Showing papers by "Trinity College, Dublin published in 2008"
TL;DR: Graphene dispersions with concentrations up to approximately 0.01 mg ml(-1), produced by dispersion and exfoliation of graphite in organic solvents such as N-methyl-pyrrolidone are demonstrated.
Abstract: Fully exploiting the properties of graphene will require a method for the mass production of this remarkable material. Two main routes are possible: large-scale growth or large-scale exfoliation. Here, we demonstrate graphene dispersions with concentrations up to approximately 0.01 mg ml(-1), produced by dispersion and exfoliation of graphite in organic solvents such as N-methyl-pyrrolidone. This is possible because the energy required to exfoliate graphene is balanced by the solvent-graphene interaction for solvents whose surface energies match that of graphene. We confirm the presence of individual graphene sheets by Raman spectroscopy, transmission electron microscopy and electron diffraction. Our method results in a monolayer yield of approximately 1 wt%, which could potentially be improved to 7-12 wt% with further processing. The absence of defects or oxides is confirmed by X-ray photoelectron, infrared and Raman spectroscopies. We are able to produce semi-transparent conducting films and conducting composites. Solution processing of graphene opens up a range of potential large-area applications, from device and sensor fabrication to liquid-phase chemistry.
5,600 citations
TL;DR: It is concluded that soluble Aβ oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.
Abstract: Alzheimer's disease constitutes a rising threat to public health. Despite extensive research in cellular and animal models, identifying the pathogenic agent present in the human brain and showing that it confers key features of Alzheimer's disease has not been achieved. We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease. The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus. Soluble Abeta from Alzheimer's disease brain also disrupted the memory of a learned behavior in normal rats. These various effects were specifically attributable to Abeta dimers. Mechanistically, metabotropic glutamate receptors were required for the LTD enhancement, and N-methyl D-aspartate receptors were required for the spine loss. Co-administering antibodies to the Abeta N-terminus prevented the LTP and LTD deficits, whereas antibodies to the midregion or C-terminus were less effective. Insoluble amyloid plaque cores from Alzheimer's disease cortex did not impair LTP unless they were first solubilized to release Abeta dimers, suggesting that plaque cores are largely inactive but sequester Abeta dimers that are synaptotoxic. We conclude that soluble Abeta oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.
3,325 citations
TL;DR: This work has shown that during the demolition phase of apoptosis, members of the caspase family of cysteine proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules.
Abstract: Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses. Much of what happens during the demolition phase of apoptosis is orchestrated by members of the caspase family of cysteine proteases. These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules.
2,372 citations
Massachusetts Institute of Technology1, Harvard University2, Broad Institute3, Cardiff University4, University College London5, University of Edinburgh6, Trinity College, Dublin7, Karolinska Institutet8, Uppsala University9, University of Southern California10, University of Aberdeen11, University of North Carolina at Chapel Hill12, QIMR Berghofer Medical Research Institute13, Royal College of Surgeons in Ireland14, National Health Service15, University of Oxford16, Queen Mary University of London17, State University of New York System18, University of Coimbra19
TL;DR: A genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls provides strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.
Abstract: Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73 - 90% ( ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants ( CNVs) have been identified in individual patients with schizophrenia(2-7) and also in neurodevelopmental disorders(8-11), but large- scale genome- wide surveys have not been performed. Here we report a genome- wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high- density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15- fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single- occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo- cardio- facial syndrome, which includes psychotic symptoms in 30% of patients(12). Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome- wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.
1,465 citations
International Agency for Research on Cancer1, Russian Academy2, Nofer Institute of Occupational Medicine3, Charles University in Prague4, Fred Hutchinson Cancer Research Center5, University of Liverpool6, Cancer Care Ontario7, Princess Margaret Cancer Centre8, Women's College, Kolkata9, Norwegian University of Science and Technology10, German Cancer Research Center11, University of Cambridge12, Umeå University13, University of Bremen14, French Institute of Health and Medical Research15, University of Turin16, University of Aberdeen17, University of Padua18, Newcastle University19, University of Glasgow20, Trinity College, Dublin21
TL;DR: The results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
Abstract: Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
1,226 citations
Cardiff University1, University of Birmingham2, Broad Institute3, University of Pittsburgh4, University of Pennsylvania5, Harvard University6, University of Aberdeen7, King's College London8, Trinity College, Dublin9, Royal Edinburgh Hospital10, University College London11, Royal Victoria Infirmary12
TL;DR: The results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder and found further support for the previously reported CACNA1C.
Abstract: To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.
1,182 citations
TL;DR: It is found that children and adolescents living with domestic violence are at increased risk of experiencing emotional, physical and sexual abuse, of developing emotional and behavioral problems and of increased exposure to the presence of other adversities in their lives.
1,182 citations
TL;DR: The purpose of this article is to present a step-by-step guide to facilitate understanding by presenting the critical elements of the literature review process.
Abstract: Nowadays, most nurses, pre- and post-qualification, will be required to undertake a literature review at some point, either as part of a course of study, as a key step in the research process, or as part of clinical practice development or policy. For student nurses and novice researchers it is often seen as a difficult undertaking. It demands a complex range of skills, such as learning how to define topics for exploration, acquiring skills of literature searching and retrieval, developing the ability to analyse and synthesize data as well as becoming adept at writing and reporting, often within a limited time scale. The purpose of this article is to present a step-by-step guide to facilitate understanding by presenting the critical elements of the literature review process. While reference is made to different types of literature reviews, the focus is on the traditional or narrative review that is undertaken, usually either as an academic assignment or part of the research process.
1,079 citations
TL;DR: Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications, and in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication.
Abstract: Gene duplication provides raw material for functional innovation. Recent advances have shed light on two fundamental questions regarding gene duplication: which genes tend to undergo duplication? And how does natural selection subsequently act on them? Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications. We also know that functional differences between duplicate genes can originate in several different ways, including mutations that directly impart new functions, subdivision of ancestral functions and selection for changes in gene dosage. Interestingly, in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication.
1,065 citations
Cardiff University1, University of Oxford2, University of Cambridge3, Ludwig Maximilian University of Munich4, Trinity College, Dublin5, Shanghai Jiao Tong University6, University of Bonn7, National Institutes of Health8, Fujita Health University9, Hebrew University of Jerusalem10, Northwestern University11, Stanford University12, Louisiana State University13, QIMR Berghofer Medical Research Institute14, Anschutz Medical Campus15, Emory University16, University of Iowa17, Icahn School of Medicine at Mount Sinai18, University of California, San Francisco19, Washington University in St. Louis20
TL;DR: Meta-analysis provided strongest evidence for association around ZNF804A and this strengthened when the affected phenotype including bipolar disorder included bipolar disorder and the overall pattern of replication was unlikely to occur by chance.
Abstract: We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)).
1,050 citations
TL;DR: It is clear that recognition is highly influential in health worker motivation and that adequate resources and appropriate infrastructure can improve morale significantly, but financial incentives alone are not enough to motivate health workers.
Abstract: A key constraint to achieving the MDGs is the absence of a properly trained and motivated workforce. Loss of clinical staff from low and middle-income countries is crippling already fragile health care systems. Health worker retention is critical for health system performance and a key problem is how best to motivate and retain health workers. The authors undertook a systematic review to consolidate existing evidence on the impact of financial and non-financial incentives on motivation and retention.
TL;DR: Cinchona alkaloid derivatives modified to include a (thio)urea component have emerged in the last three years as readily accessible, robust and tunable bifunctional organocatalysts for a range of synthetically useful transformations.
TL;DR: This model provides a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells, and suggests that once the H3K 27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, thereby preserving chromatin structure and transcriptional programs.
Abstract: Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.
TL;DR: A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles, which suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases.
Abstract: Background Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared. Methods We evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent–child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects. Results Three celiac disease loci — RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25 — were associated with type 1 diabetes (P<1.00×10−4). The 32-bp insertion–deletion variant on chromosome 3p21 was newly identified as a type 1 diabetes locus (P=1.81×1...
Queen Mary University of London1, Utrecht University2, Trinity College, Dublin3, University of Groningen4, University of Oxford5, Wellcome Trust Sanger Institute6, University of Leeds7, Imperial College London8, University of Sheffield9, VU University Amsterdam10, Leiden University11, National University of Ireland12, University of London13, University of Bristol14
TL;DR: This extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways and identified seven previously unknown risk regions.
Abstract: Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.
TL;DR: Accumulating evidence on how viral infection and PRR signalling pathways intersect is providing further insights into the function of the pathways involved, their constituent proteins and ways in which they could be manipulated therapeutically.
Abstract: The expression of pattern-recognition receptors (PRRs) by immune and tissue cells provides the host with the ability to detect and respond to infection by viruses and other microorganisms. Significant progress has been made from studying this area, including the identification of PRRs, such as Toll-like receptors and RIG-I-like receptors, and the description of the molecular basis of their signalling pathways, which lead to the production of interferons and other cytokines. In parallel, common mechanisms used by viruses to evade PRR-mediated responses or to actively subvert these pathways for their own benefit are emerging. Accumulating evidence on how viral infection and PRR signalling pathways intersect is providing further insights into the function of the pathways involved, their constituent proteins and ways in which they could be manipulated therapeutically.
TL;DR: The IL‐1R/Toll‐like receptor superfamily was first defined in 1998 as a family of proteins that contain the Toll‐IL‐1 receptor domain, and remarkable progress has been made in understanding of the functions of the TLRs, leading to a renaissance of interest in innate immunity.
Abstract: Summary: The interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily was first defined in 1998 as a family of proteins that contain the Toll-IL-1 receptor domain. At that time, there were a number of orphan receptors in the IL-1R branch, and the TLRs had yet to be shown to be key innate immune receptors that sense microbial products. We now know a great deal more about this superfamily, with the description of novel IL-1 family members such as IL-1F6 signaling via IL-1Rrp2 and IL33 signaling via ST2. Remarkable progress has been made in our understanding of the functions of the TLRs, leading to a renaissance of interest in innate immunity. The importance of IL-1 is also being rediscovered, with the observation that Nalp3 is a key regulator of caspase-1, the enzyme that processes pro-IL-1β into the mature cytokine. This area has therefore proved very fruitful in terms of improving our knowledge of the molecular basis for innate immunity and inflammation, and we can anticipate further discoveries in the coming years.
TL;DR: In this paper, the authors present estimates of the fraction of the adult population using formal financial intermediaries using bank and micro-finance data. And they compare these estimates with household surveys for a smaller set of countries.
Abstract: This paper presents estimates, for more than 160 countries, of the fraction of the adult population using formal financial intermediaries. The estimates are constructed by combining information on account numbers at banks and microfinance institutions (together with banking depth and GDP data) with estimates from household surveys for a smaller set of countries. An illustrative application of the data compares them with information on poverty: there is a correlation, but it is not clearly causal.
TL;DR: A minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract, is developed to improve reporting of abstracts of RCTs published in journal articles and conference proceedings.
Abstract: Background Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract
TL;DR: It is demonstrated that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL -AF4-driven gene expression.
European Bioinformatics Institute1, Natural Environment Research Council2, Wellcome Trust Sanger Institute3, University of Cambridge4, Stanford University5, Swiss Institute of Bioinformatics6, University of British Columbia7, Livestrong Foundation8, Institute for Systems Biology9, University of California, Davis10, Lockheed Martin Corporation11, University of Edinburgh12, Newcastle University13, Medical Research Council14, Aberystwyth University15, National Science Foundation16, Beilstein-Institut17, National Institutes of Health18, Boston Children's Hospital19, Norwegian University of Science and Technology20, University of Georgia21, University of California, Berkeley22, University of Texas Southwestern Medical Center23, Lancaster University24, German Cancer Research Center25, University of Manchester26, Harvard University27, Iowa State University28, Bristol-Myers Squibb29, University at Buffalo30, AstraZeneca31, Trinity College, Dublin32, Wageningen University and Research Centre33, Ghent University34
TL;DR: The Minimum Information for Biological and Biomedical Investigations (MIBBI) project aims to foster the coordinated development of minimum-information checklists and provide a resource for those exploring the range of extant checklists.
Abstract: The Minimum Information for Biological and Biomedical Investigations (MIBBI) project aims to foster the coordinated development of minimum-information checklists and provide a resource for those exploring the range of extant checklists.
TL;DR: The genome sequences of a new clinical isolate of the important human pathogen, Aspergillus fumigatus, A1163, and two closely related but rarely pathogenic species, Neosartorya fischeri NRRL181 and As pergillus clavatus NRRL1 are presented.
Abstract: We present the genome sequences of a new clinical isolate of the important human pathogen, Aspergillus fumigatus, A1163, and two closely related but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of A1163 with the recently sequenced A. fumigatus isolate Af293 has identified core, variable and up to 2% unique genes in each genome. While the core genes are 99.8% identical at the nucleotide level, identity for variable genes can be as low 40%. The most divergent loci appear to contain heterokaryon incompatibility (het) genes associated with fungal programmed cell death such as developmental regulator rosA. Cross-species comparison has revealed that 8.5%, 13.5% and 12.6%, respectively, of A. fumigatus, N. fischeri and A. clavatus genes are species-specific. These genes are significantly smaller in size than core genes, contain fewer exons and exhibit a subtelomeric bias. Most of them cluster together in 13 chromosomal islands, which are enriched for pseudogenes, transposons and other repetitive elements. At least 20% of A. fumigatus-specific genes appear to be functional and involved in carbohydrate and chitin catabolism, transport, detoxification, secondary metabolism and other functions that may facilitate the adaptation to heterogeneous environments such as soil or a mammalian host. Contrary to what was suggested previously, their origin cannot be attributed to horizontal gene transfer (HGT), but instead is likely to involve duplication, diversification and differential gene loss (DDL). The role of duplication in the origin of lineage-specific genes is further underlined by the discovery of genomic islands that seem to function as designated “gene dumps” and, perhaps, simultaneously, as “gene factories”.
TL;DR: The observations provide a molecular basis for the different phenotypes seen in mice lacking either caspase and indicate that these proteases occupy nonredundant roles within the cell death machinery.
Abstract: Members of the caspase family of cysteine proteases play central roles in coordinating the stereotypical events that occur during apoptosis. Because the major executioner caspases, caspase-3 and caspase-7, exhibit almost indistinguishable activity toward certain synthetic peptide substrates, this has led to the widespread view that these proteases occupy functionally redundant roles within the cell death machinery. However, the distinct phenotypes of mice deficient in either of these caspases, as well as mice deficient in both, is at odds with this view. These distinct phenotypes could be related to differences in the relative expression levels of caspase-3 and caspase-7 in vivo, or due to more fundamental differences between these proteases in terms of their ability to cleave natural substrates. Here we show that caspase-3 and caspase-7 exhibit differential activity toward multiple substrate proteins, including Bid, XIAP, gelsolin, caspase-6, and cochaperone p23. Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. Our observations provide a molecular basis for the different phenotypes seen in mice lacking either caspase and indicate that these proteases occupy nonredundant roles within the cell death machinery.
TL;DR: In this article, a rapid and readily reproducible seed-based method for the production of high quality silver nanoprisms in high yield is presented, where the edge length and the position of the main plasmon resonance can be readily controlled through adjustment of reaction conditions.
Abstract: A rapid and readily reproducible seed-based method for the production of high quality silver nanoprisms in high yield is presented. The edge-length and the position of the main plasmon resonance of the nanoprisms can be readily controlled through adjustment of reaction conditions. From UV-vis spectra of solutions of the nanoprisms, the inhomogeneously broadened line width of the in-plane dipole plasmon resonance is measured and trends in the extent of plasmon damping as a function of plasmon resonance energy and nanoprism size have been elucidated. In addition, an in-depth analysis of the lamellar defect structure of silver nanoprisms is provided that confirms that the defects can lead to a transformation of the crystal structure in the vicinity of the defects. These defects can combine give rise to lamellar regions, thicker than 1 nm, that extend across the crystal, where the silver atoms are arranged in a continuous hexagonal-close-packed (hcp) structure. This hcp structure has a periodicity of 2.50 A, thus explaining the 2.50 A lattice fringes that are commonly observed in 〈111〉 oriented flat-lying nanoprisms. A new understanding of the mechanisms behind anisotropic growth in silver nanoprisms is presented.
TL;DR: It was observed that mechanical non-surgical therapy could be effective in the treatment of peri-implant mucositis lesions and the adjunctive use of antimicrobial mouth rinses enhanced the outcome of mechanical therapy of such mucositIS lesions.
Abstract: OBJECTIVES: To review the literature on non-surgical treatment of peri-implant mucositis and peri-implantitis. MATERIAL AND METHODS: A search of PubMed and The Cochrane Library of the Cochrane Coll ...
TL;DR: It is expected that key management, handling of congestion, multicasting capability, and routing will remain active areas of research and development, and that DTN may continue to be an active research endeavor for at least the next few years.
Abstract: We review the rationale behind the current design of the Delay/Disruption Tolerant Networking (DTN) Architecture and highlight some remaining open issues. Its evolution, from a focus on deep space to a broader class of heterogeneous networks that may suffer disruptions, affected design decisions spanning naming and addressing, message formats, data encoding methods, routing, congestion management and security. Having now achieved relative stability with the design, additional experience is required in long-running operational environments in order to fine tune our understanding of DTN concepts and the types of capabilities that are worth the investment in implementation complexity. We expect key management, handling of congestion, multicasting capability, and routing to remain active areas of research and development, and that DTN may continue to be an active research endeavor for at least the next few years.
TL;DR: It is reported that MRSA biofilm development was promoted under mildly acidic growth conditions triggered by the addition of glucose to the growth medium and identified a novel S. aureus biofilm phenotype promoted by FnBPA and FnBPB which is apparently independent of the known ligand-binding activities of these multifunctional surface proteins.
Abstract: Device-associated infections involving biofilm remain a persistent clinical problem. We recently reported that four methicillin-resistant Staphylococcus aureus (MRSA) strains formed biofilm independently of the icaADBC-encoded exopolysaccharide. Here, we report that MRSA biofilm development was promoted under mildly acidic growth conditions triggered by the addition of glucose to the growth medium. Loss of sortase, which anchors LPXTG-containing proteins to peptidoglycan, reduced the MRSA biofilm phenotype. Furthermore introduction of mutations in fnbA and fnbB, which encode the LPXTG-anchored multifunctional fibrinogen and fibronectin-binding proteins, FnBPA and FnBPB, reduced biofilm formation by several MRSA strains. However, these mutations had no effect on biofilm formation by methicillin-sensitive S. aureus strains. FnBP-promoted biofilm occurred at the level of intercellular accumulation and not primary attachment. Mutation of fnbA or fnbB alone did not substantially affect biofilm, and expression of either gene alone from a complementing plasmid in fnbA fnbB mutants restored biofilm formation. FnBP-promoted biofilm was dependent on the integrity of SarA but not through effects on fnbA or fnbB transcription. Using plasmid constructs lacking regions of FnBPA to complement an fnbAB mutant revealed that the A domain alone and not the domain required for fibronectin binding could promote biofilm. Additionally, an A-domain N304A substitution that abolished fibrinogen binding did not affect biofilm. These data identify a novel S. aureus biofilm phenotype promoted by FnBPA and FnBPB which is apparently independent of the known ligand-binding activities of these multifunctional surface proteins.
TL;DR: In this article, a Markov continuous Markov stochastic process is used to make inference on a partially observed monotone stochastically varying rate of sedimentation in lake sediment cores.
Abstract: Summary. We propose a new and simple continuous Markov monotone stochastic process and use it to make inference on a partially observed monotone stochastic process. The process is piecewise linear, based on additive independent gamma increments arriving in a Poisson fashion. An independent increments variation allows very simple conditional simulation of sample paths given known values of the process. We take advantage of a reparameterization involving the Tweedie distribution to provide efficient computation. The motivating problem is the establishment of a chronology for samples taken from lake sediment cores, i.e. the attribution of a set of dates to samples of the core given their depths, knowing that the age–depth relationship is monotone. The chronological information arises from radiocarbon (14C) dating at a subset of depths. We use the process to model the stochastically varying rate of sedimentation.
TL;DR: The first measurement of strong magneto-chiral dichroism in an enantiopure chiral ferromagnet is reported, which is based on an enantioselective self-assembly that imposes the absolute configurations of the metal centres within chromium-manganese two-dimensional oxalate layers.
Abstract: As materials science is moving towards the synthesis, the study and the processing of new materials exhibiting well-defined and complex functions, the synthesis of new multifunctional materials is one of the important challenges. One of these complex physical properties is magneto-chiral dichroism which arises, at second order, from the coexistence of spatial asymmetry and magnetization in a material. Herein we report the first measurement of strong magneto-chiral dichroism in an enantiopure chiral ferromagnet. The ab initio synthesis of the enantiopure chiral ferromagnet is based on an enantioselective self-assembly, where a resolved chiral quaternary ammonium cation imposes the absolute configurations of the metal centres within chromium-manganese two-dimensional oxalate layers. The ferromagnetic interaction between Cr(III) and Mn(II) ions leads to a Curie temperature of 7 K. The magneto-chiral dichroic effect is enhanced by a factor of 17 when entering into the ferromagnetic phase.
TL;DR: In this article, a survey of recent research focusing on core biomarker candidates for early diagnosis, classification, progression, and prediction of Alzheimer's disease (AD) is presented. But, the most promising biomarkers derived from structural and functional neuroimaging and those measured in cerebrospinal fluid (CSF) and plasma show the greatest promise.
Abstract: Background In the earliest clinical stages of Alzheimer’s disease (AD) when symptoms are mild, clinical diagnosis can be difficult. AD pathology most likely precedes symptoms. Biomarkers can serve as early diagnostic indicators or as markers of preclinical pathologic change. Candidate biomarkers derived from structural and functional neuroimaging and those measured in cerebrospinal fluid (CSF) and plasma show the greatest promise. Unbiased exploratory approaches, eg, proteomics or cortical thickness analysis, could yield novel biomarkers. The objective of this article was to review recent progress in selected imaging and neurochemical biomarkers for early diagnosis, classification, progression, and prediction of AD. Methods We performed a survey of recent research, focusing on core biomarker candidates in AD. Results A number of in vivo neurochemistry and neuroimaging techniques, which can reliably assess aspects of physiology, pathology, chemistry, and neuroanatomy, hold promise as biomarkers. These neurobiologic measures appear to relate closely to pathophysiologic, neuropathologic, and clinical data, such as hyperphosphorylation of tau, amyloid beta (Aβ) metabolism, lipid peroxidation, pattern and rate of atrophy, loss of neuronal integrity, functional and cognitive decline, as well as risk of future decline. Current advances in the neuroimaging of mediotemporal, neocortical, and subcortical areas of the brain of mild cognitive impairment (MCI) and AD subjects are presented. CSF levels of Aβ42, tau, and hyperphosphorylated tau protein (p-tau) can distinguish subjects with MCI who are likely to progress to AD. They also show preclinical alterations that predict later development of early AD symptoms. Studies on plasma Aβ are not entirely consistent, but recent findings suggest that decreased plasma Aβ42 relative to Aβ40 might increase the risk of AD. Increased production of Aβ in aging is suggested by elevation of BACE1 protein and enzyme activity in the brain and CSF of subjects with MCI. CSF tau and p-tau are increased in MCI as well and show predictive value. Other biomarkers might indicate components of a cascade initiated by Aβ, such as oxidative stress or inflammation. These merit further study in MCI and earlier. Conclusions A number of neuroimaging candidate markers are promising, such as hippocampus and entorhinal cortex volumes, basal forebrain nuclei, cortical thickness, deformation-based and voxel-based morphometry, structural and effective connectivity by using diffusion tensor imaging, tractography, and functional magnetic resonance imaging. CSF Aβ42, BACE1, total tau, and p-tau are substantially altered in MCI and clinical AD. Other interesting novel marker candidates derived from blood are being currently proposed (phase I). Biomarker discovery through proteomic approaches requires further research. Large-scale international controlled multicenter trials (such as the U.S., European, Australian, and Japanese Alzheimer’s Disease Neuroimaging Initiative and the German Dementia Network) are engaged in phase III development of the core feasible imaging and CSF biomarker candidates in AD. Biomarkers are in the process of implementation as primary outcome variables into regulatory guideline documents regarding study design and approval for compounds claiming disease modification.