Safety verification of a fault tolerant reconfigurable autonomous goal-based robotic control system

Fault tolerance and safety verification of control systems are essential for the success of autonomous robotic systems. A control architecture called Mission Data System (MDS), developed at the Jet Propulsion Laboratory, takes a goal-based control approach. In this paper, a method for converting goal network control programs into linear hybrid systems is developed. The linear hybrid system can then be verified for safety in the presence of failures using existing symbolic model checkers. An example task is simulated in MDS and successfully verified using HyTech, a symbolic model checking software for linear hybrid systems

Energy Management of the Multi-Mission Space Exploration Vehicle Using a Goal-Oriented Control System

Safe human exploration in space missions requires careful management of limited resources such as breathable air and stored electrical energy. Daily activities for astronauts must be carefully planned with respect to such resources, and usage must be monitored as activities proceed to ensure that they can be completed while maintaining safe resource margins. Such planning and monitoring can be complex because they depend on models of resource usage, the activities being planned, and uncertainties. This paper describes a system - and the technology behind it - for energy management of the NASA-Johnson Space Center's Multi-Mission Space Exploration Vehicles (SEV), that provides, in an onboard advisory mode, situational awareness to astronauts and real-time guidance to mission operators. This new capability was evaluated during this year's Desert RATS (Research and Technology Studies) planetary exploration analog test in Arizona. This software aided ground operators and crew members in modifying the day s activities based on the real-time execution of the plan and on energy data received from the rovers

Flow cytometry-based ex vivo murine NK cell cytotoxicity assay

Direct killing of diseased cells is a hallmark function of NK cells. This protocol describes a flow-based assay to measur

Intra-Arterial Blood Pressure Characteristics during Submaximal Cycling and Recovery

The purpose of this study was to measure intra-arterial (IA) blood pressure from rest to steady-state submaximal exercise and immediately post-exercise. Beat-to-beat blood pressure was compared to breath-by-breath VO2 during steady-state and maximal exercise. Fourteen normotensive subjects volunteered. Systolic (SBP), diastolic (DBP) and mean (mBP) blood pressure was measured from rest to steady state during cycling at 45, 60, and 75% maximal power output (POmax). BP was assessed during recovery from VO2peak through 2 min of cycling at 50 W. During the rest to exercise transition, mBP decreased from 103.41 ± 9.4 to 90.1 ± 8.9 mmHg after 11.6 ± 6.2 s (

Swiss recommendations on perioperative antimicrobial prophylaxis in children

Infection following surgical procedures leads to significant morbidity and mortality in all age groups. Sterile techniques, antibiotic prophylaxis and improved postoperative wound care have contributed to the decline of surgical site infections since the early days of surgery. Recommendations on the use of perioperative antimicrobial prophylaxis exist for adults, but are rare for the paediatric population. Here, we provide a standardised approach to the effective use of antimicrobial agents for the prevention of surgical site infections in children contributing to a targeted and rational perioperative use of antibiotics in Switzerland

Error-Related Brain Activity in Patients With Obsessive-Compulsive Disorder and Unaffected First-Degree Relatives: Evidence for Protective Patterns

Background Indicators of increased error monitoring are associated with obsessive-compulsive disorder (OCD), as shown in electroencephalography and functional magnetic resonance imaging studies. As most studies used strictly controlled samples (excluding comorbidity and medication), it remains open whether these findings extend to naturalistic settings. Thus, we assessed error-related brain activity in a large, naturalistic OCD sample. We also explored which activity patterns might qualify as vulnerability endophenotypes or protective factors for the disorder. To this aim, a sample of unaffected first-degree relatives of patients with OCD was also included. Methods Participants (84 patients with OCD, 99 healthy control participants, and 37 unaffected first-degree relatives of patients with OCD) completed a flanker task while blood oxygen level–dependent responses were measured with functional magnetic resonance imaging. Aberrant error-related brain activity in patients and relatives was identified. Results Patients with OCD showed increased error-related activity in the supplementary motor area and within the default mode network, specifically in the precuneus and postcentral gyrus. Unaffected first-degree relatives showed increased error-related activity in the bilateral inferior frontal gyrus. Conclusions Increased supplementary motor area and default mode network activity in patients with OCD replicates previous studies and might indicate excessive error signals and increased self-referential error processing. Increased activity of the inferior frontal gyrus in relatives may reflect increased inhibition. Impaired response inhibition in OCD has been demonstrated in several studies and might contribute to impairments in suppressing compulsive actions. Thus, increased inferior frontal gyrus activity in the unaffected relatives of patients with OCD may have contributed to protection from symptom development

Copper(II) tetrakis(pentafluorophenyl)-β-octachloroporphyrin

The title compound, {4,5,9,10,14,15,19,20-octachloro-2,7,12, 17-tetrakis(pentafluorophenyl)-20,22,23,24- tetraazapentacyclo[l6.2.l.1^(3·6).l^(8·11).l^(13·16)]tetracosa-1,3(21),4,6,8(22),9,11, 13(23), 14, 16, 18(24), 19-dodecaene}copper(II)(CuTFPPC1_8)dichloromethane solvate, shows a large tetrahedral distortion or ruffling, with pairs of Cl atoms alternately averaging + 1.20 and -1.18 Å out of the plane of the four N atoms; the Cu atom is 0.01 Å out of the plane and the N atoms show a slight (±0.12 Å) tetrahedral distortion. A Cl atom of the solvent, at 3.515 (6) Å in an approximately axial position, is the closest non-bonded neighbor of the Cu atom

Culture expansion of CAR T cells results in aberrant DNA methylation that is associated with adverse clinical outcome

Chimeric antigen receptor (CAR) T cells provide new perspectives for treatment of hematological malignancies. Manufacturing of these cellular products includes culture expansion procedures, which may affect cellular integrity and therapeutic outcome. In this study, we investigated culture-associated epigenetic changes in CAR T cells and found continuous gain of DNAm, particularly within genes that are relevant for T cell function. Hypermethylation in many genes, such as TCF7, RUNX1, and TOX, was reflected by transcriptional downregulation. 332 CG dinucleotides (CpGs) showed an almost linear gain in methylation with cell culture time, albeit neighboring CpGs were not coherently regulated on the same DNA strands. An epigenetic signature based on 14 of these culture-associated CpGs predicted cell culture time across various culture conditions. Notably, even in CAR T cell products of similar culture time higher DNAm levels at these CpGs were associated with significantly reduced long-term survival post transfusion. Our data demonstrate that cell culture expansion of CAR T cells evokes DNA hypermethylation at specific sites in the genome and the signature may also reflect loss of potential in CAR T cell products. Hence, reduced cultivation periods are beneficial to avoid dysfunctional methylation programs that seem to be associated with worse therapeutic outcome.This research was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation − 363055819/GRK2415; WA1706/11–1; WA 1706/12–2 within CRU344/417911533; WA1706/14–1; and SFB 1506/1); and the ForTra gGmbH für Forschungstransfer der Else Kröner-Fresenius-Stiftung. Furthermore, we thank CERCA Programme / Generalitat de Catalunya for institutional support. The research leading to these results has received funding from MCIN/AEI/10.13039/501100011033 and European Commission “Next GenerationEU”/PRTR (PDC2022–133476-I00); Ministry of Research and Universities of the Catalan Government (2021 PROD 00020); and the Cellex Foundation.Peer ReviewedPostprint (published version

Reliance on Cox10 and oxidative metabolism for antigen-specific NK cell expansion

Natural killer (NK) cell effector functions are dependent on metabolic regulation of cellular function; however, less is known about in vivo metabolic pathways required for NK cell antiviral function. Mice with an inducible NK-specific deletion of Cox10, which encodes a component of electron transport chain complex IV, were generated to investigate the role of oxidative phosphorylation in NK cells during murine cytomegalovirus (MCMV) infection. Ncr1-Cox1

Treatment Pathway of Bone Sarcoma in Children, Adolescents, and Young Adults

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management approach. Little variation was found in the authors\u27 group with respect to local control or systemic therapy. Clinical trials were universally prioritized in all settings. Decisions regarding relapse therapies in the absence of a clinical trial had very minor variations initially, but a consensus was reached after a literature review and discussion. This review presents a concise document and figures as a starting point for evidence-based care for patients with these rare diseases. This framework allows prospective decision making and prioritization of clinical trials. It is hoped that this framework will inspire and focus future clinical research and thus lead to new trials to improve efficacy and reduce toxicity