bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Competitiveness of the Indian Forest-based Industry — A Reality Check
Authors: Dubey Parag
Published: February 2012

Until recently, India was a restricted market for wood products. The structural reforms initiated in the early 1990s coupled with a cautious and calibrated approach to external sector liberalization has led to a step-up in economic growth and, a ban on most domestic logging created a unique market opportunity for global forest based industries. The shortfall between demand and supply of timber could be met by the improved timber processing and marketing, which compete successfully against a range of substitute products. Given the fact that most forests and woodlots of the country are producing far below their potential, the situation calls not only for direct measures for enhancing forest productivity but also an immediate re-look at the indirect measures to protect the domestic growers both in forests and at markets.
Financial Performance Analysis of General Insurers in India
Authors: Garg Mahesh Chand , Deepti
Published: February 2012

The present study conducts a comparative evaluation on the financial performance of general insurers in India based on the ratios analysis. The current research tries to figure out the statistical significance level of similarity between an insurer and the best performing insurer in its group for each ratio and also between public and private insurers using the t-test. However, since the t-test assumes normality in the sample sets under test, all those ratios which do not satisfy the normality assumption are analyzed using Mann-Whitney U test. Normality has been checked using Kolgomorov-Smirnov test adjusted to Lilliefors corrections and Shapiro-Wilks test. The study includes four public sector and four private sector insurers. All the ratios considered cover the data for the period 1994–95 to 2005–06 for public insurers and post-liberalization period 2001–02 to 2005–06 for private insurers.
Affective Commitment as a Mediator between Psychological Climate, Job Involvement and Citizenship Behaviour
Authors: Biswas Soumendu
Published: February 2012

The psychological climate of the workplace is viewed as one of the most important environmental factors affecting an individual's workplace attitudes. At the same time, a favourable climate in the absence of organizational commitment can be a source of misuse of workplace freedom by individuals. The present article attempts to study the mediating role played by organizational commitment between psychological climate as the antecedent of job involvement and organizational citizenship behaviour. Data for the present study were collected from manufacturing as well as service sector organizations from all over India. The results and their theoretical and practical implications are discussed in detail.
HR Interventions in Turnaround Strategy: A Case Study of Rourkela Steel Plant
Authors: Mohanty Madhuchhanda , Mishra Priyadarsheenee Ipsita
Published: February 2012

Turnaround strategy is of great importance as far as the matter of survival and future of Rourkela Steel Plant (RSP) is concerned. It revived RSP from a loss-making to a profit-making organization and helped RSP to regain its previous position when it was at the verge of extinction. Moreover, as future of the entire Rourkela town depended on RSP thus with the uplift of the RSP, Rourkela which started to lose its charm, emerged as a “prosperous city” from a “dead city”. The present article is an attempt to give idea about the turn around strategies adopted by RSP and discuss and analyse in detail the various HR interventions taken by the plant to achieve turnaround for sustainable competitive advantage in the Indian Steel Industry.
Teacher as a Change Agent and Community Worker — A Co-relational Study on Organizational Climate and Teacher Morale in the High Schools of Jharkhand
Authors: Chirayath Susan
Published: February 2012

The present study entitled “Teacher as a change agent and community worker- A co- relational study on organizational climate and teacher morale in the high schools of Jharkhand” is intended to find out the type of organizational climate prevailing in the high schools of Jharkhand, morale of teachers working in those schools and the nature and extent of relationship between them.

It was thought desirable to give a brief account of the theoretical framework of the concept and the various dimensions of organizational climate and teacher morale followed by review of related studies. They arc presented in the first two sections with the following purposes: (1) for identifying the problem and its significance; (2) for formulating workable hypotheses to be tested in this investigation; and (3) for interpreting the results of the study.
Factors Influencing Job Satisfaction: A Study on the Technical Institutions in Chhattisgarh
Authors: Jeswani Saket , Dave Sumita , Praveer Saket Ranjan
Published: February 2012

Globalisation has created a cutthroat competition among the major players. Organisations are indulged in tempting the customers. They are offering tremendous benefit schemes in order to win a considerable level of customer satisfaction. But this customer satisfaction cannot be compared with the employee satisfaction as the employees play the key role and without whose effort the organisation cannot develop and survive in the market.

A study has been conducted on the teachers of technical institutions to evaluate the factors which influence job satisfaction. The paper attempts at finding out the relationship among the various factors as well as significant differences among them.
Changing Face of Human Resource Management: A Strategic Partner in Business
Authors: Bahuguna P. C. , Kumari P. , Srivastava S. K.
Published: February 2012

Various approaches and models of strategic human resource management have been developed within the framework of strategic HRM. Like many theories of organization, none are complete. Rather being right or wrong each approach points to different aspect of the process needed to develop effective strategic human resource functions. The issue of fitting HR practices to business strategy has become increasingly relevant over few years. Therefore, in the present study we have made efforts to highlight various issues that are relevant to the strategic HRM in the changing scenario of business environment. The present paper has been divided into six parts. In the first and second part, the changes occurring in the business environment and its implications for human resource functionaries have been discussed respectively. In the third part we have highlighted the changing role of human resource management. In the fourth part the historical background of strategic human resource management, its role in addressing the challenges of changing business scenario and determinants of strategic fit have been presented. In the fifth part the relationship of strategic human resource management and business performance has been reviewed and at last conclusions have been drawn that what needs to be done on the part of the HR functionaries and the organization itself to enhance the strategic fit between the various HR practices and the overall organizational strategic plan.
Effect of Financial Performance on Share Prices in the Indian Corporate Sector: An Empirical Study
Authors: Vijayakumar A.
Published: February 2012

In the last two decades, emerging capital markets have undergone drastic changes in terms of market microstructure changes, specifically in secondary markets. One of the policy concerns is the factor determining equity prices in markets. This study examined the extent to which some financial performance indicators affect the stock price. The study uses the correlation analysis, factor analysis and multiple linear regressions to analyze the impact of financial performance on the market price of the share. The regression results of the study reveals that variables taken for the study, i.e., Book value, Earnings per share, Dividend cover, Growth rate and Dividend yield have a positive association with market price of Ashok Leyland and Dividend per share and Price - Earnings ratio have a negative association with the market price of its equity shares.
Elasticity of Substitution and Returns to Scale in Manufacturing Sector of Andhra Pradesh: An Empirical Exercise
Authors: Narayana B.
Published: February 2012

In this paper, the author has attempted to study the output elasticity, nature of returns to scale and find out whether the elasticity of substitution between two inputs is different from unity or not in the manufacturing sector of Andhra Pradesh State during 1985-86 to 2005-06 by using unrestricted Cobb-Douglas, restricted log-linear and CES production functions. Major findings of the study indicate that output elasticity with respect to capital is greater than unity and returns to scale are increasing reveals that the manufacturing sector of Andhra Pradesh State is in the phase of increasing returns to scale. Further, the elasticity of output per labour with respect to capital per labour is also more than unity showing that the accumulation of capital per labour is more productive in the manufacturing sector of the State. The elasticity of substitution is significantly different from unity in the manufacturing sector which is constant elasticity of substitution represents that the production function follows constant elasticity of substitution (CES) in the manufacturing sector of State.
HR Framework for Winning in Economic Upswing: Content Analysis
Authors: Agrawal Swati
Published: February 2012

“In recession, HR should coach leaders to make prudent business decisions. Some of this means redesigning HR practices.…………Finally, HR needs to conceive of the future after the recession so that their organization is better positioned to go forward.”

(David Ulrich, 2009)

After the worst hit recession since great depression, world economy is on recovery phase. Asian economies are fastest in this trajectory of recovery. In this recent scenario, organizations are witnessing that along with the opportunities, new challenges are unfolding. During the crisis and slowdown, mostly organizations adopted the strategy of cost cutting, resulting in far reaching implications on people in the organizations. Human resources were the most affected with the crisis and the strategy of cost cutting during recession. Today with another phase in business cycle, again the key issue in front of the organizations is people issue resulting from broken psychological contract. The purpose of the paper is to outline the challenges unfolding during recovery in managing employees. Based on the content analysis and interview with HR professionals, researcher makes an attempt to create conceptual framework of HR strategies to manage employees during recovery which can be a source to consider in making human resource decisions in organizations in contemporary time.
Career in Consultancy: Problems and Prospects for Women in India
Authors: Mohapatra Mamta , Srivastava Bhupen
Published: February 2012

This paper presents a brief overview of the problems and prospects of women in consultancy across the globe and in India, the reasons for choice of consultancy as a career option and delineates the factors that facilitate and hinder the effectiveness of women consultants. The findings suggest that major reasons for choice of consultancy as a profession by women are, flexi time, autonomy and challenge that the profession offers followed by growing opportunities in the field due to high growth of economy, increasing role of service sectors and the demands on organizations to be globally competitive.
Rehabilitating Land Displaced People of Greenfield Projects in Orissa
Authors: Rath Devashis
Published: February 2012

After 50 years of Independence Orissa is all poised to take a place on the industrial map of India. Setting up new industries in greenfield areas is a mammoth task. What adds to the difficulty of such projects is acquiring land, evacuating the people, and providing them with alternative employment and rehabilitation. This article attempts to discuss the problem of rehabilitation. It deals with the factors that are potential impediments to any programme of rehabilitation and then proposes a working model as a possible guideline for the major industries setting up greenfield projects in Orissa.
Measuring Managerial Skills using a Forced-Choice Questionnaire
Authors: Ghosh Anjali
Published: February 2012

A forced-choice scale for measuring managerial skills was developed to estimate five types of managerial skills namely, decision making, leadership, conceptual ability, human relations and communication. There were 70 items in the scale presented in triadic form. Triads were formed by matching preference values of the items. Scoring keys were developed through repeated item analysis. The reliability and concurrent validity of the scales were found to be quite satisfactory. A factor analysis of the scales revealed two basic factors underlying the managerial skills, namely: (1) Planning and Analytical ability, and (2) Organizing and Directing ability.

The validity studies conducted in the present investigation are concurrent in nature. It would be good if the predictive validity of the scale is established.
The Integration of the Indian Oil Industry with the World Oil Market — A Macroeconomic Pricing Aspect
Authors: Patra Debesh C
Published: February 2012

The integration of the government owned Indian oil market with the world market marks a turning point in the industry. The era of Administered Prices brought stability; but the policy of liberalization and the need for funds makes the entry of the private sector inevitable and controlled prices impractical. Integration, however, involves risks and requires various known risk management arrangements.
A pure vision-based topological SLAM system
Authors: Lui Wen Lik Dennis , Jarvis Ray
Published: February 2012

In this paper, we present a feasible solution to the problem of autonomous navigation in initially unknown environments using a pure vision-based approach. The mobile robot performs range sensing with a unique omnidirectional stereovision system, estimates its motion using visual odometry and detects loop closures via a place recognition system as it performs topological map building and localization concurrently. Owing to the importance of performing loop closing regularly, the mobile robot is equipped with an active loop closure detection and validation system that assists it to return to target loop closing locations, validates ambiguous loop closures and provides it with the ability to overturn the decision of an incorrectly committed loop closure. A refined incremental probabilistic framework for an appearance-based place recognition system is fully described and the final system is validated in multiple experiments conducted in indoor, semi-outdoor and outdoor environments. Lastly, the performance of the probabilistic framework is compared with the rank-based framework with additional experiments conducted in the semi-autonomous mode, where the mobile robot, provided with a priori information in the form of a topological map that is built in a separate occasion in an offline manner, is required to reach its target destination.
Resinging the Temple Psalmody
Authors: Mitchell David C.
Published: February 2012

The French archaeomusicologist Suzanne Haïk-Vantoura made two important proposals that have never been fully investigated: first, that the te'amim or cantillation marks of the Hebrew scriptures did not originate with the Masoretes, but date back to temple times; second, that she had developed a system for their musical deciphering. This paper suggests that there is indeed evidence for the great antiquity of the Masoretic cantillation. It also suggests that the basic idea of Haïk-Vantoura's deciphering system—that the sublinear te'amim represent the steps of a diatonic scale—is confirmed by more recent archaeomusicological research. Finally, a comparison between the ancient tonus peregrinus to Psalm 114 and the cantillation of the same psalm deciphered according to Haïk-Vantoura's system provides strong evidence in support of her claims.
Judean Pillar Figurines and Ethnic Identity in the Shadow of Assyria
Authors: Wilson Ian Douglas
Published: February 2012

This article examines the much-debated Judean pillar figurines (JPFs), which date to the late Iron Age in the Levant and appear to be uniquely Judean artifacts. Scholarly discussion of JPFs, which has spanned a century, focuses primarily on questions of representation and use, and has contributed to the ongoing debate over the role of Asherah/asherah in monarchic Judah. The article begins with a survey of this significant discussion. Its ultimate goal, however, is to move towards a new understanding of the figurines’ popularity in the eighth and seventh centuries bce. Why did the figurines flourish in Judah during this particular period? Drawing from Antonio Gramsci's concepts of cultural hegemony and ideology, the article suggests that JPFs should be understood as part of a late Iron Age cultural discourse: the figurines represent one attempt to maintain local identity as the Neo-Assyrian empire rapidly expanded and absorbed much of the region.
An Examination of the Contextual Determinants of Self-Objectification
Authors: Fuller-Tyszkiewicz Matthew , Reynard Kelley , Skouteris Helen , McCabe Marita
Published: February 2012

