bluuebunny/crossref_metadata_2025 huggingface dataset:
University Rankings, Global Models, and Emerging Hegemony
Authors: Ishikawa Mayumi
Published: January 2009

The study analyzes how the emergence of dominant models in higher education and power they embody affect non-Western, non-English language universities such as those in Japan. Based on extended micro-level participant observation in a Japanese research university aspiring to become a “world-class” institution, their struggles and the quest for new identities are examined. The prevalent and oft-referenced university rankings and league tables give rise to de facto global standards and models, against which traditions of national language education and research as well as self-sustenance in human resources are challenged and tested. Such new modes of objectifying academic excellence alter domestic academic hierarchies and internal dynamics within universities. This study uses these insights to look critically at new dimensions of knowledge construction and an emerging hegemony in today's global higher education context.
The Challenges of Increasing Capacity and Diversity in Japanese Higher Education Through Proactive Recruitment Strategies
Authors: Kuwamura Akira
Published: January 2009

There has been fierce competition for a shrinking pool of high school graduates in the higher education market in Japan in recent years. Along came former Prime Minister Fukuda's plan for an intake of 300,000 international students by the year 2020. These have placed Japanese institutions of higher education under further pressure to sustain their student enrollments in the already competitive global higher education market over the coming decade. This article begins by showing rapidly changing trends in internationalization of Japanese higher education. It then highlights the challenges of increasing the capacity to diversify the campus population and program offerings that are facing Japanese higher education today. Some key issues revolving around such challenges are identified and then examined. Furthermore, the article stresses the importance of internationalizing both the institution and individual along the way. The article concludes with a few suggestions on approaches to internationalization.
Motivations of Hospice Volunteers
Authors: Planalp Sally , Trost Melanie
Published: January 2009

To recruit and retain volunteers, coordinators need to understand volunteers' motivations. In this study, 351 volunteers from 32 hospices in the western United States answered questions on a mailed survey about their motivations. The motivations reported were, in order of overall importance: to help others and learn, foster social relationships, feel better, and pursue career goals. Younger volunteers reported stronger career motivations, and retired and unemployed volunteers reported stronger social motivations. Volunteer coordinators should consider these motivations in communicating with potential and current volunteers, with special emphasis on compassion for those in need and the importance of helping, on fostering hospice volunteering as a learning experience, and in accessing and building social networks around hospice volunteering.
The Technical Communication Research Landscape
Authors: Blakeslee Ann M.
Published: January 2009

This article reports data from questionnaires assessing the day-to-day experiences that members of the technical communication field have in carrying out their research. The data revealed that most members experience at least some frustration and numerous constraints that prevent them from doing the kinds and amounts of research that they want to do and that may affect the quality of their research. In short, technical communication scholars face an array of challenges. This article presents examples of these challenges and ideas that respondents had both for lessening the challenges scholars face and for better preparing graduate students. It suggests several practical initiatives for addressing these challenges along with realistic strategies for implementing those initiatives.
Single Specialty Hospitals and Nurse Staffing Patterns
Authors: Carey Kathleen , Burgess James F. , Young Gary J.
Published: January 2009

Advocates of physician-owned single specialty hospitals (SSHs) maintain that, through healthy competition, SSHs pressure competitor hospitals in local markets to improve performance. This paper investigates data trends on the effects of SSH entry on a potential indicator of quality of care in general hospital competitors: nurse staffing levels. We examined registered nurse (RN) staffing from 1997 to 2004 in ten states in which there was considerable SSH entry during this period. Regression estimates used longitudinal panel data models with hospital fixed effects to compare changes in numbers of RNs in general hospitals located in markets with SSHs with general hospitals located in markets where there were no SSHs. Results indicate that hospitals located in markets with orthopedic/surgical SSH presence raised their RN nurse staffing levels. Whether or not these changes are associated with improved patient outcomes is unknown.
What To Do About a Union Neutrality Agreement?
Authors: Gilliland John C.
Published: January 2009

As union organizing of home health agencies increases, many agencies will be asked by a union to enter into a “neutrality agreement” with the union. Whether to agree to such an agreement is a very significant decision for an agency. It requires an agency to understand how such an agreement affects the unionization of its employees and the agency's own goals with regard to unionization.
Psychosocial Care in Home Health Policy
Authors: Ji Seon Lee  , Rock Barry D.
Published: January 2009

As of summer 2008, health care reform has become an important part of the 2008 presidential election. However, long-term care has been absent in the discussion of health care reform by presidential candidates. This article examines policies that govern the payers of long-term care, specifically home health care (HHC). HHC is the fastest growing industry within long-term care, as there is a growing number of older adults in need of both skilled and unskilled home care. Medicare and Medicaid are the two major payers of HHC; yet these payers do not address the psychological and social needs of the patients. Furthermore, there is a long-term care disconnect between Medicare and Medicaid that creates even larger problems for older adults in need of long-term care.
The effect of levetiracetam on tremor severity and functionality in patients with multiple sclerosis
Authors: Feys P ,   MB D’hooghe, Nagels G , Helsen WF
Published: January 2009

Background

Multiple sclerosis (MS) intention tremor is a disabling symptom, which is difficult to treat.

