bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and control of an electronic wedge brake
Authors: Han Kwangjin , Kim Myoungjune , Huh Kunsoo
Published: January 2012

The electronic wedge brake is one of the brake-by-wire systems with a self-energizing effect. It is attractive because it can produce enough braking torque with the 12-voltage system. However, the electronic wedge brake cannot be implemented unless the self-energizing effect is effectively controlled. In this study, the electronic wedge brake is modeled into dynamic equations, and a sliding mode controller is designed based on the model. The clamping force is estimated based on the simplified electronic wedge brake model and the contact point detection algorithm is also provided. The performance of the proposed controller is verified in simulations and experiments using a prototype electronic wedge brake.
Protective role of curcumin on colchicine-induced cognitive dysfunction and oxidative stress in rats
Authors: Khurana S , Jain S , Mediratta PK , Banerjee BD , Sharma KK
Published: January 2012

Dementia is a syndrome of progressive nature, affects wide range of cognitive abilities like memory, language, calculation and so on, neuropsychiatric and social deficits to impair the routine social functions. The present study was designed to assess the effect of curcumin against colchicine-induced cognitive dysfunction and oxidative stress in rats and compare it with rivastigmine. Colchicine (15 µg/5µl) was administered to male Wistar rats intracerebroventricularly (i.c.v.) by stereotaxic apparatus to induce cognitive dysfunction. Administration of colchicine caused poor retention of memory in elevated plus maze, passive avoidance apparatus and Morris water maze paradigms. Chronic treatment with curcumin (100, 200 and 400 mg/kg, p.o.) twice daily and rivastigmine (2.5 mg/kg, p.o.) daily for a period of 28 days beginning 7 days prior to colchicine injection significantly improved colchicine-induced cognitive impairment. Biochemical assessment revealed that i.c.v. colchicine injection significantly increased lipid peroxidation, depleted reduced glutathione levels and decreased acetyl cholinesterase (AChE) activity in rat brains. Chronic administration of curcumin significantly reduced the elevated lipid peroxidation, restored the reduced glutathione levels and AChE activity; however, rivastigmine failed to prevent oxidative stress. The results of the current study indicate that curcumin (100, 200 and 400 mg/kg, p.o.) twice daily has a protective role against colchicine-induced cognitive impairment and associated oxidative stress.
A National Picture of Parent and Youth Participation in IEP and Transition Planning Meetings
Authors: Wagner Mary , Newman Lynn , Cameto Renée , Javitz Harold , Valdes Kathryn
Published: January 2012

Two prospective longitudinal studies of nationally representative samples of students with disabilities—the Special Education Elementary Longitudinal Study and the National Longitudinal Transition Study–2—are used to provide a broad look at the participation of parents of 11- through 19-year-old students with disabilities in Individualized Education Plan/transition planning meetings and their satisfaction with their involvement in them. Students’ attendance and the roles played in their transition planning meetings are also examined. Logistic regression analyses identify disability characteristics; demographics; aspects of parents’ involvement, expectations, and perceptions; experiences in students’ educational histories; and features of their instructional programs that help explain variations in parent and student participation, parent satisfaction, and student roles.
Evaluation of the Medicaid Buy-In Program in Washington State
Authors: Shah Melissa Ford , Mancuso David C. , He Lijian , Kozak Stephen
Published: January 2012

This study examines the effectiveness of Washington State’s Medicaid Buy-In (MBI) program—Healthcare for Workers With Disabilities (HWD)—which gives workers with disabilities who earn too much for conventional Medicaid the opportunity to purchase full Medicaid coverage by paying a monthly premium based on a sliding income scale. The authors compare HWD enrollees who recently had conventional Medicaid coverage to a statistically matched group of individuals who had conventional Medicaid coverage in recent history and at baseline. Their findings suggest that MBI in Washington State is encouraging work, increasing earnings, and decreasing reliance on food stamps while providing medical coverage to a vulnerable population for whom continuous health insurance is particularly important.
Effect of School-Initiated Parent Outreach Activities on Parent Involvement in School Events
Authors: Frew Leigh Ann , Zhou Qiong , Duran Jaime , Kwok Oi-Man , Benz Michael R.
Published: January 2012

Parent involvement is a cornerstone of special education policy and best practice. Parents of students with disabilities participate in school events in a manner similar to parents of students without disabilities, and the benefits of parent involvement are widely recognized for all students. Recent legislation and federal funding opportunities have targeted parent outreach programs as an area of improvement for schools. Using data from the Special Education Elementary Longitudinal Study, this study examined the effect of school-initiated parent outreach activities on parent involvement in school. Parents reported greater involvement in schools that offered a greater number of outreach activities. Parent involvement was lower for older students, non-Caucasian students, students from non-two-parent households, and students from lower income households, and these lower participation rates were not differentially higher in schools that offered a greater number of parent outreach activities. Patterns and trends of parent involvement and school-initiated outreach programs are discussed, with suggestions for practitioners and future research.
The Causal Relationship Between Academic Self-Concept and Academic Achievement for Students With Disabilities
Authors: Ju Song , Zhang Dalun , Katsiyannis Antonis
Published: January 2012

This study examined the reciprocal causal effect between academic self-concept and academic achievement with family SES and parent involvement as predictive factors. Elementary and secondary groups were also compared. Data were drawn from the Special Education Elementary Longitudinal Study (SEELS). The sample consisted of 2,950 students ages 8 to 14 (Grades 1 -9) at the time of Wave 1 data collection. Structural equation modeling (SEM) was used in the data analysis. It was found that, at the elementary level, Wave 1 academic achievement predicted Wave 2 self-concept and Wave 1 self-concept predicted Wave 2 achievement. Parent home involvement was a significant predictor for Wave 1 academic achievement. At the secondary level, family SES was a significant predictor for both Wave 1 academic achievement and self-concept. Implications of the findings are discussed.
Pioglitazone Attenuates Cardiac Fibrosis and Hypertrophy in a Rat Model of Diabetic Nephropathy
Authors: Elrashidy Rania A. , Asker Mervat E. , Mohamed Hoda E.
Published: January 2012

Pioglitazone has been demonstrated to have beneficial effects on cardiovascular outcomes. However, little is known about its effect on cardiac remodeling associated with diabetic nephropathy. Therefore, this study was designed to study the effects of pioglitazone on cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. For this purpose, male Wistar albino rats were randomly assigned into 4 groups (n = 10 per group): normal (N) group, diabetic (D) group, diabetic nephropathic (DN) group received an equal amount of vehicle (0.5% carboxy methyl cellulose), and diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. Diabetic nephropathy was induced by subtotal nephrectomy plus streptozotocin (STZ) injection. The results revealed that DN rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats. In addition, enhanced lipid peroxidation and myocardial injury, evidenced by a significant increase in their serum creatine kinase-MB level were observed in DN rats. All these abnormalities were ameliorated by pioglitazone administration. Our findings suggest that upregulation of cardiac TGF-β1 gene along with the imbalance between MMP-2 and TIMP-2 expressions is critically involved in cardiac fibrosis associated with diabetic nephropathy. Pioglitazone can ameliorate cardiac remodeling by suppressing the gene expression of TGF-β1 and regulating the MMP-2/TIMP-2 system.
On the methodology for evaluation of dynamic effects of a surface bonded piezoelectric patch for active vibration control
Authors: Barannyk Oleksandr , Buckham Bradley J , Oshkai Peter
Published: January 2012

The current work presents a semi-analytic approach for calculating the influence of surface bonded piezoelectric (PZT) actuators on the free vibration of a flexible beam. A transfer matrix technique, originally developed for analyses of non-proportionally damped flexible beams, was modified to incorporate the PZT actuators' effect. Specifically, the technique's recursive calculations were significantly altered to account for the PZT actuators' tendency to couple the dynamics of node points of the flexible beam. Unlike many analyses of PZT laminated beams, the technique requires no assumptions of the revised modes' shapes, and the limits imposed by saturation voltages were incorporated. The methodology was applied to a vibration suppression application. A simple case of a single PZT patch employing angular velocity feedback was used to demonstrate and validate the calculation methodology. The sensitivities of the beam modes of vibration to the location and control gain of the PZT patch were summarized. The implementation for cases of linear velocity feedback and cases of multiple PZT patches employing mixed feedback laws were also outlined. The calculation methodology is very flexible and is of great utility in the optimization based design of smart structures
The ASRS-6 Has Two Latent Factors
Authors: Hesse Morten
Published: January 2012

Objective: To test whether the Adult Self-Report Scale for ADHD, six-items version (ASRS-6), measures inattentiveness and hyperactivity independently. Method: The ASRS-6 was completed by 234 university students and 157 outpatients treated for drug dependence. In both samples, the ASRS-6 was subjected to two confirmatory factor analyses, one testing a one-factor model and the other testing a model with two correlated factors indicating inattentiveness and hyperactivity, respectively. Test–retest reliability of the subscales was tested on a subset of the student sample ( n = 25). Results: In both samples, the one-factor solution did not fit the data, but the two-factor solution fit the data better. Subscales differed in their correlates in ways that mirror the correlates of inattentiveness and hyperactivity in the published literature on ADHD. In the student sample, the test–retest reliability was adequate for hyperactivity ( r = .70) and inattentiveness ( r = .77). Conclusion: The ASRS-6 measures two correlated constructs, rather than one unitary construct.
Are Mycobacterium avium subsp. paratuberculosis and Epstein–Barr virus triggers of multiple sclerosis in Sardinia?
Authors: Cossu Davide , Masala Speranza , Cocco Eleonora , Paccagnini Daniela , Frau Jessica , Marrosu Maria Giovanna , Sechi Leonardo A
Published: January 2012

Sardinia acts as an ideal setting for multiple sclerosis (MS) studies because its prevalence of MS is one of the highest worldwide. Several pathogens have been investigated amongst 119 Sardinian MS patients and 117 healthy controls to determine whether they might have a role in triggering MS in genetically predisposed individuals. Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein Barr virus DNA were detected in 27.5% and 17.3%, respectively, of the MS patients. Moreover an extremely high humoral immune response against MAP recombinant protein MAP FprB (homologous to human myelin P0) was observed, whereas no significant results were found against Mycobacterium tuberculosis FprA and Helicobacter pylori HP986 protein.
‘Hard work’ in a new context: Clients’ experiences of psychotherapy
Authors: Göstas Mona Wilhelmsson , Wiberg Britt , Neander Kerstin , Kjellin Lars
Published: January 2012

The aim of this study was to describe and gain an understanding of clients’ experiences of psychotherapy contracts and processes in cognitive behavioural therapy (CBT) and psychodynamic psychotherapy (PDT). Fourteen participants were interviewed after ending their psychotherapy. To get information richness they were selected with as great a variation as possible in relation to their life context. Qualitative content analysis was used to analyse the descriptions and the significance of the descriptions. Similarities between the two therapy orientations emerged throughout the informants’ experiences. These similarities were expressed in the two themes: The creation of a new context and The working method and the cooperation with the psychotherapist made up a whole. The psychotherapy process was described as ‘hard work’ in a new context, markedly different from the ordinary social context. From the informants’ perspective, the creation of a new context offered a possibility to give full attention, together with the psychotherapist, to oneself and to the problems one was grappling with. A salient feature was the informant’s responsibility for agreements in the psychotherapy contract, especially in relation to the number of sessions and the creation of cooperation with the psychotherapist. Irrespective of therapy orientation the therapeutic techniques were described as inextricably linked to the cooperation with the psychotherapist. An implication for practice and research from these findings is to give more weight to the influence of cooperation in psychotherapy techniques, irrespective of therapy orientation. Another implication is an awareness that the client’s knowledge of her/his difficulties, needs and desire for change, capacity to make an effort and to assume responsibility always have to be highlighted and have an impact on the psychotherapy contract and process.
Clinical systems improvement: it’s all about the project boundaries
Authors: Gorrell Michelle
Published: January 2012

The National Health Service (NHS) in England is facing significant challenges ahead as a result of the government’s plans to reduce national debt. The challenge for infection control practitioners will be to continue to support the development and delivery of high quality clinical services without the level of funding previously experienced over the last decade. In order to achieve this all healthcare professionals will be required to embrace improvement strategies. The purpose of this paper is therefore to report on a review of a clinical reporting and root cause analysis (CRRCA) process coordinated by a community-based infection prevention and control team. The paper outlines the issues surrounding the current CRRCA process and analyses the process using lean concepts. A series of change options are put forward in order to illustrate how a failure to effectively scope improvement project boundaries can constrain change thereby limiting the potential for productivity and quality improvement.
Characterisation of welded joints produced by FSW in AA 1100–B4C metal matrix composites
Authors: Guo J F , Gougeon P , Chen X-G
Published: January 2012

The feasibility of friction stir welding for joining AA 1100 based metal matrix composites reinforced with B4C particulate is studied for 16 and 30%B4C volume concentrations. For both composites, friction stir welding has a significant influence on the particle size distribution and the matrix grain size. For the 16% composite, the average particle size decreases after welding by ∼20% and the grain size from 15 to 5 μm as measured in the weld nugget. Tensile testing of welded joints showed up to 100% joint efficiency for both annealed AA 1100–16%B4C and AA 1100–30%B4C composite materials. However, if the ultimate tensile strength values of all the studied composites are similar at ∼130 MPa, then the weld ductility is higher for the annealed materials. Furthermore, it was observed that varying the welding speed between 100 and 275 mm min−1 does not influence the tensile properties and the particle size distribution in the nugget.
t-PA–specific modulation of a human blood-brain barrier model involves plasmin-mediated activation of the Rho kinase pathway in astrocytes
Authors: Niego Be'eri , Freeman Roxann , Puschmann Till B. , Turnley Ann M. , Medcalf Robert L.
Published: January 2012

