Gene Expression Commons: an open platform for absolute gene expression profiling.

Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000) of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/) which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples

Persistent anti-brane singularities

Anti-D-branes inserted in warped throat geometries (supported by fluxes that carry D-brane charges) develop unphysical singularities. It has been argued that these singularities could be resolved when one goes beyond the linearized approximation or includes the effects of brane polarization. In this paper we consider anti-D6 branes, whose singularities have been shown to exist at the full non-linear level, and demonstrate that there is no D8 brane polarization that can resolve the singularity. We comment on the potential implications of this result for the resolution of anti-D3 brane singularities in the Klebanov-Strassler geometry.Comment: 16 pages; v2: comments added, version to appear in JHE

Analisis Strategi Pengelolaan Ekosistem Terumbu Karang Berbasis Resiliensi (Studi Kasus di Teluk Doreri, Kabupaten Manokwari)

Pengelolaan terumbu karang berbasis resiliensi merupakan paradigma baru dan telah menjadi konsep kunci untuk mendukung kemampuan sistem terumbu karang dalam menghadapi tekanan lokal dan dampak perubahan iklim. Pengelolaan berbasis resiliensi mencakup dua aspek penting, yaitu penilaian potensi resiliensi secara spasial dan perencanaan atau strategi pengelolaan yang sesuai dengan kondisi resiliensi sistem terumbu karang. Sejauh ini penelitian-penelitian untuk menentukan indikatorindikator penilaian resiliensi telah mengalami kemajuan yang berarti, namun masih terbatas dalam kerangka kerja untuk merumuskan strategi pengelolaan berdasarkan kondisi resiliensi ekosistem terumbu karang. Penelitian ini mengkombinasikan pendekatan-pendekatan yang berbeda dalam penilaian resiliensi ekosistem terumbu karang, yaitu penilaian potensi rezime/status terumbu karang, penilaian potensi resiliensi dan penilaian potensi tekanan/stres dalam satu kerangka kerja (framework) untuk menentukan tindakan dan strategi pengelolaan ekosistem terumbu karang di kawasan Teluk Doreri, Kabupaten Manokwari. Tujuan penelitian ini adalah: 1) menganalisis status dan potensi rezim-rezim terumbu yang ada di ekosistem terumbu karang; 2) menganalisis potensi resiliensi ekologi terumbu karang; 3) menganalisis potensi tekanan aktivitas manusia terhadap terumbu karang; 4) memodelkan skenario perubahan tekanan terhadap resiliensi dan status terumbu karang; 5) merumuskan strategi pengelolaan yang mendukung resiliensi dan keberlanjutan ekosistem terumbu karang. Penelitian ini akan berkontribusi dalam mengisi kekosongan basis data terumbu karang, menyediakan informasi tentang kondisi terkini resiliensi ekosistem terumbu karang, serta berkontribusi dalam penyempurnaan kerangka kerja yang mengakomodir aspek penilaian resiliensi dalam perencanaan pengelolaan terumbu karang. Penelitian ini menerapkan metode deskriptif dengan observasi lapangan, studi dokumentasi, studi pustaka dan pemodelan statistik sebagai sumber datanya. Variabelvariabel yang digunakan dikelompokkan dalam 3 kelompok variabel, yaitu variabel proses, variabel tekanan dan variabel habitat bentik. Data dikumpulkan dengan menerapkan pendekatan lapangan (observasi dan wawancara), analisis laboratorium dan analisis spasial. Potensi rezim terumbu karang dinilai dengan menerapkan statistik deskriptif (mean±SE), analisis PSI (phase shift index), korelasi PCA, hierarchical cluster, dan K-means cluster. Pola spasial perubahan terumbu karang diperoleh melalui pemrosesan citra satelit Landsat multisensor dan multitemporal. Analisis potensi resiliensi relatif dan potensi tekanan mengikuti metode perhitungan menurut Maynard et al. (2015) yang meliputi proses kompilasi, normalisasi, pengaturan skala satu arah, perhitungan nilai rata-rata, perhitungan nilai potensi relatif dan penentuan ranking lokasi/site. Penentuan tindakan pengelolaan dilakukan melalui kueri nilai potensi resiliensi dan tekanan terhadap kriteria pengelolaan. Analisis persepsi masyarakat dilakukan melalui penerapan metode tabulasi yang didahului proses editing dan coding. Metode hybrid A’WOT diterapkan untuk analisis prioritas strategi pengelolaan ekosistem terumbu karang. Hasil menunjukkan bahwa rata-rata persentase karang hidup di Teluk Doreri 46,75%, dimana tergolong cukup baik, namun demikian ada potensi perkembangan rezim abiotik dan alga yang diperkuat dengan pola spasial tren pengurangan tutupan karang hidup yang cukup tajam dalam kurun waktu 15 tahun terakhir. Potensi resiliensi ekosistem terumbu karang umumnya masih cukup baik berdasarkan indikator-indikator proses resiliensi, namun terdapat kelemahan pada aspek indikator biomassa dan kehadiran kelompok fungsional ikan herbivora. Hampir 50% lokasi yang disurvei menghadapi potensi tekanan atau stress yang tinggi, bahkan 70% lokasi mengalami tekanan tinggi khusus dalam bentuk tekanan penangkapan. Hasil queri terhadap kriteria-kriteria penentuan area target dan tindakan pengelolaan menunjukkan bahwa pengelolaan perikanan dan penegakan hukum adalah prioritas yang utama, disamping juga pemantauan pemutihan karang (bleaching) dan dukungan pemulihan. Prioritas strategi utama adalah meningkatkan keterpaduan antar sektor dan stakeholder dalam pengelolaan terumbu karang, membangun perilaku dan partisipasi aktif masyakat dalam pelestarian dan pengelolaan ekosistem terumbu karang, dan meningkatkan pemantauan kondisi terumbu karang dan efektifitas penegakan hukum. Berdasarkan hasil disarankan program pemantauan jangka panjang juga perlu dilakukan untuk memperoleh tren indikator-indikator proses resiliensi dan tantangan resiliensi. Disamping itu perlu upaya untuk meningkatkan kesadaran, pemahaman, serta dukungan dan partisipasi masyarakat dalam pengelolaan ekosistem terumbu karang mulai dari proses perencanaan sampai pengawasan dan evaluasi

Comprehensive methylome map of lineage commitment from haematopoietic progenitors.

Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions

D-brane potentials in the warped resolved conifold and natural inflation

In this paper we obtain a model of Natural Inflation from string theory with a Planckian decay constant. We investigate D-brane dynamics in the background of the warped resolved conifold (WRC) throat approximation of Type IIB string compactifications on Calabi-Yau manifolds. When we glue the throat to a compact bulk Calabi-Yau, we generate a D-brane potential which is a solution to the Laplace equation on the resolved conifold. We can exactly solve this equation, including dependence on the angular coordinates. The solutions are valid down to the tip of the resolved conifold, which is not the case for the more commonly used deformed conifold. This allows us to exploit the effect of the warping, which is strongest at the tip. We inflate near the tip using an angular coordinate of a D5-brane in the WRC which has a discrete shift symmetry, and feels a cosine potential, giving us a model of Natural Inflation, from which it is possible to get a Planckian decay constant whilst maintaining control over the backreaction. This is because the decay constant for a wrapped brane contains powers of the warp factor, and so can be made large, while the wrapping parameter can be kept small enough so that backreaction is under control.Comment: 41 pages, 3 appendices, 1 figure, PDFLaTex; various clarifications added along with a new appendix on b-axions and wrapped D5 branes;version matches the one published in JHE

Higher Spin Black Holes from CFT

Higher spin gravity in three dimensions has explicit black holes solutions, carrying higher spin charge. We compute the free energy of a charged black hole from the holographic dual, a 2d CFT with extended conformal symmetry, and find exact agreement with the bulk thermodynamics. In the CFT, higher spin corrections to the free energy can be calculated at high temperature from correlation functions of W-algebra currents.Comment: 24 pages; v2 reference adde

The use of chlorhexidine in the prevention of alveolar osteitis after third molar extractions

Data sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medline through PubMed, Scopus, Science Direct, ISI Web of Science, Evidence-Based Dentistry, ClinicalTrials.gov, the European Union Clinical Trials Register, the Spanish General University Board database of doctoral theses in Spain (TESEO), the Spanish National Research Council (CSIC) bibliographic databases, and the Spanish Medical Index (IME).Study selection: Randomised controlled trials (RCTs) (with or without placebo) of patients of any age or gender who underwent maxillary or mandibular third molar extractions. Studies were required to have analysed the efficacy of only chlorhexidine in any concentration, formulation or treatment regimen for preventing alveolar osteitis (AO). There was no language restriction.Data extraction and synthesis: Data extraction was carried out independently by two researchers, and a third researcher was consulted in case of disagreements. When explicit data were not stated in the text, they were calculated using data from the tables where possible. In addition, authors were contacted to obtain any necessary missing information. Datasets were assessed for heterogeneity, and meta-analysis was conducted on homogenous datasets. Publication bias was assessed through funnel plots. The research was conducted and is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Results: Twenty-three studies published from 1979 to 2015, corresponding to 18 trials (16 parallel-group and two split-mouth RCTs), that reported on 2,824 third molar extractions (1,458 in experimental group and 1,366 in control group) were included. The overall relative risk (RR) was 0.53 (95% CI, 0.45-0.62; PConclusions: The use of chlorhexidine, in any formulation (rinse or gel), concentration (0.12% or 0.20%), or regimen (before, during and/or after surgery), is efficacious and effective in preventing AO in patients who have undergone third molar extraction. The findings showed that in order to prevent one case of AO, eight patients would have to be treated with chlorhexidine. Chlorhexidine gel was found to be moderately more efficacious than the rinse formulation.</p

Quantum fluctuations can promote or inhibit glass formation

The very nature of glass is somewhat mysterious: while relaxation times in glasses are of sufficient magnitude that large-scale motion on the atomic level is essentially as slow as it is in the crystalline state, the structure of glass appears barely different than that of the liquid that produced it. Quantum mechanical systems ranging from electron liquids to superfluid helium appear to form glasses, but as yet no unifying framework exists connecting classical and quantum regimes of vitrification. Here we develop new insights from theory and simulation into the quantum glass transition that surprisingly reveal distinct regions where quantum fluctuations can either promote or inhibit glass formation.Comment: Accepted for publication in Nature Physics. 22 pages, 3 figures, 1 Tabl

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

Toxic metal enrichment and boating intensity: sediment records of antifoulant copper in shallow lakes of eastern England

Tributyltin (TBT), an aqueous biocide derived from antifouling paint pollution, is known to have impacted coastal marine ecosystems, and has been reported in the sediment of the Norfolk and Suffolk Broads, a network of rivers and shallow lakes in eastern England. In the marine environment, the 1987 TBT ban has resulted in expanded use of alternative biocides, raising the question of whether these products too have impacted the Broads ecosystem and freshwaters in general. Here we examine the lake sediment record in the Norfolk and Suffolk Broads for contamination by copper (Cu) (as an active biocide agent) and zinc (Zn) (as a component of booster biocides), to assess their occurrence and potential for causing environmental harm in freshwater ecosystems. We find that, after the introduction of leisure boating, there is a statistically significant difference in Cu enrichment between heavily and lightly boated sites, while no such difference exists prior to this time. At the heavily boated sites the onset of Cu enrichment coincides with a period of rapid increase in leisure boating. Such enrichment is maintained to the present day, with some evidence of continued increase. We conclude that Cu-based antifouling has measurably contaminated lakes exposed to boating, at concentrations high enough to cause ecological harm. Similar findings can be expected at other boated freshwater ecosystems elsewhere in the world