Experimental Investigation of Load-Bearing Capacity in EN AW-2024-T3 Aluminum Alloy Sheets Strengthened by SPIF-Fabricated Stiffening Rib.

The aluminum strength-to-weight ratio has become a highly significant factor in industrial applications. Placing stiffening ribs along the surface can significantly improve the panel's resistance to bending and compression in aluminum alloys. This study used single-point incremental forming (SPIF) to fabricate stiffening ribs for 1 mm and 3 mm thick aluminum alloy EN AW-2024-T3 sheets.

Removal of a partial genomic duplication restores synaptic transmission and behavior in the MyosinVA mutant mouse Flailer.

Background: Copy number variations, and particularly duplications of genomic regions, have been strongly associated with various neurodegenerative conditions including autism spectrum disorder (ASD). These genetic variations have been found to have a significant impact on brain development and function, which can lead to the emergence of neurological and behavioral symptoms. Developing strategies to target these genomic duplications has been challenging, as the presence of endogenous copies of the duplicate genes often complicates the editing strategies.

Removal of a genomic duplication by double-nicking CRISPR restores synaptic transmission and behavior in the MyosinVA mutant mouse Flailer.

Copy number variations, and particularly duplications of genomic regions, have been strongly associated with various neurodegenerative conditions including autism spectrum disorder (ASD). These genetic variations have been found to have a significant impact on brain development and function, which can lead to the emergence of neurological and behavioral symptoms. Developing strategies to target these genomic duplications has been challenging, as the presence of endogenous copies of the duplicate genes often complicates the editing strategies.

Experimental Analysis of Perimeter Shear Strength of Composite Sandwich Structures.

The work concerns the experimental analysis of the process of destruction of sandwich structures as a result of circumferential shearing. The aim of the research was to determine the differences that occur in the destruction mechanism of such structures depending on the thickness and material of the core used. Specimens with a Rohacell foam core and a honeycomb core were made for the purposes of the research.

The Impact of 3D Printing Parameters on the Post-Buckling Behavior of Thin-Walled Structures.

This study presents the results of experimental research and numerical calculations regarding models of a typical torsion box fragment, which is a common thin-walled load-bearing structure used in aviation technology. A fragment of this structure corresponding to the spar wall was made using 3D printing. The examined system was subjected to twisting and underwent post-critical deformation.

Experimental and Numerical Studies of Low-Profile, Triangular Grid-Stiffened Plates Subjected to Shear Load in the Post-Critical States of Deformation.

Constant developments in manufacturing technology have made it possible to introduce integrally stiffened elements into load-bearing, thin-walled structures. The application of thin-walled elements with integral stiffeners potentially increases buckling and critical loads to maintain the mass of the structure and lower production costs. This paper presents the results of experimental investigations and numerical Finite Element Modelling (FEM) analyses of low-profile, isosceles grid stiffened, aluminium alloy plates subjected to pure shear load.

Experimental and Numerical Investigations of Thin-Walled Stringer-Stiffened Panels Welded with RFSSW Technology under Uniaxial Compression.

Many aircraft structures are thin walled and stringer-stiffened, and therefore, prone to a loss of stability. This paper deals with accurate and validated stability analysis of the model of aircraft skin under compressive loading. Both experimental and numerical analyzes are conducted.

Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens.

The co-engagement of fragment crystallizable (Fc) gamma receptors (FcγRs) with the Fc region of recombinant immunoglobulin monoclonal antibodies (mAbs) and its contribution to therapeutic activity has been extensively studied. For example, Fc-FcγR interactions have been shown to be important for mAb-directed effector cell activities, as well as mAb-dependent forward signaling into target cells via receptor clustering. Here we identify a function of mAbs targeting T cell-expressed antigens that involves FcγR co-engagement on antigen-presenting cells (APCs).

Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons.

Single-cell RNA sequencing (RNA-Seq) provides rich information about cell types and states. However, it is difficult to capture rare dynamic processes, such as adult neurogenesis, because isolation of rare neurons from adult tissue is challenging and markers for each phase are limited. Here, we develop Div-Seq, which combines scalable single-nucleus RNA-Seq (sNuc-Seq) with pulse labeling of proliferating cells by 5-ethynyl-2'-deoxyuridine (EdU) to profile individual dividing cells.

Tuberous sclerosis complex neuropathology requires glutamate-cysteine ligase.

Introduction: Tuberous sclerosis complex (TSC) is a genetic disease resulting from mutation in TSC1 or TSC2 and subsequent hyperactivation of mammalian Target of Rapamycin (mTOR). Common TSC features include brain lesions, such as cortical tubers and subependymal giant cell astrocytomas (SEGAs). However, the current treatment with mTOR inhibitors has critical limitations.

In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9.

Probing gene function in the mammalian brain can be greatly assisted with methods to manipulate the genome of neurons in vivo. The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) can be used to edit single or multiple genes in replicating eukaryotic cells, resulting in frame-shifting insertion/deletion (indel) mutations and subsequent protein depletion. Here, we delivered SpCas9 and guide RNAs using adeno-associated viral (AAV) vectors to target single (Mecp2) as well as multiple genes (Dnmt1, Dnmt3a and Dnmt3b) in the adult mouse brain in vivo.

CD44 regulates dendrite morphogenesis through Src tyrosine kinase-dependent positioning of the Golgi.

The acquisition of proper dendrite morphology is a crucial aspect of neuronal development towards the formation of a functional network. The role of the extracellular matrix and its cellular receptors in this process has remained enigmatic. We report that the CD44 adhesion molecule, the main hyaluronan receptor, is localized in dendrites and plays a crucial inhibitory role in dendritic tree arborization in vitro and in vivo.

CRISPR-Cas9 knockin mice for genome editing and cancer modeling.

CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells.

Cyr61, a matricellular protein, is needed for dendritic arborization of hippocampal neurons.

The shape of the dendritic arbor is one of the criteria of neuron classification and reflects functional specialization of particular classes of neurons. The development of a proper dendritic branching pattern strongly relies on interactions between the extracellular environment and intracellular processes responsible for dendrite growth and stability. We previously showed that mammalian target of rapamycin (mTOR) kinase is crucial for this process.

Mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) control the dendritic arbor morphology of hippocampal neurons.

Dendrites are the main site of information input into neurons. Their development is a multistep process controlled by mammalian target of rapamycin (mTOR) among other proteins. mTOR is a serine/threonine protein kinase that forms two functionally distinct complexes in mammalian cells: mTORC1 and mTORC2.

Developmental plasticity of the dendritic compartment: focus on the cytoskeleton.

Plasticity, the ability to undergo lasting changes in response to a stimulus, is an important attribute of neurons. It allows proper development and underlies learning, memory, and the recovery of the nervous system after severe injuries. Often, an outcome of neuronal plasticity is a structural plasticity manifested as a change of neuronal morphology.

CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology.

Dendritic arbors are compartments of neurons dedicated to receiving synaptic inputs. Their shape is an outcome of both the intrinsic genetic program and environmental signals. The microtubules and actin cytoskeleton are both crucial for proper dendritic morphology, but how they interact is unclear.

Expression of Ttyh1, a member of the Tweety family in neurons in vitro and in vivo and its potential role in brain pathology.

We have previously shown that Ttyh1 mRNA is expressed in neurons and its expression is up-regulated in the brain during epileptogenesis and epilepsy. In this study, we aimed to elucidate the role of Ttyh1 in neurons. We found widespread expression of Ttyh1 protein in neurons in vivo and in vitro.

The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum.

Background: Various drugs of abuse activate intracellular pathways in the brain reward system. These pathways regulate the expression of genes that are essential to the development of addiction. To reveal genes common and distinct for different classes of drugs of abuse, we compared the effects of nicotine, ethanol, cocaine, morphine, heroin and methamphetamine on gene expression profiles in the mouse striatum.

Role of mTOR in physiology and pathology of the nervous system.

Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that regulates several intracellular processes in response to extracellular signals, nutrient availability, energy status of the cell and stress. mTOR regulates survival, differentiation and development of neurons. Axon growth and navigation, dendritic arborization, as well as synaptogenesis, depend on proper mTOR activity.

Accumulation and dynamics of proteins of the MCM family during mouse oogenesis and the first embryonic cell cycle.

We describe the localization of three proteins of the minichromosome maintenance (MCM) family, Mcm2, -6 and -7 in mouse ovarian oocytes. We showed that Mcm proteins are stored in two forms: soluble and insoluble. Soluble Mcm2, -6 and -7 were uniformly distributed in the nuclei of ovarian oocytes.