The Nondelegation Doctrine: Alive and Well

The nondelegation doctrine is dead. It is difficult to think of a more frequently repeated or widely accepted legal conclusion. For generations, scholars have maintained that the doctrine was cast aside by the New Deal Court and is now nothing more than a historical curiosity. In this Article, we argue that the conventional wisdom is mistaken in an important respect. Drawing on an original dataset of more than one thousand nondelegation challenges, we find that, although the doctrine has disappeared at the federal level, it has thrived at the state level. In fact, in the decades since the New Deal, state courts have grown more willing to invoke the nondelegation doctrine. Despite the countless declarations of its demise, the nondelegation doctrine is, in a meaningful sense, alive and well

Endothelial cells, endoplasmic reticulum stress and oxysterols

Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress

Build orientation effect on Ti6Al4V thin-wall topography by electron beam powder bed fusion

Additive Manufacturing is a key enabling technology for Industry 4.0 and the Green Deal, allowing more efficient resources exploitation while providing innovative design to critical components. Electron Beam Powder Bed Fusion (EB-PBF) is an edge technology for many sectors, i.e. aerospace, medical, and automotive. The control of the surface finish by surface topography measurements is essential to engineer surface functional properties, whose specifications are application specific. This works investigates the effect of thin-wall orientation and surface inclination on the topography, described by areal field and feature parameters, to provide designers with a useful tool in the early stage of product development and tolerance specification and verificatio

Biomedical Co-Cr-Mo Components Produced by Direct Metal Laser Sintering

Direct Metal Laser Sintering (DMLS) is an additive manufacturing technique based on a laser power source that sinters powdered materials using a 3D CAD model. The mechanical components produced by this procedure typically show higher residual porosity and poorer mechanical properties than those obtained by traditional manufacturing techniques. In this study, samples were produced by DMLS starting from a Co-Cr-Mo powder (in the \u3b3 phase) with a composition suitable for biomedical applications. Samples were submitted to hardness measurements and structural characterization. The samples showed a hardness value remarkably higher that those commonly obtained for the same cast or wrought alloys. In fact, the HRC value measured for the samples is 47 HRC, while the usual range for CAST Co-Cr-Mo is from 25 to 35 HRC. The samples microstructure was investigated by X-ray diffraction (XRD), electron microscopy (SEM and TEM) and energy dispersive microanalysis (EDX) in order to clarify the origin of this unexpected result. The laser treatment induced a melting of the metallic Co-Cr-Mo powder, generating a phase transformation from the \u3b3 (fcc) to the e (hcp) phase. The rapid cooling of the melted powder produced the formation of e (hcp) nano-lamellae inside the \u3b3 (fcc) phase. The nano-lamellae formed an intricate network responsible for the measured hardness increase. The results suggest possible innovative applications of the DMLS technique to the production of mechanical parts in the medical and dental fields, where a high degree of personalization is required

Uphill walking at iso-efficiency speeds

Uphill walking gait has been extensively studied, but the optimal uphill speed able to enhance the metabolic demand without increasing fatigability has so far received little attention. Therefore, the aim of this study was to assess the metabolic/kinematic demand at constant speed (6 km\ub7h 121 G0 level, G2 2% uphill, G7 7% uphill) and at iso-efficiency speeds (G2IES 5.2 km\ub7h 121 2% uphill and G7IES 3.9 km\ub7h 121 7% uphill). For this aim, physically active women (n:24, Age 33.40 \ub1 4.97 years, BMI 21.62 \ub1 2.06 kg/m-2) after an 8-min warm-up were studied on a treadmill for 10\u2b9 for every walking condition with a 5\u2b9 rest in between. Average heart rate (AVG-HR), rating of perceived exertion (RPE) and kinematic variables (stance time, swing time, stride length, stride cycle, stride-length variability, stride-cycle variability and internal work) were studied. Modif\ufeffications in stance time, stride length and stride cycle (p<0.005), and lower internal-work values (p<0.001) occurred in G7IES in comparison to the other conditions. Swing time was significantly modified only in G7IES compared to G0 and G7 (p<0.001 and p<0.005, respectively). Stride-length variability and stride-cycle variability were higher in G7IES compared to the other conditions (p<0.001). G7 induced the highest AVG-HR (p<0.005) and RPE (p<0.001) compared to the other conditions. This study demonstrates that by applying the equation for uphill walking gait, it is possible to maintain a similar metabolic demand and RPE at iso-efficiency speeds during uphill compared to level walking, inducing at the same time a modification of the kinematic parameters of walking gait performed at the same slope condition

Analisi del campo di deformazione superficiale della Regione Campania da dati SAR (PS-InSAR)

Il lavoro presenta un’applicazione della tecnica dei diffusori permanenti (Permanent Scatterers) finalizzata alla caratterizzazione del campo di deformazione superficiale della Regione Campania. Per effettuare l’analisi sono state processate, tramite la tecnica PS-InSARTM, 1078 scene SAR ERS1 ed ERS2 relative al periodo giugno 1992 - gennaio 2001. Sulla base della velocità media annua di spostamento di 1.691.740 PS con coerenza maggiore di 0.65 sono state prodotte mappe di velocità media di deformazione mediante l’utilizzo di una procedura articolata nei seguenti punti: a) filtraggio dei dati effettuato sulla base dei valori di coerenza; b) produzione di mappe di velocità media di deformazione in coordinate SAR; c) generazione di mappe di velocità media di deformazione secondo le componenti verticale ed Est-Ovest; d) validazione di risultati mediante confronto con dati prodotti con differenti metodiche d’indagine. L’analisi dei risultati ottenuti ha consentito di identificare aree caratterizzate da distinti stili deformativi. Aree in subsidenza sono risultate essere, per il periodo di interesse, oltre all’area vulcanica dei Campi Flegrei, le aree costiere dei bacini dei fiumi Volturno e Sele ed il settore centrale dell’isola d’Ischia. Aree con significativi valori di sollevamento sono localizzate nel settore settentrionale del Monte Somma, nel settore centrale della Piana Campana, nel Sannio e nel Cilento. Significativi valori di velocità di spostamento in direzione EW si riscontrano, oltre che nell’area dei Campi Flegrei, nel settore appenninico del bacino del Sele e nell’area interposta tra il Somma-Vesuvio e la catena appenninica. Il quadro deformativo globale risulta essere caratterizzato da un andamento complesso, governato da una molteplicità di processi di differente natura (tettonici, vulcano-tettonici, esogeni ed antropici)

An approach to evaluate the wear of customized manufacturing fixtures through the analysis of 3D scan data

With the recent gain in popularity and adoption of additive manufacturing in various industrial sectors, quality assessments to determine the functionality of 3D printed parts are critical. This holds especially when the parts are subjected to wear as in the case of the production of customized fixtures. Some reinforced polymeric materials for additive manufacturing can be employed as a substitute for low-resistance metals like Aluminium. In this paper, a custom-made tribometer was used to simulate the wear of 3D printed fixtures of Alumide material for sheet metal inspection operations. Contact 3D scanning is used to monitor the condition of the fixture for increasing numbers of wear cycles. This study aims to calculate the wear volume of cylindrical pins starting from the surface points of 3D scan data. The methodology employs alpha shapes to obtain the progression of the volume and area of the worn zone. Experimental tests to evaluate the wear volume were carried out to compare the durability of Alumide to that of Aluminium, filling the gap of previous literature, which had focused exclusively on diametral wear. The findings indicate a better wear resistance for Alumide specimens and this work contributes to broadening the knowledge about the wear behaviour and the lifetime of 3D printed parts

A novel splicing variant of col2a1 in a fetus with achondrogenesis type ii: Interpretation of pathogenicity of in-frame deletions

Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia