bluuebunny/crossref_metadata_2025 huggingface dataset:
Prulifloxacin in the treatment of acute exacerbations of COPD in cigarette smokers
Authors: Pasqua Franco , Biscione Gianluca , Crigna Girolmina , Cazzola Mario
Published: July 2008

Smoking is associated with an increased risk of respiratory tract infection in adults likely because components in the smoke might alter properties of the epithelial cell surface. In studies with smokers suffering from acute exacerbations of COPD (AECOPD), the most common bacterial pathogens found were mainly Haemophilus influenzae, but also Streptococcus pneumoniae, Staphylococcus aureus, and Moraxella catarrhalis. Therefore, antibiotics should be effective against such possible pathogens. Prulifloxacin has demonstrated in vitro activity against all these pathogens. We designed the present study to evaluate the efficacy of prulifloxacin in the treatment of AECOPD in cigarette smokers. We enrolled 61 consecutive smokers hospitalized or out-patients of either sex with symptoms and signs compatible with the usual diagnosis criteria for AECOPD. Haemophilus influenzae was the most common bacterial species isolated in the sputum (in 42.6% of the total sample), followed by S. pneumoniae (16.5%), S. aureus (14.7%), M. catarrhalis (11.5%), and others (14.7%). Prulifloxacin 600 mg was given orally once daily for 10 days. Clinical success was observed in 91.8% of patients (67.2% cured and 24.6% improved). Bacteriological eradication rate of H. influenzae was 100%. Persistent pathogens were S. pneumoniae (2 out of 10), S. aureus (1 out of 8), M. catarrhalis (1 out of 7), and P. aeruginosa (1 out of 3). This study seems to indicate that prulifloxacin is of particular value in the treatment of AECOPD in cigarette smokers.
Effect of microstructure and chemical composition on dynamic factor of high strength steels
Authors: Qu J. , Dabboussi W. , Nemes J. , Yue S.
Published: July 2008

The high strain rate properties of high strength steels with various microstructures and static strength levels were studied by means of split Hopkinson bar apparatus in shear punch mode. The as received cold rolled sheet steels were subjected to a variety of heat treatment conditions to produce several different microstructures, namely ferrite plus pearlite (F+P), ferrite plus bainite (F+B), ferrite plus martensite (F+M) and ferrite plus bainite and retained austenite (F+B+RA). According to the variation of dynamic factor (ratio of dynamic to static strength) with static strength, two groups of microstructures with two distinct behaviours were identified, i.e. classic dual phase (ferrite plus martensite) and multiphase (including ferrite–pearlite, ferrite–bainite, etc.). It was also observed that the general dependence of microstructure on the dynamic factor was strongly influenced by chemical composition in the case of ferrite plus martensite microstructures.
Incipient grain boundary melting
Authors: Campbell J.
Published: July 2008

The porosity and loss of properties that usually follows incipient melting of grain boundary phases during heat treatment or welding is suggested to be the result of the expansion accompanying melting, which is not reversed on resolidification because of the opening of extrinsic defects introduced during casting that the author has called bifilms. The asymmetry of melted phases, and techniques that can avoid the degradation of properties are consistent with this hypothesis.
Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia
Authors: Kojima Kensuke , Konopleva Marina , Tsao Twee , Nakakuma Hideki , Andreeff Michael
Published: July 2008

Aberrant expression of Aurora kinases and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML), and preclinical data for inhibition of Aurora kinases or Mdm2 are promising. However, it remains largely unknown whether the viability of cells exposed to Aurora kinase inhibitors depends on the p53 status. We investigated the interaction of Aurora kinases and p53 pathways after their simultaneous blockades using a small-molecule pan-Aurora kinase inhibitor, MK-0457, and a selective small-molecule antagonist of Mdm2, Nutlin-3. We found that MK-0457, which itself activates p53 signaling, acts synergistically with Nutlin-3 to induce apoptosis in wild-type p53 AML cell lines OCI-AML-3 and MOLM-13 but not in p53-null HL-60 cells. MK-0457 and Nutlin-3 showed synergism in inducing p53, conformational change of Bax and Δψm loss, suggesting an involvement of p53-mediated mitochondrial apoptosis. Nutlin-3 constrained endoreduplication after Aurora inhibition via activation of a p53-dependent postmitotic checkpoint and p21 induction in pseudo-G1 cells. Our findings provide the molecular rationale for concomitant targeting of Aurora kinases and Mdm2 in AML where TP53 mutations are rare and downstream p53 signaling is mostly intact.
Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies
Authors: Titman Penny , Pink Elizabeth , Skucek Emily , O'Hanlon Katherine , Cole Tim J. , Gaspar Jane , Xu-Bayford JinHua , Jones Alison , Thrasher Adrian J. , Davies E. Graham , Veys Paul A. , Gaspar H. Bobby
Published: July 2008

