A comparative numerical analysis on the effect of welding consumables on the ballistic resistance of SMAW joints of armor steel

In the present investigation, a comparative study of ballistic impact behavior of Armox 500T (base metal) and its weldments prepared by low hydrogen ferrite (weldment-1) and austenitic stainless steel (weldment-2) consumables against 7.62 AP bullet has been performed with the help of finite element analysis code Abaqus 2017. Further, the result is validated with the experimental results. The experiment has been performed on the base metal, weldment-1, and weldment-2 against 7.62 AP bullet. Further, a two-dimensional explicit model has been developed for given purpose to simulate the bullet penetration at such high strain rate (103 s−1). Both bullet and plate are considered as deformable. Experimental results revealed that the depth of penetration in the base metal, weldment-1, and weldment-2 is 10.93, 13.65, and 15.20 mm respectively. Further computational results revealed that the depth of penetration of base metal, weldment-1, and weldment-2 is 10.11, 12.87, and 14.60 mm, respectively. Furthermore, weldment-1 shows more resistance against 7.62 AP bullet than weldment-2 in experimentation as well as FEA results. The percentage difference between experimental and FEA results are less than 10% which shows the prediction capability of FEA models. A feasibility analysis has been presented for using the welding consumables to weld the Armox 500T plate. Finally, in terms of ballistic resistance, the low hydrogen ferrite consumables are more appropriate than austenitic stainless-steel electrodes

Kinetic regulation of multi-ligand binding proteins

Background: Second messengers, such as calcium, regulate the activity of multisite binding proteins in a concentration-dependent manner. For example, calcium binding has been shown to induce conformational transitions in the calcium-dependent protein calmodulin, under steady state conditions. However, intracellular concentrations of these second messengers are often subject to rapid change. The mechanisms underlying dynamic ligand-dependent regulation of multisite proteins require further elucidation. Results: In this study, a computational analysis of multisite protein kinetics in response to rapid changes in ligand concentrations is presented. Two major physiological scenarios are investigated: i) Ligand concentration is abundant and the ligand-multisite protein binding does not affect free ligand concentration, ii) Ligand concentration is of the same order of magnitude as the interacting multisite protein concentration and does not change. Therefore, buffering effects significantly influence the amounts of free ligands. For each of these scenarios the influence of the number of binding sites, the temporal effects on intermediate apo- and fully saturated conformations and the multisite regulatory effects on target proteins are investigated. Conclusions: The developed models allow for a novel and accurate interpretation of concentration and pressure jump-dependent kinetic experiments. The presented model makes predictions for the temporal distribution of multisite protein conformations in complex with variable numbers of ligands. Furthermore, it derives the characteristic time and the dynamics for the kinetic responses elicited by a ligand concentration change as a function of ligand concentration and the number of ligand binding sites. Effector proteins regulated by multisite ligand binding are shown to depend on ligand concentration in a highly nonlinear fashion

Hyperexcitability of the local cortical circuit in mouse models of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which shift a balance between excitation and inhibition. To decipher the synaptic substrate of hyperexcitability, we examined pan-neuronal Tsc1 knockout mouse and found a reduction in surface expression of a GABA receptor (GABAR) subunit but not AMPA receptor (AMPAR) subunit. Using electrophysiological recordings, we found a significant reduction in the frequency of GABAR-mediated miniature inhibitory postsynaptic currents (GABAR-mIPSCs) but not AMPAR-mediated miniature excitatory postsynaptic currents (AMPAR-mEPSCs) in layer 2/3 pyramidal neurons. To determine a subpopulation of interneurons that are especially vulnerable to the absence of TSC1 function, we also analyzed two strains of conditional knockout mice targeting two of the prominent interneuron subtypes that express parvalbumin (PV) or somatostatin (SST). Unlike pan-neuronal knockout mice, both interneuron-specific Tsc-1 knockout mice did not develop spontaneous seizures and grew into adults. Further, the properties of AMPAR-mEPSCs and GABAR-mIPSCs were normal in both Pv-Cre and Sst-Cre x Tsc1fl/fl knockout mice. These results indicate that removal of TSC1 from all neurons in a local cortical circuit results in hyperexcitability while connections between pyramidal neurons and interneurons expressing PV and SST are preserved in the layer 2/3 visual cortex. Our study suggests that another inhibitory cell type or a combination of multiple subtypes may be accountable for hyperexcitability in TSC. Keywords: Tuberous sclerosis complex; E/I balance; AMPA receptor; GABA receptor; Autism; Epilepsy; mTOR pathwa

Sensory Experience Differentially Modulates the mRNA Expression of the Polysialyltransferases ST8SiaII and ST8SiaIV in Postnatal Mouse Visual Cortex

Polysialic acid (PSA) is a unique carbohydrate composed of a linear homopolymer of α-2,8 linked sialic acid, and is mainly attached to the fifth immunoglobulin-like domain of the neural cell adhesion molecule (NCAM) in vertebrate neural system. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII (also known as STX) and ST8SiaIV (also known as PST). By modulating adhesive property of NCAM, PSA plays a critical role in several neural development processes such as cell migration, neurite outgrowth, axon pathfinding, synaptogenesis and activity-dependent plasticity. The expression of PSA is temporally and spatially regulated during neural development and a tight regulation of PSA expression is essential to its biological function. In mouse visual cortex, PSA is downregulated following eye opening and its decrease allows the maturation of GABAergic synapses and the opening of the critical period for ocular dominance plasticity. Relatively little is known about how PSA levels are regulated by sensory experience and neuronal activity. Here, we demonstrate that while both ST8SiaII and ST8SiaIV mRNA levels decrease around the time of eye opening in mouse visual cortex, only ST8SiaII mRNA level reduction is regulated by sensory experience. Using an organotypic culture system from mouse visual cortex, we further show that ST8SiaII gene expression is regulated by spiking activity and NMDA-mediated excitation. Further, we show that both ST8SiaII and ST8SiaIV mRNA levels are positively regulated by PKC-mediated signaling. Therefore, sensory experience-dependent ST8SiaII gene expression regulates PSA levels in postnatal visual cortex, thus acting as molecular link between visual activity and PSA expression

Desynchronization of Neocortical Networks by Asynchronous Release of GABA at Autaptic and Synaptic Contacts from Fast-Spiking Interneurons

An activity-dependent long-lasting asynchronous release of GABA from identified fast-spiking inhibitory neurons in the neocortex can impair the reliability and temporal precision of activity in a cortical network

A Missense Mutation in a Highly Conserved Alternate Exon of Dynamin-1 Causes Epilepsy in Fitful Mice

Dynamin-1 (Dnm1) encodes a large multimeric GTPase necessary for activity-dependent membrane recycling in neurons, including synaptic vesicle endocytosis. Mice heterozygous for a novel spontaneous Dnm1 mutation—fitful—experience recurrent seizures, and homozygotes have more debilitating, often lethal seizures in addition to severe ataxia and neurosensory deficits. Fitful is a missense mutation in an exon that defines the DNM1a isoform, leaving intact the alternatively spliced exon that encodes DNM1b. The expression of the corresponding alternate transcripts is developmentally regulated, with DNM1b expression highest during early neuronal development and DNM1a expression increasing postnatally with synaptic maturation. Mutant DNM1a does not efficiently self-assemble into higher order complexes known to be necessary for proper dynamin function, and it also interferes with endocytic recycling in cell culture. In mice, the mutation results in defective synaptic transmission characterized by a slower recovery from depression after trains of stimulation. The DNM1a and DNM1b isoform pair is highly conserved in vertebrate evolution, whereas invertebrates have only one isoform. We speculate that the emergence of more specialized forms of DNM1 may be important in organisms with complex neuronal function

Membrane Properties and the Balance between Excitation and Inhibition Control Gamma-Frequency Oscillations Arising from Feedback Inhibition

Computational studies as well as in vivo and in vitro results have shown that many cortical neurons fire in a highly irregular manner and at low average firing rates. These patterns seem to persist even when highly rhythmic signals are recorded by local field potential electrodes or other methods that quantify the summed behavior of a local population. Models of the 30–80 Hz gamma rhythm in which network oscillations arise through ‘stochastic synchrony’ capture the variability observed in the spike output of single cells while preserving network-level organization. We extend upon these results by constructing model networks constrained by experimental measurements and using them to probe the effect of biophysical parameters on network-level activity. We find in simulations that gamma-frequency oscillations are enabled by a high level of incoherent synaptic conductance input, similar to the barrage of noisy synaptic input that cortical neurons have been shown to receive in vivo. This incoherent synaptic input increases the emergent network frequency by shortening the time scale of the membrane in excitatory neurons and by reducing the temporal separation between excitation and inhibition due to decreased spike latency in inhibitory neurons. These mechanisms are demonstrated in simulations and in vitro current-clamp and dynamic-clamp experiments. Simulation results further indicate that the membrane potential noise amplitude has a large impact on network frequency and that the balance between excitatory and inhibitory currents controls network stability and sensitivity to external inputs

Post hoc immunostaining of GABAergic neuronal subtypes following in vivo two-photon calcium imaging in mouse neocortex

GABAergic neurons in the neocortex are diverse with regard to morphology, physiology, and axonal targeting pattern, indicating functional specializations within the cortical microcircuitry. Little information is available, however, about functional properties of distinct subtypes of GABAergic neurons in the intact brain. Here, we combined in vivo two-photon calcium imaging in supragranular layers of the mouse neocortex with post hoc immunohistochemistry against the three calcium-binding proteins parvalbumin, calretinin, and calbindin in order to assign subtype marker profiles to neuronal activity. Following coronal sectioning of fixed brains, we matched cells in corresponding volumes of image stacks acquired in vivo and in fixed brain slices. In GAD67-GFP mice, more than 95% of the GABAergic cells could be unambiguously matched, even in large volumes comprising more than a thousand interneurons. Triple immunostaining revealed a depth-dependent distribution of interneuron subtypes with increasing abundance of PV-positive neurons with depth. Most importantly, the triple-labeling approach was compatible with previous in vivo calcium imaging following bulk loading of Oregon Green 488 BAPTA-1, which allowed us to classify spontaneous calcium transients recorded in vivo according to the neurochemically defined GABAergic subtypes. Moreover, we demonstrate that post hoc immunostaining can also be applied to wild-type mice expressing the genetically encoded calcium indicator Yellow Cameleon 3.60 in cortical neurons. Our approach is a general and flexible method to distinguish GABAergic subtypes in cell populations previously imaged in the living animal. It should thus facilitate dissecting the functional roles of these subtypes in neural circuitry

How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property

The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe