bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of Indoor Thermally Stratified Flows on the Basis of Eddy Viscosity/Diffusivity Model: State of the Art Review
Authors: Jun Gao  , Jia Ning Zhao  , Fu Sheng Gao  , Xu Zhang
Published: January 2009

Modeling of indoor air flow is one subject of significance in the area of building physics. As a multidisciplinary issue, the physics of air flow has been insufficiently investigated, especially for the thermally stratified flows that is widely encountered in indoor environment, and for the perimeter zones where exterior environment contributes much to the indoor thermal environment through envelops. This article tries to do an extensive survey about how to model thermally stratified flows within the RANS framework based on a literature review. First, turbulence phenomenon with the indoor thermally stratified flow is briefly interpreted. Second, the nonisotropic modification of Reynolds stress and heat flux is analyzed and the direct vertical correction is suggested to keep the simplicity of traditional EVM/EDM. Finally, a simpler nonisotropic correction is discussed, which adapts turbulent diffusion to the attenuated turbulence through modifying the isotropic turbulent viscosity and/or turbulent Prandtl number. This study, based on a limited but in-depth literature review, intends to sum up some useful suggestion on the modeling of indoor thermally stratified flows on the principles of simplicity and reliability. The motivation and objective of the present work is to achieve some fundamental guidelines for the evaluation of existing models and the exploration of new models.
Determination of the Air/Fiber Conductivity of Mineral Wool Insulations in Building Applications Using Nonlinear Estimation Methods
Authors: Veiseh S. , Hakkaki-Fard A. , Kowsary F.
Published: January 2009

The limitation of the experimental methods in determining the thermal conductivity due to the air/fiber conduction in mineral wools leads the use of inverse parameter estimation techniques. However, in some circumstances, the convergence of the inverse solution is impossible due to the correlation of the involving parameters and the existing noises in measurement data. In this article two relations are obtained to model thermal conductivity of the air/fiber conduction k(T, ρ), for glass fiber and rock wool insulations in temperatures between 0°C and 20°C, commonly encountered in building applications. Levenberg Marquardt's (LM) method is used for estimating of the unknown parameters in this article. Considering the nonlinear nature of the inverse problem and the correlation of the involving parameters and the existing noises in measurement data, the convergence of the problem is acceptable. The results obtained by the estimated parameters agree extremely well with experimental measurements of the Heat Flow Meter (HFM) apparatus conducted at the Building and Housing Research Center (BHRC).
Fibrates: where are we now?
Authors: Seth Loomba Rohit , Arora Rohit
Published: January 2009

Cardiovascular disease remains a leading cause of mortality worldwide. As dyslipidemia increases cardiovascular disease risk, proper management of dyslipidemia is one means by which to decrease cardiovascular disease risk. This review focuses on dyslipidemia treatment utilizing fibrate therapy, which targets high trigylcerides, low HDL, and high small, dense LDL, while contrasting fibrate therapy with statin therapy and combined therapy. Studies were obtained using electronic search strategies, such as Medline and Cochrane Library. Sources selected were limited to those that discussed fibrates, statins, and combined therapy, with specific emphasis placed on sources that focused on fibrates. Selected studies were then assessed for quality via analysis of the study's methodology, results, and data. Results of selected studies were then stratified using a rating system devised to determine the quality of results using the scientific evidence provided for them. Combination fibrate and statin therapy can be more effective in achieving optimal lipid levels than just fibrate or statin therapy alone without significant side effects as long as gemfibrozil is not used in therapy.
A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster
Authors: Zhang Xueqing , Lian Zheng , Padden Carolyn , Gerstein Mark B. , Rozowsky Joel , Snyder Michael , Gingeras Thomas R. , Kapranov Philipp , Weissman Sherman M. , Newburger Peter E.
Published: January 2009

We have identified an intergenic transcriptional activity that is located between the human HOXA1 and HOXA2 genes, shows myeloid-specific expression, and is up-regulated during granulocytic differentiation. The novel gene, termed HOTAIRM1 (HOX antisense intergenic RNA myeloid 1), is transcribed antisense to the HOXA genes and originates from the same CpG island that embeds the start site of HOXA1. The transcript appears to be a noncoding RNA containing no long open-reading frame; sucrose gradient analysis shows no association with polyribosomal fractions. HOTAIRM1 is the most prominent intergenic transcript expressed and up-regulated during induced granulocytic differentiation of NB4 promyelocytic leukemia and normal human hematopoietic cells; its expression is specific to the myeloid lineage. Its induction during retinoic acid (RA)–driven granulocytic differentiation is through RA receptor and may depend on the expression of myeloid cell development factors targeted by RA signaling. Knockdown of HOTAIRM1 quantitatively blunted RA-induced expression of HOXA1 and HOXA4 during the myeloid differentiation of NB4 cells, and selectively attenuated induction of transcripts for the myeloid differentiation genes CD11b and CD18, but did not noticeably impact the more distal HOXA genes. These findings suggest that HOTAIRM1 plays a role in the myelopoiesis through modulation of gene expression in the HOXA cluster.
Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo
Authors: Salter Alice B. , Meadows Sarah K. , Muramoto Garrett G. , Himburg Heather , Doan Phuong , Daher Pamela , Russell Lauren , Chen Benny , Chao Nelson J. , Chute John P.
Published: January 2009

