274 research outputs found
Ten Year Operating Test Results and Post-Test Analysis of a 1/10 Segment Stirling Sodium Heat Pipe, Phase III
High-temperature heat pipes are being evaluated for use in energy conversion applications such as fuel cells, gas turbine re-combustors, Stirling cycle heat sources; and with the resurgence of space nuclear power both as reactor heat removal elements and as radiator elements. Long operating life and reliable performance are critical requirements for these applications. Accordingly, long-term materials compatibility is being evaluated through the use of high-temperature life test heat pipes. Thermacore, Inc., has carried out a sodium heat pipe 10-year life test to establish long-term operating reliability. Sodium heat pipes have demonstrated favorable materials compatibility and heat transport characteristics at high operating temperatures in air over long time periods. A representative one-tenth segment Stirling Space Power Converter heat pipe with an Inconel 718 envelope and a stainless steel screen wick has operated for over 87,000 hr (10 yr) at nearly 700 C. These life test results have demonstrated the potential for high-temperature heat pipes to serve as reliable energy conversion system components for power applications that require long operating lifetime with high reliability. Detailed design specifications, operating history, and post-test analysis of the heat pipe and sodium working fluid are described
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Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells.
Enhancers for embryonic stem (ES) cell-expressed genes and lineage-determining factors are characterized by conventional marks of enhancer activation in ES cells1-3, but it remains unclear whether enhancers destined to regulate cell-type-restricted transcription units might also have distinct signatures in ES cells. Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells
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lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs.
Although recent studies have indicated roles of long non-coding RNAs (lncRNAs) in physiological aspects of cell-type determination and tissue homeostasis, their potential involvement in regulated gene transcription programs remains rather poorly understood. The androgen receptor regulates a large repertoire of genes central to the identity and behaviour of prostate cancer cells, and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy. Here we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bind successively to the androgen receptor and strongly enhance both ligand-dependent and ligand-independent androgen-receptor-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the carboxy-terminally acetylated androgen receptor on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM1, to the androgen receptor amino terminus that is methylated by DOT1L. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited pygopus 2 PHD domain enhances selective looping of androgen-receptor-bound enhancers to target gene promoters in these cells. In 'resistant' prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full-length androgen receptor, causing ligand-independent activation of the androgen receptor transcriptional program and cell proliferation. Conditionally expressed short hairpin RNA targeting these lncRNAs in castration-resistant prostate cancer cell lines strongly suppressed tumour xenograft growth in vivo. Together, these results indicate that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumours
Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents
Rationale: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations
Constraining the Twomey effect from satellite observations: issues and perspectives
The Twomey effect describes the radiative forcing
associated with a change in cloud albedo due to an increase
in anthropogenic aerosol emissions. It is driven by the perturbation
in cloud droplet number concentration (1Nd; ant)
in liquid-water clouds and is currently understood to exert
a cooling effect on climate. The Twomey effect is the key
driver in the effective radiative forcing due to aerosol–cloud
interactions, but rapid adjustments also contribute. These
adjustments are essentially the responses of cloud fraction
and liquid water path to 1Nd; ant and thus scale approximately
with it. While the fundamental physics of the influence
of added aerosol particles on the droplet concentration
(Nd) is well described by established theory at the particle
scale (micrometres), how this relationship is expressed at the
large-scale (hundreds of kilometres) perturbation, 1Nd; ant,
remains uncertain. The discrepancy between process understanding
at particle scale and insufficient quantification at
the climate-relevant large scale is caused by co-variability of
aerosol particles and updraught velocity and by droplet sink
processes. These operate at scales on the order of tens of metres at which only localised observations are available and at
which no approach yet exists to quantify the anthropogenic
perturbation. Different atmospheric models suggest diverse
magnitudes of the Twomey effect even when applying the
same anthropogenic aerosol emission perturbation. Thus, observational
data are needed to quantify and constrain the
Twomey effect. At the global scale, this means satellite data.
There are four key uncertainties in determining 1Nd; ant,
namely the quantification of (i) the cloud-active aerosol – the
cloud condensation nuclei (CCN) concentrations at or above
cloud base, (ii) Nd, (iii) the statistical approach for inferring
the sensitivity of Nd to aerosol particles from the satellite
data and (iv) uncertainty in the anthropogenic perturbation
to CCN concentrations, which is not easily accessible from
observational data. This review discusses deficiencies of current
approaches for the different aspects of the problem and
proposes several ways forward: in terms of CCN, retrievals
of optical quantities such as aerosol optical depth suffer from
a lack of vertical resolution, size and hygroscopicity information,
non-direct relation to the concentration of aerosols,
difficulty to quantify it within or below clouds, and the problem
of insufficient sensitivity at low concentrations, in addition
to retrieval errors. A future path forward can include
utilising co-located polarimeter and lidar instruments, ideally
including high-spectral-resolution lidar capability at two
wavelengths to maximise vertically resolved size distribution
information content. In terms of Nd, a key problem is the lack
of operational retrievals of this quantity and the inaccuracy of
the retrieval especially in broken-cloud regimes. As for the
Nd-to-CCN sensitivity, key issues are the updraught distributions
and the role of Nd sink processes, for which empirical
assessments for specific cloud regimes are currently the best
solutions. These considerations point to the conclusion that past studies using existing approaches have likely underestimated
the true sensitivity and, thus, the radiative forcing due
to the Twomey effect
Dynamic Career Models and Inequality Research: A Reexamination of the Sørensen Model
This article presents a reexamination of the Sørensen model. This model derives the pattern of individual careers from structural considerations. If longitudinal data on individual careers are available, Sørensen's model provides two methods to infer the underlying structural parameter. This structural parameter gives a useful measure for unequal career chances. An implementation of these methods, using firm data, shows, however, that they lead to contradictory conclusions; this is shown to be the result of some unrealistic assumptions Sørensen uses in his derivation. Some more realistic assumptions are suggested that produce reasonable results. Finally, it is shown that despite these modifications, the main conclusions of the Sørensen model are preserved. This seems to be promising for future work with this model
Further clinical and molecular delineation of the 15q24 microdeletion syndrome
Background Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis. Aim To further delineate the features of the 15q24 microdeletion syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients. Methods Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient. Results Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8-10 times less frequently than 1q21 or 15q13 microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 microdeletion syndrome. Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 microdeletion syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1-Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 microdeletions should receive a thorough neurodevelopmental evaluation, physical, occupational and speech therapies, and regular audiologic and ophthalmologic screenin
Precipitation sensitivity to autoconversion rate in a numerical weather-prediction model
Aerosols are known to significantly affect cloud and precipitation patterns and intensity, but these interactions are ignored or very simplistically handled in climate and numerical weather-prediction (NWP) models. A suite of one-way nested Met Office Unified Model (UM) runs, with a single-moment bulk microphysics scheme was used to study two convective cases with contrasting characteristics observed in southern England. The autoconversion process that converts cloud water to rain is directly controlled by the assumed droplet number. The impact of changing cloud droplet number concentration (CDNC) on cloud and precipitation evolution can be inferred through changes to the autoconversion rate. This was done for a range of resolutions ranging from regional NWP (1 km) to high resolution (up to 100 m grid spacing) to evaluate the uncertainties due to changing CDNC as a function of horizontal grid resolution. The first case is characterised by moderately intense convective showers forming below an upper-level potential vorticity anomaly, with a low freezing level. The second case, characterised by one persistent stronger storm, is warmer with a deeper boundary layer. The colder case is almost insensitive to even large changes in CDNC, while in the warmer case a change of a factor of 3 in assumed CDNC affects total surface rain rate by ~17%. In both cases the sensitivity to CDNC is similar at all grid spacings <1 km. The contrasting sensitivities of these cases are induced by their contrasting ice-phase proportion. The ice processes in this model damp the precipitation sensitivity to CDNC. For this model the convection is sensitive to CDNC when the accretion process is more significant than the melting process and vice versa
Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review: Diagnosis and Management of PCD
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung disease resulting in chronic oto‐sino‐pulmonary disease in both children and adults. Many physicians incorrectly diagnose PCD or eliminate PCD from their differential diagnosis due to inexperience with diagnostic testing methods. Thus far, all therapies used for PCD are unproven through large clinical trials. This review article outlines consensus recommendations from PCD physicians in North America who have been engaged in a PCD centered research consortium for the last 10 years. These recommendations have been adopted by the governing board of the PCD Foundation to provide guidance for PCD clinical centers for diagnostic testing, monitoring, and appropriate short and long‐term therapeutics in PCD patients. Pediatr Pulmonol. 2016;51:115–132. © 2015 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc
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