Estudios mecánicos y funcionales de biomoléculas a nivel de moléculas individuales

Dentro de la célula se generan fuerzas mecánicas en muchos procesos moleculares fundamentales, tales como catálisis enzimática, movimiento de motores moleculares, segregación de cromosomas, formación de vesículas, etc. Los recientes avances tecnológicos han permitido la aplicación y medición de fuerzas sobre biomoléculas con extrema precisión a nivel de moléculas individuales. Estas nuevas metodologías permiten, visualizar y atrapar a moléculas únicas. Entre estos instrumentos de manipulación se encuentran las pinzas ópticas y magnéticas y las técnicas de visualización tenemos los instrumentos fluorescentes como FCS y TIRF. Además al estudiar de una molécula a la vez, se puede obtener información que en estudios de asamblea estadística o in multiplo se esconden dentro del promedio de la población. Por ejemplo eventos raros como pausas o retrocesos de sistemas biológicos se observan que de otra manera se promediaría y no se detectarían en la población. En la presentación se mostrarán los tipos de datos que se obtienen a partir de estos instrumentos y el análisis de las fluctuaciones de las proteínas a nivel de moléculas individuales. Se mostrará en particular cómo una chaperona esencial (BiP) en el retículo endoplásmico ejerce su función para ayudar al correcto plegamiento de proteínas.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Inferring muscle functional roles of the ostrich pelvic limb during walking and running using computer optimization

Owing to their cursorial background, ostriches (Struthio camelus) walk and run with high metabolic economy, can reach very fast running speeds and quickly execute cutting manoeuvres. These capabilities are believed to be a result of their ability to coordinate muscles to take advantage of specialized passive limb structures. This study aimed to infer the functional roles of ostrich pelvic limb muscles during gait. Existing gait data were combined with a newly developed musculoskeletal model to generate simulations of ostrich walking and running that predict muscle excitations, force and mechanical work. Consistent with previous avian electromyography studies, predicted excitation patterns showed that individual muscles tended to be excited primarily during only stance or swing. Work and force estimates show that ostrich gaits are partially hip-driven with the bi-articular hip–knee muscles driving stance mechanics. Conversely, the knee extensors acted as brakes, absorbing energy. The digital extensors generated large amounts of both negative and positive mechanical work, with increased magnitudes during running, providing further evidence that ostriches make extensive use of tendinous elastic energy storage to improve economy. The simulations also highlight the need to carefully consider non-muscular soft tissues that may play a role in ostrich gait

Relax, Don't RAN Translate It

The (GGGGCC)n repeat expansion in C9orf72, which is the most common cause of frontotemporal dementia and amyotrophic lateral sclerosis, is translated through repeat-associated non-AUG (RAN) translation. In this issue of Neuron, Cheng et al. (2019) report that the helicase DDX3X, which unwinds (or relaxes) RNA, suppresses RAN translation and toxicity

The experiences of new graduate midwives working in midwifery continuity of care models in Australia

© 2015 Elsevier Ltd. Background: Midwifery continuity of care has been shown to be beneficial to women through reducing interventions and other maternal and neonatal morbidity. In Australia, numerous government reports recognise the importance of midwifery models of care that provide continuity. Given the benefits, midwives, including new graduate midwives, should have the opportunity to work in these models of care. Historically, new graduates have been required to have a number of years' experience before they are able to work in these models of care although a small number have been able to move into these models as new graduates. Aim: to explore the experiences of the new graduate midwives who have worked in midwifery continuity of care, in particular, the support they received; and, to establish the facilitators and barriers to the expansion of new graduate positions in midwifery continuity of care models. Method: a qualitative descriptive study was undertaken framed by the concept of continuity of care. Findings: the new graduate midwives valued the relationship with the women and with the group of midwives they worked alongside. The ability to develop trusting relationships, consolidate skills and knowledge, be supported by the group and finally feeling prepared to work in midwifery continuity of care from their degree were all sub-themes. All of these factors led to the participants feeling as though they were 'becoming a real midwife'. Conclusions: this is the first study to demonstrate that new graduate midwives value working in midwifery continuity of care - they felt well prepared to work in this way from their degree and were supported by midwives they worked alongside. The participants reported having more confidence to practice when they have a relationship with the woman, as occurs in these models

The challenge of employing and managing new graduate midwives in midwifery group practices in hospitals

© 2016 John Wiley & Sons Ltd. AIM(S): This study explores the views of midwifery managers and key stakeholders, regarding the facilitators and barriers to employing new graduate midwives in midwifery continuity of care models.BACKGROUND: Maternity services in Australia are shifting towards midwifery continuity of care models, where midwives work in small group practices, requiring a change to the management of staff. Public policy in Australia supports maternity services to be reconfigured in this way. Historically, experienced midwives work in these models, as demand grows; new graduates are employed to staff the models.METHOD(S): A qualitative descriptive approach exploring the manager's experience of employing new graduate's in the models. Managers, clinical educators and hospital midwifery consultants (n = 15) were recruited by purposeful sampling.RESULTS: Drivers, enablers, facilitators and barriers to employing new graduates in the models were identified. Visionary leadership enabled the managers to employ new graduates in the models through initial and ongoing support. Managing the myths stemming from fear of employing new graduates to work in midwifery continuity of care models was challenging.CONCLUSION: Managers and other key stakeholders provide initial and ongoing support through orientation and providing a reduced workload.IMPLICATIONS FOR NURSING MANAGEMENT: Visionary leadership can be seen as critical to supporting new graduates into midwifery continuity of care models. The challenges for management to overcome include managing the myths stemming from fear of employing new graduates to work in a flexible way around the needs of the women within an organisation culture

Can homogeneous nucleation resolve the inner core nucleation paradox?

The formation of Earth's solid inner core is thought to mark a profound change in the evolution of the deep Earth and the power that is available to generate the geomagnetic field. Previous studies generally find that the inner core nucleated around 0.5–1 billion years ago, but neglect the fact that homogeneous liquids must be cooled far below their melting point in order for solids to form spontaneously. The classical theory of nucleation predicts that the core must be undercooled by several hundred K, which is incompatible with estimates of the core's present-day temperature. This “inner core nucleation paradox” therefore asserts that the present inner core should not have formed, leaving a significant gap in our understanding of deep Earth evolution. In this paper we explore the nucleation process in as yet untested iron-rich systems which may comprise the Earth's early core. We find that 1 mol.% Si and S increase the supercooling required to freeze the inner core compared to pure iron by 400 K and 1000 K respectively. 10 mol.% O reduces the required inner core nucleation supercooling to 730 K and 3 mol.% C to only 612 K, which is close to resolving the paradox but still requires that the inner core formed recently

Heat and fluid flow in a scraped-surface heat exchanger containing a fluid with temperature-dependent viscosity

Scraped-surface heat exchangers (SSHEs) are extensively used in a wide variety of industrial settings where the continuous processing of fluids and fluid-like materials is involved. The steady non-isothermal flow of a Newtonian fluid with temperature-dependent viscosity in a narrow-gap SSHE when a constant temperature difference is imposed across the gap between the rotor and the stator is investigated. The mathematical model is formulated and the exact analytical solutions for the heat and fluid flow of a fluid with a general dependence of viscosity on temperature for a general blade shape are obtained. These solutions are then presented for the specific case of an exponential dependence of viscosity on temperature. Asymptotic methods are employed to investigate the behaviour of the solutions in several special limiting geometries and in the limits of weak and strong thermoviscosity. In particular, in the limit of strong thermoviscosity (i.e., strong heating or cooling and/or strong dependence of viscosity on temperature) the transverse and axial velocities become uniform in the bulk of the flow with boundary layers forming either just below the blade and just below the stationary upper wall or just above the blade and just above the moving lower wall. Results are presented for the most realistic case of a linear blade which illustrate the effect of varying the thermoviscosity of the fluid and the geometry of the SSHE on the flow

CEPSim: Modelling and Simulation of Complex Event Processing Systems in Cloud Environments

The emergence of Big Data has had profound impacts on how data are stored and processed. As technologies created to process continuous streams of data with low latency, Complex Event Processing (CEP) and Stream Processing (SP) have often been related to the Big Data velocity dimension and used in this context. Many modern CEP and SP systems leverage cloud environments to provide the low latency and scalability required by Big Data applications, yet validating these systems at the required scale is a research problem per se. Cloud computing simulators have been used as a tool to facilitate reproducible and repeatable experiments in clouds. Nevertheless, existing simulators are mostly based on simple application and simulation models that are not appropriate for CEP or for SP. This article presents CEPSim, a simulator for CEP and SP systems in cloud environments. CEPSim proposes a query model based on Directed Acyclic Graphs (DAGs) and introduces a simulation algorithm based on a novel abstraction called event sets. CEPSim is highly customizable and can be used to analyze the performance and scalability of user-defined queries and to evaluate the effects of various query processing strategies. Experimental results show that CEPSim can simulate existing systems in large Big Data scenarios with accuracy and precision

Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF). Vascular endothelial growth factor (VEGF) concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO) is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. METHODS: 27 IPF patients were studied (maximum follow-up 65 months). Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs) were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC) % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB) % predicted. RESULTS: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. CONCLUSION: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF. KEYWORDS: alveolar nitric oxide; idiopathic pulmonary fibrosis; vascular endothelial growth facto