Characteristics of speech motor development in children.

Pulsed ultrasound was used to study tongue movements in the speech of 11 children, aged 3 yrs 3 mo to 11 yrs 6 mo. The stimuli were CV syllables that were produced at a normal speech rate with alternate vowels stressed. In Ss over 6 yrs of age, the pattern of tongue dorsum movement was identical to that observed in adults. For all Ss, the maximum velocity of tongue dorsum raising and lowering was correlated with the extent of the gesture. The slope of the relationship differed for stressed and unstressed vowels, although the differences were not consistent prior to age 6 yrs. For all Ss, the correlation between displacement and peak velocity was accompanied by a relatively constant interval from the initiation of the movement to the point of maximum velocity. The similarity in the tongue dorsum kinematics of children and adults is consistent with the idea that speech motor development involves a refinement of basic modes of motor operation rather than any significant change in the control of the speech apparatus. The speech data obtained are characteristic of systems that can be described by 2nd-order differential equations. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evolution of the germ line-soma relationship in vertebrate embryos

The germ line and soma together maintain genetic lineages from generation to generation: the germ line passes genetic information between generations; the soma is the vehicle for germ line transmission, and is shaped by natural selection. The germ line and somatic lineages arise simultaneously in early embryos, but how their development is related depends on how primordial germ cells (PGC) are specified. PGCs are specified by one of two means. Epigenesis describes the induction of PGCs from pluripotent cells by signals from surrounding somatic tissues. In contrast, PGCs in many species are specified cell-autonomously by maternally derived molecules, known as germ plasm, and this is called preformation. Germ plasm inhibits signaling to PGCs; thus, they are specified cell-autonomously. Germ plasm evolved independently in many animal lineages, suggesting convergent evolution, and therefore it would be expected to convey a selective advantage. But, what this is remains unknown. We propose that the selective advantage that drives the emergence of germ plasm in vertebrates is the disengagement of germ line specification from somatic influences. This liberates the evolution of gene regulatory networks (GRNs) that govern somatic development, and thereby enhances species evolvability, a well-recognized selective advantage. We cite recent evidence showing that frog embryos, which contain germ plasm, have modified GRNs that are not conserved in axolotls, which represent more basal amphibians and employ epigenesis. We also present the correlation of preformation with enhanced species radiations, and we discuss the mutually exclusive trajectories influenced by germ plasm or pluripotency, which shaped chordate evolution.     

The dynamic behaviour of parallel programs under process migration

We have studied the interaction between process-based parallel programs whose characteristics change in various ways at run time and the operation of load-balancing, as implemented by process migration. In order to do this, we propose a simple performance model, whose parameters represent features of the program's execution such as the frequency and regularity of the changes in computational characteristics, and conduct a series of experiments involving simulated executions of synthetic programs with controlled parameter values. From these we can deduce the relative importance of the parameters from the point of view of their influence on performance. We can explain our observations in terms of a simplified stochastic model that relates local changes in load to global behaviour. We show that the dynamics of load-balancing can be represented approximately by a first-order difference equation, and that the distributed process migration algorithm is consistent with a behaviour on the global scale which can be regarded as that of a traditional feedback controller.     

Strong Magnetic Field Annealing for Improved Phthalocyanine Organic Thin-Film Transistors

Thin-film microstructure, morphology, and polymorphism can be controlled and optimized to improve the performance of carbon-based electronics. Thermal or solvent vapor annealing are common post-deposition processing techniques; however, it can be difficult to control or destructive to the active layer or substrates. Here, the use of a static, strong magnetic field (SMF) as a non-destructive process for the improvement of phthalocyanine (Pc) thin-film microstructure, increasing organic thin-film transistor (OTFTs) mobility by twofold, is demonstrated. Grazing incident wide-angle X-ray scattering (GIWAXS), X-ray diffraction (XRD), and atomic force microscopy (AFM) elucidate the effect of SMF on both para- and diamagnetic Pc thin-films when subjected to a magnetic field. A SMF is found to increase the concentration of oxygen-induced radical species within the Pc thin-film, lending a paramagnetic character to ordinarily diamagnetic metal-free Pc and resulting in magnetic field induced changes to its thin-film microstructures. In a nitrogen environment, without competing degradation effects of molecular oxygen, SMF processing is found to favorably improve charge transport characteristics and increase OTFT mobility. Thus, post-deposition thin-film annealing with a magnetic field is presented as an alternative and promising technique for future thin-film engineering applications.     

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity**

Small molecules inducing protein degradation are important pharmacological tools to interrogate complex biology and are rapidly translating into clinical agents. However, to fully realise the potential of these molecules, selectivity remains a limiting challenge. Herein, we addressed the issue of selectivity in the design of CRL4^CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs). Thalidomide derivatives used to generate CRL4^CRBN recruiting PROTACs have well described intrinsic monovalent degradation profiles by inducing the recruitment of neo-substrates, such as GSPT1, Ikaros and Aiolos. We leveraged structural insights from known CRL4^CRBN neo-substrates to attenuate and indeed remove this monovalent degradation function in well-known CRL4^CRBN molecular glues degraders, namely CC-885 and Pomalidomide. We then applied these design principles on a previously published BRD9 PROTAC (dBRD9-A) and generated an analogue with improved selectivity profile. Finally, we implemented a computational modelling pipeline to show that our degron blocking design does not impact PROTAC-induced ternary complex formation. We believe that the tools and principles presented in this work will be valuable to support the development of targeted protein degradation.