Stability of the Shallow Axisymmetric Parabolic-Conic Bimetallic Shell by Nonlinear Theory

In this contribution, we discuss the stress, deformation, and snap-through conditions of thin, axi-symmetric, shallow bimetallic shells of so-called parabolic-conic and plate-parabolic type shells loaded by thermal loading. According to the theory of the third order that takes into account the balance of forces on a deformed body, we present a model with a mathematical description of the system geometry, displacements, stress, and thermoelastic deformations. The equations are based on the large displacements theory. We numerically calculate the deformation curve and the snap-through temperature using the fourth-order Runge-Kutta method and a nonlinear shooting method. We show how the temperature of both snap-through depends on the point where one type of the rotational curve transforms into another

Pukotine na kalupima (alatima) za tlačno lijevanje uslijed toplinskog umora

Die-casting dies are exposed to high thermal and mechanical loads. Thermal fatigue cracking of dies due to thermal cycling may importantly shorten the life-time of the die. Cracks degrade the surface quality of dies and consequently the surface of castings. In this study, thermal fatigue cracking of dies was analyzed during the process of die casting aluminium alloys. During the process cracks were observed and measured and their location and size were determined. Thermal and mechanical loads cause high local stresses and consequently surface cracks. First cracks occur as early as after 2000 cycles and propagate progressively with cycles.Kalupi (alati) za lijevanje pod tlakom su izloženi velikim toplinskim i mehaničkim opterećenjima. Pukotine uslijed toplinskog umora su zbog izmjene toplinskih ciklusa važan ograničavajući mehanizam životnoga vijeka kalupa. Pukotine smanjuju (degradiraju) kvalitetu površine kalupa i posljedično površinu odljevka. U ovom radu su analizirane pukotine nastale na kalupu zbog toplinskog umora tokom tlačnog lijevanja aluminija. Tokom procesa su promatranjem i mjerenjem utvrđene lokacije i veličine nastalih pukotina na kalupu. Toplinska i mehanička opterećenja uzrokuju velika lokalna naprezanja i posljedično pukotine na površini kalupa. Prva pukotina pojavljuje se već nakon 2000 ciklusa i progresivno se širi povećanjem broja ciklusa

Pukotine na kalupima (alatima) za tlačno lijevanje uslijed toplinskog umora

Die-casting dies are exposed to high thermal and mechanical loads. Thermal fatigue cracking of dies due to thermal cycling may importantly shorten the life-time of the die. Cracks degrade the surface quality of dies and consequently the surface of castings. In this study, thermal fatigue cracking of dies was analyzed during the process of die casting aluminium alloys. During the process cracks were observed and measured and their location and size were determined. Thermal and mechanical loads cause high local stresses and consequently surface cracks. First cracks occur as early as after 2000 cycles and propagate progressively with cycles.Kalupi (alati) za lijevanje pod tlakom su izloženi velikim toplinskim i mehaničkim opterećenjima. Pukotine uslijed toplinskog umora su zbog izmjene toplinskih ciklusa važan ograničavajući mehanizam životnoga vijeka kalupa. Pukotine smanjuju (degradiraju) kvalitetu površine kalupa i posljedično površinu odljevka. U ovom radu su analizirane pukotine nastale na kalupu zbog toplinskog umora tokom tlačnog lijevanja aluminija. Tokom procesa su promatranjem i mjerenjem utvrđene lokacije i veličine nastalih pukotina na kalupu. Toplinska i mehanička opterećenja uzrokuju velika lokalna naprezanja i posljedično pukotine na površini kalupa. Prva pukotina pojavljuje se već nakon 2000 ciklusa i progresivno se širi povećanjem broja ciklusa

Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine

In the development of the mammalian intestine, Notch and Wnt/{beta}-catenin signals control stem cell maintenance and their differentiation into absorptive and secretory cells. Mechanisms that regulate differentiation of progenitors into the three secretory lineages, goblet, paneth, or enteroendocrine cells, are not fully understood. Using conditional mutagenesis in mice, we observed that Shp2-mediated MAPK signaling determines the choice between paneth and goblet cell fates and also affects stem cells, which express the leucine-rich repeat-containing receptor 5 (Lgr5). Ablation of the tyrosine phosphatase Shp2 in the intestinal epithelium reduced MAPK signaling and led to a reduction of goblet cells while promoting paneth cell development. Conversely, conditional mitogen-activated protein kinase kinase 1 (Mek1) activation rescued the Shp2 phenotype, promoted goblet cell and inhibited paneth cell generation. The Shp2 mutation also expanded Lgr5+ stem cell niches, which could be restricted by activated Mek1 signaling. Changes of Lgr5+ stem cell quantities were accompanied by alterations of paneth cells, indicating that Shp2/MAPK signaling might affect stem cell niches directly or via paneth cells. Remarkably, inhibition of MAPK signaling in intestinal organoids and cultured cells changed the relative abundance of Tcf4 isoforms and by this, promoted Wnt/{beta}-catenin activity. The data thus show that Shp2-mediated MAPK signaling controls the choice between goblet and paneth cell fates by regulating Wnt/{beta}-catenin activity

Wnt/β-catenin signalling induces MLL to create epigenetic changes in salivary gland tumours

We show that activation of Wnt/{beta}-catenin and attenuation of Bmp signals, by combined gain- and loss-of-function mutations of {beta}-catenin and Bmpr1a, respectively, results in rapidly growing, aggressive squamous cell carcinomas (SCC) in the salivary glands of mice. Tumours contain transplantable and hyperproliferative tumour propagating cells, which can be enriched by fluorescence activated cell sorting (FACS). Single mutations stimulate stem cells, but tumours are not formed. We show that {beta}-catenin, CBP and Mll promote self-renewal and H3K4 tri-methylation in tumour propagating cells. Blocking {beta}-catenin-CBP interaction with the small molecule ICG-001 and small-interfering RNAs against {beta}-catenin, CBP or Mll abrogate hyperproliferation and H3K4 tri-methylation, and induce differentiation of cultured tumour propagating cells into acini-like structures. ICG-001 decreases H3K4me3 at promoters of stem cell-associated genes in vitro and reduces tumour growth in vivo. Remarkably, high Wnt/{beta}-catenin and low Bmp signalling also characterize human salivary gland SCC and head and neck SCC in general. Our work defines mechanisms by which {beta}-catenin signals remodel chromatin and control induction and maintenance of tumour propagating cells. Further, it supports new strategies for the therapy of solid tumours

Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells

Differentiation and lineage specification are controlled by cooperation of growth factor signalling. The involvement of epigenetic regulators in lineage specification remains largely elusive. Here, we show that the histone methyltransferase Mll1 prevents intestinal progenitor cells from differentiation, whereas it is also involved in secretory lineage specification of Paneth and goblet cells. Using conditional mutagenesis in mice and intestinal organoids, we demonstrate that loss of Mll1 renders intestinal progenitor cells permissive for Wnt-driven secretory differentiation. However, Mll1-deficient crypt cells fail to segregate Paneth and goblet cell fates. Mll1 deficiency causes Paneth cell-determined crypt progenitors to exhibit goblet cell features by unleashing Mapk signalling, resulting in increased numbers of mixed Paneth/goblet cells. We show that loss of Mll1 abolishes the pro-proliferative effect of Mapk signalling in intestinal progenitor cells and promotes Mapk-induced goblet cell differentiation. Our data uncover Mll1 and its downstream targets Gata4/6 as a regulatory hub of Wnt and Mapk signalling in the control of lineage specification of intestinal secretory Paneth and goblet cells

Cognitive Functioning in Patients Remitted from Recurrent Depression: Comparison with Acutely Depressed Patients and Controls and Follow-up of a Mindfulness-Based Cognitive Therapy Trial

Mindfulness-Based Cognitive Therapy (MBCT) is a promising intervention to prevent depressive relapse. Yet beyond efficacy studies, little is known regarding the mechanisms that could be modified through MBCT. Objectives of the present study were twofold: determine whether cognitive functioning was altered among patients remitted from depression at admission in a MBCT trial; and document possible changes during the trial and follow-up. In a cross-sectional perspective, cognitive functioning (autobiographical memory, shifting capacities, dysfunctional attitudes, mindful attention awareness and rumination habits) was first compared between 36 patients remitted from depression, 20 acutely depressed patients and 20 control participants. In a longitudinal perspective, changes in the remitted sample were explored during a MBCT plus Treatment As Usual versus Treatment As Usual randomized controlled trial and 9-month follow-up. Performances of remitted patients were similar to the ones of control participants for autobiographical memories, shifting capacities, and mindful attention awareness, whereas levels of rumination and dysfunctional attitudes were significantly elevated. Participation in the MBCT program was accompanied with a significant decrease of dysfunctional attitudes that continued up to 9-month postintervention. No other change was observed that was specific to MBCT. Results suggest that MBCT might help people to identify dysfunctional attitudes at a very early stage and to avoid engaging further in these attitude

Bioinspired Ciliary Force Sensor for Robotic Platforms

© 2017 IEEE. The detection of small forces is of great interest in any robotic application that involves interaction with the environment (e.g., objects manipulation, physical human-robot interaction, minimally invasive surgery), since it allows the robot to detect the contacts early on and to act accordingly. In this letter, we present a sensor design inspired by the ciliary structure frequently found in nature, consisting of an array of permanently magnetized cylinders (cilia) patterned over a giant magnetoresistance sensor (GMR). When these cylinders are deformed in shape due to applied forces, the stray magnetic field variation will change the GMR sensor resistivity, thus enabling the electrical measurement of the applied force. In this letter, we present two 3 mm × 3 mm prototypes composed of an array of five cilia with 1 mm of height and 120 and 200 μm of diameter for each prototype. A minimum force of 333 μ N was measured. A simulation model for determining the magnetized cylinders average stray magnetic field is also presented

The epigenetic regulator Mll1 is required for Wnt-driven intestinal tumorigenesis and cancer stemness

Wnt/β-catenin signaling is crucial for intestinal carcinogenesis and the maintenance of intestinal cancer stem cells. Here we identify the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5(+) stem cells and human colon carcinomas with increased nuclear β-catenin. High levels of MLL1 are associated with poor survival of colon cancer patients. The genetic ablation of Mll1 in mice prevents Wnt/β-catenin-driven adenoma formation from Lgr5(+) intestinal stem cells. Ablation of Mll1 decreases the self-renewal of human colon cancer spheres and halts tumor growth of xenografts. Mll1 controls the expression of stem cell genes including the Wnt/β-catenin target gene Lgr5. Upon the loss of Mll1, histone methylation at the stem cell promoters switches from activating H3K4 tri-methylation to repressive H3K27 tri-methylation, indicating that Mll1 sustains stem cell gene expression by antagonizing gene silencing through polycomb repressive complex 2 (PRC2)-mediated H3K27 tri-methylation. Transcriptome profiling of Wnt-mutated intestinal tumor-initiating cells reveals that Mll1 regulates Gata4/6 transcription factors, known to sustain cancer stemness and to control goblet cell differentiation. Our results demonstrate that Mll1 is an essential epigenetic regulator of Wnt/β-catenin-induced intestinal tumorigenesis and cancer stemness