bluuebunny/crossref_metadata_2025_split huggingface dataset:
Set theoretic formulation of performance reliability of multiple response time‐variant systems due to degradations in system components
Authors: Son Young Kap , Savage Gordon J. 
Published: May 2006

AbstractThis paper presents a design stage method for assessing performance reliability of systems with multiple time‐variant responses due to component degradation. Herein the system component degradation profiles over time are assumed to be known and the degradation of the system is related to component degradation using mechanistic models. Selected performance measures (e.g. responses) are related to their critical levels by time‐dependent limit‐state functions. System failure is defined as the non‐conformance of any response and unions of the multiple failure regions are required. For discrete time, set theory establishes the minimum union size needed to identify a true incremental failure region. A cumulative failure distribution function is built by summing incremental failure probabilities. A practical implementation of the theory can be manifest by approximating the probability of the unions by second‐order bounds. Further, for numerical efficiency probabilities are evaluated by first‐order reliability methods (FORM). The presented method is quite different from Monte Carlo sampling methods. The proposed method can be used to assess mean and tolerance design through simultaneous evaluation of quality and performance reliability. The work herein sets the foundation for an optimization method to control both quality and performance reliability and thus, for example, estimate warranty costs and product recall. An example from power engineering shows the details of the proposed method and the potential of the approach. Copyright © 2006 John Wiley & Sons, Ltd.
Regular subgraphs of random graphs
Authors: Bollobás Béla , Kim Jeong Han , Verstraëte Jacques 
Published: May 2006

AbstractIn this paper, we prove that there exists a function ρk = (4 + o(1))k such that G(n,ρ/n) contains a k−regular graph with high probability whenever ρ > ρk. In the case of k = 3, it is also shown that G(n,ρ/n) contains a 3−regular graph with high probability whenever ρ > λ ≈︁ 5.1494. These are the first constant bounds on the average degree in G(n,p) for the existence of a k−regular subgraph. We also discuss the appearance of 3−regular subgraphs in cores of random graphs. © 2006 Wiley Periodicals, Inc. Random Struct. Alg., 2006
Non‐parametric estimation for baseline hazards function and covariate effects with time‐dependent covariates
Authors: Gao Feng , Manatunga Amita K. , Chen Shande 
Published: May 2006

AbstractOften in many biomedical and epidemiologic studies, estimating hazards function is of interest. The Breslow's estimator is commonly used for estimating the integrated baseline hazard, but this estimator requires the functional form of covariate effects to be correctly specified. It is generally difficult to identify the true functional form of covariate effects in the presence of time‐dependent covariates. To provide a complementary method to the traditional proportional hazard model, we propose a tree‐type method which enables simultaneously estimating both baseline hazards function and the effects of time‐dependent covariates. Our interest will be focused on exploring the potential data structures rather than formal hypothesis testing. The proposed method approximates the baseline hazards and covariate effects with step‐functions. The jump points in time and in covariate space are searched via an algorithm based on the improvement of the full log‐likelihood function. In contrast to most other estimating methods, the proposed method estimates the hazards function rather than integrated hazards. The method is applied to model the risk of withdrawal in a clinical trial that evaluates the anti‐depression treatment in preventing the development of clinical depression. Finally, the performance of the method is evaluated by several simulation studies. Copyright © 2006 John Wiley & Sons, Ltd.
Observing local and global properties of metabolic pathways: ‘load points’ and ‘choke points’ in the metabolic networks
Authors: Rahman Syed Asad , Schomburg Dietmar 
Published: May 2006

Abstract
Motivation: The local and global aspects of metabolic network analyses allow us to identify enzymes or reactions that are crucial for the survival of the organism(s), therefore directing us towards the discovery of potential drug targets.
Results: We demonstrate a new method (‘load points’) to rank the enzymes/metabolites in the metabolic network and propose a model to determine and rank the biochemical lethality in metabolic networks (enzymes/metabolites) through ‘choke points’. Based on an extended form of the graph theory model of metabolic networks, metabolite structural information was used to calculate the k-shortest paths between metabolites (the presence of more than one competing path between substrate and product). On the basis of these paths and connectivity information, load points were calculated and used to empirically rank the importance of metabolites/enzymes in the metabolic network. The load point analysis emphasizes the role that the biochemical structure of a metabolite, rather than its connectivity (hubs), plays in the conversion pathway.
In order to identify potential drug targets (based on the biochemical lethality of metabolic networks), the concept of choke points and load points was used to find enzymes (edges) which uniquely consume or produce a particular metabolite (nodes). A non-pathogenic bacterial strain Bacillus subtilis 168 (lactic acid producing bacteria) and a related pathogenic bacterial strain Bacillus anthracis Sterne (avirulent but toxigenic strain, producing the toxin Anthrax) were selected as model organisms. The choke point strategy was implemented on the pathogen bacterial network of B.anthracis Sterne. Potential drug targets are proposed based on the analysis of the top 10 choke points in the bacterial network. A comparative study between the reported top 10 bacterial choke points and the human metabolic network was performed. Further biological inferences were made on results obtained by performing a homology search against the human genome.
Availability: The load and choke point modules are introduced in the Pathway Hunter Tool (PHT), the basic version of which is available on
Contact: d.schomburg@uni-koeln.de
Supplementary information: Supplementary data are available on Bioinformatics online.
Integration Host Factor is required for FarR repression of the farAB‐encoded efflux pump of Neisseria gonorrhoeae
Authors: Lee Eun‐Hee , Hill Stuart A. , Napier Ruth , Shafer William M. 
Published: May 2006

SummaryThe farAB operon encodes an efflux pump system that mediates the resistance of Neisseria gonorrhoeae to antimicrobial long‐chain fatty acids. We previously observed that expression of farAB is negatively regulated by the FarR repressor. In this study, we examined the molecular mechanism by which FarR represses expression of farAB. DNase I footprinting analysis, coupled with a deletion analysis of the farAB promoter region, indicated that FarR binds to three sites (termed sites A, B and C) within the DNA sequence upstream of farA; genetic analysis revealed, however, that site B is not required for FarR repression of farAB. This repression also required the presence of Integration Host Factor (IHF), which was found to bind to sequences located between FarR binding sites A and C. We determined that IHF binding to the farAB promoter region could inhibit transcription in vitro and that such binding induced a bending of the target DNA, which we propose to be important in regulating this operon. IHF binding to the promoter region was found to stabilize the binding of FarR to its binding sites A and C and as a consequence, enhanced repression of farAB expression mediated by FarR. We propose a model in which expression of the farAB‐encoded efflux pump in N. gonorrhoeae is modulated by the DNA binding activities of FarR and IHF.
PDR16‐mediated azole resistance in Candida albicans
Authors: Saidane Saloua , Weber Sandra , De Deken Xavier , St‐Germain Guy , Raymond Martine 
Published: May 2006

SummaryMany Candida albicans azole‐resistant (AR) clinical isolates overexpress the CDR1 and CDR2 genes encoding homologous multidrug transporters of the ATP‐binding cassette family. We show here that these strains also overexpress the PDR16 gene, the orthologue of Saccharomyces cerevisiae PDR16 encoding a phosphatidylinositol transfer protein of the Sec14p family. It has been reported that S. cerevisiae pdr16Δ mutants are hypersusceptible to azoles, suggesting that C. albicans PDR16 may contribute to azole resistance in these isolates. To address this question, we deleted both alleles of PDR16 in an AR clinical strain overexpressing the three genes, using the mycophenolic acid resistance flipper strategy. Our results show that the homozygous pdr16Δ/pdr16Δ mutant is approximately twofold less resistant to azoles than the parental strain whereas reintroducing a copy of PDR16 in the mutant restored azole resistance, demonstrating that this gene contributes to the AR phenotype of the cells. In addition, overexpression of PDR16 in azole‐susceptible (AS) C. albicans and S. cerevisiae strains increased azole resistance by about twofold, indicating that an increased dosage of Pdr16p can confer low levels of azole resistance in the absence of additional molecular alterations. Taken together, these results demonstrate that PDR16 plays a role in C. albicans azole resistance.
Bacillus subtilis Fnr senses oxygen via a [4Fe‐4S] cluster coordinated by three cysteine residues without change in the oligomeric state
Authors: Reents Heike , Gruner Ines , Harmening Ute , Böttger Lars H. , Layer Gunhild , Heathcote Peter , Trautwein Alfred X. , Jahn Dieter , Härtig Elisabeth 
Published: May 2006