Hematopoietic stem cells (HSCs) reside in association with bone marrow (BM) sinusoidal vessels in vivo, but the function of BM endothelial cells (ECs) in regulating hematopoiesis is unclear. We hypothesized that hematopoietic regeneration following injury is regulated by BM ECs. BALB/c mice were treated with total body irradiation (TBI) and then infused with C57Bl6-derived endothelial progenitor cells (EPCs) to augment endogenous BM EC activity. TBI caused pronounced disruption of the BM vasculature, BM hypocellularity, ablation of HSCs, and pancytopenia in control mice, whereas irradiated, EPC-treated mice displayed accelerated recovery of BM sinusoidal vessels, BM cellularity, peripheral blood white blood cells (WBCs), neutrophils, and platelets, and a 4.4-fold increase in BM HSCs. Systemic administration of anti–VE-cadherin antibody significantly delayed hematologic recovery in both EPC-treated mice and irradiated, non–EPC-treated mice compared with irradiated controls. These data demonstrate that allogeneic EPC infusions can augment hematopoiesis and suggest a relationship between BM microvascular recovery and hematopoietic reconstitution in vivo.
Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia
Authors: Kim Dong Hwan (Dennis) , Xu Wei , Ma Clement , Liu Xiangdong , Siminovitch Katherine , Messner Hans A. , Lipton Jeffrey H.
Published: January 2009

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, characterized by the presence of BCR/ABL fusion gene. It is unclear which cellular events drive BCR/ABL gene translocation or initiate leukemogenesis in CML. Bcl-2 promotes survival of hematopoietic stem cells. Accordingly, apoptosis-related pathway may involve in the leukemogenesis of CML. In the current study, we evaluated 80 single nucleotide polymorphism (SNP) markers involved in the pathways of apoptosis (n = 30), angiogenesis (n = 7), myeloid cell growth (n = 14), xenobiotic metabolism (n = 13), WT1 signaling (n = 7), interferon signaling (n = 4), and others (n = 5) in 170 CML patients and 182 healthy controls. In a single-marker analysis, the following SNPs were identified including VEGFA, BCL2, CASP7, JAK3, CSF3, and HOCT1. In the multivariate logistic model with these SNPs and covariates, only BCL2 (rs1801018) was significantly associated with the susceptibility to CML (P = .05; odds ratio [OR] 2.16 [1.00-4.68]). In haplotype analyses, haplotype block of BCL2 consistently showed significant association with the susceptibility to CML. Risk allele analysis showed that a greater number of risk alleles from BCL2 SNP correlated to increasing risk of CML (overall P = .1, OR 1.84 [1.06-3.22] for 3-4 risk alleles vs 0-1 risk alleles). The current study indicated that BCL2 SNP seemed to be associated with increasing susceptibility to CML.
Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality
Authors: Niessen Frank , Furlan-Freguia Christian , Fernández José A. , Mosnier Laurent O. , Castellino Francis J. , Weiler Hartmut , Rosen Hugh , Griffin John H. , Ruf Wolfram
Published: January 2009

Protease activated receptor 1 (PAR1) signaling can play opposing roles in sepsis, either promoting dendritic cell (DC)–dependent coagulation and inflammation or reducing sepsis lethality due to activated protein C (aPC) therapy. To further define this PAR1 paradox, we focused on the vascular effects of PAR1 signaling. Pharmacological perturbations of the intravascular coagulant balance were combined with genetic mouse models to dissect the roles of endogenously generated thrombin and aPC during escalating systemic inflammation. Acute blockade of the aPC pathway with a potent inhibitory antibody revealed that thrombin-PAR1 signaling increases inflammation-induced vascular hyperpermeability. Conversely, aPC-PAR1 signaling and the endothelial cell PC receptor (EPCR) prevented vascular leakage, and pharmacologic or genetic blockade of this pathway sensitized mice to LPS-induced lethality. Signaling-selective aPC variants rescued mice with defective PC activation from vascular leakage and lethality. Defects in the aPC pathway were fully compensated by sphingosine 1 phosphate receptor 3 (S1P3) deficiency or by selective agonists of the S1P receptor 1 (S1P1), indicating that PAR1 signaling contributes to setting the tone for the vascular S1P1/S1P3 balance. Thus, the activating proteases and selectivity in coupling to S1P receptor subtypes determine vascular PAR1 signaling specificity in systemic inflammatory response syndromes in vivo.
Lentivirus-mediated transgene delivery to the hippocampus reveals sub-field specific differences in expression
Authors: van Hooijdonk Lenneke WA , Ichwan Muhammad , Dijkmans Thomas F , Schouten Theo G , de Backer Marijke WA , Adan Roger AH , Verbeek Fons J , Vreugdenhil Erno , Fitzsimons Carlos P
Published: January 2009

Background

In the adult hippocampus, the granule cell layer of the dentate gyrus is a heterogeneous structure formed by neurons of different ages, morphologies and electrophysiological properties. Retroviral vectors have been extensively used to transduce cells of the granule cell layer and study their inherent properties in an intact brain environment. In addition, lentivirus-based vectors have been used to deliver transgenes to replicative and non-replicative cells as well, such as post mitotic neurons of the CNS. However, only few studies have been dedicated to address the applicability of these widespread used vectors to hippocampal cells in vivo. Therefore, the aim of this study was to extensively characterize the cell types that are effectively transduced in vivo by VSVg-pseudotyped lentivirus-based vectors in the hippocampus dentate gyrus.

