Generation of stable suspension producer cell lines for serum-free lentivirus production.

The production of lentiviral vectors (LVs) pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G) is limited by the associated cytotoxicity of the envelope and by the production methods used, such as transient transfection of adherent cell lines. In this study, we established stable suspension producer cell lines for scalable and serum-free LV production derived from two stable, inducible packaging cell lines, named GPRG and GPRTG. The established polyclonal producer cell lines produce self-inactivating (SIN) LVs carrying a WAS-T2A-GFP construct at an average infectious titer of up to 4.

High yield sterile filtration process for highly concentrated lentiviral vectors.

The development and manufacture of biopharmaceuticals are subject to strict regulations that specify the required minimum quality of the products. A key measure to meet these quality requirements is the integration of a sterile filtration step into the commercial manufacturing process. Whereas common procedures for most biologics exist, this is challenging for lentiviral vector (LVV) production for ex vivo gene therapy.

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats.

Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects.

Development and clinical implementation of a digital system for risk assessments for radiation therapy.

Before introducing new treatment techniques, an investigation of hazards due to unintentional radiation exposures is a reasonable activity for proactively increasing patient safety. As dedicated software is scarce, we developed a tool for risk assessment to design a quality management program based on best practice methods, i.e.

Synthetic CTs for MRI-only brain RT treatment: integration of immobilization systems.

Purpose: Auxiliary devices such as immobilization systems should be considered in synthetic CT (sCT)-based treatment planning (TP) for MRI-only brain radiotherapy (RT). A method for auxiliary device definition in the sCT is introduced, and its dosimetric impact on the sCT-based TP is addressed.

Methods: T1-VIBE DIXON was acquired in an RT setup.

End-to-end testing for stereotactic radiotherapy including the development of a Multi-Modality phantom.

Purpose: A new insert for a commercially available end-to-end test phantom was designed and in-house manufactured by 3D printing. Subsequently, the insert was tested for different stereotactic radiation therapy workflows (SRS, SBRT, FSRT, and Multimet) also in comparison to the original insert.

Material And Methods: Workflows contained imaging (MR, CT), treatment planning, positioning, and irradiation.

Cervical Artery Dissection and Sports.

Cervical artery dissection (CeAD) occurring in the context of sports is a matter of concern for CeAD patients. They seek advice on the role of sports in CeAD and on the safety of resuming sports after CeAD. The scarcity of studies and guidelines addressing these issues poses a challenge.

Quality assurance for dynamic tumor tracking.

The purpose of this work was to develop a treatment plan verification routine for a linear accelerator dedicated to SBRT treatments with gimbal based dynamic tumor tracking using three commercially available phantoms. The accelerator system has two special features: It operates with a rotation of the ring shaped gantry instead of a couch rotation and target motion can be compensated for via a gimbal system (dynamic tumor tracking, DTT). DTT plans were each measured with the three different phantoms.

Prescriptive analytics in public-sector decision-making: A framework and insights from charging infrastructure planning.

In this work, we investigate the challenges public-sector organizations face when seeking to leverage prescriptive analytics and provide insights into the public value such data-driven tools and methods can provide. Using the strategic triangle of value, legitimacy, and operational capacity as a starting point, we derive a framework to assess public-sector prescriptive analytics initiatives, along with six guiding questions that structure the assessment process. We present a case study applying prescriptive analytics to the placement of charge points in urban areas, a critical challenge many municipalities are currently facing in the transition towards electric mobility.

Rare genetic variants in patients with cervical artery dissection.

Introduction: The potential role of genetic alterations in cervical artery dissection (CeAD) pathogenesis is poorly understood. We aimed to identify pathogenic genetic variants associated with cervical artery dissection by using whole exome sequencing.

Patients And Methods: CeAD-patients with either a family history of cervical artery dissection (f-CeAD) or recurrent cervical artery dissection (r-CeAD) from the CeAD-databases of two experienced stroke centres were analysed by whole exome sequencing.

Artery occlusion independently predicts unfavorable outcome in cervical artery dissection.

Objective: To assess the impact of dissected artery occlusion (DAO) on functional outcome and complications in patients with cervical artery dissection (CeAD).

Methods: We analyzed combined individual patient data from 3 multicenter cohorts of consecutive patients with CeAD (the Cervical Artery Dissection and Ischemic Stroke Patients [CADISP]-Plus consortium dataset). Patients with data on DAO and functional outcome were included.

Method for a motion model based automated 4D dose calculation.

