Characterization of FBK 3D pixel sensor modules based on RD53A readout chip for the ATLAS ITk

CERN is planning to upgrade its Large Hadron Collider to the High Luminosity phase (HL-LHC), pushing detector technologies to cope with unprecedently demanding performance in terms of particle rate and radiation hardness. The ATLAS experiment decided to equip the innermost layer (L0) of its Inner Tracker (ITk) with small-pitch 3D pixels of two different geometries, i.e., 25 µm × 100 µm for the central barrel and 50 µm × 50 µm for the lateral rings. A new generation of 3D pixels featuring these small-pitch dimensions and reduced active thickness (∼150 µm) has been developed to this purpose within a collaboration of INFN and FBK since 2014. Recently, the R&D activities have been focused on the characterization of modules based on sensors compatible with the RD53A readout chip, which were tested in laboratory and at beam lines. In this paper, we report on the characterization of modules irradiated with protons up to a fluence of 1 × 1016 neq/cm2, including threshold tuning and noise measurements, and results from beam tests performed at DESY. Moreover, we will discuss about the electrical characteristics at wafer level and at module level before and after irradiation.

The Micromegas Surface Commissioning For the ATLAS New Small Wheel

In order to cope with the required precision tracking and trigger capabilities from Run III onward in the ATLAS experiment, the innermost layer of the Muon Spectrometer end-cap (Small Wheels) will be upgraded. Each of the two New Small Wheels (NSW) will be equipped with eight layers of MicroMegas (MM) detectors and eight layers of small-strip Thin Gap Chambers (sTGC), both arranged in two quadruplets. MM detectors of large size (up to 3m2) will be employed for the first time in HEP experiments. Four different types of MM quadruplet modules (SM1, SM2, LM1, LM2), built by different Institutes, compose the NSW. The modules are then sent to CERN, integrated into double wedges (DW), tested and sent for commissioning on the wheel itself. At the commissioning stage the MM double wedges along with the sTGC wedges are assembled together into sectors which are then installed and tested on the wheel. Each wheel comprises 8 small (made of SM1 and SM2 modules) and 8 large (made of LM1 and LM2 modules) sectors, in order to provide full coverage of the end caps. The first of the two wheels (NSW-A) has been fully commissioned, installed in ATLAS and the first tests are currently ongoing. The second wheel (NSW-C) is currently under commissioning and is expected to be ready by October this year.

Extracellular Vesicles in Airway Homeostasis and Pathophysiology

The epithelial–mesenchymal trophic unit (EMTU) is a morphofunctional entity involved in the maintenance of the homeostasis of airways as well as in the pathogenesis of several diseases, including asthma and chronic obstructive pulmonary disease (COPD). The “muco-microbiotic layer” (MML) is the innermost layer of airways made by microbiota elements (bacteria, viruses, archaea and fungi) and the surrounding mucous matrix. The MML homeostasis is also crucial for maintaining the healthy status of organs and its alteration is at the basis of airway disorders. Nanovesicles produced by EMTU and MML elements are probably the most important tool of communication among the different cell types, including inflammatory ones. How nanovesicles produced by EMTU and MML may affect the airway integrity, leading to the onset of asthma and COPD, as well as their putative use in therapy will be discussed here.

Catestatin selects for the colonization of antimicrobial-resistant gut bacterial communities

The gut microbiota is in continuous interaction with the innermost layer of the gut, namely the epithelium. Among the various functions of the gut epithelium, is to keep the microbes at bay to avoid overstimulation of the underlying mucosa immune cells. To do so, the gut epithelia secrete a variety of antimicrobial peptides, such as catestatin (CST). As a defense mechanism, gut microbes have evolved antimicrobial resistance mechanisms to counteract the killing effect of the secreted peptides. To this end, we treated wild-type mice and mice with a knockout in the CST coding region of the chromogranin-A gene (CST-KO) with CST for 15 consecutive days. CST treatment was associated with a shift in the diversity and composition of the microbiota in the CST-KO mice. This effect was less prominent in WT mice. Levels of the microbiota-produced short-chain fatty acids, in particular, butyrate and acetate were significantly increased in CST-treated CST-KO mice but not the WT group. Remarkably, both CST-treated CST-KO and WT mice showed a significant increase in microbiota-harboring phosphoethanolamine transferase-encoding genes, which facilitate their antimicrobial resistance. Finally, we show that CST was degraded by Escherichia coli via an omptin-protease and that the abundance of this gene was significantly higher in metagenomic datasets collected from patients with Crohn's disease but not with ulcerative colitis. Overall, this study illustrates how the endogenous antimicrobial peptide, CST, shapes the microbiota composition in the gut and primes further research to uncover the role of bacterial resistance to CST in disease states such as inflammatory bowel disease.

Single-Cell RNA Sequencing Reveals Endothelial Cell Transcriptome Heterogeneity Under Homeostatic Laminar Flow

Objective: Endothelial cells (ECs) that form the innermost layer of all vessels exhibit heterogeneous cell behaviors and responses to pro-angiogenic signals that are critical for vascular sprouting and angiogenesis. Once vessels form, remodeling and blood flow lead to EC quiescence, and homogeneity in cell behaviors and signaling responses. These changes are important for the function of mature vessels, but whether and at what level ECs regulate overall expression heterogeneity during this transition is poorly understood. Here, we profiled EC transcriptomic heterogeneity, and expression heterogeneity of selected proteins, under homeostatic laminar flow. Approach and Results: Single-cell RNA sequencing and fluorescence microscopy were used to characterize heterogeneity in RNA and protein gene expression levels of human ECs under homeostatic laminar flow compared to nonflow conditions. Analysis of transcriptome variance, Gini coefficient, and coefficient of variation showed that more genes increased RNA heterogeneity under laminar flow relative to genes whose expression became more homogeneous, although small subsets of cells did not follow this pattern. Analysis of a subset of genes for relative protein expression revealed little congruence between RNA and protein heterogeneity changes under flow. In contrast, the magnitude of expression level changes in RNA and protein was more coordinated among ECs in flow versus nonflow conditions. Conclusions: ECs exposed to homeostatic laminar flow showed overall increased heterogeneity in RNA expression levels, while expression heterogeneity of selected cognate proteins did not follow RNA heterogeneity changes closely. These findings suggest that EC homeostasis is imposed post-transcriptionally in response to laminar flow.

Ovule development, megasporogenesis, and megagametogenesis of Fouquieria fasciculata (Willd. ex Roem. & Schult.) Nash (Fouquieriaceae)

Background: Fouquieriaceae is a small family that consists of a single genus, Fouquieria, with eleven species occurring mostly in arid and semiarid regions of Mexico and the southwestern United States. The development of the ovule and the female gametophyte has been poorly characterized in species of the family; thus, it is proposed to carry out a detailed study on the development of the ovule, megasporogenesis and megagametogenesis in Fouquieria fasciculata. Questions: How are the developmental patterns of the ovule and the female gametophyte in Fouquieria fasciculata? Study species: Fouquieria fasciculata (Willd. ex Roem. & Schult.) Nash (Fouquieriaceae). Methods: Embryology, morphology and histochemical tests of floral buds and flowers at pre-anthesis of Fouquieria fasciculata were examined using light microscopy and scanning electron microscopy. Results: The ovules of Fouquieria fasciculata are anatropous, bitegmic and tenuinucellate, and the micropyle is formed by the inner integument. The innermost layer cells of the inner integument form an integumentary tapetum or endothelium. The cells of integumentary tapetum are characterized by very conspicuous wall thickenings on the inner tangential side, and are radially elongated surrounding the nucellus. The pattern of development of the female gametophyte is monosporic Polygonum-type, and the formation of a lateral haustorium was observed. Conclusions: This investigation describes in detail the development of the ovule and the female gametophyte ofFouquieria fasciculata. Our results show interesting features, such as the differentiation of an integumentary tapetum, a monosporic Polygonum-type pattern of development and the formation of lateral haustorial arm in the female gametophyte.

Estimation of Dose Enhancement for Inhomogeneous Distribution of Nanoparticles: A Monte Carlo Study

High atomic number nanoparticles are of increasing interest in radiotherapy due to their significant positive impact on the local dose applied to the treatment site. In this work, three types of metal nanoparticles were utilized to investigate their dose enhancement based on the GATE Monte Carlo simulation tool. Gold, gadolinium, and silver were implanted at three different concentrations to a 1 cm radius sphere to mimic a cancerous tumor inside a 10 × 10 × 30 cm3 water phantom. The innermost layer of the tumor represents a necrotic region, where the metal nanoparticles uptake is assumed to be zero, arising from hypoxic conditions. The nanoparticles were defined using the mixture technique, where nanoparticles are added to the chemical composition of the tumor. A directional 2 × 2 cm2 monoenergetic photon beam was used with several energies ranging from 50 keV to 4000 keV. The dose enhancement factor (DEF) was measured for all three metal nanoparticles under all beam energies. The maximum DEF was ~7 for silver nanoparticles with the 50 keV beam energy at the highest nanoparticle concentration of 30 mg/g of water. Gold followed the same trend as it registered the highest DEF at the 50 keV beam energy with the highest concentration of nanoparticles at 30 mg/g, while gadolinium registered the highest at 100 keV.

Segmental Representation of Intimal Thickness in Ascending Aorta as Early Clinical Marker of Aging

Background: Intimal thickness is the innermost layer of aorta; play a vital role in development of atherosclerotic changes. It may vary in the different parts of the aorta and may increase with age. Methods: 120 aortas of adult human forensic bodies were taken. Histological slides were formed and the thickness of different segments of aorta were measured microscopically. Data were statically analyzed using ANOVA, p test methods. Results and Discussion: There is no significant difference of Intimal thickness in different segments of ascending aorta though it significantly increase with age may be due to accumulation of medial SMCs into intima. Results agree with previous workers. Conclusion: No significant difference between different segments of ascending aorta and it increase with age showing the aging aorta and early sign of atherosclerotic changes. KEY WORDS: Aging, Intimal thickness, Age Groups, Smooth Muscle Cells, Medial thickness.

Reconstruction of Light Organ in Squid With The Histological Method of Electron Transmission Microscope

The light organ is an electronic device that can emit light. However, there are light organs in animals that can produce light naturally. Loligo duvaucelii is a species whose biolumenesence comes from fluorescent bacteria that live in symbiosis in its ink sacs. This study aims to determine in detail the construction of the squid light organ using the transmission electron microscopy (TEM) method. The results showed that this type of squid has a pair of light organs attached to the dorso-lateral ink sac. The light organ is spherical, some are found on the surface and some are embedded on the wall of the ink sac. It consists of a lens that is located on the outer surface of the ink sac, and a sac of light organs (embedded on the wall of the ink sac) with channels connecting the pocket to the mantle cavity. The wall of the sac of the light organ consists of three layers, namely the innermost layer which is multi-fold with microvilli on the cell surface and between the folds of the sac populated with bacteria, the dense layer that acts as a reflector, and the pigment layer. Cilia are observed on the surface of the duct connecting the sac with the mantle cavity. This study concluded that the construction of the squid light organ has a convex-shaped lens structure and is muscular. In the pockets of light organs, a dense population of bacteria is found. The reflector consists of many layers, and the pigment layer contains many granules.