Results

In the present study we used Vesicular Stomatitis Virus G glycoprotein-pseudotyped lentivirual vectors to express EGFP from three different promoters in the mouse hippocampus. In contrast to lentiviral transduction of pyramidal cells in CA1, we identified sub-region specific differences in transgene expression in the granule cell layer of the dentate gyrus. Furthermore, we characterized the cell types transduced by these lentiviral vectors, showing that they target primarily neuronal progenitor cells and immature neurons present in the sub-granular zone and more immature layers of the granule cell layer.

Conclusion

Our observations suggest the existence of intrinsic differences in the permissiveness to lentiviral transduction among various hippocampal cell types. In particular, we show for the first time that mature neurons of the granule cell layer do not express lentivirus-delivered transgenes, despite successful expression in other hippocampal cell types. Therefore, amongst hippocampal granule cells, only adult-generated neurons are target for lentivirus-mediated transgene delivery. These properties make lentiviral vectors excellent systems for overexpression or knockdown of genes in neuronal progenitor cells, immature neurons and adult-generated neurons of the mouse hippocampus in vivo.
Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease
Authors: Marsillach Judit , Camps Jordi , Ferré Natàlia , Beltran Raul , Rull Anna , Mackness Bharti , Mackness Michael , Joven Jorge
Published: January 2009

Background

Paraoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved.

Methods

CCl4 was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured.

Results

High levels of PON1 and MCP-1 expression were observed at 12th week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl4-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARδ expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005) and between PON1 and the amount of activated stellate cells (P = 0.001).

Conclusion

Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.
Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: A population based case-control study
Authors: Liu Chen-yu , Hsu Yi-Hsiang , Wu Ming-Tsang , Pan Pi-Chen , Ho Chi-Kung , Su Li , Xu Xin , Li Yi , Christiani David C ,   the Kaohsiung Leukemia Research Group
Published: January 2009

Background

Consumption of cured/smoked meat and fish leads to the formation of carcinogenicN-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia.

Methods

A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses.

Results

Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15–2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37–0.83) and bean-curd (OR = 0.55; 95% CI: 0.34–0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea.

Conclusion

Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.
Luteal blood flow and luteal function
Authors: Takasaki Akihisa , Tamura Hiroshi , Taniguchi Ken , Asada Hiromi , Taketani Toshiaki , Matsuoka Aki , Yamagata Yoshiaki , Shimamura Katsunori , Morioka Hitoshi , Sugino Norihiro
Published: January 2009

Background

Blood flow in the corpus luteum (CL) is associated with luteal function. The present study was undertaken to investigate whether luteal function can be improved by increasing CL blood flow in women with luteal phase defect (LFD).

Methods

Blood flow impedance in the CL was measured by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a resistance index (RI). The patients with both LFD [serum progesterone (P) concentrations < 10 ng/ml during mid-luteal phase] and high CL-RI (≥ 0.51) were given vitamin-E (600 mg/day, n = 18), L-arginine (6 g/day, n = 14) as a potential nitric oxide donor, melatonin (3 mg/day, n = 13) as an antioxidant, or HCG (2,000 IU/day, n = 10) during the subsequent menstrual cycle.

Results

In the control group (n = 11), who received no medication to increase CL blood flow, only one patient (9%) improved in CL-RI and 2 patients (18%) improved in serum P. Vitamin-E improved CL-RI in 15 patients (83%) and improved serum P in 12 patients (67%). L-arginine improved CL-RI in all the patients (100%) and improved serum P in 10 patients (71%). HCG improved CL-RI in all the patients (100%) and improved serum P in 9 patients (90%). Melatonin had no significant effect.

Conclusion

Vitamin-E or L-arginine treatment improved luteal function by decreasing CL blood flow impedance. CL blood flow is a critical factor for luteal function.
Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFα-induced MEK/ERK signalling
Authors: Rockel Jason S , Bernier Suzanne M , Leask Andrew
Published: January 2009

Introduction

TNFα is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNFα activates mitogen-activated kinase kinase (MEK)/extracellular regulated kinase (ERK) in chondrocytes; however, the overall functional relevance of MEK/ERK to TNFα-regulated gene expression in chondrocytes is unknown.

Methods

Chondrocytes were treated with TNFα with or without the MEK1/2 inhibitor U0126 for 24 hours. Microarray analysis and real-time PCR analyses were used to identify genes regulated by TNFα in a MEK1/2-dependent fashion. Promoter/reporter, immunoblot, and electrophoretic mobility shift assays were used to identify transcription factors whose activity in response to TNFα was MEK1/2 dependent. Decoy oligodeoxynucleotides bearing consensus transcription factor binding sites were introduced into chondrocytes to determine the functionality of our results.

Results

Approximately 20% of the genes regulated by TNFα in chondrocytes were sensitive to U0126. Transcript regulation of the cartilage-selective matrix genes Col2a1, Agc1 and Hapln1, and of the matrix metalloproteinase genes Mmp-12 and Mmp-9, were U0126 sensitive – whereas regulation of the inflammatory gene macrophage Csf-1 was U0126 insensitive. TNFα-induced regulation of Sox9 and NFκB activity was also U0126 insensitive. Conversely, TNFα-increased early growth response 1 (Egr-1) DNA binding was U0126 sensitive. Transfection of chondrocytes with cognate Egr-1 oligodeoxynucleotides attenuated the ability of TNFα to suppress Col2a1, Agc1 or Hapln1 mRNA expression.

Conclusions

Our results suggest that MEK/ERK and Egr1 are required for TNFα-regulated catabolic and anabolic genes of the cartilage extracellular matrix, and hence may represent potential targets for drug intervention in osteoarthritis or rheumatoid arthritis.
Macrophage fusion, giant cell formation, and the foreign body response require matrix metalloproteinase 9
Authors: MacLauchlan Susan , Skokos Eleni A , Meznarich Norman , Zhu Dana H , Raoof Sana , Shipley J Michael , Senior Robert M , Bornstein Paul , Kyriakides Themis R
Published: January 2009

Macrophages undergo fusion to form multinucleated giant cells in several pathologic conditions, including the foreign body response (FBR). We detected high levels of matrix metalloproteinase (MMP)-9 during macrophage fusion in vitro and in foreign body giant cells (FBGCs) in vivo. Wild-type (WT) bone marrow-derived macrophages were induced to fuse with IL-4 in the presence of MMP-9 function-blocking antibodies and displayed reduced fusion. A similar defect, characterized by delayed shape change and abnormal morphology, was observed in MMP-9 null macrophages. Analysis of the FBR in MMP-9 null mice was then pursued to evaluate the significance of these findings. Specifically, mixed cellulose ester disks and polyvinyl alcohol sponges were implanted s.c. in MMP-9 null and WT mice and excised 2–4 weeks later. Histochemical and immunohistochemical analyses indicated equal macrophage recruitment between MMP-9 null and WT mice, but FBGC formation was compromised in the former. In addition, MMP-9 null mice displayed abnormalities in extracellular matrix assembly and angiogenesis. Consistent with a requirement for MMP-9 in fusion, we also observed reduced MMP-9 levels in MCP-1 null macrophages, previously shown to be defective in FBGC formation. Collectively, our studies show abnormalities in MMP-9 null mice during the FBR and suggest a role for MMP-9 in macrophage fusion.
Global Tobacco Problem Getting Worse, Not Better
Authors: Jatoi Ismail , Cummings K. Michael , Cazap Eduardo
Published: January 2009

Tobacco use is declining in most industrialized countries but that does not mean the tobacco problem is going away. Unless aggressive steps are taken to change consumption trends, current tobacco-related cancer deaths will increase dramatically in the next few decades.
Medical Errors: Physician and Institutional Responsibilities
Authors: Rodriguez Maria Alma , Storm Courtney D. , Burris Howard A.
Published: January 2009

When it comes to medical errors, honesty is always the best practice for your practice.
Combined Receptor Antagonist Stimulation of the Hypothalamic-Pituitary-Adrenal Axis Test Identifies Impaired Negative Feedback Sensitivity to Cortisol in Obese Men
Authors: Mattsson Cecilia , Reynolds Rebecca M. , Simonyte Kotryna , Olsson Tommy , Walker Brian R.
Published: January 2009

Context: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie disorders including obesity, depression, cognitive decline, and the metabolic syndrome. Conventional tests of HPA axis negative feedback rely on glucocorticoid receptor (GR) agonists such as dexamethasone but do not test feedback by endogenous cortisol, potentially mediated by both GR and mineralocorticoid receptors (MR).

Objective: The objective of the study was to use a combination of GR (RU38486, mifepristone) and MR (spironolactone) antagonists to explore the poorly understood activation of the HPA axis that occurs in obesity.

Design: This was a double-blind, placebo-controlled, randomized, crossover study.

Setting: The study was conducted at a clinical research facility.

Participants: Participants included 15 lean (body mass index 22.0 ± 1.6 kg/m2) and 16 overweight/obese (body mass index 30.1 ± 3.5 kg/m2) men.

Intervention: Subjects attended on four occasions for blood and saliva sampling every 30 min between 1800 and 2200 h. At 1100 and 1600 h before visits, subjects took 200 mg spironolactone, 400 mg RU38486, 200 mg spironolactone + 400 mg RU38486, or placebo orally.

Main Outcome Measures: Serum cortisol levels after drug or placebo were measured.

Results: Cortisol levels did not differ between lean and obese after placebo. Spironolactone and RU38486 alone had modest effects, increasing cortisol by less than 50% in both groups. However, combined spironolactone plus RU38486 elevated cortisol concentrations substantially, more so in lean than obese men [2.9- (0.3) vs. 2.2 (0.3)-fold elevation, P = 0.002].

Conclusions: Combined receptor antagonist stimulation of the HPA axis reveals redundancy of MR and GR in negative feedback in humans. Obese men have impaired responses to combined receptor antagonist stimulation, suggesting impaired negative feedback by endogenous cortisol. Such an approach may be useful to dissect abnormal HPA axis control in neuropsychiatric and other disorders.
Phenotypic and Molecular Evaluation of a Chromosome 1q Region with Linkage and Association to Type 2 Diabetes in Humans
Authors: Wang Hua , Hays Nicholas P. , Das Swapan K. , Craig Rebekah L. , Chu Winston S. , Sharma Neeraj , Elbein Steven C.
Published: January 2009

Objective: Linkage to type 2 diabetes (T2D) is well replicated on chromosome 1q21-q23. Within this region, T2D was associated with common single nucleotide polymorphisms that marked an extended linkage disequilibrium block, including the liver pyruvate kinase gene (PKLR), in several European-derived populations. In this study we sought to determine the molecular basis for the association and the phenotypic consequences of the risk haplotype.

Research Design and Methods: Genes surrounding PKLR were resequenced in European-American and African-American cases and controls, and association with T2D was tested. Copy number variants (CNVs) were tested for four regions with real-time PCR. Expression of genes in the region was tested in adipose and muscle from nondiabetic subjects with each genotype. Insulin secretion, insulin sensitivity, and hepatic glucose production were tested in nondiabetic individuals with each haplotype combination.

Results: No coding variant in the region was associated with T2D. CNVs were rare and not associated with T2D. PKLR was not expressed in available tissues, but expression of genes HCN3, CLK2, SCAMP3, and FDPS was not associated with haplotype combinations in adipose or muscle. Haplotype combinations were not associated with insulin secretion or peripheral insulin sensitivity, but homozygous carriers of the risk haplotype had increased hepatic glucose production during hyperinsulinemia.

Conclusions: Noncoding variants in the PKLR region likely alter gene expression of one or more genes. Our extensive physiological and molecular studies suggest increased hepatic glucose production and reduced hepatic insulin sensitivity, thus pointing to PKLR itself as the most likely candidate gene in this population.
Simulation of a freight train brake system with 120 valves
Authors: Wei W , Lin Y
Published: January 2009

A freight car air brake system simulation model that is based on air flow dynamics and function principle of the ‘120’ control valve is established. Functions of unsteady air flows in the air brake pipes, the boundary conditions used in the air brake system, and the calculation method for pressures in the brake pipe, brake cylinder, and auxiliary air reservoir are discussed. A comparison of the simulation results with the experiment test results is made to verify the validity of the simulation. The results of the simulations, including long and short train with large and small pressure reduction service brake application, release, and emergency brake application, show good consistence with the experiment results on pressure change and its timing in the brake pipe, brake cylinder, and auxiliary reservoir, with the exception of long train at small pressure reduction application. This indicates that the simulation model can correctly predict the pressure behaviour of the unsteady air flows in the air brake system and component movements in the ‘120’ control valve. The model can simulate braking characteristics of a freight train consisting of up to four locomotives. The simulation results can be used to successfully predict the braking distances and to assist longitudinal, dynamic, and impact force analyses of a train. The simulation is useful in the design, research, and development of brake systems and can provide insight into how components of the ‘120’ air brake control valve work.
Study of the structure design and optimization theory for a railway intelligent transportation system
Authors: Zhuo Wang , Li-Min Jia , Yong Qin
Published: January 2009

Railway intelligent transportation system (RITS) is the combination of intelligent transportation system (ITS) and rail transportation. RITS is the important part of ITS, which is taken for the senior development stage of rail transportation. The concept of RITS is put first forward in this paper. Based on the study and analysis of the RITS system framework in China, it is proposed that the essence of the RITS structure design and optimization problem is how to determine and optimize the mapping relations between the logical structure and physical structure, and taking this point as start, to try to set up the RITS structure design theory-oriented system realization. The technical route is to define the mapping relations between logical structure and physical structure, making a set of structure design alternatives. With the target system, the fuzzy matter-unit optimization method is adopted to achieve optimization, thereby obtaining the best from structure design alternatives. The design and optimization theory applied to the RITS system framework is a relative systematic approach that can solve similar problems existing in other information systems.
Design and analysis of low-stress and low-noise lightweight railway wheel
Authors: Akama M , Sasakura M , Furuno K
Published: January 2009

The finite-element and boundary-element methods were applied to develop the low-stress and low-noise lightweight railway wheel. First, stress analyses for the existing wheels under the condition of drag braking or track loading were performed. Following these analyses, a design methodology was developed and applied, leading to the development of new plate shapes of the wheel, whose stresses generated were lower than those of conventional wheels. Candidate plate shapes were selected based on the analyses. Next, eigenvalue analyses and transient dynamic analyses were carried out for the wheels. At the same time, to verify the analytical results, these wheels were manufactured and experiments implemented. Finally, acoustic analyses were performed and results compared with those obtained by field measurements. From this study, a new plate shape of the lightweight railway wheel was obtained, which reduces the radiated noise as well as the maximum stresses generated in the plate region to a remarkable extent.
Effect of collector deformable modes in pantograph—catenary dynamic interaction
Authors: Collina A , Lo Conte A , Carnevale M
Published: January 2009

The aim of the paper is to highlight the influence of the deformable modes of the collector of high-speed pantograph on the quality of current collection. The study was first conducted with an experimental survey on a few collectors for high-speed pantographs, in order to determine their modal parameters and dynamic responses in relation with their structures. Subsequently, a comparison with finite-element modelling was performed, comparing the calculated natural frequencies and mode shapes with the measured ones. Finally, the influence of the deformable modes on the dynamic interaction between pantograph and catenary was analysed, using a simulation model developed in previous works, incorporating the deformable modes of the collector into the model of the pantograph, by means of the experimentally defined modal parameters. The objective of this analysis was to investigate, in particular, the effect of the contact wire irregularity on the contact force up to 100 Hz.
Regio- and Stereoselective Subterminal Hydroxylations of n-Decane by Fungi in a Liquid–Liquid Interface Bioreactor (L–L IBR)
Authors: Oda Shinobu , Isshiki Kunio , Ohashi Shinichi
Published: January 2009

This article may be the first report to describe the excellent regio- and stereoselective subterminal hydroxylations of n-alkane with microorganisms. Approximately 2000 fungal strains were screened for the regioselective hydroxylation of n-decane with a solid–liquid interface bioreactor, which is a microbial transformation device on an interface between an agar plate and an organic phase (n-decane). Although Beauveria bassiana ATCC 7159, a typical fungus having a strong and versatile hydroxylating ability, mainly produced a mixture of 2-, 3-, 4-, and 5-decanone regioisomers into a n-decane layer, Monilliela sp. NAP 00702 and Rhizopus oryzae R-38-8 typically accumulated 4- and 5-decanols into the n-decane layer, respectively. Although a small amount of 4- and 5-decanones were also produced, the regioselectivity at C-4 and C-5 positions of n-decane reached 99 and 90%, respectively. Furthermore, the hydroxylation of n-decane with Monilliela sp. NAP 00702 stereoselectively proceeded to afford almost 100% ee of (−)-4-decanol.
Design of Porphyrin Nanoclusters toward Discovery of Novel Properties and Functions
Authors: Tsuda Akihiko
Published: January 2009

We have designed a variety of functional metalloporphyrin nanoclusters, connected via covalent or noncovalent linkages, since a discovery of fused bismetalloporphyrins [Ar3P]2(II) and [Ar3P]2(III) (Schemes 1–10 include symbols of the compounds), which have a strong π-electronic interaction over the bisporphyrin array. Among them, the following three topics are described in this review article. (1) Fused porphyrin nanoclusters: Directly fused oligoporphyrins, obtained through oxidative fused reactions of metalloporphyrins, show extremely strong π-electronic communications among the multiporphyrin components. (2) Self-assembled porphyrin nanoclusters: A zinc complex of meso–meso linked bisporphyrin [PyP]2(I) bearing 4-pyridyl substituents, which allow Zn–N coordination interaction, forms a homochiral box-shaped cyclic tetramer {[PyP]2(I)}4. Its rotamers upon insertion of an oligoalkynylene bridge between the two porphyrin components [PyP]2(≡)n (n = 1, 2, and 4) result in “conformational solvatochromism in nonpolar solvents” in n = 2 and “chiroptical sensing of asymmetric hydrocarbons” in n = 4, due to molecular recognition of solvents at the nanoscale cavity of box-shaped architecture. While a zinc porphyrin bearing a 3-pyridyl substituent (3-Py)P forms a cyclic tetramer with considerable structural distortion, its π-extended derivative (3-Py)P(≡)1 bearing a trimethylsilylethynyl group shows “supramolecular thermochromism” with a vivid color change, due to a temperature-dependent self-assembling event. A supramolecular polymer of J-aggregated zinc porphyrin dendrimer DP can visualize chiroptically a macroscopic chirality of vortex flows, generated by mechanical rotary stirring of a fluid. (3) Inorganic–organic nanocomposites: A giant ring-shaped polyoxomolybdate cluster MC having a large cavity with a diameter of approximately 2.3 nm accommodates up to three molecules of aminophenyl-substituted metalloporphyrins TAP via hydrogen-bonding interactions, resulting in formation of discrete inorganic/organic inclusion complexes. Template-assisted cofacial assembly of MC by an oligomeric p-phenylenebutadiynylene rigid rod molecule bearing ammonium ion pendants PBn allows formation of an inorganic/organic one-dimensional (1D) nano-object, having a polypseudorotaxane structure.
Doubly Thiazole Orange-Labeled DNA for Live Cell RNA Imaging
Authors: Kubota Takeshi , Ikeda Shuji , Okamoto Akimitsu
Published: January 2009

A hybridization-sensitive, quencher-free fluorescent probe for RNA detection has been designed using the concept of fluorescence quenching caused by the intramolecular excitonic interaction of fluorescence dyes. We synthesized a doubly thiazole orange-labeled nucleoside showing high fluorescence intensity for a hybrid with the target RNA and effective quenching for the single-stranded state. The probe was applied to living HeLa cells using microinjection to visualize intracellular mRNA localization. Immediately after injection of the probe into the cell, fluorescence from the probe hybridizing with the target RNA was observed. This fluorescence rapidly decreased upon addition of a competitor DNA. This probe realized a large, rapid, and reversible change in fluorescence intensity in sensitive response to the amount of target RNA, and facilitated spatiotemporal monitoring of the behavior of intracellular RNA.
Photoinduced Proton Transfer in 2-(2′-Hydroxynaphthalenyl)benzoxazole: Observation of Fluorescence with a Small Stokes Shift Induced by Excited-State Intramolecular Proton Transfer
Authors: Kanda Tomoko , Momotake Atsuya , Shinohara Yoshihiro , Sato Tomoo , Nishimura Yoshinobu , Arai Tatsuo
Published: January 2009

2-(2′-Hydroxynaphthalenyl)benzoxazole (1) emits fluorescence with small Stokes shift from its excited tautomer (K*), produced by excited-state intramolecular proton transfer. Intramolecular hydrogen bonding may be responsible for this phenomenon on comparison with the results of 2-(2′-hydroxyphenyl)benzoxazole (HBO) and 2-(naphthalene-1-yl)benzoxazole (2) as a reference compound.
Silylboranes as New Tools in Organic Synthesis
Authors: Ohmura Toshimichi , Suginome Michinori
Published: January 2009

New reactivities of silylboranes are described with their applications to organic synthesis. The silylboranes add to unsaturated organic compounds such as alkynes, alkenes, 1,3-dienes, and allenes in the presence of nickel, palladium, and platinum catalysts. Reactions with isocyanide proceed in the absence of catalysts, giving 1,1-addition products. The silaborations proceed in highly regio- and stereoselective manners, leading to the formation of organic compounds bearing silyl and boryl groups. Silaborations accompanied by regioselective C–C bond cleavage in three-membered rings take place in the reactions of methylenecyclopropane and vinylcyclopropane derivatives. Unsaturated organic molecules, e.g., 1,3-diene and aldehyde, undergo silaborative C–C coupling reactions in the presence of transition-metal catalysts. Enantioselective silaboration of terminal allenes and silaborative C–C cleavage of meso-methylenecyclopropanes have been achieved. Silaborations in which the stereochemical course, i.e., cis and trans stereoselectivities, is governed by the ligand have been established in platinum-catalyzed intramolecular silaborations of alkenes. Synthetic applications of the silaboration products through Suzuki–Miyaura coupling, one-carbon homologation, oxidation, allylation, and Rh-catalyzed conjugate addition are also described. Synthesis of silylboranes, including those having heteroatom functional groups at the silicon atoms, is summarized.
Elongated Lifetime of Unstable Colored Species by Intermolecular Hydrogen Bond Formation in Photochromic Crystals
Authors: Johmoto Kohei , Sekine Akiko , Uekusa Hidehiro , Ohashi Yuji
Published: January 2009

The crystallization of N-3,5-di-tert-butylsalicylidene-3-carboxyaniline (1) from a methanol solution gave three crystal forms, 1α, 1β, and 1γ. The colorless 1α and pale yellow 1β turned red when they were irradiated with UV light whereas orange 1γ showed no color change. The lifetimes of the colored crystals were estimated to be 17 and 780 min at room temperature for 1α and 1β, respectively, from IR spectra. The structure of the colored 1α crystal was analyzed by X-ray at 93 K. In addition to the original enol form of 1, the trans-keto form appeared on the difference electron density map with an occupancy factor of 0.117(2). This indicates that the color change was caused by the structural change from the enol to trans-keto form, which is the same as the color change previously reported in the crystal of N-3,5-di-tert-butylsalicylidene-3-nitroaniline (2) (lifetime, 1200 min). It was made clear from the structures of the trans-keto forms in the crystals of 1α, 1β, and 2 that the lifetime of the unstable colored form should be determined by the possibility and the strength of the intermolecular hydrogen bond formation of the N–H group of the trans-keto form to the neighboring molecules.
Intermolecular Hydrogen Bonds between a Radical and a Diamagnetic Matrix: CW-ESR Investigations of 2,6-Di-tert-butyl-4-hydroxymethylphenol
Authors: Yamaji Toshiki , Saiful Islam SM , Baba Masaaki , Yamauchi Seigo , Yamauchi Jun
Published: January 2009

We propose a novel formation model of an intermolecular hydrogen bond between radicals and a diamagnetic matrix in the condensed phase. W-band and multi-frequency ESR studies revealed that the polycrystalline radical sample generated from PbO2 oxidation of 2,6-di-tert-butyl-4-hydroxymethylphenol in toluene solution in vacuum at room temperature has an anomalously large 1H-hyperfine interaction. It was concluded that this interaction is attributed to hydrogen bonding between thepara-OH or the phenolic OH of the primary phenol. Although the phenol shows interesting radical chemical reactions unlike other 2,6-di-tert-butylphenol derivatives, the generated radical species were successfully defined by the solution ESR investigations. This may be the first ESR observation of an anomalously large hyperfine doublet structure coming from a proton on an intermolecular hydrogen bond between a radical and a diamagnetic phenol.which is a paramagnetic center in the molecular structure of the radicals and the
Coarse-grained modeling of large RNA molecules with knowledge-based potentials and structural filters
Authors: Jonikas Magdalena A. , Radmer Randall J. , Laederach Alain , Das Rhiju , Pearlman Samuel , Herschlag Daniel , Altman Russ B.
Published: January 2009

