238 research outputs found

    Primordial black hole and wormhole formation by domain walls

    Get PDF
    In theories with a broken discrete symmetry, Hubble sized spherical domain walls may spontaneously nucleate during inflation. These objects are subsequently stretched by the inflationary expansion, resulting in a broad distribution of sizes. The fate of the walls after inflation depends on their radius. Walls smaller than a critical radius fall within the cosmological horizon early on and collapse due to their own tension, forming ordinary black holes. But if a wall is large enough, its repulsive gravitational field becomes dominant much before the wall can fall within the cosmological horizon. In this ``supercritical'' case, a wormhole throat develops, connecting the ambient exterior FRW universe with an interior baby universe, where the exponential growth of the wall radius takes place. The wormhole pinches off in a time-scale comparable to its light-crossing time, and black holes are formed at its two mouths. As discussed in previous work, the resulting black hole population has a wide distribution of masses and can have significant astrophysical effects. The mechanism of black hole formation has been previously studied for a dust-dominated universe. Here we investigate the case of a radiation-dominated universe, which is more relevant cosmologically, by using numerical simulations in order to find the initial mass of a black hole as a function of the wall size at the end of inflation. For large supercritical domain walls, this mass nearly saturates the upper bound according to which the black hole cannot be larger than the cosmological horizon. We also find that the subsequent accretion of radiation satisfies a scaling relation, resulting in a mass increase by about a factor of 2

    MyBP-C: one protein to govern them all

    Get PDF
    The heart is an extraordinarily versatile pump, finely tuned to respond to a multitude of demands. Given the heart pumps without rest for decades its efficiency is particularly relevant. Although many proteins in the heart are essential for viability, the non-essential components can attract numerous mutations which can cause disease, possibly through alterations in pumping efficiency. Of these, myosin binding protein C is strongly over-represented with ~ 40% of all known mutations in hypertrophic cardiomyopathy. Therefore, a complete understanding of its molecular function in the cardiac sarcomere is warranted. In this review, we revisit contemporary and classical literature to clarify both the current standing of this fast-moving field and frame future unresolved questions. To date, much effort has been directed at understanding MyBP-C function on either thick or thin filaments. Here we aim to focus questions on how MyBP-C functions at a molecular level in the context of both the thick and thin filaments together. A concept that emerges is MyBP-C acts to govern interactions on two levels; controlling myosin access to the thin filament by sequestration on the thick filament, and controlling the activation state and access of myosin to its binding sites on the thin filament. Such affects are achieved through directed interactions mediated by phosphorylation (of MyBP-C and other sarcomeric components) and calcium

    Interferência na qualidade dos frutos de morangueiro ocasionada pelo uso de agentes de controle biológico de doenças

    Get PDF
    The strawberry is a fruit of great market acceptance and it is much appreciated throughout the world, besides being very important for small farmers, generating employment and income. Nevertheless, this crop is affected by various diseases that require control, so that producers eventually use chemical fungicides, which, besides contaminating soil and water, eventually contaminate the fruit. In an attempt to reduce the amount of pesticides used in the strawberry crop, a lot of research on biological control of diseases has been done. However, the biological control of diseases in strawberries should not interfere negatively in fruit quality. Thus, this study aimed to evaluate the acidity, pH and total soluble solids (ºBrix) of strawberries treated with Saccharomyces cerevisiae, Saccharomyces boulardii and Bacillus cereus, agents used in the biological control of diseases. None of the treatments affected the pH and total titratable acidity; however, S. cerevisiae increased the content of total soluble solids, improving the quality of strawberries.O morango é um fruto de grande aceitação e muito apreciado por todo o mundo, além de ser de grande importância para pequenos agricultores, gerando trabalho e renda. Porém, essa cultura é atacada por diversas doenças, o que faz seu controle necessário, de modo que os produtores recorrem ao uso de fungicidas químicos, os quais, além de contaminarem o solo e a água, acabam por contaminar os frutos. Na tentativa de se reduzir a carga de agrotóxicos utilizados no cultivo do morangueiro, tem-se pesquisado o controle biológico de doenças. No entanto, o controle biológico de doenças no morangueiro não deve interferir de maneira negativa na qualidade dos frutos. Dessa maneira, este trabalho teve como objetivo avaliar a acidez, o pH e os sólidos solúveis totais (ºBrix) em frutos de morangueiros tratados com Saccharomyces cerevisiae, Saccharomyces boulardii e Bacillus cereus, agentes utilizados no controle biológico de doenças. Nenhum dos tratamentos interferiu no pH e na acidez titulável total; porém, S. cerevisiae proporcionou aumento do teor de sólidos solúveis totais, melhorando sua qualidade

