bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifestyle Interventions and the Prevention and Treatment of Type 2 Diabetes
Authors: Weber Mary Beth , Twombly Jennifer G. , Venkat Narayan K.M. , Phillips Lawrence S.
Published: July 2010

The diabetes epidemic is fueled by a societal increase in insulin resistance, caused by lifestyle factors, particularly excessive caloric intake and physical inactivity. Aging also plays a role in the increase in insulin resistance; however, even in older populations, the increase in insulin resistance appears to be attributable mainly to age-related obesity and inactivity. Insulin resistance reflects deposition of visceral, hepatic, and intramyocellular fat, while toxic messages from the adipose organ (free fatty acids, cytokines, and oxidative stress) impair insulin action to restrain glucose production in the liver and promote glucose disposal in muscle. Unexercised muscle is also insulin resistant because of intracellular sequestration of glucose transporters. These processes lead to hyperglycemia if compensatory secretion of insulin is inadequate due to decreases in pancreatic β -cell function and mass, ultimately resulting in the development of prediabetes and, later, type 2 diabetes mellitus (T2DM). Lifestyle interventions, programs that promote diabetes risk reduction and weight loss through behavior change, increased physical activity, and dietary modification, can decrease insulin resistance and prevent or delay the development of prediabetes and progression to T2DM. Lifestyle interventions are also important to improve diabetes management, particularly early in the natural history before loss of β -cell function and mass is so extensive that multidrug pharmacologic therapy is required. Effective interventions often include both an increase in physical activity (ideally, at least 150 minutes per week of moderate-to-vigorous aerobic exercise and strength training) and dietary modification to promote weight loss. major contributor to morbidity and mortality. T2DM can lead to renal dysfunction, peripheral and autonomic neuropathy, vision problems, and cardiovascular disease.2 In the United States alone, from 2005 to 2050, the prevalence of diagnosed diabetes is expected to more than double from 5.6% to 12.0%.3 In 2005 to 2006, the prevalence of prediabetes and diabetes combined was estimated to be 42.3% for Americans aged 20 years or older. The total prevalence of
Evaluation of the Standardized MDI-Spacer Checklist on Pediatric Asthma Management
Authors: Ozkaya Emin , Samanci N. , Güler N.
Published: July 2010

A metered-dose inhaler (MDI) with spacer allows for the delivery of maintenance therapy for childhood asthma. In this study, the authors aimed to assess the possible effects of inhalation skills in the use of an MDI with a small-volume spacer on asthma outcome in asthmatic children. The study group consisted of 66 asthmatic children between 7 and 11 years of age (mean ± SD, 8.2 ± 1.7 years) and a control group that consisted of 54 asthmatic children between 7 and 12 years of age (mean ± SD, 7.7 ± 0.9 years). All subjects were prescribed fluticasone propionate 125 µg 1 puff by an MDI with a small-volume Aerochamber spacer twice daily for 12 weeks. Inhalation skill scoring was made using the standardized MDI spacer checklist. Spirometric measurements and Health-related qualify-of-life measures were performed before and at the end of the 12-week treatment. There was no significant correlation between asthma outcome measures and MDI spacer checklist scores in children with asthma ( r = 1.76, P > .05). Moreover, the MDI spacer checklist scores were not statistically different between the study and control groups ( P > .05). This finding suggests that the standardized MDI spacer checklist scale scores have no significant impact on asthma outcome in children with asthma.
Role Preference Characteristics in Persons With Asthma
Authors: Estes Tracy S.
Published: July 2010

Asthma self-management requires the patient and health care provider to work together. Understanding what role asthma patients prefer may improve adherence to the prescribed treatment plan and improve clinical outcomes. Role preference is how a patient prefers to participate in the decision making with their health care provider. There are 3 role preferences: passive, collaborative, and active. The objective of this study was to describe role preference characteristics in persons with asthma. The study sample consisted of 225 patients with asthma. Data collection included demographic and clinical characteristics. Patients were categorized into passive, collaborative, and active role groups using the Control Preferences Scale. Noninferential and inferential statistics were used to describe and explore the sample. Most demographic and clinical characteristics were not significantly different among the 3 role preference groups, except for education and environmental irritant exposures. Education level was significantly different in the sample, with lower education associated with passive role preference. Environmental irritant exposure was significantly different between collaborative and active role preference groups, suggesting active role preference patients are exposed to more environmental irritants. Asthma patient role preferences tend not to have the same associations that patients with other chronic diseases have. Age, gender, ethnicity, income, disease severity, and previous hospital admissions were not associated with passive role preference. However, highest level of education and environmental irritant exposures did vary by role preference. Health care providers should try to tailor the patient–health care provider relationship around the patient’s education level. Furthermore, health care providers should recognize how role preference may influence a patient’s willingness to employ environmental control measures.
Phenotypically identical hemopoietic stem cells isolated from different regions of bone marrow have different biologic potential
Authors: Grassinger Jochen , Haylock David N. , Williams Brenda , Olsen Gemma H. , Nilsson Susan K.
Published: July 2010

Hemopoietic stem cells (HSCs) reside within a specified area of the bone marrow (BM) cavity called a “niche” that modulates HSC quiescence, proliferation, differentiation, and migration. Our previous studies have identified the endosteal BM region as the site for the HSC niche and demonstrated that hemopoietic stem and progenitor populations (HSPCs, LSK) isolated from different BM regions exhibit significantly different hemopoietic potential. In this study, we have analyzed subpopulations of LSK cells isolated from different regions of the BM and showed that CD150+CD48−LSK HSCs within the endosteal BM region have superior proliferative capacity and homing efficiency compared with CD150+CD48−LSK HSCs isolated from the central BM. Furthermore, we show, for the first time, that a subset of CD150+CD48+LSK progenitor cells, previously defined as B-lymphoid primed hemopoietic cells, are capable of multilineage reconstitution, however, only when isolated from the endosteal region. In addition, we provide evidence for an unrecognized role of CD48 in HSC homing. Together, our data provide strong evidence that highly purified HSCs show functional differences depending on their origin within the BM and that the most primitive HSCs reside within the endosteal BM region.
Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance
Authors: Campbell Kirsteen J. , Bath Mary L. , Turner Marian L. , Vandenberg Cassandra J. , Bouillet Philippe , Metcalf Donald , Scott Clare L. , Cory Suzanne
Published: July 2010

Diverse human cancers with poor prognosis, including many lymphoid and myeloid malignancies, exhibit high levels of Mcl-1. To explore the impact of Mcl-1 overexpression on the hematopoietic compartment, we have generated vavP-Mcl-1 transgenic mice. Their lymphoid and myeloid cells displayed increased resistance to a variety of cytotoxic agents. Myelopoiesis was relatively normal, but lymphopoiesis was clearly perturbed, with excess mature B and T cells accumulating. Rather than the follicular lymphomas typical of vavP-BCL-2 mice, aging vavP-Mcl-1 mice were primarily susceptible to lymphomas having the phenotype of a stem/progenitor cell (11 of 30 tumors) or pre-B cell (12 of 30 tumors). Mcl-1 overexpression dramatically accelerated Myc-driven lymphomagenesis. Most vavP-Mcl-1/ Eμ-Myc mice died around birth, and transplantation of blood from bitransgenic E18 embryos into unirradiated mice resulted in stem/progenitor cell tumors. Furthermore, lethally irradiated mice transplanted with E13 fetal liver cells from Mcl-1/Myc bitransgenic mice uniformly died of stem/progenitor cell tumors. When treated in vivo with cyclophosphamide, tumors coexpressing Mcl-1 and Myc transgenes were significantly more resistant than conventional Eμ-Myc lymphomas. Collectively, these results demonstrate that Mcl-1 overexpression renders hematopoietic cells refractory to many cytotoxic insults, perturbs lymphopoiesis and promotes malignant transformation of hematopoietic stem and progenitor cells.
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production
Authors: Souza Anselmo S , Giudice Angela , Pereira Júlia MB , Guimarães Luís H , de Jesus Amelia R , de Moura Tatiana R , Wilson Mary E , Carvalho Edgar M , Almeida Roque P
Published: July 2010

Background

Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of theL. (V.) braziliensisisolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance ofL. (V.) braziliensisto NO and nonresponsiveness to antimony therapy and cytokine production.

Methods

We evaluated thein vitrotoxicity of NO against the promastigotes stages ofL. (V.) braziliensisisolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants fromLeishmaniainfected macrophage were used to measure TNF-α and IL-10 levels.

Results

Using NaNO2(pH 5.0) as the NO source,L. (V.) braziliensisisolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) thanL. (V.) braziliensisisolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistantL. (V.) braziliensisisolated from responsive and refractory patients. NO-resistantL. (V.) braziliensisisolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptibleL. (V.) braziliensisisolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistantL. (V.) braziliensisas compared to macrophages infected with NO-susceptibleL. (V.) braziliensis(p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels.

Conclusion

These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.
Evidence for alternative quaternary structure in a bacterial Type III secretion system chaperone
Authors: Barta Michael L , Zhang Lingling , Picking Wendy L , Geisbrecht Brian V
Published: July 2010

Background

Type III secretion systems are a common virulence mechanism in many Gram-negative bacterial pathogens. These systems use a nanomachine resembling a molecular needle and syringe to provide an energized conduit for the translocation of effector proteins from the bacterial cytoplasm to the host cell cytoplasm for the benefit of the pathogen. Prior to translocation specialized chaperones maintain proper effector protein conformation. The class II chaperone, Invasion plasmid gene (Ipg) C, stabilizes two pore forming translocator proteins. IpgC exists as a functional dimer to facilitate the mutually exclusive binding of both translocators.

Results

In this study, we present the 3.3 Å crystal structure of an amino-terminally truncated form (residues 10-155, denoted IpgC10-155) of the class II chaperone IpgC from Shigella flexneri. Our structure demonstrates an alternative quaternary arrangement to that previously described for a carboxy-terminally truncated variant of IpgC (IpgC1-151). Specifically, we observe a rotationally-symmetric "head-to- head" dimerization interface that is far more similar to that previously described for SycD from Yersinia enterocolitica than to IpgC1-151. The IpgC structure presented here displays major differences in the amino terminal region, where extended coil-like structures are seen, as opposed to the short, ordered alpha helices and asymmetric dimerization interface seen within IpgC1-151. Despite these differences, however, both modes of dimerization support chaperone activity, as judged by a copurification assay with a recombinant form of the translocator protein, IpaB.

Conclusions

From primary to quaternary structure, these results presented here suggest that a symmetric dimerization interface is conserved across bacterial class II chaperones. In light of previous data which have described the structure and function of asymmetric dimerization, our results raise the possibility that class II chaperones may transition between asymmetric and symmetric dimers in response to changes in either biochemical modifications (e.g. proteolytic cleavage) or other biological cues. Such transitions may contribute to the broad range of protein-protein interactions and functions attributed to class II chaperones.
Managing hyperemesis gravidarum: a multimodal challenge
Authors: Jueckstock JK , Kaestner R , Mylonas I
Published: July 2010

Up to 90% of pregnant women experience nausea and vomiting. When prolonged or severe, this is known as hyperemesis gravidarum (HG), which can, in individual cases, be life threatening. In this article the aetiology, diagnosis and treatment strategies will be presented based on a selective literature review. Treatment strategies range from outpatient dietary advice and antiemetic drugs to hospitalization and intravenous (IV) fluid replacement in persistent or severe cases. Alternative methods, such as acupuncture, are not yet evidence based but sometimes have a therapeutic effect.

In most cases, the condition is self limiting and subsides by around 20 weeks gestation. More severe forms require medical intervention once other organic causes of nausea and vomiting have been excluded. In addition, a psychosomatic approach is often helpful.

In view of its potential complexity, general practitioners and obstetricians should be well informed about HG and therapy should be multimodal.
Long Lasting Pain Hypersensitivity following Ligation of the Tendon of the Masseter Muscle in Rats: A Model of Myogenic Orofacial Pain
Authors: Guo Wei , Wang Hu , Zou Shiping , Wei Feng , Dubner Ronald , Ren Ke
Published: July 2010

Background:

A major subgroup of patients with temporomandibular joint (TMJ) disorders have masticatory muscle hypersensitivity. To study myofacial temporomandibular pain, a number of preclinical models have been developed to induce myogenic pain of the masseter muscle, one of the four muscles involved in mastication. The currently used models, however, generate pain that decreases over time and only lasts from hours to weeks and hence are not suitable for studying chronicity of the myogenic pain in TMJ disorders. Here we report a model of constant myogenic orofacial pain that lasts for months.

Results:

The model involves unilateral ligation of the tendon of the anterior superficial part of the rat masseter muscle (TASM). The ligation of the TASM was achieved with two chromic gut (4.0) ligatures via an intraoral approach. Nocifensive behavior of the rat was assessed by probing the skin site above the TASM with a series of von Frey filaments. The response frequencies were determined and an EF50 value, defined as the von Frey filament force that produces a 50% response frequency, was derived and used as a measure of mechanical sensitivity. Following TASM ligation, the EF50 of the injured side was significantly reduced and maintained throughout the 8-week observation period, suggesting the presence of mechanical hyperalgesia/allodynia. In sham-operated rats, the EF50 of the injured side was transiently reduced for about a week, likely due to injury produced by the surgery. Somatotopically relevant Fos protein expression was indentified in the subnucleus caudalis of the spinal trigeminal sensory complex. In the same region, persistent upregulation of NMDA receptor NR1 phosphorylation and protein expression and increased expression of glial markers glial fibrillary acidic protein (astroglia) and CD1 1b (microglia) were found. Morphine (0.4–8 mg/kg, s.c.) and duloxetine (0.4–20 mg/kg, i.p.), a selective serotonin-norepinephrine reuptake inhibitor, produced dose-dependent attenuation of hyperalgesia.

Conclusions:

Ligation injury of the TASM in rats led to long-lasting and constant mechanical hypersensitivity of myogenic origin. The model will be particularly useful in studying the chronicity of myogenic pain TMJ disorders. The model can also be adapted to other regions of the body for studying pathology of painful tendinopathy seen in sports injury, muscle overuse, and rheumatoid arthritis.
Does the cortisol response to stress mediate the link between expressed emotion and oppositional behavior in Attention-Deficit/Hyperactivity-Disorder (ADHD)?
Authors: Christiansen Hanna , Oades Robert D , Psychogiou Lamprini , Hauffa Berthold P , Sonuga-Barke Edmund J
Published: July 2010

Background

Expressed Emotions (EE) are associated with oppositional behavior (OPB) in children with Attention Deficit/Hyperactivity Disorder (ADHD). EE has been linked to altered stress responses in some disorders, but ADHD has not been studied. We test the hypothesis that OPB in ADHD is mediated by altered stress-related cortisol reactivity to EE.

Methods

Two groups of children (with/without ADHD) and their respective parents were randomly assigned to two different conditions with/without negative emotion and participated in an emotion provocation task. Parents' EE, their ratings of their children's OPB and their children's salivary cortisol levels were measured.

Results

Low parental warmth was associated with OPB in ADHD. High levels of parental EE elicited a larger cortisol response. Stress-related cortisol reactivity mediated the EE-OPB link for all children. This highlights the general importance of parent-child interactions on externalizing behavior problems.

Conclusion

High EE is a salient stressor for ADHD children that leads to increased levels of cortisol and OPB. The development of OPB might be mediated by the stress-response to high EE.
Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors
Authors: Caenepeel Sean , Renshaw-Gegg Lisa , Baher Angelo , Bush Tammy L , Baron Will , Juan Todd , Manoukian Raffi , Tasker Andrew S , Polverino Anthony , Hughes Paul E
Published: July 2010

Background

Activating mutations in Kit receptor tyrosine kinase or the related platelet-derived growth factor receptor (PDGFR) play an important role in the pathogenesis of gastrointestinal stromal tumors (GIST).

Methods

This study investigated the activity of motesanib, an inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3; PDGFR; and Kit, against primary activating Kit mutants and mutants associated with secondary resistance to imatinib. Single- and double-mutant isoforms of Kit were evaluated for their sensitivity to motesanib or imatinib in autophosphorylation assays and in Ba/F3 cell proliferation assays.

Results

Motesanib inhibited Kit autophosphorylation in CHO cell lines expressing primary activating mutations in exon 9 (AYins503-504, IC50 = 18 nM) and exon 11 (V560 D, IC50 = 5 nM; Δ552-559, IC50 = 1 nM). Motesanib also demonstrated activity against kinase domain mutations conferring imatinib resistance (V560D/V654A, IC50 = 77 nM; V560D/T670I, IC50 = 277 nM; Y823 D, IC50 = 64 nM) but failed to inhibit the imatinib-resistant D816V mutant (IC50 > 3000 nM). Motesanib suppressed the proliferation of Ba/F3 cells expressing Kit mutants with IC50 values in good agreement with those observed in the autophosphorylation assays.

Conclusions

In conclusion, our data suggest that motesanib possesses inhibitory activity against primary Kit mutations and some imatinib-resistant secondary mutations.
Maintenance of cytomegalovirus-specific CD4pos T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments
Authors: Davignon Jean-Luc , Boyer Jean-Frédéric , Jamard Bénédicte , Nigon Delphine , Constantin Arnaud , Cantagrel Alain
Published: July 2010

Introduction

Anti-tumor necrosis factor (TNF)-α biotherapies have considerably changed the treatment of rheumatoid arthritis (RA). However, serious infections are a major concern in patients with rheumatic diseases treated with anti-TNF-α. Little is known about viral, especially latent, infections in anti-TNF-α treatments. Infections by cytomegalovirus (CMV), a β-herpes virus, are frequent and induce a strong CD4pos T-cell immunity, which participates in the control of infection. We thus have chosen to analyze the CD4pos T-cell response to CMV antigens as a model of antiviral response in RA patients treated with anti-TNF-α. CD28 expression was evaluated.

Methods

We have measured the CD4pos response to CMV antigens in RA patients, before and after initiation of treatment with an anti-TNF-α agent. The intracellular production of interferon (IFN)-γ in total and CD28neg CD4pos T cells in response to CMV antigens (Ags) was evaluated with flow cytometry. The proliferation of total CD4pos T cells in the presence of CMV antigens was measured with 3H-thymidine incorporation.

Results

Anti-TNF-α treatments impaired neither the anti-CD4pos anti-CMV IFN-γ response nor the proliferative response in patients. The percentage of CD28neg CD4pos cells remained constant.

Conclusions

Our data suggest that the CD4pos T-cell response against CMV is not altered by anti-TNF-α treatments and that infection remains controlled in treated RA patients latently infected with CMV. Our observation brings new insight into the current knowledge of the risks of infection in patients treated with anti-TNF-α biotherapies.
Quantifying the mechanisms of domain gain in animal proteins
Authors: Buljan Marija , Frankish Adam , Bateman Alex
Published: July 2010

Background

Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms.

Results

Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events.

Conclusions

The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.
Minireview: Organizational Hypothesis: Instances of the Fingerpost
Authors: Breedlove S. Marc
Published: July 2010

There is now compelling evidence that the ratio of the length of the second digit divided by the length of the fourth digit (2D:4D) is affected by prenatal androgens in humans. This ratio is greater in females than males from fetal life through adulthood, correlates with polymorphism in the androgen receptor gene in men, is feminine in XY androgen insensitivity syndrome, and masculinized in congenital adrenal hyperplasia. Using 2D:4D as a correlate, researchers have found evidence that prenatal androgens affect many sexually differentiated human behaviors, including sexual orientation in women (but not in men), attention deficit disorder, autism, eating disorders, aggression, and risk-taking. In each case, lower 2D:4D, indicative of greater prenatal androgen stimulation, is associated with behavior more commonly displayed by males than females. The correlation between 2D:4D and prenatal androgen stimulation is too imperfect to accurately predict the phenotype of a particular individual, even in terms of sex. However, digit ratio is the best available retrospective marker of average differences in prenatal androgen stimulation between groups of people, and/or correlations of prenatal androgen stimulation with particular behaviors and characteristics within a group. Thus digit ratios offer a valid test of the organizational hypothesis that androgens act early in life to masculinize various human behaviors.
Hyperinsulinemia Precedes Insulin Resistance in Mice Lacking Pancreatic β-Cell Leptin Signaling
Authors: Gray Sarah L. , Donald Christine , Jetha Arif , Covey Scott D. , Kieffer Timothy J.
Published: July 2010

The adipocyte hormone leptin acts centrally and peripherally to regulate body weight and glucose homeostasis. The pancreatic β-cell has been shown to be a key peripheral target of leptin, with leptin suppressing insulin synthesis and secretion from β-cells both in vitro and in vivo. Mice with disrupted leptin signaling in β-cells (leprflox/flox RIPcre tg+ mice) display hyperinsulinemia, insulin resistance, glucose intolerance, obesity, and reduced fasting blood glucose. We hypothesized that hyperinsulinemia precedes the development of insulin resistance and increased adiposity in these mice with a defective adipoinsular axis. To determine the primary defect after impaired β-cell leptin signaling, we treated leprflox/flox RIPcre tg+ mice with the insulin sensitizer metformin or the insulin-lowering agent diazoxide with the rationale that pharmacological improvement of the primary defect would alleviate the secondary symptoms. We show that improving insulin sensitivity with metformin does not normalize hyperinsulinemia, whereas lowering insulin levels with diazoxide improves insulin sensitivity. Taken together, these results suggest that hyperinsulinemia precedes insulin resistance in β-cell leptin receptor-deficient mice, with insulin resistance developing as a secondary consequence of excessive insulin secretion. Therefore, pancreatic β-cell leptin receptor-deficient mice may represent a model of obesity-associated insulin resistance that is initiated by hyperinsulinemia.
A Randomized, Controlled Trial of Vitamin D Supplementation upon Musculoskeletal Health in Postmenarchal Females
Authors: Ward K. A. , Das G. , Roberts S. A. , Berry J. L. , Adams J. E. , Rawer R. , Mughal M. Z.
Published: July 2010

Context: There has been a resurgence of vitamin D deficiency rickets throughout the developed world, with infants and adolescents being primarily affected. Adolescence is a crucial period for muscle and bone mineral accumulation.

Objective: The aim was to determine the effect of vitamin D supplementation on the adolescent musculoskeletal system.

Design and Setting: We conducted a community-based, double-blind, randomized controlled trial in a secondary school.

Participants: Postmenarchal 12- to 14-yr-old females participated in the trial. Ninety-nine were screened, 73 were included in randomized controlled trial, and 69 completed the trial. There were no adverse events.

Intervention: Four doses of 150,000 IU vitamin D2 (ergocalciferol) were given over 1 yr.

Main Outcome Measures: Dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and jumping mechanography were used.

Results: At follow-up, 25-hydroxyvitamin D [25(OH)D] status was 56.0 ± 8.9 nmol/liter in the intervention group and 15.8 ± 6.6 nmol/liter in controls. There were no effects of supplementation on bone; however, for muscle function, efficiency of movement improved in the vitamin D-treated group. There was an interaction between baseline 25(OH)D concentration and response to vitamin D supplementation for muscle jump velocity.

Conclusions: Despite improvements in 25(OH)D status, treatment with vitamin D2 was not shown to increase mineral accretion, bone geometry or strength, muscle force, or power. There were greater increases in jump velocity in girls with the lowest baseline 25(OH)D concentrations. Lack of effect of intervention after the period of peak mineral and muscle mass accretion suggests that earlier action is required.
Haplotype Analysis Discriminates Genetic Risk for DR3-Associated Endocrine Autoimmunity and Helps Define Extreme Risk for Addison’s Disease
Authors: Baker Peter R. , Baschal Erin E. , Fain Pam R. , Triolo Taylor M. , Nanduri Priyaanka , Siebert Janet C. , Armstrong Taylor K. , Babu Sunanda R. , Rewers Marian J. , Gottlieb Peter A. , Barker Jennifer M. , Eisenbarth George S.
Published: July 2010

Context: Multiple autoimmune disorders (e.g. Addison’s disease, type 1 diabetes, celiac disease) are associated with HLA-DR3, but it is likely that alleles of additional genes in linkage disequilibrium with HLA-DRB1 contribute to disease.

Objective: The objective of the study was to characterize major histocompatability complex (MHC) haplotypes conferring extreme risk for autoimmune Addison’s disease (AD).

Design, Setting, and Participants: Eighty-six 21-hydroxylase autoantibody-positive, nonautoimmune polyendocrine syndrome type 1, Caucasian individuals collected from 1992 to 2009 with clinical AD from 68 families (12 multiplex and 56 simplex) were genotyped for HLA-DRB1, HLA-DQB1, MICA, HLA-B, and HLA-A as well as high density MHC single-nucleotide polymorphism (SNP) analysis for 34.

Main Outcome Measures: AD and genotype were measured.

Result: Ninety-seven percent of the multiplex individuals had both HLA-DR3 and HLA-B8 vs. 60% of simplex AD patients (P = 9.72 × 10−4) and 13% of general population controls (P = 3.00 × 10−19). The genotype DR3/DR4 with B8 was present in 85% of AD multiplex patients, 24% of simplex patients, and 1.5% of control individuals (P = 4.92 × 10−191). The DR3-B8 haplotype of AD patients had HLA-A1 less often (47%) than controls (81%, P = 7.00 × 10−5) and type 1 diabetes patients (73%, P = 1.93 × 10−3). Analysis of 1228 SNPs across the MHC for individuals with AD revealed a shorter conserved haplotype (3.8) with the loss of the extended conserved 3.8.1 haplotype approximately halfway between HLA-B and HLA-A.

Conclusion: Extreme risk for AD, especially in multiplex families, is associated with haplotypic DR3 variants, in particular a portion (3.8) but not all of the conserved 3.8.1 haplotype.
Circulating Pigment Epithelium-Derived Factor Levels Are Associated with Insulin Resistance and Decrease after Weight Loss
Authors: Sabater Mònica , Moreno-Navarrete Jose M. , José Ortega Francisco , Pardo Gerard , Salvador Javier , Ricart Wifredo , Frühbeck Gema , Fernández-Real José Manuel
Published: July 2010

Objective: We aimed to study circulating pigment epithelium-derived factor (PEDF) in vivo in association with insulin resistance and in vitro in human adipocytes.

Methods: Circulating PEDF (ELISA) and metabolic profile were assessed in 125 Caucasian men. PEDF levels were also assessed in an independent cohort of subjects (n = 33) to study the effects of changing insulin action. PEDF gene expression and secretion were measured during differentiation of human preadipocytes.

Results: In all subjects, PEDF was positively associated with body mass index (r = 0.326; P < 0.0001), waist-to-hip ratio (r = 0.380; P < 0.0001), HbA1c, and fasting triglycerides and negatively with insulin sensitivity (r = −0.320; P < 0.0001). PEDF levels were significantly increased in subjects with altered glucose tolerance and type 2 diabetes. Of the inflammatory markers measured, PEDF levels were positively associated with serum soluble TNF-α receptor 1 and IL-10 in obese subjects. Interestingly, weight loss led to significantly decreased PEDF concentration from 34.8 ± 19.3 to 22.5 ± 14.2 μg/ml (P < 0.0001). Multiple linear regression analyses revealed that insulin sensitivity contributed independently to explain 14% of the variance in PEDF levels after controlling for the effects of body mass index, age, and log fasting triglycerides. Differences in PEDF observed after weight loss were related to changes in obesity, insulin resistance, and blood pressure measures. PEDF gene expression and secretion increased during differentiation of human preadipocytes.

Conclusion: Circulating PEDF is associated with insulin sensitivity. The findings show, for the first time in humans, that PEDF concentrations decrease significantly after weight loss in association with blood pressure. PEDF seems to be involved in human adipocyte biology.
The activation of membrane targeted CaMK-II in the zebrafish Kupffer's vesicle is required for left-right asymmetry
Authors: Francescatto Ludmila , Rothschild Sarah C. , Myers Alexandra L. , Tombes Robert M.
Published: July 2010

Intracellular calcium ion (Ca2+) elevation on the left side of the mouse embryonic node or zebrafish Kupffer's vesicle (KV) is the earliest asymmetric molecular event that is functionally linked to lateral organ placement in these species. In this study, Ca2+/CaM-dependent protein kinase (CaMK-II) is identified as a necessary target of this Ca2+ elevation in zebrafish embryos. CaMK-II is transiently activated in approximately four interconnected cells along the anterior left wall of the KV between the six- and 12-somite stages, which is coincident with known left-sided Ca2+ elevations. Within these cells, activated CaMK-II is observed at the surface and in clusters, which appear at the base of some KV cilia. Although seven genes encode catalytically active CaMK-II in early zebrafish embryos, one of these genes also encodes a truncated inactive variant (αKAP) that can hetero-oligomerize with and target active enzyme to membranes. αKAP, β2 CaMK-II and γ1 CaMK-II antisense morpholino oligonucleotides, as well as KV-targeted dominant negative CaMK-II, randomize organ laterality and southpaw (spaw) expression in lateral plate mesoderm (LPM). Left-sided CaMK-II activation was most dependent on an intact KV, the PKD2 Ca2+ channel and γ1 CaMK-II; however, αKAP, β2 CaMK-II and the RyR3 ryanodine receptor were also necessary for full CaMK-II activation. This is the first report to identify a direct Ca2+-sensitive target in left-right asymmetry and supports a model in which membrane targeted CaMK-II hetero-oligomers in nodal cells transduce the left-sided PKD2-dependent Ca2+ signals to the LPM.
Design and Control of an Upper-Wedge-Type Electronic Brake
Authors: Jo C-H , Lee S-M , Song H-L , Cho Y-S , Kim I , Hyun D-Y , Kim H-S
Published: July 2010

An electronic wedge brake (EWB) uses the wedge principle to provide a self-reinforcement mechanism, resulting in reduced current to the actuation motor. However, this mechanism can lead to an unstable open-loop system. In this study, an upper-wedge moving-type EWB is developed and a control algorithm is proposed to follow the target clamping force and to prevent jamming of the EWB system using the push—pull control of the actuator. The performance of the EWB is evaluated using a dynamometer and a simulator. Based on testing and simulation, the clamping force and braking time of the proposed EWB are shown to be satisfactory with respect to the required braking deceleration.
Strategy for vibration reduction of a centrifugal turbo blower in a fuel cell electric vehicle based on vibrational power flow analysis
Authors: Kim Y S , Kim E Y , Lee S-K
Published: July 2010

A centrifugal turbo blower is one of the important parts used for generating electric power in a fuel cell electric vehicle (FCEV). The impeller blades of the centrifugal turbo blower must rotate at a high speed to generate electric power. The unbalance and asymmetry of the rotating parts, such as impeller blades, become causes of the heavy vibration of the centrifugal turbo blower. This vibration is transmitted to the chassis frame of the FCEV through vibration isolators and becomes one of the major sources of interior noise in the FCEV. Therefore, the vibration generated from a centrifugal turbo blower should be attenuated properly to reduce the interior noise. To achieve this effectively, quantification of the vibration energy flow through the isolators is necessary, since it gives information on the quantification of the vibrational energy flow from the centrifugal turbo blower to the chassis frame. Information on the vibrational power flow at each vibration isolator identifies the vibration transmission path. In this paper, a simple equation is derived to calculate the vibration power flow through each vibration isolator. With this equation, the vibrational power flow through each isolator is numerically simulated. In this simulation, the vibration generated from the centrifugal turbo blower is predicted using the multi-body dynamic analysis of a three-dimensional model of the centrifugal turbo blower based on computer-aided engineering. These simulated results are confirmed by measurement of the vibration power flow generated from the centrifugal turbo blower in a laboratory.
The effects of heat transfer on performance and exergy destruction for a turbocharged, spark-ignition engine
Authors: Lawand V J , Caton J A
Published: July 2010

The use of the second law of thermodynamics is a powerful means for assessing the performance of engines, and is the only way to determine the destruction of exergy. This work has examined a turbocharged, spark-ignition engine in some detail, and in particular, has quantified the effects of varying the engine cylinder heat transfer.

A thermodynamic simulation was developed to investigate these effects from both the first law and second law perspectives. The engine used for this study was a 3.8l, V-6, turbocharged engine with an intercooler. The engine was examined for various levels of heat transfer. The exergy values associated with the components of the turbocharger along with the engine components were quantified as a percentage of fuel exergy. For the base case operating conditions (full load, 2000r/min) about 20.5 per cent of the exergy was destroyed during the combustion process, and the turbocharger components were responsible for less than 1 per cent of the exergy destruction. As the heat transfer level decreased, work increased only slightly while the exhaust energy and exergy increased much more significantly. Although engine performance was altered as the heat transfer level was changed, the destruction of exergy remained nearly constant.
Cavitation formation and modelling for fluid film bearings: A review
Authors: Braun M J , Hannon W M
Published: July 2010

Even though the list of references associated with this review is rather extensive, in no way does it exhaust the vast literature dedicated to the study of cavitation. The intent was to summarize (i) advances in analytical and numerical modelling, (ii) draw attention to the thermodynamic aspects of cavitation, and (iii) do so while reflecting on physical or experimental observations.
Fretting Damage of Ni—MoS2 Coatings: Friction Coefficient and Accumulated Dissipated Energy Evolutions
Authors: Kim K , Korsunsky A M
Published: July 2010

This article describes fretting wear damage of Ni—MoS2 coatings in terms of the friction coefficient (COF) and accumulated dissipated energy. Multi-layer dry lubricant coatings containing the elements Mo and S are known to maintain low friction under reciprocal relative displacement, and are considered for this purpose in fan blade attachments within aero-engines. The durability of these coatings for a dovetail connection needs to be investigated in order to help design calculations and overhaul scheduling. Experimental characterization of durability can be achieved by measuring COF as a function of the number of fretting cycles, or, alternatively, the accumulated sliding distance. Dissipated energy is also considered as an alternative indicator for characterizing fretting wear damage. In this article, fretting wear tests with Ni—MoS2 coatings and various surface treatments were performed using idealized contact geometries and loading conditions similar to those found in aero-engine components. Additionally, COF evolutions of Ni—MoS2 coatings were numerically determined as a function of accumulated dissipated energy. A direct comparison between a numerical evolution and a measured one was performed, and excellent agreement between the two evolutions was obtained.
Near Infrared Spectroscopy Calibration Transfer for Quantitative Analysis of Fish Meal Mixed with Soybean Meal
Authors: Shi Guangtao , Han Lujia , Yang Zengling , Chen Longjian , Liu Xian
Published: July 2010

The objective of this study was to explore the feasibility of near infrared (NIR) spectra calibration model transfer techniques in quantitative analysis of fish meal mixed with soybean meal. One dispersive NIR instrument (Foss 6500) and one Fourier transform (FT) instrument (Nicolet Antaris) were used in this study. The effect of slope/bias correction, local centring, direct standardisation (DS) and piece-wise direct standardisation (PDS) on calibration transfer were studied. When the calibration model based on the Foss 6500 was used directly for the spectra scanned on Nicolet Antaris, it produced unsatisfactory prediction with the RMSEP= 10.81% and bias=-9.73%. However, the predictions were greatly improved after the calibration transfer based on slope/bias correction ( RMSEP=3.19%, bias=0.64.%), local centring ( RMSEP=2.91%, bias=0.50%), DS( RMSEP=3.06%, bias=1.26%) and PDS ( RMSEP=2.54%, bias=0.77%) with the validation set VNI. In order to test the transferability of the four calibration transfer technologies, another independent external validation set (VEI) was used to test the transferability of the four calibration transfer technologies. Similar results were obtained with the prediction ( RMSEP=2.71%, bias=0.64%) for PDS, followed by local centring method ( RMSEP=2.98%, bias=0.52%), DS method ( RMSEP=3.18%, bias=0.96%) and slope/bias correction ( RMSEP=3.24%, bias=0.60%). These findings demonstrated that calibration model transfer technology may be an appropriate tool to quantitatively analyse fish meal mixed with soybean meal.
Evaluation of Spectral Pretreatments, Partial Least Squares, Least Squares Support Vector Machines and Locally Weighted Regression for Quantitative Spectroscopic Analysis of Soils
Authors: Igne Benoit , Reeves James B. , McCarty Gregory , Hively W. Dean , Lund Eric , Hurburgh Charles R.
Published: July 2010

Soil testing requires the analysis of large numbers of samples in the laboratory that is often time consuming and expensive. Mid-infrared spectroscopy (mid-IR) and near infrared (NIR) spectroscopy are fast, non-destructive and inexpensive analytical methods that have been used for soil analysis, in the laboratory and in the field, to reduce the need for measurements using complex chemical/physical analyses. A comparison of the use of spectral pretreatment as well as the implementation of linear and non-linear regression methods was performed. This study presents an overview of the use of infrared spectroscopy for the prediction of five physical (sand, silt and clay) and chemical (total carbon and total nitrogen) soil parameters with near and mid-infrared units in bench top and field set-ups. Even though no significant differences existed among pretreatment methods, models using second derivatives performed better. The implementation of partial least squares (PLS), least squares support vector machines (LS-SVM) and locally weighted regression (LWR) for the development of the calibration models showed that the LS-SVM did not out-perform linear methods for most components while LWR that creates simpler models performed well. The present results tend to show that soil models are quite sensitive to the complexity of the model. The ability of LWR to select only the appropriate samples did help in the development of robust models. Results also proved that field units performed as well as bench-top instruments. This was true for both near infrared and mid-infrared technology. Finally, analysis of field moist samples was not as satisfactory as using dried-ground samples regardless of the chemometrics methods applied.
Large Scale Laboratory Testing of Low Mobility Compaction Grouts for Drilled Shaft Tips
Authors: Pooranampillai Suthan , Elfass Sherif , Vanderpool Walt , Norris Gary
Published: July 2010

While post grouting of drilled shaft tips is an acknowledged means of mobilizing shaft base resistance at low values of displacement, much uncertainty exists among engineering professionals as to the conditions under which this option may be entertained. The impact of diverse factors such as soil gradation and soil relative density, overburden pressures, and grouting methods utilized needs to be properly understood. This paper details the laboratory test set-up utilized by researchers toward studying the impact of such factors on post grouting and resultant shaft base capacity increase. The focus of this paper is on the different components of the test set-up considered during the design and implementation stage. Several unique aspects dealt with as a part of this study and elaborated on herein include the testing chamber dimensions, method of overburden pressure application, soil deposition technique, grouting methodology employed for the low mobility compaction grout utilized, load testing protocol, and instrumentation. Sample test results included indicate satisfactory load resistance increase through grouting with a low mobility compaction grout. The performance of this set-up during the testing phase indicated applicability for use in large scale laboratory testing of low mobility grouts and drilled shaft foundations.
Statistical Calibration of ASTM C150 Bogue-Derived Phase Limits to Directly Determined Phases by Quantitative X-Ray Powder Diffraction
Authors: Stutzman Paul , Leigh Stefan
Published: July 2010

Statistical analyses of companion Bogue (ASTM C150-07) and quantitative X-ray powder diffraction (QXRD) estimates for cement phases are used to establish the most likely linear relationship between these two measurement techniques for alite, belite, aluminate, ferrite, and for the combinations (C3S+4.75⋅C3A) and (C4AF+2⋅C3A) used to characterize heat of hydration and sulfate resistance, respectively. This cross-calibration was performed using published data from more than 194 Portland cements, spanning more than 50 years of manufacture. Each resulting calibration is a linear relationship, reported with 99 % Working–Hotelling–Scheffé confidence limits from the least-squares regression. Fieller calibration intervals are used to report bounds for the QXRD values corresponding to the Bogue limits given in ASTM C150-07, Table 1. Such bounds could allow either technique to be used for phase estimation to assess the compliance of a Portland cement.