Objectives

To investigate the effects of levetiracetam, an antiepileptic drug, on tremor severity and related functionality in MS.

Methods

A randomized, double-blind, placebo-controlled, cross-over study examined the effects of 6 weeks of oral levetiracetam administration (starting dose = 250 mg/day, maximal dose = 2000 mg/day) in 18 MS patients with disabling intention tremor. Primary outcome was Fahn’s Tremor Rating Scale (FTRS) A&B. Secondary outcome measures were the nine-hole peg test, patient’s opinion rated with the visual analog scale, FTRS C, and an activities of daily life questionnaire and validated tremor indexes derived during the performance of a digitized spiral drawing task and a wrist step-tracking task. Repeated measures analysis of variance and Friedman tests were applied.

Results

In all, 14 patients completed the trial. Maximal dose intake ranged from 1000 to most commonly 2000 mg, depending on patients’ tolerance level. No significant effects of levetiracetam were found for any outcome measure. Further analyses on subgroups with different tremor severity showed no differential effects. Eight patients reported adverse events such as fatigue and stomach ache.

Conclusions

Levetiracetam intake of 2000 mg/day did not affect tremor severity or functionality in patients with MS.
Experiences of partners of people in the early stages of multiple sclerosis
Authors: Bogosian A , Moss-Morris R , Yardley L , Dennison L
Published: January 2009

Background

Partners of people with multiple sclerosis are known to experience a heavy physical and psychological burden. However, little research has explored, in detail, the partners’ experience in the first years after diagnosis. The aim of this study was to explore and describe the experiences of partners of people who are in the relatively early stages of multiple sclerosis.

Methods

Fifteen semi-structured telephone interviews were conducted to assess partners’ concerns and difficulties. Data were audio-taped, transcribed, and analysed using an inductive thematic analysis.

Results

Key themes were being unsure of what the future might hold and feeling helpless and out of control. Furthermore, partners reported that other people could not understand and support them, which led to a feeling of social isolation.

Conclusion

The research illustrates the disruptive impact that MS has on partners’ lives and highlights the need for support to focus on partners’ needs even in early stages of the disease.
Self-assessment of the Training of Vascular Fellows: Survey Results of 219 Vascular Fellows From 2004 Through 2007
Authors: Hingorani Anil P , Ascher Enrico , Marks Natalie , Shiferson Alexander , Patel Nirav , Gopal Kapil , Jacob Theresa
Published: January 2009

Introduction. In an attempt to identify the concerns of vascular fellows regarding their training in vascular surgery, we conducted a survey consisting of 22 questions at an annual national meeting from 2004 to 2007. Methods. The fellows were asked to assess various aspects of their training as excellent, satisfactory, or mixed. Results. 76% were satisfied with their endovascular experience during their fellowship while 82% were satisfied with their experience with open cases. The distribution of non-learning cases was felt to be excellent, satisfactory, or required some or much improvement in: 45%, 44%, 8%, and 2% respectively. However, only 61% felt that their vascular laboratory experience was excellent or satisfactory. Only 36% actually performed the vascular duplex exam, and only 49% felt that they would feel comfortable in managing a vascular laboratory. Conclusions. The results of this Survey suggest that several significant issues are reflected in the minds of vascular trainees.
Aortic, Celiac Axis, and Superior Mesenteric Artery Thrombosis Associated With Sigmoid Colon Adenocarcinoma and Hypercoagulable State
Authors: Serck Luke C. , Cogbill Thomas H.
Published: January 2009

A patient with sigmoid colon adenocarcinoma and hypercoagulable state developed acute visceral ischemia secondary to thrombus involving the suprarenal aorta, celiac axis and superior mesenteric artery. A large, laminated fibrin thrombus was removed via supraceliac aortotomy. Attempts to clear thrombus from branches of the celiac axis and superior mesenteric artery by open and catheter-based techniques were of limited success. Extensive visceral infarction ensued and the patient died.
A Principal’s Dilemma
Authors: Oluwole Joseph O.
Published: January 2009

This case highlights one principal’s struggle to reconcile his philosophy of full inclusion with the best interests of a student with serious emotional disturbance. It raises a number of issues that bring to light challenges posed by a system of full inclusion. It also provides an opportunity for educational leadership students and administrators to critically confront and appreciate the ethical and legal dilemmas presented in the provision of special education services to students with serious disabilities.
Study of internal stress of amorphous Ni–W alloy films
Authors: Liu R. , Wang H. , Li X.-P. , Ding G.-F.
Published: January 2009

The present paper introduces the effect of W content, pH, current density, pulse ratio and stress reducers on the internal stress of Ni–W alloy films in the system of citrate amine HEDP. Morphologies of Ni–W alloy films were also investigated. The results showed that the internal stress was closely related to W content of alloy films. pH had an important effect on the internal stress of amorphous Ni–W alloy films and there were some cracks in the electrodeposits surface when pH value was in the range 5·5–6·0. Internal stress varied obviously with different current densities, however there were no obvious cracks in amorphous Ni–W alloy films. Internal stress was affected slightly by pulse ratio and stress reducers, and morphologies of amorphous Ni–W alloy films had little change with different pulse ratios and stress reducers.
Modelling of dealumination of aluminium silicate molecular sieves
Authors: Ma G. W. , Teng J. W. , Zhao G. L. , Zhang H. N. , Xie Z. K.
Published: January 2009

A simplified treatment of the dealumination of aluminium silicate (zeolite like) molecular sieves has been developed that considers both the diffusion of aluminium atoms and the formation and migration of vacancy sites. The instantaneous concentration of aluminium atoms as a function of time and location has been derived according to Fick's second law. Critical parameters affecting the dealumination process are discussed. The calculated results agree with the ratios of silicon to aluminium reported in the literature from infrared and 27Al NMR spectroscopy studies on the commercial aluminium silicate molecular sieves materials Mordenite and ZSM-5, following exposure to air and water vapour.
High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle
Authors: Tipping Alex J. , Pina Cristina , Castor Anders , Hong Dengli , Rodrigues Neil P. , Lazzari Lorenza , May Gillian E. , Jacobsen Sten Eirik W. , Enver Tariq
Published: January 2009

Evidence suggests the transcription factor GATA-2 is a critical regulator of murine hematopoietic stem cells. Here, we explore the relation between GATA-2 and cell proliferation and show that inducing GATA-2 increases quiescence (G0 residency) of murine and human hematopoietic cells. In human cord blood, quiescent fractions (CD34+CD38−HoechstloPyronin Ylo) express more GATA-2 than cycling counterparts. Enforcing GATA-2 expression increased quiescence of cord blood cells, reducing proliferation and performance in long-term culture-initiating cell and colony-forming cell (CFC) assays. Gene expression analysis places GATA-2 upstream of the quiescence regulator MEF, but enforcing MEF expression does not prevent GATA-2–conferred quiescence, suggesting additional regulators are involved. Although known quiescence regulators p21CIP1 and p27KIP1 do not appear to be responsible, enforcing GATA-2 reduced expression of regulators of cell cycle such as CCND3, CDK4, and CDK6. Enforcing GATA-2 inhibited human hematopoiesis in vivo: cells with highest exogenous expression (GATA-2hi) failed to contribute to hematopoiesis in nonobese diabetic–severe combined immunodeficient (NOD-SCID) mice, whereas GATA-2lo cells contributed with delayed kinetics and low efficiency, with reduced expression of Ki-67. Thus, GATA-2 activity inhibits cell cycle in vitro and in vivo, highlighting GATA-2 as a molecular entry point into the transcriptional program regulating quiescence in human hematopoietic stem and progenitor cells.
Increased T-bet+ cytotoxic effectors and type I interferon–mediated processes in chronic graft-versus-host disease of the oral mucosa
Authors: Imanguli Matin M. , Swaim William D. , League Stacy C. , Gress Ronald E. , Pavletic Steven Z. , Hakim Frances T.
Published: January 2009

Although chronic graft-versus-host disease (cGVHD) is a major long-term complication of allogeneic hematopoietic stem cell transplantation, little is known of its pathogenesis. We have systematically examined oral mucosa among cGVHD patients and determined that the clinical severity of oral cGVHD was correlated with apoptotic epithelial cells, often found adjacent to infiltrating effector-memory T cells expressing markers of cytotoxicity and type I cytokine polarization. Accumulation of T-bet+ T-cell effectors was associated with both increased proliferation and the expression of the type I chemokine receptor CXCR3. Concurrently, in both infiltrating cells and keratinocytes, we observed increased expression of the CXCR3 ligand MIG (CXCL9) and interleukin-15 (IL-15), type I interferon (IFN)–inducible factors that support the migration, type I differentiation, and expansion of alloreactive effectors. In severely affected mucosa, we observed high levels of MxA, a protein specifically induced by type I IFN, and signal transducer and activator of transcription 1 (STAT1) phosphorylation, a critical step in the IFN-signaling pathway, along with increased numbers of plasmacytoid dendritic cells. These data challenge the current paradigm of cGVHD as a type II cytokine–driven disorder and support the model that oral cGVHD results from type I IFN–driven immigration, proliferation, and differentiation of T-bet+ type I T effectors. The clinical trials are registered at http://www.clinicaltrials.gov as NCT00331968.
Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features
Authors: Figueroa Maria E. , Wouters Bas J. , Skrabanek Lucy , Glass Jacob , Li Yushan , Erpelinck-Verschueren Claudia A. J. , Langerak Anton W. , Löwenberg Bob , Fazzari Melissa , Greally John M. , Valk Peter J. M. , Melnick Ari , Delwel Ruud
Published: January 2009

Acute myeloid leukemia is a heterogeneous disease from the molecular and biologic standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients who shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, whereas the rest presented with silencing of this gene and coexpression of certain T-cell markers. DNA methylation studies revealed that these 2 groups of patients could be readily segregated in an unsupervised fashion based on their DNA methylation profiles alone. Furthermore, CEBPA silencing was associated with the presence of an aberrant DNA hypermethylation signature, which was not present in the CEBPA mutant group. This aberrant hypermethylation occurred more frequently at sites within CpG islands. CEBPA-silenced leukemias also displayed marked hypermethylation compared with normal CD34+ hematopoietic cells, whereas CEBPA mutant cases showed only mild changes in DNA methylation compared with these normal progenitors. Biologically, CEBPA-silenced leukemias presented with a decreased response to myeloid growth factors in vitro.
Murine neonatal recent thymic emigrants are phenotypically and functionally distinct from adult recent thymic emigrants
Authors: Opiela Shannon J. , Koru-Sengul Tulay , Adkins Becky
Published: January 2009

In contrast to adults, the murine neonatal CD4+ compartment contains a high frequency of recent thymic emigrants (RTEs). However, the functional capabilities of these cells in neonates are relatively unknown. Moreover, it has not been determined whether RTEs from neonates and adults are comparable. Here we have directly compared neonatal and adult CD4+ RTEs for the first time, using a transgenic mouse strain that allows for the identification and purification of RTEs. Our data demonstrate that RTEs from murine neonates and adults are phenotypically and functionally distinct. In particular, although the magnitude of RTEs cytokine responses from both age groups is dependent on the conditions of activation, neonatal RTEs always exhibited higher levels of effector Th1/Th2 cytokine production than adult RTEs. In addition, neonatal, but not adult, RTEs showed early proliferation in response to stimulation with interleukin-7 alone. This was associated with faster kinetics of interleukin-7Rα down-regulation and higher levels of pSTAT5 in neonatal RTEs. These quantitative and qualitative differences in the neonatal and adult RTEs populations may at least partially explain the diverse responses that are elicited in vivo in neonates in response to different conditions of antigen exposure.
Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain
Authors: Gaufin Thaidra , Gautam Rajeev , Kasheta Melissa , Ribeiro Ruy , Ribka Erin , Barnes Mary , Pattison Melissa , Tatum Coty , MacFarland Jeanne , Montefiori David , Kaur Amitinder , Pandrea Ivona , Apetrei Cristian
Published: January 2009

We investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20+ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.
Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease
Authors: Sarantopoulos Stefanie , Stevenson Kristen E. , Kim Haesook T. , Cutler Corey S. , Bhuiya Nazmim S. , Schowalter Michael , Ho Vincent T. , Alyea Edwin P. , Koreth John , Blazar Bruce R. , Soiffer Robert J. , Antin Joseph H. , Ritz Jerome
Published: January 2009

Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell–activating factor (BAFF) levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF/B-cell ratios compared with patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre–germinal center (GC) B cells and post-GC “plasmablast-like” cells, suggesting in vivo BAFF dependence of these 2 CD27+ B-cell subsets. Circulating CD27+ B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27+ B cells in the first year after HSCT. These studies delineate specific abnormalities of B-cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease.
Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency
Authors: Neven Bénédicte , Leroy Sandrine , Decaluwe Hélène , Le Deist Francoise , Picard Capucine , Moshous Despina , Mahlaoui Nizar , Debré Marianne , Casanova Jean-Laurent , Dal Cortivo Liliane , Madec Yoann , Hacein-Bey-Abina Salima , de Saint Basile Geneviève , de Villartay Jean-Pierre , Blanche Stéphane , Cavazzana-Calvo Marina , Fischer Alain
Published: January 2009

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for severe combined immunodeficiency (SCID). Detailed assessment of the long-term outcome of HSCT, ie, the occurrence of clinical events and the quality and stability of immune reconstitution, is now required. We performed a single-center retrospective analysis of the long-term outcome of HSCT in 90-patient cohort followed for between 2 and 34 years (median, 14 years). Clinical events and immune reconstitution data were collected. Almost half the patients have experienced one or more significant clinical events, including persistent chronic graft-versus-host disease (GVHD), autoimmune and inflammatory manifestations, opportunistic and nonopportunistic infections, chronic human papilloma virus (HPV) infections, and a requirement for nutritional support. With the notable exception of severe HPV infection, these complications tend to become less common 15 years later after HSCT. A multivariate analysis showed that the occurrence of these events correlated with non–genoidentical donors, diagnosis of Artemis SCID, and quality of immune reconstitution. In most cases, HSCT enables long-term survival with infrequent sequelae. However, the occurrence of relatively late-onset complications is a concern that requires specific means of prevention and justifies careful patient follow-up.
Caspase-7 deficiency protects from endotoxin-induced lymphocyte apoptosis and improves survival
Authors: Lamkanfi Mohamed , Moreira Lilian O. , Makena Patrudu , Spierings Diana C. J. , Boyd Kelli , Murray Peter J. , Green Douglas R. , Kanneganti Thirumala-Devi
Published: January 2009

Extensive apoptosis of leukocytes during sepsis and endotoxic shock constitutes an important mechanism linked to the excessive mortality associated with these disorders. Caspase inhibitors confer protection from endotoxin-induced lymphocyte apoptosis and improve survival, but it is not clear which caspases mediate lipopolysaccharide (LPS)–induced lymphocyte apoptosis and mortality. We report here that the apoptotic executioner caspase-7 was activated in the splenocytes of LPS-injected mice, suggesting a role for caspase-7 in lymphocyte apoptosis. Indeed, caspase-7–deficient mice were resistant to LPS-induced lymphocyte apoptosis and were markedly protected from LPS-induced lethality independently of the excessive production of serum cytokines. These results reveal for the first time a nonredundant role for caspase-7 in vivo and identify caspase-7 inhibition as a component of the mechanism by which caspase inhibitors protect from endotoxin-induced mortality.
Distinct roles of stress-activated protein kinases in Fanconi anemia type C–deficient hematopoiesis
Authors: Saadatzadeh M. Reza , Bijangi-Vishehsaraei Khadijeh , Kapur Reuben , Haneline Laura S.
Published: January 2009

The underlying molecular mechanisms that promote bone marrow failure in Fanconi anemia are incompletely understood. Evidence suggests that enhanced apoptosis of hematopoietic precursors is a major contributing factor. Previously, enhanced apoptosis of Fanconi anemia type C–deficient (Fancc−/−) progenitors was shown to involve aberrant p38 MAPK activation. Given the importance of c-Jun N-terminal kinase (JNK) in the stress response, we tested whether enhanced apoptosis of Fancc−/− cells also involved altered JNK activation. In Fancc−/− murine embryonic fibroblasts, tumor necrosis factor α (TNF-α) induced elevated JNK activity. In addition, JNK inhibition protected Fancc−/− murine embryonic fibroblasts and c-kit+ bone marrow cells from TNF-α-induced apoptosis. Importantly, hematopoietic progenitor assays demonstrated that JNK inhibition enhanced Fancc−/− colony formation in the presence of TNF-α. Competitive repopulation assays showed that Fancc−/− donor cells cultured with the JNK inhibitor had equivalent levels of donor chimerism compared with Fancc−/− donor cells cultured with vehicle control. In contrast, culturing Fancc−/− cells with a p38 MAPK inhibitor significantly increased repopulating ability, supporting an integral role of p38 MAPK in maintaining Fancc−/− hematopoietic stem cell function. Taken together, these data suggest that p38 MAPK, but not JNK, has a critical role in maintaining the engraftment of Fancc−/−-reconstituting cells under conditions of stress.
The structure of the ankyrin-binding site of β-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties
Authors: Stabach Paul R. , Simonović Ivana , Ranieri Miranda A. , Aboodi Michael S. , Steitz Thomas A. , Simonović Miljan , Morrow Jon S.
Published: January 2009

Spectrin and ankyrin participate in membrane organization, stability, signal transduction, and protein targeting; their interaction is critical for erythrocyte stability. Repeats 14 and 15 of βI-spectrin are crucial for ankyrin recognition, yet the way spectrin binds ankyrin while preserving its repeat structure is unknown. We have solved the crystal structure of the βI-spectrin 14,15 di-repeat unit to 2.1 Å resolution and found 14 residues critical for ankyrin binding that map to the end of the helix C of repeat 14, the linker region, and the B-C loop of repeat 15. The tilt (64°) across the 14,15 linker is greater than in any published di-repeat structure, suggesting that the relative positioning of the two repeats is important for ankyrin binding. We propose that a lack of structural constraints on linker and inter-helix loops allows proteins containing spectrin-like di-repeats to evolve diverse but specific ligand-recognition sites without compromising the structure of the repeat unit. The linker regions between repeats are thus critical determinants of both spectrin's flexibility and polyfunctionality. The putative coupling of flexibility and ligand binding suggests a mechanism by which spectrin might participate in mechanosensory regulation.
Patterns of exon-intron architecture variation of genes in eukaryotic genomes
Authors: Zhu Liucun , Zhang Ying , Zhang Wen , Yang Sihai , Chen Jian-Qun , Tian Dacheng
Published: January 2009

Background

The origin and importance of exon-intron architecture comprises one of the remaining mysteries of gene evolution. Several studies have investigated the variations of intron length, GC content, ordinal position in a gene and divergence. However, there is little study about the structural variation of exons and introns.

Results

We investigated the length, GC content, ordinal position and divergence in both exons and introns of 13 eukaryotic genomes, representing plant and animal. Our analyses revealed that three basic patterns of exon-intron variation were present in nearly all analyzed genomes (P< 0.001 in most cases): an ordinal reduction of length and divergence in both exon and intron, a co-variation between exon and its flanking introns in their length, GC content and divergence, and a decrease of average exon (or intron) length, GC content and divergence as the total exon numbers of a gene increased. In addition, we observed that the shorter introns had either low or high GC content, and the GC content of long introns was intermediate.

Conclusion

Although the factors contributing to these patterns have not been identified, our results provide three important clues: common factor(s) exist and may shape both exons and introns; the ordinal reduction patterns may reflect a time-orderly evolution; and the larger first and last exons may be splicing-required. These clues provide a framework for elucidating mechanisms involved in the organization of eukaryotic genomes and particularly in building exon-intron structures.
Characteristics of acute congestive heart failure with normal ejection fraction and less elevated B-type natriuretic peptide
Authors: Shimamoto Ken , Koike Natsuha , Mizuochi Kiyoko , Honma Miho , Kasai Yufuko , Sakai Akiko , Fujita Etsuko , Kawana Masatoshi
Published: January 2009

Background

Heterogeneity in B-type natriuretic peptide (BNP) levels, especially among individuals with acute heart failure with normal left ventricular ejection fraction (HFNEF), can cause confusion in interpreting results. We investigated the characteristics of cases of acute HFNEF with only modestly elevated BNP.

Methods

One hundred forty-two patients with acute or acute exacerbation of chronic HFNEF were divided into two groups by BNP level: BNP < 100 pg/ml (NB group, n = 45) and BNP ≥ 100 pg/ml (B group, n = 97). We compared clinical findings, echocardiography results, and neurohormonal factors between these two groups.

Results

In the NB group, a history of open-heart surgery (OHS) was more frequent (71% vs. 22%, p < 0.0001) and hypertension was less frequent (p = 0.0005). Left atrial diameter (LAd) was higher (p = 0.0026), while interventricular septal thickness, posterior wall thickness, relative wall thickness, left ventricular mass index were lower (p = 0.0005, p = 0.0225, p = 0.0114, p = 0.0051, respectively) in the NB group. In patients with HFNEF, a history of OHS remained an independent predictor of BNP level (< 100 pg/ml) after adjustment for hypertension, age, LAd, and interventricular septal thickness (odds ratio 3.6, p = 0.0252).

Conclusion

We found associations between acute HFNEF with less elevated BNP and a history of OHS. In a patient suspected of HFNEF, a history of OHS is considered diagnostic evidence of presence of diastolic heart failure when plasma levels of BNP are less elevated.
Alteration of renal respiratory Complex-III during experimental type-1 diabetes
Authors: Munusamy Shankar , Saba Hamida , Mitchell Tanecia , Megyesi Judit K , Brock Robert W , MacMillan-Crow Lee Ann
Published: January 2009

Background

Diabetes has become the single most common cause for end-stage renal disease in the United States. It has been established that mitochondrial damage occurs during diabetes; however, little is known about what initiates mitochondrial injury and oxidant production during the early stages of diabetes. Inactivation of mitochondrial respiratory complexes or alteration of their critical subunits can lead to generation of mitochondrial oxidants, mitochondrial damage, and organ injury. Thus, one goal of this study was to determine the status of mitochondrial respiratory complexes in the rat kidney during the early stages of diabetes (5-weeks post streptozotocin injection).

Methods

Mitochondrial complex activity assays, blue native gel electrophoresis (BN-PAGE), Complex III immunoprecipitation, and an ATP assay were performed to examine the effects of diabetes on the status of respiratory complexes and energy levels in renal mitochondria. Creatinine clearance and urine albumin excretion were measured to assess the status of renal function in our model.

Results

Interestingly, of all four respiratory complexes only cytochrome c reductase (Complex-III) activity was significantly decreased, whereas two Complex III subunits, Core 2 protein and Rieske protein, were up regulated in the diabetic renal mitochondria. The BN-PAGE data suggested that Complex III failed to assemble correctly, which could also explain the compensatory upregulation of specific Complex III subunits. In addition, the renal F0F1-ATPase activity and ATP levels were increased during diabetes.

Conclusion

In summary, these findings show for the first time that early (and selective) inactivation of Complex-III may contribute to the mitochondrial oxidant production which occurs in the early stages of diabetes.
Extramedullary leukemia in children presenting with proptosis
Authors: Murthy Ramesh , Vemuganti Geeta K , Honavar Santosh G , Naik Milind , Reddy Vijayanand
Published: January 2009

Background

We highlight the orbital manifestations of acute myeloid leukemia and the role of peripheral blood smear in the diagnosis of these cases. A total of 12 patients who presented with proptosis and were subsequently diagnosed to have acute myeloid leukemia based on incision biopsy or peripheral blood smear were included in the study.

Results

A retrospective review of all cases of acute myeloid leukemia presenting to the Orbital clinic was performed. The age at presentation, gender, presenting features, duration of symptoms and fundus features were noted. In addition the temporal relationship of the orbital disease to the diagnosis of leukemia, laterality, location of the orbital mass, imaging features and the diagnostic tools used to diagnose leukemia were noted. The median age at presentation was 6 years. The male: female ratio was 0.7:1. None of these patients had been diagnosed earlier as having acute myeloid leukemia. The presenting features included proptosis in all patients, orbital mass in 5 (41.7%), visual symptoms in 2 (16.7%) and subconjunctival hemorrhage in one patient (8.3%). A diagnosis of acute myeloid leukemia was established by incision biopsy in 4 patients, subsequently confirmed by peripheral blood smear testing and bone marrow biopsy in 2 patients which revealed the presence of systemic involvement. Imprint smears of the biopsy identified blasts in 2 of 4 cases. In 8 patients presenting with ocular manifestations, diagnosis was established by peripheral blood smear examination alone which revealed a diagnosis of acute myeloid leukemia.

Conclusion

A peripheral blood smear should be performed in all cases of sudden onset proptosis or an orbital mass in children and young adults along with an orbital biopsy. It can always be complemented with a bone marrow biopsy especially in cases of aleukemic leukemia or when the blood smear is inconclusive.
Do Asian breast cancer patients have poorer survival than their western counterparts? A comparison between Singapore and Stockholm
Authors: Tan Benita Kiat Tee , Lim Gek Hsiang , Czene Kamila , Hall Per , Chia Kee Seng
Published: January 2009

Introduction

The difference in breast cancer incidence and prognosis between ethnic groups seeks an explanation. We have recently shown that Swedish women are two to three times more likely to be diagnosed with breast cancer compared with Singaporean women. In the present paper, we compare breast cancer survival in the two countries.

Methods

We compared the survival of 10,287 Singaporean women and 17,090 Swedish women with breast cancer. Relative survival ratios were used to describe the prognosis in the two populations. A Poisson regression model was used to calculate relative risks for different follow-up periods, age groups, time of diagnosis and disease stages.

Results

The majority of the Swedish women had local cancer (80%) compared with Singaporean women (51%). The overall 5-year relative survival of the Swedish women appeared better (80%) than that of the Singaporean women (70%). A similar survival pattern was observed, however, between the two countries in a stage-by-stage comparison. Survival improved for all women in Singapore over the two decades, but only in the premenopausal women in Stockholm. In 1980 to 1989, premenopausal Singaporean women had 27% increased risk of death compared with Swedish women, adjusted for stage and year of follow-up, while the postmenopausal women had 48% increased risk. In 1990 to 1999, this risk decreased by 19% and 22% for the premenopausal and postmenopausal Singaporean women compared with the Swedish women.

Conclusions

The stage-dependent prognosis was similar for Singaporean women and for Swedish women. Singaporean women, both premenopausal and postmenopausal, had pronounced improvement in prognosis over the calendar periods, probably contributed by marked economic improvement, leading to better medical facilities and management with increased awareness of patients to diagnosis and treatment, as well as improved treatment options. Improvement seen only in the premenopausal women in Stockholm was probably due to improved treatment options.
Benefits of intensive insulin therapy on neuromuscular complications in routine daily critical care practice: a retrospective study
Authors: Hermans Greet , Schrooten Maarten , Van Damme Philip , Berends Noor , Bouckaert Bernard , De Vooght Wouter , Robberecht Wim , Berghe Greet Van den
Published: January 2009

Introduction

Intensive insulin therapy (IIT) reduced the incidence of critical illness polyneuropathy and/or myopathy (CIP/CIM) and the need for prolonged mechanical ventilation (MV ≥ 14 days) in two randomised controlled trials (RCTs) on the effect of IIT in a surgical intensive care unit (SICU) and medical intensive care unit (MICU). In the present study, we investigated whether these effects are also present in daily clinical practice when IIT is implemented outside of a study protocol.

Methods

We retrospectively studied electrophysiological data from patients in the SICU and MICU, performed because of clinical weakness and/or weaning failure, before and after routine implementation of IIT. CIP/CIM was diagnosed by abundant spontaneous electrical activity on electromyography. Baseline and outcome variables were compared using Student's t-test, Chi-squared or Mann-Whitney U-test when appropriate. The effect of implementing IIT on CIP/CIM and prolonged MV was assessed using univariate analysis and multivariate logistic regression analysis (MVLR), correcting for baseline and ICU risk factors.

Results

IIT significantly lowered mean (± standard deviation) blood glucose levels (from 144 ± 20 to 107 ± 10 mg/dl, p < 0.0001) and significantly reduced the diagnosis of CIP/CIM in the screened long-stay patients (125/168 (74.4%) to 220/452 (48.7%), p < 0.0001). MVLR identified implementing IIT as an independent protective factor (p < 0.0001, odds ratio (OR): 0.25 (95% confidence interval (CI): 0.14 to 0.43)). MVLR confirmed the independent protective effect of IIT on prolonged MV (p = 0.002, OR:0.40 (95% CI: 0.22–0.72)). This effect was statistically only partially explained by the reduction in CIP/CIM.

