Showing papers by "University of Geneva published in 2009"
TL;DR: It is argued that increased awareness of the implications of spatial bias in surveys, and possible modeling remedies, will substantially improve predictions of species distributions and as large an effect on predictive performance as the choice of modeling method.
Abstract: Most methods for modeling species distributions from occurrence records require additional data representing the range of environmental conditions in the modeled region. These data, called background or pseudo-absence data, are usually drawn at random from the entire region, whereas occurrence collection is often spatially biased toward easily accessed areas. Since the spatial bias generally results in environmental bias, the difference between occurrence collection and background sampling may lead to inaccurate models. To correct the estimation, we propose choosing background data with the same bias as occurrence data. We investigate theoretical and practical implications of this approach. Accurate information about spatial bias is usually lacking, so explicit biased sampling of background sites may not be possible. However, it is likely that an entire target group of species observed by similar methods will share similar bias. We therefore explore the use of all occurrences within a target group as biased background data. We compare model performance using target-group background and randomly sampled background on a comprehensive collection of data for 226 species from diverse regions of the world. We find that target-group background improves average performance for all the modeling methods we consider, with the choice of background data having as large an effect on predictive performance as the choice of modeling method. The performance improvement due to target-group background is greatest when there is strong bias in the target-group presence records. Our approach applies to regression-based modeling methods that have been adapted for use with occurrence data, such as generalized linear or additive models and boosted regression trees, and to Maxent, a probability density estimation method. We argue that increased awareness of the implications of spatial bias in surveys, and possible modeling remedies, will substantially improve predictions of species distributions.
2,307 citations
University of Paris-Sud1, French Institute of Health and Medical Research2, Institut Gustave Roussy3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, University of Gothenburg11, Boston Children's Hospital12, University of Freiburg13, Buck Institute for Research on Aging14, University of California, San Francisco15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Yale University25, Howard Hughes Medical Institute26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, Stony Brook University45, University of Göttingen46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells
2,218 citations
TL;DR: An overview of the seven articles included in this special issue is provided and several avenues for future research are suggested.
Abstract: Organizational ambidexterity has emerged as a new research paradigm in organization theory, yet several issues fundamental to this debate remain controversial. We explore four central tensions here: Should organizations achieve ambidexterity through differentiation or through integration? Does ambidexterity occur at the individual or organizational level? Must organizations take a static or dynamic perspective on ambidexterity? Finally, can ambidexterity arise internally, or do firms have to externalize some processes? We provide an overview of the seven articles included in this special issue and suggest several avenues for future research.
1,946 citations
TL;DR: Recent evidence for structural forms of synaptic plasticity in the mammalian cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively.
Abstract: Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.
1,696 citations
National Institutes of Health1, University of Geneva2, Johns Hopkins University3, University of Washington4, Erasmus University Rotterdam5, University of Texas Health Science Center at Houston6, University of Iceland7, Boston University8, Cedars-Sinai Medical Center9, Harvard University10, Group Health Cooperative11
TL;DR: A genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium identifies 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10−7.
Abstract: Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7). The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 × 10(-8)) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.
1,333 citations
Christine G. Elsik1, Christine G. Elsik2, Christine G. Elsik3, Ross L. Tellam2 +325 more•Institutions (65)
TL;DR: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage and provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
Abstract: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
1,144 citations
TL;DR: This work uses two novel and specific mTOR kinase domain inhibitors (PP242 and PP30) to show that pharmacological inhibition of mTOR blocks the phosphorylation of Akt at S473 and prevents its full activation, and shows that the TORKinib PP242 is a more effective mTORC1 inhibitor than rapamycin.
Abstract: The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals These signaling functions are distributed between at least two distinct mTOR protein complexes: mTORC1 and mTORC2 mTORC1 is sensitive to the selective inhibitor rapamycin and activated by growth factor stimulation via the canonical phosphoinositide 3-kinase (PI3K)-->Akt-->mTOR pathway Activated mTORC1 kinase up-regulates protein synthesis by phosphorylating key regulators of mRNA translation By contrast, mTORC2 is resistant to rapamycin Genetic studies have suggested that mTORC2 may phosphorylate Akt at S473, one of two phosphorylation sites required for Akt activation; this has been controversial, in part because RNA interference and gene knockouts produce distinct Akt phospho-isoforms The central role of mTOR in controlling key cellular growth and survival pathways has sparked interest in discovering mTOR inhibitors that bind to the ATP site and therefore target both mTORC2 and mTORC1 We investigated mTOR signaling in cells and animals with two novel and specific mTOR kinase domain inhibitors (TORKinibs) Unlike rapamycin, these TORKinibs (PP242 and PP30) inhibit mTORC2, and we use them to show that pharmacological inhibition of mTOR blocks the phosphorylation of Akt at S473 and prevents its full activation Furthermore, we show that TORKinibs inhibit proliferation of primary cells more completely than rapamycin Surprisingly, we find that mTORC2 is not the basis for this enhanced activity, and we show that the TORKinib PP242 is a more effective mTORC1 inhibitor than rapamycin Importantly, at the molecular level, PP242 inhibits cap-dependent translation under conditions in which rapamycin has no effect Our findings identify new functional features of mTORC1 that are resistant to rapamycin but are effectively targeted by TORKinibs These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease
1,129 citations
TL;DR: Present global priorities for adolescent health policy are an important but insufficient response to prevent mortality in an age-group in which more than two in five deaths are due to intentional and unintentional injuries.
1,091 citations
TL;DR: It is shown that both SUTs and CUTs display distinct patterns of distribution at specific locations, changing the view of how a genome is transcribed and indicating that bidirectionality is an inherent feature of promoters.
Abstract: Genome-wide pervasive transcription has been reported in many eukaryotic organisms, revealing a highly interleaved transcriptome organization that involves hundreds of previously unknown non-coding RNAs. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs). One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function. Single-gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs or their generation itself. So far, a complete transcriptome architecture including SUTs and CUTs has not been described in any organism. Knowledge about the position and genome-wide arrangement of these transcripts will be instrumental in understanding their function. Here we provide a comprehensive analysis of these transcripts in the context of multiple conditions, a mutant of the exosome machinery and different strain backgrounds of Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct patterns of distribution at specific locations. Most of the newly identified transcripts initiate from nucleosome-free regions (NFRs) associated with the promoters of other transcripts (mostly protein-coding genes), or from NFRs at the 3' ends of protein-coding genes. Likewise, about half of all coding transcripts initiate from NFRs associated with promoters of other transcripts. These data change our view of how a genome is transcribed, indicating that bidirectionality is an inherent feature of promoters. Such an arrangement of divergent and overlapping transcripts may provide a mechanism for local spreading of regulatory signals-that is, coupling the transcriptional regulation of neighbouring genes by means of transcriptional interference or histone modification.
979 citations
Posted Content•
TL;DR: In this article, the authors compare the potential of different quantum repeater protocols quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons, and compare different approaches to realize quantum repeaters.
Abstract: The distribution of quantum states over long distances is limited by photon loss. Straightforward amplification as in classical telecommunications is not an option in quantum communication because of the no-cloning theorem. This problem could be overcome by implementing quantum repeater protocols, which create long-distance entanglement from shorter-distance entanglement via entanglement swapping. Such protocols require the capacity to create entanglement in a heralded fashion, to store it in quantum memories, and to swap it. One attractive general strategy for realizing quantum repeaters is based on the use of atomic ensembles as quantum memories, in combination with linear optical techniques and photon counting to perform all required operations. Here we review the theoretical and experimental status quo of this very active field. We compare the potential of different approaches quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons.
930 citations
TL;DR: Observations of the transiting planet GJ’1214b are reported, finding that the planetary mass and radius are consistent with a composition of primarily water enshrouded by a hydrogen–helium envelope that is only 0.05% of the mass of the planet.
Abstract: A decade ago, the detection of the first transiting extrasolar planet provided a direct constraint on its composition and opened the door to spectroscopic investigations of extrasolar planetary atmospheres. Because such characterization studies are feasible only for transiting systems that are both nearby and for which the planet-to-star radius ratio is relatively large, nearby small stars have been surveyed intensively. Doppler studies and microlensing have uncovered a population of planets with minimum masses of 1.9-10 times the Earth's mass (M[symbol:see text]), called super-Earths. The first constraint on the bulk composition of this novel class of planets was afforded by CoRoT-7b (refs 8, 9), but the distance and size of its star preclude atmospheric studies in the foreseeable future. Here we report observations of the transiting planet GJ 1214b, which has a mass of 6.55M[symbol:see text]), and a radius 2.68 times Earth's radius (R[symbol:see text]), indicating that it is intermediate in stature between Earth and the ice giants of the Solar System. We find that the planetary mass and radius are consistent with a composition of primarily water enshrouded by a hydrogen-helium envelope that is only 0.05% of the mass of the planet. The atmosphere is probably escaping hydrodynamically, indicating that it has undergone significant evolution during its history. The star is small and only 13 parsecs away, so the planetary atmosphere is amenable to study with current observatories.
University of Geneva1, Howard Hughes Medical Institute2, Max Planck Society3, University of California, Los Angeles4, University of Lausanne5, Imperial College London6, University College London7, École Polytechnique Fédérale de Lausanne8, Picower Institute for Learning and Memory9, Janelia Farm Research Campus10, University of California, San Francisco11
TL;DR: A chronic cranial window is described to obtain optical access to the mouse cerebral cortex for long-term imaging and the entire dendritic and axonal arbor of individual neurons can be reconstructed.
Abstract: To understand the cellular and circuit mechanisms of experience-dependent plasticity, neurons and their synapses need to be studied in the intact brain over extended periods of time. Two-photon excitation laser scanning microscopy (2PLSM), together with expression of fluorescent proteins, enables high-resolution imaging of neuronal structure in vivo. In this protocol we describe a chronic cranial window to obtain optical access to the mouse cerebral cortex for long-term imaging. A small bone flap is replaced with a coverglass, which is permanently sealed in place with dental acrylic, providing a clear imaging window with a large field of view (approximately 0.8-12 mm(2)). The surgical procedure can be completed within approximately 1 h. The preparation allows imaging over time periods of months with arbitrary imaging intervals. The large size of the imaging window facilitates imaging of ongoing structural plasticity of small neuronal structures in mice, with low densities of labeled neurons. The entire dendritic and axonal arbor of individual neurons can be reconstructed.
TL;DR: In this paper, a component process model for emotion processing is proposed and compared with some of its major competitors, focusing on the dynamic aspect of emotion processes, in particular the sequence of appraisal checks and the synchronisation of response systems, and the capacity of the model to predict individual differences in emotional responding.
Abstract: Emotion is conceptualised as an emergent, dynamic process based on an individual's subjective appraisal of significant events. It is argued that theoretical models of emotion need to propose an architecture that reflects the essential nature and functions of emotion as a psychobiological and cultural adaptation mechanism. One proposal for such a model and its underlying dynamic architecture, the component process model, is briefly sketched and compared with some of its major competitors. Recent empirical evidence in support of the model is reviewed. Special emphasis is given to the dynamic aspect of emotion processes, in particular the sequence of appraisal checks and the synchronisation of response systems, as well as the capacity of the model to predict individual differences in emotional responding.
TL;DR: Factors influencing hand hygiene compliance, the impact of hand hygiene promotion on healthcare-associated pathogen cross-transmission and infection rates, and challenging issues related to the universal adoption of alcohol-based hand rub as a critical system change are reviewed.
Austrian Institute of Technology1, Télécom ParisTech2, University of Geneva3, Masaryk University4, Centre national de la recherche scientifique5, University of Surrey6, Toshiba7, Ludwig Maximilian University of Munich8, Austrian Academy of Sciences9, University of Vienna10, University of Waterloo11, University of Erlangen-Nuremberg12, BearingPoint13, Université de Montréal14, Max Planck Society15, Siemens16
TL;DR: The paper presents the architecture and functionality of the principal networking agent?the SECOQC node module, which enables the authentic classical communication required for key distillation, manages the generated key material, determines a communication path between any destinations in the network, and realizes end-to-end secure transport of key material between these destinations.
Abstract: In this paper, we present the quantum key distribution (QKD) network designed and implemented by the European project SEcure COmmunication based on Quantum Cryptography (SECOQC) (2004?2008), unifying the efforts of 41 research and industrial organizations. The paper summarizes the SECOQC approach to QKD networks with a focus on the trusted repeater paradigm. It discusses the architecture and functionality of the SECOQC trusted repeater prototype, which has been put into operation in Vienna in 2008 and publicly demonstrated in the framework of a SECOQC QKD conference held from October 8 to 10, 2008. The demonstration involved one-time pad encrypted telephone communication, a secure (AES encryption protected) video-conference with all deployed nodes and a number of rerouting experiments, highlighting basic mechanisms of the SECOQC network functionality.The paper gives an overview of the eight point-to-point network links in the prototype and their underlying technology: three plug and play systems by id Quantique, a one way weak pulse system from Toshiba Research in the UK, a coherent one-way system by GAP Optique with the participation of id Quantique and the AIT Austrian Institute of Technology (formerly ARC), an entangled photons system by the University of Vienna and the AIT, a continuous-variables system by Centre National de la Recherche Scientifique (CNRS) and THALES Research and Technology with the participation of Universit? Libre de Bruxelles, and a free space link by the Ludwig Maximillians University in Munich connecting two nodes situated in adjacent buildings (line of sight 80?m). The average link length is between 20 and 30?km, the longest link being 83?km.The paper presents the architecture and functionality of the principal networking agent?the SECOQC node module, which enables the authentic classical communication required for key distillation, manages the generated key material, determines a communication path between any destinations in the network, and realizes end-to-end secure transport of key material between these destinations.The paper also illustrates the operation of the network in a number of typical exploitation regimes and gives an initial estimate of the network transmission capacity, defined as the maximum amount of key that can be exchanged, or alternatively the amount of information that can be transmitted with information theoretic security, between two arbitrary nodes.
TL;DR: The data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity, and identifies multiple expressive quantitative trait loci per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene.
Abstract: Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity.
TL;DR: CABG might be a better option for patients with diabetes and patients aged 65 years or older because it is found mortality to be lower in these subgroups, so choice of treatment should depend on patient preferences for other outcomes.
TL;DR: It is suggested that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.
Abstract: In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.
Marche Polytechnic University1, University of Strasbourg2, Stellenbosch University3, Université libre de Bruxelles4, University of Geneva5, University of Chicago6, Ludwig Maximilian University of Munich7, University of Modena and Reggio Emilia8, Lister Hospital9, Maastricht University10, Columbia University11
TL;DR: In this article, a collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy.
Abstract: A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalized in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.
TL;DR: While 5-year survival following surgery for colorectal liver metastasis approaches 50%, over one-half of patients develop recurrence within 2 years, suggesting that patients undergoing repeat surgery for recurrent metastasis have similar patterns of recurrence and RFS time.
Abstract: OBJECTIVE(S): To investigate rates and patterns of recurrence in patients following curative intent surgery for colorectal liver metastasis. BACKGROUND: Outcomes following surgical management of colorectal liver metastasis have largely focused on overall survival. Contemporary data on rates and patterns of recurrence following surgery for colorectal liver metastasis are limited. METHODS: One thousand six hundred sixty-nine patients treated with surgery (resection +/- radiofrequency ablation [RFA]) for colorectal liver metastasis between 1982 and 2008 were identified from an international multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. RESULTS: At the time of the initial liver-directed surgery, surgical treatment was resection only (90.2%), resection plus RFA (8.0%), or RFA alone (1.8%). While 5-year overall survival was 47.3%, 947 (56.7%) patients recurred with a median RFS time of 16.3 months. First recurrence site was intrahepatic only (43.2%), extrahepatic only (35.8%), intra- and extrahepatic (21.0%). There was no difference in RFS based on site of recurrence (intrahepatic: 16.9 months; extrahepatic: 16.6 months; intra- and extrahepatic: 16.2 month; P > 0.05). Receipt of adjuvant chemotherapy was associated with overall recurrence risk (hazard ratio [HR] = 0.56), while history of RFA (HR = 2.39, P = 0.001) and R1 margin status (HR = 1.36) were predictive of intrahepatic recurrence. Pattern of recurrence and RFS remained similar following repeat surgery for recurrent disease. CONCLUSIONS: While 5-year survival following surgery for colorectal liver metastasis approaches 50%, over one-half of patients develop recurrence within 2 years. The pattern of failure is distributed relatively equally among intrahepatic, extrahepatic, and intra- plus extrahepatic sites. Patients undergoing repeat surgery for recurrent metastasis have similar patterns of recurrence and RFS time.
TL;DR: In this paper, the authors reported the discovery of very shallow (ΔF/F ≈ 3.4× 10 −4 ) periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which they interpret as caused by a transiting companion.
