All-inkjet-printed thin-film transistors: manufacturing process reliability by root cause analysis

We report on the detailed electrical investigation of all-inkjet-printed thin-film transistor (TFT) arrays focusing on TFT failures and their origins. The TFT arrays were manufactured on flexible polymer substrates in ambient condition without the need for cleanroom environment or inert atmosphere and at a maximum temperature of 150 degrees C. Alternative manufacturing processes for electronic devices such as inkjet printing suffer from lower accuracy compared to traditional microelectronic manufacturing methods. Furthermore, usually printing methods do not allow the manufacturing of electronic devices with high yield (high number of functional devices). In general, the manufacturing yield is much lower compared to the established conventional manufacturing methods based on lithography. Thus, the focus of this contribution is set on a comprehensive analysis of defective TFTs printed by inkjet technology. Based on root cause analysis, we present the defects by developing failure categories and discuss the reasons for the defects. This procedure identifies failure origins and allows the optimization of the manufacturing resulting finally to a yield improvement

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus

Mutant Huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits

Copyright © 2011 Elsevier Inc. All rights reserved

Dwarfism in mice lacking collagen-binding integrins α2β1 and α11β1 is caused by severely diminished IGF-1 levels

© 2012 by The American Society for Biochemistry and Molecular Biology, Inc

High-fat feeding promotes obesity via insulin receptor/PI3k-dependent inhibition of SF-1 VMH neurons

© 2011 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved

PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response

Insulin- and leptin-stimulated phosphatidylinositol-3 kinase (PI3K) activation has been demonstrated to play a critical role in central control of energy homeostasis. To delineate the importance of pathways downstream of PI3K specifically in pro-opiomelanocortin (POMC) cell regulation, we have generated mice with selective inactivation of 3-phosphoinositide-dependent protein kinase 1 (PDK1) in POMC-expressing cells (PDK1(Delta POMC) mice). PDK1(Delta POMC) mice initially display hyperphagia, increased body weight, and impaired glucose metabolism caused by reduced hypothalamic POMC expression. On the other hand, PDK1(Delta POMC) mice exhibit progressive, severe hypocortisolism caused by loss of POW-expressing corti-cotrophs in the pituitary. Expression of a dominant-negative mutant of FOXO1 specifically in POW cells is sufficient to ameliorate positive energy balance in PDK1(Delta POMC) mice but cannot restore regular pituitary function. These results reveal important but differential roles for PDK1 signaling in hypothalamic and pituitary POMC cells in the control of energy homeostasis and stress response.</p

Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism

c-Jun N-terminal kinase (JNK) 1-dependent signaling plays a crucial role in the development of obesity-associated insulin resistance. Here we demonstrate that JNK activation not only occurs in peripheral tissues, but also in the hypothalamus and pituitary of obese mice. To resolve the importance of JNK1 signaling in the hypothalamic/pituitary circuitry, we have generated mice with a conditional inactivation of JNK1 in nestin-expressing cells (JNK1ΔNES mice). JNK1ΔNES mice exhibit improved insulin sensitivity both in the CNS and in peripheral tissues, improved glucose metabolism, as well as protection from hepatic steatosis and adipose tissue dysfunction upon high-fat feeding. Moreover, JNK1ΔNES mice also show reduced somatic growth in the presence of reduced circulating growth hormone (GH) and insulin-like growth factor 1 (IGF1) concentrations, as well as increased thyroid axis activity. Collectively, these experiments reveal an unexpected, critical role for hypothalamic/pituitary JNK1 signaling in the coordination of metabolic/endocrine homeostasis

The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry

Dopaminergic (DA) signaling governs the control of complex behaviors, and its deregulation has been implicated in a wide range of diseases. Here we demonstrate that inactivation of the Fto gene, encoding a nucleic acid demethylase, impairs dopamine receptor type 2 (D2R) and type 3 (D3R) (collectively, 'D2-like receptor')-dependent control of neuronal activity and behavioral responses. Conventional and DA neuron-specific Fto knockout mice show attenuated activation of G protein-coupled inwardly-rectifying potassium (GIRK) channel conductance by cocaine and quinpirole. Impaired D2-like receptor-mediated autoinhibition results in attenuated quinpirole-mediated reduction of locomotion and an enhanced sensitivity to the locomotor- and reward-stimulatory actions of cocaine. Analysis of global N(6)-methyladenosine (m(6)A) modification of mRNAs using methylated RNA immunoprecipitation coupled with next-generation sequencing in the midbrain and striatum of Fto-deficient mice revealed increased adenosine methylation in a subset of mRNAs important for neuronal signaling, including many in the DA signaling pathway. Several proteins encoded by these mRNAs had altered expression levels. Collectively, FTO regulates the demethylation of specific mRNAs in vivo, and this activity relates to the control of DA transmission