Wide Band Propagation in Train-to-Train Scenarios - Measurement Campaign and First Results

Within the next decades the railway systems will change to fully autonomous high speed trains (HSTs). An increase in efficiency and safety and a reduction of costs would go hand in hand. Today’s centralized railway management system and established regulations can not cope with trains driving within the absolute braking distance as it would be necessary for electronic coupling or platooning maneuvers. Hence, to ensure safety and reliability, new applications and changes in the train control and management are necessary. Such changes demand new reliable control communication links between train-to-train (T2T) and future developments on train-to-ground (T2G). T2G will be covered by long term evolution-railway (LTE-R) which shall replace today’s global system for mobile communications-railway (GSM-R). The decentralized T2T communication is hardly investigated and no technology has been selected. This publication focuses on the wide band propagation for T2T scenarios and describes a extensive channel sounding measurement campaign with two HSTs. First results of T2T communication at high speed conditions in different environments are presented

Performance Evaluation of Network Slicing for Aerial Vehicle Communications

Using 5G networks for flying vehicles is an opportunity to provide reliable connectivity while reducing cost and requirements on size, weight and power consumption. Network slicing is one feature which is particularly of interest. It enables a reliable aerial vehicle control slice independent from payload communication, such as video streaming to the ground. For the Unmanned Aerial Vehicle (UAV) use case, we rely on a 5G testbed that serves cars on an operational highway and trains on a parallel rail section. To test the effectiveness of network slicing, we show that the UAV control slice is unaffected by an overloaded UAV payload slice.Expósito García, A.; Hofmann, S.; Sous, C.; García, L.; Baltaci, A.; Bach, C.; Wellens, R.... (2019). Performance Evaluation of Network Slicing for Aerial Vehicle Communications. IEEE. 1-6. https://doi.org/10.1109/ICCW.2019.8756738S1

First Analysis of Inside Train Communication with ITS-G5 Measurement Data

Interest in wireless communication systems in the vehicular domain is growing apace leading to the adjustment of current standards to be suitable for the more challenging and varying channel conditions. These adjustments lead to the introduction of the standards Global System for Mobile Communications - Railway (GSM-R), Long Term Evolution - Railway (LTE-R) and Intelligent Transport Systems operating in the 5 GHz frequency band (ITS-G5). First measurement results of ITS-G5 based communications for Intra-Train scenarios are presented in this paper. The performance of an ITS-G5 data link is analyzed and influences on the propagation channel from the inside and outside environment of the train are investigated for different link distances and different speed. The results show the possibility of applying such technology for Intra-Train communications for future wireless applications

Optimizing a therapeutic humanized follicle-stimulating hormone-blocking antibody formulation by protein thermal shift assay

Biopharmaceutical products are formulated using several Food and Drug Administration (FDA) approved excipients within the inactive ingredient limit to maintain their storage stability and shelf life. Here, we have screened and optimized different sets of excipient combinations to yield a thermally stable formulation for the humanized follicle-stimulating hormone (FSH)-blocking antibody, MS-Hu6. We used a protein thermal shift assay in which rising temperatures resulted in the maximal unfolding of the protein at the melting temperature (T ). To determine the buffer and pH for a stable solution, four different buffers with a pH range from 3 to 8 were screened. This resulted in maximal T s at pH 5.62 for Fab in phosphate buffer and at pH 6.85 for Fc in histidine buffer. Upon testing a range of salt concentrations, MS-Hu6 was found to be more stable at lower concentrations, likely due to reduced hydrophobic effects. Molecular dynamics simulations revealed a higher root-mean-square deviation with 1 mM than with 100 mM salt, indicating enhanced stability, as noted experimentally. Among the stabilizers tested, Tween 20 was found to yield the highest T and reversed the salt effect. Among several polyols/sugars, trehalose and sucrose were found to produce higher thermal stabilities. Finally, binding of recombinant human FSH to MS-Hu6 in a final formulation (20 mM phosphate buffer, 1 mM NaCl, 0.001% w/v Tween 20, and 260 mM trehalose) resulted in a thermal shift (increase in T ) for the Fab, but expectedly not in the Fc domain. Given that we used a low dose of MS-Hu6 (1 μM), the next challenge would be to determine whether 100-fold higher, industry-standard concentrations are equally stable

FSH-blocking therapeutic for osteoporosis

Pharmacological and genetic studies over the past decade have established the follicle-stimulating hormone (FSH) as an actionable target for diseases affecting millions, namely osteoporosis, obesity, and Alzheimer\u27s disease. Blocking FSH action prevents bone loss, fat gain and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a K of 7.52 nM. Using a GLP-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using Zr-labelled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. MS-Hu6 displayed a β phase t of 7.5 days (180 hours) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. MS-Hu6 showed the same level of \u27humanness\u27 as human IgG1 and was non-immunogenic in ELISPOT assays for IL-2 and IFNg in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing

Optimizing a therapeutic humanized follicle-stimulating hormone-blocking antibody formulation by protein thermal shift assay

Biopharmaceutical products are formulated using several Food and Drug Administration (FDA) approved excipients within the inactive ingredient limit to maintain their storage stability and shelf life. Here, we have screened and optimized different sets of excipient combinations to yield a thermally stable formulation for the humanized follicle-stimulating hormone (FSH)-blocking antibody, MS-Hu6. We used a protein thermal shift assay in which rising temperatures resulted in the maximal unfolding of the protein at the melting temperature (Tm ). To determine the buffer and pH for a stable solution, four different buffers with a pH range from 3 to 8 were screened. This resulted in maximal Tm s at pH 5.62 for Fab in phosphate buffer and at pH 6.85 for Fc in histidine buffer. Upon testing a range of salt concentrations, MS-Hu6 was found to be more stable at lower concentrations, likely due to reduced hydrophobic effects. Molecular dynamics simulations revealed a higher root-mean-square deviation with 1 mM than with 100 mM salt, indicating enhanced stability, as noted experimentally. Among the stabilizers tested, Tween 20 was found to yield the highest Tm and reversed the salt effect. Among several polyols/sugars, trehalose and sucrose were found to produce higher thermal stabilities. Finally, binding of recombinant human FSH to MS-Hu6 in a final formulation (20 mM phosphate buffer, 1 mM NaCl, 0.001% w/v Tween 20, and 260 mM trehalose) resulted in a thermal shift (increase in Tm ) for the Fab, but expectedly not in the Fc domain. Given that we used a low dose of MS-Hu6 (1 μM), the next challenge would be to determine whether 100-fold higher, industry-standard concentrations are equally stable

FSH blockade improves cognition in mice with Alzheimer\u27s disease

Alzheimer\u27s disease has a higher incidence in older women, with a spike in cognitive decline that tracks with visceral adiposity, dysregulated energy homeostasis and bone loss during the menopausal transition. Inhibiting the action of follicle-stimulating hormone (FSH) reduces body fat, enhances thermogenesis, increases bone mass and lowers serum cholesterol in mice. Here we show that FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-β and Tau deposition and impair cognition in mice displaying features of Alzheimer\u27s disease. Blocking FSH action in these mice abrogates the Alzheimer\u27s disease-like phenotype by inhibiting the neuronal C/EBPβ-δ-secretase pathway. These data not only suggest a causal role for rising serum FSH levels in the exaggerated Alzheimer\u27s disease pathophysiology during menopause, but also reveal an opportunity for treating Alzheimer\u27s disease, obesity, osteoporosis and dyslipidaemia with a single FSH-blocking agent

First-in-class humanized FSH blocking antibody targets bone and fat.

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with