The reference window for reduced perturbation of the reference wave in electrical biasing off-axis electron holography.

The perturbation of the reference wave due to electric stray fields represents a major challenge in quantitative electron holographic investigations. By introducing a focused-ion-beam-milled rectangular hole, the reference window, in an area of nearly constant electrostatic potential of the sample, this perturbation can be significantly reduced. The edge of the window forms a closed conducting loop, acting similarly to a Faraday cage, shielding the influence of the stray field on the reference wave to some extent.

A simple and intuitive model for long-range 3D potential distributions of in-operando TEM-samples: Comparison with electron holographic tomography.

Electron holography is a powerful tool to investigate the properties of micro- and nanostructured electronic devices. A meaningful interpretation of the holographic data, however, requires an understanding of the 3D potential distribution inside and outside the sample. Standard approaches to resolve these potential distributions involve projective tilt series and their tomographic reconstruction, in addition to extensive simulations.

A new MVA ancestor-derived oncolytic vaccinia virus induces immunogenic tumor cell death and robust antitumor immune responses.

Vaccinia viruses (VACVs) are versatile therapeutic agents and different features of various VACV strains allow for a broad range of therapeutic applications. Modified VACV Ankara (MVA) is a particularly altered VACV strain that is highly immunogenic, incapable of replicating in mammalian hosts, and broadly used as a safe vector for vaccination. Alternatively, Western Reserve (WR) or Copenhagen (Cop) are VACV strains that efficiently replicate in cancer cells and, therefore, are used to develop oncolytic viruses.

Three dimensional classification of dislocations from single projections.

Many material properties are governed by dislocations and their interactions. The reconstruction of the three-dimensional structure of a dislocation network so far is mainly achieved by tomographic tilt series with high angular ranges, which is experimentally challenging and additionally puts constraints on possible specimen geometries. Here, we show a way to reveal the three dimensional location of dislocations and simultaneously classify their type from single 4D scanning transmission electron microscopy measurements.

Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation.

Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease.

[Infectious diseases as you have never read them (second part…)].

The Covid-19 epidemic has turned our lives upside down; surprisingly certain aspects of this infection can also make you smile, as well as certain modes of transmission of infectious agents that we have grouped together in the form of an original "blooper" of infectious diseases.

Navigation with Augmented Reality in a Hospital.

To improve wayfinding in hospitals or other complex buildings a prototype of an indoor navigation app was implemented that uses Augmented Reality for positioning and guiding users. The iOS and Android app allow the navigation from anywhere inside an area of 690 m2. In a usability test 8 from 12 users preferred using the app over a map or verbal directions.

CCR2 monocytes repair cerebrovascular damage caused by chronic social defeat stress.

Immune surveillance of the brain plays an important role in health and disease. Peripheral leukocytes patrol blood-brain barrier interfaces, and after injury, monocytes cross the cerebrovasculature and follow a pattern of pro- and anti-inflammatory activity leading to tissue repair. We have shown that chronic social defeat (CSD) causes scattered vasculature disruptions.

Mitophagy in the basolateral amygdala mediates increased anxiety induced by aversive social experience.

Psychosocial stress is a common risk factor for anxiety disorders. The cellular mechanism for the anxiogenic effect of psychosocial stress is largely unclear. Here, we show that chronic social defeat (CSD) stress in mice causes mitochondrial impairment, which triggers the PINK1-Parkin mitophagy pathway selectively in the amygdala.

Activation of interferon regulatory factor 3 by replication-competent vaccinia viruses improves antitumor efficacy mediated by T cell responses.

Recently, oncolytic vaccinia viruses (VACVs) have shown their potential to provide for clinically effective cancer treatments. The reason for this clinical usefulness is not only the direct destruction of infected cancer cells but also activation of immune responses directed against tumor antigens. For eliciting a robust antitumor immunity, a dominant T helper 1 (Th1) cell differentiation of the response is preferred, and such polarization can be achieved by activating the Toll-like receptor 3 (TLR3)-interferon regulatory factor 3 (IRF3) signaling pathway.

A simplified method for bronchoalveolar lavage in mice by orotracheal intubation avoiding tracheotomy.

Bronchoalveolar lavage (BAL) represents an important method to sample immune cells and soluble substances from the lungs of humans and animals suffering from respiratory disease. The mouse is the most commonly used model organism to study lung disease. Performing BAL in mice is difficult due to their small size and the currently used method requires tracheotomy, a complex and time-consuming procedure.

B-cells are abnormal in psychosocial stress and regulate meningeal myeloid cell activation.

There is increasing interest in how immune cells, including those within the meninges at the blood-brain interface, influence brain function and mood disorders, but little data on humoral immunity in this context. Here, we show that in mice exposed to psychosocial stress, there is increased splenic B cell activation and secretion of the immunoregulatory cytokine interleukin (IL)-10. Meningeal B cells were prevalent in homeostasis but substantially decreased following stress, whereas Ly6C monocytes increased, and meningeal myeloid cells showed augmented expression of activation markers.

Modulation of Cell Surface Receptor Expression by Modified Vaccinia Virus Ankara in Leukocytes of Healthy and HIV-Infected Individuals.

Viral vectors are increasingly used as delivery means to induce a specific immunity in humans and animals. However, they also impact the immune system, and it depends on the given context whether this is beneficial or not. The attenuated vaccinia virus strain modified vaccinia virus Ankara (MVA) has been used as a viral vector in clinical studies intended to treat and prevent cancer and infectious diseases.

Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting .

Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired.

Diverse roles of phosphatidate phosphatases in insect development and metabolism.

The conversion of the glycerophospholipid phosphatidic acid (PA) into diacylglycerol (DAG) is essential for the biosynthesis of membrane phospholipids and storage fats. Importantly, both PA and DAG can also serve signaling functions in the cell. The dephosphorylation of PA that yields DAG can be executed by two different classes of enzymes, Mg-dependent lipins and Mg-independent lipid phosphate phosphatases.

Analysis of cerebrovascular dysfunction caused by chronic social defeat in mice.

Psychological stress and affective disorders are clinically associated with hypertension and vascular disease, but the biological links between the conditions have not been fully explored. To examine this relationship, we used chronic social defeat (CSD) stress, which produces anxiety-like and depressive-like behavioral declines in susceptible mice. In such mice, CSD also produces cerebrovascular microbleeds in scattered locations.

PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study.

Background: Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success.

Commensal microbiota drive the functional diversification of colon macrophages.

Mononuclear phagocytes are a heterogeneous population of leukocytes essential for immune homeostasis that develop tissue-specific functions due to unique transcriptional programs driven by local microenvironmental cues. Single cell RNA sequencing (scRNA-seq) of colonic myeloid cells from specific pathogen free (SPF) and germ-free (GF) C57BL/6 mice revealed extensive heterogeneity of both colon macrophages (MPs) and dendritic cells (DCs). Modeling of developmental pathways combined with inference of gene regulatory networks indicate two major trajectories from common CCR2 precursors resulting in colon MP populations with unique transcription factors and downstream target genes.

Nef-induced CCL2 Expression Contributes to HIV/SIV Brain Invasion and Neuronal Dysfunction.

C-C motif chemokine ligand 2 (CCL2) is a chemoattractant for leukocytes including monocytes, T cells, and natural killer cells and it plays an important role in maintaining the integrity and function of the brain. However, there is accumulating evidence that many neurological diseases are attributable to a dysregulation of CCL2 expression. Acquired immune deficiency syndrome (AIDS) encephalopathy is a severe and frequent complication in individuals infected with the human immunodeficiency virus (HIV) or the simian immunodeficiency virus (SIV).

Nanosecond electron holography by interference gating.

The interference gating is a novel method for robust time-resolved electron holographic measurements by directly switching the interference. Here, a new arrangement is presented in which a biprism in the condenser aperture as a fast electric phase shifter is used to control the interference pattern. High-frequency stimulation of the electric phase shifter in the gigahertz range are performed and observed via electron holography, proving the feasibility of interference gating in the upper picosecond range.

The Behavioral Sequelae of Social Defeat Require Microglia and Are Driven by Oxidative Stress in Mice.

Chronic social defeat (CSD) in male mice can produce anxiety and aberrant socialization. Animals susceptible to CSD show activation of microglia, which have elevated levels of oxidative stress markers. We hypothesized that microglia and reactive oxygen species (ROS) production contribute to the CSD stress-induced changes in affective behavior.

Components for Material Master Data Management in Swiss Hospitals.

The material master data catalogue in large hospitals may well exceed 50'000 articles required at one or another location for patient diagnosis and treatment. Most hospitals use a commercial material management IT system to deal with orders, eProcurement, incoming goods, warehouse management, internal commissioning and distribution. An analysis in three Swiss hospitals (including a hospital chain) demonstrated however, that despite existing standards maintenance of the material master data catalogue is often done manually based on different incoming formats such as csv, mail etc.

Current Reasons for Not Using Clinical Pathways in Practice.

Clinical pathways are often promoted as the holy grail of efficient healthcare provision. However, our experiences during the Swiss research project Hospital of the Future demonstrated that most Swiss hospitals do not implement clinical pathways in the sense of '… a document describing the common process of a multidisciplinary treatment for a particular type of patient'. In this paper, we will discuss reasons for the lack of pathway implementations.