Mixture distribution modelling of the sensitivities of a digital 3-axis MEMS accelerometers large batch

Huge quantities of low-cost analogue or digital MEMS sensors, in the order of millions per week, are produced by manufacturers. Their use is broad, from consumer electronic devices to Industry 4.0, Internet of Things and Smart Cities. In many cases, such sensors have to be calibrated by accredited laboratories to provide traceable measurements. However, at present, such a massive number of sensors cannot be calibrated and large-scale calibration systems and procedures are still missing. A first step to implementing these methods can be based on the distribution of the sensitivities of the large batches produced. Such distribution is also useful for sensor network end-users who need a single sensitivity, with the associated uncertainty, to be attributed to the whole network. Recently, a large batch of 100 digital 3-axis MEMS accelerometers was calibrated with a primary calibration system developed at INRiM and suitable for 3-axis accelerometers. Distributions of their sensitivities as a function of axis and frequency were analyzed and their non-normal behaviour was shown. However, in the preliminary phase of the study, the calibration uncertainties were not considered in these distributions. Therefore, in this paper, a mixture distribution modelling, based on Monte Carlo simulations and aimed at including the calibration uncertainties in the sensitivity distributions, is implemented and the resulting distributions are compared to the previous ones in histogram form. These distributions are also fitted with Johnson's unbounded and bimodal functions to get continuous distributions. This paper represents a further step towards the development of large-scale statistical calibration methods

Hydrogels for 3D neural tissue models: understanding cell-material interactions at a molecular level.

The development of 3D neural tissue analogs is of great interest to a range of biomedical engineering applications including tissue engineering of neural interfaces, treatment of neurodegenerative diseases and in vitro assessment of cell-material interactions. Despite continued efforts to develop synthetic or biosynthetic hydrogels which promote the development of complex neural networks in 3D, successful long-term 3D approaches have been restricted to the use of biologically derived constructs. In this study a poly (vinyl alcohol) biosynthetic hydrogel functionalized with gelatin and sericin (PVA-SG), was used to understand the interplay between cell-cell communication and cell-material interaction. This was used to probe critical short-term interactions that determine the success or failure of neural network growth and ultimately the development of a useful model. Complex primary ventral mesencephalic (VM) neural cells were encapsulated in PVA-SG hydrogels and critical molecular cues that demonstrate mechanosensory interaction were examined. Neuronal presence was constant over the 10 day culture, but the astrocyte population decreased in number. The lack of astrocytic support led to a reduction in neural process outgrowth from 24.0 ± 1.3 μm on Day 7 to 7.0 ± 0.1 μm on Day 10. Subsequently, purified astrocytes were studied in isolation to understand the reasons behind PVA-SG hydrogel inability to support neural network development. It was proposed that the spatially restrictive nature (or tight mesh size) of PVA-SG hydrogels limited the astrocytic actin polymerization together with a cytoplasmic-nuclear translocation of YAP over time, causing an alteration in their cell cycle. This was confirmed by the evaluation of p27/Kip1 gene that was found to be upregulated by a twofold increase in expression at both Days 7 and 10 compared to Day 3, indicating the quiescent stage of the astrocytes in PVA-SG hydrogel. Cell migration was further studied by the quantification of MMP-2 production that was negligible compared to 2D controls, ranging from 2.7 ± 2.3% on Day 3 to 5.3 ± 2.9% on Day 10. This study demonstrates the importance of understanding astrocyte-material interactions at the molecular level, with the need to address spatial constraints in the 3D hydrogel environment. These findings will inform the design of future hydrogel constructs with greater capacity for remodeling by the cell population to create space for cell migration and neural process extension

A respiração de Cheyne-Stokes em pacientes com insuficiência cardíaca congestiva: causas e conseqüências

