Irradiance calibration with solar diffuser

The sun's energy is used in combination of movable and fixed diffuser plates, windows and apertures which are positioned in a series of test sequences (modes) for reflectance monitoring and calibration without the use of man-made sources. There are three embodiments, or implementations, of the invention--one embodiment uses two diffusers--a working diffuser and a secondary diffuser--the second embodiment uses three diffusers, a working diffuser, a secondary diffuser and a reference diffuser--and the third embodiment uses two diffusers--a working diffuser and a secondary diffuser, the latter also functioning as a cover for the working diffuser. The movable diffusers are mounted on rotatable cones and, in all embodiments, the sun is blocked from reaching the diffusers when not in use. Thus, the sun is used as a stable source for calibration and monitoring and the sun/diffuser combination is used in such a way that the response of all elements of the optical subsystem of the TOMS can be unambiguously and efficiently characterized with high accuracy and precision

Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia

The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor κB (NF-κB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-κB–induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced α-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications

The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing.

Transcriptional regulation in eukaryotes occurs at promoter-proximal regions wherein transcriptionally engaged RNA polymerase II (Pol II) pauses before proceeding toward productive elongation. The role of chromatin in pausing remains poorly understood. Here, we demonstrate that the histone deacetylase SIRT6 binds to Pol II and prevents the release of the negative elongation factor (NELF), thus stabilizing Pol II promoter-proximal pausing. Genetic depletion of SIRT6 or its chromatin deficiency upon glucose deprivation causes intragenic enrichment of acetylated histone H3 at lysines 9 (H3K9ac) and 56 (H3K56ac), activation of cyclin-dependent kinase 9 (CDK9)-that phosphorylates NELF and the carboxyl terminal domain of Pol II-and enrichment of the positive transcription elongation factors MYC, BRD4, PAF1, and the super elongation factors AFF4 and ELL2. These events lead to increased expression of genes involved in metabolism, protein synthesis, and embryonic development. Our results identified SIRT6 as a Pol II promoter-proximal pausing-dedicated histone deacetylase

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function

A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis.

Transcription factors are frequently altered in leukaemia through chromosomal translocation, mutation or aberrant expression(1). AML1-ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukaemia, is a transcription factor implicated in both gene repression and activation(2). AML1-ETO oligomerization, mediated by the NHR2 domain, is critical for leukaemogenesis(3-6), making it important to identify co-regulatory factors that 'read' the NHR2 oligomerization and contribute to leukaemogenesis(4). Here we show that, in human leukaemic cells, AML1-ETO resides in and functions through a stable AML1-ETO-containing transcription factor complex (AETFC) that contains several haematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukaemogenesis. Within the AETFC complex, AML1-ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins. Crystallographic analysis of the NHR2-N2B complex reveals a unique interaction pattern in which an N2B peptide makes direct contact with side chains of two NHR2 domains as a dimer, providing a novel model of how dimeric/oligomeric transcription factors create a new protein-binding interface through dimerization/oligomerization. Intriguingly, disruption of this interaction by point mutations abrogates AML1-ETO-induced haematopoietic stem/progenitor cell self-renewal and leukaemogenesis. These results reveal new mechanisms of action of AML1-ETO, and provide a potential therapeutic target in t(8;21)-positive acute myeloid leukaemia

Direct Recruitment of Polycomb Repressive Complex 1 to Chromatin by Core Binding Transcription Factors

Polycomb repressive complexes (PRCs) play key roles in developmental epigenetic regulation. Yet the mechanisms that target PRCs to specific loci in mammalian cells remain incompletely understood. In this study we show that Bmi1, a core component of Polycomb Repressive Complex 1 (PRC1), binds directly to the Runx1/CBFβ transcription factor complex. Genome-wide studies in megakaryocytic cells demonstrate significant chromatin occupancy overlap between the PRC1 core component Ring1b and Runx1/CBFβ and functional regulation of a considerable fraction of commonly bound genes. Bmi1/Ring1b and Runx1/CBFβ deficiencies generate partial phenocopies of one another in vivo. We also show that Ring1b occupies key Runx1 binding sites in primary murine thymocytes and that this occurs via PRC2-independent mechanisms. Genetic depletion of Runx1 results in reduced Ring1b binding at these sites in vivo. These findings provide evidence for site-specific PRC1 chromatin recruitment by core binding transcription factors in mammalian cells.Stem Cell and Regenerative Biolog

Использование голосового интерфейса для взаимодействия пользователя с веб-сервисом

В статье рассмотрены виды существующих интерфейсов взаимодействия пользователя с ЭВМ, приводится сравнительный анализ характеристик интерфейсов. Подробно рассматривается голосовой интерфейс и его использование для взаимодействия пользователя с веб-сервисом

Vertebral body stenting: a new method for vertebral augmentation versus kyphoplasty

Vertebroplasty and kyphoplasty are well-established minimally invasive treatment options for compression fractures of osteoporotic vertebral bodies. Possible procedural disadvantages, however, include incomplete fracture reduction or a significant loss of reduction after balloon tamp deflation, prior to cement injection. A new procedure called “vertebral body stenting” (VBS) was tested in vitro and compared to kyphoplasty. VBS uses a specially designed catheter-mounted stent which can be implanted and expanded inside the vertebral body. As much as 24 fresh frozen human cadaveric vertebral bodies (T11-L5) were utilized. After creating typical compression fractures, the vertebral bodies were reduced by kyphoplasty (n = 12) or by VBS (n = 12) and then stabilized with PMMA bone cement. Each step of the procedure was performed under fluoroscopic control and analysed quantitatively. Finally, static and dynamic biomechanical tests were performed. A complete initial reduction of the fractured vertebral body height was achieved by both systems. There was a significant loss of reduction after balloon deflation in kyphoplasty compared to VBS, and a significant total height gain by VBS (mean ± SD in %, p < 0.05, demonstrated by: anterior height loss after deflation in relation to preoperative height [kyphoplasty: 11.7 ± 6.2; VBS: 3.7 ± 3.8], and total anterior height gain [kyphoplasty: 8.0 ± 9.4; VBS: 13.3 ± 7.6]). Biomechanical tests showed no significant stiffness and failure load differences between systems. VBS is an innovative technique which allows for the possibly complete reduction of vertebral compression fractures and helps maintain the restored height by means of a stent. The height loss after balloon deflation is significantly decreased by using VBS compared to kyphoplasty, thus offering a new promising option for vertebral augmentation