The Vero system can treat intra-fractionally moving tumors with gimbaled dynamic tumor tracking (DTT) by rotating the treatment beam so that it follows the motion of the tumor. However, the changes in the beam geometry and the constant breathing motion of the patient influence the dose applied to the patient. This study aims to perform a full 4D dose reconstruction for thirteen patients treated with DTT at the Vero system at the Universitätsklinikum Erlangen and investigates the temporal resolution required to perform an accurate 4D dose reconstruction.

Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke.

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months.

Isolating the effect of cycling on local business environments in London.

We investigate whether increasing cycling activity affects the emergence of new local businesses. Historical amenity data from OpenStreetMap is used to quantify change in shop and sustenance amenity counts. We apply an instrumental variable framework to investigate a causal relationship and to account for endogeneity in the model.

Performance of gimbal-based dynamic tumor tracking for treating liver carcinoma.

Background: Since the introduction of tumor tracking in radiotherapy, it is possible to ensure a precise irradiation of moving targets. To follow the tumor movement, most systems rely on the detection of implanted markers and correlation models between the internal and external patient movement. This study reports the clinical workflow and first results of the dynamic tumor tracking (DTT) performance for patients with liver carcinoma at the Vero SBRT system of the University Hospital Erlangen regarding the detection of the internal marker and the changes of the determined correlation models.

Motor imagery in chronic neglect: An fMRI pilot study.

Aim: Previous studies indicate the effectiveness of motor imagery training in stroke patients. To determine whether patients showing chronic visuospatial neglect symptoms may profit from motor imagery training, it is important to assess how the brain implements motor imagery when cortical systems involved in attentional control are impaired.

Method: Therefore, in this pilot study, nine chronic neglect patients with right-hemispheric stroke performed motor imagery of a finger opposition task during functional magnetic resonance imaging (fMRI).

Determinants and outcome of multiple and early recurrent cervical artery dissections.

Objective: To assess putative risk factors and outcome of multiple and early recurrent cervical artery dissection (CeAD).

Methods: We combined data from 2 multicenter cohorts and compared patients with multiple CeAD at initial diagnosis, early recurrent CeAD within 3 to 6 months, and single nonrecurrent CeAD. Putative risk factors, clinical characteristics, functional outcome, and risk of recurrent ischemic events were assessed.

Recurrence of cervical artery dissection: An underestimated risk.

Objective: To explore the recurrence of cervical artery dissection (CeAD).

Methods: A single-center consecutive series of 282 CeAD patients was prospectively recruited during first admission from 1995 to 2012. Patients with a follow-up of at least 1 year (n = 238) were eligible for the current analysis.

Familial aortic disease and a large duplication in chromosome 16p13.1.

Background And Purpose: A recurrent duplication of chromosome 16p13.1 was associated with aortic dissection as well as with cervical artery dissection. We explore the segregation of this duplication in a family with familial aortic disease.

Changes of mitochondrial ultrastructure and function during ageing in mice and .

Ageing is a progressive decline of intrinsic physiological functions. We examined the impact of ageing on the ultrastructure and function of mitochondria in mouse and fruit flies () by electron cryo-tomography and respirometry. We discovered distinct age-related changes in both model organisms.

Next generation sequencing analysis of patients with familial cervical artery dissection.

Background: The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection.

Patients And Methods: Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing.

Genetic Imbalance in Patients with Cervical Artery Dissection.

Background: Genetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed.

Analysis of Mitochondrial Membrane Protein Complexes by Electron Cryo-tomography.

The visualization of membrane protein complexes in their natural membrane environment is a major goal in an emerging area of research termed structural cell biology. Such approaches provide important information on the spatial distribution of protein complexes in their resident cellular membrane systems and on the structural organization of multi-subunit membrane protein assemblies. We have developed a method to specifically label active membrane protein complexes in their native membrane environment with electron-dense nanoparticles coupled to an activating ligand, in order to visualize them by electron cryo-tomography.

Cervical artery dissection in patients ≥60 years: Often painless, few mechanical triggers.

Objective: In a cohort of patients diagnosed with cervical artery dissection (CeAD), to determine the proportion of patients aged ≥60 years and compare the frequency of characteristics (presenting symptoms, risk factors, and outcome) in patients aged <60 vs ≥60 years.

Methods: We combined data from 3 large cohorts of consecutive patients diagnosed with CeAD (i.e.

A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro.

Fusion of mitochondrial outer membranes is crucial for proper organelle function and involves large GTPases called mitofusins. The discrete steps that allow mitochondria to attach to one another and merge their outer membranes are unknown. By combining an in vitro mitochondrial fusion assay with electron cryo-tomography (cryo-ET), we visualize the junction between attached mitochondria isolated from Saccharomyces cerevisiae and observe complexes that mediate this attachment.