The authors used a discrete choice conjoint design to examine the relative contributions of previously identified contextual factors (clothing, looks, company, and comments) for eliciting instances of appearance-related self-consciousness in a sample of 250 female undergraduates. The findings revealed that individuals differed in their relative weighting of each of the four contextual factors. Latent class analysis identified two distinct response profiles: one group reported appearance-related commentary as most likely to trigger an instance of appearance self-consciousness, whereas a second group prioritized self-perceived level of attractiveness as most likely to prompt self-consciousness. On average, the looks-prioritizing group that had higher body mass index were more dissatisfied with their appearance, and felt greater social pressure to conform to appearance-related standards. The use of a discrete choice conjoint design also allowed the authors to investigate the interplay between situational- and trait-based variables in the elicitation of appearance self-consciousness. Their findings suggest that the negative effects of appearance comments and/or perceived unattractiveness on appearance self-consciousness may be offset by access to a friendship network. Furthermore, the finding that individuals differed in their responses to various contextual influences on appearance-related consciousness suggests that a one-size-fits-all model of the relationship between environment and appearance self-consciousness may underestimate the complexity of this relationship. The authors discuss the treatment implications of these findings, as well as the need for further research to ensure that other, relevant contextual factors have not been neglected.
“. . . He’s Just Swapped His Fists for the System” The Governance of Gender through Custody Law
Authors: Elizabeth Vivienne , Gavey Nicola , Tolmie Julia
Published: February 2012

In this article, we investigate the state’s role in the reproduction of relations of male dominance between separated parents through custody law. We argue that three “logics” shape the current operation of family law—durability, gender neutrality and present/future temporality—such that custody law is not simply a mechanism of dispute resolution between parents; it is also a vehicle for the differential production, positioning, and regulation of mothers and fathers as postseparation parents. Drawing on interviews with 21 mothers, we show that the outcome of the state’s governance of gender through custody law for women in dispute over care and contact arrangements is that nonresident fathers are able to engage in nonreciprocal exercises of power over resident mothers. The consequence for resident mothers is that nonresident fathers are able to legitimately use the law to threaten and coerce mothers, and to protect their interests and rights at the expense of mothers’ needs for and rights to security and autonomy.
Design, modeling, and controlling of a large-scale magnetorheological shock absorber under high impact load
Authors: Hu Hongsheng , Jiang Xuezheng , Wang Jiong , Li Yancheng
Published: February 2012

In this article, an MRD50 type of large-scale magnetorheological shock absorber was designed and manufactured in Smart Materials and Structures Laboratory of Nanjing University of Science and Technology. Upon providing a brief background on magnetorheological dampers, the detailed structure of this developed large-scale magnetorheological shock absorber was depicted. A suit of hardware-in-the-loop simulation platform under high impact load excitation was introduced for a weapon system. A series of tests were conducted to establish the dynamic behaviors of magnetorheological shock absorber under impact loads. The test results show that the inertia damping force should not be ignored like a common magnetorheological damper because of the large acceleration from the impact load. Based on the theory model and the experimental data, index parameters of magnetorheological fluid and other structural parameters in Herschel–Bulkley-Inertia model were identified by using the least square algorithm. In order to evaluate the controllability of large-scale magnetorheological shock absorber applied into high impact loads, three control algorithms, including on–off control, proportional–integral–derivative control, and fuzzy control algorithm, were used in tests to control the dynamic behavior of magnetorheological shock absorber, and some results of the controllability tests were exhibited in this article. In conclusion, the results indicated that the developed large-scale magnetorheological shock absorber was indeed able to effectively control the recoil dynamics.
Design optimization of a shape memory alloy–actuated robotic catheter
Authors: Crews John H , Buckner Gregory D
Published: February 2012

In this article, we present a method for optimizing the design of a shape memory alloy–actuated robotic catheter. Highly maneuverable robotic catheters have the potential to revolutionize the treatment of cardiac diseases such as atrial fibrillation. To operate effectively, the catheter must navigate within the confined spaces of the heart, motivating the need for a tight bending radius. The design process is complicated by the shape memory alloy’s hysteretic relationships between strain, stress, and temperature. This article addresses the modeling and optimization of both a single-tendon and antagonistic tendon robotic catheter using COMSOL Multiphysics Modeling and Simulation software. Several design variables that affect the actuator behavior are considered; these include the shape memory alloy tendon radius and its prestrain, the shape memory alloy tendon offset from the neutral axis of the flexible beam, the flexible beam radius and elastic modulus, and the thermal boundary condition between the shape memory alloy tendon and the beam. A genetic algorithm is used to optimize the radius of curvature of the two catheter designs. Both a single-crystal and polycrystalline models are implemented in COMSOL and are experimentally validated.
Analysis of Measurement Tools of Fear of Falling for High-Risk, Community-Dwelling Older Adults
Authors: Greenberg Sherry A.
Published: February 2012

Fear of falling has many health consequences among older adults and may lead to curtailment of activities, immobility, functional dependence, falls, and serious injury. The lack of clarity as to how to best measure fear of falling among high-risk, community-dwelling older adults defined as those who are nursing home eligible, functionally dependent, and vulnerable is further complicated by the multiple definitions used throughout the science. Fear of falling is important to measure effectively if we are to develop and test interventions to promote safe aging in place and prevent injury and institutionalization. This integrative review, 1982 to the present, leads to the conclusion that the Falls Efficacy Scale-International (FES-I) long form stands out as the most appropriate measurement tool to best assess fear of falling in this unique, understudied, and underserved population.
Analyzing Differentiation in the Classroom
Authors: VanTassel-Baska Joyce
Published: February 2012

The use of a classroom observation tool to monitor differentiation strategies is described, and relevant research findings using the form are reported. The advantages for using this approach to document differentiation are discussed as are the reasons teachers may question its intent. Applications for practice include its use as a self-assessment tool to guide teaching improvement in differentiation.
Developing and Sustaining Professionalism Within Gifted Education
Authors: Coleman Mary Ruth , Gallagher James J. , Job Jennifer
Published: February 2012

This article calls for a new paradigm of professionalism in the field of gifted education. The definition of professionalism varies, and yet the need for a common vision of professionalism in the field is necessary to strengthen gifted education in the future. The authors delineate a framework for sustaining professionalism within the field and ask for commitment from the field’s stakeholders to long-range planning, fidelity with flexibility, and a collaborative infrastructure.
A Lack of Awareness and Emphasis in Preservice Teacher Training
Authors: Berman Kimberly M. , Schultz Robert A. , Weber Christine L.
Published: February 2012

Gifted and talented (GT) learners in most classroom settings endure unchallenging curriculum, a slow pace of instruction, and a state of ignorance by many of their general education teachers. The authors wanted to know how in-service teachers, preservice teacher candidates, and preservice education students viewed GT learners. The authors also wanted to know how their respondents felt about teacher training specific to the nature and needs of GT learners. Information was gathered via pre/postcourse questionnaires to describe existing beliefs and assumptions that individuals in various phases of teacher development held regarding GT learners. Findings suggest that the preconceived beliefs held by individuals about GT learners guide the willingness and approaches used to teach children more so than specific training in the nature/needs of learners.
Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: a systematic review
Authors: Balak Deepak MW , Hengstman Gerald JD , Çakmak Aysun , Thio H Bing
Published: February 2012

Glatiramer acetate and interferon-beta are approved first-line disease-modifying treatments (DMTs) for multiple sclerosis (MS). DMTs can be associated with cutaneous adverse events, which may influence treatment adherence and patient quality of life. In this systematic review, we aimed to provide an overview of the clinical spectrum and the incidence of skin reactions associated with DMTs. A systematic literature search was performed up to May 2011 in Medline, Embase, and Cochrane databases without applying restrictions in study design, language, or publishing date. Eligible for inclusion were articles describing any skin reaction related to DMTs in MS patients. Selection of articles and data extraction were performed by two authors independently. One hundred and six articles were included, of which 41 (39%) were randomized controlled trials or cohort studies reporting incidences of mainly local injection-site reactions. A large number of patients had experienced some form of localized injection-site reaction: up to 90% for those using subcutaneous formulations and up to 33% for those using an intramuscular formulation. Sixty-five case-reports involving 106 MS patients described a wide spectrum of cutaneous adverse events, the most frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various immune-mediated inflammatory skin diseases. DMTs for MS are frequently associated with local injection-site reactions and a wide spectrum of generalized cutaneous adverse events, in particular, the subcutaneous formulations. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of DMT.
How does decentralization affect electoral competition of state-wide parties? Evidence from Spain
Authors: León Sandra
Published: February 2012

The literature is still undecided on whether sub-state elections conform more to a national or regional logic of voting. In this article, I argue that the impact of national politics on regional elections is contingent upon the level of decentralization. I hypothesize that the greater the number of policy areas and resources in the hands of regional governments, the lesser the influence of national coat-tails on regional elections. Using the electoral results of the Spanish Socialist Party in national and regional elections from 1979 to 2009, the empirical analysis shows that regional politicians’ electoral performance is correlated to that of their national counterparts. However, this correlation has weakened as regional governments have gained greater decision-making and financing powers. This has been particularly evident in elections when the regional branch of the party rules a single-party government and competes against strong regionalist parties.
Why the behavioural sciences need the concept of the culture-ready brain
Authors: Whitehead Charles
Published: February 2012

From the conceptual gulf dividing social from biological anthropology this paper infers an ideological problem affecting science as a whole. Cultural biases have tended to inhibit or subvert appropriate theorizing and research into unique aspects of the human mind, brain and behaviour. To resolve this problem I suggest that we need a systematic anthropological critique of ‘collective deceptions’ affecting western science, and greater anthropological collaboration with neuroscience and other disciplines. I discuss recent imaging studies which may contribute to a better understanding of the culture-ready brain. Taken in conjunction with fossil and archaeological data, the findings seem more consistent with a ‘play and display’ hypothesis of hominid brain expansion than with current cognocentric hypotheses, suggesting new directions for research. Such research, I argue, could assist integration between behavioural disciplines.
Negative dialectics in miserable times: Notes on Adorno and social praxis
Authors: Bonefeld Werner
Published: February 2012

Adorno’s social theory dissolves the dogmatic posture of reified things. Its critical intention is to decipher the human social practice hidden in things. For Adorno, the social practice that counts is the one that fights barbarism, and for this fight to succeed, it has to tackle the social preconditions that make barbarism possible. A social practice that fails to do just that partakes in the false world of bourgeois society that it ostensibly seeks to overcome. In this context, Adorno argues, on the one hand, that the fight against barbarism is impossible because every social practice is the same. On the other, he says that negation is the only alternative to the falsehood of bourgeois society. The essay explores Adorno’s Negative Dialectics to examine this paradox and to decipher its conception of social practice in a reified world. What does it mean to say ‘no’?
Tick-Borne Infections—A Growing Public Health Threat to School-Age Children
Authors: Hamlen Ronald
Published: February 2012

School nurses are experts in school health services and frequently front-line providers of care for school-age children presenting with symptoms of physical illness or behavioral, cognitive, learning, and/or psychological problems possibly due to tick-borne infections. School nurses need to know how to protect children on school property and during school sponsored outdoor activities from being bitten by ticks that can transmit diseases. Since infection prevention is a primary objective in health care, this article will empower school nurses with key information about how to accomplish this goal.
Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure
Authors: Khoury H. Jean , Cortes Jorge E. , Kantarjian Hagop M. , Gambacorti-Passerini Carlo , Baccarani Michele , Kim Dong-Wook , Zaritskey Andrey , Countouriotis Athena , Besson Nadine , Leip Eric , Kelly Virginia , Brümmendorf Tim H.
Published: February 2012

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier–estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.
Blood T-cell receptor diversity decreases during the course of HIV infection, but the potential for a diverse repertoire persists
Authors: Baum Paul D. , Young Jennifer J. , Schmidt Diane , Zhang Qianjun , Hoh Rebecca , Busch Michael , Martin Jeffrey , Deeks Steven , McCune Joseph M.
Published: February 2012

HIV infection results in a decrease in circulating CD4+ T-cell and naive T-cell numbers. If such losses were associated with an erosion of T-cell receptor (TCR) repertoire diversity in the peripheral T-cell pool, this might exacerbate the state of persistent immunodeficiency. Existing methods for the analysis of the TCR repertoire have demonstrated skewed distributions of TCR genes in HIV-infected subjects but cannot directly measure TCR diversity. Here we used AmpliCot, a quantitative assay based on DNA hybridization kinetics, to measure TCR diversity in a cross-sectional comparison of 19 HIV-infected persons to 18 HIV-uninfected controls. HIV-infected persons had a 10-fold decrease in total TCR repertoire diversity in 1.5 mL of blood compared with uninfected controls, with decreased diversity correlating most closely with a lower CD4+ T-cell percentage. Nonetheless, the TCR repertoire diversity of sort-purified T-cell subpopulations in HIV-infected and HIV-uninfected subjects was comparable. These observations suggest that the TCR repertoire diversity changes in whole blood during HIV disease progression are primarily the result of changes in the number and proportion of T-cell subpopulations and that most HIV-infected persons may retain a sufficiently diverse TCR repertoire to permit immune reconstitution with antiretroviral therapy alone, without thymopoiesis.
Development and function of murine RORγt+ iNKT cells are under TGF-β signaling control
Authors: Havenar-Daughton Colin , Li Shamin , Benlagha Kamel , Marie Julien C.
Published: February 2012

Invariant natural killer T (iNKT) cells have the ability to rapidly secret cytokines in response to diverse stimuli, and therefore influence numerous immune reactions. Although IFN-γ and IL-4 are thought to dominate iNKT cytokine production, a distinct subset of iNKT cells, expressing RORγt and producing IL-17, has now been identified in both mice and humans. Although a role in pathogen and allergic responses has been assigned to the RORγt+ iNKT subset, factors controlling their development and function remain illusive. Here, we demonstrate that RORγt+ iNKT-cell differentiation obeys transforming growth factor-β (TGF-β) signaling control, different from that described for conventional iNKT cells. We reveal that TGF-β signaling, and particularly its SMAD4-dependent pathway, is required for both the survival of RORγt+ iNKT cells during their development and IL-17 production at the periphery. Moreover, constitutive TGF-β signaling in RORγt+ iNKT cells drives higher peripheral numbers and increased tissue distribution. Finally, we found that SMAD4-dependent TGF-β signaling is mandatory for the peripheral expansion of the RORγt+ iNKT cells responding to inflammatory signals. Thus, this work demonstrates that both the development and responsiveness of the newly described IL-17–producing iNKT cell subset is under the control of a dedicated TGF-β signaling pathway.
Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia
Authors: Beekman Renée , Valkhof Marijke G. , Sanders Mathijs A. , van Strien Paulette M. H. , Haanstra Jurgen R. , Broeders Lianne , Geertsma-Kleinekoort Wendy M. , Veerman Anjo J. P. , Valk Peter J. M. , Verhaak Roel G. , Löwenberg Bob , Touw Ivo P.
Published: February 2012

Severe congenital neutropenia (SCN) is a BM failure syndrome with a high risk of progression to acute myeloid leukemia (AML). The underlying genetic changes involved in SCN evolution to AML are largely unknown. We obtained serial hematopoietic samples from an SCN patient who developed AML 17 years after the initiation of G-CSF treatment. Next- generation sequencing was performed to identify mutations during disease progression. In the AML phase, we found 12 acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co-occurred in a subpopulation of progenitor cells already in the early SCN phase. This population expanded over time, whereas clones harboring only CSF3R mutations disappeared from the BM. The other 9 mutations were only apparent in the AML cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred autonomous proliferation to myeloid progenitors was found. We conclude that progression from SCN to AML is a multistep process, with distinct mutations arising early during the SCN phase and others later in AML development. The sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a driver of leukemic transformation in this case of SCN.
On the viability of Escherichia colicells lacking DNA topoisomerase I
Authors: Stockum Anna , Lloyd Robert G , Rudolph Christian J
Published: February 2012

Background

Manipulations of the DNA double helix during replication, transcription and other nucleic acid processing cause a change of DNA topology, which results in torsional stress. This stress is relaxed by DNA topoisomerases, a class of enzymes present in all domains of life. Negatively supercoiled DNA is relaxed by type IA topoisomerases that are widespread in bacteria, archaea and eukaryotes. InEscherichia colithere is conflicting data about viability ofΔtopAcells lacking topoisomerase I.

Results

In this study we sought to clarify whetherE. colicells lacking topoisomerase I are viable by using a plasmid-based lethality assay that allowed us to investigate the phenotype ofΔtopAcells without the presence of any compensatory mutations. Our results show that cells lacking topoisomerase I show an extreme growth defect and cannot be cultured without the accumulation of compensatory mutations. This growth defect can be partially suppressed by overexpression of topoisomerase III, the other type IA topoisomerase inE. coli, suggesting that the accumulation of torsional stress is, at least partially, responsible for the lethality ofΔtopAcells. The absence of RNase HI strongly exacerbates the phenotype of cells lacking topoisomerase I, which supports the idea that the processing of RNA:DNA hybrids is vitally important inΔtopAcells. However, we did not observe suppression of theΔtopAphenotype by increasing the level of R-loop processing enzymes, such as RNase HI or RecG.

Conclusions

Our data show unambiguously thatE. colicells are not viable in the absence of DNA topoisomerase I without the presence of compensatory mutations. Furthermore, our data suggest that the accumulation of R-loops is not the primary reason for the severe growth defect of cells lacking topoisomerase I, which is in contrast to the current literature. Potential reasons for this discrepancy are discussed.
Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer
Authors: Magbanua Mark Jesus M , Sosa Eduardo V , Scott Janet H , Simko Jeff , Collins Colin , Pinkel Dan , Ryan Charles J , Park John W
Published: February 2012

Background

The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment.

Methods

We developed a novel approach to isolate CTCs away from hematopoietic cells with high purity, enabling genomic analysis of these cells. The isolation protocol involves immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). To evaluate the feasibility of isolation of CTCs by IE/FACS and downstream genomic profiling, we conducted a pilot study in patients with metastatic castration resistant prostate cancer (CRPC). Twenty (20) sequential CRPC patients were assayed using CellSearch™. Twelve (12) patients positive for CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate CTCs. Genomic DNA of CTCs was subjected to whole genome amplification (WGA) followed by gene copy number analysis via array comparative genomic hybridization (aCGH).

