MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution

The linear sequence of DNA provides invaluable information about genes and their regulatory elements along chromosomes. However, to fully understand gene function and regulation, we need to dissect how genes physically fold in the three-dimensional nuclear space. Here we describe immuno-OligoSTORM, an imaging strategy that reveals the distribution of nucleosomes within specific genes in super-resolution, through the simultaneous visualization of DNA and histones. We combine immuno-OligoSTORM with restraint-based and coarse-grained modeling approaches to integrate super-resolution imaging data with Hi-C contact frequencies and deconvoluted micrococcal nuclease-sequencing information. The resulting method, called Modeling immuno-OligoSTORM, allows quantitative modeling of genes with nucleosome resolution and provides information about chromatin accessibility for regulatory factors, such as RNA polymerase II. With Modeling immuno-OligoSTORM, we explore intercellular variability, transcriptional-dependent gene conformation, and folding of housekeeping and pluripotency-related genes in human pluripotent and differentiated cells, thereby obtaining the highest degree of data integration achieved so far to our knowledge

Superilles Pilot al Districte de les Corts

A la coberta: Barris inclusius, barris sostenibles a velocitat humana. Programa d'impuls de Superilles Pilot a Barcelon

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Stratal patterns and sedimentary facies in tidal point bars

Tidal channels play a key role in the evolution of coastal environments and commonly dominate tidal landscapes. These channels commonly show a clear meandering pattern which shapes the architectural geometries of sedimentary successions accumulated in tidal coastal realms. Nevertheless, a limited number of studies analysed the morphodynamic evolution of tidal meanders and the related point bar sedimentary bodies, whose internal architecture and sedimentary facies distribution remain still poorly explored, as highlighted by their scarce documentation in the rock record. The capability of reading the signature of tidal processes in sedimentary successions represents a powerful tool for paleo-environmental reconstructions. Detecting tidal channel deposits will contribute to studies on Holocene deposits and ancient rocks, with implications spanning from adaptation of natural systems to anthropic pressure to subsurface exploration for georesources. The present work aims at improving our understanding of the relationship between the evolution of tidal meander bends and the related sedimentary products, through the investigation of different research issues (RI), including: i) the influence of vertical aggradation and substrate compaction in shaping geometries of tidal point bars (RI1); ii) the reconstruction of three-dimensional architecture of tidal point bars, through a numerical modelling approach, developed under different aggradational conditions and planform transformation styles (RI2); iii) the relationship between mechanisms of bar growth and internal facies arrangements (RI3); and iv) the analysis of piracy-controlled geometries of point bar bodies (RI4). These research issues have been carried out in different tidal settings, including microtidal (Venice Lagoon, Italy – RI1, 2, and 4) and macrotidal (Bay of Mont Saint Michel, France – RI3) environments; both in modern (RI1, 2, 3, and 4) and ancient record (Eocene deposits of the Tremp-Graus Basin, Spain – RI4). A multidisciplinary approach has been adopted for modern examples, with different methodologies encompassing remote sensing techniques (i.e. historical aerial photos and LiDAR topographic time-series analysis), geomorphological field observations, sedimentary core analysis, and 3D forward stratigraphic modelling. The analysis of the ancient case study examples relies on classical outcrop sedimentology approach, which included line-drawing of photomosaics, bed-by-bed logging, and collection of paleo-flow measurements. The main results from this work highlighted that: I) geometries of tidal point bars can vary following aggradational conditions of surrounding overbank areas, along with changes in local accommodation space and channel discharge. These are, in turn, influenced by differential substrate compaction and channel network evolution; II) 3D geometries of point bars developed by slowly migrating tidal channels under aggradational conditions, differ from tabular bodies envisaged by traditional point bar models. Indeed, their geometries are shaped by the planform and vertical shift of channel bends; III) tidal meanders can expand alternating accretionary stages along seaward and landward side of point bars. In this contest, large amounts of mud-rich deposits are stored in their axial zone, where rhythmic tidal deposition is better recorded; IV) occurrence of densely-drained tidal networks prevents channel bends to freely meander and causes interaction with adjacent channels triggering piracies. These piracies cause premature deactivation of sinuous channels and hinder the development of laterally extensive point bar bodies

Risk management in a company

Obsahem tématu práce je stále aktuálnější téma risk managementu. Práce je věnována rozboru finanční situace dvou konkrétních podniků vstupujících do fúze a rizikům s touto fúzí spojených. Část této bakalářské práce je věnována obecnému shrnutí některých vybraných metod analýz. V další části práce jsou zkoumána aktiva obou podniků, použitím finanční analýzy, konkrétně poměrovými ukazateli. Na závěr je provedená analýza rizik ohrožujících tuto fúzi technikou brainstormingu a What If analýzou. Je zde provedená komparace obou podniků a navržená doporučení, jak s riziky následně nakládat.The content of the topic of the thesis is becoming increasingly topical theme of risk management. The work is devoted to the analysis of the financial situation of two particular companies entering into mergers and risks associated with the merger. Part of this work is devoted to a general summary of certain selected methods of analysis. In a further part of the work investigated the assets of both companies, using financial analysis, specifically the relative indicators. At the end, is conducted an analysis of the risks to this merger, by the technique of brainstorming and What If analysis. There is a comparison of both companies and the proposed recommendations as to the risks of consequential costs.Ústav regionálních a bezpečnostních vědStudentce byla položena otázka, kterou položil vedoucí bakalářské práce: Jaká další opatření doporučujete pro zmírnění rizik uvedených na str. 44? V diskusi byla studentce položena otázka na graf, který uvádí na straně 25 bakalářské práce, konkrétně na vyjádření veličiny horizontální osy a vztah prezentovaných veličin

Stratal patterns and sedimentary facies in tidal point bars

Tidal channels play a key role in the evolution of coastal environments and commonly dominate tidal landscapes. These channels commonly show a clear meandering pattern which shapes the architectural geometries of sedimentary successions accumulated in tidal coastal realms. Nevertheless, a limited number of studies analysed the morphodynamic evolution of tidal meanders and the related point bar sedimentary bodies, whose internal architecture and sedimentary facies distribution remain still poorly explored, as highlighted by their scarce documentation in the rock record. The capability of reading the signature of tidal processes in sedimentary successions represents a powerful tool for paleo-environmental reconstructions. Detecting tidal channel deposits will contribute to studies on Holocene deposits and ancient rocks, with implications spanning from adaptation of natural systems to anthropic pressure to subsurface exploration for georesources. The present work aims at improving our understanding of the relationship between the evolution of tidal meander bends and the related sedimentary products, through the investigation of different research issues (RI), including: i) the influence of vertical aggradation and substrate compaction in shaping geometries of tidal point bars (RI1); ii) the reconstruction of three-dimensional architecture of tidal point bars, through a numerical modelling approach, developed under different aggradational conditions and planform transformation styles (RI2); iii) the relationship between mechanisms of bar growth and internal facies arrangements (RI3); and iv) the analysis of piracy-controlled geometries of point bar bodies (RI4). These research issues have been carried out in different tidal settings, including microtidal (Venice Lagoon, Italy – RI1, 2, and 4) and macrotidal (Bay of Mont Saint Michel, France – RI3) environments; both in modern (RI1, 2, 3, and 4) and ancient record (Eocene deposits of the Tremp-Graus Basin, Spain – RI4). A multidisciplinary approach has been adopted for modern examples, with different methodologies encompassing remote sensing techniques (i.e. historical aerial photos and LiDAR topographic time-series analysis), geomorphological field observations, sedimentary core analysis, and 3D forward stratigraphic modelling. The analysis of the ancient case study examples relies on classical outcrop sedimentology approach, which included line-drawing of photomosaics, bed-by-bed logging, and collection of paleo-flow measurements. The main results from this work highlighted that: I) geometries of tidal point bars can vary following aggradational conditions of surrounding overbank areas, along with changes in local accommodation space and channel discharge. These are, in turn, influenced by differential substrate compaction and channel network evolution; II) 3D geometries of point bars developed by slowly migrating tidal channels under aggradational conditions, differ from tabular bodies envisaged by traditional point bar models. Indeed, their geometries are shaped by the planform and vertical shift of channel bends; III) tidal meanders can expand alternating accretionary stages along seaward and landward side of point bars. In this contest, large amounts of mud-rich deposits are stored in their axial zone, where rhythmic tidal deposition is better recorded; IV) occurrence of densely-drained tidal networks prevents channel bends to freely meander and causes interaction with adjacent channels triggering piracies. These piracies cause premature deactivation of sinuous channels and hinder the development of laterally extensive point bar bodies

Sedimentology of a hypertidal point bar (Mont‐Saint‐Michel Bay, north‐western France) revealed by combining lidar time‐series and sedimentary core data

International audienceIntertidal meanders developed on salt marshes are known to expand and produce inclined heterolithic stratification rich in fine-grained sediments and to bear evidence for rhythmic deposition in the upper part of the inner meander bend(i.e. the upper part of the point bar). This occurs because the lower point-bar deposits are washed by strong currents, which remove mud drapes and develop discontinuous record of tidal cycles. Although these criteria are widely accepted, facies models for tidal point bars still lack a three-dimensional perspective and overlook the along-bend variability of sediment distribution. The present study focuses on a hypertidal point bar belonging to the upper-intertidal domain of the Mont-Saint-Michel Bay (France), and it analyses the sedimentology of a 3D time-framed accretionary package formed between 28 March 2012 and 29 November 2012 by means of lidar topographic data, geomorphological field surveys and sedimentological core data. To define the 3D time-framed accretionary package, data from thirteen lidar topographic surveys were used to create the point-bar synthetic stratigraphy. Data shows that over the study period the point bar expanded alternating deposition along its seaward and landward sides, pointing out the occurrence of depositional patterns more complex than a simple progressive expansion of the bend. The thickest deposits were accumulated in the point-bar-apex zone, where the largest amount of mud was also stored. High sediment accretion in the bend-apex zone is ascribed to the development of low-energy conditions due to flow and bed configuration. High accretion rate of the point-bar-apex zone promoted also a better preservation of rhythmites, which are almost missing from deposits accumulated along the point-bar sides. This study remarks that preservation of mud and tidal rhythmites within intertidal-point-bar deposits is controlled, not only by their elevation with respect to the tidal range, but also by their location along the point bar

Depicting architecture and sedimentology of a hypertidal point bar through Lidar and sedimentary-core data

International audienceMorphodynamic behaviour of tidal meanders and internal architecture of related sedimentary bodies havereceived scarce attention, although they are ubiquitous features of coastal landscapes. Expansion of tidalmeanders is known to produce a progressive increase of bend sinuosity, along with accretion of point-bardeposits and formation of inclined heterolithic strata. These deposits are considered to be rich in fine-grainedsediments and tend to record tidal rhythmic deposition in the upper part of the bar, being the lower bar depositsdominated by erosional and bypass processes. Although these criteria are widely accepted, faciesmodels for tidal point bars still lack a 3D perspective and overlook the along-bend variability of sedimentaryprocesses. This knowledge gap can have a direct impact on understanding intra-point-bar heterogeneitiesand connectivity, with implications for reservoir production. The present study focuses on a 3 m deep tidalmeandering channel located in the salt marshes of the hypertidal Mont-Saint-Michel Bay (France), and investigatessedimentology of a time-framed bar accretionary package by means of Lidar-topographic data,geomorphological-field surveys and sedimentary cores. The studied accretionary package was accretedalong the bar between 28/03/2012 and 29/11/2012. Integration between Lidar and sedimentary-core datashows that over this time the bar expanded alternating depositional phases along its seaward and landwardside. The maximum thickness of deposits was accumulated in the bar apex zone, and just landwardof it, where the largest amount of mud was also stored. High accretion rate of the bar apex zone endorsedalso a better preservation of rhythmites, which are almost missing from deposits accumulated along thebar sides (i.e. close to riffles). We suggest that alternating depositional loci and high sediment accretion atthe bend apex zone emerge due to a combination of factors, including: i) the spatio-temporal asymmetricnature of tidal currents, which influenced deposition and preservation of flood and ebb deposits along thebend; and ii) the development of low-energy conditions at the apex due to ebb and flood flow configuration,which also promoted mud settling.This study highlights that mud and tidal rhythmites are not uniformly distributed within point-bar deposits,and their occurrence is strongly controlled by the asymmetric and mutually evasive nature of ebb and floodtides