own libertarian rhetoric in defence of a free media sought to acknowledge the realities of decolonization, while retaining pre-war cultural values.
Modelling and analysis of mechanical behaviour of carbon nanotube reinforced composites
Authors: Joshi U A , Sharma S C , Harsha S P
Published: August 2011

In this paper, the mechanical properties of carbon nanotube reinforced composites are evaluated based on the continuum mechanics approach using a hexagonal representative volume element (RVE) under lateral loading conditions. It is paramount in such analyses that the correct boundary conditions be imposed, such that they simulate the actual deformation within the composite. Numerical equations are used to evaluate the mechanical properties from numerical solutions for the hexagonal RVEs under the lateral load case. An extended rule of mixtures is applied to evaluate the effective axial Young’s modulus, for validation of the proposed model. For the RVEs having long carbon nanotube, better values of stiffness in axial direction are found as compared to stiffness in the lateral direction. Also, the comparative evaluation of both square and hexagonal RVEs with short carbon nanotubes is presented here. The short carbon nanotube is not found to be as effective as long carbon nanotube in reinforcing the composite.
Experimental investigations to study the effect of carbon nanotubes reinforced in cement-based matrix composite beams
Authors: Hunashyal A M , Sundeep G V , Quadri S S , Banapurmath N R
Published: August 2011

The present paper investigates the behaviour of cement beams reinforced with multi-walled carbon nanotubes (MWCNTs). The addition of MWCNTs was varied at 0.25, 0.5, 0.65, 0.75, 0.85, and 1 per cent by weight of cement. Dispersion of MWCNTs was carried out using ultrasonic energy. Composite beams were tested under flexure in order to evaluate their mechanical properties such as flexural strength and load–deflection criteria. These results were then compared with those from plain cement control beams. The present work also investigated the optimum percentage of MWCNTs that gives the best results in terms of both enhanced properties and economy. Scanning electron microscopy was conducted to examine the bond between the MWCNTs and the cement matrix.
What is the relationship between diabetes and depression? A qualitative meta-synthesis of patient experience of co-morbidity
Authors: Gask Linda , Macdonald Wendy , Bower Peter
Published: August 2011

Aims: To develop an explanatory framework concerning patient experience of diabetes and depression and the relationship between these disorders; to better understand how interventions and health services should be delivered for this group of patients.

Methods: The study used meta-synthesis. Published qualitative studies were identified using a structured search, and themes synthesized across studies to develop a new explanatory framework.

Results: Searches of three databases identified 5506 papers, and 22 were included. Diagnosis of diabetes and the impact of symptoms on functioning were associated with varied psychological reactions, not all of which are negative, and the concept of ‘depression’ only captures aspects of the experience. Similarly, the relationship between diabetes and relationships with professionals and family were variable, with relationships serving as both a buffer of the effects of diabetes and potentially as a cause of further difficulties for patients. Depression and other psychological states were significant barriers to effective coping. Definition of ‘self’ emerged as a key potential moderator of the relationship between depression and diabetes.

Conclusions: The variability in psychological reactions to diabetes suggested three key clinical implications, reflecting increasing levels of complexity for practitioners.
Clinical complexity and the effectiveness of an intervention for depressed diabetes patients
Authors: Piette John D , Valenstein Marcia , Himle Joseph , Duffy Sonia , Torres Trissa , Vogel Mark , Richardson Caroline
Published: August 2011

Objectives: In a trial completed in 2010, US patients with diabetes and depression were randomized to usual care or telephone cognitive behavioural therapy that emphasized physical activity. Twelve-month intervention effects were observed for blood pressure, depression, and pedometer-measured step-counts. This study examined variation in intervention effects across patient subgroups defined by a measure of clinical complexity.

Methods: Three groups of patients were identified at baseline using the Vector Model of Complexity that recognizes socioeconomic, biological, behavioural, and other determinants of treatment response. Complexity-by-intervention interactions were examined using regression models.

Results: Intervention effects for blood pressure, depression, and step-counts differed across complexity levels (each p < 0.01). Effects on Beck Depression Inventory scores were greater in the low-complexity group (−8.8) than in the medium- (−3.2) or high-complexity groups (−2.7). Physical activity effects also were greatest in the low-complexity group (increase of 1498 steps per day). In contrast, systolic blood pressure effects were greater among intervention patients with high complexity (−8.5 mmHg).

Conclusions: This intervention had varying impacts on physical and mental health depending on patients' clinical complexity. Physical activity and depressive symptom gains may be more likely among less complex patients, although more complex patients may achieve cardiovascular benefits through decreased blood pressures.
Functioning and disability in multiple sclerosis from the patient perspective
Authors: Coenen Michaela , Basedow-Rajwich Birgit , König Nicolaus , Kesselring Jürg , Cieza Alarcos
Published: August 2011

Multiple sclerosis (MS) has a great impact on functioning and disability. The perspective of those who experience the health problem has to be taken into account to obtain an in-depth understanding of functioning and disability. The objective was to describe the areas of functioning and disability and relevant contextual factors in MS from the patient perspective. A qualitative study using focus group methodology was performed. The sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. The meaning condensation procedure was used for data analysis. Identified concepts were linked to International Classification of Functioning, Disability and Health (ICF) categories according to established linking rules. Six focus groups with a total of 27 participants were performed. In total, 1327 concepts were identified and linked to 106 ICF categories of the ICF components Body Functions, Activities and Participation and Environmental Factors. This qualitative study reports on the impact of MS on functioning and disability from the patient perspective. The participants in this study provided information about all physical aspects and areas of daily life affected by the disease, as well as the environmental factors influencing their lives.
Water-skiing biomechanics: a study of intermediate skiers
Authors: Runciman R J
Published: August 2011

This research project was initiated to examine the water-skiing biomechanics of the intermediate skier. The hypothesis was that equipment used by the skier would have a significant effect on the loads that they encountered during skiing and on their athletic performance.

Nine intermediate water skiers were instrumented and performed a series of standard water-skiing manoeuvres. Skiing participants, conditions, and equipment used for the study were chosen where possible to represent those typically encountered by the average intermediate skier.

The results from the study showed that water-start rope loads of up to 2.45 times body weight were sometimes encountered and that average running rope loads of 0.35–0.41 times body weight were observed. The choice of equipment was found to make a statistically significant impact on the rope loads both for water starting and while skiing. The rope loads for starting and skiing were significantly lower when using a large square-tailed water ski that was included in this study.

The intermediate skiers in this study achieved no statistically significant performance advantage when using competitive-style tapered water skis when compared with the square-tailed and larger water ski included in the study.
The aerodynamic drag and axial rotation of an arrow
Authors: Park J L
Published: August 2011

The down-range behaviour of arrows has a strong influence on an archer’s ability to obtain good scores. A major input to that performance is the arrow’s aerodynamic drag. A wide variety of arrow types are available, and within each type there are a number of sizes and combinations of the various component parts of the arrow. Consequently the drag can be expected to vary significantly from arrow to arrow. In addition, the arrow’s fletching is usually set at an angle to the shaft’s longitudinal axis, causing the arrow to spin in order to minimize inaccuracies due to, for example, arrow straightness variation, and this will also affect the down-range behaviour. This paper provides a means of calculating the arrow’s drag and axial spin, and uses that to compare predicted down-range velocity with that measured for three quite different, but representative arrows. The method is compared with methods developed by Rheingans and Liston.
ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters
Authors: Huang Royston-Luke , Teo Ziqiang , Chong Han Chung , Zhu Pengcheng , Tan Ming Jie , Tan Chek Kun , Lam Chee Ren Ivan , Sng Ming Keat , Leong David Tai Wei , Tan Suet Mien , Kersten Sander , Ding Jeak Ling , Li Hoi Yeung , Tan Nguan Soon
Published: August 2011

Vascular disruption induced by interactions between tumor-secreted permeability factors and adhesive proteins on endothelial cells facilitates metastasis. The role of tumor-secreted C-terminal fibrinogen-like domain of angiopoietin-like 4 (cANGPTL4) in vascular leakiness and metastasis is controversial because of the lack of understanding of how cANGPTL4 modulates vascular integrity. Here, we show that cANGPTL4 instigated the disruption of endothelial continuity by directly interacting with 3 novel binding partners, integrin α5β1, VE-cadherin, and claudin-5, in a temporally sequential manner, thus facilitating metastasis. We showed that cANGPTL4 binds and activates integrin α5β1-mediated Rac1/PAK signaling to weaken cell–cell contacts. cANGPTL4 subsequently associated with and declustered VE-cadherin and claudin-5, leading to endothelial disruption. Interfering with the formation of these cANGPTL4 complexes delayed vascular disruption. In vivo vascular permeability and metastatic assays performed using ANGPTL4-knockout and wild-type mice injected with either control or ANGPTL4-knockdown tumors confirmed that cANGPTL4 induced vascular leakiness and facilitated lung metastasis in mice. Thus, our findings elucidate how cANGPTL4 induces endothelial disruption. Our findings have direct implications for targeting cANGPTL4 to treat cancer and other vascular pathologies.
CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity
Authors: Sakakibara Keiichi , Saito Naoya , Sato Takuji , Suzuki Atsushi , Hasegawa Yoko , Friedman Jonathan M. , Kufe Donald W. , VonHoff Daniel D. , Iwami Tadahiko , Kawabe Takumi
Published: August 2011

CRM1 plays an important role in the nuclear export of cargo proteins bearing nuclear exporting signal sequences. Leptomycin B (LMB), a well-known CRM1 inhibitor, possesses strong antitumor properties. However, its toxicity prevents it from being clinically useful. In this study, we demonstrate that a novel compound, CBS9106, inhibits CRM1-dependent nuclear export, causing arrest of the cell cycle and inducing apoptosis in a time- and dose-dependent manner for a broad spectrum of cancer cells, including multiple myeloma cells. CBS9106 reduces CRM1 protein levels significantly without affecting CRM1 mRNA expression. This effect could be reversed by adding bortezomib or LMB. Moreover, CBS9106-biotin allows capture of CRM1 protein by streptavidin beads in a competitive manner with LMB and vice versa. Mass spectrometric analysis shows that CBS9106 reacts with a synthetic CRM1 peptide that contains Cys528 but not with a Cys528 mutant peptide. Oral administration of CBS9106 significantly suppresses tumor growth and prolongs survival in mice bearing tumor xenograft without a significant loss in body weight. A reduced level of CRM1 protein is also observed in tumor xenografts isolated from mice treated with CBS9106. Taken together, these results indicate that CBS9106 is a novel reversible CRM1 inhibitor and a promising clinical candidate.
Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia: a nationwide study
Authors: Nielsen Sune F. , Bojesen Stig E. , Birgens Henrik S. , Nordestgaard Børge G.
Published: August 2011

Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1.2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain cancer, and NHL, similar to patients with childhood leukemia.
Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice
Authors: Steinbicker Andrea U. , Bartnikas Thomas B. , Lohmeyer Lisa K. , Leyton Patricio , Mayeur Claire , Kao Sonya M. , Pappas Alexandra E. , Peterson Randall T. , Bloch Donald B. , Yu Paul B. , Fleming Mark D. , Bloch Kenneth D.
Published: August 2011

Bone morphogenetic protein (BMP) signaling induces hepatic expression of the peptide hormone hepcidin. Hepcidin reduces serum iron levels by promoting degradation of the iron exporter ferroportin. A relative deficiency of hepcidin underlies the pathophysiology of many of the genetically distinct iron overload disorders, collectively termed hereditary hemochromatosis. Conversely, chronic inflammatory conditions and neoplastic diseases can induce high hepcidin levels, leading to impaired mobilization of iron stores and the anemia of chronic disease. Two BMP type I receptors, Alk2 (Acvr1) and Alk3 (Bmpr1a), are expressed in murine hepatocytes. We report that liver-specific deletion of either Alk2 or Alk3 causes iron overload in mice. The iron overload phenotype was more marked in Alk3- than in Alk2-deficient mice, and Alk3 deficiency was associated with a nearly complete ablation of basal BMP signaling and hepcidin expression. Both Alk2 and Alk3 were required for induction of hepcidin gene expression by BMP2 in cultured hepatocytes or by iron challenge in vivo. These observations demonstrate that one type I BMP receptor, Alk3, is critically responsible for basal hepcidin expression, whereas 2 type I BMP receptors, Alk2 and Alk3, are required for regulation of hepcidin gene expression in response to iron and BMP signaling.
12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation
Authors: Singh Nikhlesh K. , Kundumani-Sridharan Venkatesh , Rao Gadiparthi N.
Published: August 2011

To understand the mechanisms by which 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) activates Rac1 in the induction of angiogenesis, we studied the role of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase and αPix. 15(S)-HETE stimulated Rac1 in a sustained manner in human dermal microvascular endothelial cells (HDMVECs). Simvastatin, a potent inhibitor of HMG-CoA reductase, suppressed 15(S)-HETE–induced Rac1 activation in HDMVECs affecting their migration and tube formation. 15(S)-HETE by inducing HMG-CoA reductase expression caused increased farnesylation and membrane translocation of Rac1 where it became activated by Src-dependent αPix stimulation. Mevalonate rescued 15(S)-HETE–induced Rac1 farnesylation and membrane translocation in HDMVECs and the migration and tube formation of these cells from inhibition by simvastatin. Down-regulation of αPix inhibited 15(S)-HETE–induced HDMVEC migration and tube formation. Hind-limb ischemia induced Rac1 farnesylation and activation leading to increased angiogenesis and these effects were blocked by simvastatin and rescued by mevalonate in WT mice. In contrast, hind-limb ischemia failed to induce Rac1 farnesylation and activation as well as angiogenic response in 12/15-Lox−/− mice. Activation of Src and αPix were also compromised at least to some extent in 12/15-Lox−/− mice compared with WT mice in response to hind-limb ischemia. Together, these findings demonstrate for the first time that HMG-CoA reductase plays a determinant role in 12/15-Lox–induced angiogenesis.
Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand
Authors: Jain Ashish , Kovacs Joseph A. , Nelson David L. , Migueles Stephen A. , Pittaluga Stefania , Fanslow William , Fan Xiying , Wong Duane W. , Massey Justin , Hornung Ronald , Brown Margaret R. , Spinner Jacob J. , Liu Shuying , Davey Victoria , Hill Harry A. , Ochs Hans , Fleisher Thomas A.
Published: August 2011

X-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.03 mg/kg for 22 weeks, and after a 12-week drug-free interval, the dose was increased to 0.05 mg/kg for an additional 22 weeks of treatment. Although specific antibody responses to T cell–dependent antigens was lacking, administration of rCD40 resulted in acquisition of the capacity to mount cutaneous delayed type hypersensitivity reactions that disappeared during the drug-free interval as well as the postbiologic follow-up period. With rCD40L treatment, patient T cells developed a new capacity to respond to T-cell mitogens with synthesis of IFN-γ and TNF-α. Intracellular cytokine staining studies showed that both CD4+ and CD8+ T cells participated in this response. Finally, CD40L therapy was associated with changes in lymph node size and architecture based on comparison of biopsies taken before and after therapy. This clinical study showed that rCD40L is capable of improving T cell–immune function in patients with XHM.
EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma*
Authors: Kempf Werner , Pfaltz Katrin , Vermeer Maarten H. , Cozzio Antonio , Ortiz-Romero Pablo L. , Bagot Martine , Olsen Elise , Kim Youn H. , Dummer Reinhard , Pimpinelli Nicola , Whittaker Sean , Hodak Emmilia , Cerroni Lorenzo , Berti Emilio , Horwitz Steve , Prince H. Miles , Guitart Joan , Estrach Teresa , Sanches José A. , Duvic Madeleine , Ranki Annamari , Dreno Brigitte , Ostheeren-Michaelis Sonja , Knobler Robert , Wood Gary , Willemze Rein
Published: August 2011

Primary cutaneous CD30+ lymphoproliferative disorders (CD30+ LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30+ LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30+ LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30+ LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30+ LPDs.
Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)
Authors: Palumbo Antonio , Bringhen Sara , Ludwig Heinz , Dimopoulos Meletios A. , Bladé Joan , Mateos Maria V. , Rosiñol Laura , Boccadoro Mario , Cavo Michele , Lokhorst Henk , Zweegman Sonja , Terpos Evangelos , Davies Faith , Driessen Christoph , Gimsing Peter , Gramatzki Martin , Hàjek Roman , Johnsen Hans E. , Leal Da Costa Fernando , Sezer Orhan , Spencer Andrew , Beksac Meral , Morgan Gareth , Einsele Hermann , San Miguel Jesus F. , Sonneveld Pieter
Published: August 2011

Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes.
Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects
Authors: Jeong Hyo-Soon , Lee Seung Hoon , Yun Hye-Young , Baek Kwang Jin , Kwon Nyoun Soo , Park Kyoung-Chan , Kim Dong-Seok
Published: August 2011

Background

Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.

Methods

Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.

Results

SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.

Conclusions

Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.
Neighborhood disparities in stroke and myocardial infarction mortality: a GIS and spatial scan statistics approach
Authors: Pedigo Ashley , Aldrich Tim , Odoi Agricola
Published: August 2011

Background

Stroke and myocardial infarction (MI) are serious public health burdens in the US. These burdens vary by geographic location with the highest mortality risks reported in the southeastern US. While these disparities have been investigated at state and county levels, little is known regarding disparities in risk at lower levels of geography, such as neighborhoods. Therefore, the objective of this study was to investigate spatial patterns of stroke and MI mortality risks in the East Tennessee Appalachian Region so as to identify neighborhoods with the highest risks.

Methods

Stroke and MI mortality data for the period 1999-2007, obtained free of charge upon request from the Tennessee Department of Health, were aggregated to the census tract (neighborhood) level. Mortality risks were age-standardized by the direct method. To adjust for spatial autocorrelation, population heterogeneity, and variance instability, standardized risks were smoothed using Spatial Empirical Bayesian technique. Spatial clusters of high risks were identified using spatial scan statistics, with a discrete Poisson model adjusted for age and using a 5% scanning window. Significance testing was performed using 999 Monte Carlo permutations. Logistic models were used to investigate neighborhood level socioeconomic and demographic predictors of the identified spatial clusters.

Results

There were 3,824 stroke deaths and 5,018 MI deaths. Neighborhoods with significantly high mortality risks were identified. Annual stroke mortality risks ranged from 0 to 182 per 100,000 population (median: 55.6), while annual MI mortality risks ranged from 0 to 243 per 100,000 population (median: 65.5). Stroke and MI mortality risks exceeded the state risks of 67.5 and 85.5 in 28% and 32% of the neighborhoods, respectively. Six and ten significant (p < 0.001) spatial clusters of high risk of stroke and MI mortality were identified, respectively. Neighborhoods belonging to high risk clusters of stroke and MI mortality tended to have high proportions of the population with low education attainment.

Conclusions

These methods for identifying disparities in mortality risks across neighborhoods are useful for identifying high risk communities and for guiding population health programs aimed at addressing health disparities and improving population health.
Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma
Authors: Shueng Pei-Wei , Shen Bing-Jie , Wu Le-Jung , Liao Li-Jen , Hsiao Chi-Huang , Lin Yu-Chin , Cheng Po-Wen , Lo Wu-Chia , Jen Yee-Min , Hsieh Chen-Hsi
Published: August 2011

Background

To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC).

Methods

Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction.

Results

After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively.

Conclusion

HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings.
Feedback, Self-Esteem, and Performance in Organizations
Authors: Kuhnen Camelia M. , Tymula Agnieszka
Published: August 2011

We examine whether private feedback about relative performance can mitigate moral hazard in competitive environments by modifying the agents' self-esteem. In our experimental setting, people work harder and expect to rank better when told that they may learn their ranking, relative to cases when feedback will not be provided. Individuals who ranked better than expected decrease output but expect a better rank in the future, whereas those who ranked worse than expected increase output but lower their future rank expectations. Feedback helps create a ratcheting effect in productivity, mainly because of the fight for dominance at the top of the rank hierarchy. Our findings suggest that organizations can improve employee productivity by changing the likelihood of feedback, the reference group used to calculate relative performance, and the informativeness of the feedback message.

This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
The Party's Over: The Role of Earnings Guidance in Resolving Sentiment-Driven Overvaluation
Authors: Seybert Nicholas , Yang Holly I.
Published: August 2011

This paper shows that an important link between investor sentiment and firm overvaluation is optimistic earnings expectations, and that management earnings guidance helps resolve sentiment-driven overvaluation. Using previously identified firm characteristics, we find that most of the negative returns to uncertain firms in months following high-sentiment periods fall within the three-day window around the issuance of management earnings guidance. Comparisons of guidance months to nonguidance months show that guidance issuance affects the magnitude and not just the daily distribution of negative returns. There is also some evidence of negative returns around earnings announcements for firms that previously issued guidance, suggesting that guidance does not entirely correct optimistic earnings expectations. To provide additional insight into the strength of the guidance effect, we show that the market reacts more strongly to surprises, particularly negative surprises, following high-sentiment periods. Finally, firms with higher transient institutional ownership are less likely to guide, and their guidance is less likely to contain bad news following high-sentiment periods, indicating that managers with a short-term focus are hesitant to correct optimistic market expectations.

This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Skill, Luck, and the Multiproduct Firm: Evidence from Hedge Funds
Authors: de Figueiredo Rui J. P. , Rawley Evan
Published: August 2011

We formalize the idea that when managers require external investment to expand, higher-skilled firms will be more likely to diversify in equilibrium, even though managers can exploit asymmetric information about their ability to raise capital from investors. We exploit the timing of new fund launches in the hedge fund industry to distinguish between agency and capability effects in firm product diversification decisions, using a large survivor-bias-free panel data set on the hedge fund industry from 1994 to 2006. Empirically we show that diversifying firms' excess returns are high relative to those of other firms prior to diversification and fall within firm following diversification, but are six basis points higher per month per unit of risk ex post compared to a matched sample of focused firms. The evidence suggests that managers exploit asymmetric information about their own ability to time diversification decisions; yet, the discipline of markets ensures that better firms diversify, on average. The results provide large-sample empirical evidence that agency effects and firm capabilities jointly influence diversification decisions.

This paper was accepted by Bruno Cassiman, business strategy.