Product Integration of Established Crash Sensors for Safety Applications in Lightweight Vehicles.

The functionality of products increases when more sensors are used. This trend also affects future automobiles and becomes even more relevant in connected and autonomous applications. Concerning automotive lightweight design, carbon fibre-reinforced polymers (CFRP) are suitable materials. However, their drawbacks include the relatively high manufacturing costs of CFRP components in addition to the difficulty of recycling. To compensate for the increased expenditure, the integration of automotive sensors in CFRP vehicle structures provides added value. As a new approach, established sensors are integrated into fibre-reinforced polymer (FRP) structures. The sensors are usually mounted to the vehicle. The integration of sensors into the structure saves weight and space. Many other approaches specifically develop new sensors for integration into FRP structures. With the new approach, there is no need for elaborate development of new sensors since established sensors are used. The present research also showed that the range of applications of the sensors can be extended by the integration. The present paper outlines the functional behaviour of the integrated sensor utilized for crashing sensing. First of all, the integration quality of the sensor is relevant. Different requirements apply to the usual mounting of the sensor. The self-sensing structure must fulfil those requirements. Moreover, unfamiliar characteristics of the new surrounding structure might affect the sensing behaviour. Thus, the sensing behaviour of the self-sensing composite was analyzed in detail. The overarching objective is the general integration of sensors in products with reasonable effort.

Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides.

BACKGROUND: Therapeutic treatment options for chronic autoimmune disorders such as multiple sclerosis (MS) rely largely on the use of non-specific immunosuppressive drugs, which are not able to cure the disease. Presently, approaches to induce antigen-specific tolerance as a therapeutic approach; for example, by peptide-based tolerogenic 'inverse' vaccines have regained great interest. We have previously shown that coupling of peptides to carriers can enhance their capacity to induce regulatory T cells in vivo. METHOD: In this present study, we investigated whether the tolerogenic potential of immunodominant myelin T-cell epitopes can be improved by conjugation to the synthetic carrier polyethylene glycol (PEG) in an experimental autoimmune encephalomyelitis (EAE) mouse model for chronic MS (MOG C57BL/6). RESULTS: Preventive administration of the PEGylated antigenic peptide could strongly suppress the development of EAE, accompanied by reduced immune cell infiltration in the central nervous system (CNS). Depletion of regulatory T cells (Tregs) abrogated the protective effect indicating that Tregs play a crucial role in induction of antigen-specific tolerance in EAE. Treatment during the acute phase of disease was safe and did not induce immune activation. However, treatment at the peak of disease did not affect the disease course, suggesting that either induction of Tregs does not occur in the highly inflamed situation, or that the immune system is refractory to regulation in this condition. CONCLUSION: PEGylation of antigenic peptides is an effective and feasible strategy to improve tolerogenic (Treg-inducing) peptide-based vaccines, but application for immunotherapy of overt disease might require modifications or combination therapies that simultaneously suppress effector mechanisms.

Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer.

In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved "precision" drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC.

Bipolar radiofrequency-induced thermofusion of intestinal anastomoses--feasibility of a new anastomosis technique in porcine and rat colon.

PURPOSE: In recent years, vessel sealing has become a well-established method in surgical practice for sealing and transecting vessels. Since this technology depends on the fusion of collagen fibers abundantly present in the intestinal wall, it should also be possible to create intestinal anastomoses by thermofusion. Bipolar radiofrequency-induced thermofusion of intestinal tissue may replace traditionally used staples or sutures in the future. The aim of this study was to evaluate the feasibility of fusing intestinal tissue ex vivo by bipolar radiofrequency-induced thermofusion. MATERIALS AND METHODS: An experimental setup for temperature-controlled bipolar radiofrequency-induced thermofusion of porcine (n = 30) and rat (n = 18) intestinal tissue was developed. Colon samples were harvested and then anastomosed, altering compressive pressure to examine its influence on anastomotic bursting pressure during radiofrequency-induced anastomotic fusion. For comparison, mechanical stapler anastomoses of porcine colonic samples and conventional suturing of rat colonic samples identical to those used for fusion experiments were prepared, and burst pressure was measured. RESULTS: All thermofused colonic anastomoses were primarily tight and leakage proof. For porcine colonic samples, an optimal interval of compressive pressure (1,125 mN/mm(2)) with respect to a high amount of burst pressure (41 mmHg) was detected. The mean bursting pressure for mechanical stapler anastomosis was 60.7 mmHg and did not differ from the thermofusion (p = 0.15). Furthermore, the mean bursting pressure for thermofusion of rat colonic samples was up to 69.5 mmHg for a compressive pressure of 140 mN/mm(2). CONCLUSION: These results confirm the feasibility to create experimental intestinal anastomoses using bipolar radiofrequency-induced thermofusion. The stability of the induced thermofusion showed no differences when compared to that of conventional anastomoses. Bipolar radiofrequency-induced thermofusion of intestinal tissue represents an innovative approach for achieving gastrointestinal anastomoses.

Experimental investigation on the avoidance of self-excited vibrations.

Self-excited vibrations are observed in many technical applications. Frictional contacts are often involved in the mechanism which generates vibrations. Reasons for the excitation mechanisms are decreasing friction characteristics depending on the sliding velocity, fluctuating normal loads or different geometrical effects. First, the mechanisms are explained using simple examples. The practical relevance of self-excited, friction-induced vibrations is exemplified with three technical systems: a system with an axial seal; a tread block of a tyre; and a disc brake. The knowledge of the excitation mechanism is necessary to introduce successfully design countermeasures. These measures to avoid self-excited vibrations are important to solve practical problems. They are the main focus of this work. Further, additional passive and active subsystems are described and validated experimentally. Therefore, a large range of design, active and passive solutions are given.

Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

Seventy-one patients with acute myeloid leukemia (AML), most of them (63/71) considered ineligible for conventional allogeneic hematopoietic stem cell transplantation (HSCT), were enrolled into a phase 2 study on reduced-intensity myeloablative conditioning with fractionated 8-Gy total body irradiation (TBI) and fludarabine (120 mg/m2). Patients received mobilized peripheral blood stem cells (n = 68) or bone marrow (n = 3) from siblings (n = 39) or unrelated donors (n = 32). Thirty-six patients received a transplant in complete remission (CR) and 35 had untreated or refractory disease (non-CR). Median patient age was 51 years (range, 20-66 years). Sustained engraftment was attained in all evaluable patients. With a median follow-up of 25.9 months (range, 3.7-61.2 months) in surviving patients, probabilities of overall survival for patients who received a transplant in CR and non-CR were 81% and 21% at 2 years, respectively. Relapse-free survival rates were 78% and 16%. The cumulative incidence of nonrelapse mortality (NRM) in CR patients was 8% at 2 years and beyond but amounted to 37% at 2 years in non-CR patients. Outcome data in this poor-risk population indicate that allogeneic HSCT from related or unrelated donors with 8-Gy TBI/fludarabine conditioning is feasible with low NRM and preserved antileukemic activity in AML patients in first or later CR.

Paracrine interactions of basic fibroblast growth factor and interleukin-6 in multiple myeloma.

Myeloma cells express basic fibroblast growth factor (bFGF), an angiogenic cytokine triggering marrow neovascularization in multiple myeloma (MM). In solid tumors and some lymphohematopoietic malignancies, angiogenic cytokines have also been shown to stimulate tumor growth via paracrine pathways. Since interleukin-6 (IL-6) is a potent growth and survival factor for myeloma cells, we have studied the effects of bFGF on IL-6 secretion by bone marrow stromal cells (BMSCs) and its potential reverse regulation in myeloma cells. Both myeloma-derived cell lines and myeloma cells isolated from the marrow of MM patients were shown to express and secrete bFGF. Cell-sorting studies identified myeloma cells as the predominant source of bFGF in MM marrow. BMSCs from MM patients and control subjects expressed high-affinity FGF receptors R1 through R4. Stimulation of BMSCs with bFGF induced a time- and dose-dependent increase in IL-6 secretion (median, 2-fold; P <.001), which was completely abrogated by anti-bFGF antibodies. Conversely, stimulation with IL-6 enhanced bFGF expression and secretion by myeloma cell lines (2-fold; P =.02) as well as MM patient cells (up to 3.6-fold; median, 1.5-fold; P =.002). This effect was inhibited by anti-IL-6 antibody. When myeloma cells were cocultured with BMSCs in a noncontact transwell system, both IL-6 and bFGF concentrations in coculture supernatants increased 2- to 3-fold over the sum of basal concentrations in the monoculture controls. The IL-6 increase was again partially, but significantly, inhibited by anti-bFGF. The data demonstrate a paracrine interaction between myeloma and marrow stromal cells triggered by mutual stimulation of bFGF and IL-6.