13 research outputs found
Investigating the complexity of cGMP-dependent protein kinase type Iα regulation by reactive oxygen species and cyclic nucleotides
No full textAuthor response: Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control
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Predicting evolutionarily stable strategies from functional responses of Sonoran Desert annuals to precipitation
No full textFor many decades, researchers have studied how plants use bet-hedging strategies to insure against unpredictable, unfavourable conditions. We improve upon earlier analyses by explicitly accounting for how variable precipitation affects annual plant species' bet-hedging strategies. We consider how the survival rates of dormant seeds (in a 'seed bank') interact with precipitation responses to influence optimal germination strategies. Specifically, we incorporate how response to resource availability (i.e. the amount of offspring (seeds) generated per plant in response to variation in desert rainfall) influences the evolution of germination fractions. Using data from 10 Sonoran Desert annual plants, we develop models that explicitly include these responses to model fitness as a function of precipitation. For each of the species, we identify the predicted evolutionarily stable strategies (ESSs) for the fraction of seeds germinating each year and then compare our estimated ESS values to the observed germination fractions. We also explore the relative importance of seed survival and precipitation responses in shaping germination strategies by regressing ESS values and observed germination fractions against these traits. We find that germination fractions are lower for species with higher seed survival, with lower reproductive success in dry years, and with better yield responses in wet years. These results illuminate the evolution of bet-hedging strategies in an iconic system, and provide a framework for predicting how current and future environmental conditions may reshape those strategies
Predicting Evolutionarily Stable Strategies from Functional Responses of Sonoran Desert Annuals to Precipitation
No full textAbstractFor many decades, researchers have studied how plants use bet-hedging strategies to insure against unpredictable, unfavorable conditions. We improve upon earlier analyses by explicitly accounting for how variable precipitation affects annual plant species’ bet-hedging strategies. We consider how the survival rates of dormant seeds (in a ‘seed bank’) interact with precipitation responses to influence optimal germination strategies. Specifically, we incorporate how response to resource availability (i.e. the amount of offspring (seeds) generated per plant in response to variation in desert rainfall) influences the evolution of germination fractions. Using data from 10 Sonoran Desert annual plants, we develop models that explicitly include these responses to model fitness as a function of precipitation. For each of the species, we identify the predicted evolutionarily stable strategies (ESS) for the fraction of seeds germinating each year and then compare our estimated ESS values to the observed germination fractions. We also explore the relative importance of seed survival and precipitation responses in shaping germination strategies by regressing ESS values and observed germination fractions against these traits. We find that germination fractions are lower for species with higher seed survival, with lower reproductive success in dry years, and with better yield responses in wet years. These results illuminate the evolution of bethedging strategies in an iconic system, and provide a framework for predicting how current and future environmental conditions may reshape those strategies.</jats:p
Predicting evolutionarily stable strategies from functional responses of Sonoran Desert annuals to precipitation
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Data-driven treatment selection for seamless phase II/III trials incorporating early-outcome data
No full textSeamless phase II/III clinical trials are conducted in two stages with treatment selection at the first stage. In the first stage, patients are randomized to a control or one of k > 1 experimental treatments. At the end of this stage, interim data are analysed, and a decision is made concerning which experimental treatment should continue to the second stage. If the primary endpoint is observable only after some period of follow-up, at the interim analysis data may be available on some early outcome on a larger number of patients than those for whom the primary endpoint is available. These early endpoint data can thus be used for treatment selection. For two previously proposed approaches, the power has been shown to be greater for one or other method depending on the true treatment effects and correlations. We propose a new approach that builds on the previously proposed approaches and uses data available at the interim analysis to estimate these parameters and then, on the basis of these estimates, chooses the treatment selection method with the highest probability of correctly selecting the most effective treatment. This method is shown to perform well compared with the two previously described methods for a wide range of true parameter values. In most cases, the performance of the new method is either similar to or, in some cases, better than either of the two previously proposed methods. © 2014 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd
TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation
No full textThe interaction between TACC3 (transforming acidic coiled coil protein 3) and the microtubule polymerase ch-TOG (colonic, hepatic tumor overexpressed gene) is evolutionarily conserved. Loading of TACC3–ch-TOG onto spindle microtubules requires the phosphorylation of TACC3 by Aurora-A kinase and the subsequent interaction of TACC3 with clathrin to form a microtubule binding surface. Whether there is a pool of TACC3–ch-TOG that is independent of clathrin in human cells, and what is the function of this pool, are open questions. Here, we report that TACC3 is recruited to the plus-ends of microtubules by its association with ch-TOG and that this pool is independent of phosphorylation and binding to clathrin. The plus-end binding of TACC3–ch-TOG persists in interphase and we propose that one cellular function of TACC3–ch-TOG is to modulate cell migration. We also describe the distinct subcellular pools of TACC3, ch-TOG and clathrin. TACC3 is often described as a centrosomal protein, but we show that there is no significant population of TACC3 at centrosomes. The delineation of distinct protein pools reveals a simplified view of how these proteins are organized and controlled by post-translational modification
Ez-Zemahşerî ve El-Unmûzec adlı eseri
No full textHicri V. asrın sonlarında ve h. VI. asrın başlarında İslam âleminin yetişdirdiği büyük âlimlerinden olan Zemahşerî, büyük bir müfessir, muhaddis ve nahiv âlimidir. Zemahşerî islâmî ve alet bilimleri literatüründe önemli bir yeri haizdir. Bilhassa nahiv alanındaki görüşleri ile kendisinden sonraki âlimleri etkilemiştir. Bu çalışmada bu denli bir müellifin hayatı, ilmî şahsiyeti ve nahiv ilmi hakkında yazdığı el-Unmûzec fi'n-Nahv adlı eseri incelenmiştir. Zemahşerî'nin nahiv ilmine yeni başlayanlar için yazdığı bu eserde nahiv kaidelerini öz bir şekilde ele almıştır. Daha sonra bu kaideleri âyet ve meşhur örneklemeler ile pekiştirmiştir. Bağdat nahiv ekolüne mensup olan Zemahşerî görüşlerinin çoğunda Basralıların görüşü doğrultusundadır. Ancak mümkün mertebe bu eserinde tartışmalara yer vermemiştir. Müellifin bu veciz eseri isim, fiil ve harf olmak üzere üç ana bölümden oluşmaktadır. Bu eserin en önemli kaynağı Zemahşerî'nin el-Mufassal adlı eseridir. Zemahşerî'nin el-Unmûzec fi'n-Nahv adlı eseri, muhtasar olarak yazılan eserler için adeta bir dönüm noktası olarak kabul edilmiştir. Bu eser birçok kere şerhedilmeye mazhar olmuştur. Aynı zamanda eskilerden beri medreselerde Arpaça öğrenimi için okutulan bu eser doğu medreselerinde hala okutulmakta ve talebeler tarafından ezberlenmektedir. Bu bakımdan el-Unmûzec'in nahiv alanında öğrencilere büyük katkısı olmuştur. Bu çalışmayla bu derece önemli olan bir eser akademik olarak incelenmiştir.Zemahshari one of the great scholars raised by the Islamic world in the end of the Hijri V. century and the verse of hijri VI century. He is a great mufassir, muhaddis and scholar in Arabic language. Zemahshari has an important place in the literature of Islam and linguistics. Especially with his views in the Arabic syntax area, he influenced the subsequent scholars. In this study, the life and scientific personality of the author and hes book al-Unmûzec fi'n-Nahv are examined. Zemahshari, in this work, has dealt with the grammatical bases in a certain way. He then strengthened these bases with Quranic verses and famous examples. It belongs to the Baghdad gremer school. Many of the views fit the views of the Basra school. However, as far as possible, this work has not included any discussion. This short work of the author is composed of three parts; name, verb and letter. The most important source of this work is Zemahshari's al-Mufassal. Zemahshari's al-Unmûzec fi'n-Nahv was accepted as a turning point for the short works. This work has been described many times. At the same time, this work, which was taught to learn Arabic in the meditations, is still taught in eastern medallions and memorized by students. In this respect, al-Unmûzec's contribution to the students in the field of Arabic syntax has been great. In this study a work of such importance has been studied academically
Appendix A123 from Predicting evolutionarily stable strategies from functional responses of sonoran desert annuals to precipitation
No full textAppendices A1 (ESS Calculations), A2 (Nondimensionalization), and A3 (System Design)
Synthesis of the Rheb and K-Ras4B GTPases
No full textFarnesylated and carboxymethylated Rheb (see picture) and K-Ras4B GTPases were synthesized in useful amounts by a combination of expressed protein ligation and solid-phase lipopeptide synthesis. The functionality of the proteins was proven by biochemical, biophysical, and cell-based investigations
