High-precision tabletop microplotter for flexible on-demand material deposition in printed electronics and device functionalization

Microstructuring, in particular, the additive functionalization of surfaces with, e.g., conductive or bioactive materials plays a crucial role in many applications in sensing or printed electronics. Mostly, the lithography steps are made prior to assembling functionalized surfaces into the desired places of use within a bigger device as a microfluidic channel or an electronic casing. However, when this is not possible, most lithography techniques struggle with access to recessed or inclined/vertical surfaces for geometrical reasons. In particular, for “on-the-fly” printing aiming to add microstructures to already existing devices on demand and maybe even for one-time trials, e.g., in prototyping, a flexible “micropencil” allowing for direct write under direct manual control and on arbitrarily positioned surfaces would be highly desirable. Here, we present a highly flexible, micromanipulator-based setup for capillary printing of conductive and biomaterial ink formulations that can address a wide range of geometries as exemplified on vertical, recessed surfaces and stacked 3D scaffolds as models for hard to access surfaces. A wide range of feature sizes from tens to hundreds of micrometer can be obtained by the choice of capillary sizes and the on-demand in situ writing capabilities are demonstrated with completion of a circuit structure by gold line interconnects deposited with the setup

Constraint of the Nuclear Dissipation Coefficient in Fission of Hypernuclei

Experimental studies of nuclear fission induced by fusion, transfer, spallation, fragmentation, and electromagnetic reactions in combination with state-of-the-art calculations are successful to investigate the nuclear dissipation mechanism in normal nuclear matter, containing only nucleons. The dissipation mechanism has been widely studied by the use of many different fission observables and nowadays the dissipation coefficients involved in transport theories are well constrained. However, the existence of hypernuclei and the possible presence of hyperons in neutron stars make it necessary to extend the investigation of the nuclear dissipation coefficient to the strangeness sector. In this Letter, we use fission reactions of hypernuclei to constrain for the first time the dissipation coefficient in hypernuclear matter, observing that this coefficient increases a factor of 6 in presence of a single $\Lambda$-hyperon with respect to normal nuclear matter.Comment: 6 pages, 2 figure

Hypertonic Saline Is Effective in the Prevention and Treatment of Mucus Obstruction, but Not Airway Inflammation, in Mice with Chronic Obstructive Lung Disease

Recent evidence suggests that inadequate hydration of airway surfaces is a common mechanism in the pathogenesis of airway mucus obstruction. Inhaled hypertonic saline (HS) induces osmotic water flux, improving hydration of airway surfaces. However, trials in patients with obstructive lung diseases are limited. The aim of this study was to investigate effects of HS on mucus obstruction and airway inflammation in the prevention and treatment of obstructive lung disease in vivo. We, therefore, used the β-epithelial Na+ channel (βENaC)–overexpressing mouse as a model of chronic obstructive lung disease and determined effects of preventive and late therapy with 3% HS and 7% HS on pulmonary mortality, airway mucus obstruction, and inflammation. We found that preventive treatment with 3% HS and 7% HS improved growth, reduced mortality, and reduced mucus obstruction in neonatal βENaC-overexpressing mice. In adult βENaC-overexpressing mice with chronic lung disease, mucus obstruction was significantly reduced by 7% HS, but not by 3% HS. Treatment with HS triggered airway inflammation with elevated keratinocyte chemoattractant levels and neutrophils in airways from wild-type mice, but reduced keratinocyte chemoattractant in chronic neutrophilic inflammation in adult βENaC-overexpressing mice. Our data demonstrate that airway surface rehydration with HS provides an effective preventive and late therapy of mucus obstruction with no consistent effects on inflammation in chronic lung disease. These results suggest that, through mucokinetic effects, HS may be beneficial for patients with a spectrum of obstructive lung diseases, and that additional strategies are required for effective treatment of associated airway inflammation

Validity and reliability of the VOAA-DDD to assess spontaneous hand use with a video observation tool in children with spastic unilateral cerebral palsy

Contains fulltext : 80999.pdf (publisher's version ) (Open Access)BACKGROUND: In 2003 new computer software, the VOAA (Video Observations Aarts and Aarts), was designed to score and evaluate two important aspects of spontaneous upper limb use, i.e. overall duration and frequency of specific behaviours. The aim of this study was to investigate the test-retest, interrater and intrarater reliability and the construct validity of a new module, the VOAA-DDD, to determine developmental disregard in children with spastic unilateral cerebral palsy (CP). METHODS: A test-retest design with three raters for reliability and a two-group design for construct validity were used. Subjects were a total of 20 children with spastic unilateral CP equally divided in two age groups (2.5-5 and 5-8 years), and 56 healthy children of the same age groups. Overall duration and frequency of specific behaviours of the affected arm and hand were assessed during a task demanding ('stringing beads') and a task stimulating ('decorating a muffin') the use of both hands. Reliability was estimated by intraclass correlation coefficients (ICCs). Construct validity was assessed by comparing children with CP to healthy children. RESULTS: All ICCs exceeded 0.87. In contrast with healthy children, children with CP used their affected hand less during the 'muffin' task compared to the 'beads' task. Of the children with CP, 90% in the age group of 2.5-5 years and 50% in the age group of 5-8 years showed values exceeding the extreme values of healthy controls, respectively, indicating developmental disregard. CONCLUSION: The VOAA-DDD is a reliable and valid instrument to assess spontaneous use of the affected arm and hand in order to determine developmental disregard in children with spastic unilateral CP

Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease–related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group

Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. Methods: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze–thawing. We measured amyloid beta (Aβ)42 and 40 peptides with six assays, and Aβ oligomerization-tendency (OAβ), amyloid precursor protein (APP)699-711, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181. Results: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aβ and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations. Discussion: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings

The K+ Channel Opener 1-EBIO Potentiates Residual Function of Mutant CFTR in Rectal Biopsies from Cystic Fibrosis Patients

BACKGROUND: The identification of strategies to improve mutant CFTR function remains a key priority in the development of new treatments for cystic fibrosis (CF). Previous studies demonstrated that the K⁺ channel opener 1-ethyl-2-benzimidazolone (1-EBIO) potentiates CFTR-mediated Cl⁻ secretion in cultured cells and mouse colon. However, the effects of 1-EBIO on wild-type and mutant CFTR function in native human colonic tissues remain unknown. METHODS: We studied the effects of 1-EBIO on CFTR-mediated Cl⁻ secretion in rectal biopsies from 47 CF patients carrying a wide spectrum of CFTR mutations and 57 age-matched controls. Rectal tissues were mounted in perfused micro-Ussing chambers and the effects of 1-EBIO were compared in control tissues, CF tissues expressing residual CFTR function and CF tissues with no detectable Cl⁻ secretion. RESULTS: Studies in control tissues demonstrate that 1-EBIO activated CFTR-mediated Cl⁻ secretion in the absence of cAMP-mediated stimulation and potentiated cAMP-induced Cl⁻ secretion by 39.2±6.7% (P<0.001) via activation of basolateral Ca²⁺-activated and clotrimazole-sensitive KCNN4 K⁺ channels. In CF specimens, 1-EBIO potentiated cAMP-induced Cl⁻ secretion in tissues with residual CFTR function by 44.4±11.5% (P<0.001), but had no effect on tissues lacking CFTR-mediated Cl⁻ conductance. CONCLUSIONS: We conclude that 1-EBIO potentiates Cl⁻secretion in native CF tissues expressing CFTR mutants with residual Cl⁻ channel function by activation of basolateral KCNN4 K⁺ channels that increase the driving force for luminal Cl⁻ exit. This mechanism may augment effects of CFTR correctors and potentiators that increase the number and/or activity of mutant CFTR channels at the cell surface and suggests KCNN4 as a therapeutic target for CF

CNS-targeted glucocorticoid reduces pathology in mouse model of amyotrophic lateral sclerosis

Hallmarks of CNS inflammation, including microglial and astrocyte activation, are prominent features in post-mortem tissue from amyotrophic lateral sclerosis (ALS) patients and in mice overexpressing mutant superoxide dismutase-1 (SOD1 G93A ). Administration of non-targeted glucocorticoids does not significantly alter disease progression, but this may reflect poor CNS delivery. Here, we sought to discover whether CNS-targeted, liposomal encapsulated glucocorticoid would inhibit the CNS inflammatory response and reduce motor neuron loss. SOD1 G93A mice were treated with saline, free methylprednisolone (MP, 10 mg/kg/week) or glutathione PEGylated liposomal MP (2B3-201, 10 mg/kg/week) and compared to saline treated wild-type animals. Animals were treated weekly with intravenous injections for 9 weeks from 60 days of age. Weights and motor performance were monitored during this period. At the end of the experimental period (116 days) mice were imaged using T 2-weighted MRI for brainstem pathology; brain and spinal cord tissue were then collected for histological analysis