Understanding the function of complex RNA molecules depends critically on understanding their structure. However, creating three-dimensional (3D) structural models of RNA remains a significant challenge. We present a protocol (the nucleic acid simulation tool [NAST]) for RNA modeling that uses an RNA-specific knowledge-based potential in a coarse-grained molecular dynamics engine to generate plausible 3D structures. We demonstrate NAST's capabilities by using only secondary structure and tertiary contact predictions to generate, cluster, and rank structures. Representative structures in the best ranking clusters averaged 8.0 ± 0.3 Å and 16.3 ± 1.0 Å RMSD for the yeast phenylalanine tRNA and the P4-P6 domain of the Tetrahymena thermophila group I intron, respectively. The coarse-grained resolution allows us to model large molecules such as the 158-residue P4-P6 or the 388-residue T. thermophila group I intron. One advantage of NAST is the ability to rank clusters of structurally similar decoys based on their compatibility with experimental data. We successfully used ideal small-angle X-ray scattering data and both ideal and experimental solvent accessibility data to select the best cluster of structures for both tRNA and P4-P6. Finally, we used NAST to build in missing loops in the crystal structures of the Azoarcus and Twort ribozymes, and to incorporate crystallographic data into the Michel–Westhof model of the T. thermophila group I intron, creating an integrated model of the entire molecule. Our software package is freely available at https://simtk.org/home/nast.
Comparison and functional implications of the 3D architectures of viral tRNA-like structures
Authors: Hammond John A. , Rambo Robert P. , Filbin Megan E. , Kieft Jeffrey S.
Published: January 2009

RNA viruses co-opt the host cell's biological machinery, and their infection strategies often depend on specific structures in the viral genomic RNA. Examples are tRNA-like structures (TLSs), found at the 3′ end of certain plant viral RNAs, which can use the cell's aminoacyl tRNA-synthetases (AARSs) to drive addition of an amino acid to the 3′ end of the viral RNA. TLSs are multifunctional RNAs involved in processes such as viral replication, translation, and viral RNA stability; these functions depend on their fold. Experimental result-based structural models of TLSs have been published. In this study, we further examine these structures using a combination of biophysical and biochemical approaches to explore the three-dimensional (3D) architectures of TLSs from the turnip yellow mosaic virus (TYMV), tobacco mosaic virus (TMV), and brome mosaic virus (BMV). We find that despite similar function, these RNAs are biophysically diverse: the TYMV TLS adopts a characteristic tRNA-like L shape, the BMV TLS has a large compact globular domain with several helical extensions, and the TMV TLS aggregates in solution. Both the TYMV and BMV TLS RNAs adopt structures with tight backbone packing and also with dynamic structural elements, suggesting complexities and subtleties that cannot be explained by simple tRNA mimicry. These results confirm some aspects of existing models and also indicate how these models can be improved. The biophysical characteristics of these TLSs show how these multifunctional RNAs might regulate various viral processes, including negative strand synthesis, and also allow comparison with other structured RNAs.
Erythrocyte Sedimentation Rate Measurements by TEST 1 Better Reflect Inflammation Than Do Those by the Westergren Method in Patients With Malignancy, Autoimmune Disease, or Infection
Authors: Cha Choong-Hwan , Park Chan-Jeoung , Cha Young Joo , Kim Hyun Kyung , Kim Duck Hee , Honghoon  , Bae Jae Hoon , Jung Jae-Seol , Jang Seongsoo , Chi Hyun-Sook , Lee Dong Soon , Cho Han-Ik
Published: January 2009

We compared the TEST 1 (Alifax, Padova, Italy) and Westergren methods of measuring the erythrocyte sedimentation rate (ESR) to assess inflammation. The ESR was measured by both methods in 154 blood samples from patients with malignancy (n = 69), autoimmune disease (n = 44), or infection (n = 41). Total protein, albumin, and C-reactive protein (CRP) levels were measured in each plasma sample, and albumin and α1-, α2-, β1-, β2-, and γ-globulin fractions were measured by capillary electrophoresis. TEST 1 ESR values were significantly lower than the Westergren values, by 10.9 mm/h. We found that the correlations of TEST 1 ESR values with inflammatory protein levels (total protein, globulin, CRP, and α1-, α2-, β2-, and γ-globulin) were better than those obtained using the Westergren method. These findings indicate that ESR measurements by TEST 1 reflect inflammation better than do those by the Westergren method in patients with malignancy, autoimmune disease, or infection.
Worse Outcome in Primary Glioblastoma Multiforme With Concurrent Epidermal Growth Factor Receptor and p53 Alteration
Authors: Ruano Yolanda , Ribalta Teresa , de Lope Ángel Rodríguez , Campos-Martín Yolanda , Fiaño Concepción , Pérez-Magán Elisa , Hernández-Moneo José-Luis , Mollejo Manuela , Meléndez Bárbara
Published: January 2009

Primary glioblastoma multiforme (GBM), in contrast with secondary GBM, has been associated with the presence of EGFR amplification and absence of p53 mutation. In this study, we analyzed relevant molecular and clinical variables in 194 primary GBMs and tested them for survival analysis. Although most of the tumors showed a mutually exclusive pattern, concurrent alterations of EGFR and p53 were detected. Survival analysis of CDK4 amplification revealed a highly significant association with a worse clinical outcome (P = .01), whereas MDM2, CDK6, PTEN, and p21 were not associated with patient survival. Multivariate analysis including the significant clinical and molecular variables revealed CDK4 amplification, age, and radiotherapy to be markers with independent prognostic value. In addition, the primary GBM tumors showing simultaneous EGFR and p53 alterations were significantly associated with worse survival (P < .01). These results highlight the prognostic value of CDK4 amplification and of simultaneous EGFR-p53 alterations in the clinical outcome of patients with primary GBM.