Abstract: Aims. We report the discovery of very shallow (ΔF/F ≈ 3.4× 10 −4 ), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results. We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40 �� or triple systems are almost excluded with a 8 × 10 −4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10 −5 day and a radius of Rp = 1.68 ± 0.09 REarth .A nalysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. Conclusions. CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800–2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived.
TL;DR: It is reported that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses and represents a novel adaptive pro‐survival response against stress.
Abstract: Mitochondria are dynamic organelles, the morphology of which results from an equilibrium between two opposing processes, fusion and fission. Mitochondrial fusion relies on dynamin-related GTPases, the mitofusins (MFN1 and 2) in the outer mitochondrial membrane and OPA1 (optic atrophy 1) in the inner mitochondrial membrane. Apart from a role in the maintenance of mitochondrial DNA, little is known about the physiological role of mitochondrial fusion. Here we report that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses. This process precedes mitochondrial fission when it is triggered by apoptotic stimuli such as UV irradiation or actinomycin D. Stress-induced mitochondrial hyperfusion (SIMH) is independent of MFN2, BAX/BAK, and prohibitins, but requires L-OPA1, MFN1, and the mitochondrial inner membrane protein SLP-2. In the absence of SLP-2, L-OPA1 is lost and SIMH is prevented. SIMH is accompanied by increased mitochondrial ATP production and represents a novel adaptive pro-survival response against stress.
TL;DR: It is suggested that higher CS systematically affect preferences and choices in ways that favor economic success, and in particular, the ability to plan strongly predict perseverance on the job in a setting with a substantial financial penalty for early exit.
Abstract: Economic analysis has so far said little about how an individual's cognitive skills (CS) are related to the individual's economic preferences in different choice domains, such as risk taking or saving, and how preferences in different domains are related to each other. Using a sample of 1,000 trainee truckers we report three findings. First, there is a strong and significant relationship between an individual's CS and preferences. Individuals with better CS are more patient, in both short- and long-run. Better CS are also associated with a greater willingness to take calculated risks. Second, CS predict social awareness and choices in a sequential Prisoner's Dilemma game. Subjects with better CS more accurately forecast others' behavior and differentiate their behavior as a second mover more strongly depending on the first-mover's choice. Third, CS, and in particular, the ability to plan, strongly predict perseverance on the job in a setting with a substantial financial penalty for early exit. Consistent with CS being a common factor in all of these preferences and behaviors, we find a strong pattern of correlation among them. These results, taken together with the theoretical explanation we offer for the relationships we find, suggest that higher CS systematically affect preferences and choices in ways that favor economic success.
TL;DR: The World Health Organization's Guidelines on Hand Hygiene in Health Care have been issued by WHO Patient Safety on 5 May 2009 on the occasion of the launch of the Save Lives: Clean Your Hands initiative as mentioned in this paper.
Abstract: The World Health Organization's Guidelines on Hand Hygiene in Health Care have been issued by WHO Patient Safety on 5 May 2009 on the occasion of the launch of the Save Lives: Clean Your Hands initiative. The Guidelines represent the contribution of more than 100 international experts and provide a comprehensive overview of essential aspects of hand hygiene in health care, evidence- and consensus-based recommendations, and lessons learned from testing their Advanced Draft and related implementation tools.
TL;DR: The mechanisms that shape B-cell responses at the extremes of age are described and how they could be taken into account to design more effective immunization strategies for these high-risk age groups are described.
Abstract: Infants and the elderly share a high vulnerability to infections and therefore have specific immunization requirements. Inducing potent and sustained B-cell responses is as challenging in infants as it is in older subjects. Several mechanisms to explain the decreased B-cell responses at the extremes of age apply to both infants and the elderly. These include intrinsic B-cell limitations as well as numerous microenvironmental factors in lymphoid organs and the bone marrow. This Review describes the mechanisms that shape B-cell responses at the extremes of age and how they could be taken into account to design more effective immunization strategies for these high-risk age groups.
TL;DR: The results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.
Abstract: We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 x 10(-8)). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.
TL;DR: The cumulative evidence from recent genomic and genetic analyses pointing toward an unexpected variety of mechanisms that lead to symbiosis with legumes is reviewed.
TL;DR: All 45 anterior maxillary single-tooth implants fulfilled strict success criteria for dental implants with regard to osseointegration, including the absence of peri-implant radiolucency, implant mobility, suppuration, and pain.
Abstract: Background: To validate the concept of early implant placement for use in the esthetically sensitive anterior maxilla, clinical trials should ideally include objective esthetic criteria when assessing outcome parameters.Methods: In this cross-sectional, retrospective 2- to 4-year study involving 45 patients treated with maxillary anterior single-tooth implants according to the concept of early implant placement, a novel comprehensive index, comprising pink esthetic score and white esthetic score (PES/WES; the highest possible combined score is 20), was applied for the objective esthetic outcome assessment of anterior single-tooth implants.Results: All 45 anterior maxillary single-tooth implants fulfilled strict success criteria for dental implants with regard to osseointegration, including the absence of peri-implant radiolucency, implant mobility, suppuration, and pain. The mean total PES/WES was 14.7 ± 1.18 (range: 11 to 18). The mean total PES of 7.8 ± 0.88 (range: 6 to 9) documents favorable overall p...
TL;DR: The design and implementation of the new UniProt website is discussed, which was released in July 2008, and how it improves data access for users with different levels of experience, as well as to machines for programmatic access is shown.
Abstract: The UniProt consortium was formed in 2002 by groups from the Swiss Institute of Bioinformatics (SIB), the European Bioinformatics Institute (EBI) and the Protein Information Resource (PIR) at Georgetown University, and soon afterwards the website http://www.uniprot.org
was set up as a central entry point to UniProt resources. Requests to this address were redirected to one of the three organisations' websites. While these sites shared a set of static pages with general information about UniProt, their pages for searching and viewing data were different. To provide users with a consistent view and to cut the cost of maintaining three separate sites, the consortium decided to develop a common website for UniProt. Following several years of intense development and a year of public beta testing, the http://www.uniprot.org
domain was switched to the newly developed site described in this paper in July 2008. The UniProt consortium is the main provider of protein sequence and annotation data for much of the life sciences community. The http://www.uniprot.org
website is the primary access point to this data and to documentation and basic tools for the data. These tools include full text and field-based text search, similarity search, multiple sequence alignment, batch retrieval and database identifier mapping. This paper discusses the design and implementation of the new website, which was released in July 2008, and shows how it improves data access for users with different levels of experience, as well as to machines for programmatic access. http://www.uniprot.org/
is open for both academic and commercial use. The site was built with open source tools and libraries. Feedback is very welcome and should be sent to help@uniprot.org. The new UniProt website makes accessing and understanding UniProt easier than ever. The two main lessons learned are that getting the basics right for such a data provider website has huge benefits, but is not trivial and easy to underestimate, and that there is no substitute for using empirical data throughout the development process to decide on what is and what is not working for your users.
TL;DR: The cleavage by OMA1 causes an accumulation of the short OPA1 variants, and the role ofm-AAA proteases in ensuring a balance of long and short Opa1 isoforms is investigated.
Abstract: Mitochondrial fusion depends on the dynamin-like guanosine triphosphatase OPA1, whose activity is controlled by proteolytic cleavage. Dysfunction of mitochondria induces OPA1 processing and results in mitochondrial fragmentation, allowing the selective removal of damaged mitochondria. In this study, we demonstrate that two classes of metallopeptidases regulate OPA1 cleavage in the mitochondrial inner membrane: isoenzymes of the adenosine triphosphate (ATP)-dependent matrix AAA (ATPase associated with diverse cellular activities [m-AAA]) protease, variable assemblies of the conserved subunits paraplegin, AFG3L1 and -2, and the ATP-independent peptidase OMA1. Functionally redundant isoenzymes of the m-AAA protease ensure the balanced accumulation of long and short isoforms of OPA1 required for mitochondrial fusion. The loss of AFG3L2 in mouse tissues, down-regulation of AFG3L1 and -2 in mouse embryonic fibroblasts, or the expression of a dominant-negative AFG3L2 variant in human cells decreases the stability of long OPA1 isoforms and induces OPA1 processing by OMA1. Moreover, cleavage by OMA1 causes the accumulation of short OPA1 variants if mitochondrial DNA is depleted or mitochondrial activities are impaired. Our findings link distinct peptidases to constitutive and induced OPA1 processing and shed new light on the pathogenesis of neurodegenerative disorders associated with mutations in m-AAA protease subunits.