Brain organoids: Filling the need for a human model of neurological disorder

Neurological disorders are among the leading causes of death worldwide, accounting for almost all onsets of dementia in the elderly, and are known to negatively affect motor ability, mental and cognitive performance, as well as overall wellbeing and happiness. Currently, most neurological disorders go untreated due to a lack of viable treatment options. The reason for this lack of options is s poor understanding of the disorders, primarily due to research models that do not translate well into the human in vivo system. Current models for researching neurological disorders, neurodevelopment, and drug interactions in the central nervous system include in vitro monolayer cell cultures, and in vivo animal models. These models have shortcomings when it comes to translating research about disorder pathology, development, and treatment to humans. Brain organoids are three-dimensional (3D) cultures of stem cell-derived neural cells that mimic the development of the in vivo human brain with high degrees of accuracy. Researchers have started developing these miniature brains to model neurodevelopment, and neuropathology. Brain organoids have been used to model a wide range of neurological disorders, including the complex and poorly understood neurodevelopmental and neurodegenerative disorders. In this review, we discuss the brain organoid technology, placing special focus on the different brain organoid models that have been developed, discussing their strengths, weaknesses, and uses in neurological disease modeling

Glass glass transition and new dynamical singularity points in an analytically solvable p-spin glass like model

We introduce and analytically study a generalized p-spin glass like model that captures some of the main features of attractive glasses, recently found by Mode Coupling investigations, such as a glass/glass transition line and dynamical singularity points characterized by a logarithmic time dependence of the relaxation. The model also displays features not predicted by the Mode Coupling scenario that could further describe the attractive glasses behavior, such as aging effects with new dynamical singularity points ruled by logarithmic laws or the presence of a glass spinodal line

Why do some asthma patients respond poorly to glucocorticoid therapy?

Glucocorticosteroids are the first-line therapy for controlling airway inflammation in asthma. They bind intracellular glucocorticoid receptors to trigger increased expression of anti-inflammatory genes and suppression of pro-inflammatory gene activation in asthmatic airways. In the majority of asthma patients, inhaled glucocorticoids are clinically efficacious, improving lung function and preventing exacerbations. However, 5–10 % of the asthmatic population respond poorly to high dose inhaled and then systemic glucocorticoids. These patients form a category of severe asthma associated with poor quality of life, increased morbidity and mortality, and constitutes a major societal and health care burden. Inadequate therapeutic responses to glucocorticoid treatment is also reported in other inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease; however, asthma represents the most studied steroid-refractory disease. Several cellular and molecular events underlying glucocorticoid resistance in asthma have been identified involving abnormalities of glucocorticoid receptor signaling pathways. These events have been strongly related to immunological dysregulation, genetic, and environmental factors such as cigarette smoking or respiratory infections. A better understanding of the multiple mechanisms associated with glucocorticoid insensitivity in asthma phenotypes could improve quality of life for people with asthma but would also provide transferrable knowledge for other inflammatory diseases. In this review, we provide an update on the molecular mechanisms behind steroid-refractory asthma. Additionally, we discuss some therapeutic options for treating those asthmatic patients who respond poorly to glucocorticoid therapy

redesign and manufacturing of a metal towing hook via laser additive manufacturing with powder bed

Abstract An approach to redesign and manufacture a metal towing hook via Selective Laser Melting is discussed. Some reference criteria and general guidelines are considered step-by-step to concurrently address lightening, manufacturability and job planning. Grounds are given for the application of Additive Manufacturing for complex components to the purpose of material saving and increased safety factor

Keck and Gemini spectral characterization of Lucy mission fly-by target (152830) Dinkinesh

Recently, the inner main belt asteroid (152830) Dinkinesh was identified as an additional fly-by target for the Lucy mission. The heliocentric orbit and approximate absolute magnitude of Dinkinesh are known, but little additional information was available prior to its selection as a target. In particular, the lack of color spectrophotometry or spectra made it impossible to assign a spectral type to Dinkinesh from which its albedo could be estimated. We set out to remedy this knowledge gap by obtaining visible wavelength spectra with the Keck telescope on 2022 November 23 and with Gemini-South on 2022 December 27. The spectra measured with the Keck I/Low Resolution Imaging Spectrometer (LRIS) and the Gemini South/Gemini Multi-Object Spectrograph South (GMOS-S) are most similar to the average spectrum of S- and Sq-type asteroids. The most diagnostic feature is the $\approx$15$\pm$1$\%$ silicate absorption feature at $\approx$0.9-1.0~micron. Small S- and Sq-type asteroids have moderately high albedos ranging from 0.17-0.35. Using this albedo range for Dinkinesh in combination with measured absolute magnitude, it is possible to derive an effective diameter and surface brightness for this body. The albedo, size and surface brightness are important inputs required for planning a successful encounter by the Lucy spacecraft.Comment: 7 pages, 1 figure. Under review in Icaru

Fatigue assessment of Ti-6Al-4V titanium alloy laser welded joints in absence of filler material by means of full-field techniques

The aim of this research activity was to study the fatigue behavior of laser welded joints of titanium alloy, in which the welding was performed using a laser source and in the absence of filler material, by means of unconventional full field techniques: Digital Image Correlation (DIC), and Infrared Thermography (IRT). The DIC technique allowed evaluating the strain gradients around the welded zone. The IRT technique allowed analyzing the thermal evolution of the welded surface during all the fatigue tests. The fatigue limit estimated using the Thermographic Method corresponds with good approximation to the value obtained from the experimental fatigue tests. The obtained results provided useful information for the development of methods and models to predict the fatigue behavior of welded T-joints in titanium alloy

Computational simulation methodologies for mechanobiological modelling: a cell-centred approach to neointima development in stents

The design of medical devices could be very much improved if robust tools were available for computational simulation of tissue response to the presence of the implant. Such tools require algorithms to simulate the response of tissues to mechanical and chemical stimuli. Available methodologies include those based on the principle of mechanical homeostasis, those which use continuum models to simulate biological constituents, and the cell-centred approach, which models cells as autonomous agents. In the latter approach, cell behaviour is governed by rules based on the state of the local environment around the cell; and informed by experiment. Tissue growth and differentiation requires simulating many of these cells together. In this paper, the methodology and applications of cell-centred techniques—with particular application to mechanobiology—are reviewed, and a cell-centred model of tissue formation in the lumen of an artery in response to the deployment of a stent is presented. The method is capable of capturing some of the most important aspects of restenosis, including nonlinear lesion growth with time. The approach taken in this paper provides a framework for simulating restenosis; the next step will be to couple it with more patient-specific geometries and quantitative parameter data

disk laser welding of ti 6al 4v titanium alloy plates in t joint configuration

Abstract Titanium alloys are employed in a wide range of applications, ranging from aerospace to medicine. In particular, Ti-6Al-4V is the most common, thanks to an excellent combination of low density, high specific strength and corrosion resistance. Laser welding has been increasingly considered as an alternative to traditional techniques to join titanium alloys. An increase in penetration depth and a reduction of possible welding defects is indeed achieved; moreover a smaller grain size in the fused zone is benefited in comparison to either TIG and plasma arc welding, thus providing an increase in the tensile strength of the welded structures. The aim of this work is to study disk-laser welding of 3.2mm thick Ti-6Al-4V plates in T-joint configuration without using a filler wire, defining the influence of different process parameters. The issue concerning the clamping of the plates is discussed and a proper device is developed to carry out welds. A structured plan has to be carried out in order to characterize the process thus discussing the response variables. Power and welding speed are considered as crucial input variables since they determine the thermal input to the work-piece; furthermore, given the particular configuration analyzed, tilt angle is considered as a further variable, whereas focus position is fixed below the upper surface to obtain a full penetration. Welding beads have been first examined with a coordinate measuring machine to study distortions, and then from a morphological point of view. Eventually, Vickers microhardness testing has been conducted to discuss structural changes in fusion and heat affected zone due to welding thermal cycles

Near-infrared spectroscopy-intravascular ultrasound: Scientific basis and clinical applications

Coronary angiography underestimates the magnitude of the atherosclerotic burden and cannot detect the presence of disease in the early phases. Recognition of these inherent limitations of angiography has been an impetus for the development of other coronary imaging techniques. The novel near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) catheters can detect and quantify the presence of lipid core in the atherosclerotic plaque and associate it with other features such as lumen size and plaque architecture. Lipid-rich plaques are known to pose a higher risk of distal embolization during interventions and plaque disruption. The aim of this manuscript is the review of the potential clinical and research applications of this technology as highlighted by recent studies