bluuebunny/crossref_metadata_2025 huggingface dataset:
mSpecs: a software tool for the administration and editing of mass spectral libraries in the field of metabolomics
Authors: Thielen Bernhard , Heinen Stephanie , Schomburg Dietmar
Published: August 2009

Background

Metabolome analysis with GC/MS has meanwhile been established as one of the "omics" techniques. Compound identification is done by comparison of the MS data with compound libraries. Mass spectral libraries in the field of metabolomics ought to connect the relevant mass traces of the metabolites to other relevant data, e.g. formulas, chemical structures, identification numbers to other databases etc. Since existing solutions are either commercial and therefore only available for certain instruments or not capable of storing such information, there is need to provide a software tool for the management of such data.

Results

Here we present mSpecs, an open source software tool to manage mass spectral data in the field of metabolomics. It provides editing of mass spectra and virtually any associated information, automatic calculation of formulas and masses and is extensible by scripts. The graphical user interface is capable of common techniques such as copy/paste, undo/redo and drag and drop. It owns import and export filters for the major public file formats in order to provide compatibility to commercial instruments.

Conclusion

mSpecs is a versatile tool for the management and editing of mass spectral libraries in the field of metabolomics. Beyond that it provides capabilities for the automatic management of libraries though its scripting functionality. mSpecs can be used on all major platforms and is licensed under the GNU General Public License and available athttp://mspecs.tu-bs.de.
Ovarian cancer detection from metabolomic liquid chromatography/mass spectrometry data by support vector machines
Authors: Guan Wei , Zhou Manshui , Hampton Christina Y , Benigno Benedict B , Walker L DeEtte , Gray Alexander , McDonald John F , Fernández Facundo M
Published: August 2009

Background

The majority of ovarian cancer biomarker discovery efforts focus on the identification of proteins that can improve the predictive power of presently available diagnostic tests. We here show that metabolomics, the study of metabolic changes in biological systems, can also provide characteristic small molecule fingerprints related to this disease.

Results

In this work, new approaches to automatic classification of metabolomic data produced from sera of ovarian cancer patients and benign controls are investigated. The performance of support vector machines (SVM) for the classification of liquid chromatography/time-of-flight mass spectrometry (LC/TOF MS) metabolomic data focusing on recognizing combinations or "panels" of potential metabolic diagnostic biomarkers was evaluated. Utilizing LC/TOF MS, sera from 37 ovarian cancer patients and 35 benign controls were studied. Optimum panels of spectral features observed in positive or/and negative ion mode electrospray (ESI) MS with the ability to distinguish between control and ovarian cancer samples were selected using state-of-the-art feature selection methods such as recursive feature elimination and L1-norm SVM.

Conclusion

Three evaluation processes (leave-one-out-cross-validation, 12-fold-cross-validation, 52-20-split-validation) were used to examine the SVM models based on the selected panels in terms of their ability for differentiating control vs. disease serum samples. The statistical significance for these feature selection results were comprehensively investigated. Classification of the serum sample test set was over 90% accurate indicating promise that the above approach may lead to the development of an accurate and reliable metabolomic-based approach for detecting ovarian cancer.
MULTI-K: accurate classification of microarray subtypes using ensemble k-means clustering
Authors: Kim Eun-Youn , Kim Seon-Young , Ashlock Daniel , Nam Dougu
Published: August 2009

Background

Uncovering subtypes of disease from microarray samples has important clinical implications such as survival time and sensitivity of individual patients to specific therapies. Unsupervised clustering methods have been used to classify this type of data. However, most existing methods focus on clusters with compact shapes and do not reflect the geometric complexity of the high dimensional microarray clusters, which limits their performance.

Results

We present a cluster-number-based ensemble clustering algorithm, called MULTI-K, for microarray sample classification, which demonstrates remarkable accuracy. The method amalgamates multiple k-means runs by varying the number of clusters and identifies clusters that manifest the most robust co-memberships of elements. In addition to the original algorithm, we newly devised the entropy-plot to control the separation of singletons or small clusters. MULTI-K, unlike the simple k-means or other widely used methods, was able to capture clusters with complex and high-dimensional structures accurately. MULTI-K outperformed other methods including a recently developed ensemble clustering algorithm in tests with five simulated and eight real gene-expression data sets.

Conclusion

The geometric complexity of clusters should be taken into account for accurate classification of microarray data, and ensemble clustering applied to the number of clusters tackles the problem very well. The C++ code and the data sets tested are available from the authors.
An integrated genetic linkage map for silkworms with three parental combinations and its application to the mapping of single genes and QTL
Authors: Zhan Shuai , Huang Jianhua , Guo Qiuhong , Zhao Yunpo , Li Weihua , Miao Xuexia , Goldsmith Marian R , Li Muwang , Huang Yongping
Published: August 2009

Background

Bombyx mori, the domesticated silkworm, is a well-studied model insect with great economic and scientific significance. Although more than 400 mutations have been described in silkworms, most have not been identified, especially those affecting economically-important traits. Simple sequence repeats (SSRs) are effective and economical tools for mapping traits and genetic improvement. The current SSR linkage map is of low density and contains few polymorphisms. The purpose of this work was to develop a dense and informative linkage map that would assist in the preliminary mapping and dissection of quantitative trait loci (QTL) in a variety of silkworm strains.

Results

Through an analysis of > 50,000 genotypes across new mapping populations, we constructed two new linkage maps covering 27 assigned chromosomes and merged the data with previously reported data sets. The integrated consensus map contains 692 unique SSR sites, improving the density from 6.3 cM in the previous map to 4.8 cM. We also developed 497 confirmed neighboring markers for corresponding low-polymorphism sites, with 244 having polymorphisms. Large-scale statistics on the SSR type were suggestive of highly efficient markers, based upon which we searched 16,462 available genomic scaffolds for SSR loci. With the newly constructed map, we mapped single-gene traits, the QTL of filaments, and a number of ribosomal protein genes.

Conclusion

The integrated map produced in this study is a highly efficient genetic tool for the high-throughput mapping of single genes and QTL. Compared to previous maps, the current map offers a greater number of markers and polymorphisms; thus, it may be used as a resource for marker-assisted breeding.
Identification of novel endogenous antisense transcripts by DNA microarray analysis targeting complementary strand of annotated genes
Authors: Numata Koji , Osada Yuko , Okada Yuki , Saito Rintaro , Hiraiwa Noriko , Nakaoka Hajime , Yamamoto Naoyuki , Watanabe Kazufumi , Okubo Kazue , Kohama Chihiro , Kanai Akio , Abe Kuniya , Kiyosawa Hidenori
Published: August 2009

Background

Recent transcriptomic analyses in mammals have uncovered the widespread occurrence of endogenous antisense transcripts, termed natural antisense transcripts (NATs). NATs are transcribed from the opposite strand of the gene locus and are thought to control sense gene expression, but the mechanism of such regulation is as yet unknown. Although several thousand potential sense-antisense pairs have been identified in mammals, examples of functionally characterized NATs remain limited. To identify NAT candidates suitable for further functional analyses, we performed DNA microarray-based NAT screening using mouse adult normal tissues and mammary tumors to target not only the sense orientation but also the complementary strand of the annotated genes.

Results

First, we designed microarray probes to target the complementary strand of genes for which an antisense counterpart had been identified only in human public cDNA sources, but not in the mouse. We observed a prominent expression signal from 66.1% of 635 target genes, and 58 genes of these showed tissue-specific expression. Expression analyses of selected examples (Acaa1b and Aard) confirmed their dynamic transcription in vivo. Although interspecies conservation of NAT expression was previously investigated by the presence of cDNA sources in both species, our results suggest that there are more examples of human-mouse conserved NATs that could not be identified by cDNA sources. We also designed probes to target the complementary strand of well-characterized genes, including oncogenes, and compared the expression of these genes between mammary cancerous tissues and non-pathological tissues. We found that antisense expression of 95 genes of 404 well-annotated genes was markedly altered in tumor tissue compared with that in normal tissue and that 19 of these genes also exhibited changes in sense gene expression. These results highlight the importance of NAT expression in the regulation of cellular events and in pathological conditions.

Conclusion

Our microarray platform targeting the complementary strand of annotated genes successfully identified novel NATs that could not be identified by publically available cDNA data, and as such could not be detected by the usual "sense-targeting" microarray approach. Differentially expressed NATs monitored by this platform may provide candidates for investigations of gene function. An advantage of our microarray platform is that it can be applied to any genes and target samples of interest.
Recovery and characterization of a Citrus clementinaHort. ex Tan. 'Clemenules' haploid plant selected to establish the reference whole Citrus genome sequence
Authors: Aleza Pablo , Juárez José , Hernández María , Pina José A , Ollitrault Patrick , Navarro Luis
Published: August 2009

Background

In recent years, the development of structural genomics has generated a growing interest in obtaining haploid plants. The use of homozygous lines presents a significant advantage for the accomplishment of sequencing projects. Commercial citrus species are characterized by high heterozygosity, making it difficult to assemble large genome sequences. Thus, the International Citrus Genomic Consortium (ICGC) decided to establish a reference whole citrus genome sequence from a homozygous plant. Due to the existence of important molecular resources and previous success in obtaining haploid clementine plants, haploid clementine was selected as the target for the implementation of the reference whole genome citrus sequence.

Results

To obtain haploid clementine lines we used the technique of in situ gynogenesis induced by irradiated pollen. Flow cytometry, chromosome counts and SSR marker (Simple Sequence Repeats) analysis facilitated the identification of six different haploid lines (2n = x = 9), one aneuploid line (2n = 2x+4 = 22) and one doubled haploid plant (2n = 2x = 18) of 'Clemenules' clementine. One of the haploids, obtained directly from an original haploid embryo, grew vigorously and produced flowers after four years. This is the first haploid plant of clementine that has bloomed and we have, for the first time, characterized the histology of haploid and diploid flowers of clementine. Additionally a double haploid plant was obtained spontaneously from this haploid line.

Conclusion

The first haploid plant of 'Clemenules' clementine produced directly by germination of a haploid embryo, which grew vigorously and produced flowers, has been obtained in this work. This haploid line has been selected and it is being used by the ICGC to establish the reference sequence of the nuclear genome of citrus.
Nationwide epidemiological study of severe gallstone disease in Taiwan
Authors: Huang John , Chang Chia-Hsuin , Wang Juin-Ling , Kuo Hsu-Ko , Lin Jou-Wei , Shau Wen-Yi , Lee Po-Huang
Published: August 2009

Background

Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20.

Methods

A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution.

Results

The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy.

Conclusion

This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.
Mutations at codons 178, 200-129, and 232 contributed to the inherited prion diseases in Korean patients
Authors: Choi Bo-Yeong , Kim Su Yeon , Seo So-Young , An Seong Soo A , Kim SangYun , Park Sang-Eun , Lee Seung-Han , Choi Yun-Ju , Kim Sang-Jin , Kim Chi-Kyeong , Park Jun-Sun , Ju Young-Ran
Published: August 2009

Background

Polymorphisms of the human prion protein gene (PRNP) contribute to the genetic determinants of Creutzfeldt-Jakob disease (CJD). Numerous polymorphisms in the promoter regions as well as the open reading frame of PRNP were investigated. Greater than 90% of Korean, Chinese, and Japanese carry the homozygote 129 MM codon. In Korea, polymorphisms have not been comprehensively studied, except codons 129 and 219 in PRNP among Korean CJD cases. Although polymorphisms at codons 129 and 219 play an important role in susceptibility to sporadic CJD, patients with other polymorphisms in PRNP exhibited critical distinctions of clinical symptoms.

Methods

The genetic analyses of PRNP were carried out among probable CJD patients in comparison with the results from magnetic resonance imaging (MRI) and electroencephalogram (EEG).

Results

The molecular analyses revealed that three mutations at codons D178N, E200K, and M232R in heterozygosity. Patients with the D178N and M232R mutations had a 129MM codon, whereas the patient with the E200K mutation showed 129MV heterozygosity. They all revealed strong 14-3-3 positive signals. The 67-year-old patient with the D178N-129M mutation showed progressive gait disturbance and dysarthria was in progress. The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms. The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms.

Conclusion

Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.
Seasonal effects of influenza on mortality in a subtropical city
Authors: Yang Lin , Wong Chit Ming , Chan King Pan , Chau Patsy Yuen Kwan , Ou Chun Quan , Chan Kwok Hung , Peiris JS Malik
Published: August 2009

Background

Influenza has been associated with a heavy burden of mortality. In tropical or subtropical regions where influenza viruses circulate in the community most of the year, it is possible that there are seasonal variations in the effects of influenza on mortality, because of periodic changes in environment and host factors as well as the frequent emergence of new antigenically drifted virus strains. In this paper we explored this seasonal effect of influenza.

Methods

A time-varying coefficient Poisson regression model was fitted to the weekly numbers of mortality of Hong Kong from 1996 to 2002. Excess risks associated with influenza were calculated to assess the seasonal effects of influenza.

Results

We demonstrated that the effects of influenza were higher in winter and late spring/early summer than other seasons. The two-peak pattern of seasonal effects of influenza was found for cardio-respiratory disease and sub-categories pneumonia and influenza, chronic obstructive pulmonary disease, cerebrovascular diseases and ischemic heart disease as well as for all-cause deaths.

Conclusion

The results provide insight into the possibility that seasonal factors may have impact on virulence of influenza besides their effects on virus transmission. The results warrant further studies into the mechanisms behind the seasonal effect of influenza.
HLA-DR and HLA-DQ alleles in patients from the south of Brazil: markers for leprosy susceptibility and resistance
Authors: da Silva Samira A , Mazini Priscila S , Reis Pâmela G , Sell Ana M , Tsuneto Luiza T , Peixoto Paulo R , Visentainer Jeane EL
Published: August 2009

Background

Many epidemiological studies have shown that the genetic factors of the host play a role in the variability of clinical response to infection caused by M. leprae. With the purpose of identifying genes of susceptibility, the present study investigated the possible role of HLA-DRB1 and DQA1/DQB1 alleles in susceptibility to leprosy, and whether they account for the heterogeneity in immune responses observed following infection in a Southern Brazilian population.

Methods

One hundred and sixty-nine leprosy patients and 217 healthy controls were analyzed by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers(One Lambda®, CA, USA).

Results

There was a positive association of HLA-DRB1*16 (*1601 and *1602) with leprosy per se (7.3% vs. 3.2%, P = 0.01, OR = 2.52, CI = 1.26–5.01), in accord with previous serological studies, which showed DR2 as a marker of leprosy. Although, HLA-DQA1*05 frequency (29.8% vs. 20.9%, P = 0.0424, OR = 1.61, CI = 1.09–2.39) was higher in patients, and HLA-DQA1*02 (3.0% vs. 7.5%, P = 0.0392, OR = 0.39, CI = 0.16 – 0.95) and HLA-DQA1*04 (4.0% vs. 9.1%, P = 0.0314, OR = 0.42, CI = 0.19 – 0.93) frequencies lower, P-values were not significant after the Bonferroni's correction. Furthermore, HLA-DRB1*1601 (9.0% vs. 1.8%; P = 0.0016; OR = 5.81; CI = 2.05–16.46) was associated with susceptibility to borderline leprosy compared to control group, and while HLA-DRB1*08 (11.2% vs. 1.2%; P = 0.0037; OR = 12.00; CI = 1.51 – 95.12) was associated with susceptibility to lepromatous leprosy, when compared to tuberculoid leprosy, DRB1*04 was associated to protection.

Conclusion

These data confirm the positive association of HLA-DR2 (DRB1*16) with leprosy per se, and the protector effect of DRB1*04 against lepromatous leprosy in Brazilian patients.
Expression and prognostic significance of THBS1, Cyr61 and CTGF in esophageal squamous cell carcinoma
Authors: Zhou Zhu-Qing , Cao Wei-Hua , Xie Jian-Jun , Lin Jing , Shen Zhong-Ying , Zhang Qing-Ying , Shen Jin-Hui , Xu Li-Yan , Li En-Min
Published: August 2009

Background

Thrombospondin1 (THBS1), cystene-rich protein 61 (Cyr61) and connective tissue growth factor (CTGF) are all involved in the transforming growth factor-beta (TGF-β) signal pathway, which plays an important role in the tumorigenesis. The purpose of this study is to explore the expression and prognostic significance of these proteins in esophageal squamous cell carcinoma (ESCC).

Methods

We used immunohistochemistry and western blotting to examine the expression status of THBS1, Cyr61 and CTGF in ESCC. Correlations of THBS1, Cyr61 and CTGF over-expressions with various clinicopathologic factors were also determined by using the Chi-square test or Fisher's exact probability test. Survival analysis was assessed by the Kaplan-Meier analysis and the log-rank test. Relative risk was evaluated by the multivariate Cox proportional hazards model.

Results

THBS1, Cyr61 and CTGF were all over-expressed in ESCC. THBS1 over-expression was significantly associated with TNM stage (P= 0.029) and regional lymph node involvement (P= 0.026). Kaplan-Meier survival analysis showed that over-expression of THBS1, Cyr61 or CTGF was related to poor survival of ESCC patients (P= 0.042,P= 0.020,P= 0.018, respectively). Multivariate Cox analysis demonstrated that Cyr61 and CTGF were independent factors in prognosis of ESCC.

Conclusion

Cyr61, CTGF and THBS1 were all over-expressed in ESCC and might be new molecular markers to predict the prognosis of ESCC patients.
Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma
Authors: Pretscher Dominik , Distel Luitpold V , Grabenbauer Gerhard G , Wittlinger Michael , Buettner Maike , Niedobitek Gerald
Published: August 2009

Background

Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes.

Methods

We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system.

Results

We demonstrate a relative expansion of FoxP3+ regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infitrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8+ T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8+ TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment.

Conclusion

Our results suggest that alterations in lymphocyte distribution in regional lymph nodes rather than at the primary tumour site may be relevant for patient prognosis. Moreover, we demonstrate that in addition to cellular immunity humoral immune responses may be clinically relevant in anti-tumour immunity.
Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication
Authors: Guimarães Fernando SF , Abud Ana PR , Oliveira Simone M , Oliveira Carolina C , César Beatriz , Andrade Lucas F , Donatti Lucélia , Gabardo Juarez , Trindade Edvaldo S , Buchi Dorly F
Published: August 2009

Background

Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180.

Methods

Here we studied the interaction of mouse lymph node lymphocytes, co-cultured in vitro with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells.

Results

Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25+) lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes.

Conclusion

Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells.
Impact of leg lengthening on viscoelastic properties of the deep fascia
Authors: Wang Hai-Qiang , Wei Yi-Yong , Wu Zi-Xiang , Luo Zhuo-Jing
Published: August 2009

Background

Despite the morphological alterations of the deep fascia subjected to leg lengthening have been investigated in cellular and extracellular aspects, the impact of leg lengthening on viscoelastic properties of the deep fascia remains largely unknown. This study aimed to address the changes of viscoelastic properties of the deep fascia during leg lengthening using uniaxial tensile test.

Methods

Animal model of leg lengthening was established in New Zealand white rabbits. Distraction was initiated at a rate of 1 mm/day and 2 mm/day in two steps, and preceded until increases of 10% and 20% in the initial length of tibia had been achieved. The deep fascia specimens of 30 mm × 10 mm were clamped with the Instron 1122 tensile tester at room temperature with a constant tensile rate of 5 mm/min. After 5 load-download tensile tests had been performed, the specimens were elongated until rupture. The load-displacement curves were automatically generated.

Results

The normal deep fascia showed typical viscoelastic rule of collagenous tissues. Each experimental group of the deep fascia after leg lengthening kept the properties. The curves of the deep fascia at a rate of 1 mm/day with 20% increase in tibia length were the closest to those of normal deep fascia. The ultimate tension strength and the strain at rupture on average of normal deep fascia were 2.69 N (8.97 mN/mm2) and 14.11%, respectively. The increases in ultimate tension strength and strain at rupture of the deep fascia after leg lengthening were statistically significant.

Conclusion

The deep fascia subjected to leg lengthening exhibits viscoelastic properties as collagenous tissues without lengthening other than increased strain and strength. Notwithstanding different lengthening schemes result in varied viscoelastic properties changes, the most comparable viscoelastic properties to be demonstrated are under the scheme of a distraction rate of 1 mm/day and 20% increase in tibia length.
The cyanobacterial cell division factor Ftn6 contains an N-terminal DnaD-like domain
Authors: Marbouty Martial , Saguez Cyril , Chauvat Franck
Published: August 2009

Background

DNA replication and cell cycle as well as their relationship have been extensively studied in the two model organisms E. coli and B. subtilis. By contrast, little is known about these processes in cyanobacteria, even though they are crucial to the biosphere, in utilizing solar energy to renew the oxygenic atmosphere and in producing the biomass for the food chain. Recent studies have allowed the identification of several cell division factors that are specifics to cyanobacteria. Among them, Ftn6 has been proposed to function in the recruitment of the crucial FtsZ proteins to the septum or the subsequent Z-ring assembly and possibly in chromosome segregation.

Results

In this study, we identified an as yet undescribed domain located in the conserved N-terminal region of Ftn6. This 77 amino-acids-long domain, designated here as FND (Ftn6 N-T erminal D omain), exhibits striking sequence and structural similarities with the DNA-interacting module, listed in the PFAM database as the DnaD-like domain (pfam04271). We took advantage of the sequence similarities between FND and the DnaD-like domains to construct a homology 3D-model of the Ftn6 FND domain from the model cyanobacterium Synechocystis PCC6803. Mapping of the conserved residues exposed onto the FND surface allowed us to identify a highly conserved area that could be engaged in Ftn6-specific interactions.

Conclusion

Overall, similarities between FND and DnaD-like domains as well as previously reported observations on Ftn6 suggest that FND may function as a DNA-interacting module thereby providing an as yet missing link between DNA replication and cell division in cyanobacteria. Consistently, we also showed that Ftn6 is involved in tolerance to DNA damages generated by UV rays.
Direct costs associated with the appropriateness of hospital stay in elderly population
Authors: Mould-Quevedo Joaquín F , García-Peña Carmen , Contreras-Hernández Iris , Juárez-Cedillo Teresa , Espinel-Bermúdez Claudia , Morales-Cisneros Gabriela , Sánchez-García Sergio
Published: August 2009

Background

Ageing of Mexican population implies greater demand of hospital services. Nevertheless, the available resources are used inadequately. In this study, the direct medical costs associated with the appropriateness of elderly populations hospital stay are estimated.

Methods

Appropriateness of hospital stay was evaluated with the Appropriateness Evaluation Protocol (AEP). Direct medical costs associated with hospital stay under the third-party payer's institutional perspective were estimated, using as information source the clinical files of 60 years of age and older patients, hospitalized during year 2004 in a Regional Hospital from the Mexican Social Security Institute (IMSS), in Mexico City.

Results

The sample consisted of 724 clinical files, with a mean of 5.3 days (95% CI = 4.9–5.8) of hospital stay, of which 12.4% (n = 90) were classified with at least one inappropriate patient day, with a mean of 2.2 days (95% CI = 1.6 – 2.7). The main cause of inappropriateness days was the inexistence of a diagnostic and/or treatment plan, 98.9% (n = 89). The mean cost for an appropriate hospitalization per patient resulted in US$1,497.2 (95% CI = US$323.2 – US$4,931.4), while the corresponding mean cost for an inappropriate hospitalization per patient resulted in US$2,323.3 (95% CI = US$471.7 – US$6,198.3), (p < 0.001).

Conclusion

Elderly patients who were inappropriately hospitalized had a higher rate of inappropriate patient days. The average of inappropriate patient days cost is considerably higher than appropriate days. In this study, inappropriate hospital-stay causes could be attributable to physicians and current organizational management.
Audience effects in the Atlantic molly (Poecilia mexicana)–prudent male mate choice in response to perceived sperm competition risk?
Authors: Ziege Madlen , Mahlow Kristin , Hennige-Schulz Carmen , Kronmarck Claudia , Tiedemann Ralph , Streit Bruno , Plath Martin
Published: August 2009

Background

Multidirectional interactions in social networks can have a profound effect on mate choice behavior; e.g., Poecilia mexicana males show weaker expression of mating preferences when being observed by a rival. This may be an adaptation to reduce sperm competition risk, which arises because commonly preferred female phenotypes will receive attention also from surrounding males, and/or because other males can copy the focal male's mate choice. Do P. mexicana males indeed respond to perceived sperm competition risk? We gave males a choice between two females and repeated the tests under one of the following conditions: (1) an empty transparent cylinder was presented (control); (2) another ("audience") male inside the cylinder observed the focal male throughout the 2nd part, or (3) the audience male was presented only before the tests, but could not eavesdrop during the actual choice tests (non-specific sperm competition risk treatments); (4) the focal male could see a rival male interact sexually with the previously preferred, or (5) with the non-preferred female before the 2nd part of the tests (specific sperm competition risk treatments).

Results

The strength of individual male preferences declined slightly also during the control treatment (1). However, this decrease was more than two-fold stronger in audience treatment (2), i.e., with non-specific sperm competition risk including the possibility for visual eavesdropping by the audience male. No audience effect was found in treatments (3) and (5), but a weak effect was also observed when the focal male had seen the previously preferred female sexually interact with a rival male (treatment 4; specific sperm competition risk).

Conclusion

When comparing the two 'non-specific sperm competition risk' treatments, a very strong effect was found only when the audience male could actually observe the focal male during mate choice [treatment (2)]. This suggests that focal males indeed attempt to conceal their mating preferences so as to prevent surrounding males from copying their mate choice. When there is no potential for eavesdropping [treatment (3)], non-specific specific sperm competition risk seems to play a minor or no role. Our results also show that P. mexicana males tend to share their mating effort more equally among females when the resource value of their previously preferred mate decreases after mating with a rival male (perceived specific sperm competition risk), but this effect is comparatively weak.
Efficacy and safety of bilateral continuous theta burst stimulation (cTBS) for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial
Authors: Arfeller Carola , Vonthein Reinhard , Plontke Stefan K , Plewnia Christian
Published: August 2009

Background

Tinnitus, the perception of sound and noise in absence of an auditory stimulus, has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex. Transient modulation of tinnitus by repetitive transcranial magnetic stimulation (rTMS) indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies. However, the therapeutic efficacy of rTMS in tinnitus is still unclear, individual response is variable, and the optimal stimulation area disputable. Recently, continuous theta burst stimulation (cTBS) has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability.

Methods

48 patients with chronic subjective tinnitus will be included in this randomized, placebo controlled, three-arm trial. The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex, the temporoparietal associaction cortex, or to the lower occiput (sham condition) every working day for four weeks. Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Questionnaire (TQ). Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment. Audiologic and speech audiometric measurements will be performed to assess potential side effects. The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation. The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus.

Trial registration

The trial was registered with the clinical trials register of http://www.clinicaltrials.gov (NCT00518024).
Salvage of failed free flaps used in head and neck reconstruction
Authors: Novakovic Daniel , Patel Rajan S , Goldstein David P , Gullane Patrick J
Published: August 2009

Free flap success rates are in excess of 95%. Vascular occlusion (thrombosis) remains the primary reason for flap loss, with venous thrombosis being more common than arterial occlusion. The majority of flap failures occur within the first 48 hours. With early recognition and intervention of flap compromise salvage is possible. Successful salvage rates range from 28% to over 90%. Rapid re-exploration in this clinical setting is crucial to maximise the chances of flap salvage. If salvage is not feasible or unsuccessful then non-surgical methods of salvage may be employed with some possibility of success. The purpose of this article is to review the causes of free flap failure and to highlight the available options for salvage.
Community-wide analysis of microbial genome sequence signatures
Authors: Dick Gregory J , Andersson Anders F , Baker Brett J , Simmons Sheri L , Thomas Brian C , Yelton A Pepper , Banfield Jillian F
Published: August 2009

Background

Analyses of DNA sequences from cultivated microorganisms have revealed genome-wide, taxa-specific nucleotide compositional characteristics, referred to as genome signatures. These signatures have far-reaching implications for understanding genome evolution and potential application in classification of metagenomic sequence fragments. However, little is known regarding the distribution of genome signatures in natural microbial communities or the extent to which environmental factors shape them.

Results

We analyzed metagenomic sequence data from two acidophilic biofilm communities, including composite genomes reconstructed for nine archaea, three bacteria, and numerous associated viruses, as well as thousands of unassigned fragments from strain variants and low-abundance organisms. Genome signatures, in the form of tetranucleotide frequencies analyzed by emergent self-organizing maps, segregated sequences from all known populations sharing < 50 to 60% average amino acid identity and revealed previously unknown genomic clusters corresponding to low-abundance organisms and a putative plasmid. Signatures were pervasive genome-wide. Clusters were resolved because intra-genome differences resulting from translational selection or protein adaptation to the intracellular (pH ~5) versus extracellular (pH ~1) environment were small relative to inter-genome differences. We found that these genome signatures stem from multiple influences but are primarily manifested through codon composition, which we propose is the result of genome-specific mutational biases.

Conclusions

An important conclusion is that shared environmental pressures and interactions among coevolving organisms do not obscure genome signatures in acid mine drainage communities. Thus, genome signatures can be used to assign sequence fragments to populations, an essential prerequisite if metagenomics is to provide ecological and biochemical insights into the functioning of microbial communities.
Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion
Authors: Song Lanying , Li Yunhong , Wang Kai , Wang Ya-Zhou , Molotkov Andrei , Gao Lifang , Zhao Tianyu , Yamagami Takashi , Wang Yongping , Gan Qini , Pleasure David E. , Zhou Chengji J.
Published: August 2009

Neither the mechanisms that govern lip morphogenesis nor the cause of cleft lip are well understood. We report that genetic inactivation of Lrp6, a co-receptor of the Wnt/β-catenin signaling pathway, leads to cleft lip with cleft palate. The activity of a Wnt signaling reporter is blocked in the orofacial primordia by Lrp6 deletion in mice. The morphological dynamic that is required for normal lip formation and fusion is disrupted in these mutants. The expression of the homeobox genes Msx1 and Msx2 is dramatically reduced in the mutants, which prevents the outgrowth of orofacial primordia, especially in the fusion site. We further demonstrate that Msx1 and Msx2 (but not their potential regulator Bmp4) are the downstream targets of the Wnt/β-catenin signaling pathway during lip formation and fusion. By contrast, a `fusion-resistant'gene, Raldh3 (also known as Aldh1a3), that encodes a retinoic acid-synthesizing enzyme is ectopically expressed in the upper lip primordia of Lrp6-deficient embryos, indicating a region-specific role of the Wnt/β-catenin signaling pathway in repressing retinoic acid signaling. Thus, the Lrp6-mediated Wnt signaling pathway is required for lip development by orchestrating two distinctively different morphogenetic movements.
Numerical investigation of a multiple injection strategy on the development of high-pressure diesel sprays
Authors: Tonini S , Gavaises M , Theodorakakos A , Cossali G E
Published: August 2009

Computational fluid dynamics results are presented providing information on the influence of multiple injection strategy on fuel vaporization characteristics under conditions typical of direct injection, turbocharged, high-speed automotive diesel engines. The fuel is assumed to be injected from a high-pressure common rail injector nozzle. Focus is given on the number of multiple injections and dwell-time on the evaporating spray plume development. Comparison between the different cases is performed in terms of liquid and vapour penetration curves, the spatial distribution of the air—fuel equivalence ratio and the fuel vapour spatial distribution difference between the cases considered. The results confirm that, under the operating conditions investigated, the liquid penetration length, known to freeze at a distance from the nozzle exit, is not significantly affected by the injection strategy, while vapour penetration follows the time-shift of the dwell-time. Longer dwell-times retard the diffusion of the vapour in the carrier gas. Although injection of small fuel quantities prior to the main pulse does not affect the liquid penetration, it contributes up to 5 per cent more stoichiometric fuel vapour present in the area of observed auto-ignition sites. Post injection and splitting of the main injection in two pulses modify the vapour distribution by creating two spatially separated fuel-rich zones.
Determination of passenger car interior space for foot controls accommodation
Authors: Klarin M M , Spasojević-Brkić V K , Sajfert Z D , Žunjić A G , Nikolić M S
Published: August 2009

This study shows that the automobile is still not well enough adapted for human beings, especially in the part of the interior where the foot controls are located. When designing passenger vehicles ergonomically, the anthropometric limitations are as important as the technical limitations. Moreover, exacting contemporary economic and ecological requirements mean that the interior of the standard passenger vehicle must be designed to reduce front surface and air resistance to a minimum. The present authors offer a new method for designing the part of the interior of standard passenger vehicles where the foot controls are located as an indivisible part of the whole interior, with interrelated functional links using anthropometric limitations. These vary according to region and country and change with time. This study uses anthropometric data for drivers from Serbia from 1976 to 2007. The objective was, taking into account vehicle interior height limitations, to accommodate the largest range of anthropometric dimensions, from the fifth-percentile woman to the 95th-percentile man, which was accomplished using a new method for model accommodation optimization. Furthermore, comfort and a safe steering position are assured. The existence of the O point is required as the origin of a coordinate system with x, y, and z axes for the man—vehicle system and this enables the mechanical and mathematical functions to be defined more accurately within the system. By applying the suggested method and processing the data acquired, an optimum space for foot controls was obtained. The space for foot control location lies horizontally along the x axis forward from the O point by 320mm and vertically along the z axis by 230mm. The space height along the z axis is 465mm. The space is determined in four segments by the anthropomeasures of the foot of the 95th-percentile man and the fifth-percentile woman, first starting from the floor line to the point (−320mm, 230mm). Also, it is determined by the height of 465mm of the 95th-percentile man to the point (50mm, 465mm), when the space as far as the lower half of the windshield glass is defined by the fifth-percentile woman. In this way, a larger space is needed for seating of the fifth-percentile woman than would be needed if only the 95th-percentile man were seated.
A statistical approach to comparing wheel hub forging processes
Authors: Osma A
Published: August 2009

Structural components used in the automotive industry offer an attractive opportunity for exploring alternate material sources and different manufacturing routes because economic globalization continually intensifies competition and increases costs. While economic parameters are important in the choice of manufacturing process, the final decision is usually dictated by desirable component characteristics and reliability. Integrated process flows involving steel making, forging, and heat treatments can reduce the impact on forged and heat-treated hubs. However, speed differences in hot forging operations, sources, and heat treatment equipment differences still influence the ultimate manufacturing decision. The aim of this study is to demonstrate interdisciplinary effort in comparing two different wheel hub forging processes by quantifying final product characteristics that are linked to their microstructures and to understand the possible impacts on quality assurance of the final parts. Brinell hardness measurements were performed as part of the analysis, and both non-parametric and parametric statistical procedures were applied to data taken from samples that were manufactured under real industry conditions. In addition, scanning electron microscopy was utilized to support analytical results.