bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Concrete Pressure Vessels in the Framework of Continuum Damage Mechanics
Authors: Ganjiani M. , Naghdabadi R. , Asghari M.
Published: October 2011

In this article, a constitutive model in the framework of continuum damage mechanics is proposed to simulate the elastic behavior of concrete in tension and compression states. We assume two parts for Gibbs potential energy function: elastic and damage parts. In order to obtain the elastic-damage constitutive relation with the internal variables, two damage thermodynamic release rates in tension and compression derived from the elastic part of Gibbs potential energy are introduced. Also, two anisotropic damage tensors (tension and compression) are defined which characterize the tensile and compressive behaviors of concrete. Furthermore, two different linear hardening rules for tension and compression states are adopted for characterizing the damage evolution. The spectral decomposition technique is used to resolve the stress tensor into tensile and compressive components. The accuracy and performance of the proposed model are validated by comparing the predicted results with different experimental data, such as monotonic uniaxial tension and compression tests, and monotonic biaxial compression test. As an application, an analytic closed-form solution for a concrete thick-walled cylinder is obtained. It is shown that two damages: tensile damage [Formula: see text] and shear damage [Formula: see text] propagate in the cylinder. These two damages introduce anisotropy in the elastic behavior of the concrete structure. The influence of these two damages is investigated on the stress field in the cylinder. It is found that effect of shear damage [Formula: see text] on radial and tangential stresses as well as the effect of tensile damage [Formula: see text] on radial stress are negligible, while the effect of tensile damage [Formula: see text] on the tangential stress in a concrete thick-walled cylinder is significant.
Simulation of Ductile Fracture of Slabs Subjected to Dynamic Loading Using Cohesive Elements
Authors: Nilsson K. , Lidström P.
Published: October 2011

Dynamic loading of elastic-plastic slabs is studied numerically using a finite element approach, where introduction of cohesive elements enables fracture. For the bulk material, J2-flow theory is chosen as constitutive model, whereas the behavior of the cohesive elements is described by an irreversible cohesive law. The fracture behavior is governed solely by the cohesive elements, which are incorporated in the original mesh after a certain deformation state is reached. It is found that cohesive elements that are introduced early in the simulation are able to sustain the shape of the slab, so that necking and specimen fracture may occur at a location that does not coincide with the position of the first developed cohesive zone. This is an important feature, especially in the case of multiple necking. The influence of introducing cohesive elements on the deformation behavior is studied by comparison of contour plots describing the time development of normalized strain rates. Numerical simulations where the insertion of cohesive elements is enabled are compared with corresponding results where the material model only consists of J2-flow theory. Differences in the simulated material response, such as delay in the onset of necking, indicate that depending on the aim of the study, introduction of cohesive elements will influence the observed results. In addition, the proportion of kinetic energy of the post-fracture fragment compared to the amount of input work as function of imposed loading velocity is studied along with the effect of changing specimen aspect ratio.
Systematic Lifecycle Design for Sustainable Product Development
Authors: Lu B. , Zhang J. , Xue D. , Gu P.
Published: October 2011

Sustainable product development (SPD) requires that product designs achieve minimal or zero environmental impacts, in addition to satisfying the traditional design criteria, such as product functionality, quality, features, costs, and time to market. Environmental evaluations must, therefore, be incorporated into the design stage. In this research, a product design process model is proposed that includes three design requirements, two design tasks, and three comprehensive assessment streams. The functional requirement is derived from the customers’ needs, reflecting the product's functional purpose; the environmental requirement reflects society's need for protecting natural resources and the environment; and, the economic requirement ensures the company's basic business goals. Accordingly, SPD aims to simultaneously carry out the two tasks of designing products’ physical and lifecycle structures. In the assessment phase of product design, three assessment streams, including lifecycle quality (LCQ) analysis, lifecycle assessment (LCA) and lifecycle cost (LCC), are conducted with respect to the functional, environmental, and economic evaluations. A process-based analysis concept is proposed for the analysis of LCQ, LCA, and LCC evaluations. A simplified LCA is used for the environmental evaluations. Detailed assessment techniques are also developed for effective design evaluations. A case study example is provided to illustrate the methods and models.
The Social Networking Arena
Authors: Clipson Timothy W. , Wilson S. Ann , DuFrene Debbie D.
Published: October 2011

Social networking via texting, Facebook, Twitter, and similar media is enormously popular with students, though it often leads to communication challenges along gender lines. Research supports the fact that men and women have divergent expectations for social networking and use it differently. Students can benefit from classroom experiences that raise their awareness of communication challenges associated with social networking and encourage them to assess their own areas for improvement.
Corporate Responsibility in Communication
Authors: Lehtimäki Hanna , Kujala Johanna , Heikkinen Anna
Published: October 2011

The paper examines how the tensions of corporate responsibility are articulated and reconciled in a controversial situation of a foreign investment. We conducted a conventionalist analysis on the company press releases in a case where a Finnish forest industry company invested in a pulp mill in South America. The findings show that the use of language in press releases mobilizes certain stakeholders while reassuring others, and that the argumentation used creates value-neutral communication, making it possible to pursue strategic goals despite competing values. For teaching, we provide insights on how to communicate in a conflict situation.
The Extended Parallel Process Model
Authors: Popova Lucy
Published: October 2011

This article examines constructs, propositions, and assumptions of the extended parallel process model (EPPM). Review of the EPPM literature reveals that its theoretical concepts are thoroughly developed, but the theory lacks consistency in operational definitions of some of its constructs. Out of the 12 propositions of the EPPM, a few have not been tested explicitly and not a single one received unequivocal empirical support. This article proposes alternative operationalization for some of the constructs and examines some assumptions of this theory, such as additive relationship between the constructs, the role of time and issue of thresholds, and disregard for the existing state of the audience. Finally, the role of the EPPM as a potential foundation for a general theory of negative emotional appeals is addressed.
Ecological Contexts in the Development of Coalitions for Youth Violence Prevention
Authors: Bess Kimberly D. , Speer Paul W. , Perkins Douglas D.
Published: October 2011

Community coalitions are a recognized strategy for addressing pressing public health problems. Despite the promise of coalitions as an effective prevention strategy, results linking coalition efforts to positive community outcomes are mixed. To date, research has primarily focused on determining organizational attributes related to successful internal coalition functioning. The authors’ research complements and adds to this literature by offering a network conceptualization of coalition formation in which coalition participation is studied within the broader context of local organizational networks both within and beyond a coalition. The authors examine participation in the first year of a youth violence prevention coalition exploring both differences between participating and nonparticipating organizations and levels of participation. Each network variable, reflecting prior collaboration and being viewed by other organizations as a local leader, approximately doubled the explained variance in coalition participation beyond the predictive power of all available organizational attributes combined. Results suggest that initial coalition participation emerged out of a preexisting network of interorganizational relations and provide an alternative perspective on coalition formation that goes beyond conceptual orientations that treat coalitions as bounded organizational entities that exist apart from the communities in which they are embedded.
Senior Customers' Service Encounter Preferences
Authors: Grougiou Vassiliki , Pettigrew Simone
Published: October 2011

Growing segment size and increasing affluence have resulted in a substantial increase in the purchasing power of the senior market. Seniors spend a higher proportion of their total expenditure on services relative to younger consumers, making them an important target market for many service providers. However, seniors' particular concern with the social aspects of service delivery has been recognized as an important managerial issue. To provide further insight into this issue, in-depth interviews and projective techniques were conducted with 60 Scottish seniors of diverse demographic profiles. The findings support previous research indicating that seniors may evaluate service encounters primarily according to the social benefits resulting from them. In the present study, the social benefits sought appeared to be largely determined by seniors' social identities, which were influenced by past experiences as customers and employees. A model of how seniors evaluate their service encounter interactions is suggested, and managerial implications and directions for further research are provided. In particular, the model emphasizes the need for service providers to appreciate the characteristics of frontline service staff that are conducive to satisfactory service encounters for seniors.
Using Social Network Analysis to Predict Early Collaboration Within Health Advocacy Coalitions
Authors: Honeycutt Todd C. , Strong Debra A.
Published: October 2011

Within coalitions of consumer advocates formed to advance health insurance coverage expansions, engaging in united advocacy activities soon after formation might be an important precursor to attaining coalition effectiveness in shaping policy. In this article, the authors apply social network analysis (SNA) to examine how organizational characteristics and interorganizational relationships related to early collaboration on advocacy activities within advocacy coalitions. All interorganizational relationships the authors assessed were significantly associated with early collaboration in advocacy activities, with communication most associated with the differences in collaboration observed across coalitions. Among organizational characteristics, having more resources—as measured by the number of recent policy maker contacts and being the organization that directly received the grant—were statistically significant. Their findings suggest that even organizations that have not worked together before can become engaged in collaborative activities at a relatively early stage. They also show that SNA techniques can usefully be applied to advocacy evaluations.
Pre-existing beliefs and expectations influence judgments of novel health information
Authors: Chang Dong-Seon , Kang O-Seok , Kim Hwa-Hyun , Kim Ho-Sun , Lee Hyejung , Park Hi-Joon , Kim Hackjin , Chae Younbyoung
Published: October 2011

The present study examined whether health information is judged differently depending on pre-existing beliefs and expectations. People’s initial beliefs and expectations were assessed by a questionnaire about acupuncture and a trustworthiness and preference rating task of doctors’ faces. Then, newspaper headlines about novel acupuncture treatment were shown and rated for their feasibility in a normal and framed condition. The judged feasibility of the newspaper headlines correlated strongly with initial beliefs about acupuncture in the normal condition, and with initial expectations towards a doctor’s face in the framed condition. Thus, as suggested by Bayes Theorem, pre-existing beliefs and expectations influence judgments of novel health information.
When punishment and philanthropy mix: Voluntary organizations and the governance of the domestic violence offender
Authors: Singh Rashmee
Published: October 2011

This article examines the administration of community based punishment in Toronto’s specialized domestic violence courts. Voluntary organizations play an integral role in the Ontario government’s strategy to manage domestic violence. Currently, an array of ‘mainstream’ and ‘ethno-specific’ community agencies operate as quasi-criminal justice organizations to rehabilitate and supervise court mandated offenders. Despite their categorization however, both types of organizations largely cater to the same demographics. The discussion explores the techniques of governance service providers deploy when counseling their clientele. The emergence of two differing regimes of power, one emphasizing care and the other discipline, along the mythological categories of the ‘mainstream’ and ‘ethno-specific’ illuminate the constitutive effects of organizational habits on the delivery of punishment.
The conditions of tolerance
Authors: Muldoon Ryan , Borgida Michael , Cuffaro Michael
Published: October 2011

The philosophical tradition of liberal political thought has come to see tolerance as a crucial element of a liberal political order. However, while much has been made of the value of toleration, little work has been done on individual-level motivations for tolerant behavior. In this article, we seek to develop an account of the rational motivations for toleration and of where the limits of toleration lie. We first present a very simple model of rational motivations for toleration. Key to this model is an application of David Ricardo’s model of trade to thinking about toleration. This model supports the claim that we always have reasons to be as tolerant as possible. We then explore why we do not always see tolerant attitudes in the actual world, and point to some potential preconditions for toleration that the initial model does not capture. Subsequently, we examine a more detailed model that allows us to investigate more carefully the conditions under which tolerant behavior can be rewarded. We conclude by arguing that a consideration of self-interested motivations for toleration is essential to the success of a robust theory of toleration for a diverse society, but that even this approach has its limitations.
Life is not a camping trip – on the desirability of Cohenite socialism
Authors: Ronzoni Miriam
Published: October 2011

In Why Not Socialism?, GA Cohen defines socialism as the combined application of two moral principles: the egalitarian principle and the principle of community. The desirability of a social order organized around these two principles is illustrated by the ‘camping trip’ example. After describing the fundamental features of the camping trip scenario at reasonable length, Cohen argues that the desirability of such a social model is nearly self-explanatory, concluding therefore that the most significant challenges to socialism lie in its feasibility. This article argues that the desirability of the camping trip model as an appropriate ideal for society is less obvious than Cohen acknowledges. To argue my point, I shall compare the camping trip with another social practice that is equally small sized and characterized by strong emotional ties among its members, but in which the conditions of what I shall call ‘goal-monism’ and discontinuity in time do not hold, namely, the family.
A Qualitative Mediation Study to Evaluate a School-Based Tobacco Prevention Program in India (Project MYTRI)
Authors: Bate S. Lewis , Stigler Melissa H. , Thompson Marilyn S. , MacKinnon David P. , Arora Monika , Perry Cheryl L. , Reddy K. Srinath
Published: October 2011

Causal mediating processes were examined using qualitative methods to evaluate a tobacco-use prevention program for adolescents in India, Project MYTRI (Mobilizing Youth for Tobacco-Related Initiatives in India). Interviews were conducted with Project MYTRI leaders and staff persons. The focus of the interviews was to learn about the program implementation and to characterize how Project MYTRI classroom sessions altered student-level psychosocial risk factors (mediators) to prevent or reduce tobacco use among students in intervention schools in Delhi and Chennai. From qualitative analysis, key mediating variables were identified (students’ tobacco knowledge, skills development, beliefs about tobacco, intentional beliefs, advocacy beliefs, and self-efficacy beliefs), a qualitative mediation path model was drawn, causal processes were described, and contextual influences (potential moderators) were explained. The qualitative findings complemented the results of statistical mediation analysis, yielding a detailed and contextualized description of how Project MYTRI affected students.
The Bizarre Request for Amputation
Authors: Barnes Rachel
Published: October 2011

Apotemnophilia is a condition where sufferers wish to be an amputee. Currently, belief in the medical profession is that it is part of the spectrum of body dysmorphic disorder and as such patients are denied surgical correction. This can lead sufferers to extreme lengths. Proponents seek to have the disorder reclassified to a body identity integrity disorder such as gender identity disorder. In this way treatment modalities could be reassessed.
Inflammation
Authors: Johnston Craig A.
Published: October 2011

Lifestyle interventions show considerable promise in improving levels of inflammation. This review discusses how these improvements in inflammation are consistent with a “small changes” approach.
Wind generation’s contribution to supporting peak electricity demand – meteorological insights
Authors: Brayshaw D J , Dent C , Zachary S
Published: October 2011

Wind generation’s contribution to meeting extreme peaks in electricity demand is a key concern for the integration of wind power. In Great Britain (GB), robustly assessing this contribution directly from power system data (i.e. metered wind-supply and electricity demand) is difficult as extreme peaks occur infrequently (by definition) and measurement records are both short and inhomogeneous.

Atmospheric circulation-typing combined with meteorological reanalysis data is proposed as a means to address some of these difficulties, motivated by a case study of the extreme peak demand events in January 2010. A preliminary investigation of the physical and statistical properties of these circulation types suggests that they can be used to identify the conditions that are most likely to be associated with extreme peak demand events.

Three broad cases are highlighted as requiring further investigation. The high-over-Britain anticyclone is found to be generally associated with very low winds but relatively moderate temperatures (and therefore moderate peak demands, somewhat in contrast to the classic low-wind cold snap that is sometimes apparent in the literature). In contrast, both longitudinally extended blocking over Scotland/Scandinavia and latitudinally extended troughs over western Europe appear to be more closely linked to the very cold GB temperatures (usually associated with extreme peak demands). In both of these latter situations, wind resource averaged across GB appears to be more moderate.
Autologous osteochondral graft for traumatic defects of finger joints
Authors: Wu W. C. , Fok M. W. M. , Fung K. Y. , Tam K. H.
Published: October 2011

Finger joint defects in 16 adults were treated with an autologous osteochondral graft from the base of the second metacarpal, the radial styloid, the base of the third metacarpal or the trapezoid and these patients were followed up from between 12 and 62 months. There was no donor site morbidity. One patient had resorption of the graft and developed pain. The joint was subsequently fused. The mean range of movement was 55.8% of the opposite normal joint. At follow up, 15 patients had no discomfort or mild discomfort. Three had mild narrowing of the joint space and two had slight joint subluxation. Only two patients with concomitant severe injury to the same limb had difficulty performing daily activities. Ten were open injuries and these had poorer outcomes. A hemicondylar defect of a finger joint can be treated using an osteochondral graft obtained from the same hand.
Conservative treatment of pediatric trigger thumb: follow-up for over 4 years
Authors: Jung H. J. , Lee J. S. , Song K. S. , Yang J. J.
Published: October 2011

We analyzed the outcomes of our conservative treatment for pediatric trigger thumb. Since March 2004, we have used conservative treatment for all patients with pediatric trigger thumb. We prospectively analyzed 30 patients in whom 35 thumbs were affected (10 right, 15 left, 5 bilateral). The mean age at diagnosis was 28 (11–50) months. The treatment consisted of passive exercises performed by the children’s mothers, 10–20 times daily. How reliably this was performed is unproven. Trigger thumb severity was graded as 0A (extension beyond 0°), 0B (extension to 0°), 1 (active extension with triggering), 2 (passive extension with triggering), and 3 (cannot extend either actively or passively i.e. locked). At diagnosis, six of the 35 thumbs (17%) were grade 1, 25 (71%) were grade 2, and four (11%) were grade 3. After a mean follow-up period of 63 (range, 49–73) months, 28 thumbs (80%) were grade 0A or 0B, 5 (14%) were grade 1 and 2 (6%) were grade 2. The bilateral cases and the patients who initially had grade 3 severity had significantly more unfavorable results than the other patients. This study suggests that conservative treatment for pediatric trigger thumb is a successful method, although cases that present with bilateral involvement or locking (grade 3) should be considered for early surgical release.
Health Measures and Diet in Mexican American Adolescents in Chicago
Authors: Kouba Joanne
Published: October 2011

Recent trends in health patterns place Mexican American (MA) youth at risk for future problems. The purpose of this study was to describe the prevalence of risk factors for chronic disease, characterize nutrient intake, and explore their relationships in MA adolescents. A total of 50 adolescent-parent pairs were recruited from a predominantly MA high school in Chicago. Student data included information on glucose, lipids, blood pressure, anthropometrics, and diet recalls. Family history and anthropometric measures were obtained from a parent. Prevalence of overweight (OW) and obesity were 18% and 26%, respectively. Body mass index was positively associated with systolic blood pressure, LDL, waist circumference, and parental weight status and inversely related to intake of calories, carbohydrate, folate, grains, and the healthy eating index. Prevalence of undesirable fasting glucose was 28%, undesirable total cholesterol was 33%, undesirable LDL was 22%, and undesirable HDL was 24.5%. The metabolic syndrome was more prevalent in men than women. All correlations noted are significant (P < .05).
Medical Audit of the Quality of Diabetes Care
Authors: Bener Abdulbari , Abdulmalik Mariam , Al-Kazaz Mohammed , Mohammed Abdul-Ghani , Sanya Rahima , Buhmaid Sara , Al-Harthy Munjid , Zirie Mahmoud
Published: October 2011

Objective: To assess the quality of diabetes care provided to patients attending primary care settings and hospitals in the State of Qatar. Design: Observational cohort study. Setting: The survey was carried out in primary health care centers and hospitals. Subjects and Methods: The study was conducted from January 2010 to August 2010 among diabetic patients attending primary health care centers and hospitals. Among the patients participating, 575 were from hospitals and 1103 from primary health care centers. Face-to-face interviews were conducted using a structured questionnaire including sociodemographic, clinical, and satisfaction score of the patients. Results: The mean age of the primary care diabetic patients was 46.1 ± 15.1 years and 44.5 ± 14.8 years for hospital patients ( P = .03). There was a significant difference observed in terms of age group, gender, marital status, occupation, and consanguinity of the diabetic patients in both medical settings ( P < .001). Overweight was less prevalent in primary care patients than in hospital diabetes mellitus patients (40.4% vs 46.4%). A significant variation was observed in the mean values of blood glucose (−0.76), HbA1C (−0.78), LDL (−0.01), albumin (−0.37), bilirubin (−0.76), and triglyceride (−0.01) in primary care patients compared to the mean values of the preceding year. Overall, complications were lower in primary care diabetic patients, and patients attending primary care were more satisfied with the diabetes care. Conclusion: The present study revealed that in general, primary health care provided a better quality of care to diabetic patients compared to that of hospitals. Also, primary care patients had a better satisfaction score towards diabetes care.
Implementation of a Diabetes Management Program for Patients in a Rural Primary Care Office
Authors: Daly Jeanette M. , Xu Yinghui , Levy Barcey T. , Bedell David A. , Marquardt Michael D. , Vonderhaar Kathleen M. , James Paul A.
Published: October 2011

Objective: A diabetes management program was implemented in a rural primary care office for those who did not choose to consult a multidisciplinary specialty care. The purposes of this study were to describe the current practices and health care provider management of patients with diabetes in a rural primary care office and determine differences between Hispanic and non-Hispanic persons concerning diabetes self-care behaviors, barriers to self-care, and their association with glycosylated hemoglobin level. Methods: A retrospective medical record review of diabetes-related medical information was completed. Results: Sixty-one (74%) of the 83 patients with diabetes completed the questionnaire and had the diabetes management program implemented (problem summary and clinical summary generated). Medical record review was completed for 83 (100%) subjects. Glycosylated hemoglobin was significantly higher for the younger group and women. Hispanic women and married persons had significantly higher glycosylated hemoglobin than did non-Hispanic and unmarried persons. Hispanic persons who were obese had significantly higher glycosylated hemoglobin. Self-care behaviors for managing diabetes were different by group. Non-Hispanic subjects reported taking their diabetes medications 99% of the time and Hispanic subjects 50% of the time. Discussion: It was feasible to implement a diabetes management program in a rural primary care setting, and its implementation highlighted the ethnic differences for Hispanics and non-Hispanics in diabetes self-care behavior, barriers to self-care, and family support for diabetes management. The implementation of the diabetes management program, though, was time-consuming and costly and was facilitated outside of the usual realm of practice.
AP-1 elements and TCL1 protein regulate expression of the gene encoding protein tyrosine phosphatase PTPROt in leukemia
Authors: Motiwala Tasneem , Zanesi Nicola , Datta Jharna , Roy Satavisha , Kutay Huban , Checovich Allyn M. , Kaou Mohamed , Zhong Yiming , Johnson Amy J. , Lucas David M. , Heerema Nyla A. , Hagan John , Mo Xiaokui , Jarjoura David , Byrd John C. , Croce Carlo M. , Jacob Samson T.
Published: October 2011

We previously demonstrated that the gene encoding PTPROt, the truncated form of protein tyrosine phosphatase receptor type O expressed predominantly in hematopoietic cells, is a candidate tumor suppressor and is down-regulated in chronic lymphocytic leukemia (CLL). Here, we show that PTPROt expression is significantly reduced in CD19+ spleen B cells from Eμ-T cell leukemia 1 (TCL1) transgenic mice relative to the wild-type mice. Strikingly, as much as a 60% decrease in PTPROt expression occurs at 7 weeks independently of promoter methylation. To elucidate the potential mechanism for this early suppression of PTPROt in these mice, we explored the role of activating protein-1 (AP-1) in its expression. We first demonstrate that AP-1 activation by 12-O-tetradecanoylphorbol-13-acetate induces PTPROt expression with concurrent recruitment of c-fos and c-jun to its promoter. The PTPROt promoter is also responsive to over- and underexpression of AP-1, confirming the role of AP-1 in PTPROt expression. Next, we demonstrate that TCL1 can repress the PTPROt promoter by altering c-fos expression and c-jun activation state. Finally, using primary CLL cells we have shown an inverse relationship between TCL1 and PTPROt expression. These findings further substantiate the role of TCL1 in PTPROt suppression and its importance in the pathogenesis of CLL.
Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice
Authors: Lilla Jennifer N. , Chen Ching-Cheng , Mukai Kaori , BenBarak Maya J. , Franco Christopher B. , Kalesnikoff Janet , Yu Mang , Tsai Mindy , Piliponsky Adrian M. , Galli Stephen J.
Published: October 2011

It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/6 mice in which Cre recombinase is expressed under the control of a segment of the carboxypeptidase A3 (Cpa3) promoter. C57BL/6-Cpa3-Cre; Mcl-1fl/fl mice are severely deficient in mast cells (92%-100% reduced in various tissues analyzed) and also have a marked deficiency in basophils (58%-78% reduced in the compartments analyzed), whereas the numbers of other hematopoietic cell populations exhibit little or no changes. Moreover, Cpa3-Cre; Mcl-1fl/fl mice exhibited marked reductions in the tissue swelling and leukocyte infiltration that are associated with both mast cell- and IgE-dependent passive cutaneous anaphylaxis (except at sites engrafted with in vitro–derived mast cells) and a basophil- and IgE-dependent model of chronic allergic inflammation, and do not develop IgE-dependent passive systemic anaphylaxis. Our findings support the conclusion that Mcl-1 is required for normal mast cell and basophil development/survival in vivo in mice, and also suggest that Cpa3-Cre; Mcl-1fl/fl mice may be useful in analyzing the roles of mast cells and basophils in health and disease.
Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia
Authors: Karp Judith E. , Vener Tatiana I. , Raponi Mitch , Ritchie Ellen K. , Smith B. Douglas , Gore Steven D. , Morris Lawrence E. , Feldman Eric J. , Greer Jacqueline M. , Malek Sami , Carraway Hetty E. , Ironside Valerie , Galkin Steven , Levis Mark J. , McDevitt Michael A. , Roboz Gail R. , Gocke Christopher D. , Derecho Carlo , Palma John , Wang Yixin , Kaufmann Scott H. , Wright John J. , Garret-Mayer Elizabeth
Published: October 2011

Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771.
The neonatal Fc receptor (FcRn) is not required for IVIg or anti-CD44 monoclonal antibody–mediated amelioration of murine immune thrombocytopenia
Authors: Crow Andrew R. , Suppa Sara J. , Chen Xi , Mott Patrick J. , Lazarus Alan H.
Published: October 2011

To definitively determine whether the neonatal Fc receptor (FcRn) is required for the acute amelioration of immune thrombocytopenia (ITP) by IVIg, we used FcRn-deficient mice in a murine ITP model. Mice injected with antiplatelet antibody in the presence or absence of IVIg displayed no difference in platelet-associated IgG between FcRn deficient versus C57BL/6 mice. FcRn-deficient mice treated with high-dose (2 g/kg) IVIg or a low–dose (2 mg/kg) of an IVIg-mimetic CD44 antibody were, however, protected from thrombocytopenia to an equivalent extent as wild-type mice. To verify and substantiate the results found with FcRn-deficient mice, we used β2-microglobulin–deficient mice (which do not express functional FcRn) and found that IVIg or CD44 antibody also protected them from thrombocytopenia. These data suggest that for both high-dose IVIg as well as low-dose CD44 antibody treatment in an acute ITP model, FcRn expression is neither necessary nor required.
Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection
Authors: Kok Wai Ling , Denney Laura , Benam Kambez , Cole Suzanne , Clelland Colin , McMichael Andrew J , Ho Ling-Pei
Published: October 2011

Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6ChiLy6G– inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (Jα18−/− mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology.
Serine phosphorylation of FcγRI cytoplasmic domain directs lipid raft localization and interaction with protein 4.1G
Authors: Gibson Andrew W , Li Xinrui , Wu Jianming , Baskin Julie G , Raman Chander , Edberg Jeffrey C , Kimberly Robert P
Published: October 2011

