Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi.

BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the mitogen-activated protein (MAP) kinase pathway. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. Here we report frequent somatic mutations in the heterotrimeric G protein alpha-subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea (46%). The mutations occur exclusively in codon 209 in the Ras-like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention

Aerospace industry in Queretaro, Mexico: a perspective of regional innovation system

Using the theoretical perspective of the Regional Innovation System (RIS), this paper analyzes the structure of the aerospace industry in Mexico, focusing on the region of Querétaro, Mexico. The objective of the research is to analyze the development, growth prospects , key agents and their interrelations of the aerospace industry in the Queretaro region from the perspective of the RIS. The aerospace industry in Querétaro has more than 40 companies, research centers and universities, intermediate and government agencies that focus on the aerospace industry, the region has presented rates of economic growth above the national average in the last 6 years, however to achieve the consolidation of the aerospace industry towards an RIS requires greater efforts of articulation and coordination among the agents that make up the system, it can be achieved through strategies and policies in joint collaboration for the consolidation of the industry in the region.N/

Role of Post‐Acute Care in Readmissions for Preexisting Healthcare‐Associated Infections

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153607/1/jgs16208.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153607/2/jgs16208_am.pd

Leadership Lessons: Developing Mentoring Infrastructure for GEMSSTAR Scholars

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149305/1/jgs15787_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149305/2/jgs15787.pd

Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops

PTDC/BIA-MOL/30438/2017 PTDC/MED-OUT/4301/2020 RiboMed 857119 PD/BD/128292/2017 LCF/PR/HP21/52310016 PTDC/BIA-MOL/6624/2020 PTDC/MED-ONC/7864/2020DNA oxidation by ten-eleven translocation (TET) family enzymes is essential for epigenetic reprogramming. The conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) initiates developmental and cell-type-specific transcriptional programs through mechanisms that include changes in the chromatin structure. Here, we show that the presence of 5hmC in the transcribed gene promotes the annealing of the nascent RNA to the template DNA strand, leading to the formation of an R-loop. Depletion of TET enzymes reduced global R-loops in the absence of gene expression changes, whereas CRISPR-mediated tethering of TET to an active gene promoted the formation of R-loops. The genome-wide distribution of 5hmC and R-loops shows a positive correlation in mouse and human stem cells and overlap in half of all active genes. Moreover, R-loop resolution leads to differential expression of a subset of genes that are involved in crucial events during stem cell proliferation. Altogether, our data reveal that epigenetic reprogramming via TET activity promotes co-transcriptional R-loop formation, disclosing new mechanisms of gene expression regulation.publishersversionpublishe

A lean six sigma framework for continuous and incremental improvement in the oil and gas sector

This article aims to explore synergies between Lean Production (LP) and Six Sigma principles in order to propose a Lean Six Sigma (LSS) framework for continuous and incremental improvement in the oil and gas sector. The Three-Dimensional LSS Framework seeks to provide various combinations about the integration between LP principles, DMAIC cycle and PDCA cycle to support operations management needs. Design/methodology/approach - The research method is composed of two main steps: (i) diagnostic of current problems and proposition of a conceptual framework that qualitatively integrates synergistic aspects of LP and Six Sigma; and (ii) analysis of the application of the construct through semi-structured interviews with leaders from oil and gas companies to assess and validate the proposed framework. Findings - As a result, a conceptual framework of LSS is developed contemplating the integration of LP and Six Sigma and providing a systemic and holistic approach to problemsolving through continuous and incremental improvement in the oil and gas sector. Originality/value - This research is different from previous studies because it integrates LP principles, DMAIC and PDCA cycles into a unique framework that fulfils a specific need of oil and gas sector. It presents a customized LSS framework that guides wastes and costs reduction, while enhances quality and reduces process variability to elevate efficiency in operations management of this sector. The paper type is an original research that present new and original scientific findings.N/

Functional upgrading in China’s export processing sector

Functional upgrading occurs when a firm acquires more sophisticated functions within an existing value chain. In this paper, we analyze if there is evidence of this type of upgrading in China’s export processing regime by investigating dynamics in the relative prevalence of Import & Assembly (IA) versus Pure Assembly (PA) processing trade over the period 2000-2013. Firms in both regimes provide similar manufacturing services to foreign companies, but IA firms also conduct the sophisticated tasks of quality control, searching, financing and storing imported materials. Consistent with a trend of functional upgrading, we show that the share of IA trade in total processing trade has increased rapidly during the period 2000-2006, both overall and within product categories. Furthermore, we find that this trend has gone hand in hand with improvements in a sector’s labor productivity and unit values. Against expectations, we find that this process has slowed down notably during the period 2006-2013.status: publishe

Late-Holocene climatic variability south of the Alps as recorded by lake-level fluctuations at Lake Ledro, Trentino, Italy

International audienceA lake-level record for the late Holocene at Lake Ledro (Trentino, northeastern Italy) is presented. It is based on the sediment and pollen analysis of a 1.75 m high stratigraphic section observed on the southern shore (site Ledro I) and a 3.2 m long sediment core taken from a littoral mire on the southeastern shore (site Ledro II). The chronology is derived from 15 radiocarbon dates and pollen stratigraphy. The late-Holocene composite record established from these two sediment sequences gives evidence of centennial-scale fluctuations with highstands at c. 3400, 2600, 1700, 1200 and 400 cal. BP, in agreement with various palaeohydro-logical records established in central and northern Italy, as well as north of the Alps. In addition, high lake-level conditions at c. 2000 cal. BP may be the equivalent of stronger river discharge observed at the same time in Central Italy's rivers. In agreement with the lake-level record of Accesa (Tuscany), the Ledro record also suggests a relatively complex palaeohydrological pattern for the period around 4000 cal. BP. On a millennial scale, sediment hiatuses observed in the lower part of the Ledro I sediment sequence indicate that, except for a high-stand occurring just after 7500 cal. BP, lower lake levels generally prevailed rather before c. 4000 cal. BP than afterwards. Finally, the lake-level data obtained at Lake Ledro indicate that the relative continuity of settlements in humid areas of northern Italy during the Bronze Age (in contrast to their general abandonment north of the Alps between c. 3450 and 3150 cal. BP), does not reflect different regional patterns of climatic and palaeohy-drological conditions. In contrast, the rise in lake level dated to c. 3400 cal. BP at Ledro appears to coincide with a worldwide climate reversal, observed in both the hemispheres, while palaeoenvironmental and archaeological data collected at Lake Ledro may suggest, as a working hypothesis, a relative emancipation of proto-historic societies from climatic conditions

Survival and long-term maintenance of tertiary trees in the Iberian Peninsula during the Pleistocene. First record of Aesculus L.

The Italian and Balkan peninsulas have been places traditionally highlighted as Pleistocene glacial refuges. The Iberian Peninsula, however, has been a focus of controversy between geobotanists and palaeobotanists as a result of its exclusion from this category on different occasions. In the current paper, we synthesise geological, molecular, palaeobotanical and geobotanical data that show the importance of the Iberian Peninsula in the Western Mediterranean as a refugium area. The presence of Aesculus aff. hippocastanum L. at the Iberian site at Cal Guardiola (Tarrasa, Barcelona, NE Spain) in the Lower– Middle Pleistocene transition helps to consolidate the remarkable role of the Iberian Peninsula in the survival of tertiary species during the Pleistocene. The palaeodistribution of the genus in Europe highlights a model of area abandonment for a widely-distributed species in the Miocene and Pliocene, leading to a diminished and fragmentary presence in the Pleistocene and Holocene on the southern Mediterranean peninsulas. Aesculus fossils are not uncommon within the series of Tertiary taxa. Many appear in the Pliocene and suffer a radical impoverishment in the Lower–Middle Pleistocene transition. Nonetheless some of these tertiary taxa persisted throughout the Pleistocene and Holocene up to the present in the Iberian Peninsula. Locating these refuge areas on the Peninsula is not an easy task, although areas characterised by a sustained level of humidity must have played an predominant role

Adaptive Computerized Working Memory Training in Patients With Mild Cognitive Impairment. A Randomized Double-Blind Active Controlled Trial

ObjectiveWe investigated if a 5-week computerized adaptive working memory training program (Cogmed®) of 20 to 25 sessions would be effective in improving the working memory capacity and other neuropsychological functions compared to a non-adaptive working memory training program (active-controlled) in adult patients with mild cognitive impairment (MCI).MethodsThis randomized double-blinded active control trial included 68 individuals aged 43 to 88 years, 45 men and 23 women, who were diagnosed with MCI at four Memory clinics. The study sample was randomized by block randomization to either adaptive or non-adaptive computerized working memory training. All participants completed the training, and were assessed with a comprehensive neuropsychological test battery before the intervention, and at 1 and 4 months after training.ResultsCompared to the non-adaptive training group, the adaptive training group did not show significantly greater improvement on the main outcome of working memory performance at 1 and 4 months after training.ConclusionNo difference were found between the two types of training on the primary outcome of working memory, or on secondary outcomes of cognitive function domains, in this sample of MCI patients. Hence, the hypothesis that the adaptive training program would lead to greater improvements compared to the non-adaptive training program was not supported. Within group analyses was not performed due to the stringent RCT design