    Dynamic Near-Infrared Optical Imaging of 2-Deoxyglucose Uptake by Intracranial Glioma of Athymic Mice

    Get PDF
    BACKGROUND: It is recognized that cancer cells exhibit highly elevated glucose metabolism compared to non-tumor cells. We have applied in vivo optical imaging to study dynamic uptake of a near-infrared dye-labeled glucose analogue, 2-deoxyglucose (2-DG) by orthotopic glioma in a mouse model. METHODOLOGY AND PRINCIPAL FINDINGS: The orthotopic glioma model was established by surgically implanting U87-luc glioma cells into the right caudal nuclear area of nude mice. Intracranial tumor growth was monitored longitudinally by bioluminescence imaging and MRI. When tumor size reached >4 mm diameter, dynamic fluorescence imaging was performed after an injection of the NIR labeled 2-DG, IRDye800CW 2-DG. Real-time whole body images acquired immediately after i.v. infusion clearly visualized the near-infrared dye circulating into various internal organs sequentially. Dynamic fluorescence imaging revealed significantly higher signal intensity in the tumor side of the brain than the contralateral normal brain 24 h after injection (tumor/normal ratio, TNR = 2.8+/-0.7). Even stronger contrast was achieved by removing the scalp (TNR = 3.7+/-1.1) and skull (TNR = 4.2+/-1.1) of the mice. In contrast, a control dye, IRDye800CW carboxylate, showed little difference (1.1+/-0.2). Ex vivo fluorescence imaging performed on ultrathin cryosections (20 microm) of tumor bearing whole brain revealed distinct tumor margins. Microscopic imaging identified cytoplasmic locations of the 2-DG dye in tumor cells. CONCLUSION AND SIGNIFICANCE: Our results suggest that the near-infrared dye labeled 2-DG may serve as a useful fluorescence imaging probe to noninvasively assess intracranial tumor burden in preclinical animal models

    Single-molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils

    Get PDF
    Muscle contraction is controlled at two levels: the thin and the thick filaments. The latter level of control involves three states of myosin heads: active, disordered relaxed (DRX), and super-relaxed (SRX), the distribution of which controls the number of myosins available to interact with actin. How these are controlled is still uncertain. Using fluorescently labeled ATP, we were able to spatially assign the activity of individual myosins within the sarcomere. We observed that SRX comprises 53% of all heads in the C-zone compared with 35% and 44% in the P- and D-zones, respectively. The recently FDA-approved hypertrophic cardiomyopathy drug, mavacamten (mava), significantly decreased DRX, favoring SRX in both the C- and D-zones at 60% and 63%, respectively. Since thick filament regulation is in part regulated by the myosin-binding protein-C (MyBP-C), we also studied PKA phosphorylation. This had the opposite effect as mava, specifically in the C-zone where it decreased SRX to 34%, favoring DRX. These results directly show that excess concentrations of mava do increase SRX, but the effect is limited across the sarcomere, suggesting mava is less effective on skeletal muscle. In addition, we show that PKA directly affects the contractile machinery of skeletal muscle leading to the liberation of repressed heads. Since the effect is focused on the C-zone, this suggests it is likely through MyBP-C phosphorylation, although our data suggest that a further reserve of myosins remain that are not accessible to PKA treatment

    Cytosolic interactome protects against protein unfolding in a single molecule experiment

    Get PDF
    Single molecule techniques are particularly well suited for investigating the processes of protein folding and chaperone assistance. However, current assays provide only a limited perspective on the various ways in which the cellular environment can influence the folding pathway of a protein. In this study, a single molecule mechanical interrogation assay is developed and used to monitor protein unfolding and refolding within a cytosolic solution. This allows to test the cumulative topological effect of the cytoplasmic interactome on the folding process. The results reveal a stabilization against forced unfolding for partial folds, which are attributed to the protective effect of the cytoplasmic environment against unfolding and aggregation. This research opens the possibility of conducting single molecule molecular folding experiments in quasi-biological environments.Pharmacolog

    Circuit topology approach for the comparative analysis of intrinsically disordered proteins

    Get PDF
    Intrinsically disordered proteins (IDPs) lack a stable native conformation, making it challenging to characterize their structure and dynamics. Key topological motifs with fundamental biological relevance are often hidden in the conformational noise, eluding detection. Here, we develop a circuit topology toolbox to extract conformational patterns, critical contacts, and timescales from simulated dynamics of intrinsically disordered proteins. We follow the dynamics of IDPs by providing a smart low-dimensionality representation of their three-dimensional (3D) configuration in the topology space. Such an approach allows us to quantify topological similarity in dynamic systems, therefore providing a pipeline for structural comparison of IDPs.Pharmacolog

    SMART-KG: Hybrid Shipping for SPARQL Querying on the Web

    Get PDF
    While Linked Data (LD) provides standards for publishing (RDF) and (SPARQL) querying Knowledge Graphs (KGs) on the Web, serving, accessing and processing such open, decentralized KGs is often practically impossible, as query timeouts on publicly available SPARQL endpoints show. Alternative solutions such as Triple Pattern Fragments (TPF) attempt to tackle the problem of availability by pushing query processing workload to the client side, but suffer from unnecessary transfer of irrelevant data on complex queries with large intermediate results. In this paper we present smart-KG, a novel approach to share the load between servers and clients, while significantly reducing data transfer volume, by combining TPF with shipping compressed KG partitions. Our evaluations show that smart-KG outperforms state-of-the-art client-side solutions and increases server-side availability towards more cost-effective and balanced hosting of open and decentralized KGs

    Pulpal sequelae after trauma to anterior teeth among adult Nigerian dental patients

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Epidemiological studies show that about 11.6% to 33.0% of all boys and about 3.6% to 19.3% of all girls suffer dental trauma of varying severity before the age of 12 years. Moderate injuries to the periodontium such as concussion and subluxation are usually associated with relatively minor symptoms and hence may go unnoticed by the patient or the dentist, if consulted. Patients with these kinds of injuries present years after a traumatic accident most of the time with a single discoloured tooth. This study sets out to document the incidence of various posttraumatic sequelae of discoloured anterior teeth among adult Nigerian dental patients.</p> <p>Methods</p> <p>One hundred and sixty eight (168) traumatized discoloured anterior teeth in 165 patients were studied. Teeth with root canal treatment were excluded from the study. Partial obliteration was recorded when the pulp chamber or root canal was not discernible or reduced in size on radiographs, total obliteration was recorded when pulp chamber and root canal were not discernible. A retrospective diagnosis of concussion was made from patient's history of trauma to the tooth without abnormal loosening, while subluxation was made from patient's history of trauma to the tooth with abnormal loosening.</p> <p>Results</p> <p>Of the 168 traumatized discoloured anterior teeth, 47.6% and 31.6% had partial and total obliteration of the pulp canal spaces respectively, 20.8% had pulpal necrosis. Concussion and subluxation injuries resulted more in obliteration of the pulp canal space, while fracture of the teeth resulted in more pulpal necrosis (p < 0.001). Injuries sustained during the 1<sup>st </sup>and 2<sup>nd </sup>decade of life resulted more in obliteration of the pulp canal space, while injuries sustained in the 3<sup>rd </sup>decade resulted in more pulpal necrosis.</p> <p>Conclusion</p> <p>Calcific metamorphosis developed more in teeth with concussion and subluxation injuries. Pulpal necrosis occurred more often in traumatized teeth including fractures.</p
    • …
    corecore