bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative inference of dynamic regulatory pathways via microarray data
Authors: Chang Wen-Chieh , Li Chang-Wei , Chen Bor-Sen
Published: March 2005

Background

The cellular signaling pathway (network) is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach.

Results

In this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network) to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network). Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data.

Conclusion

We focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory pathway in Arabidopsis thaliana and metabolic shift pathway from fermentation to respiration in yeast Saccharomyces cerevisiae, are reconstructed using microarray data to evaluate the performance of our proposed method. In the circadian regulatory pathway, we identified mainly the interactions between the biological clock and the photoperiodic genes consistent with the known regulatory mechanisms. We also discovered the now less-known regulations between crytochrome and phytochrome. In the metabolic shift pathway, the casual relationship of enzymatic genes could be detected properly.
Inclusion of Scar/WAVE3 in a similar complex to Scar/WAVE1 and 2
Authors: Stovold Craig F , Millard Thomas H , Machesky Laura M
Published: March 2005

Background

The Scar/WAVE family of proteins mediates signals to actin assembly by direct activation of the Arp2/3 complex. These proteins have been characterised as major regulators of lamellipodia formation downstream of Rac activation and as members of large protein complexes.

Results

We have investigated the interactions of the three human Scar/WAVE isoforms with several previously described binding partners for Scar/WAVE 1 or 2. We find that all three Scar/WAVE isoforms behave similarly and are likely to participate in the same kinds of protein complexes that regulate actin assembly.

Conclusion

Differences between Scar/WAVE proteins are therefore likely to be at the level of tissue distribution or subtle differences in the affinity for specific binding partners.
cAMP controls cytosolic Ca2+ levels in Dictyostelium discoideum
Authors: Lusche Daniel F , Bezares-Roder Karen , Happle Kathrin , Schlatterer Christina
Published: March 2005

Background

Differentiating Dictyostelium discoideum amoebae respond upon cAMP-stimulation with an increase in the cytosolic free Ca2+ concentration ([Ca2+]i) that is composed of liberation of stored Ca2+ and extracellular Ca2+-influx. In this study we investigated whether intracellular cAMP is involved in the control of [Ca2+]i.

Results

We analyzed Ca2+-fluxes in a mutant that is devoid of the main cAMP-phosphodiesterase (PDE) RegA and displays an altered cAMP metabolism. In suspensions of developing cells cAMP-activated influx of extracellular Ca2+ was reduced as compared to wild type. Yet, single cell [Ca2+]i-imaging of regA- amoebae revealed a cAMP-induced [Ca2+]i increase even in the absence of extracellular Ca2+. The cytosolic presence of the cAMP PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) induced elevated basal [Ca2+]i in both, mutant and wild type cells. Under this condition wild type cells displayed cAMP-activated [Ca2+]i-transients also in nominally Ca2+-free medium. In the mutant strain the amplitude of light scattering oscillations and of accompanying cAMP oscillations were strongly reduced to almost basal levels. In addition, chemotactic performance during challenge with a cAMP-filled glass capillary was altered by EGTA-incubation. Cells were more sensitive to EGTA treatment than wild type: already at 2 mM EGTA only small pseudopods were extended and chemotactic speed was reduced.

Conclusion

We conclude that there is a link between the second messengers cAMP and Ca2+. cAMP-dependent protein kinase (PKA) could provide for this link as a membrane-permeable PKA-activator also increased basal [Ca2+]i of regA- cells. Intracellular cAMP levels control [Ca2+]i by regulating Ca2+-fluxes of stores which in turn affect Ca2+-influx, light scattering oscillations and chemotactic performance.
Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation
Authors: Becker Scott A , Palsson Bernhard Ø
Published: March 2005

Background

Several strains of bacteria have sequenced and annotated genomes, which have been used in conjunction with biochemical and physiological data to reconstruct genome-scale metabolic networks. Such reconstruction amounts to a two-dimensional annotation of the genome. These networks have been analyzed with a constraint-based formalism and a variety of biologically meaningful results have emerged. Staphylococcus aureus is a pathogenic bacterium that has evolved resistance to many antibiotics, representing a significant health care concern. We present the first manually curated elementally and charge balanced genome-scale reconstruction and model of S. aureus' metabolic networks and compute some of its properties.

Results

We reconstructed a genome-scale metabolic network of S. aureus strain N315. This reconstruction, termed i SB619, consists of 619 genes that catalyze 640 metabolic reactions. For 91% of the reactions, open reading frames are explicitly linked to proteins and to the reaction. All but three of the metabolic reactions are both charge and elementally balanced. The reaction list is the most complete to date for this pathogen. When the capabilities of the reconstructed network were analyzed in the context of maximal growth, we formed hypotheses regarding growth requirements, the efficiency of growth on different carbon sources, and potential drug targets. These hypotheses can be tested experimentally and the data gathered can be used to improve subsequent versions of the reconstruction.

Conclusion

iSB619 represents comprehensive biochemically and genetically structured information about the metabolism of S. aureus to date. The reconstructed metabolic network can be used to predict cellular phenotypes and thus advance our understanding of a troublesome pathogen.
Elevated creatine kinase activity in primary hepatocellular carcinoma
Authors: Meffert Georg , Gellerich Frank N , Margreiter Raimund , Wyss Markus
Published: March 2005

Background

Inconsistent findings have been reported on the occurrence and relevance of creatine kinase (CK) isoenzymes in mammalian liver cells. Part of this confusion might be due to induction of CK expression during metabolic and energetic stress.

Methods

The specific activities and isoenzyme patterns of CK and adenylate kinase (AdK) were analysed in pathological liver tissue of patients undergoing orthotopic liver transplantation.

Results

The brain-type, cytosolic BB-CK isoenzyme was detected in all liver specimens analysed. Conversely, CK activity was strongly increased and a mitochondrial CK (Mi-CK) isoenzyme was detected only in tissue samples of two primary hepatocellular carcinomas (HCCs).

Conclusion

The findings do not support significant expression of CK in normal liver and most liver pathologies. Instead, many of the previous misconceptions in this field can be explained by interference from AdK isoenzymes. Moreover, the data suggest a possible interplay between p53 mutations, HCC, CK expression, and the growth-inhibitory effects of cyclocreatine in HCC. These results, if confirmed, could provide important hints at improved therapies and cures for HCC.
Using item response theory to explore the psychometric properties of extended matching questions examination in undergraduate medical education
Authors: Bhakta Bipin , Tennant Alan , Horton Mike , Lawton Gemma , Andrich David
Published: March 2005

Background

As assessment has been shown to direct learning, it is critical that the examinations developed to test clinical competence in medical undergraduates are valid and reliable. The use of extended matching questions (EMQ) has been advocated to overcome some of the criticisms of using multiple-choice questions to test factual and applied knowledge.

Methods

We analysed the results from the Extended Matching Questions Examination taken by 4th year undergraduate medical students in the academic year 2001 to 2002. Rasch analysis was used to examine whether the set of questions used in the examination mapped on to a unidimensional scale, the degree of difficulty of questions within and between the various medical and surgical specialties and the pattern of responses within individual questions to assess the impact of the distractor options.

Results

Analysis of a subset of items and of the full examination demonstrated internal construct validity and the absence of bias on the majority of questions. Three main patterns of response selection were identified.

Conclusion

Modern psychometric methods based upon the work of Rasch provide a useful approach to the calibration and analysis of EMQ undergraduate medical assessments. The approach allows for a formal test of the unidimensionality of the questions and thus the validity of the summed score. Given the metric calibration which follows fit to the model, it also allows for the establishment of items banks to facilitate continuity and equity in exam standards.
Fuzzy species among recombinogenic bacteria
Authors: Hanage William P , Fraser Christophe , Spratt Brian G
Published: March 2005

Background

It is a matter of ongoing debate whether a universal species concept is possible for bacteria. Indeed, it is not clear whether closely related isolates of bacteria typically form discrete genotypic clusters that can be assigned as species. The most challenging test of whether species can be clearly delineated is provided by analysis of large populations of closely-related, highly recombinogenic, bacteria that colonise the same body site. We have used concatenated sequences of seven house-keeping loci from 770 strains of 11 named Neisseria species, and phylogenetic trees, to investigate whether genotypic clusters can be resolved among these recombinogenic bacteria and, if so, the extent to which they correspond to named species.

Results

Alleles at individual loci were widely distributed among the named species but this distorting effect of recombination was largely buffered by using concatenated sequences, which resolved clusters corresponding to the three species most numerous in the sample, N. meningitidis, N. lactamica and N. gonorrhoeae. A few isolates arose from the branch that separated N. meningitidis from N. lactamica leading us to describe these species as 'fuzzy'.

Conclusion

A multilocus approach using large samples of closely related isolates delineates species even in the highly recombinogenic human Neisseria where individual loci are inadequate for the task. This approach should be applied by taxonomists to large samples of other groups of closely-related bacteria, and especially to those where species delineation has historically been difficult, to determine whether genotypic clusters can be delineated, and to guide the definition of species.
Physiological characterisation of a pH- and calcium-dependent sodium uptake mechanism in the freshwater crustacean,Daphnia magna
Authors: Glover Chris N. , Wood Chris M.
Published: March 2005

Daphnia are highly sensitive to sodium metabolism disruption caused by aquatic acidification and ionoregulatory toxicants, due to their finely balanced ion homeostasis. Nine different water chemistries of varying pH (4, 6 and 8) and calcium concentration (0, 0.5 and 1 mmol l–1) were used to delineate the mechanism of sodium influx in Daphnia magna. Lowering water pH severely inhibited sodium influx when calcium concentration was high, but transport kinetic analysis revealed a stimulated sodium influx capacity (Jmax) when calcium was absent. At low pH increasing water calcium levels decreased Jmax and raised Km (decreased sodium influx affinity), while at high pH the opposite pattern was observed (elevated Jmax and reduced Km). These effects on sodium influx were mirrored by changes in whole body sodium levels. Further examination of the effect of calcium on sodium influx showed a severe inhibition of sodium uptake by 100 μmol l–1 calcium gluconate at both low (50 μmol l–1) and high (1000 μmol l–1) sodium concentrations. At high sodium concentrations,stimulated sodium influx was noted with elevated calcium levels. These results, in addition to data showing amiloride inhibition of sodium influx(Ki=180 μmol l–1), suggest a mechanism of sodium influx in Daphnia magna that involves the electrogenic 2Na+/1H+ exchanger.
Social experience and pheromonal perception can change male–male interactions inDrosophila melanogaster
Authors: Svetec Nicolas , Ferveur Jean-François
Published: March 2005

Social interaction with conspecifics can influence the developing brain and behaviour of the exposed animal. This experience can involve the exchange and retention of visual, chemical, acoustic and tactile signals. When several Drosophila melanogaster male flies are associated with mated females in the presence of food, they show frequent aggressive interactions. To measure the role of social experience on male–male interaction, two tester males – naïve or exposed to sibling(s) during a variable period of their adult development – were confronted in the absence of female and food. The two males displayed homosexual courtship and aggressive behaviours, the frequency, intensity and directionality of which varied according to their experience. The effect of social experience was greatly enhanced between transgenic males partially defective for pheromonal perception, indicating that male inhibitory pheromones are normally used to repress male–male interaction.
The role of the mesothoracic spiracles in respiration in flighted and flightless dung beetles
Authors: Duncan Frances D. , Byrne Marcus J.
Published: March 2005

The relative role of the mesothoracic and abdominal spiracles in respiration was examined using flow-through respirometry in four dung beetle species from different habitats. Two species of flightless beetles, Scarabaeus (Pachysoma) gariepinus and Scarabaeus (Pachysoma) striatum, from the arid western region of southern Africa and a large flighted species, Pachylomerus femoralis, from a more mesic habitat were compared with Circellium bacchus, a flightless beetle from a low rainfall eastern area. All species showed a form of the discontinuous gas exchange pattern at rest. The mesic flighted species used a closed, flutter, open, cycle (CFO)while those species from more arid habitats used a closed, ventilation, cycle(CV) or a closed, burst cycle (CB). The relative importance of the mesothoracic spiracles in CO2 emission varied between the species,even between those from the same genus and habitat. C. bacchus and P. femoralis represent extremes of CO2 emission from the mesothoracic spiracles; from almost total to almost none, respectively. Overall, mesothoracic CO2 emission and convection were more pronounced in the dry habitat species, supporting the hypothesis that both strategies aid in the reduction of water loss.
Acute actions of testosterone on contractile function of isolated rat ventricular myocytes
Authors: Golden Kish L , Marsh James D , Jiang Yang , Moulden Jerome
Published: March 2005

Variation between the sexes in cardiac function have been established. The extent to which sex hormones are responsible for these differences is unclear. The current study was designed to determine whether testosterone acts acutely to enhance contractility of cultured rat ventricular myocytes. Following a 24-h treatment with testosterone (1 μM), isolated rat ventricular myocytes display a 21% increase (P < 0.01) in peak shortening and an 18% decrease (P < 0.02) in time to peak shortening. In accordance with this change, testosterone treatment produced an 18% decline (P < 0.002) in the time to relengthening when compared to vehicle-treated controls. These results provide the first evidence that short-term androgen exposure acts directly to stimulate contractility of isolated rat ventricular myocytes and thus may play a role in regulating cardiac performance in males and thereby contribute to sex differences in cardiac function.
Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids
Authors: Peracchi M , Gebbia C , Basilisco G , Quatrini M , Tarantino C , Vescarelli C , Massironi S , Conte D
Published: March 2005

Objective: In atrophic body gastritis (ABG) chronic hypergastrinaemia stimulates enterochromaffin-like (ECL) cell proliferation with development of cell hyperplasia, dysplasia and possibly type-1 gastric carcinoids. As circulating chromogranin A (CgA) levels are a marker of neuroendocrine tumours, we evaluated the clinical usefulness of CgA assay in ABG patients to detect those with carcinoids.

Design and methods: Plasma CgA levels were measured using a commercial ELISA in 45 healthy volunteers, nine patients with type-1 gastric carcinoids and 43 consecutive ABG patients (21 without and 22 with ECL cell hyperplasia/dysplasia).

Results: CgA levels were significantly higher in ABG patients with and without gastric carcinoids than in healthy subjects (P < 0.001). The highest values occurred in patients with carcinoids (median (interquartile range): 58.1 (44.5–65.3) U/l) and with ECL cell hyperplasia/dysplasia (35.5 (31.8–48.65) U/l) but there were no significant differences in CgA among the various subgroups of ABG patients classified according to ECL cell status. Nevertheless, in ABG patients without carcinoids CgA values correlated with the presence and severity of ECL cell lesions (r
s = 0.428, P < 0.01). The sensitivity and specificity of the CgA assay in identifying patients with carcinoids were 100 and 23% respectively.

Conclusions: CgA plasma levels reflect the histological degree of ECL cell lesions in patients with ABG but the assay specificity is too low to detect among these patients those with gastric carcinoids.
Laser Drilled Microholes in Zirconia Coated Surfaces using Two Variants to Implement the Effusion Cooling of First Stage Turbine Blades
Authors: Lugscheider E. , Bobzin K. , Maes M. , Lackner K. , Poprawe R. , Kreutz E. W. , Willach J.
Published: March 2005

The present paper describes the development of new constructive principles for highly loaded components to exhaust the available potential of increasing the total efficiency of the “ideal combined cycle power plant of the year 2025”. For that purpose, optimized cycle design and flow duct for working fluid and cooling fluid have to be realized and new material solutions have to be tested to control the increased maximum cycle temperatures and pressures.
Titelbild: Methane and Carbon Dioxide Storage in a Porous van der Waals Crystal (Angew. Chem. 12/2005)
Authors: Sozzani P. , Bracco S. , Comotti A. , Ferretti L. , Simonutti R.
Published: March 2005

Wie ein Bienenvolk sich in den hexagonalen Waben eines Bienenstocks geborgen fühlt, so werden CH4‐ und CO2‐Moleküle durch schwache CH⋅⋅⋅π‐Wechselwirkungen in den offenporigen Van‐der‐Waals‐Kristallen von Tris‐o‐phenylendioxycyclotriphosphazen stabilisiert. Das supramolekulare Netzwerk ist hinreichend beständig und kann eine große Zahl von Gasmolekülen aufnehmen. In ihrer Zuschrift auf S. 1850 ff. beschreiben P. Sozzani et al. die Absorptionseigenschaften der Kristalle, und sie beobachten die in den Nanokanälen eingeschlossenen Gasmoleküle spektroskopisch.
Cover Picture: Methane and Carbon Dioxide Storage in a Porous van der Waals Crystal (Angew. Chem. Int. Ed. 12/2005)
Authors: Sozzani P. , Bracco S. , Comotti A. , Ferretti L. , Simonutti R.
Published: March 2005

Like a swarm of bees who find shelter in the hexagonal cells of the beehive, CH4 and CO2 molecules are stabilized by weak CH⋅⋅⋅π interactions within the open‐pore van der Waals crystals of tris‐o‐phenylenedioxycyclotriphosphazene. The supramolecular network is sufficiently robust to store a large number of gas molecules. In their Communication on page 1816 ff., P. Sozzani et al. describe the absorption properties of the crystals and the spectroscopic observation of gases trapped in the nanochannels.
Structure and in vitro antibacterial activity of BuSnCl3−n[(OPPh2)(SPPh2)N]n (n = 1, 2)
Authors: Rotar Adina , Silvestru Anca , Silvestru Cristian , Drake John E. , Hursthouse Michael B. , Light Mark E. , Bunaciu Liana , Bunaciu Petre
Published: March 2005

BuSnCl2[(OPPh2)(SPPh2)N] (1) and BuSnCl[(OPPh2)(SPPh2)N]2 (2) were prepared by reacting BuSnCl3 and K[(OPPh2)(SPPh2)N], in 1:1 and 1:2 molar ratios. The compounds were investigated in solution by multinuclear (1H, 13C, 31P, 119Sn) NMR spectroscopy. Variable‐temperature 31P NMR studies indicate dynamic behaviour in solution. The solid‐state molecular structure was established by single‐crystal X‐ray diffraction revealing 5‐ and 6‐coordinated metal atoms in 1 and 2, respectively, as a result of the monometallic biconnective behaviour of the monothioimidodiphosphinato moieties. Preliminary results on the in vitro biological activity are reported. Copyright © 2005 John Wiley & Sons, Ltd.
Image coding usingM‐channel paraunitary filterbanks: Design with regularity and signal extension method
Authors: Oka Tomohiro , Uto Toshiyuki , Ikehara Masaaki
Published: March 2005

This paper proposes a signal extension method to realize image coding byM‐channel paraunitary filter banks and a lattice configuration of the latter satisfying regularity. In the conversion code for finitely long signals such as images, nonextensional convolution is important for efficient coding without increasing the number of coded pixels. To this end, nonextensional convolution is realized in a generalM‐channel filter bank. Also, a signal extension method is proposed using singular value decomposition so that the extended signals are smooth. Next, in theM‐channel paraunitary filter banks, a design method is proposed that is based on the lattice configuration satisfying the first‐order regularity so that the DC leakage is prevented. Finally, the proposed method is applied to coding of various stationary images and the effectiveness of the method is demonstrated. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(7): 52–60, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20134
Category recognition system using two ultrasonic sensors and combinational logic circuit
Authors: Moritake Yusuke , Hikawa Hiroomi
Published: March 2005

In this paper, we employ a technique that is used to recognize a material from the reflected ultrasonic waves and propose a category recognition system using two ultrasonic sensors. In this system, the reflected waveforms are handled as two‐dimensional images, and which category an object belongs to is instantaneously recognized by pattern matching to reference data by a combinatorial logic circuit. In this system, combinations of information such as the material, angle, and distance of the object are set as the recognition categories. The pattern matching is carried out by a combinatorial logic circuit created directly from the reference data. The recognition experiments with measured waveform data performed according to the proposed method demonstrated the features of the proposed system and its effectiveness when applied to recognition under specific conditions. With five materials set as the categories, the results show that a recognition rate of nearly 100% was obtained, and high recognition results were obtained for almost all of the materials when the categories were extended to combinations of the material, angle, and distance. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(7): 33–42, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20147
Speed improvement of FPGA by mixing multiple‐gate‐width routing switches
Authors: Matsumoto Yohei , Masaki Akira
Published: March 2005

In comparison with ASIC, FPGA is slower in speed and has a smaller logic size that can be integrated. The main cause is the routing switches. Optimization of the gate width of the transistors used is important. Previously, a single gate width has been assumed for all of the path transistors in the optimization. In the present research, a structure is conceived in which multiple gate widths are mixed. The operating speed is increased by about 20% relative to conventional structures. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(7): 14–22, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20154
Method to recover lost Internet packets using (n, k, m) convolutional codes
Authors: Arai Masayuki , Yamaguchi Anna , Fukumoto Satoshi , Iwasaki Kazuhiko
Published: March 2005

A lost packet recovery method is proposed by using (n, k, m) convolutional codes. The amount of computation in encoding and decoding as well as the lost packet recovery capability are evaluated. In the proposed method, a packet with a length ofqbits is considered as a symbol onGF(2q) for application of the convolutional codes. It is recognized that on the Internet the packet loss position can be identified. Then, decoding is applied to a lossy communications channel on the packet level. First, the procedures for coding and decoding are presented. Subsequently, the packet loss recovery characteristic in the proposed method is analyzed. The condition for recovery of all lost packets is discussed. In the proposed method, linear simultaneous equations can be developed from the generating matrix and the packet loss positions. If these equations have a unique solution, all packet losses can be recovered. Also, by means of the lost packet recovery simulation, the recovery capability and computational complexity of the proposed method are evaluated. Under the model in which packets are independently lost, the method is compared with the packet recovery method using (n, k) Reed–Solomon codes with identicalnandk. Simulation shows that packet recovery by (n, k, m) convolutional codes is effective in the area where the packet loss rate is rather low. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(7): 1–13, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20155
Cumulative 5‐year diagnoses of CIN2, CIN3 or cervical cancer after concurrent high‐risk HPV and cytology testing in a primary screening setting
Authors: Hoyer Heike , Scheungraber Cornelia , Kuehne‐Heid Rosemarie , Teller Karin , Greinke Christiane , Leistritz Sabine , Ludwig Beate , Dürst Matthias , Schneider Achim
Published: March 2005

The aim of our study was to assess the cumulative 5‐year diagnoses of CIN2, CIN3 or invasive cervical cancer (CIN2+) after concurrent screening by high‐risk HPV test and Pap smear in a primary screening setting. Four thousand thirty‐four women from Eastern Thuringia/Germany were recruited from 1996 to 1998 for baseline screening that included routine cytology, high‐risk HPV testing by consensus primer PCR GP5+/6+ and routine colposcopy. After a median of 59 months 3,153 women participated in final screening using identical methods. Women with abnormal cytology or colposcopy or a positive high‐risk HPV test at any time during the study period were recalled for expert colposcopy and histologic verification. CIN2+ was detected in 160 women resulting in a cumulative 5‐year proportion of 4.4% (95% CI: 3.7–5.0%). Of 3,702 women who were high‐risk HPV negative at baseline, 34 (1.1–95% CI: 0.7–1.4%) had either prevalent CIN2+ or developed CIN2+ within the observation period. HPV/cytology double negatives at baseline were at lowest risk for CIN2+ (1.0–95% CI: 0.7–1.4%) compared to screening positives (16.8–100% depending on combined test results). The 5‐year negative predictive value in HPV−/Cyto− women was 99.0% (95% CI: 98.6–99.3%). This suggests that a prolongation of the screening intervals in this group is feasible. However, it should be noted that 1 woman developed a microinvasive carcinoma within the observation period. Moreover, 2 women with prevalent cancer were missed by both tests. The prognostic relevance of concurrent high‐risk HPV/cytology screening needs to be verified further by randomized trials. © 2005 Wiley‐Liss, Inc.
Tobacco‐specific nitrosamines in smokeless tobacco products marketed in India
Authors: Stepanov Irina , Hecht Stephen S. , Ramakrishnan Sreevidya , Gupta Prakash C.
Published: March 2005

Smokeless tobacco products are a known cause of oral cancer in India. Carcinogenic tobacco‐specific nitrosamines in these products are believed to be at least partially responsible for cancer induction, but there have been no recent analyses of their amounts. We quantified levels of 4 tobacco‐specific nitrosamines, N′‐nitrosonornicotine (NNN), N′‐nitrosoanatabine (NAT), N′‐nitrosoanabasine (NAB) and 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), in 32 products marketed currently in India. Levels of nitrate, nitrite and nicotine were also determined. The highest levels of tobacco‐specific nitrosamines were found in certain brands of khaini, zarda and other smokeless tobacco products. Concentrations of NNN and NNK in these products ranged from 1.74–76.9 and 0.08–28.4 μg/g, respectively. Levels of tobacco‐specific nitrosamines in gutka were generally somewhat lower than in these products, but still considerably higher than nitrosamine levels in food. Tobacco‐specific nitrosamines were rarely detected in supari, which does not contain tobacco, or in tooth powders. The results of our study demonstrate that exposure to substantial amounts of carcinogenic tobacco‐specific nitrosamines through use of smokeless tobacco products remains a major problem in India. © 2005 Wiley‐Liss, Inc.
Chlamydia trachomatis infection and persistence of human papillomavirus
Authors: Silins Ilvars , Ryd Walter , Strand Anders , Wadell Göran , Törnberg Sven , Hansson Bengt Göran , Wang Xiaohong , Arnheim Lisen , Dahl Viktor , Bremell Daniel , Persson Kenneth , Dillner Joakim , Rylander Eva
Published: March 2005

Human papillomavirus (HPV) persistence is the major cause of cervical cancer, but most HPV infections will not persist and risk factors for HPV persistence are not well known. Chlamydia (C.) trachomatis infection seems to also be associated with cervical cancer. We investigated whether C. trachomatis infection is a risk factor for HPV persistence. In a cohort of 12,527 women participating in a population‐based HPV screening trial in Sweden, 6,418 women completed testing for HPV DNA by general primer PCR and typing by reverse dot blot hybridization. On average 19 months later, 303 women that had been HPV‐positive and had normal cytology at enrollment completed a new HPV test. Environmental exposures were assessed by an 87‐item questionnaire. Previous sexually transmitted infections were also investigated by serology. At follow‐up, 44% of the women were positive for the same type of HPV DNA as at enrollment. Persistence correlated with length of follow‐up (p < 0.01) and condom use seemed to protect against HPV persistence (p < 0.05). The most significant risk factor for persistent presence of HPV DNA was self‐reported history of previous C. trachomatis infection (relative risk in multivariate model = 2.09; 95% confidence interval = 1.05–4.18). We conclude that persistence of oncogenic HPV infections is more likely among women with a previous C. trachomatis infection. © 2005 Wiley‐Liss, Inc.
Cytotoxic effects of γδ T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy
Authors: Sato Kiyoshi , Kimura Shinya , Segawa Hidekazu , Yokota Asumi , Matsumoto Seiji , Kuroda Junya , Nogawa Masaki , Yuasa Takeshi , Kiyono Yasushi , Wada Hiromi , Maekawa Taira
Published: March 2005

Nitrogen containing‐bisphosphonates (N‐BPs), widely used to treat bone diseases, have direct antitumor effects via the inactivation of Ras proteins. In addition to the direct antitumor activities, N‐BPs expand gdγδT cells, which exhibit major histocompatibility complex‐unrestricted lytic activity. BPs accumulate intermediate metabolites which may be tumor antigens in target cells. The purpose of our study was to clarify the cytotoxicity of gdγδ T cells expanded ex vivo by the most potent N‐BP, zoledronate (ZOL). Especially, we focused on the importance of pretreatment against target cells also with ZOL; 1 mμM ZOL plus IL‐2 increased the absolute number of gdγδT cells 298–768 fold for 14 days incubation. The small cell lung cancer and fibrosarcoma cell lines pretreated with 5 mμM ZOL showed a marked increase in sensitivity to lysis by gdγδT cells. While, untreated cell lines were much less sensitive to lysis by gdT cells. Video microscopy clearly demonstrated that gdγδT cells killed target cells pre‐treated with ZOL within 3 hr. Pretreatment with 80 mμg/kg ZOL also significantly enhanced the antitumor activity of gdγδT cells in mice xenografted with SBC‐5 cells. These findings show that ZOL significantly stimulated the proliferation of gdγδT cells and that gdγδT cells required pre‐treatment with ZOL for cytotoxic activity against target cells. © 2005 Wiley‐Liss, Inc.
Hepatitis C infection is not associated with systemic HIV‐associated non‐hodgkin's lymphoma: A cohort study
Authors: Waters Laura , Stebbing Justin , Mandalia Sundhiya , Young Anne Marie , Nelson Mark , Gazzard Brian , Bower Mark
Published: March 2005

Immunosuppression induced by the human immunodeficiency virus (HIV) increases the risk of developing non‐Hodgkin's lymphoma (NHL). As the hepatitis C virus (HCV) has been implicated in the development of B cell lymphomas, we compared the incidence of systemic NHL during HIV infection compared to HIV and HCV co‐infection. Of 5,832 individuals studied during the era of highly active anti‐retroviral therapy (HAART), 102 patients were diagnosed with systemic NHL. The incidence of systemic NHL was 6.9 of 104 patient years during HIV infection compared to 7.1 of 104 patient years during HIV alone (p = 0.9). In this immunocompromised patient population, there was no association between HCV infection and an increased risk of lymphoma. © 2005 Wiley‐Liss, Inc.
A simple method for faster nonbonded force evaluations
Authors: Shen Min‐Yi , Freed Karl F.
Published: March 2005

Accurate approximations are introduced for the evaluation of inverse interparticle distances such that square root or division operations are not required in the computation of interparticle interactions and forces. These generally applicable approximations are illustrated by incorporation into the protein simulation package TINKER (Pappu, R. V.; Hart, R. K.; Ponder, J. W. J Phys Chem B 1998, 102, 9725; Ponder, J. W.; Richards, F. M. J Comput Chem 1987, 8, 1016; Dudek, M. J.; Ramnarayan, K.; Ponder, J. W. J Comput Chem 1998, 19, 548) along with several other speed enhancement strategies. With these modifications, implicit solvent Langevin dynamics simulations of proteins are performed factors of 4.6 times faster than the modified open source distributed program. Programming speedups are obtained by extensive vectorization, simplification of the inner loop to avoid IF statements, and by using lookup tables for the distance dependent “dielectric constant” in implicit solvent models. Benchmarks are provided for the all‐atom, implicit solvent dynamics of Met‐enkephalin, the villin headpiece, the B1 domain of protein‐G, and barnase. We also discuss the more general applicability of the approximation methods to explicit solvent simulations and of look‐up tables for other implicit solvent models such as the generalized Born models. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 691–698, 2005
Relationship between renal anemia and prognostic stages of IgA nephropathy
Authors: Aruga Seiki , Horiuchi Tomohide , Shou Ichiyu , Tashiro Kyouichi , Kurusu Atsushi , Fukui Mitsumine , Horikoshi Satoshi , Tomino Yasuhiko
Published: March 2005

In 2002, the Joint Committee of the Special Study Group on Progressive Glomerular Diseases, Ministry of Health, Labor and Welfare of Japan newly revised the clinical guidelines for IgA nephropathy (Sakai et al.: Jpn J Nephrol 37:417–421, 1995; Tomino and Sakai: Clin Exp Nephrol, 7, 93–97, 2003). The prognostic stages were classified into four groups: the good prognosis group (Group I), relatively good prognosis group (Group II), relatively poor prognosis group (Group III), and poor prognosis group (Group IV). The relationship between the levels of Hb, Ht, and RBC in peripheral blood and the renal prognostic stages was determined in 62 patients with IgA nephropathy in the present study. The mean levels of Hb, Ht, and RBC were significantly lower in Group IV than in Group I (P<0.05). However, there were no significant changes in the levels of serum creatinine (s‐Cr) or creatinine clearance (CCr) among these four groups. It appears that the levels of Hb, Ht, and RBC in peripheral blood may be important clinical parameters for the evaluation of prognostic stages in patients with IgA nephropathy. J. Clin. Lab. Anal. 19:80–83, 2005. © 2005 Wiley‐Liss, Inc.
Effective repetitive dystrophin gene transfer into skeletal muscle of adult mdx mice using a helper‐dependent adenovirus vector expressing the coxsackievirus and adenovirus receptor (CAR) and dystrophin
Authors: Uchida Yuji , Maeda Yasushi , Kimura En , Yamashita Satoshi , Nishida Yasuto , Arima Toshiyuki , Hirano Teruyuki , Uyama Eiichiro , Mita Shuji , Uchino Makoto
Published: March 2005

Background

The helper‐dependent adenovirus (HDAd) vector is less immunogenic and has a larger cloning capacity of up to 37 kb enough to carry the full‐length dystrophin cDNA. However, high and long‐term expression of dystrophin transduced to mature muscle still remains difficult. One of the main reasons for this is that the expression of the coxsackievirus and adenovirus receptor (CAR) is very low in mature muscle.

Methods

We have constructed two different HDAd vectors. One contains the LacZ and the murine full‐length dystrophin expression cassette (HDAdLacZ‐dys), and the other is a new, improved vector containing the CAR and the dystrophin expression cassette (HDAdCAR‐dys).

Results

We initially demonstrated high dystrophin expression and prevention of the dystrophic pathology in mdx muscle injected during the neonatal phase with HDAdLacZ‐dys. Furthermore, we demonstrated that repeated injections of HDAdCAR‐dys into mature muscle led to approximately nine times greater dystrophin‐positive fibers in number than a single injection, thereby recovering the expression of dystrophin‐associated proteins. This data has also shown that HDAdCAR‐dys enabled administration of adenovirus (Ad) vector to the host with pre‐existing immunity to the same serotype of Ad.

Conclusions

Repetitive injections of the HDAd vector containing the CAR and the dystrophin expression cassette could improve the efficiency of subsequent dystrophin gene transfer to mature mdx muscle. This result suggests that our new HDAd vector will provide a novel gene therapy strategy for Duchenne muscular dystrophy, raising the prospects for gene therapy of other hereditary myopathies. Copyright © 2005 John Wiley & Sons, Ltd.
A branch‐and‐price algorithm for the capacitated p‐median problem
Authors: Ceselli Alberto , Righini Giovanni
Published: March 2005

The capacitated p‐median problem is the variation of the well‐known p‐median problem in which a demand is associated to each user, a capacity is associated to each candidate median, and the total demand of the users associated to the same median must not exceed its capacity. We present a branch‐and‐price algorithm, that exploits column generation, heuristics and branch‐and‐bound to compute optimal solutions. We compare our branch‐and‐price algorithm with other methods proposed so far, and we present computational results both on test instances taken from the literature and on random instances with different values of the ratio between the number of medians and the number of users. © 2004 Wiley Periodicals, Inc. NETWORKS, Vol. 45(3), 125–142 2005
Late effect of prenatal irradiation on the hippocampal histology and brain weight in adult mice
Authors: Hossain M. , Chetana M. , Devi P. Uma
Published: March 2005

We studied the changes in the brain weight and hippocampal histology in adult offspring exposed to 0.25–1.5 Gy of 60Co gamma radiations during day 14 or 17 of gestation. Irradiation with 0.5–1.5 Gy produced a significant decrease in brain weight of the offspring at 6 and 12 months of age. Exposure to 1 Gy at day 14 or 17 of gestation resulted in significant decrease in the number of neurons in the CA3 and CA4 regions of hippocampus of 200 μm length, while 1.5 Gy significantly affected CA1 region also. The fetal period (13–18 days of gestation) of mouse development is an active phase of brain development involving proliferation, migration and differentiation of cerebral cortex and associated structures. The present results show that exposure at this period of mouse development to moderate doses of gamma radiation can induce permanent deficits in the brain histology, which can adversely affect the learning and memory in adults.
Physical Examination of the Carpal Bones by Orthopaedic and Accident and Emergency Surgeons
Authors: JAYASEKERA N. , AKHTAR N. , COMPSON J. P.
Published: March 2005

Our aim was to test knowledge of carpal bone surface anatomy among orthopaedic and accident and emergency surgeons. A survey of 58 surgeons was conducted. Each was asked to palpate seven points on five commonly injured carpal bones. Eight surgeons declined to participate. Five of the remaining 50 correctly palpated all surface markings. Six failed to accurately palpate even a single point. The scaphoid waist and trapezial ridge were accurately palpated by 47 surgeons. The median score for all participants was 3 correctly identified points. The majority of orthopaedic and accident and emergency surgeons do not perform an accurate physical examination of the carpal bones. The ancient art of history taking, precise physical examination and elucidation of a confident diagnosis is at risk of being replaced with tentative diagnoses and imaging techniques that are expensive and time consuming. We believe that basic anatomical teaching is inadequate.
Full Thickness Skin Graft for Nail Unit Reconstruction
Authors: LAZAR A. , ABIMELEC P. , DUMONTIER C.
Published: March 2005

A retrospective study of 13 patients assessed the use of a full thickness skin graft for nail unit reconstruction after total nail unit removal for nail bed malignancies. No failures of the graft were observed and no patient had recurrence of the malignant tumour at 4 year follow-up. Full thickness skin grafting is a simple procedure which provides a good cosmetic outcome and does not produce significant donor site morbidity.
Calmyonemin: Identification and distribution throughout thecell cycle in Entodinium bursa (ciliate)
Authors: Vigues Bernard , David Christine
Published: March 2005

Summary— The ciliature in most entodiniomorphid ciliates is restricted to the cell apex, forming ciliary crowns that can be rapidly retracted under stress conditions. In a previous study, calmyonemin, a 23 kDa analog of centrin, has been characterized from ciliated cortical zones in Eudiplodinium maggii; its localization in subkinetal myonemes, ie bundles of contractile filaments powering retraction of the ciliature, was demonstrated by immunoelectron microscopy (David and Vigues (1994) Cell Motil Cytoskeleton, 27, 169–179). Here we used immunofluorescence microscopy to determine the distribution of calmyonemin and its variations throughout the cell cycle in Entodinium bursa. Labelling of morphostatic cells with anti‐calmyonemin antibody reveals immunoreactivity at the base of the ciliature, in circumciliary lips, around the cytoproct and in an endoplasmic array originating from the post‐oral region and extending down to the posterior part of the cell. All arrays of calmyonemin from the parental cell remain unaffected during cell division except the endoplasmic array which undergoes a transient resorption followed by synchronous reassembly in the two future products of division. The assembly of subkinetal myonemes in the sub‐equatorial zone is described in relation with the main features of oral morphogenesis previously revealed by others using silver impregnation techniques and light microscopy.
Cytochemical and immunocytochemical studyof nuclear structures of Lacandonia schismatica
Authors: Agredano‐Moreno Lourdes , Jiménez‐García Luis Felipe , Echevería Olga M. , Martinet Esteban , Ramos Clara , Nin Gerardo H. Vázquez
Published: March 2005

Summary— The interphase nucleus of the cells of several tissues of Lacandonia schismatica was studied using electron microscopy cytochemical and immunocytochemical methods. The EDTA staining procedure, preferential for RNP, contrasted the Lacandonia granules and perichromatin fibrils. These granules were found to be relatively resistant to RNAse hydrolysis, but they were easily digested if RNAse treatment was carried out after a short hydrolysis with pronase. Bismuth oxynitrate stained granular structures about 17 nm in diameter and the periphery of a few Lacandonia granules. The anti=snURNPs bound to RNP‐containing fibrils in the perichromatin and interchromatin space and also to the periphery of some Lacandonia granules. Immunolabeling of DNA demonstrated numerous filaments of extended chromatin in the perichromatin and interchromatin spaces which were closely related to Lacandonia granules. These observations suggested that Lacandonia granules are equivalent to Balbiani ring granules of nuclei with polytene chromosomes and to perichromatin granules of other plant and animal nuclei. The small number of Lacandonia granules labeled in their periphery by anti‐snURNP mAb were interpreted as being immature granules in the process of formation. The external or annular part of the ring‐shaped structures is heavily labeled by anti‐URNP mAbs but scarcely stained by the EDTA procedure. These features indicate that this region contains abundant proteins associated with snURNAs but probably little snURNAs. The synaptonemal‐like complexes previously found in the interphase nuclei of Lacandonia are formed by two parallel masses of compact chromatin, which react with anti‐DNA, and a central clear space crossed by fiber. Most of these fibers do not react with tests for DNA or RNA and are probably composed of proteins. The EDTA procedure contrasts some fibrils at the internal aspect of the masses of compact chromatin, suggesting the presence of remnants of the lateral element of a synaptonemal complex.
Universal Jurisdiction for International Core Crimes: Recent Developments in Belgium
Authors: Ongena Tom , Van Daele Ignace
Published: March 2005

Belgian legislation gives the national criminal justice system far reaching competence to prosecute international core crimes. International and national judicial decisions as well as policy considerations may however dictate restrictions.