Formin3 Regulates Dendritic Architecture and is Required for Somatosensory Nociceptive Behavior

Cell-type specific dendritic morphologies emerge via complex growth mechanisms modulated by intrinsic and extrinsic signaling coupled with activity-dependent regulation. Combined, these processes converge on cytoskeletal effectors to direct dendritic arbor development, stabilize mature architecture, and facilitate structural plasticity. Transcription factors (TFs) function as essential cell intrinsic regulators of dendritogenesis involving both combinatorial and cell-type specific effects, however the molecular mechanisms via which these TFs govern arbor development and dynamics remain poorly understood. Studies in Drosophila dendritic arborization (da) sensory neurons have revealed combinatorial roles of the TFs Cut and Knot in modulating dendritic morphology, however putative convergent nodal points of Cut/Knot cytoskeletal regulation remain elusive. Here we use a combined neurogenomic, bioinformatic, and genetic approach to identify and molecularly characterize downstream effectors of these TFs. From these analyses, we identified Formin3 (Form3) as a convergent transcriptional target of both Cut and Knot. We demonstrate that Form3 functions cell-autonomously in class IV (CIV) da neurons to stabilize distal higher order branching along the proximal-distal axis of dendritic arbors. Furthermore, live confocal imaging of multi-fluor cytoskeletal reporters and IHC analyses reveal that form3 mutants exhibit a specific collapse of the dendritic microtubule (MT) cytoskeleton, the functional consequences of which include defective dendritic trafficking of mitochondria and satellite Golgi. Biochemical analyses reveal Form3 directly interacts with MTs via the FH1/FH2 domains. Form3 is predicted to interact with two alpha-tubulin N-acetyltransferases (ATAT1) suggesting it may promote MT stabilization via acetylation. Analyses of acetylated dendritic MTs supports this hypothesis as defects in form3 lead to reductions, whereas overexpression promotes increases in MT acetylation. Neurologically, mutations in Inverted Formin 2 (INF2; the human ortholog of form3) have been causally linked to dominant intermediate Charcot-Marie-Tooth (CMT) disease E. CMT sensory neuropathies lead to distal sensory loss resulting in a reduced ability to sense heat, cold, and pain. Intriguingly, disruption of form3 function in CIV nociceptive neurons results in a severe impairment in nocifensive behavior in response to noxious heat, which can be rescued by expression of INF2 revealing shared primordial functions in regulating nociception and providing novel mechanistic insights into the potential etiological bases of CMT sensory neuropathies

Distributed memory compiler methods for irregular problems: Data copy reuse and runtime partitioning

Outlined here are two methods which we believe will play an important role in any distributed memory compiler able to handle sparse and unstructured problems. We describe how to link runtime partitioners to distributed memory compilers. In our scheme, programmers can implicitly specify how data and loop iterations are to be distributed between processors. This insulates users from having to deal explicitly with potentially complex algorithms that carry out work and data partitioning. We also describe a viable mechanism for tracking and reusing copies of off-processor data. In many programs, several loops access the same off-processor memory locations. As long as it can be verified that the values assigned to off-processor memory locations remain unmodified, we show that we can effectively reuse stored off-processor data. We present experimental data from a 3-D unstructured Euler solver run on iPSC/860 to demonstrate the usefulness of our methods

Knowledge of anganwadi workers about integrated child development services: a study in Sitamarhi district of Bihar, India

Background: The anganwadi worker (AWW) is the backbone of integrated child development services (ICDS) for delivering the services of the program. Being a key functionary, her level of knowledge regarding various components of ICDS is linked to the ultimate outcome of the ICDS program. Thus, this study was aimed to assess the level of knowledge among AWW regarding services of ICDS.Methods: This was a cross sectional study in which level of knowledge regarding ICDS among anganwadi worker was assessed using structured questionnaire. The primary outcome of the study is the knowledge of AWW about ICDS component services. Descriptive statistics was presented as frequency and percentage for categorical variable. The knowledge of AWW was assessed by knowledge score made under all the themes of the questionnaire and was presented as mean and median score. Analysis was done in STATA version 14.2.Results: Nearly 55% of the respondents were not aware about ICDS services. Whereas majority had knowledge on growth monitoring and immunization respectively, above the median score, only 39% of AWW had knowledge on nutritional supplementation above median score. The variables such as education level and training of AWW showed significant association with the knowledge of ICDS components.Conclusions: There is need for improving knowledge and awareness about various ICDS components and the training quality provided to AWWs

Corporate Entrepreneurship in the Digital Era: The Cascading Effect through Operations

This study examines a firm’s response to perceived changes in the environment, such as the growth of the digital era, at different levels of a firm—beginning with the adoption of corporate entrepreneurship (CE) down to process renewal (PR). We further explore if the technological intensity of a firm, high-tech or low-tech intensity, influences its choice of mode for organisational renewal (OR)—use of internal competence or outside acquisition—to exploit the opportunities created by the digital era. Using survey data from 170 firms, we test a sequential relationship among environmental changes (growth of the digital era), CE, OR and finally PR that involves operating procedures at the functional level. We conclude by identifying the study’s interdisciplinary contributions, which open new research avenues in the field of CE

Geometry Processing for SLS/HIP

SLS/HIP is a new net shape manufacturing method that combines the strengths of direct selective laser sintering and hot isostatic pressing. Direct selective laser sintering is a rapid manufacturing technique that can produce high density metal parts of complex geornetry with an integral, gas iinpenneable skin. These parts can then be directly post-processed by containerless HIP. Sophisticated processing of the part geometry is required to facilitate the desired results from SLS/HIP. This paper presents geometry processing algorithms being developed for in-situ canning of SLS/HIP components. This research is funded by DARPA IONR contract NO00 14-95-C-0 139 titled "Low Cost Metal Processing Using SLS/HIP".Mechanical Engineerin

Early Dark Energy beyond slow-roll: implications for cosmic tensions

In this work, we explore the possibility that Early Dark Energy (EDE) is dynamical in nature and study its effect on cosmological observables. We introduce a parameterization of the equation of state allowing for an equation of state $w$ differing considerably from cosmological constant (cc, $w={-1}$) and vary both the initial $w_i$ as well final $w_f$ equation of state of the EDE fluid. This idea is motivated by the fact that in many models of EDE, the scalar field may have some kinetic energy when it starts to behave like EDE before the CMB decoupling. We find that the present data have a mild preference for non-cc early dark energy $( w_i= -0.78)$ using Planck+BAO+Pantheon+S$H_0$ES data sets, leading to $\Delta \chi^2_{\rm min}$ improvement of -2.5 at the expense of one more parameter. However, $w_i$ is only weakly constrained, with $w_i < -0.56$ at $1\sigma$. We argue that allowing for $w_i\neq -1$ can play a role in decreasing the $\sigma_8$ parameter. Yet, in practice the decrease is only $\sim0.4\sigma$ and $\sigma_8$ is still larger than weak lensing measurements. We conclude that while promising, a dynamical EDE cannot resolve both $H_0$ and $\sigma_8$ tensions simultaneously.Comment: 8 figures, Comments are most welcom

Failure of evaporator tubes initiated by lamellar tearing during the commissioning of a waste heat recovery boiler

Successive failures of several new evaporator tubes during commissioning and trial run of a waste heat recovery boiler has been analyzed. The evaporator tubes are cold bent into U-shape and subsequently TIG welded to a 24-mm thick wear plate on either sides of the tube immediately adjacent to the bend. The failed samples showed stepped longitudinal cracks along the rolling direction and parallel to the weld fusion boundary at the fireside surface of the inner bend of the tube,prominently at the center of the bend. It was found that the failure of the evaporator tubes at the tube bends was initiated by lamellar tearing because of inherent defects in the material (segregation leading to banded structure), improper processing of material (inclusions with high aspect ratios along the rolling direction) and accelerated by high transverse shrinkage stresses over the entire bend portion of the tube introduced by the weld. The pre-existing fine cracks in the welded evaporator tube initiated by lamellar tearing have subsequently opened up during service when the total strain in the region increased because of steam pressure resulting in catastrophic failure of the tubes. Contrary to expectation, many of the elongated inclusions were found to be iron oxide scales and only few were manganese sulfide stringers enveloped by iron oxide scales. The iron oxide inclusions were resolved from the manganese sulfide by scanning electron microscopy and EDS spot analysis of the inclusions