Many cellular components are transported using a combination of the actin- and microtubule-based transport systems. However, how these two systems work together to allow well-regulated transport is ...not clearly understood. We investigate this question in the Xenopus melanophore model system, where three motors, kinesin II, cytoplasmic dynein, and myosin V, drive aggregation or dispersion of pigment organelles called melanosomes. During dispersion, myosin V functions as a "molecular ratchet" to increase outward transport by selectively terminating dynein-driven minus end runs. We show that there is a continual tug-of-war between the actin and microtubule transport systems, but the microtubule motors kinesin II and dynein are likely coordinated. Finally, we find that the transition from dispersion to aggregation increases dyneinmediated motion, decreases myosin V-mediated motion, and does not change kinesin II-dependent motion. Down-regulation of myosin V contributes to aggregation by impairing its ability to effectively compete with movement along microtubules.
The Paris Agreement calls for efforts to limit anthropogenic global warming to less than 1.5 °C above preindustrial levels. However, natural internal variability may exacerbate anthropogenic warming ...to produce temporary excursions above 1.5 °C. Such excursions would not necessarily exceed the Paris Agreement, but would provide a warning that the threshold is being approached. Here we develop a new capability to predict the probability that global temperature will exceed 1.5 °C above preindustrial levels in the coming 5 years. For the period 2017 to 2021 we predict a 38% and 10% chance, respectively, of monthly or yearly temperatures exceeding 1.5 °C, with virtually no chance of the 5‐year mean being above the threshold. Our forecasts will be updated annually to provide policy makers with advanced warning of the evolving probability and duration of future warming events.
Plain Language Summary
The Paris Agreement calls for efforts to limit human‐induced global warming to less than 1.5 °C above preindustrial levels. Observations of global mean temperature contain both human‐induced temperature change and superimposed natural variability. Natural variability may temporarily add to the underlying human‐induced warming, leading to observed temperatures that are higher than 1.5 °C for short‐term periods. This would not necessarily exceed the Paris agreement, which is usually interpreted to refer to long‐term averages, but would give an important indication that the threshold is being approached. If exceedance occurs, policy makers will require guidance regarding how long temperatures will remain above the threshold. Here we develop a new capability to predict the likelihood that global temperature will exceed 1.5 °C above preindustrial levels in the coming 5 years. We use decadal climate predictions that are regularly produced by several international climate prediction centers. Importantly, these predictions take into account the observed present day conditions since this is essential to predict the evolution of natural variability. For the period 2017 to 2021 we predict a 38% and 10% chance, respectively, of monthly or yearly temperatures exceeding 1.5 °C, with virtually no chance of the 5‐year mean being above the threshold. We will update our forecasts every year to provide policy makers with advanced warning of the evolving probability and duration of future warming events.
Key Points
Early temporary excursions above 1.5 °C would provide a warning that one of the Paris Agreement thresholds is being approached
Initialized climate predictions indicate a 38% (10%) chance of at least 1 month (year) exceeding 1.5 °C in the 5 year period 2017‐2021
Five‐year mean temperatures above 1.5 °C are extremely unlikely in this period
The synthesis, SAR studies, and pharmacokinetic properties of oxadiazole based tubulin inhibitor class are reported. This class of compounds binds to the colchicine site on tubulin and has ...antimitotic activity with nanomolar potency against tumor cell lines including cells with MDR phenotype.
Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1
μM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (
10, EC
50
=
7.8
nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure–activity relationships for this novel series of antimitotic agents.
Large sparse linear systems of equations are ubiquitous in science, engineering and beyond. This open access monograph focuses on factorization algorithms for solving such systems. It presents ...classical techniques for complete factorizations that are used in sparse direct methods and discusses the computation of approximate direct and inverse factorizations that are key to constructing general-purpose algebraic preconditioners for iterative solvers. A unified framework is used that emphasizes the underlying sparsity structures and highlights the importance of understanding sparse direct methods when developing algebraic preconditioners. Theoretical results are complemented by sparse matrix algorithm outlines. This monograph is aimed at students of applied mathematics and scientific computing, as well as computational scientists and software developers who are interested in understanding the theory and algorithms needed to tackle sparse systems. It is assumed that the reader has completed a basic course in linear algebra and numerical mathematics.
Melanophores move pigment organelles (melanosomes) from the cell center to the periphery and vice-versa. These bidirectional movements require cytoplasmic microtubules and microfilaments and depend ...on the function of microtubule motors and a myosin. Earlier we found that melanosomes purified from Xenopus melanophores contain the plus end microtubule motor kinesin II, indicating that it may be involved in dispersion (Rogers, S.L., I.S. Tint, P.C. Fanapour, and V.I. Gelfand. 1997. Proc. Natl. Acad. Sci. USA. 94: 3720-3725). Here, we generated a dominant-negative construct encoding green fluorescent protein fused to the stalk-tail region of Xenopus kinesin-like protein 3 (Xklp3), the 95-kD motor subunit of Xenopus kinesin II, and introduced it into melanophores. Overexpression of the fusion protein inhibited pigment dispersion but had no effect on aggregation. To control for the specificity of this effect, we studied the kinesin-dependent movement of lysosomes. Neither dispersion of lysosomes in acidic conditions nor their clustering under alkaline conditions was affected by the mutant Xklp3. Furthermore, microinjection of melanophores with SUK4, a function-blocking kinesin antibody, inhibited dispersion of lysosomes but had no effect on melanosome transport. We conclude that melanosome dispersion is powered by kinesin II and not by conventional kinesin. This paper demonstrates that kinesin II moves membrane-bound organelles.
Las orquídeas (familia Orchidaceae) son susceptibles a diversos factores bióticos y abióticos que afectan su desarrollo y calidad. Entre ellos, Cymbidium mosaic virus (CymMV) y Odontoglossum ringspot ...virus (ORSV) son los patógenos más frecuentes y de mayor importancia económica a nivel mundial. La transmisión mecánica de estos virus y la multiplicación principalmente agámica de las orquídeas hacen necesario contar con material madre libre de virus. El objetivo de este trabajo fue elaborar reactivos de diagnóstico para la detección de CymMV y ORSV. Se elaboró un antisuero policlonal contra CymMV+ORSV que se tituló 1:10000 mediante NC-ELISA. El antisuero fue procesado y se obtuvieron IgG e IgG-conjugada anti CymMV+ORSV dilución1:500 para su utilización en DAS-ELISA. La capacidad inmunodiagnóstica de esta técnica se evaluó mediante el análisis de muestras provenientes de orquídeas con síntomas característicos de infección viral, recolectadas en viveros comerciales de la ciudad de Córdoba, Argentina. La presencia de virosis se detectó en el 22 % de las muestras estudiadas y en el 75 % de los establecimientos relevados. La capacidad de estos reactivos para identificar CymMV, ORSV e infecciones mixtas en orquídeas permitirá agilizar y economizar los análisis. Esto representaría una ventaja para las detecciones a gran escala.
This paper deals with a method of designing PID controllers. Generalized Laguerre functions were used for this task. Generalized Laguerre functions generate an orthogonal base in the time domain and ...the operator domain. This property of generalized Laguerre functions is beneficially used for the design of the PID controller. Parameters for generalized Laguerre function PID controllers are computed from the Laguerre series of the open loop and the Laguerre series of the ideal open loop. To satisfy this goal, the plant transfer function, the controller transfer function, and the ideal open loop transfer function are transformed into a generalized Laguerre functions base. Three examples are shown to present this method.
Balanced Incomplete Factorization Bru, Rafael; Tůma, M.
SIAM journal on scientific computing,
01/2008, Letnik:
30, Številka:
5
Journal Article
Recenzirano
Odprti dostop
In this paper we present a new incomplete factorization of a square matrix into triangular factors in which we get standard $LU$ or $LDL^T$ factors (direct factors) and their inverses (inverse ...factors) at the same time. Algorithmically, we derive this method from the approach based on the Sherman-Morrison formula R. Bru, J. Cerdán, J. Marín, and J. Mas, SIAM J. Sci. Comput., 25 (2003), pp. 701-715. In contrast to the robust incomplete decomposition (RIF) algorithm M. Benzi and M. Tu ma, Numer. Linear Algebra Appl., 10 (2003), pp. 385-400 the direct and inverse factors here directly influence each other throughout the computation. Consequently, the algorithm to compute the approximate factors may mutually balance dropping in the factors and control their conditioning in this way. For the symmetric positive definite case, we derive the theory and present an algorithm for computing the incomplete $LDL^T$ factorization, and we discuss experimental results. We call this new approximate $LDL^T$ factorization the balanced incomplete factorization (BIF). Our experimental results confirm that this factorization is very robust and may be useful in solving difficult ill conditioned problems by preconditioned iterative methods. Moreover, the internal coupling of the computation of direct and inverse factors results in much shorter setup times (times to compute approximate decomposition) than RIF, a method of a similar and very high level of robustness. We also derive and present the theory for the general nonsymmetric case, but do not discuss its implementation.
Complex resuscitation may necessitate "miniteams" (ie, "intubation team" and "central-line team") or "special teams" (nurses discuss how to mix infusions; doctors discuss advanced airway techniques). ......we preemptively identify a Captain (typically a doctor) and Co-leader (typically a nurse). ...the team expands further and the patient is protected by a wider safety net. "D": Debrief/Defuse Debriefs can save future lives 14. ...performing the debrief immediately after the critical incident (or simulation) is likely to defuse team tension and the corrosive effect of members blaming themselves or others.
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