Optimization Design on Ventilation Openings of Super Large Circular Coal Storage Dome

In order to reduce the pollution of the atmospheric environment, the super large coal storage warehouse has gradually become the main coal storage mode of power plants and other enterprises. However, due to the enclosed structural form, volatile coal dust and coal seam volatile combustible gas concentration is too high, which resulting in increased risk of ignition detonation. Therefore, this paper based on ventilation engineering theory and combined with CFD which focus on natural ventilation used in large diameter (D = 100 m) circular coal storage dome. The impact of opening modes, opening positions and opening size of super large circular coal storage dome on ventilated characteristics were also studied. The designed method of ventilated openings for super large circular coal storage dome is further proposed

Ectopic A-lattice seams destabilize microtubules

Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe

Detection of Gene Expression in an Individual Cell Type within a Cell Mixture Using Microarray Analysis

BACKGROUND: A central issue in the design of microarray-based analysis of global gene expression is the choice between using cells of single type and a mixture of cells. This study quantified the proportion of lipopolysaccharide (LPS) induced differentially expressed monocyte genes that could be measured in peripheral blood mononuclear cells (PBMC), and determined the extent to which gene expression in the non-monocyte cell fraction diluted or obscured fold changes that could be detected in the cell mixture. METHODOLOGY/PRINCIPAL FINDINGS: Human PBMC were stimulated with LPS, and monocytes were then isolated by positive (Mono+) or negative (Mono-) selection. The non-monocyte cell fraction (MonoD) remaining after positive selection of monocytes was used to determine the effect of non-monocyte cells on overall expression. RNA from LPS-stimulated PBMC, Mono+, Mono- and MonoD samples was co-hybridised with unstimulated RNA for each cell type on oligonucleotide microarrays. There was a positive correlation in gene expression between PBMC and both Mono+ (0.77) and Mono- (0.61-0.67) samples. Analysis of individual genes that were differentially expressed in Mono+ and Mono- samples showed that the ability to detect expression of some genes was similar when analysing PBMC, but for others, differential expression was either not detected or changed in the opposite direction. As a result of the dilutional or obscuring effect of gene expression in non-monocyte cells, overall about half of the statistically significant LPS-induced changes in gene expression in monocytes were not detected in PBMC. However, 97% of genes with a four fold or greater change in expression in monocytes after LPS stimulation, and almost all (96-100%) of the top 100 most differentially expressed monocyte genes were detected in PBMC. CONCLUSIONS/SIGNIFICANCE: The effect of non-responding cells in a mixture dilutes or obscures the detection of subtle changes in gene expression in an individual cell type. However, for studies in which only the most highly differentially expressed genes are of interest, separating and analysing individual cell types may be unnecessary

Epistasis of Transcriptomes Reveals Synergism between Transcriptional Activators Hnf1α and Hnf4α

The transcription of individual genes is determined by combinatorial interactions between DNA–binding transcription factors. The current challenge is to understand how such combinatorial interactions regulate broad genetic programs that underlie cellular functions and disease. The transcription factors Hnf1α and Hnf4α control pancreatic islet β-cell function and growth, and mutations in their genes cause closely related forms of diabetes. We have now exploited genetic epistasis to examine how Hnf1α and Hnf4α functionally interact in pancreatic islets. Expression profiling in islets from either Hnf1a+/− or pancreas-specific Hnf4a mutant mice showed that the two transcription factors regulate a strikingly similar set of genes. We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1α on Hnf4a gene transcription. Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1α and Hnf4α regulate common targets synergistically. Hnf1α binding in Hnf4a-deficient islets was decreased in selected targets, but remained unaltered in others, thus suggesting that the mechanisms for synergistic regulation are gene-specific. These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1α and Hnf4α control a common islet-cell regulatory program that is defective in human monogenic diabetes

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Gene expression profiling integrated into network modelling reveals heterogeneity in the mechanisms of BRCA1 tumorigenesis

Background: gene expression profiling has distinguished sporadic breast tumour classes with genetic and clinical differences. Less is known about the molecular classification of familial breast tumours, which are generally considered to be less heterogeneous. Here, we describe molecular signatures that define BRCA1 subclasses depending on the expression of the gene encoding for oestrogen receptor, ESR1. Methods: for this purpose, we have used the Oncochip v2, a cancer-related cDNA microarray to analyze 14 BRCA1-associated breast tumours. Results: signatures were found to be molecularly associated with different biological processes and transcriptional regulatory programs. The signature of ESR1-positive tumours was mainly linked to cell proliferation and regulated by ER, whereas the signature of ESR1-negative tumours was mainly linked to the immune response and possibly regulated by transcription factors of the REL/NFκB family. These signatures were then verified in an independent series of familial and sporadic breast tumours, which revealed a possible prognostic value for each subclass. Over-expression of immune response genes seems to be a common feature of ER-negative sporadic and familial breast cancer and may be associated with good prognosis. Interestingly, the ESR1-negative tumours were substratified into two groups presenting slight differences in the magnitude of the expression of immune response transcripts and REL/NFκB transcription factors, which could be dependent on the type of BRCA1 germline mutation. Conclusion: this study reveals the molecular complexity of BRCA1 breast tumours, which are found to display similarities to sporadic tumours, and suggests possible prognostic implications

Effect of tube diameter and capillary number on platelet margination and near-wall dynamics

The effect of tube diameter $D$ and capillary number $Ca$ on platelet margination in blood flow at $\approx 37\%$ tube haematocrit is investigated. The system is modelled as three-dimensional suspension of deformable red blood cells and nearly rigid platelets using a combination of the lattice-Boltzmann, immersed boundary and finite element methods. Results show that margination is facilitated by a non-diffusive radial platelet transport. This effect is important near the edge of the cell-free layer, but it is only observed for $Ca > 0.2$, when red blood cells are tank-treading rather than tumbling. It is also shown that platelet trapping in the cell-free layer is reversible for $Ca \leq 0.2$. Only for the smallest investigated tube ($D = 10 \mu\text{m}$) margination is essentially independent of $Ca$. Once platelets have reached the cell-free layer, they tend to slide rather than tumble. The tumbling rate is essentially independent of $Ca$ but increases with $D$. Tumbling is suppressed by the strong confinement due to the relatively small cell-free layer thickness at $\approx 37\%$ tube haematocrit.Comment: 16 pages, 10 figure

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators