Sinking of light intruders in a shaken granular bed

We present an experimental study of the displacement of a light intruder immersed in a vibrated granular bed. Using high speed video we resolve the motion, during one cycle of oscillation, of a cylindrical object inside a Plexiglas box partially filled with grains. We report experimental evidence that, in the absence of convection, at least two forces are behind the intruder’s motion: an air drag force—due to the airflow through the granular bed—and a buoyancy force produced by an air-mediated granular fluid

Safety and efficacy of balloon-mounted stent in the treatment of symptomatic intracranial atherosclerotic disease: a multicenter experience

Background Randomized clinical trials have failed to prove that the safety and efficacy of endovascular treatment for symptomatic intracranial atherosclerotic disease (ICAD) is better than that of medical management. A recent study using a self-expandable stent showed acceptable lower rates of periprocedural complications. Objective To study the safety and efficacy of a balloon-mounted stent (BMS) in the treatment of symptomatic ICAD. Methods Prospectively maintained databases from 15 neuroendovascular centers between 2010 and 2020 were reviewed. Patients were included if they had severe symptomatic intracranial stenosis in the target artery, medical management had failed, and they underwent intracranial stenting with BMS after 24 hours of the qualifying event. The primary outcome was the occurrence of stroke and mortality within 72 hours after the procedure. Secondary outcomes were the occurrence of stroke, transient ischemic attacks (TIAs), and mortality on long-term follow-up. Results A total of 232 patients were eligible for the analysis (mean age 62.8 years, 34.1% female). The intracranial stenotic lesions were located in the anterior circulation in 135 (58.2%) cases. Recurrent stroke was the qualifying event in 165 (71.1%) while recurrent TIA was identified in 67 (28.9%) cases. The median (IQR) time from the qualifying event to stenting was 5 (2–20.75) days. Strokes were reported in 13 (5.6%) patients within 72 hours of the procedure; 9 (3.9%) ischemic and 4 (1.7%) hemorrhagic, and mortality in 2 (0.9%) cases. Among 189 patients with median follow-up time 6 (3–14.5) months, 12 (6.3%) had TIA and 7 (3.7%) had strokes. Three patients (1.6%) died from causes not related to stroke. Conclusion Our study has shown that BMS may be a safe and effective treatment for medically refractory symptomatic ICAD. Additional prospective randomized clinical trials are warranted

The NAD+-Dependent SIRT1 Deacetylase Translates a Metabolic Switch into Regulatory Epigenetics in Skeletal Muscle Stem Cells

SummaryStem cells undergo a shift in metabolic substrate utilization during specification and/or differentiation, a process that has been termed metabolic reprogramming. Here, we report that during the transition from quiescence to proliferation, skeletal muscle stem cells experience a metabolic switch from fatty acid oxidation to glycolysis. This reprogramming of cellular metabolism decreases intracellular NAD+ levels and the activity of the histone deacetylase SIRT1, leading to elevated H4K16 acetylation and activation of muscle gene transcription. Selective genetic ablation of the SIRT1 deacetylase domain in skeletal muscle results in increased H4K16 acetylation and deregulated activation of the myogenic program in SCs. Moreover, mice with muscle-specific inactivation of the SIRT1 deacetylase domain display reduced myofiber size, impaired muscle regeneration, and derepression of muscle developmental genes. Overall, these findings reveal how metabolic cues can be mechanistically translated into epigenetic modifications that regulate skeletal muscle stem cell biology

Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci

We characterized DNA methylation quantitative trait loci (mQTLs) in a large collection (n = 166) of human fetal brain samples spanning 56-166 d post-conception, identifying >16,000 fetal brain mQTLs. Fetal brain mQTLs were primarily cis-acting, enriched in regulatory chromatin domains and transcription factor binding sites, and showed substantial overlap with genetic variants that were also associated with gene expression in the brain. Using tissue from three distinct regions of the adult brain (prefrontal cortex, striatum and cerebellum), we found that most fetal brain mQTLs were developmentally stable, although a subset was characterized by fetal-specific effects. Fetal brain mQTLs were enriched amongst risk loci identified in a recent large-scale genome-wide association study (GWAS) of schizophrenia, a severe psychiatric disorder with a hypothesized neurodevelopmental component. Finally, we found that mQTLs can be used to refine GWAS loci through the identification of discrete sites of variable fetal brain methylation associated with schizophrenia risk variants

Targeted Deletion of p73 in Mice Reveals Its Role in T Cell Development and Lymphomagenesis

Transcriptional silencing of the p73 gene through methylation has been demonstrated in human leukemias and lymphomas. However, the role of p73 in the malignant process remains to be explored. We show here that p73 acts as a T cell-specific tumor suppressor in a genetically defined mouse model, and that concomitant ablation of p53 and p73 predisposes mice to an increased incidence of thymic lymphomas compared to the loss of p53 alone. Our results demonstrate a causal role for loss of p73 in progression of T cell lymphomas to the stage of aggressive, disseminated disease. We provide evidence that tumorigenesis in mice lacking p53 and p73 proceeds through mechanisms involving altered patterns of gene expression, defects in early T cell development, impaired apoptosis, and the ensuing accumulation of chromosomal aberrations. Collectively, our data imply that tumor suppressive properties of p73 are highly dependent on cellular context, wherein p73 plays a major role in T cell development and neoplasia

Infectious Diseases, Social, Economic and Political Crises, Anthropogenic Disasters and Beyond: Venezuela 2019 – Implications for Public Health and Travel Medicine

During last months, there have been a significant increase in the evidences showing the catastrophic health situation in Venezuela. There are multiple epidemics, increase in emerging and reemerging infectious, tropical and parasitic diseases as consequences of the social, economic and political crises, which would be considered today a clearly anthropogenic disaster. Venezuela is facing in 2019, the worse sanitary conditions, with multiple implications for public health and travel medicine. So far, from a global perspective, this situation will be an impediment for the achievement of the sustainable development goals (SDG) in 2030. In this multiauthor review, there is a comprehensive analysis of the situation for infectious diseases, non-communicable diseases, their impact in the Americas region, given the migration crisis as well as the comparative status of the SDG 2030. This discussion can provide input for prioritizing emerging health problems and establish a future agenda

Infectious Diseases, Social, Economic and Political Crises, Anthropogenic Disasters and Beyond: Venezuela 2019 – Implications for Public Health and Travel Medicine

During last months, there have been a significant increase in the evidences showing the catastrophic health situation in Venezuela. There are multiple epidemics, increase in emerging and reemerging infectious, tropical and parasitic diseases as consequences of the social, economic and political crises, which would be considered today a clearly anthropogenic disaster. Venezuela is facing in 2019, the worse sanitary conditions, with multiple implications for public health and travel medicine. So far, from a global perspective, this situation will be an impediment for the achievement of the sustainable development goals (SDG) in 2030. In this multiauthor review, there is a comprehensive analysis of the situation for infectious diseases, non-communicable diseases, their impact in the Americas region, given the migration crisis as well as the comparative status of the SDG 2030. This discussion can provide input for prioritizing emerging health problems and establish a future agenda

Transformative sensemaking: Development in Whose Image? Keyan Tomaselli and the semiotics of visual representation

The defining and distinguishing feature of homo sapiens is its ability to make sense of the world, i.e. to use its intellect to understand and change both itself and the world of which it is an integral part. It is against this backdrop that this essay reviews Tomaselli's 1996 text, Appropriating Images: The Semiotics of Visual Representation/ by summarizing his key perspectives, clarifying his major operational concepts and citing particular portions from his work in support of specific perspectives on sense-making. Subsequently, this essay employs his techniques of sense-making to interrogate the notion of "development". This exercise examines and confirms two interrelated hypotheses: first, a semiotic analysis of the privileged notion of "development" demonstrates its metaphysical/ ideological, and thus limiting, nature especially vis-a-vis the marginalized, excluded, and the collective other, the so-called Developing Countries. Second, the interrogative nature of semiotics allows for an alternative reading and application of human potential or skills in the quest of a more humane social and global order, highlighting thereby the transformative implications of a reflexive epistemology.Web of Scienc