Conclusions

Implementing IIT in routine daily practice in critically ill patients evoked a similar beneficial effect on neuromuscular function as that observed in two RCTs. IIT significantly improved glycaemic control and significantly and independently reduced the electrophysiological incidence of CIP/CIM. This reduction partially explained the beneficial effect of IIT on prolonged MV.
IL-21 ensures TGF-β1-induced IgA isotype expression in mouse Peyer’s patches
Authors: Seo Goo-Young , Youn Jeehee , Kim Pyeung-Hyeun
Published: January 2009

It is well established that TGF-β1 induces IgA and IgG2b class-switching recombination in murine B cells. In the present study, we assessed the activity of IL-21 along with TGF-β1 in Ig synthesis by murine spleen B cells. IL-21 showed antiproliferative activity on LPS-activated splenic B cells, comparable with that of TGF-β1. IL-21 alone had little effect on IgA secretion and decreased other isotypes. Likewise, IL-21 also did not alter the TGF-β1-induced IgA synthesis and concurrently diminished the syntheses of IgM and IgG2a, which were repressed by TGF-β1. Unexpectedly, IL-21 inhibited the TGF-β1-induced IgG2b production. This IL-21 effect was examined using B cells from IL-21R knockout mice, where the IgA production profile was paralleled by that seen in wild-type B cells. However, the inhibitory effect of IL-21 on TGF-β1-induced IgG2b synthesis was not seen in the IL-21R−/− mouse, suggesting that IL-21 causes TGF-β1-stimulated B cells to decrease IgG2b synthesis. Expression patterns of Ig germ-line α(GLα)/GLγ2b transcripts under the influence of TGF-β1 and IL-21 were paralleled by IgA/IgG2b secretion. This was also observed in the activities of GLα and GLγ2b promoters. These results indicate that IL-21 decreases IgG2b secretion mainly through inhibition of GLγ2b transcription and is ultimately associated with selective IgA secretion induced by TGF-β1. Our results showed that IL-21 was expressed in greater magnitude in Peyer’s patches (PP) than in spleen. These results suggest that IL-21 has an important effect on selective IgA+ B cell commitment in PP.
Micromachining of coarse-grained multi-phase material
Authors: Mian A J , Driver N , Mativenga P T
Published: January 2009

The high demand of miniaturized components, coupled with geometric and material range limitations of traditional lithographic techniques has generated a strong interest in micromechanical machining. In micromachining the so-called size effect is a dominant factor. This is attributed to the fact that the unit or physical size of the material to be removed can be of the same order of magnitude as the tool edge radius or grain size. This paper explores the micro-machinability of multi-phase ferrite—pearlite steel that has a relatively large average grain size (10 μm). The investigation and cutting tests examined the effect of undeformed chip thickness, tool edge radius, and workpiece grain size on the specific cutting force, burr size, surface finish, and tool wear. The work clearly shows that micro tool edge radius and workpiece material grain size are valuable inputs in determining micromilling conditions that ensure the best surface finish and reduced burr size. Cutting conditions recommendations are also put forwards for roughing and finishing passes in micromilling of AISI 1045 tool steel.
On the skew network corresponding to Bricard's doubly collapsible octahedron
Authors: Baker J E
Published: January 2009

A prompt contributor to discussion of Bricard's marvellous revelation of deformable octahedra was Bennett, who related the findings to planar, spherical, and skew assemblages, the last-named consisting of a network formed by his own remarkable four-bar linkage. Since that time, many investigations have been directed to each of Bricard's and Bennett's linkages, but rarely to the notion of a connection between them. The present article draws upon recent discoveries of six-bar linkages synthesized from Bennett isograms to establish a surprising integration of three different families of six-bars and the skew network engendered by the doubly collapsible octahedron.
Modelling and analysis of delta ferrite content in claddings deposited by flux cored arc welding using a neural network
Authors: Palani P K , Murugan N
Published: January 2009

Measurement of delta ferrite in cladding gives important insight into the future mechanical and corrosion resistant behaviour of the cladded structures. The amount of delta ferrite formed during cladding is influenced by process parameters such as welding speed, welding current, and nozzle-to-plate distance. Therefore, it is essential to predict the effect of these parameters on the formation of delta ferrite. This article discusses the development of an artificial neural network model to predict the delta ferrite content in austenitic stainless-steel claddings deposited by the flux cored arc welding process. A novel approach of using the design of experiments to collect data to train the network has been adopted in this investigation. The study revealed that the delta ferrite content can be predicted more accurately using the neural networks with a minimum number of experiments. The results also indicated that welding current and speed have a significant influence on the amount of ferrite and the interaction effects of these parameters play a major role in determining ferrite in the claddings.