Cheyne-Stokes respiration is a form of periodic breathing in which central apneas and hypopneas alternate with periods of hyperventilation, producing a waxing and waning pattern of tidal volume. This review focuses on the causes and consequences of Cheyne-Stokes respiration in patients with congestive heart failure, in whom the prevalence is strikingly high and ranges from 30% to 50%. Several factors have been implicated in the genesis of Cheyne-Stokes respiration, including low cardiac output and recurrent hypoxia. The key pathophysiological mechanism triggering Cheyne-Stokes respiration is hyperventilation and low arterial CO2 (PaCO2) that when below the apneic threshold triggers a central apnea. Hyperventilation is associated with pulmonary congestion, and Cheyne-Stokes respiration is more prone to occur during sleep, when the respiratory system is mainly dependent on chemical control. It is associated with recurrent dips in oxygen saturation and arousals from sleep, with oscillations in blood pressure and heart rate, sympathetic activation and increased risk of ventricular tachycardia. Cheyne-Stokes respiration is an independent marker of poor prognosis and may participate in a vicious cycle, further stressing the failing heart.A respiração de Cheyne-Stokes é uma forma de respiração periódica na qual apnéias e hipopnéias se alternam com períodos de hiperpnéias que apresentam um padrão crescendo e decrescendo de volume corrente. Esta revisão enfoca as causa e conseqüências da respiração de Cheyne- Stokes em pacientes com insuficiência cardíaca congestiva na qual a prevalência é extremamente alta e varia entre 30 a 50%. Vários fatores foram implicados na gênese da respiração de Cheyne-Stokes, incluindo baixo debito cardíaco e hipoxia recorrente. Hiperventilacão e baixos níveis de CO2 arterial (PaCO2), que quando abaixo do limiar de apnéia desencadeiam apnéia central são os mecanismos fisiopatológicos chave na gênese da respiração de Cheyne-Stokes. Hiperventilação está associada com congestão pulmonar, e a respiração de Cheyne-Stokes tem uma tendência maior de ocorrer durante o sono, quando o centro respiratório é dependente principalmente do controle químico. A respiração de Cheyne-Stokes está associada a quedas recorrentes da saturação de oxigênio e ao despertar do sono, com oscilações recorrentes na freqüência cardíaca, pressão arterial, aumento da atividade simpática e risco aumentado de taquicardia ventricular. A respiração de Cheyne-Stokes é um marcador independente de mau prognostico e provavelmente participa de um ciclo vicioso que contribui para a deterioração cardíaca

First thermostable CLIP-tag by rational design applied to an archaeal O6-alkyl-guanine-DNA-alkyl-transferase

Self-labelling protein tags (SLPs) are resourceful tools that revolutionized sensor imaging, having the versatile ability of being genetically fused with any protein of interest and undergoing activation with alternative probes specifically designed for each variant (namely, SNAP-tag, CLIP-tag and Halo-tag). Commercially available SLPs are highly useful in studying molecular aspects of mesophilic organisms, while they fail in characterizing model organisms that thrive in harsh conditions. By applying an integrated computational and structural approach, we designed a engineered variant of the alkylguanine-DNA-alkyl-transferase (OGT) from the hyper-thermophilic archaeon Saccharolobus solfataricus (SsOGT), with no DNA-binding activity, able to covalently react with O6-benzyl-cytosine (BC-) derivatives, obtaining the first thermostable CLIP-tag, named SsOGT-MC8. The presented construct is able to recognize and to covalently bind BC- substrates with a marked specificity, displaying a very low activity on orthogonal benzyl-guanine (BG-) substrate and showing a remarkable thermal stability that broadens the applicability of SLPs. The rational mutagenesis that, starting from SsOGT, led to the production of SsOGT-MC8 was first evaluated by structural predictions to precisely design the chimeric construct, by mutating specific residues involved in protein stability and substrate recognition. The final construct was further validated by biochemical characterization and X-ray crystallography, allowing us to present here the first structural model of a CLIP-tag establishing the molecular determinants of its activity, as well as proposing a general approach for the rational engineering of any O6-alkylguanine-DNA-alkyl-transferase turning it into a SNAP- and a CLIP-tag variant

Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis

Background Periostin is highly expressed in eosinophilic oesophagitis (EoE), but has not been extensively studied as a non-invasive biomarker. Aim To assess whether serum periostin distinguished EoE from controls at baseline, had utility for monitoring treatment response, or was associated with IL-13 levels. Methods This was a sub-analysis of a prospective cohort study of adults undergoing out-patient upper endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. Controls were subjects with either GERD or dysphagia without EoE. EoE patients were treated with swallowed/topical steroids and had repeat endoscopy/biopsy. Serum periostin levels for cases and controls were compared at baseline, and pre/post-treatment levels were compared for cases. Serum IL-13 and tissue expression of periostin were also assessed. Results A total of 61 incident EoE cases and 87 controls were analysed. Despite a marked increase in tissue periostin expression in cases, the median baseline serum periostin level was only slightly higher in cases than controls (22.1 ng/mL vs. 20.7; P = 0.04); there was no change in post-treatment levels. There was also no difference in serum periostin for cases by histologic response or atopic status. There was a strong trend towards higher serum IL-13 levels in cases in the highest periostin quartile (57.1 pg/mL vs. 2.6; P = 0.07). Conclusions Serum periostin levels were similar in cases and controls, and there were no changes post-treatment. Given elevated IL-13 levels in the EoE patients with the highest periostin levels, future studies could explore periostin as a biomarker in EoE, perhaps in the setting of anti-IL-13 therapy

Microfluidic encapsulation method to produce stable liposomes containing iohexol

Since the discovery of X-rays in the late 1890s, several medical imaging techniques have been developed, such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Ultrasound Imaging, which are used daily to diagnose, monitor, or treat medical conditions. Some of these techniques include the use of contrast agents to enhance the contrast images, therefore, toxic effects must be considered. Among these, Contrast-Induced Nephropathy (CIN) is an acute renal failure resulting from the administration of iodinated contrast media (CM). To date, there is no definitive treatment for CIN and several prevention approaches have been evaluated. Nanoparticles (NPs) represent a promising strategy for treatment and prevention of CIN, due to their ability to deliver CM during diagnosis imaging. In this study, iohexol-containing liposomes were produced using microfluidic technique for first time. Several phosphocholine lipids (e.g. DMPC, DOPC, DPPC and DSPC) with cholesterol (2:1 ratio) were investigated and DLS, FTIR and in vitro release studies at 37 °C were performed, with stability studies conducted on the best formulation. The microfluidic method allowed to obtain a high encapsulation efficiency (over 70%), and release profiles showed an iohexol release around or less than 0.12 mg/ml after 2 h for the majority of the formulations, which is not toxic to the kidney cells

Minimization of defects generation in laser welding process of steel alloy for automotive application

Laser welding (LW) thanks to its flexibility, limited energy consumption and simple realization has a prominent role in several industrial sectors. LW process requires careful parameters' tuning to avoid generating internal defects in the microstructure or a poor weld depth, which reduce the joining mechanical strength and result in waste. This work exploits a supervised machine learning algorithm to optimize the process parameters to minimize the generated defects, while catering for design specifications and tolerances to predict defect generation probability. The work outputs a predictive quality control model to reduce non-destructive controls in the LW of aluminum for automotive applications

Analysis of residual plastic deformation of blanked sheets out of automotive aluminium alloys through hardness map

Reducing overall vehicle weight is essential to reduce fuel consumption and pollutant emission and to improve noise, vibration, and harshness (NVH) performances. The substitution with lighter alloys can involve the grand majority of vehicle components, depending on the market sector. In several applications, e.g., chassis, pulleys, and viscodampers, metal sheets are formed in several steps, each of whom work-hardens the material reducing the available residual plasticity. Typically, the process is designed via FEM, whose results are affected by the initial conditions, often neglected, and is performed on pre-processed materials from suppliers. In this regard, correctly simulating the first step of the process is critical. However, the related initial conditions, in terms of residual stress and strain induced by former preliminary operations, are often neglected. This work proposes a quick and economical experimental procedure based on a hardness map to estimate initial conditions and to validate FEM results. The procedure allows evaluating the material's residual plasticity, which is necessary to process engineers to design following manufacturing steps. The approach is demonstrated on an industrially relevant case study, i.e., the blanking of an AA 5754, in use for water pump pulleys

An unusual cause of alveolar hemorrhage post hematopoietic stem cell transplantation: A case report

BACKGROUND: Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported. CASE PRESENTATION: We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock. CONCLUSION: Strongyloides stercoralis hyperinfection is an unusual cause of alveolar hemorrhage early after hematopoietic stem cell transplant with very high mortality