SummaryThe oxygen regulator Fnr is part of the regulatory cascade in Bacillus subtilis for the adaptation to anaerobic growth conditions. In vivo complementation experiments revealed the essential role of only three cysteine residues (C227, C230, C235) at the C‐terminus of B. subtilis Fnr for the transcriptional activation of the nitrate reductase operon (narGHJI) and nitrite extrusion protein gene (narK) promoters. UV/VIS, electron paramagnetic spin resonance (EPR) and Mössbauer spectroscopy experiments in combination with iron and sulphide content determinations using anaerobically purified recombinant B. subtilis Fnr identified the role of these three cysteine residues in the formation of one [4Fe‐4S]2+ cluster per Fnr molecule. The obtained Mössbauer parameters are supportive for a [4Fe‐4S]2+ cluster with three cysteine ligated iron sites and one non‐cysteine ligated iron site. Gel filtration experiments revealed a stable dimeric structure for B. subtilis Fnr which is independent of the presence of the [4Fe‐4S]2+ cluster. Gel mobility shift and in vitro transcription assays demonstrated the essential role of an intact [4Fe‐4S]2+ cluster for promoter binding and transcriptional activation. An amino acid exchange introduced in the proposed αD‐helix of B. subtilis Fnr (G149S) abolished its in vivo and in vitro activities indicating its importance for intramolecular signal transduction. The clear differences in the localization and coordination of the [4Fe‐4S] cluster and in the organization of the oligomeric state between Escherichia coli and B. subtilis Fnr indicate differences in their mode of action.
Antigenic variation with a twist – the Borrelia story
Authors: Norris Steven J. 
Published: May 2006

SummaryA common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface‐exposed antigen. In this issue of Molecular Microbiology, Dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia hermsii. This elaborate, plasmid‐encoded system involves an expression site that can acquire either variable large protein (vlp) or variable small protein (vsp) surface lipoprotein genes from 59 different archival copies. The archival vlp and vsp genes are arranged in clusters on at least five different plasmids. Gene conversion occurs through recombination events at upstream homology sequences (UHS) found in each gene copy, and at downstream homology sequences (DHS) found periodically among the vlp/vsp archival genes. Previous studies have shown that antigenic variation in relapsing fever Borrelia not only permits the evasion of host antibody responses, but can also result in changes in neurotropism and other pathogenic properties. The vlsE antigenic variation locus of Lyme disease spirochaetes, although similar in sequence to the relapsing fever vlp genes, has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes. These two systems thus appear to represent divergence from a common precursor followed by functional convergence to create two distinct antigenic variation processes.
Fern endemism and its correlates: contribution from an elevational transect in Costa Rica
Authors: Kluge Jürgen , Kessler Michael 
Published: May 2006

ABSTRACTWe studied the distribution patterns of endemic ferns along an elevational gradient of 3400 m in Costa Rica, Central America. We related the endemism patterns of the whole species set and separated for life forms and microhabitats according to topography and environmental factors. Fern species were surveyed in 156 plots each with an area of 400 m2, with up to five plots at every elevational step of 100 m. Global range size for every species was compiled from literature data, and species restricted to the mountain range from Costa Rica and adjacent western Panama were defined as endemic (24.5% of all species recorded). We found patterns of endemism rates mostly peaking at mid‐elevation, but when separated for different life forms and microhabitats, some deviations from the overall pattern emerged. High constant humidity and reduced surface area were closely related to high levels of endemism. High humidity is discussed as a general predictor for high endemism rates in concert with highest overall richness. Restricted area of elevational belts, indicating a fragmented habitat, leads to a higher degree of population isolation and thus species differentiation. However, both interpretations were not fully supported by our data. Most importantly, endemism rates were fairly low on mountain tops that have the smallest available area in a topographically highly fragmented setting. In contrast, endemic species were more common than widespread species at the highest elevations. History and climatic shifts are assumed to play a role in this respect.
Integrating DNA data and traditional taxonomy to streamline biodiversity assessment: an example from edaphic beetles in the Klamath ecoregion, California, USA
Authors: Caesar Ryan M. , Sörensson Mikael , Cognato Anthony I. 
Published: May 2006

ABSTRACTConservation and land management decisions may be misguided by inaccurate or misinterpreted knowledge of biodiversity. Non‐systematists often lack taxonomic expertise necessary for an accurate assessment of biodiversity. Additionally, there are far too few taxonomists to contribute significantly to the task of identifying species for specimens collected in biodiversity studies. While species level identification is desirable for making informed management decisions concerning biodiversity, little progress has been made to reduce this taxonomic deficiency. Involvement of non‐systematists in the identification process could hasten species identification. Incorporation of DNA sequence data has been recognized as one way to enhance biodiversity assessment and species identification. DNA data are now technologically and economically feasible for most scientists to apply in biodiversity studies. However, its use is not widespread and means of its application has not been extensively addressed. This paper illustrates how such data can be used to hasten biodiversity assessment of species using a little‐known group of edaphic beetles. Partial mitochondrial cytochrome oxidase I was sequenced for 171 individuals of feather‐wing beetles (Coleoptera: Ptiliidae) from the Klamath ecoregion, which is part of a biodiversity hotspot, the California Floristic Province. A phylogram of these data was reconstructed via parsimony and the strict consensus of 28,000 equally parsimonious trees was well resolved except for peripheral nodes. Forty‐two voucher specimens were selected for further identification from clades that were associated with many synonymous and non‐synonymous nucleotide changes. A ptiliid taxonomic expert identified nine species that corresponded to monophyletic groups. These results allowed for a more accurate assessment of ptiliid species diversity in the Klamath ecoregion. In addition, we found that the number of amino acid changes or percentage nucleotide difference did not associate with species limits. This study demonstrates that the complementary use of taxonomic expertise and molecular data can improve both the speed and the accuracy of species‐level biodiversity assessment. We believe this represents a means for non‐systematists to collaborate directly with taxonomists in species identification and represents an improvement over methods that rely solely on parataxonomy or sequence data.
Open partial nephrectomy: outcomes from two UK centres
Authors: RAY ELEANOR R. , TURNEY BENJAMIN W. , SINGH RAJINDER , CHANDRA ASHISH , CRANSTON DAVID W. , O’BRIEN TIMOTHY S. 
Published: May 2006

OBJECTIVETo define the current achievable outcomes from open partial nephrectomy (OPN) in the UK at a time when other treatments for small kidney tumours are increasingly being advocated. Current knowledge of the effectiveness of OPN is limited by the fact that published data are almost exclusively derived from a very few centres of established world renown.PATIENTS AND METHODSWe retrospectively reviewed 100 consecutive planned OPNs in 90 patients at two UK centres; 93 operations were for suspected cancer. The median (range) tumour size was 3.8 (1.2–9) cm. In all, 42 OPNs were imperative for patients with a single kidney (14), synchronous bilateral tumours (20), or renal impairment alone (eight). In 42 patients with a tumour of ≤ 4 cm and a normal contralateral kidney the decision to do OPN was considered elective. There were 10 additional operations in seven patients with Von Hippel‐Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney.RESULTSIn all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozen‐section analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re‐operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3–50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow‐up of 24 (1–69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence.CONCLUSIONOPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer.
Prostate stem cell antigen predicts tumour recurrence in superficial transitional cell carcinoma of the urinary bladder
Authors: ELSAMMAN ESSAM , FUKUMORI TOMOHARU , KASAI TOSHINORI , NAKATSUJI HIROYOSHI , NISHITANI MASA‐AKI , TOIDA KAZUNORI , ALI NERMIN , KANAYAMA HIRO‐OMI 
Published: May 2006

OBJECTIVESTo evaluate the relationship between prostate stem cell antigen (PSCA) expression level in transitional cell carcinoma (TCC) of the urinary bladder and various clinicopathological features, including stage and grade; and to determine whether PSCA mRNA expression predicts disease recurrence in superficial (not muscle‐invasive) TCC of the bladder.PATIENTS AND METHODSReal‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) was performed on 97 TCC tissue samples and in 36 samples of normal bladder urothelium; the findings were analysed in relation to clinicopathological factors. Immunohistochemical expression was examined using light and confocal immunofluorescence microscopy to validate the RT‐PCR data.RESULTSTwenty‐seven patients developed disease recurrence, while the remaining 22 had no evidence of recurrence of superficial TCC of the bladder. There was significantly higher PSCA mRNA expression in TCC than in normal urothelium samples (P = 0.008). Superficial (TaT1) tumours had significantly higher PSCA expression than muscle‐invasive (≥ pT2) tumours (P < 0.001). There was no significant difference between patients with G1–2 tumours and those with G3 tumours (P = 0.109). Immunohistochemical analysis showed markedly greater PSCA expression in superficial than invasive TCC. Notably, from a multivariate analysis, the expression level of PSCA was an independent predictor of disease recurrence in superficial TCC (P = 0.012).CONCLUSIONSThese findings suggest that the PSCA expression level measured by real‐time RT‐PCR could be a valuable prognostic marker for tumour recurrence in superficial TCC of the bladder.