Showing papers by "University of Cambridge published in 2005"
TL;DR: Emergency ligation of bleeding oesophageal varices using the Milnes Walker technique was performed in 38 patients, and in patients with good preoperative liver function this rose to 71% and the simple scoring system for grading the severity of disturbance of liver function was found to be of value in predicting the outcome of surgery.
Abstract: Emergency ligation of bleeding oesophageal varices using the Milnes Walker technique was performed in 38 patients. Haemorrhage continued or recurred in hospital in 11 patients, all of whom subsequently died. A further 10 patients died in hospital following operation from hepatic failure and a variety of other causes. Five patients were finally considered suitable for elective shunt surgery, but of 12 patients who were discharged without a further operation, only 2 have re-bled. Although the overall 6-month survival was 32 per cent, in patients with good preoperative liver function this rose to 71 per cent, and the simple scoring system for grading the severity of disturbance of liver function was found to be of value in predicting the outcome of surgery.
Since the results of emergency ligation of bleeding oesophageal varices in our hands have been so disappointing we are currently using it less and are trying the mesenteric caval jump graft as an emergency operation for the control of bleeding varices.
7,262 citations
TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
Abstract: BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by homologous recombination. These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer.
5,650 citations
TL;DR: Detailed estimates of dementia prevalence for each world region are believed to constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.
4,891 citations
TL;DR: It is shown how derivatives of the GPW energy functional, namely ionic forces and the Kohn–Sham matrix, can be computed in a consistent way and the computational cost is scaling linearly with the system size, even for condensed phase systems of just a few tens of atoms.
4,047 citations
TL;DR: It is hypothesized that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation.
Abstract: Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use--when a drug is voluntarily taken because it has reinforcing, often hedonic, effects--through loss of control over this behavior, such that it becomes habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.
3,439 citations
TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.
3,326 citations
02 May 2005
TL;DR: The design options for migrating OSes running services with liveness constraints are considered, the concept of writable working set is introduced, and the design, implementation and evaluation of high-performance OS migration built on top of the Xen VMM are presented.
Abstract: Migrating operating system instances across distinct physical hosts is a useful tool for administrators of data centers and clusters: It allows a clean separation between hard-ware and software, and facilitates fault management, load balancing, and low-level system maintenance.By carrying out the majority of migration while OSes continue to run, we achieve impressive performance with minimal service downtimes; we demonstrate the migration of entire OS instances on a commodity cluster, recording service downtimes as low as 60ms. We show that that our performance is sufficient to make live migration a practical tool even for servers running interactive loads.In this paper we consider the design options for migrating OSes running services with liveness constraints, focusing on data center and cluster environments. We introduce and analyze the concept of writable working set, and present the design, implementation and evaluation of high-performance OS migration built on top of the Xen VMM.
3,186 citations
TL;DR: The authors conducted a quantitative meta-analysis of 668 sets of activation coordinates in Talairach space reported in 24 primary studies of n-back task variants manipulating process (location vs. identity monitoring) and content (verbal or nonverbal) of working memory.
Abstract: One of the most popular experimental paradigms for functional neuroimaging studies of working memory has been the n-back task, in which subjects are asked to monitor the identity or location of a series of verbal or nonverbal stimuli and to indicate when the currently presented stimulus is the same as the one presented n trials previously. We conducted a quantitative meta-analysis of 668 sets of activation coordinates in Talairach space reported in 24 primary studies of n-back task variants manipulating process (location vs. identity monitoring) and content (verbal or nonverbal) of working memory. We found the following cortical regions were activated robustly (voxelwise false discovery rate = 1%): lateral premotor cortex; dorsal cingulate and medial premotor cortex; dorsolateral and ventrolateral prefrontal cortex; frontal poles; and medial and lateral posterior parietal cortex. Subsidiary meta-analyses based on appropriate subsets of the primary data demonstrated broadly similar activation patterns for identity monitoring of verbal stimuli and both location and identity monitoring of nonverbal stimuli. There was also some evidence for distinct frontoparietal activation patterns in response to different task variants. The functional specializations of each of the major cortical components in the generic large-scale frontoparietal system are discussed. We conclude that quantitative meta-analysis can be a powerful tool for combining results of multiple primary studies reported in Talairach space. Here, it provides evidence both for broadly consistent activation of frontal and parietal cortical regions by various versions of the n-back working memory paradigm, and for process- and content-specific frontoparietal activation by working memory.
2,960 citations
TL;DR: The development of a set of software applications that use the Data Model and its associated libraries, thus validating the approach and providing a pipeline for high‐throughput analysis of NMR data.
Abstract: To address data management and data exchange problems in the nuclear magnetic resonance (NMR) community, the Collaborative Computing Project for the NMR community (CCPN) created a "Data Model" that describes all the different types of information needed in an NMR structural study, from molecular structure and NMR parameters to coordinates. This paper describes the development of a set of software applications that use the Data Model and its associated libraries, thus validating the approach. These applications are freely available and provide a pipeline for high-throughput analysis of NMR data. Three programs work directly with the Data Model: CcpNmr Analysis, an entirely new analysis and interactive display program, the CcpNmr FormatConverter, which allows transfer of data from programs commonly used in NMR to and from the Data Model, and the CLOUDS software for automated structure calculation and assignment (Carnegie Mellon University), which was rewritten to interact directly with the Data Model. The ARIA 2.0 software for structure calculation (Institut Pasteur) and the QUEEN program for validation of restraints (University of Nijmegen) were extended to provide conversion of their data to the Data Model. During these developments the Data Model has been thoroughly tested and used, demonstrating that applications can successfully exchange data via the Data Model. The software architecture developed by CCPN is now ready for new developments, such as integration with additional software applications and extensions of the Data Model into other areas of research.
2,906 citations
TL;DR: The authors develop a novel theoretical framework to explain cross-language data, which they label a psycholinguistic grain size theory of reading and its development.
Abstract: The development of reading depends on phonological awareness across all languages so far studied. Languages vary in the consistency with which phonology is represented in orthography. This results in developmental differences in the grain size of lexical representations and accompanying differences in developmental reading strategies and the manifestation of dyslexia across orthographies. Differences in lexical representations and reading across languages leave developmental “footprints” in the adult lexicon. The lexical organization and processing strategies that are characteristic of skilled reading in different orthographies are affected by different developmental constraints in different writing systems. The authors develop a novel theoretical framework to explain these cross-language data, which they label a psycholinguistic grain size theory of reading and its development.
2,437 citations
TL;DR: It is demonstrated that the use of an appropriate hydroxyl-free gate dielectric—such as a divinyltetramethylsiloxane-bis(benzocyclobutene) derivative (BCB; ref. 6)—can yield n-channel FET conduction in most conjugated polymers, revealing that electrons are considerably more mobile in these materials than previously thought.
Abstract: Organic semiconductors have been the subject of active research for over a decade now, with applications emerging in light-emitting displays and printable electronic circuits. One characteristic feature of these materials is the strong trapping of electrons but not holes1: organic field-effect transistors (FETs) typically show p-type, but not n-type, conduction even with the appropriate low-work-function electrodes, except for a few special high-electron-affinity2,3,4 or low-bandgap5 organic semiconductors. Here we demonstrate that the use of an appropriate hydroxyl-free gate dielectric—such as a divinyltetramethylsiloxane-bis(benzocyclobutene) derivative (BCB; ref. 6)—can yield n-channel FET conduction in most conjugated polymers. The FET electron mobilities thus obtained reveal that electrons are considerably more mobile in these materials than previously thought. Electron mobilities of the order of 10-3 to 10-2 cm2 V-1 s-1 have been measured in a number of polyfluorene copolymers and in a dialkyl-substituted poly(p-phenylenevinylene), all in the unaligned state. We further show that the reason why n-type behaviour has previously been so elusive is the trapping of electrons at the semiconductor–dielectric interface by hydroxyl groups, present in the form of silanols in the case of the commonly used SiO2 dielectric. These findings should therefore open up new opportunities for organic complementary metal-oxide semiconductor (CMOS) circuits, in which both p-type and n-type behaviours are harnessed.
Durham University1, University of Edinburgh2, ETH Zurich3, Johns Hopkins University4, Queen's University5, Liverpool John Moores University6, University of New South Wales7, Rutherford Appleton Laboratory8, University of Bristol9, Australian National University10, University of Cambridge11, California Institute of Technology12, Australia Telescope National Facility13, University College London14, University of Nottingham15
TL;DR: In this paper, a power-spectrum analysis of the final 2DF Galaxy Redshift Survey (2dFGRS) employing a direct Fourier method is presented, and the covariance matrix is determined using two different approaches to the construction of mock surveys, which are used to demonstrate that the input cosmological model can be correctly recovered.
Abstract: We present a power-spectrum analysis of the final 2dF Galaxy Redshift Survey (2dFGRS), employing a direct Fourier method. The sample used comprises 221 414 galaxies with measured redshifts. We investigate in detail the modelling of the sample selection, improving on previous treatments in a number of respects. A new angular mask is derived, based on revisions to the photometric calibration. The redshift selection function is determined by dividing the survey according to rest-frame colour, and deducing a self-consistent treatment of k-corrections and evolution for each population. The covariance matrix for the power-spectrum estimates is determined using two different approaches to the construction of mock surveys, which are used to demonstrate that the input cosmological model can be correctly recovered. We discuss in detail the possible differences between the galaxy and mass power spectra, and treat these using simulations, analytic models and a hybrid empirical approach. Based on these investigations, we are confident that the 2dFGRS power spectrum can be used to infer the matter content of the universe. On large scales, our estimated power spectrum shows evidence for the ‘baryon oscillations’ that are predicted in cold dark matter (CDM) models. Fitting to a CDM model, assuming a primordial n s = 1 spectrum, h = 0.72 and negligible neutrino mass, the preferred
TL;DR: In this article, the authors introduce the current state of development in the application of ferroelectric thin films for electronic devices and discuss the physics relevant for the performance and failure of these devices.
Abstract: This review covers important advances in recent years in the physics of thin-film ferroelectric oxides, the strongest emphasis being on those aspects particular to ferroelectrics in thin-film form. The authors introduce the current state of development in the application of ferroelectric thin films for electronic devices and discuss the physics relevant for the performance and failure of these devices. Following this the review covers the enormous progress that has been made in the first-principles computational approach to understanding ferroelectrics. The authors then discuss in detail the important role that strain plays in determining the properties of epitaxial thin ferroelectric films. Finally, this review ends with a look at the emerging possibilities for nanoscale ferroelectrics, with particular emphasis on ferroelectrics in nonconventional nanoscale geometries.
TL;DR: Refugees resettled in western countries could be about ten times more likely to have post-traumatic stress disorder than age-matched general populations in those countries.
Research Institute of Molecular Pathology1, Ludwig Maximilian University of Munich2, University of Colorado Boulder3, University of Cambridge4, Centro Nacional de Investigaciones Cardiovasculares5, Autonomous University of Madrid6, University of Navarra7, University of Barcelona8, Howard Hughes Medical Institute9
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.
TL;DR: It is shown that the best type of farming for species persistence depends on the demand for agricultural products and on how the population densities of different species on farmland change with agricultural yield, and that high-yield farming may allow more species to persist.
Abstract: World food demand is expected to more than double by 2050. Decisions about how to meet this challenge will have profound effects on wild species and habitats. We show that farming is already the greatest extinction threat to birds (the best known taxon), and its adverse impacts look set to increase, especially in developing countries. Two competing solutions have been proposed: wildlife-friendly farming (which boosts densities of wild populations on farmland but may decrease agricultural yields) and land sparing (which minimizes demand for farmland by increasing yield). We present a model that identifies how to resolve the trade-off between these approaches. This shows that the best type of farming for species persistence depends on the demand for agricultural products and on how the population densities of different species on farmland change with agricultural yield. Empirical data on such density-yield functions are sparse, but evidence from a range of taxa in developing countries suggests that high-yield farming may allow more species to persist.
TL;DR: The authors proposed a modified version of Swamy's test of slope homogeneity for panel data models where the cross section dimension (N) could be large relative to the time series dimension (T).
Abstract: This paper proposes a modified version of Swamy's test of slope homogeneity for panel data models where the cross section dimension (N) could be large relative to the time series dimension (T). The proposed test exploits the cross section dispersion of individual slopes weighted by their relative precision. In the case of models with strictly exogenous regressors and normally distributed errors, the test is shown to have a standard normal distribution. Using Monte Carlo experiments, it is shown that the test has the correct size and satisfactory power in panels with strictly exogenous regressors for various combinations of N and T. For autoregressive (AR) models the proposed test performs well for moderate values of the root of the autoregressive process. But for AR models with roots near unity a bias-corrected bootstrapped version of the test is proposed which performs well even if N is large relative to T. The proposed cross section dispersion tests are applied to testing the homogeneity of slopes in autoregressive models of individual earnings using the PSID data. The results show statistically significant evidence of slope heterogeneity in the earnings dynamics, even when individuals with similar educational backgrounds are considered as sub-sets.
TL;DR: It is shown here how linear and quadratic Taylor-series expansions and least-squares approximations of the maximum-likelihood translation function lead to likelihood-enhanced translation functions, which can be calculated by FFT and which are more sensitive to the correct translation than the traditional correlation-coefficient fast translation function.
Abstract: This paper is a companion to a recent paper on fast rotation functions [Storoni et al. (2004), Acta Cryst. D60, 432–438], which showed how a Taylor-series expansion of the maximum-likelihood rotation function leads to improved likelihood-enhanced fast rotation functions. In a similar manner, it is shown here how linear and quadratic Taylor-series expansions and least-squares approximations of the maximum-likelihood translation function lead to likelihood-enhanced translation functions, which can be calculated by FFT and which are more sensitive to the correct translation than the traditional correlation-coefficient fast translation function. These likelihood-enhanced translation targets for molecular-replacement searches have been implemented in the program Phaser using the Computational Crystallography Toolbox (cctbx).
TL;DR: In this article, the materials, charge-transport, and device physics of solution-processed organic field-effect transistors are reviewed, focusing in particular on the physics of the active semiconductor/dielectric interface.
Abstract: Field-effect transistors based on solution-processible organic semiconductors have experienced impressive improvements in both performance and reliability in recent years, and printing-based manufacturing processes for integrated transistor circuits are being developed to realize low-cost, large-area electronic products on flexible substrates. This article reviews the materials, charge-transport, and device physics of solution-processed organic field-effect transistors, focusing in particular on the physics of the active semiconductor/dielectric interface. Issues such as the relationship between microstructure and charge transport, the critical role of the gate dielectric, the influence of polaronic relaxation and disorder effects on charge transport, charge-injection mechanisms, and the current understanding of mechanisms for charge trapping are reviewed. Many interesting questions on how the molecular and electronic structures and the presence of defects at organic/organic heterointerfaces influence the device performance and stability remain to be explored.
TL;DR: A survey and comparison of various Structured and Unstructured P2P overlay networks is presented, categorize the various schemes into these two groups in the design spectrum, and discusses the application-level network performance of each group.
Abstract: Over the Internet today, computing and communications environments are significantly more complex and chaotic than classical distributed systems, lacking any centralized organization or hierarchical control. There has been much interest in emerging Peer-to-Peer (P2P) network overlays because they provide a good substrate for creating large-scale data sharing, content distribution, and application-level multicast applications. These P2P overlay networks attempt to provide a long list of features, such as: selection of nearby peers, redundant storage, efficient search/location of data items, data permanence or guarantees, hierarchical naming, trust and authentication, and anonymity. P2P networks potentially offer an efficient routing architecture that is self-organizing, massively scalable, and robust in the wide-area, combining fault tolerance, load balancing, and explicit notion of locality. In this article we present a survey and comparison of various Structured and Unstructured P2P overlay networks. We categorize the various schemes into these two groups in the design spectrum, and discuss the application-level network performance of each group.
Wellcome Trust Sanger Institute1, J. Craig Venter Institute2, George Washington University3, University of Glasgow4, University of Oxford5, Newcastle University6, University of Bordeaux7, University of Cambridge8, Oregon Health & Science University9, University of Dundee10, Imperial College London11, Case Western Reserve University12, Yale University13, Université catholique de Louvain14, University of Iowa15, Wellcome Trust16
TL;DR: Comparisons of the cytoskeleton and endocytic trafficking systems of Trypanosoma brucei with those of humans and other eukaryotic organisms reveal major differences.
Abstract: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
TL;DR: A previously unidentified antigenic subtype of HA (H16), detected in viruses circulating in black-headed gulls in Sweden, is described and proposed that sequence analyses of HA and NA genes of influenza A viruses be used for the rapid identification of existing and novel HA andNA subtypes.
Abstract: In wild aquatic birds and poultry around the world, influenza A viruses carrying 15 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been described. Here we describe a previously unidentified antigenic subtype of HA (H16), detected in viruses circulating in black-headed gulls in Sweden. In agreement with established criteria for the definition of antigenic subtypes, hemagglutination inhibition assays and immunodiffusion assays failed to detect specific reactivity between H16 and the previously described subtypes H1 to H15. Genetically, H16 HA was found to be distantly related to H13 HA, a subtype also detected exclusively in shorebirds, and the amino acid composition of the putative receptor-binding site of H13 and H16 HAs was found to be distinct from that in HA subtypes circulating in ducks and geese. The H16 viruses contained NA genes that were similar to those of other Eurasian shorebirds but genetically distinct from N3 genes detected in other birds and geographical locations. The European gull viruses were further distinguishable from other influenza A viruses based on their PB2, NP, and NS genes. Gaining information on the full spectrum of avian influenza A viruses and creating reagents for their detection and identification will remain an important task for influenza surveillance, outbreak control, and animal and public health. We propose that sequence analyses of HA and NA genes of influenza A viruses be used for the rapid identification of existing and novel HA and NA subtypes.
TL;DR: The Artemis Comparison Tool (ACT) allows an interactive visualisation of comparisons between complete genome sequences and associated annotations and so inherits powerful searching and analysis tools.
Abstract: The Artemis Comparison Tool (ACT) allows an interactive visualisation of comparisons between complete genome sequences and associated annotations. The comparison data can be generated with several different programs; BLASTN, TBLASTX or Mummer comparisons between genomic DNA sequences, or orthologue tables generated by reciprocal FASTA comparison between protein sets. It is possible to identify regions of similarity, insertions and rearrangements at any level from the whole genome to base-pair differences. ACT uses Artemis components to display the sequences and so inherits powerful searching and analysis tools. ACT is part of the Artemis distribution and is similarly open source, written in Java and can run on any Java enabled platform, including UNIX, Macintosh and Windows.
Availability: ACT is freely available (under a GPL licence) for download from the Sanger Institute web site, http://www.sanger.ac.uk
Contact: artemis@sanger.ac.uk
TL;DR: This work shows a rapid, massive conversion of proliferative crypt cells into post-mitotic goblet cells after conditional removal of the common Notch pathway transcription factor CSL/RBP-J and indicates that γ-secretase inhibitors, developed for Alzheimer's disease, might be of therapeutic benefit in colorectal neoplastic disease.
Abstract: The self-renewing epithelium of the small intestine is ordered into stem/progenitor crypt compartments and differentiated villus compartments. Recent evidence indicates that the Wnt cascade is the dominant force in controlling cell fate along the crypt-villus axis. Here we show a rapid, massive conversion of proliferative crypt cells into post-mitotic goblet cells after conditional removal of the common Notch pathway transcription factor CSL/RBP-J. We obtained a similar phenotype by blocking the Notch cascade with a gamma-secretase inhibitor. The inhibitor also induced goblet cell differentiation in adenomas in mice carrying a mutation of the Apc tumour suppressor gene. Thus, maintenance of undifferentiated, proliferative cells in crypts and adenomas requires the concerted activation of the Notch and Wnt cascades. Our data indicate that gamma-secretase inhibitors, developed for Alzheimer's disease, might be of therapeutic benefit in colorectal neoplastic disease.
TL;DR: A systematic review of previous studies of the prevalence of PDD using PubMed to search the literature suggests that 24 to 31% of PD patients have dementia, and that 3 to 4% of the dementia in the population would be due to PDD.
Abstract: Prevalence rates of depressive disorders in Parkinson's disease (PD) vary widely across studies, ranging from 2.7% to more than 90%. The aim of this systematic review was to calculate average prevalences of depressive disorders taking into account the different settings and different diagnostic approaches of studies. Using Medline on Pubmed, a systematic literature search was carried out for studies of depression in Parkinson's disease. A total of 104 articles were included and assessed for quality; 51 articles fulfilled the quality criteria. Multiple publications from the same database were not included in the meta-analysis. In the remaining 36 articles, the weighted prevalence of major depressive disorder was 17% of PD patients, that of minor depression 22% and dysthymia 13%. Clinically significant depressive symptoms, irrespective of the presence of a DSM defined depressive disorder, were present in 35%. In studies using a (semi) structured interview to establish DSM criteria, the reported prevalence of major depressive disorder was 19%, while in studies using DSM criteria without a structured interview, the reported prevalence of major depressive disorder was 7%. Population studies report lower prevalence rates for both major depressive disorder and the clinically significant depressive symptoms than studies in other settings. This systematic review suggests that the average prevalence of major depressive disorder in PD is substantial, but lower than generally assumed.
TL;DR: There is a significant repression of quadruplexes in the coding strand of exonic regions, which suggests that quadruplex-forming patterns are disfavoured in sequences that will form RNA.
Abstract: Guanine-rich DNA sequences of a particular form have the ability to fold into four-stranded structures called G-quadruplexes. In this paper, we present a working rule to predict which primary sequences can form this structure, and describe a search algorithm to identify such sequences in genomic DNA. We count the number of quadruplexes found in the human genome and compare that with the figure predicted by modelling DNA as a Bernoulli stream or as a Markov chain, using windows of various sizes. We demonstrate that the distribution of loop lengths is significantly different from what would be expected in a random case, providing an indication of the number of potentially relevant quadruplex-forming sequences. In particular, we show that there is a significant repression of quadruplexes in the coding strand of exonic regions, which suggests that quadruplex-forming patterns are disfavoured in sequences that will form RNA.
TL;DR: This work directly demonstrates transcriptional bursting in Escherichia coli, similar to that indirectly inferred for eukaryotes, and extends protein-based approaches by counting the integer-valued number of transcript with single-molecule resolution.
TL;DR: There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.
Abstract: Context Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.
Wellcome Trust Sanger Institute1, Seattle Biomed2, Katholieke Universiteit Leuven3, GATC Biotech4, Max Planck Society5, Washington University in St. Louis6, University of Trieste7, International Centre for Genetic Engineering and Biotechnology8, European Bioinformatics Institute9, University of São Paulo10, National Scientific and Technical Research Council11, Université catholique de Louvain12, University of London13, University of Edinburgh14, University of Glasgow15, University of Wisconsin-Madison16, University of York17, University of Cambridge18, University of Washington19
TL;DR: The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Tritryp genomes suggest that the mechanisms regulating RNA polymerase II–directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling.
Abstract: Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.
George Washington University1, Seattle Biomed2, University of Washington3, J. Craig Venter Institute4, Karolinska Institutet5, University of California, Los Angeles6, Universidade Federal de Minas Gerais7, Uppsala University8, Centre national de la recherche scientifique9, University of Glasgow10, University of Cambridge11, Federal University of São Paulo12, Children's Hospital Oakland Research Institute13, Johns Hopkins University School of Medicine14, National Research Council15, University of Oxford16, University of London17, University of Massachusetts Amherst18, Oswaldo Cruz Foundation19, University of Buenos Aires20, Central University of Venezuela21, National University of Singapore22, University of Georgia23
TL;DR: Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
Abstract: Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.