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Showing papers by "University of Barcelona published in 2005"


Journal ArticleDOI
TL;DR: The prevention of Cirrhosis can prevent the development of HCC and progression from chronic HCV infection to advanced fibrosis or cirrhosis may be prevented in 40% of patients who are sustained responders to new antiviral strategies, such as pegylated interferon and ribavirin.

5,557 citations


Journal ArticleDOI
TL;DR: In this paper, a review of the Kuramoto model of coupled phase oscillators is presented, with a rigorous mathematical treatment, specific numerical methods, and many variations and extensions of the original model that have appeared in the last few years.
Abstract: Synchronization phenomena in large populations of interacting elements are the subject of intense research efforts in physical, biological, chemical, and social systems. A successful approach to the problem of synchronization consists of modeling each member of the population as a phase oscillator. In this review, synchronization is analyzed in one of the most representative models of coupled phase oscillators, the Kuramoto model. A rigorous mathematical treatment, specific numerical methods, and many variations and extensions of the original model that have appeared in the last few years are presented. Relevant applications of the model in different contexts are also included.

2,864 citations


Journal ArticleDOI
TL;DR: It is found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4 early and accumulated during the tumorigenic process, which is a common hallmark of human tumor cells.
Abstract: CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.

1,807 citations


Journal ArticleDOI
TL;DR: The magnetocaloric effect (MCE) in paramagnetic materials has been widely used for attaining very low temperatures by applying a magnetic field isothermally and removing it adiabatically as discussed by the authors.
Abstract: The magnetocaloric effect (MCE) in paramagnetic materials has been widely used for attaining very low temperatures by applying a magnetic field isothermally and removing it adiabatically. The effect can also be exploited for room-temperature refrigeration by using giant MCE materials. Here we report on an inverse situation in Ni-Mn-Sn alloys, whereby applying a magnetic field adiabatically, rather than removing it, causes the sample to cool. This has been known to occur in some intermetallic compounds, for which a moderate entropy increase can be induced when a field is applied, thus giving rise to an inverse magnetocaloric effect. However, the entropy change found for some ferromagnetic Ni-Mn-Sn alloys is just as large as that reported for giant MCE materials, but with opposite sign. The giant inverse MCE has its origin in a martensitic phase transformation that modifies the magnetic exchange interactions through the change in the lattice parameters.

1,680 citations


Journal ArticleDOI
22 Jun 2005-JAMA
TL;DR: Characteristics of patients with S aureus IE vary significantly by region, and further studies are required to determine the causes of regional variation.
Abstract: ContextThe global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown.ObjectivesTo document the international emergence of health care–associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE.Design, Setting, and ParticipantsProspective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003.Main Outcome MeasureIn-hospital mortality.ResultsS aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care−associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care−associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons).ConclusionsS aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.

1,101 citations


Journal ArticleDOI
TL;DR: A new graphical user-friendly interface for Multivariate Curve Resolution using Alternating Least Squares has been developed as a freely available MATLAB toolbox.

950 citations


Journal ArticleDOI
08 Sep 2005-Nature
TL;DR: It is shown that the Crooks fluctuation theorem can be used to determine folding free energies for folding and unfolding processes occurring in weak as well as strong nonequilibrium regimes, thereby providing a test of its validity under such conditions.
Abstract: Atomic force microscopes and optical tweezers are widely used to probe the mechanical properties of individual molecules and molecular interactions, by exerting mechanical forces that induce transitions such as unfolding or dissociation. These transitions often occur under nonequilibrium conditions and are associated with hysteresis effects-features usually taken to preclude the extraction of equilibrium information from the experimental data. But fluctuation theorems allow us to relate the work along nonequilibrium trajectories to thermodynamic free-energy differences. They have been shown to be applicable to single-molecule force measurements and have already provided information on the folding free energy of a RNA hairpin. Here we show that the Crooks fluctuation theorem can be used to determine folding free energies for folding and unfolding processes occurring in weak as well as strong nonequilibrium regimes, thereby providing a test of its validity under such conditions. We use optical tweezers to measure repeatedly the mechanical work associated with the unfolding and refolding of a small RNA hairpin and an RNA three-helix junction. The resultant work distributions are then analysed according to the theorem and allow us to determine the difference in folding free energy between an RNA molecule and a mutant differing only by one base pair, and the thermodynamic stabilizing effect of magnesium ions on the RNA structure.

938 citations


Journal ArticleDOI
TL;DR: Intention-to-treat analysis has shown that wide extended indications lead to 25% 5-year survival rates, and molecular markers are needed to better select the candidates for surgery.
Abstract: Surveillance programs in cirrhotic patients enable the detection of hepatocellular carcinoma (HCC) at early stages, when the tumor is amenable to curative treatments (60% of cases in Japan; 25 to 40% in Europe and the United States). Resection is the mainstay of treatment in noncirrhotic patients and in cirrhotics with well-preserved liver function. In modern series, a perioperative mortality < or = 3% and 5-year survival rates above 50% are expected. Tumor recurrence complicates half of the cases at 3 years, but there is no unquestionable preventive treatment. Liver transplantation provides excellent outcomes applying the Milan criteria (single nodule < or = 5 cm or two or three nodules < or = 3 cm), with 5-year survival rates of 70% and low recurrence rates. Although expansion of selection criteria is appealing, it should be assessed in the setting of prospective well-designed studies. Intention-to-treat analysis has shown that wide extended indications lead to 25% 5-year survival rates. Living donor liver transplantation is having a minor impact in HCC management. Molecular markers are needed to better select the candidates for surgery.

828 citations


Journal ArticleDOI
TL;DR: In this article, the concept of the continuous shape measures is summarized and the derived tools, the shape maps and the path deviation functions are described, the main stereochemical trends that have been deduced from the application of such tools to more than 23,000 crystallographically independent fragments of coordination numbers between four and eight are also summarized.

827 citations


Journal ArticleDOI
TL;DR: The ALFALFA project as discussed by the authors uses a two-pass, minimum intrusion, drift scan observing technique that samples the same region of sky at two separate epochs to aid in the discrimination of cosmic signals from noise and terrestrial interference.
Abstract: The recently initiated Arecibo Legacy Fast ALFA (ALFALFA) survey aims to map ~7000 deg2 of the high Galactic latitude sky visible from Arecibo, providing a H I line spectral database covering the redshift range between -1600 and 18,000 km (s-1) with ~5 km s(-1) resolution. Exploiting Arecibo's large collecting area and small beam size, ALFALFA is specifically designed to probe the faint end of the H I mass function in the local universe and will provide a census of H I in the surveyed sky area to faint flux limits, making it especially useful in synergy with wide-area surveys conducted at other wavelengths. ALFALFA will also provide the basis for studies of the dynamics of galaxies within the Local Supercluster and nearby superclusters, allow measurement of the H I diameter function, and enable a first wide-area blind search for local H I tidal features, H I absorbers at z < 0.06, and OH megamasers in the redshift range 0.16 < z < 0.25. Although completion of the survey will require some 5 years, public access to the ALFALFA data and data products will be provided in a timely manner, thus allowing its application for studies beyond those targeted by the ALFALFA collaboration. ALFALFA adopts a two-pass, minimum intrusion, drift scan observing technique that samples the same region of sky at two separate epochs to aid in the discrimination of cosmic signals from noise and terrestrial interference. Survey simulations, which take into account large-scale structure in the mass distribution and incorporate experience with the ALFA system gained from tests conducted during its commissioning phase, suggest that ALFALFA will detect on the order of 20,000 extragalactic H I line sources out to z ~ 0.06, including several hundred with H I masses M(HI) < 10(7.5) M ?.

768 citations


Journal ArticleDOI
TL;DR: The authors present a technique which takes into account the physical electromagnetic spectrum responses of sensors during the fusion process, which produces images closer to the image obtained by the ideal sensor than those obtained by usual wavelet-based image fusion methods.
Abstract: Usual image fusion methods inject features from a high spatial resolution panchromatic sensor into every low spatial resolution multispectral band trying to preserve spectral signatures and improve spatial resolution to that of the panchromatic sensor. The objective is to obtain the image that would be observed by a sensor with the same spectral response (i.e., spectral sensitivity and quantum efficiency) as the multispectral sensors and the spatial resolution of the panchromatic sensor. But in these methods, features from electromagnetic spectrum regions not covered by multispectral sensors are injected into them, and physical spectral responses of the sensors are not considered during this process. This produces some undesirable effects, such as resolution overinjection images and slightly modified spectral signatures in some features. The authors present a technique which takes into account the physical electromagnetic spectrum responses of sensors during the fusion process, which produces images closer to the image obtained by the ideal sensor than those obtained by usual wavelet-based image fusion methods. This technique is used to define a new wavelet-based image fusion method.

Journal ArticleDOI
TL;DR: In this paper, the structural and magnetic transformations in the Heusler-based system are studied by x-ray diffraction, optical microscopy, differential scanning calorimetry, and magnetization.
Abstract: Structural and magnetic transformations in the Heusler-based system ${\mathrm{Ni}}_{0.50}{\mathrm{Mn}}_{0.50\ensuremath{-}x}{\mathrm{Sn}}_{x}$ are studied by x-ray diffraction, optical microscopy, differential scanning calorimetry, and magnetization. The structural transformations are of austenitic-martensitic character. The austenite state has an $L{2}_{1}$ structure, whereas the structures of the martensite can be $10M$, $14M$, or $L{1}_{0}$ depending on the Sn composition. For samples that undergo martensitic transformations below and around room temperature, it is observed that the magnetic exchange in both parent and product phases is ferromagnetic, but the ferromagnetic exchange, characteristic of each phase, is found to be of different strength. This gives rise to different Curie temperatures for the austenitic and martensitic states.

Journal ArticleDOI
TL;DR: This work proposes and analyzes a model capable of generating random uncorrelated scale-free networks with no multiple and self-connections based on the classical configuration model, with an additional restriction on the maximum possible degree of the vertices.
Abstract: Uncorrelated random scale-free networks are useful null models to check the accuracy and the analytical solutions of dynamical processes defined on complex networks. We propose and analyze a model capable of generating random uncorrelated scale-free networks with no multiple and self-connections. The model is based on the classical configuration model, with an additional restriction on the maximum possible degree of the vertices. We check numerically that the proposed model indeed generates scale-free networks with no two- and three-vertex correlations, as measured by the average degree of the nearest neighbors and the clustering coefficient of the vertices of degree k , respectively.

Journal ArticleDOI
TL;DR: Reference polyhedra, shape maps, and minimal-distortion interconversion paths are presented for eight-vertex polyhedral and polygonal structures within the CShM framework, and structural classification is shown to be greatly facilitated by these tools.
Abstract: A stereochemical study of polyhedral eight-vertex structures is presented, based on continuous shape measures (CShM). Reference polyhedra, shape maps, and minimal-distortion interconversion paths are presented for eight-vertex polyhedral and polygonal structures within the CShM framework. The application of these stereochemical tools is analyzed for several families of experimental structures: 1) coordination polyhedra of molecular transition-metal coordination compounds, classified by electron configuration and ligands; 2) edge-bonded polyhedra, including cubane structures, realgar, and metal clusters; 3) octanuclear transition-metal supramolecular architectures; and 4) coordination polyhedra in extended structures in inorganic solids. Structural classification is shown to be greatly facilitated by these tools, and the detection of less common structures, such as the gyrobifastigium, is straightforward.

Journal ArticleDOI
TL;DR: In this paper, a test statistic for the null hypothesis of panel stationarity that allows for the presence of multiple structural breaks is proposed and applied to typical panel data of real per capita GDP in a set of OECD countries.
Abstract: Summary This paper proposes a test statistic for the null hypothesis of panel stationarity that allows for the presence of multiple structural breaks. Two different specifications are considered depending on the structural breaks affecting the individual effects and/or the time trend. The model is flexible enough to allow the number of breaks and their position to differ across individuals. The test is shown to have a standard normal limit distribution with a good finite sample performance. It is applied to typical panel data of real per capita GDP in a set of OECD countries.

Journal ArticleDOI
TL;DR: In this paper, a coherent field-theory-derived quantum-mechanical scheme was proposed to calculate the properties of bound states made by two or more heavy quarks.
Abstract: We briefly review how nonrelativistic effective field theories give us a definition of the QCD potentials and a coherent field-theory-derived quantum-mechanical scheme to calculate the properties of bound states made by two or more heavy quarks. In this framework heavy quarkonium properties depend only on the QCD parameters (quark masses and αs) and nonpotential corrections are systematically accounted for. The relation between the form of the nonperturbative potentials and the low-energy QCD dynamics is also discussed.

Journal ArticleDOI
TL;DR: The multi-lingual hypomania checklist (HCL-32) as mentioned in this paper has been developed and is being tested internationally and has been used for self-assessment of hypomanic symptoms.

Journal ArticleDOI
TL;DR: Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

Journal ArticleDOI
28 Dec 2005-JAMA
TL;DR: Although the level of evidence is higher for CPAP, there are no significant differences in clinical outcomes when comparing CPAP vs NIPSV, and both modalities showed a significant decrease in the "need to intubate" rate compared with conventional therapy.
Abstract: ContextIn patients with acute cardiogenic pulmonary edema noninvasive ventilation may reduce intubation rate, but the impact on mortality and the superiority of one technique over another have not been clearly establishedObjectiveTo systematically review and quantitatively synthesize the short-term effect of noninvasive ventilation on major clinical outcomesData SourcesMEDLINE and EMBASE (from inception to October 2005) and Cochrane databases (library issue 4, 2005) were searched to identify relevant randomized controlled trials and systematic reviews published from January 1, 1988, to October 31, 2005Study Selection and Data ExtractionIncluded trials were all parallel studies comparing noninvasive ventilation to conventional oxygen therapy in patients with acute pulmonary edema Comparisons of different techniques, either continuous positive airway pressure (CPAP) or bilevel noninvasive pressure support ventilation (NIPSV), were also includedData SynthesisFifteen trials were selected Overall, noninvasive ventilation significantly reduced the mortality rate by nearly 45% compared with conventional therapy (risk ratio [RR], 055; 95% confidence interval [CI], 040-078; P = 72 for heterogeneity) The results were significant for CPAP (RR, 053; 95% CI, 035-081; P = 44 for heterogeneity) but not for NIPSV (RR, 060; 95% CI, 034-105; P = 76 for heterogeneity), although there were fewer studies in the latter Both modalities showed a significant decrease in the “need to intubate” rate compared with conventional therapy: CPAP (RR, 040; 95% CI, 027-058; P = 21 for heterogeneity), NIPSV (RR, 048; 95% CI, 030-076; P = 24 for heterogeneity), and together (RR, 043; 95% CI, 032-057; P = 20 for heterogeneity) There were no differences in intubation or mortality rates in the analysis of studies comparing the 2 techniquesConclusionsNoninvasive ventilation reduces the need for intubation and mortality in patients with acute cardiogenic pulmonary edema Although the level of evidence is higher for CPAP, there are no significant differences in clinical outcomes when comparing CPAP vs NIPSV

Journal ArticleDOI
TL;DR: It is the whole set of antioxidant defenses (ascorbate, glutathione, carotenoids, tocopherols and other isoprenoids, flavonoids and enzymatic antioxidants) rather than a single antioxidant, which helps plants to withstand environmental stress.

Journal ArticleDOI
TL;DR: It is shown how optical encryption methods based on double random phase keys are vulnerable to an organized attack of the chosen-ciphertext type and cast doubts on the present security of these techniques.
Abstract: We show how optical encryption methods based on double random phase keys are vulnerable to an organized attack of the chosen-ciphertext type. The decryption key can be easily obtained by an opponent who has repeated access to either the encryption or decryption machines. However, we have also devised a solution that prevents the attack. Our results cast doubts on the present security of these techniques.

Journal ArticleDOI
TL;DR: The fortran 77 code system elsepa for the calculation of elastic scattering of electrons and positrons by atoms, positive ions and molecules is presented and implements approximate factorization methods that allow the fast calculation of Elastic cross sections for much higher energies.

Journal ArticleDOI
TL;DR: These findings are the first to suggest that polyphenolic compounds are able to cross the blood brain barrier and localize in various brain regions important for learning and memory.
Abstract: Research has shown that fruits and vegetables containing high levels of polyphenolics (flavonoids) display high total antioxidant activity. Our laboratory found that various fruit and vegetable extracts, particularly blueberry (BB), were effective in reversing age-related deficits in neuronal signaling and behavioral parameters following 8 weeks of feeding, possibly due to their polyphenolic content. However, it was unclear if these phytonutrients were able to directly access the brain from dietary BB supplementation (BBS). The present study examined whether different classes of polyphenols could be found in brain areas associated with cognitive performance following BBS. Thus, 19 month old F344 rats were fed a control or 2% BB diet for 8-10 weeks and tested in the Morris water maze (MWM), a measure of spatial learning and memory. LC-MS analyses of anthocyanins in the diet and subsequently in different brain regions of BBS and control rats were carried out. Several anthocyanins (cyanidin-3-O-beta-galactoside, cyanidin-3-O-beta-glucoside, cyanidin-3-O-beta-arabinose, malvidin-3-O-beta-galactoside, malvidin-3-O-beta-glucoside, malvidin-3-O-beta-arabinose, peonidin-3-O-beta-arabinose and delphinidin-3-O-beta-galactoside) were found in the cerebellum, cortex, hippocampus or striatum of the BBS rats, but not the controls. These findings are the first to suggest that polyphenolic compounds are able to cross the blood brain barrier and localize in various brain regions important for learning and memory. Correlational analyses revealed a relationship between MWM performance in BBS rats and the total number of anthocyanin compounds found in the cortex. These findings suggest that these compounds may deliver their antioxidant and signaling modifying capabilities centrally.

