Design of a pulse power supply unit for micro-ECM

Electrochemical micro-machining (μECM) requires a particular pulse power supply unit (PSU) to be developed in order to achieve desired machining performance. This paper summarises the development of a pulse PSU meeting the requirements of μECM. The pulse power supply provides tens of nanosecond pulse duration, positive and negative bias voltages and a polarity switching functionality. It fulfils the needs for tool preparation with reversed pulsed ECM on the machine. Moreover, the PSU is equipped with an ultrafast overcurrent protection which prevents the tool electrode from being damaged in case of short circuits. The developed pulse PSU was used to fabricate micro-tools out of 170 μm WC-Co alloy shafts via micro-electrochemical turning and drill deep holes via μECM in a disk made of 18NiCr6. The electrolyte used for both processes was a mixture of sulphuric acid and NaNO3 aqueous solutions.The research reported in this paper is supported by the European Commission within the project “Minimizing Defects in Micro-Manufacturing Applications (MIDEMMA)” (FP7-2011-NMP-ICT-FoF-285614

Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells

TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR)

Erratum to: Synthesis and Magnetic Properties of Nearly Monodisperse CoFe2O4 Nanoparticles Through a Simple Hydrothermal Condition

<p>Abstract</p> <p>Nearly monodisperse cobalt ferrite (CoFe₂O₄) nanoparticles without any size-selection process have been prepared through an alluring method in an oleylamine/ethanol/water system. Well-defined nanospheres with an average size of 5.5 nm have been synthesized using metal chloride as the law materials and oleic amine as the capping agent, through a general liquid&#8211;solid-solution (LSS) process. Magnetic measurement indicates that the particles exhibit a very high coercivity at 10 K and perform superparamagnetism at room temperature which is further illuminated by ZFC/FC curves. These superparamagnetic cobalt ferrite nanomaterials are considered to have potential application in the fields of biomedicine. The synthesis method is possible to be a general approach for the preparation of other pure binary and ternary compounds.</p

Potential for pancreatic maturation of differentiating human embryonic stem cells is sensitive to the specific pathway of definitive endoderm commitment

This study provides a detailed experimental and mathematical analysis of the impact of the initial pathway of definitive endoderm (DE) induction on later stages of pancreatic maturation. Human embryonic stem cells (hESCs) were induced to insulin-producing cells following a directed-differentiation approach. DE was induced following four alternative pathway modulations. DE derivatives obtained from these alternate pathways were subjected to pancreatic progenitor (PP) induction and maturation and analyzed at each stage. Results indicate that late stage maturation is influenced by the initial pathway of DE commitment. Detailed quantitative analysis revealed WNT3A and FGF2 induced DE cells showed highest expression of insulin, are closely aligned in gene expression patterning and have a closer resemblance to pancreatic organogenesis. Conversely, BMP4 at DE induction gave most divergent differentiation dynamics with lowest insulin upregulation, but highest glucagon upregulation. Additionally, we have concluded that early analysis of PP markers is indicative of its potential for pancreatic maturation. © 2014 Jaramillo et al

Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. Methodology and Principal Findings: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3b, LC3B, Atg4, Atg5/12, Atg.7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1-1- mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. Conclusions: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. © 2008 Chen et al

Study of deposition parameters for the fabrication of ZnO thin films using femtosecond laser

Femtosecond (fs) pulsed laser deposition (fs-PLD) of ZnO thin film on borosilicate glass substrates is reported in this work. The effect of important fs-PLD parameters such as target–substrate distance, laser pulse energy and substrate temperature on structure, morphology, optical transparency and luminescence of as-deposited films is discussed. XRD analysis reveals that all the films grown using the laser energy range 120–230 μJ are polycrystalline when they are deposited at room temperature in a ~10−5 Torr vacuum. Introducing 0.7 mTorr oxygen pressure, the films show preferred c-axis growth and transform into a single-crystal-like film when the substrate temperature is increased to 100 °C. The scanning electron micrographs show the presence of small nano-size grains at 25 °C, which grow in size to the regular hexagonal shape particles at 100 °C. Optical transmission of the ZnO film is found to increase with an increase in crystal quality. Maximum transmittance of 95 % in the wavelength range 400–1400 nm is achieved for films deposited at 100 °C employing a laser pulse energy of 180 μJ. The luminescence spectra show a strong UV emission band peaked at 377 nm close to the ZnO band gap. The shallow donor defects increase at higher pulse energies and higher substrate temperatures, which give rise to violet-blue luminescence. The results indicate that nano-crystalline ZnO thin films with high crystalline quality and optical transparency can be fabricated by using pulses from fs lasers