The high-affinity IgG receptor (CD64, FcγRI) has several special capacities, including the receptor-stimulated cleavage of the cell surface B cell-activating factor of the TNF superfamily (TNFSF13B). With the use of the yeast two-hybrid system, we and others have shown that FcγRI interacts with protein 4.1G (EPB41L2). Our mutational analyses identified two required 4.1G-interacting regions in the FcγRI CY and one FcγRI-interacting site in the C-terminus of protein 4.1G. Herein, we explore mechanism(s) that may regulate the interaction between protein 4.1G and FcγRI CY and influence FcγRI membrane mobility and function. We show that FcγRI CY interacts with protein 4.1G in vitro and that FcγRI coimmunoprecipitates protein 4.1G in freshly isolated human PBMC. With the use of immunostaining, we show that FcγRI colocalizes with protein 4.1G in unstimulated U937 cells, in which the FcγRI CY is constitutively serine-phosphorylated, but significant uncoupling occurs following FcγRI cross-linking, suggesting phosphoserine-regulated interaction. In vitro, protein 4.1G interacted preferentially with CK2-phosphorylated FcγRI CY, and compared with WT FcγRI, a nonphosphorylatable FcγRI mutant receptor was excluded from lipid rafts, suggesting a key role for protein 4.1G in targeting phosphorylated FcγRI to rafts. These data are consistent with a phosphoserine-dependent tethering role for protein 4.1G in maintaining FcγRI in lipid rafts and provide insight into the unique phosphoserine-based regulation of receptor signaling by FcγRI CY.
Access to Health Care for Undocumented Migrants: A Comparative Policy Analysis of England and the Netherlands
Authors: Grit Kor , den Otter Joost J. , Spreij Anneke
Published: October 2011

The presence of undocumented migrants is increasing in many Western countries despite wide-ranging attempts by governments to increase border security. Measures taken to control the influx of immigrants include policies that restrict access to publicly funded health care for undocumented migrants. These restrictions to health care access are controversial, and evidence suggests they do not always have the intended effect. This study provides a comparative analysis of institutional, actor-related, and contextual factors that have influenced health care policy development on undocumented migrants in England and the Netherlands. For undocumented migrants, England restricts its access to care at the point of service, while the Netherlands restricts through the payment system for services. The study includes an analysis of policy papers and semistructured, in-depth interviews with various actors in both countries. Findings confirm the influence of such contextual factors as immigration considerations and cost concerns on health care policy making in this area. However, these factors cannot explain the differences between the two countries. Previously enacted policies, especially the organization of the health care system, affected the kind of restrictions for undocumented migrants. Concerns about the side effects of generous treatment of undocumented migrants on other groups played a substantial role in formulating restrictive policies in both countries. Evidently, policy development and implementation is critically affected by institutional rules, which govern the degree of influence that doctors and professional medical associations have on the policy process.
The Legitimacy of Vaccine Critics: What Is Left After the Autism Hypothesis?
Authors: Kirkland Anna
Published: October 2011

The last dozen years have seen a massive transnational mobilization of the legal, political, and research communities in response to the worrisome hypothesis that vaccines could have a link to childhood autism and other developmental conditions. Vaccine critics, some already organized and some composed of newly galvanized parents, developed an alternate world of internally legitimating studies, blogs, conferences, publications, and spokespeople to affirm a connection. When the consensus turned against the autism hypothesis, these structures and a committed membership base unified all the organizations in resistance. This article examines the relationship between mobilization based on science and the trajectory of legitimacy vaccine criticism has taken. I argue that vaccine critics have run up against the limits of legitimate scientific argument and are now in the curious position of both doubling down on credibility-depleting stances and innovating new and possibly resonant formulations.
Why We Should Eliminate Personal Belief Exemptions to Vaccine Mandates
Authors: Lantos John D. , Jackson Mary Anne , Harrison Christopher J.
Published: October 2011

We argue that personal belief exemptions to the mandate for childhood immunizations should not be allowed. Parents who choose not to immunize their children put both their own children and other children at risk. Other children are at risk because unimmunized children go to school or day care when they are contagious but asymptomatic, exposing many more children to potentially dangerous infections. The risks to children from disease are much higher than the risks of vaccines. There are, of course, some bona fide reasons why children should not be immunized. Some children have known allergies or other medical contraindications to certain immunizations. Immunization refusals based on parental beliefs, however, do not fall into this category. In those cases, children are denied the protection of immunizations without any medical or scientific justification. By eliminating personal belief exemptions to those childhood vaccines associated with contagious diseases that have high rates of childhood mortality, we would better protect children and would more fairly spread the burdens of this important public health program.
Pre-steady-state kinetic analysis of the three Escherichia coli pseudouridine synthases TruB, TruA, and RluA reveals uniformly slow catalysis
Authors: Wright Jaden R. , Keffer-Wilkes Laura C. , Dobing Selina R. , Kothe Ute
Published: October 2011

Pseudouridine synthases catalyze formation of the most abundant modification of functional RNAs by site-specifically isomerizing uridines to pseudouridines. While the structure and substrate specificity of these enzymes have been studied in detail, the kinetic and the catalytic mechanism of pseudouridine synthases remain unknown. Here, the first pre-steady-state kinetic analysis of three Escherichia coli pseudouridine synthases is presented. A novel stopped-flow absorbance assay revealed that substrate tRNA binding by TruB takes place in two steps with an overall rate of 6 sec−1. In order to observe catalysis of pseudouridine formation directly, the traditional tritium release assay was adapted for the quench-flow technique, allowing, for the first time, observation of a single round of pseudouridine formation. Thereby, the single-round rate constant of pseudouridylation (kΨ) by TruB was determined to be 0.5 sec−1. This rate constant is similar to the kcat obtained under multiple-turnover conditions in steady-state experiments, indicating that catalysis is the rate-limiting step for TruB. In order to investigate if pseudouridine synthases are characterized by slow catalysis in general, the rapid kinetic quench-flow analysis was also performed with two other E. coli enzymes, RluA and TruA, which displayed rate constants of pseudouridine formation of 0.7 and 0.35 sec−1, respectively. Hence, uniformly slow catalysis might be a general feature of pseudouridine synthases that share a conserved catalytic domain and supposedly use the same catalytic mechanism.
Tailored Scoring Rules for Probabilities
Authors: Johnstone David J. , Jose Victor Richmond R. , Winkler Robert L.
Published: October 2011

When scoring rules were first widely used, they were developed as a way to measure the accuracy of probability forecasts ex post. Ex ante, proper scoring rules encourage honestly reported and sharper probabilities, both of which increase the forecaster's expected score. Most applications utilize standard off-the-shelf scoring rules. In the spirit of decision analysis, we develop proper scoring rules that are tailored to specific decision-making problems and to the utility functions of particular decision makers. We show how these rules, which are intended for situations where a decision maker consults an expert to assess a probability, not only encourage honest reporting, but also reward sharpness in a way that aligns the interests of the expert and the decision maker. We also illustrate the generation of tailored scoring rules in numerical form, which is useful when analytical expressions for the tailored rules cannot be obtained or are too complex to be helpful in practice. Finally, we show how these numerical scoring rules can be presented to the expert in graphical or tabular form and suggest that this could be desirable even for standard scoring rules.
Efficient Two-Dimensional Packing Algorithms for Mobile WiMAX
Authors: Lodi Andrea , Martello Silvano , Monaci Michele , Cicconetti Claudio , Lenzini Luciano , Mingozzi Enzo , Eklund Carl , Moilanen Jani
Published: October 2011

We present the result of research, developed within Nokia Siemens Networks, to solve the downlink sub-frame allocation problem in Mobile WiMAX (IEEE 802.16) technology in its full complexity, while simultaneously fulfilling real-life constraints on processing power and delay. We describe the IEEE 802.16 standard, and introduce two system models. A theoretical analysis of the two-dimensional packing problems originated by such models shows that they are both 𝒩𝒫-hard in the strong sense. From a practical point of view, the processing budget for scheduling in the base station was estimated to be 1 ms on a state-of-the-art PC. Thus, we introduce two highly efficient heuristics that were developed to handle the system practically. A thorough computational analysis of their optimization characteristics and a system-level evaluation in realistic scenarios proved that the algorithms offer significant capacity gain in Mobile WiMAX systems that translate to increased operator revenues.

This paper was accepted by Dimitris Bertsimas, optimization.
A Multiechelon Inventory Problem with Secondary Market Sales
Authors: Angelus Alexandar
Published: October 2011

We consider a finite-horizon, multiechelon inventory system in which the surplus of stock can be sold (i.e., disposed) in the secondary markets at each stage in the system. What are called nested echelon order-up-to policies are shown to be optimal for jointly managing inventory replenishments and secondary market sales. Under a general restriction on model parameters, we establish that it is optimal not to both sell off excess stock and replenish inventory. Secondary market sales complicate the structure of the system, so that the classical Clark and Scarf echelon reformulation no longer allows for the decomposition of the objective function under the optimal policy. We introduce a novel class of policies, referred to as the disposal saturation policies, and show that there exists a disposal saturation policy, determined recursively by a single base-stock level at each echelon, that achieves the decomposition of this problem. The resulting optimal replenishment policy is shown to be the echelon base-stock policy. We demonstrate the heuristic performance of this disposal saturation policy through a series of numerical studies: except at extreme ranges of model parameters, the policy provides a very good approximation to the optimal policy while avoiding the curse of dimensionality. We also conduct numerical studies to determine the value of the secondary markets for multistage supply chains and assess its sensitivity to model parameters. The results provide potentially useful insights for companies seeking to enter or develop secondary markets for supply chains.

This paper was accepted by Martin Lariviere, operations management.