Results

CTCs from nine (9) patients successfully profiled were observed to have multiple copy number aberrations including those previously reported in primary prostate tumors such as gains in 8q and losses in 8p. High-level copy number gains at the androgen receptor (AR) locus were observed in 7 (78%) cases. Comparison of genomic profiles between CTCs and archival primary tumors from the same patients revealed common lineage. However, high-level copy number gains in the AR locus were observed in CTCs, but not in the matched archival primary tumors.

Conclusions

We developed a new approach to isolate prostate CTCs without significant leukocyte admixture, and to subject them to genome-wide copy number analysis. Our assay may be utilized to explore genomic events involved in cancer progression, e.g. development of castration resistance and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner.
Metalorganic chemical vapor deposition growth of InAs/GaSb type II superlattices with controllable As
x
Sb1-xinterfaces
Authors: Li Li-Gong , Liu Shu-Man , Luo Shuai , Yang Tao , Wang Li-Jun , Liu Feng-Qi , Ye Xiao-Ling , Xu Bo , Wang Zhan-Guo
Published: February 2012

InAs/GaSb type II superlattices were grown on (100) GaSb substrates by metalorganic chemical vapor deposition (MOCVD). A plane of mixed As and Sb atoms connecting the InAs and GaSb layers was introduced to compensate the tensile strain created by the InAs layer in the SL. Characterizations of the samples by atomic force microscopy and high-resolution X-ray diffraction demonstrate flat surface morphology and good crystalline quality. The lattice mismatch of approximately 0.18% between the SL and GaSb substrate is small compared to the MOCVD-grown supperlattice samples reported to date in the literature. Considerable optical absorption in 2- to 8-μm infrared region has been realized.

PACS: 78.67.Pt; 81.15.Gh; 63.22.Np; 81.05.Ea
Dipeptidyl peptidase IV, aminopeptidase N and DPIV/APN-like proteases in cerebral ischemia
Authors: Röhnert Peter , Schmidt Werner , Emmerlich Patrick , Goihl Alexander , Wrenger Sabine , Bank Ute , Nordhoff Karsten , Täger Michael , Ansorge Siegfried , Reinhold Dirk , Striggow Frank
Published: February 2012

Background

Cerebral inflammation is a hallmark of neuronal degeneration. Dipeptidyl peptidase IV, aminopeptidase N as well as the dipeptidyl peptidases II, 8 and 9 and cytosolic alanyl-aminopeptidase are involved in the regulation of autoimmunity and inflammation. We studied the expression, localisation and activity patterns of these proteases after endothelin-induced occlusion of the middle cerebral artery in rats, a model of transient and unilateral cerebral ischemia.

Methods

Male Sprague-Dawley rats were used. RT-PCR, immunohistochemistry and protease activity assays were performed at different time points, lasting from 2 h to 7 days after cerebral ischemia. The effect of protease inhibitors on ischemia-dependent infarct volumes was quantified 7 days post middle cerebral artery occlusion. Statistical analysis was conducted using the t-test.

Results

Qualitative RT-PCR revealed these proteases in ipsilateral and contralateral cortices. Dipeptidyl peptidase II and aminopeptidase N were up-regulated ipsilaterally from 6 h to 7 days post ischemia, whereas dipeptidyl peptidase 9 and cytosolic alanyl-aminopeptidase were transiently down-regulated at day 3. Dipeptidyl peptidase 8 and aminopeptidase N immunoreactivities were detected in cortical neurons of the contralateral hemisphere. At the same time point, dipeptidyl peptidase IV, 8 and aminopeptidase N were identified in activated microglia and macrophages in the ipsilateral cortex. Seven days post artery occlusion, dipeptidyl peptidase IV immunoreactivity was found in the perikarya of surviving cortical neurons of the ipsilateral hemisphere, whereas their nuclei were dipeptidyl peptidase 8- and amino peptidase N-positive. At the same time point, dipeptidyl peptidase IV, 8 and aminopeptidase N were targeted in astroglial cells. Total dipeptidyl peptidase IV, 8 and 9 activities remained constant in both hemispheres until day 3 post experimental ischemia, but were increased (+165%) in the ipsilateral cortex at day 7. In parallel, aminopeptidase N and cytosolic alanyl-aminopeptidase activities remained unchanged.

Conclusions

Distinct expression, localization and activity patterns of proline- and alanine-specific proteases indicate their involvement in ischemia-triggered inflammation and neurodegeneration. Consistently, IPC1755, a non-selective protease inhibitor, revealed a significant reduction of cortical lesions after transient cerebral ischemia and may suggest dipeptidyl peptidase IV, aminopeptidase N and proteases with similar substrate specificity as potentially therapy-relevant targets.