Tissue-type plasminogen activator (t-PA) can modulate permeability of the neurovascular unit and exacerbate injury in ischemic stroke. We examined the effects of t-PA using in vitro models of the blood-brain barrier. t-PA caused a concentration-dependent increase in permeability. This effect was dependent on plasmin formation and potentiated in the presence of plasminogen. An inactive t-PA variant inhibited the t-PA–mediated increase in permeability, whereas blockade of low-density lipoprotein receptors or exposed lysine residues resulted in similar inhibition, implying a role for both a t-PA receptor, most likely a low-density lipoprotein receptor, and a plasminogen receptor. This effect was selective to t-PA and its close derivative tenecteplase. The truncated t-PA variant reteplase had a minor effect on permeability, whereas urokinase and desmoteplase were ineffective. t-PA also induced marked shape changes in both brain endothelial cells and astrocytes. Changes in astrocyte morphology coincided with increased F-actin staining intensity, larger focal adhesion size, and elevated levels of phosphorylated myosin. Inhibition of Rho kinase blocked these changes and reduced t-PA/plasminogen–mediated increase in permeability. Hence plasmin, generated on the cell surface selectively by t-PA, modulates the astrocytic cytoskeleton, leading to an increase in blood-brain barrier permeability. Blockade of the Rho/Rho kinase pathway may have beneficial consequences during thrombolytic therapy.
Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production
Authors: Fortes Guilherme B. , Alves Leticia S. , de Oliveira Rosane , Dutra Fabianno F. , Rodrigues Danielle , Fernandez Patricia L. , Souto-Padron Thais , De Rosa María José , Kelliher Michelle , Golenbock Douglas , Chan Francis K. M. , Bozza Marcelo T.
Published: January 2012

Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4−/− or to Myd88−/− macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1−/−) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS.
R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes
Authors: Nian Hua , Geng Wen-Qing , Cui Hua-Lu , Bao Ming-jia , Zhang Zi-ning , Zhang Min , Pan Ying , Hu Qing-Hai , Shang Hong
Published: January 2012

Background

Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication.

Methods

Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.

Results

We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes.

Conclusions

Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.
Psychological characteristics in high-risk MSM in China
Authors: Chen Guanzhi , Li Yang , Zhang Beichuan , Yu Zengzhao , Li Xiufang , Wang Lixin , Yu Ziming
Published: January 2012

Background

Men who have sex with men (MSM) have become a high-risk group of HIV infection in China. To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk subpopulation of people extremely difficult.

Methods

A total of 714 questionnaires were retrieved from the database of a Chinese government-sponsored National Key Research Project titled "Risk Analysis and Strategic Prevention of HIV Transmission from MSM to the General Population in China". The respondents were categorized into a high-risk group and a control group. Their behavioral, social and psychological characteristics were comparatively analyzed.

Results

Of the 714 MSM analyzed, 59 (8.26%) had high-risk homosexual behaviors. This sub-group of MSM had a higher in-marriage rate, a higher monthly income, heavier alcohol consumption and more serious problems with sexual abuse in childhood, intentional suicide attempts and mistaken assumption on condom's role in protecting HIV infection, as compared with the control group (P < 0.05). In contrast, the two groups did not differ significantly the sexual orientation, level of education, types of profession, drug use, condom use and experience of social stigma and discrimination (P > 0.05). A vast majority of the individuals in both behavior categories expressed support of legally protected gay clubs as well as gay marriage legislation in China. There was a strong correlation between high-risk behaviors and sexual abuse in childhood, alcohol drinking, income level and a mistaken belief in perfect HIV protection through the use of condoms.

Conclusions

MSM with and without high-risk homosexual behaviors have different social and psychological characteristics, which should be taken into account when implementing behavioral and therapeutic interventions aimed at preventing HIV/AIDS transmission among MSM as well as from MSM to the general population in China.
VPA: an R tool for analyzing sequencing variants with user-specified frequency pattern
Authors: Hu Qiang , Wang Dan , Yan Li , Zhao Hua , Liu Song
Published: January 2012

Background

The massive amounts of genetic variant generated by the next generation sequencing systems demand the development of effective computational tools for variant prioritization.

Findings

VPA (Variant Pattern Analyzer) is an R tool for prioritizing variants with specified frequency pattern from multiple study subjects in next-generation sequencing study. The tool starts from individual files of variant and sequence calls and extract variants with user-specified frequency pattern across the study subjects of interest. Several position level quality criteria can be incorporated into the variant extraction. It can be used in studies with matched pair design as well as studies with multiple groups of subjects.

Conclusions

VPA can be used as an automatic pipeline to prioritize variants for further functional exploration and hypothesis generation. The package is implemented in the R language and is freely available from http://vpa.r-forge.r-project.org.
STAT1-deficient mice spontaneously develop estrogen receptor α-positive luminal mammary carcinomas
Authors: Chan Szeman Ruby , Vermi William , Luo Jingqin , Lucini Laura , Rickert Charles , Fowler Amy M , Lonardi Silvia , Arthur Cora , Young Larry JT , Levy David E , Welch Michael J , Cardiff Robert D , Schreiber Robert D
Published: January 2012

Introduction

Although breast cancers expressing estrogen receptor-α (ERα) and progesterone receptors (PR) are the most common form of mammary malignancy in humans, it has been difficult to develop a suitable mouse model showing similar steroid hormone responsiveness. STAT transcription factors play critical roles in mammary gland tumorigenesis, but the precise role of STAT1 remains unclear. Herein, we show that a subset of human breast cancers display reduced STAT1 expression and that mice lacking STAT1 surprisingly develop ERα+/PR+ mammary tumors.

Methods

We used a combination of approaches, including histological examination, gene targeted mice, gene expression analysis, tumor transplantaion, and immunophenotyping, to pursue this study.

Results

Forty-five percent (37/83) of human ERα+ and 22% (17/78) of ERα- breast cancers display undetectable or low levels of STAT1 expression in neoplastic cells. In contrast, STAT1 expression is elevated in epithelial cells of normal breast tissues adjacent to the malignant lesions, suggesting that STAT1 is selectively downregulated in the tumor cells during tumor progression. Interestingly, the expression levels of STAT1 in the tumor-infiltrating stromal cells remain elevated, indicating that single-cell resolution analysis of STAT1 level in primary breast cancer biopsies is necessary for accurate assessment. Female mice lacking functional STAT1 spontaneously develop mammary adenocarcinomas that comprise > 90% ERα+/PR+ tumor cells, and depend on estrogen for tumor engraftment and progression. Phenotypic marker analyses demonstrate that STAT1-/- mammary tumors arise from luminal epithelial cells, but not myoepithelial cells. In addition, the molecular signature of the STAT1-/- mammary tumors overlaps closely to that of human luminal breast cancers. Finally, introduction of wildtype STAT1, but not a STAT1 mutant lacking the critical Tyr701 residue, into STAT1-/- mammary tumor cells results in apoptosis, demonstrating that the tumor suppressor function of STAT1 is cell-autonomous and requires its transcriptional activity.

Conclusions

Our findings demonstrate that STAT1 suppresses mammary tumor formation and its expression is frequently lost during breast cancer progression. Spontaneous mammary tumors that develop in STAT1-/- mice closely recapitulate the progression, ovarian hormone responsiveness, and molecular characteristics of human luminal breast cancer, the most common subtype of human breast neoplasms, and thus represent a valuable platform for testing novel treatments and detection modalities.
Genetic adaptation to high altitude in the Ethiopian highlands
Authors: Scheinfeldt Laura B , Soi Sameer , Thompson Simon , Ranciaro Alessia , Woldemeskel Dawit , Beggs William , Lambert Charla , Jarvis Joseph P , Abate Dawit , Belay Gurja , Tishkoff Sarah A
Published: January 2012

Background

Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude.

Results

We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels.

Conclusions

We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.
The role of the Src family kinase Lyn in the immunomodulatory activities of cathelicidin peptide LL-37 on monocytic cells
Authors: Nijnik Anastasia , Pistolic Jelena , Cho Patricia , Filewod Niall C J , Falsafi Reza , Ramin Alexander , Harder Kenneth W , Hancock Robert E W
Published: January 2012

Cathelicidin LL-37 is a multifunctional, immunomodulatory and antimicrobial host-defense peptide of the human immune system. Here, we identified the role of SFKs in mediating the chemokine induction activity of LL-37 in monocytic cells. LL-37 induced SFK phosphorylation; and chemical inhibitors of SFKs suppressed chemokine production in response to LL-37 stimulation. SFKs were required for the downstream activation of AKT, but Ca2+-flux and MAPK induction were SFK-independent. Through systematic siRNA knockdown of SFK members, a requirement for Lyn in mediating LL-37 activity was identified. The involvement of Lyn in cathelicidin activities was further confirmed using Lyn-knockout mouse BMDMs. The role of SFKs and Lyn was also demonstrated in the activities of the synthetic cationic IDR peptides, developed as novel, immunomodulatory therapeutics. These findings elucidate the common molecular mechanisms mediating the chemokine induction activity of natural and synthetic cationic peptides in monocytic cells and identify SFKs as a potential target for modulating peptide responses.
Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease
Authors: Tawara Isao , Sun Yaping , Liu Chen , Toubai Tomomi , Nieves Evelyn , Evers Rebecca , Alrubaie Mariem , Mathewson Nathan , Tamaki Hiroya , Reddy Pavan
Published: January 2012

IL-10 is a key immune-regulatory cytokine, and its gene polymorphisms correlate with severity of clinical GVHD. IL-10 is made by a variety of donor and host cells, but the functional relevance of its source and its role in the biology of acute GVHD are not well understood. We used preclinical models to examine the relevance of IL-10−/− in donor and host cellular subsets on the severity of GVHD. IL-10−/− in host tissues or in the donor grafts did not alter donor Teff-mediated severity of GVHD. Furthermore, neither host-derived nor donor Teff-derived IL-10 was required for regulation of GVHD by WT CD4+CD25+ donor Tregs. By contrast, Treg-derived IL-10, although not obligatory, was necessary for optimal reduction of GVHD by mature donor Tregs. Importantly, IL-10 from donor BM grafts was also critical for optimal donor Treg-mediated suppression of GVHD. Together, these data suggest that IL-10 does not contribute to the induction of GVHD severity by the Teffs. However, donor BM graft and Treg-derived IL-10 are important for donor Treg-mediated suppression of GVHD.
Pulmonary lymphatic drainage to the mediastinum based on computed tomographic observations of the primary complex of pulmonary histoplasmosis
Authors: Takahashi Koji , Sasaki Tomoaki , Nabaa Basim , van Beek Edwin Junior , Stanford William , Aburano Tamio
Published: January 2012

Background

In the primary infection of pulmonary histoplasmosis, pulmonary lesions are commonly solitary and associated with hilar and/or mediastinal nodal diseases, which spontaneously resolve, resulting in calcifications in individuals with normal cellular immunity.

Purpose

To assess the lymphatic drainage to the mediastinum from each pulmonary segment and lobe using computed tomographic (CT) observations of a calcified primary complex pulmonary histoplasmosis and predict which patients with N2 disease that would benefit from surgery.

Material and Methods

We collected 585 CT studies of patients with primary complex histoplasmosis consisting of solitary calcified pulmonary lesions and calcified hilar and/or mediastinal nodal disease. Using the N stage criteria of non-small cell lung cancer, we assessed the distribution of the involved hilar and mediastinal nodes depending on the pulmonary segment of the lesion, with a focus on skip involvement. We also assessed the correlation between the incidence of N1and skip N2 involvement and the mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups.

Results

Skip involvement was common in the apical segment (9/45, 20.0%), posterior segment (7/31, 22.6%), and mediolbasal segment (13/20, 65.0%) in the right lung, and in the apicoposterior segment (7/55, 12.7%), lateral basal segment (6/26, 23.1%), and posterobasal segment (16/47, 34.0%) in the left lung. The incidence of skip involvement in each segment showed a significant inverse correlation with that of N1 involvement (r = –0.51, P <0.05) in both lungs. The mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups in all segments of both lungs were 1.4 (434/301) and 1.2 (93/77), and the former was significantly greater than the latter ( P <0.01).

Conclusion

Our data showed a predictable pattern of segmental and lobar lymphatic drainage to the mediastinum and suggested that skip involvement could represent the initial mediastinal node involvement via direct lymphatic drainage.
Mammography and ultrasonography evaluation of unexpected focal 18F-FDG uptakes in breast on PET/CT
Authors: Kim Mi Young , Cho Nariya , Chang Jung Min , Yun Bo La , Bae Min Sun , Kang Keon Wook , Moon Woo Kyung
Published: January 2012

Background

Unexpected focal 18F-FDG breast uptakes are occasionally identified on PET/CT due to its increased use for cancer staging and follow-up. The need for their characterization has been suggested.

Purpose

To retrospectively evaluate the diagnostic value of ultrasonography (US) in distinguishing benign from malignant lesions for unexpected focal 18F-FDG uptakes in breast on PET/CT scans.

Material and Methods

Between April 2004 and January 2010, 27 focal 18F-FDG breast uptakes in 27 patients (age range 33–62 years; mean age 46 years) among 5214 patients who had undergone PET/CT scans were retrospectively analyzed. The American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) final assessment categories of the US and the maximum standardized uptake values (SUVs) of the lesions were compared between the benign and malignant lesions.

Results

Of the 27 lesions, 15 (56%) lesions were malignant. The rate of malignancy, according to the final assessment category on the US, was 0% (0 of 6) for category 3, 60% for category 4 (9 of 15), and 100% (6 of 6) for category 5 ( P = 0.001). The US evaluation revealed a sensitivity of 100% (15 of 15) and a specificity of 50% (6 of 12). The average maximum SUV of the malignant lesions was greater than that of the benign lesions (4.12 ± 1.94 vs. 1.94 ± 0.82; P = 0.001).

Conclusion

US evaluation of unexpected focal 18F-FDG uptakes on PET/CT scans can accurately distinguish benign lesions from malignant lesions.
Telecytology in East Africa: a feasibility study of forty cases using a static imaging system
Authors: Kumar Neeta , Busarla Satya Vara Prasad , Sayed Shahin , Kirimi Jesca Muthoni , Okiro Patricia , Gakinya Samuel Mukono , Moloo Zahir , Sohani Aliyah R
Published: January 2012

We conducted a pilot study to assess the feasibility of telecytology as a diagnostic tool in difficult cases originating from a hospital in East Africa. Forty cytology cases considered difficult by a referring pathologist were posted on a telepathology website. Six pathologists independently assessed the static images. Telecytology diagnoses were compared with the consensus diagnoses made on glass slides and also with the histogical diagnoses when available. The diagnostic agreement of the six pathologists was 71–93% and tended to be higher for pathologists with more experience. Reasons for discordance included poor image quality, presence of diagnostic cells in thick areas of smears, sampling bias and screening errors. The consensus diagnoses agreed with histological diagnoses in all 17 cases in which a biopsy was performed. Diagnostic accuracy rates (i.e. telecytology diagnosis vs. histological diagnosis) for individual pathologists were 65–88%. To ensure diagnostic accuracy both referring and consulting pathologists must have adequate training in cytology, image acquisition and image-based diagnosis and the diagnostic questions of importance must be clearly communicated by the referring pathologist when posting a case.
Telemedicine interventions for substance-use disorder: a literature review
Authors: Young Lance Brendan
Published: January 2012

A literature review was conducted to identify research into multiple-contact (i.e. extended) telemedicine interventions for substance-use disorder. The goals were: (1) to describe the methodology used to evaluate telemedicine interventions; (2) to identify the range of interventions which have been formally evaluated; and (3) to summarize the findings. Fourteen databases and Google Scholar were searched, as well as bibliographies of relevant papers and online conference abstracts. There were 50 studies which met the inclusion criteria, of which 50% were randomized controlled trials. The studies most frequently reported the effect on substance use and 61% of those findings fully supported telemedicine interventions. Although the studies reported persistent challenges in sustaining participation, 76% of the studies reporting on satisfaction indicated that participants were enthusiastic supporters of telemedicine. Only 30% of reviewed studies addressed the effect on resource utilization. The majority of studies reported evidence of clinical effectiveness, which justifies continued research in the field.
The first three years of an inpatient adolescent forensic service
Authors: Hill Simon A , Preston Jackie
Published: January 2012

Bluebird House opened in February 2008. It was built to fill the gap of inpatient adolescent forensic services covering the South and South-West of England. This article describes the development of this highly specialized unit in its first three years.
Investor Inattention and the Market Impact of Summary Statistics
Authors: Gilbert Thomas , Kogan Shimon , Lochstoer Lars , Ozyildirim Ataman
Published: January 2012

We show that U.S. stock and Treasury futures prices respond sharply to recurring stale information releases. In particular, we identify a unique macroeconomic series—the U.S. Leading Economic Index® (LEI)—which is released monthly and constructed as a summary statistic of previously released inputs. We show that a front-running strategy that trades S&P 500 futures in the direction of the announcement a day before its release and then trades in the opposite direction of the announcement following its release generates an average annual return of close to 8%. These patterns are more pronounced for high beta stocks, for stocks that are more difficult to arbitrage, and during times when investors' sensitivity to firm-specific stale information is high. Treasury futures exhibit similar, albeit less pronounced, price patterns. Other measures of information arrival, such as price volatility and volume, spike following the release. These empirical findings suggest that some investors are inattentive to the stale nature of the information included in the LEI releases, instead interpreting it as new information, and thereby causing temporary yet significant mispricing.

This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Strategy for Quickest Second Meeting of Two Agents in Two Locations
Authors: Weber Richard
Published: January 2012

Howard [Howard, J. V. 2006. Unsolved symmetric rendezvous search problems: Some old and some new. Presentation, Sixth International Workshop in Search Games and Rendezvous, July 26, London School of Economics, London] has described a simply but nontrivial symmetric rendezvous search game in which two players are initially placed in two distinct locations. The game is played in discrete steps, at each of which each player can either stay where she is or move to the other location. When the players are in the same location for the first time they do not see one another, but when they are in the same location for a second time, then they meet. We wish to find a strategy such that, if both players follow it independently, then the expected number of steps at which this second meeting occurs is minimized. Howard conjectured that the optimal strategy is 3-Markovian, such that in each successive block of three steps the players should, with equal probability, do SSS, SMS, MSM, MMM, where “M” means move and “S” means stay. We prove that this strategy is optimal.
Should Dentists be Concerned about the Weight of their Patients?
Authors: Comyn Caroline , Kendall Nick , Wright Desmond
Published: January 2012

This opinion paper considers obesity and its relationship to dental practice. Twenty-three per cent of people in England are estimated to be obese, a figure that is predicted to continue rising. It follows that obese patients are frequently encountered in general dental practice. The authors review the links between obesity and dental health, the possible barriers and challenges to providing dental care for obese people, and how these may be overcome. They also report the findings of a London survey investigating the current provision of specialist dental services for obese patients who cannot be treated in a standard dental chair. Services across London were highly variable and in some areas no provision was identified. The implications of the rising prevalence of obesity for service planners and practitioners are also discussed.
Parenting Stress and Child Behavior Problems: A Transactional Relationship Across Time
Authors: Neece Cameron L , Green Shulamite A , Baker Bruce L
Published: January 2012

Parenting stress and child behavior problems have been posited to have a transactional effect on each other across development. However, few studies have tested this model empirically. The authors investigated the relationship between parenting stress and child behavior problems from ages 3 to 9 years old among 237 children, 144 of whom were typically developing and 93 who were identified as developmentally delayed. Behavior problems and parenting stress covaried significantly across time for both groups of children. Cross-lagged panel analyses generally supported a bidirectional relationship between parenting stress and child behavior problems for mothers and fathers.
Expression and Cellular Localization of Inducible Nitric Oxide Synthase in Lipopolysaccharide-treated Rat Kidneys
Authors: Choi Jae-Youn , Nam Sun-Ah , Jin Dong-Chan , Kim Jin , Cha Jung-Ho
Published: January 2012

Although inducible nitric oxide synthase (iNOS) is known to play significant roles in the kidney, its renal localization has long been controversial. To resolve this issue, the authors identified iNOS-positive cell types in rat kidneys using double immunohistochemistry and confirmed iNOS positivity using enzyme histochemistry with NADPH-diaphorase (NADPH-d) and in situ RT-PCR. Adult male Sprague-Dawley rats were injected intraperitoneally with lipopolysaccharide (LPS) or saline as a control and sacrificed at various time intervals after injection. Quantitative real-time reverse transcriptase polymerase chain reaction showed that iNOS was not expressed in control kidneys but was induced in LPS-treated kidneys. iNOS immunostaining was strongest 6 to 18 hr after injection and decreased gradually to control levels by day 7. Double immunohistochemistry and NADPH-d revealed that iNOS expression was induced in the interstitial cells, glomerular parietal epithelial cells, the proximal part of the short-looped descending thin limb, the upper and middle papillary parts of the long-looped descending thin limb, some inner medullary collecting duct cells, and almost all calyceal and papillary epithelial cells. The present study determines the precise localization of iNOS in LPS-treated rat kidneys and provides an important morphological basis for examining the roles of iNOS in sepsis-induced acute kidney injury.
Localization of Transforming Growth Factor Beta Receptor II Interacting Protein-1 in Bone and Teeth
Authors: Ramachandran Amsaveni , Ravindran Sriram , George Anne
Published: January 2012

Transforming growth factor beta receptor II (TGFβR-II) interacting protein 1 (TRIP-1) is a WD-40 protein that binds to the cytoplasmic domain of the TGF-β type II receptor in a kinase-dependent manner. To investigate the role of TRIP-1 in mineralized tissues, we examined its pattern of expression in cartilage, bone, and teeth and analyzed the relationship between TRIP-1 overexpression and mineralized matrix formation. Results demonstrate that TRIP-1 was predominantly expressed by osteoblasts, odontoblasts, and chondrocytes in these tissues. Interestingly, TRIP-1 was also localized in the extracellular matrix of bone and at the mineralization front in dentin, suggesting that TRIP-1 is secreted by nonclassical secretory mechanisms, as it is devoid of a signal peptide. In vitro nucleation studies demonstrate a role for TRIP-1 in nucleating calcium phosphate polymorphs. Overexpression of TRIP-1 favored osteoblast differentiation of undifferentiated mesenchymal cells with an increase in mineralized matrix formation. These data indicate an unexpected role for TRIP-1 during development of bone, teeth, and cartilage.