Journal ArticleDOI
TL;DR: There is no firm evidence to establish the optimal first-line treatment for small single HCC in patients with well-preserved liver function, and several other treatments, such as immunotherapy, internal radiation, tamoxifen, or anti-androgen agents, have not shown any relevant anti-tumoral effect or survival benefit.
Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, and its incidence will further increase, to reach a plateau in 2015–2020. The natural history of the disease is quite well known, except for its early stages, because the majority of patients at this stage are treated with radical approaches. Staging systems are key to predict the prognostics of patients with cancer, to stratify the patients according to prognostic variables in the setting of clinical trials, and to guide the therapeutic approach. The current knowledge of the disease, however, is not sufficient for recommending a staging system to be used worldwide. The conventional staging systems—Okuda stage, and TNM stage—have shown important limitations for classifying patients. Several new systems have been recently proposed, but only three of them have been validated. The Barcelona Clinic Liver Cancer (BCLC) staging classification links the stage of the disease to a specific treatment strategy. The Japan Integrated Staging (JIS) score has been proposed and used in Japan, although it needs Western validation. The Cancer of the Liver Italian Program (CLIP) score is mainly proposed for patients with advanced tumors. Early detection of HCC through surveillance programs allows the application of potentially curative therapies, such as resection, liver transplantation, and percutaneous ablation in patients with early tumors. The applicability of these treatments varies according to geographical distribution: from 50% to 70% of cases in Japan; 25% to 40% of cases in Europe and the United States; and fewer than 10% in Africa. There are no randomized controlled trials (RCTs) comparing any of the three major therapies. These studies are not feasible in the West. Therefore, there is no firm evidence to establish the optimal first-line treatment for small single HCC in patients with well-preserved liver function. Resection and transplantation achieve the best outcomes in well-selected candidates (5-year survival of 60%–70%), and compete as the first option from an intention-to-treat perspective. If surgery is precluded, local, nonsurgical therapies are applied. Percutaneous treatments provide good results (5-year survival of 40%–50%), but are unable to achieve response rates and outcomes comparable to those for surgical treatments, even when applied as the first option. Radiofrequency thermal ablation provides slightly better objective response rates than ethanol injection, but no survival advantages have been fully demonstrated. The remaining treatments have been assessed in the setting of around 70 RCTs conducted during the past 25 years. Chemoembolization has been shown to provide modest survival advantages in two RCTs and a metaanalysis, and is currently the mainstay of treatment in 10% of the whole HCC population. The ideal candidates for this option are patients with well-preserved liver function (Child-Pugh class A) and multinodular asymptomatic tumors without vascular invasion. Further RCTs are needed to assess the best chemotherapeutic agent and the ideal re-treatment schedule. There is no firstline option for patients with advanced HCC (vascular invasion, extrahepatic spread, or cancer-related symptoms). Systemic doxorubicin provides partial responses in 10% of cases, without proven survival advantages, and well-known treatment-related complications. Several other treatments, such as immunotherapy, internal radiation, tamoxifen, or anti-androgen agents, have not shown any relevant anti-tumoral effect or survival benefit. New drugs, such as tyrosine kinase inhibitors and anti-angiogenic agents, are currently being tested in the setting of clinical trials.

Journal ArticleDOI
TL;DR: The data indicate that hepatorenal syndrome is the result of a decrease in cardiac output in the setting of a severe arterial vasodilation, and plasma renin activity and cardiac output were the only independent predictors of hepat Lorenal syndrome.

Journal ArticleDOI
TL;DR: In this paper, the radial velocity data from a large survey performed with the CORAVEL spectrovelocimeter was used to analyze the radial velocities of stars in the solar neighbourhood.
Abstract: The availability of the Hipparcos Catalogue has triggered many kinematic and dynamical studies of the solar neighbourhood. Nevertheless, those studies generally lacked the third component of the space velocities, i.e., the radial velocities. This work presents the kinematic analysis of 5952 K and 739 M giants in the solar neighbourhood which includes for the first time radial velocity data from a large survey performed with the CORAVEL spectrovelocimeter. It also uses proper motions from the Tycho-2 catalogue, which are expected to be more accurate than the Hipparcos ones. An important by-product of this study is the observed fraction of only 5.7% of spectroscopic binaries among M giants as compared to 13.7% for K giants. After excluding the binaries for which no center-of-mass velocity could be estimated, 5311 K and 719 M giants remain in the final sample. The UV -plane constructed from these data for the stars with precise parallaxes (%) reveals a rich small-scale structure, with several clumps corresponding to the Hercules stream, the Sirius moving group, and the Hyades and Pleiades superclusters. A maximum-likelihood method, based on a Bayesian approach, has been applied to the data, in order to make full use of all the available stars (not only those with precise parallaxes) and to derive the kinematic properties of these subgroups. Isochrones in the Hertzsprung-Russell diagram reveal a very wide range of ages for stars belonging to these groups. These groups are most probably related to the dynamical perturbation by transient spiral waves (as recently modelled by De Simone et al. [CITE]) rather than to cluster remnants. A possible explanation for the presence of young group/clusters in the same area of the UV -plane is that they have been put there by the spiral wave associated with their formation, while the kinematics of the older stars of our sample has also been disturbed by the same wave. The emerging picture is thus one of dynamical streams pervading the solar neighbourhood and travelling in the Galaxy with similar space velocities. The term dynamical stream is more appropriate than the traditional term supercluster since it involves stars of different ages, not born at the same place nor at the same time. The position of those streams in the UV -plane is responsible for the vertex deviation of for the whole sample. Our study suggests that the vertex deviation for younger populations could have the same dynamical origin. The underlying velocity ellipsoid, extracted by the maximum-likelihood method after removal of the streams, is not centered on the value commonly accepted for the radial antisolar motion: it is centered on km s-1 . However, the full data set (including the various streams) does yield the usual value for the radial solar motion, when properly accounting for the biases inherent to this kind of analysis (namely, km s-1 ). This discrepancy clearly raises the essential question of how to derive the solar motion in the presence of dynamical perturbations altering the kinematics of the solar neighbourhood: does there exist in the solar neighbourhood a subset of stars having no net radial motion which can be used as a reference against which to measure the solar motion?

Journal ArticleDOI
27 Apr 2005-JAMA
TL;DR: The revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC in patients fulfilling these criteria, and both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations.
Abstract: ContextThe selection of individuals for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite instability.ObjectiveTo establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers.Design, Setting, and PatientsA prospective, multicenter, nationwide study (the EPICOLON study) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1, 2000, and October 31, 2001.InterventionsMicrosatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age, personal or family history, and tumor characteristics. Patients whose tumors exhibited microsatellite instability and/or lack of protein expression underwent MSH2/MLH1 germline testing.Main Outcome MeasuresEffectiveness and efficiency of both microsatellite instability testing and immunostaining, either directly or previous selection of patients according to the revised Bethesda guidelines, were evaluated with respect to the presence of MSH2/MLH1 germline mutations.ResultsTwo hundred eighty-seven patients (23.5%) fulfilled the revised Bethesda guidelines. Ninety-one patients (7.4%) had a mismatch repair deficiency, with tumors exhibiting either microsatellite instability (n = 83) or loss of protein expression (n = 81). Germline testing identified 11 mutations (0.9%) in either MSH2 (7 cases) or MLH1 (4 cases) genes. Strategies based on either microsatellite instability testing or immunostaining previous selection of patients according to the revised Bethesda guidelines were the most effective (sensitivity, 81.8% and 81.8%; specificity, 98.0% and 98.2%; positive predictive value, 27.3% and 29.0%, respectively) to identify MSH2/MLH1 gene carriers. Logistic regression analysis confirmed the revised Bethesda guidelines as the most discriminating set of clinical parameters (odds ratio, 33.3; 95% confidence interval, 4.3-250; P = .001).ConclusionThe revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC. In patients fulfilling these criteria, both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations.