Hematopoietic stem cell transplantation (HSCT) is a highly successful treatment for severe congenital immunodeficiencies. However, some studies have suggested that children may experience cognitive difficulties after HSCT. This large-scale study assessed cognitive and behavioral function for the cohort of children treated by HSCT at one center between 1979 and 2003 to determine the frequency and severity of problems and to identify risk factors. A total of 105 patients were assessed on standardized measures of cognitive and emotional and behavioral function together with a control group of unaffected siblings. The average IQ for the cohort was 85 (95% confidence interval, 81-90), significantly lower than both the population average of 100 (P < .001) and unaffected siblings. Multivariate analysis indicated that the underlying genetic defect, diagnosis of adenosine deaminase-deficient severe combined immunodeficiency, and consanguinity were associated with worse outcome but that age at transplantation and chemotherapy conditioning were not. Children treated by HSCT for severe immunodeficiency have an increased risk of long-term cognitive difficulties and associated emotional and behavioral difficulties. The specific genetic diagnosis, consanguinity, and severe clinical course are associated with poor outcome. Long-term follow-up of these patients should include screening to identify and manage these problems more effectively.
The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival
Authors: O'Shea Derville , O'Riain Ciarán , Taylor Claire , Waters Rachel , Carlotti Emanuela , MacDougall Finlay , Gribben John , Rosenwald Andreas , Ott German , Rimsza Lisa M. , Smeland Erlend B. , Johnson Nathalie , Campo Elias , Greiner Timothy C. , Chan Wing C. , Gascoyne Randy D. , Wright George , Staudt Louis M. , Lister T. Andrew , Fitzgibbon Jude
Published: July 2008

The International Prognostic Index and the Follicular Lymphoma International Prognostic Index are widely used for the risk assessment of follicular lymphoma (FL). Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. Because TP53 mutations are associated with poor prognosis in hematologic malignancies, we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated with older age (P = .02) and higher International Prognostic Index score (P = .04). On multivariate analysis, TP53 mutation correlated with shorter progression-free survival (P < .001) and overall survival (P = .009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (P = .016) and with an unfavorable gene expression-based survival predictor score (P < .001), demonstrating for the first time that molecular features of the malignant cell may correlate with the nature of the immune response in FL.
A tale of two symmetrical tails: Structural and functional characteristics of palindromes in proteins
Authors: Sheari Armita , Kargar Mehdi , Katanforoush Ali , Arab Shahriar , Sadeghi Mehdi , Pezeshk Hamid , Eslahchi Changiz , Marashi Sayed-Amir
Published: July 2008

Background

It has been previously shown that palindromic sequences are frequently observed in proteins. However, our knowledge about their evolutionary origin and their possible importance is incomplete.

Results

In this work, we tried to revisit this relatively neglected phenomenon. Several questions are addressed in this work. (1) It is known that there is a large chance of finding a palindrome in low complexity sequences (i.e. sequences with extreme amino acid usage bias). What is the role of sequence complexity in the evolution of palindromic sequences in proteins? (2) Do palindromes coincide with conserved protein sequences? If yes, what are the functions of these conserved segments? (3) In case of conserved palindromes, is it always the case that the whole conserved pattern is also symmetrical? (4) Do palindromic protein sequences form regular secondary structures? (5) Does sequence similarity of the two "sides" of a palindrome imply structural similarity? For the first question, we showed that the complexity of palindromic peptides is significantly lower than randomly generated palindromes. Therefore, one can say that palindromes occur frequently in low complexity protein segments, without necessarily having a defined function or forming a special structure. Nevertheless, this does not rule out the possibility of finding palindromes which play some roles in protein structure and function. In fact, we found several palindromes that overlap with conserved protein Blocks of different functions. However, in many cases we failed to find any symmetry in the conserved regions of corresponding Blocks. Furthermore, to answer the last two questions, the structural characteristics of palindromes were studied. It is shown that palindromes may have a great propensity to form α-helical structures. Finally, we demonstrated that the two sides of a palindrome generally do not show significant structural similarities.

Conclusion

We suggest that the puzzling abundance of palindromic sequences in proteins is mainly due to their frequent concurrence with low-complexity protein regions, rather than a global role in the protein function. In addition, palindromic sequences show a relatively high tendency to form helices, which might play an important role in the evolution of proteins that contain palindromes. Moreover, reverse similarity in peptides does not necessarily imply significant structural similarity. This observation rules out the importance of palindromes for forming symmetrical structures. Although palindromes frequently overlap with conserved Blocks, we suggest that palindromes overlap with Blocks only by coincidence, rather than being involved with a certain structural fold or protein domain.
Extended Field Laser Confocal Microscopy (EFLCM): Combining automated Gigapixel image capture with in silicovirtual microscopy
Authors: Flaberg Emilie , Sabelström Per , Strandh Christer , Szekely Laszlo
Published: July 2008

Background

Confocal laser scanning microscopy has revolutionized cell biology. However, the technique has major limitations in speed and sensitivity due to the fact that a single laser beam scans the sample, allowing only a few microseconds signal collection for each pixel. This limitation has been overcome by the introduction of parallel beam illumination techniques in combination with cold CCD camera based image capture.

Methods

Using the combination of microlens enhanced Nipkow spinning disc confocal illumination together with fully automated image capture and large scale in silico image processing we have developed a system allowing the acquisition, presentation and analysis of maximum resolution confocal panorama images of several Gigapixel size. We call the method Extended Field Laser Confocal Microscopy (EFLCM).

Results

We show using the EFLCM technique that it is possible to create a continuous confocal multi-colour mosaic from thousands of individually captured images. EFLCM can digitize and analyze histological slides, sections of entire rodent organ and full size embryos. It can also record hundreds of thousands cultured cells at multiple wavelength in single event or time-lapse fashion on fixed slides, in live cell imaging chambers or microtiter plates.

Conclusion

The observer independent image capture of EFLCM allows quantitative measurements of fluorescence intensities and morphological parameters on a large number of cells. EFLCM therefore bridges the gap between the mainly illustrative fluorescence microscopy and purely quantitative flow cytometry. EFLCM can also be used as high content analysis (HCA) instrument for automated screening processes.
Complete genome sequence of the extremely acidophilic methanotroph isolate V4, Methylacidiphilum infernorum, a representative of the bacterial phylum Verrucomicrobia
Authors: Hou Shaobin , Makarova Kira S , Saw Jimmy HW , Senin Pavel , Ly Benjamin V , Zhou Zhemin , Ren Yan , Wang Jianmei , Galperin Michael Y , Omelchenko Marina V , Wolf Yuri I , Yutin Natalya , Koonin Eugene V , Stott Matthew B , Mountain Bruce W , Crowe Michelle A , Smirnova Angela V , Dunfield Peter F , Feng Lu , Wang Lei , Alam Maqsudul
Published: July 2008

Background

The phylum Verrucomicrobia is a widespread but poorly characterized bacterial clade. Although cultivation-independent approaches detect representatives of this phylum in a wide range of environments, including soils, seawater, hot springs and human gastrointestinal tract, only few have been isolated in pure culture. We have recently reported cultivation and initial characterization of an extremely acidophilic methanotrophic member of the Verrucomicrobia, strain V4, isolated from the Hell's Gate geothermal area in New Zealand. Similar organisms were independently isolated from geothermal systems in Italy and Russia.

Results

We report the complete genome sequence of strain V4, the first one from a representative of the Verrucomicrobia. Isolate V4, initially named "Methylokorus infernorum" (and recently renamed Methylacidiphilum infernorum) is an autotrophic bacterium with a streamlined genome of ~2.3 Mbp that encodes simple signal transduction pathways and has a limited potential for regulation of gene expression. Central metabolism of M. infernorum was reconstructed almost completely and revealed highly interconnected pathways of autotrophic central metabolism and modifications of C1-utilization pathways compared to other known methylotrophs. The M. infernorum genome does not encode tubulin, which was previously discovered in bacteria of the genus Prosthecobacter, or close homologs of any other signature eukaryotic proteins. Phylogenetic analysis of ribosomal proteins and RNA polymerase subunits unequivocally supports grouping Planctomycetes, Verrucomicrobia and Chlamydiae into a single clade, the PVC superphylum, despite dramatically different gene content in members of these three groups. Comparative-genomic analysis suggests that evolution of the M. infernorum lineage involved extensive horizontal gene exchange with a variety of bacteria. The genome of M. infernorum shows apparent adaptations for existence under extremely acidic conditions including a major upward shift in the isoelectric points of proteins.

Conclusion

The results of genome analysis of M. infernorum support the monophyly of the PVC superphylum. M. infernorum possesses a streamlined genome but seems to have acquired numerous genes including those for enzymes of methylotrophic pathways via horizontal gene transfer, in particular, from Proteobacteria.

Reviewers

This article was reviewed by John A. Fuerst, Ludmila Chistoserdova, and Radhey S. Gupta.
Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer
Authors: Thirthagiri E , Lee SY , Kang P , Lee DS , Toh GT , Selamat S , Yoon S-Y , Taib NA Mohd , Thong MK , Yip CH , Teo SH
Published: July 2008

Introduction

The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1 or BRCA2 genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia.

Method

A total of 187 breast cancer patients with either early-onset breast cancer (at age ≤ 40 years) or a personal and/or family history of breast or ovarian cancer were comprehensively tested by full sequencing of both BRCA1 and BRCA2. Two algorithms to predict the presence of mutations, the Manchester Scoring System and BOADICEA, were evaluated.

Results

Twenty-seven deleterious mutations were detected (14 in BRCA1 and 13 in BRCA2), only one of which was found in two unrelated individuals (BRCA2 490 delCT). In addition, 47 variants of uncertain clinical significance were identified (16 in BRCA1 and 31 in BRCA2). Notably, many mutations are novel (13 of the 30 BRCA1 mutations and 24 of the 44 BRCA2). We report that while there were an equal proportion of BRCA1 and BRCA2 mutations in the Chinese population in our study, there were significantly more BRCA2 mutations among the Malays. In addition, we show that the predictive power of the BOADICEA risk-prediction model and the Manchester Scoring System was significantly better for BRCA1 than BRCA2, but that the overall sensitivity, specificity and positive-predictive value was lower in this population than has been previously reported in Caucasian populations.

Conclusion

Our study underscores the need for larger collaborative studies among non-Caucasian populations to validate the role of genetic testing and the use of risk-prediction models in ensuring that the other populations in the world may also benefit from the genomics and genetics era.
The transcriptional program underlying the physiology of clostridial sporulation
Authors: Jones Shawn W , Paredes Carlos J , Tracy Bryan , Cheng Nathan , Sillers Ryan , Senger Ryan S , Papoutsakis Eleftherios T
Published: July 2008

Background

Clostridia are ancient soil organisms of major importance to human and animal health and physiology, cellulose degradation, and the production of biofuels from renewable resources. Elucidation of their sporulation program is critical for understanding important clostridial programs pertaining to their physiology and their industrial or environmental applications.

Results

Using a sensitive DNA-microarray platform and 25 sampling timepoints, we reveal the genome-scale transcriptional basis of the Clostridium acetobutylicum sporulation program carried deep into stationary phase. A significant fraction of the genes displayed temporal expression in six distinct clusters of expression, which were analyzed with assistance from ontological classifications in order to illuminate all known physiological observations and differentiation stages of this industrial organism. The dynamic orchestration of all known sporulation sigma factors was investigated, whereby in addition to their transcriptional profiles, both in terms of intensity and differential expression, their activity was assessed by the average transcriptional patterns of putative canonical genes of their regulon. All sigma factors of unknown function were investigated by combining transcriptional data with predicted promoter binding motifs and antisense-RNA downregulation to provide a preliminary assessment of their roles in sporulation. Downregulation of two of these sigma factors, CAC1766 and CAP0167, affected the developmental process of sporulation and are apparently novel sporulation-related sigma factors.

Conclusion

This is the first detailed roadmap of clostridial sporulation, the most detailed transcriptional study ever reported for a strict anaerobe and endospore former, and the first reported holistic effort to illuminate cellular physiology and differentiation of a lesser known organism.
Association of Low Sodium-Iodide Symporter Messenger Ribonucleic Acid Expression in Malignant Thyroid Nodules with Increased Intracellular Protein Staining
Authors: Sodré Ana Karina M. B. , Rubio Ileana G. S. , Galrão Ana Luiza R. , Knobel Meyer , Tomimori Eduardo K. , Alves Venâncio A. F. , Kanamura Cristina T. , Buchpiguel Carlos A. , Watanabe Tomoco , Friguglietti Celso U. M. , Kulcsar Marco A. V. , Medeiros-Neto Geraldo , Camargo Rosalinda Y. A.
Published: July 2008

Context: The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules.

Objective: The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls).

Design: NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples.

Results: When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%).

Conclusion: We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.
Zinc Transporter-8 Gene (SLC30A8) Is Associated with Type 2 Diabetes in Chinese
Authors: Xiang Jie , Li Xiao-Ying , Xu Min , Hong Jie , Huang Yun , Tan Jiao-Rong , Lu Xi , Dai Meng , Yu Bing , Ning Guang
Published: July 2008

Context: Several genome-wide association studies identified a strong association of SLC30A8 with type 2 diabetes in individuals of European ancestry. The effect of the association of rs13266634 with type 2 diabetes or related glycemic traits has not been fully extended to non-European populations, and a comprehensive examination of common variants in the gene has not yet been carried out in Han Chinese.

Objective: The objective of the study was to investigate the association of SLC30A8 with type 2 diabetes in Chinese.

Design: A comprehensive gene-based association study was performed using 14 tagging single-nucleotide polymorphism (SNPs) of SLC30A8 in Han Chinese subjects with normal glucose tolerance (NGT; n = 721), impaired glucose regulation (IGR; n = 375), and type 2 diabetes (n = 521).

Results: A significant association for SNP rs13266634 was observed between patients with type 2 diabetes and NGT controls (P = 0.016). The association was also observed between combined type 2 diabetes/IGR and NGT subjects (P = 0.002). The adjusted odds ratios for homozygote CC vs. TT at this locus were 1.71 for type 2 diabetes (95% confidence interval 1.19–2.45, P = 0.002) and 1.77 for type 2 diabetes and IGR (95% confidence interval 1.29–2.42, P = 0.0001). We further studied the genotype-phenotype correlation in 70 Han Chinese using iv glucose tolerance test and found an association between SNP rs13266634 and acute insulin response to glucose and disposition index (adjusted P = 0.012 and 0.004, respectively).

Conclusions: Our results provide evidence that SLC30A8 is a susceptible locus for type 2 diabetes in Chinese population, and its variant can influence insulin secretion.
Regulation of Kalirin by Cdk5
Authors: Xin Xiaonan , Wang Yanping , Ma Xin-ming , Rompolas Panteleimon , Keutmann Henry T. , Mains Richard E. , Eipper Betty A.
Published: July 2008

Kalirin, one of the few Rho guanine nucleotide exchange factors (GEFs) that contains spectrin-like repeats, plays a critical role in axon extension and maintenance of dendritic spines. PC12 cells were used to determine whether Cdk5, a critical participant in both processes, regulates the action of Kalirin. Expression of Kalirin-7 in nondifferentiated PC12 cells caused GEF-activity-dependent extension of broad cytoplasmic protrusions; coexpression of dominant-negative Cdk5 largely eliminated this response. The spectrin-like repeat region of Kalirin plays an essential role in this response, which is not mimicked by the GEF domain alone. Thr1590, which follows the first GEF domain of Kalirin, is the only Cdk5 phosphorylation site in Kalirin-7. Although mutant Kalirin-7 with Ala1590 retains GEF activity, it is unable to cause extension of protrusions. Kalirin-7 with an Asp1590 mutation has slightly increased GEF activity and dominant-negative Cdk5 fails to block its ability to cause extension of protrusions. Phosphorylation of Thr1590 causes a slight increase in GEF activity and Kalirin-7 solubility. Dendritic spines formed by cortical neurons in response to the expression of Kalirin-7 with Ala1590 differ in shape from those formed in response to wild-type Kalirin-7 or Kalirin-7 containing Asp1590. The presence of Thr1590 in each major Kalirin isoform would allow Cdk5 to regulate Kalirin function throughout development.
Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L
Authors: Tamai Shoko , Iida Hiroshi , Yokota Sadaki , Sayano Tomoko , Kiguchiya Shoko , Ishihara Naotada , Hayashi Jun-Ichi , Mihara Katsuyoshi , Oka Toshihiko
Published: July 2008

LETM1 is located in the chromosomal region that is deleted in patients suffering Wolf-Hirschhorn syndrome; it encodes a homolog of the yeast protein Mdm38 that is involved in mitochondrial morphology. Here, we describe the LETM1-mediated regulation of the mitochondrial volume and its interaction with the mitochondrial AAA-ATPase BCS1L that is responsible for three different human disorders. LETM1 is a mitochondrial inner-membrane protein with a large domain extruding to the matrix. The LETM1 homolog LETM2 is a mitochondrial protein that is expressed preferentially in testis and sperm. LETM1 downregulation caused mitochondrial swelling and cristae disorganization, but seemed to have little effect on membrane fusion and fission. Formation of the respiratory-chain complex was impaired by LETM1 knockdown. Cells lacking mitochondrial DNA lost active respiratory chains but maintained mitochondrial tubular networks, indicating that mitochondrial swelling caused by LETM1 knockdown is not caused by the disassembly of the respiratory chains. LETM1 was co-precipitated with BCS1L and formation of the LETM1 complex depended on BCS1L levels, suggesting that BCS1L stimulates the assembly of the LETM1 complex. BCS1L knockdown caused disassembly of the respiratory chains as well as LETM1 downregulation and induced distinct changes in mitochondrial morphology.
An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells
Authors: Wang Hongbo , Sun Daqian , Ji Peng , Mohler James , Zhu Liang
Published: July 2008

Androgen–androgen-receptor (androgen-AR) signaling in normal prostate epithelium promotes terminal luminal epithelial cell differentiation. In androgen-dependent prostate-cancer cells, androgen-AR signaling gains the ability to promote both differentiation and proliferation. How this signaling promotes proliferation of androgen-dependent prostate-cancer cells and its relationship with the differentiation-promoting functions of the AR are important issues regarding the biology of androgen-dependent prostate-cancer cells. Herein, we report the identification of an AR-Skp2 pathway in prostate-cancer cells that depend on the AR for proliferation; in this pathway, AR is a robust upstream regulator of Skp2 through blocking the D-box-dependent degradation of this protein, and Skp2, in turn, serves as an essential downstream effector of AR in promoting proliferation independently of the differentiation-promoting function of AR. These results provide new knowledge on how AR functions in androgen-dependent prostate-cancer cells and identify strategies to specifically target the proliferation-promoting function of AR without compromising cancer-cell differentiation.
Ca2+ oscillation frequency regulates agonist-stimulated gene expression in vascular endothelial cells
Authors: Zhu Liping , Luo Yougen , Chen Taoxiang , Chen Fengrong , Wang Tao , Hu Qinghua
Published: July 2008

A physiological membrane-receptor agonist typically stimulates oscillations, of varying frequencies, in cytosolic Ca2+ concentration ([Ca2+]i). Whether and how [Ca2+]i oscillation frequency regulates agonist-stimulated downstream events, such as gene expression, in non-excitable cells remain unknown. By precisely manipulating [Ca2+]i oscillation frequency in histamine-stimulated vascular endothelial cells (ECs), we demonstrate that the gene expression of vascular cell adhesion molecule 1 (VCAM1) critically depends on [Ca2+]i oscillation frequency in the presence, as well as the absence, of histamine stimulation. However, histamine stimulation enhanced the efficiency of [Ca2+]i-oscillation-frequency-regulated VCAM1 gene expression, versus [Ca2+]i oscillations alone in the absence of histamine stimulation. Furthermore, a [Ca2+]i oscillation frequency previously observed to be the mean frequency in histamine-stimulated ECs was found to optimize VCAM1 mRNA expression. All the above effects were abolished or attenuated by blocking histamine-stimulated generation of intracellular reactive oxygen species (ROS), another intracellular signaling pathway, and were restored by supplementary application of a low level of H2O2. Endogenous NF-κB activity is similarly regulated by [Ca2+]i oscillation frequency, as well as its co-operation with ROS during histamine stimulation. This study shows that [Ca2+]i oscillation frequency cooperates with ROS to efficiently regulate agonist-stimulated gene expression, and provides a novel and general strategy for studying [Ca2+]i signal kinetics in agonist-stimulated downstream events.
Computational fluid dynamics investigation of some wind turbine rotor design parameters
Authors: Gómez-Iradi S , Barakos G N
Published: July 2008

This article presents an investigation of the relative importance of key design parameters of a horizontal axis wind turbine (HAWT) blade. Computational fluid dynamics (CFD) is used as the main tool, after validation against experimental data of the (National Aeronautics and Space Administration/National Renewable Energy Laboratory) NREL/NASA-Ames Phase VI wind tunnel campaign. Tip and root sections, blade aspect ratio, and pitch angle were analysed and all CFD calculations were performed using a compressible Reynolds-averaged Navier—Stokes solver. CFD grids of advanced multi-block topologies were used including up to 4.5 million cells. A grid convergence study indicated that a resolution of 3.4 million cells was adequate for the selected flow conditions, which correspond to an upwind wind turbine at 0° yaw angle, 7 m/s wind speed, and 72 r/min rotational speed. Various root and tip configurations were considered and the results obtained indicate that the exact representation of the root and tip geometry of an HAWT has a small but finite effect in the thrust and torque levels at working conditions. This effect is however secondary to the effects of aspect ratio and blade pitch.
Assessment of tidal current energy in the Minas Passage, Bay of Fundy
Authors: Karsten R H , McMillan J M , Lickley M J , Haynes R D
Published: July 2008

The tidal power available for electricity generation from in-stream turbines placed in the Minas Passage of the Bay of Fundy is examined. A previously derived theory is adapted to model the effect of turbine drag on the flow through the Minas Passage and the tidal amplitude in the Minas Basin. The theoretical maximum power production over a tidal cycle is determined by the product of the amplitude of the forcing tide in the Bay of Fundy and the undisturbed volumetric flowrate through the Minas Passage. Although the extraction of the maximum power will reduce the flowrate through the Minas Passage and the tides in the Minas Basin by over 30 per cent, a significant portion of the maximum power can be extracted with little change in tidal amplitude as the initial power generation causes only an increase in the phase lag of the basin tides. Two-dimensional, finite-element, numerical simulations of the Bay of Fundy—Gulf of Maine system agree remarkably well with the theory. The simulations suggest that a maximum of 7 GW of power can be extracted by turbines. They also show that any power extraction in the Minas Passage pushes the Bay of Fundy—Gulf of Maine system closer to resonance with the forcing tides, resulting in increased tidal amplitudes throughout the Gulf of Maine. Although extracting the maximum power produces significant changes, 2.5 GW of power can be extracted with a maximum 5 per cent change in the tidal amplitude at any location. Finally, the simulations suggest that a single turbine fence across the Minas Passage can extract the same power as turbines throughout the passage but that partial turbine fences are less efficient.
Distributed dynamic modelling with experimental validation on a photovoltaic solar-assisted heat pump
Authors: Ji J , He H , Pei G , He W , Liu K
Published: July 2008

The photovoltaic/thermal solar-assisted heat pump is a system that directly integrates a Rankine refrigeration device with a photovoltaic/thermal solar collector. A specially designed direct-expansion PV evaporator is employed in the system to acquire thermal energy and electricity from solar radiation simultaneously. In this paper, a distributed model is presented that describes the dynamic performance of the system. Numerical simulation was performed with instantaneous solar irradiance and ambient temperature based on the model. A testing rig was built in Hefei, China, and experiments were conducted to verify the model. The results show that high photovoltaic and thermal performance can be obtained by the system. The average electrical efficiency is around 13.02 per cent. The output electricity is about 85.5 per cent of the power consumption, which means that the system can offer most of the power consumed by itself. Neglecting the heat loss of the water box, the highest coefficient of performance (COPc) can reach up to 7.3 and the average value is around 3.41. Comparisons between the simulation results and the experimental measurements show that the model is able to give satisfactory predictions.
Electrostatic filter efficiency improvement based on velocity and pressure field numerical simulation
Authors: Rek Z , Žun I , Buljan T , Hribar T
Published: July 2008

This paper deals with the numerical simulation of exhaust gas flow through the electrostatic filter (EF) in block IV of the Šoštanj thermal power plant. Four different variants of the geometry were analysed. The exhaust gas flow was modelled as a turbulent incompressible viscous fluid flow. The commercial computational fluid dynamics package CFX-4.4 from ANSYS was used for flow analysis. The discrete models were very complex due to the internal objects such as guide vane rows, perforated screens, and electrodes. The turbulence model was the standard k—ɛ model with wall functions. Perforated screens were considered by an additional source term in momentum conservation equations. Velocity boundary conditions were obtained by interpolating the measured values on the discrete model nodes. The results of numerical simulation show that the most efficient is the variant where an additional screen is inserted between the second and the third EF volume. The maximum velocity is decreased and the distribution of velocity over the cross-section is more uniform. The increase in pressure drop was acceptable. The measurements of the velocity field after EF modification confirmed the prediction of the numerical simulation.
Tidal stream power resource assessment for Masset Sound, Haida Gwaii
Authors: Blanchfield J , Garrett C , Rowe A , Wild P
Published: July 2008

This work presents a case study for the power potential of a tidal stream connecting a bay to the open ocean. The extractable power, averaged over the tidal cycle, from Masset Sound, located in Haida Gwaii, Canada, is estimated as 79 MW when only the dominant M2 tidal constituent is included in the analysis. The value increases to 87 MW when the three dominant constituents are included. It is shown that extracting the maximum power from Masset Sound will decrease both the maximum water surface elevation within the bay and the maximum volume flowrate through the channel to approximately 58 per cent of their undisturbed values.
A review of performance degradation and failure modes for hydrogen-fuelled polymer electrolyte fuel cells
Authors: Rama P , Chen R , Andrews J
Published: July 2008

A qualitative account of the causes and effects of performance degradation and failure in hydrogen-fuelled polymer electrolyte fuel cells (PEFCs) is given in the present review. The purpose of the review is to establish a backbone understanding of the phenomenological processes that occur within the PEFC, how they interact, how they are influenced through elements of design, manufacturing and operation, and ultimately how they result in performance degradation and cell failure. In the current work, 22 common faults are identified which are induced by 48 frequent causes. The major PEFC components considered here that are susceptible to faults are the polymer electrolyte-based membrane, the anode and cathode catalyst layers, gas diffusion and microporous layers, seals and the bipolar plate. Faults pertaining to these components can cause irreversible increases in activation, mass transportation, ohmic and fuel efficiency losses, or indeed cause catastrophic cell failure.
Organizational change through Lean Thinking
Authors: Tsasis Peter , Bruce-Barrett Cindy
Published: July 2008

In production and manufacturing plants, Lean Thinking has been used to improve processes by eliminating waste and thus enhancing efficiency. In health care, Lean Thinking has emerged as a comprehensive approach towards improving processes embedded in the diagnostic, treatment and care activities of health-care organizations with cost containment results. This paper provides a case study example where Lean Thinking is not only used to improve efficiency and cost containment, but also as an approach to effective organizational change.
Telerehabilitation for service delivery in speech-language pathology
Authors: Theodoros Deborah G
Published: July 2008

Communication disorders in adults and children can have a significant effect on their quality of life and on that of their families. Speech-language pathologists face several challenges in providing assessment and treatment services to such people. Challenges include facilitating equitable access to services and providing appropriate management within a changing social and economic context. Telerehabilitation has the potential to deliver services in the home or local community via videoconferencing and through interactive computer-based therapy activities. This form of service delivery has the capacity to optimize functional outcomes by facilitating generalization of treatment effects within the person's everyday environment, and enable monitoring of communication and swallowing behaviours on a long-term basis. A number of image-based telerehabilitation applications have been used in the management of adult neurogenic speech and language disorders, stuttering, voice disorders, speech and language disorders in children, laryngectomy and swallowing dysfunction. Further development of such applications and other computer-based therapies, cost-benefit and cost-effectiveness analyses, and professional education are needed if telerehabilitation is to become an integral part of speech-language pathology practice.
Telehealth: a child and family-friendly approach to mental health-care reform
Authors: Lingley-Pottie Patricia , McGrath Patrick J
Published: July 2008

Limited access to paediatric mental health services and high drop-out rates from treatment result in poor health outcomes for families with children with mental health problems. New ways of delivering care are required. Telehealth is a promising approach. The Family Help programme employs manualized, distance treatment by telephone. Participants in the Family Help programme (both adults and children) have reported a strong therapeutic alliance with their telephone coach. Participants also described how during treatment sessions they felt comfortable and safe in their own home; they did not feel stigmatized or judged; they had little apprehension about self-disclosure and they felt that treatment was delivered at their convenience. Treatment calls were often scheduled after typical working hours. Attrition rates were found to be very low and children actively engaged in the structured, distance treatment. Evidence-based, distance delivery using non-professionals is a promising approach to the delivery of paediatric mental health care.
Non-invasive monitoring of the activities of daily living of elderly people at home – a pilot study of the usage of domestic appliances
Authors: Franco Georgina Corte , Gallay Floriane , Berenguer Marc , Mourrain Christine , Couturier Pascal
Published: July 2008

We conducted a feasibility study of a system for non-invasive monitoring of subjects at home. Electrical activity was recorded from room lights and from electrical domestic appliances; this was translated into the probability of physical activity or a particular Activity of Daily Living (ADL). Thirteen volunteer subjects were monitored for a period of 6.4 months (range 3–8). The mean age of the subjects was 80 years and they all lived alone at home; one had moderate Alzheimer's disease. A one-week validation was carried out to ascertain whether the recorded activity actually occurred. The results showed that daily and nocturnal activity could be well differentiated. The probability of having eaten, taken a bath and going to the toilet could be calculated each day. Eating was the most accurately measured ADL; toileting and bathing results were less accurate. The system appears to be a promising component of home telecare.
The availability of telecardiology consultations and transfer patterns from a remote neonatal intensive care unit
Authors: Huang Tannie , Moon-Grady Anita J , Traugott Craig , Marcin James
Published: July 2008

We examined records of all admissions to an isolated community neonatal intensive care unit (NICU) in California between 2001 and 2006. We also reviewed the echocardiograms for diagnosis, disposition of patient and necessity for transport. In 2004, a telemedicine link (mainly store-and-forward) was established to a university children's hospital (UCH) 290 km away. The number of NICU patients having an echocardiogram increased from 280 (27% of 1029 admissions) to 385 (40% of 963, P = <0.001) after telemedicine became available. There was an increase in the proportion of normal studies, from 31% to 37% ( P = 0.03), and an increase in the number of patients diagnosed with cardiac pathology from 192 (19% of all admissions) to 241 (25%, P < 0.001). Twenty-four patients were transferred for cardiac reasons during each three-year period; however seven pre-telemedicine transfers were avoidable, compared with two post-telemedicine transfers ( P = 0.06). There was a change in referral pattern (65% to the UCH pre-telemedicine, compared with 78% post-telemedicine) although it was not significant ( P = 0.10). Thus the availability of the telecardiology link was associated with increases in the utilization of echocardiography, in the proportion of normal studies, and in the percentage of neonates diagnosed with cardiac pathology without an increase in the number transferred for cardiac reasons. There was a reduction in unnecessary transfers and a strengthened relationship with the centre providing the telecardiology service.
Famciclovir-Induced Leukocytoclastic Vasculitis
Authors: Te Charles C , Le Vu , Allee Mark
Published: July 2008

Objective

To report a case of famciclovir-induced leukocytoclastic vasculitis (LCV).

Case Summary:

A 67-year-old white female presented to the hospital for evaluation of large, bilateral palpable purpura; coalescing ulcers with centra! eschars; and small, red violaceous papules on her legs and groin. Approximately 2 months prior to this hospitalization, the woman was diagnosed with shingles of her left T1–T2 nerve distribution and was treated with famciclovir 500 mg 3 times daily, which was her first exposure to this medication. Her shingles resolved; however, on day 4 of treatment, she began to notice red spots on both of her legs that began to progressively blister and increase in size. She discontinued famciclovir at that time. The rash persisted and spread to her abdomen, groin, legs, feet, and toes. She underwent punch biopsy that revealed LCV. Workup was negative for antinuclear antibody, rheumatoid factor, hepatitis B and C virus, peri nuclear-staining antineutrophil cytoplasmic antibodies, cytoplasmic-staining antineutrophil cytoplasmic antibodies, antibodies to extractable nuclear antigens, proteinase 3, and myeloperoxidase. The patient improved with daily oral steroids and local wound care.

Discussion:

LCV has been reported only once before in the English literature as of January 2008. The most common cause of LCV is medication use, but it is a diagnosis of exclusion. It is hypothesized that drugs act as haptens, which cause an immune response. An objective causality assessment using the Naranjo probability scale suggested that famciclovir was the probable cause of LCV in this patient.

Conclusions:

Healthcare professionals should be aware of the possible development of famciclovir-induced LCV.