Contamination of Mesenchymal Stem-Cells with Fibroblasts Accelerates Neurodegeneration in an Experimental Model of Parkinson’s Disease

Pre-clinical studies have supported the use of mesenchymal stem cells (MSC) to treat highly prevalent neurodegenerative diseases such as Parkinson’s disease (PD) but preliminary trials have reported controversial results. In a rat model of PD induced by MPTP neurotoxin, we first observed a significant bilateral preservation of dopaminergic neurons in the substantia nigra and prevention of motor deficits typically observed in PD such as hypokinesia, catalepsy, and bradykinesia, following intracerebral administration of human umbilical cord-derived MSC (UC-MSC) early after MPTP injury. However, surprisingly, administration of fibroblasts, mesenchymal cells without stem cell properties, as a xenotransplantation control was highly detrimental, causing significant neurodegeneration and motor dysfunction independently of MPTP. This observation prompted us to further investigate the consequences of transplanting a MSC preparation contaminated with fibroblasts, a plausible circumstance in cell therapy since both cell types display similar immunophenotype and can be manipulated in vitro under the same conditions. Here we show for the first time, using the same experimental model and protocol, that transplantation of UC-MSC induced potent neuroprotection in the brain resulting in clinical benefit. However, co-transplantation of UC-MSC with fibroblasts reverted therapeutic efficacy and caused opposite damaging effects, significantly exacerbating neurodegeneration and motor deficits in MPTP-exposed rats. Besides providing a rationale for testing UC-MSC transplantation in early phases of PD aiming at delaying disease progression, our pre-clinical study suggests that fibroblasts may be common cell contaminants affecting purity of MSC preparations and clinical outcome in stem cell therapy protocols, which might also explain discrepant clinical results

Correlating PMC-MMC Bonded Joint 3D FEA with Test

A viewgraph presentation on the correlation of Polymer Matrix Composites (PMC) and Metal Matrix Composites (MMC) bonded joints using three dimensional finite element analyses with materials tests is shown

On the Valorisation of Chitin-Derived Furans by Milling

Chitin-derived furans offer a sustainable alternative feedstock for nitrogen appended aromatic compounds. Herein, we address the challenge of using chitin-derived furans, 3-acetamido-5-acetylfuran (3A5AF) and 3-acetamido-5-furfural aldehyde (3A5F), to favour the formation of exo Diels–Alder adducts and 4-acetylaminophthalimides respectively, using a mechanochemical ball-milling technique. Mechanochemical activation is explored through the synthesis of 7-oxa-norbornene backbones with novel substitution pattern from 3A5AF in yields up to 77 % and improved exo:endo selectivity compared to solution-phase reactions. The synthesis of 4-acetylaminophthalimides from 3A5F in yields up to 79 % is also showcased from hydrazone derivatives

'Mobile Only' Users Powered by Fixed-Mobile Substitution

In a context of partial fixed-mobile substitution, we analyze fixed-mobile bundling and mobile-to-fixed off-loading in a duopoly model in which consumers buy one or two products. A joint purchase discount mitigates fixed-mobile substitutability and consequently reduces mobile-only and fixed-only consumers. Practises like introducing a small discount, applied on a bundle of multiple service or mobile-to-fixed offloading by both operators are analysed. We find that such practises do not have negative impacts on the profits of whole market and lead to both consumers' surplus and welfare gains. The investment incentives in fixed network are positive and can be boosted by FM bundling without considering regulatory intervention and before taking into account of fixed costs. The investment incentives in mobile network are more likely a situation of prisoners' dilemma where operators should invest as long as there are mobile-only consumers

Tomographic imaging of fragmented cortical bone heteroimplant and methylmethacrylate in segmental bone defect of rabbit tibia

PURPOSE: To evaluate the performance of composites consisting of fragmented cortical bone heteroimplant in association with methylmethacrylate preserved in 98% glycerin, in segmental bone defect of rabbit tibia medial metaphysis. METHODS: In this study were used twelve adult New Zealand rabbits, divided into three groups of four animals each: G30 (30 days), G60 (60 days) and G90 (90 days). The bone defects previously created in the tibia were filled with composites and both were evaluated by cone-beam computed tomography, immediately after surgery and after 30, 60, and 90 days. RESULTS: The composites fulfilled and remained in the sites of bone defects in all cases and were not registered signals of infection, migration or rejection. CONCLUSIONS: The implanted composites promoted the bone defects repair without signals of infection and/or rejection. The composites are one more option for bone defects repair

Strong Interaction Physics at the Luminosity Frontier with 22 GeV Electrons at Jefferson Lab

This document presents the initial scientific case for upgrading the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab (JLab) to 22 GeV. It is the result of a community effort, incorporating insights from a series of workshops conducted between March 2022 and April 2023. With a track record of over 25 years in delivering the world's most intense and precise multi-GeV electron beams, CEBAF's potential for a higher energy upgrade presents a unique opportunity for an innovative nuclear physics program, which seamlessly integrates a rich historical background with a promising future. The proposed physics program encompass a diverse range of investigations centered around the nonperturbative dynamics inherent in hadron structure and the exploration of strongly interacting systems. It builds upon the exceptional capabilities of CEBAF in high-luminosity operations, the availability of existing or planned Hall equipment, and recent advancements in accelerator technology. The proposed program cover various scientific topics, including Hadron Spectroscopy, Partonic Structure and Spin, Hadronization and Transverse Momentum, Spatial Structure, Mechanical Properties, Form Factors and Emergent Hadron Mass, Hadron-Quark Transition, and Nuclear Dynamics at Extreme Conditions, as well as QCD Confinement and Fundamental Symmetries. Each topic highlights the key measurements achievable at a 22 GeV CEBAF accelerator. Furthermore, this document outlines the significant physics outcomes and unique aspects of these programs that distinguish them from other existing or planned facilities. In summary, this document provides an exciting rationale for the energy upgrade of CEBAF to 22 GeV, outlining the transformative scientific potential that lies within reach, and the remarkable opportunities it offers for advancing our understanding of hadron physics and related fundamental phenomena.Comment: Updates to the list of authors; Preprint number changed from theory to experiment; Updates to sections 4 and 6, including additional figure

The case for an EIC theory alliance : theoretical challenges of the EIC

We outline the physics opportunities provided by the Electron Ion Collider (EIC). These include the study of the parton structure of the nucleon and nuclei, the onset of gluon saturation, the production of jets and heavy flavor, hadron spectroscopy and tests of fundamental symmetries. We review the present status and future challenges in EIC theory that have to be addressed in order to realize this ambitious and impactful physics program, including how to engage a diverse and inclusive workforce. In order to address these many-fold challenges, we propose a coordinated effort involving theory groups with differing expertise is needed. We discuss the scientific goals and scope of such an EIC Theory Alliance

Strong interaction physics at the luminosity frontier with 22 GeV electrons at Jefferson Lab

This document presents the initial scientific case for upgrading the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab (JLab) to 22 GeV. It is the result of a community effort, incorporating insights from a series of workshops conducted between March 2022 and April 2023. With a track record of over 25 years in delivering the world's most intense and precise multi-GeV electron beams, CEBAF's potential for a higher energy upgrade presents a unique opportunity for an innovative nuclear physics program, which seamlessly integrates a rich historical background with a promising future. The proposed physics program encompass a diverse range of investigations centered around the nonperturbative dynamics inherent in hadron structure and the exploration of strongly interacting systems. It builds upon the exceptional capabilities of CEBAF in high-luminosity operations, the availability of existing or planned Hall equipment, and recent advancements in accelerator technology. The proposed program cover various scientific topics, including Hadron Spectroscopy, Partonic Structure and Spin, Hadronization and Transverse Momentum, Spatial Structure, Mechanical Properties, Form Factors and Emergent Hadron Mass, Hadron-Quark Transition, and Nuclear Dynamics at Extreme Conditions, as well as QCD Confinement and Fundamental Symmetries. Each topic highlights the key measurements achievable at a 22 GeV CEBAF accelerator. Furthermore, this document outlines the significant physics outcomes and unique aspects of these programs that distinguish them from other existing or planned facilities. In summary, this document provides an exciting rationale for the energy upgrade of CEBAF to 22 GeV, outlining the transformative scientific potential that lies within reach, and the remarkable opportunities it offers for advancing our understanding of hadron physics and related fundamental phenomena