Journal ArticleDOI
TL;DR: This study shows that specific bacterial phylotypes are associated both with different phases of PAH degradation and with nutrient addition in a preadapted PAH-contaminated soil.
Abstract: Bacterial community dynamics and biodegradation processes were examined in a highly creosote-contaminated soil undergoing a range of laboratory-based bioremediation treatments. The dynamics of the eubacterial community, the number of heterotrophs and polycyclic aromatic hydrocarbon (PAH) degraders, and the total petroleum hydrocarbon (TPH) and PAH concentrations were monitored during the bioremediation process. TPH and PAHs were significantly degraded in all treatments (72 to 79% and 83 to 87%, respectively), and the biodegradation values were higher when nutrients were not added, especially for benzo(a)anthracene and chrysene. The moisture content and aeration were determined to be the key factors associated with PAH bioremediation. Neither biosurfactant addition, bioaugmentation, nor ferric octate addition led to differences in PAH or TPH biodegradation compared to biodegradation with nutrient treatment. All treatments resulted in a high first-order degradation rate during the first 45 days, which was markedly reduced after 90 days. A sharp increase in the size of the heterotrophic and PAH-degrading microbial populations was observed, which coincided with the highest rates of TPH and PAH biodegradation. At the end of the incubation period, PAH degraders were more prevalent in samples to which nutrients had not been added. Denaturing gradient gel electrophoresis analysis and principal-component analysis confirmed that there was a remarkable shift in the composition of the bacterial community due to both the biodegradation process and the addition of nutrients. At early stages of biodegradation, the α-Proteobacteria group (genera Sphingomonas and Azospirillum) was the dominant group in all treatments. At later stages, the γ-Proteobacteria group (genus Xanthomonas), the α-Proteobacteria group (genus Sphingomonas), and the Cytophaga-Flexibacter-Bacteroides group (Bacteroidetes) were the dominant groups in the nonnutrient treatment, while the γ-Proteobacteria group (genus Xathomonas), the β-Proteobacteria group (genera Alcaligenes and Achromobacter), and the α-Proteobacteria group (genus Sphingomonas) were the dominant groups in the nutrient treatment. This study shows that specific bacterial phylotypes are associated both with different phases of PAH degradation and with nutrient addition in a preadapted PAH-contaminated soil. Our findings also suggest that there are complex interactions between bacterial species and medium conditions that influence the biodegradation capacity of the microbial communities involved in bioremediation processes.

Journal ArticleDOI
TL;DR: Comparative genomics studies indicate that the more recently discovered ParaHox and NK clusters were linked to the Hox cluster early in evolution, and that together they constituted a 'megacluster' of homeobox genes that conspicuously contributed to body-plan evolution.
Abstract: Once called the 'Rosetta stone' of developmental biology, the homeobox continues to fascinate both evolutionary and developmental biologists. The birth of the homeotic, or Hox, gene cluster, and its subsequent evolution, has been crucial in mediating the major transitions in metazoan body plan. Comparative genomics studies indicate that the more recently discovered ParaHox and NK clusters were linked to the Hox cluster early in evolution, and that together they constituted a 'megacluster' of homeobox genes that conspicuously contributed to body-plan evolution.

Journal ArticleDOI
TL;DR: The results indicate that Mfn2 triggers mitochondrial energization, at least in part, by regulating OXPHOS expression through signals that are independent of its role as a mitochondrial fusion protein.
Abstract: Mitofusin-2 (Mfn2) is a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells and mutations in the Mfn2 gene cause Charcot-Marie-Tooth neuropathy type 2A. Here, we show that Mfn2 loss-of-function inhibits pyruvate, glucose and fatty acid oxidation and reduces mitochondrial membrane potential, whereas Mfn2 gain-of-function increases glucose oxidation and mitochondrial membrane potential. As to the mechanisms involved, we have found that Mfn2 loss-of-function represses nuclear-encoded subunits of OXPHOS complexes I, II, III and V, whereas Mfn2 overexpression induced the subunits of complexes I, IV and V. Obesity-induced Mfn2 deficiency in rat skeletal muscle was also associated with a decrease in the subunits of complexes I, II, III and V. In addition, the effect of Mfn2 overexpression on mitochondrial metabolism was mimicked by a truncated Mfn2 mutant that is inactive as a mitochondrial fusion protein. Our results indicate that Mfn2 triggers mitochondrial energization, at least in part, by regulating OXPHOS expression through signals that are independent of its role as a mitochondrial fusion protein.