Identification of time-dependent interfacial mechanical properties of adhesive by hybrid/inverse method

Interfacial mechanical properties of the adhesive bonded interface are strongly time-dependent in most engineering structures due to the viscoelasticity of the adhesive layer. To predict those properties and investigate their effect on the time-dependen

Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F

Deregulation of cap-dependent translation is associated with cancer initiation and progression. The rate-limiting step of protein synthesis is the loading of ribosomes onto mRNA templates stimulated by the heterotrimeric complex, eukaryotic initiation factor (eIF)4F. This step represents an attractive target for anticancer drug discovery because it resides at the nexus of the TOR signaling pathway. We have undertaken an ultra-high-throughput screen to identify inhibitors that prevent assembly of the eIF4F complex. One of the identified compounds blocks interaction between two subunits of eIF4F. As a consequence, cap-dependent translation is inhibited. This compound can reverse tumor chemoresistance in a genetically engineered lymphoma mouse model by sensitizing cells to the proapoptotic action of DNA damage. Molecular modeling experiments provide insight into the mechanism of action of this small molecule inhibitor. Our experiments validate targeting the eIF4F complex as a strategy for cancer therapy to modulate chemosensitivity

Intrinsically Photosensitive Retinal Ganglion Cells

Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in the absence of all rod and cone photoreceptor input. The existence of these ganglion cell photoreceptors, although predicted from observations scattered over many decades, was not established until it was shown that a novel photopigment, melanopsin, was expressed in retinal ganglion cells of rodents and primates. Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate than vertebrate photoreceptors and appears to be mediated by transient receptor potential channels. In the retina, ipRGCs provide excitatory drive to dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells via gap junctions. Several subtypes of ipRGC have been identified in rodents based on their morphology, physiology and expression of molecular markers. ipRGCs convey irradiance information centrally via the optic nerve to influence several functions including photoentrainment of the biological clock located in the hypothalamus, the pupillary light reflex, sleep and perhaps some aspects of vision. In addition, ipRGCs may also contribute irradiance signals that interface directly with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body. Here we review the early work that provided the motivation for searching for a new mammalian photoreceptor, the ground-breaking discoveries, current progress that continues to reveal the unusual properties of these neuron photoreceptors, and directions for future investigation

Long-Term Survival of Hydrated Resting Eggs from Brachionus plicatilis

Several organisms display dormancy and developmental arrest at embryonic stages. Long-term survival in the dormant form is usually associated with desiccation, orthodox plant seeds and Artemia cysts being well documented examples. Several aquatic invertebrates display dormancy during embryonic development and survive for tens or even hundreds of years in a hydrated form, raising the question of whether survival in the non-desiccated form of embryonic development depends on pathways similar to those occurring in desiccation tolerant forms

Fem Simulation of the Cross-Wedge Rolling Process for a Stepped Shaft

The paper presents the results of numerical modeling of a cross-wedge rolling process for producing a stepped shaft. The modeling was performed with commercial software Forge NxT 1.1 using the finite element method. The numerical analysis enabled the determination of changes in the shape of the workpiece, effective strain, damage function and temperature distributions, as well as variations in the forces and torque acting on the tool. The numerical results demonstrate that personal computers can today be used to model even the most difficult cases of the cross-wedge rolling process, in which complex shapes of the tools and thermal phenomena occurring during the forming process have to be taken into considerationПредставлены результаты численного моделирования процесса поперечно-клиновой прокатки для изготовления ступенчатого вала. Моделирование выполнялось на базе коммерческой программы Forge NxT 1.1 с использованием метода конечных элементов. Численное решение позволило определить изменения формы изделия, эффективной деформации, функции повреждаемости и распределения температур, а также сил и крутящих моментов, действующих на вал. Показано, что для моделирования даже наиболее трудных случаев процесса ПКП, когда необходимо учитывать сложные конфигурации изделий и тепловые явления, возникающие в процессе формоизменения, могут использоваться персональные компьютеры