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We demonstrate a method for self-sensing of a magnetically actuated prism that can be used, e.g., in a feedback-loop without the need of additional sensors. In order to use the impedance of the actuation coils as a measurement parameter, we first obtained the optimal measurement frequency that is well separated from the actuation frequencies and at the same time provides the best compromise between sensitivity to the position and robustness. We then developed a combined actuation and measurement driver, and correlated its output signal to the mechanical state of the prism using a defined calibration sequence. We demonstrate that we can reliably measure the state of each actuator and determine the tilt angle of the prism with an accuracy of ±0.1∘ in the polar angle over a range of ±4∘ and ±20 mrad in the azimuthal angle.

To examine the prevalence of glaucomatous optic neuropathy (GON) in a medium myopic to highly myopic group of patients and its association with parapapillary gamma zone and parapapillary delta zone. The retrospective observational hospital-based study included patients who had attended the Tokyo High Myopia Clinics within January 2012 and December 2012 and for whom fundus photographs were available. GON was defined based on the appearance of the optic nerve head on the fundus photographs. The study included 519 eyes (262 individuals) with a mean age of 62.0±14.3 years (range:13-89 years) and mean axial length of 29.5±2.2 mm (range:23.2-35.3mm). GON was present in 141 (27.2%; 95% confidence intervals (CI): 23.3, 31.0%) eyes. Prevalence of GON increased from 12.2% (1.7, 22.7) in eyes with an axial length of <26.5mm to 28.5% (24.4, 32.5) in eyes with an axial length of ≥26.5mm, to 32.6% (27.9, 37.2) in eyes with an axial length of ≥28mm, to 36.0% (30.5, 41.4) in eyes with an axial length of ≥29mm, and GON prevalence increased to 42.1% (35.5, 48.8) in eyes with an axial length of ≥30mm. In multivariate analysis, higher GON prevalence was associated (Nagelkerke r2: 0.28) with larger parapapillary delta zone diameter (P<0.001; odds ratio (OR):1.86;95%CI:1.33,2.61), longer axial length (P<0.001;OR:1.45;95%CI:1.26,1.67) and older age (P = 0.01;OR:1.03;95%CI:1.01,1.05). If parapapillary delta zone width was replaced by the vertical disc diameter, higher GON prevalence was associated (r2:0.24) with larger vertical optic disc diameter (P = 0.04;OR:1.70;95%CI:1.03,2.81), after adjusting for longer axial length (P<0.001;OR:1.44;95%CI:1.26,1.64) and older age (P<0.001;OR:1.04;95%CI:1.02,1.06). Axial elongation associated increase in GON prevalence (mean: 28.1% in a medium to highly myopic study population) was associated with parapapillary delta zone as surrogate for an elongated peripapillary scleral flange and with larger optic disc size.

Among various treatment options for benign prostatic hyperplasia (BPH), surgical therapy is the most invasive. As Switzerland has the highest transurethral prostatectomy rate among OECD countries, we assessed the regional variation in prostate surgery for BPH and explored potential determinants of variation. We conducted a population-based analysis using discharge data for men aged [greater than or equal to]40 years with transurethral or simple prostatectomy from all Swiss hospitals during 2013-2018. After excluding patients with genitourinary/prostate cancer, we derived hospital service areas (HSAs) by analyzing patient flows. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). We estimated the reduction in variance across HSAs of prostatectomy rates in multilevel regression models, with incremental adjustment for age, regional cultural and socioeconomic factors, disease burden, density of urologists, and the time since urologists' graduation. Overall, 44,253 prostatectomies (42,710 transurethral and 1543 simple) from 44 HSAs were analyzed. The mean age-standardized prostate surgery rate was 314 (range 166-500) per 100,000 men aged [greater than or equal to]40 years per year. The EQ was 3.01 and the SCV 5.53, indicating a high regional variation. In multivariate models, men aged 75-79 years had an 11.6-fold higher prostatectomy rate than those aged 50-54 years. French/Italian language areas had a 21% lower rate than Swiss German speaking areas. Socioeconomic factors, disease burden, and density of urologist/time since graduation were not associated with prostatectomy rates. After full adjustment, 80% of the variance in prostate surgery across HSAs remained unexplained. We found a remarkably high regional variation in prostate surgery rates for BPH within Switzerland.

Fish schooling implies an awareness of the swimmers for their companions. In flow mediated environments, in addition to visual cues, pressure and shear sensors on the fish body are critical for providing quantitative information that assists the quantification of proximity to other fish. Here we examine the distribution of sensors on the surface of an artificial swimmer so that it can optimally identify a leading group of swimmers. We employ Bayesian experimental design coupled with numerical simulations of the two-dimensional Navier Stokes equations for multiple self-propelled swimmers. The follower tracks the school using information from its own surface pressure and shear stress. We demonstrate that the optimal sensor distribution of the follower is qualitatively similar to the distribution of neuromasts on fish. Our results show that it is possible to identify accurately the center of mass and the number of the leading swimmers using surface only information.

In epilepsy, the most frequent surgical procedure is the resection of brain tissue in the temporal lobe, with seizure-free outcomes in approximately two-thirds of cases. However, consequences of surgery can vary strongly depending on the brain region targeted for removal, as surgical morbidity and collateral damage can lead to significant complications, particularly when bleeding and swelling are located near delicate functional cortical regions. Although focal thermal ablations are well-explored in epilepsy as a minimally invasive approach, hemorrhage and edema can be a consequence as the blood-brain barrier is still disrupted. Non-thermal irreversible electroporation (NTIRE), common in many other medical tissue ablations outside the brain, is a relatively unexplored method for the ablation of neural tissue, and has never been reported as a means for ablation of brain tissue in the context of epilepsy. Here, we present a detailed visualization of non-thermal ablation of neural tissue in mice and report that NTIRE successfully ablates epileptic foci in mice, resulting in seizure-freedom, while causing significantly less hemorrhage and edema compared to conventional thermal ablation. The NTIRE approach to ablation preserves the blood-brain barrier while pathological circuits in the same region are destroyed. Additionally, we see the reinnervation of fibers into ablated brain regions from neighboring areas as early as day 3 after ablation. Our evidence demonstrates that NTIRE could be utilized as a precise tool for the ablation of surgically challenging epileptogenic zones in patients where the risk of complications and hemorrhage is high, allowing not only reduced tissue damage but potentially accelerated recovery as vessels and extracellular matrix remain intact at the point of ablation.

Molecule clustering is an important mechanism underlying cellular self-organization. In the cell membrane, a variety of fundamentally different mechanisms drive membrane protein clustering into nanometre-sized assemblies. To date, it is unknown whether this clustering process can be dissected into steps differentially regulated by independent mechanisms. Using clustered syntaxin molecules as an example, we study the influence of a cytoplasmic protein domain on the clustering behaviour. Analysing protein mobility, cluster size and accessibility to myc-epitopes we show that forces acting on the transmembrane segment produce loose clusters, while cytoplasmic protein interactions mediate a tightly packed state. We conclude that the data identify a hierarchy in membrane protein clustering likely being a paradigm for many cellular self-organization processes.

The SNAREs SNAP25 and SNAP23 are proteins that are initially cytosolic after translation, but then become stably attached to the cell membrane through palmitoylation of cysteine residues. For palmitoylation to occur, membrane association is a prerequisite, but it is unclear which motif may increase the affinities of the proteins for the target membrane. In experiments with rat neuroendocrine cells, we find that a few basic amino acids in the cysteine-rich region of SNAP25 and SNAP23 are essential for plasma membrane targeting. Reconstitution of membrane-protein binding in a liposome assay shows that the mechanism involves protein electrostatics between basic amino acid residues and acidic lipids such as phosphoinositides that play a primary role in these interactions. Hence, we identify an electrostatic anchoring mechanism underlying initial plasma membrane contact by SNARE proteins, which subsequently become palmitoylated at the plasma membrane. Cells often communicate with each other by releasing chemicals that normally are stored in small membrane-bound compartments called vesicles. For example, when a neuron is stimulated, vesicles merge with its cell membrane and release their content into a gap between itself and other neurons. This complicated process involves many steps and molecules, including proteins called SNAREs. Some SNARE proteins reside at the inner side of the cell membrane and help vesicles to fuse with this membrane. Two SNARE proteins called SNAP25 and SNAP23 are produced in the liquid inside the cell and initially float freely. Eventually, these proteins become directly anchored to the cell membrane, however, not much is known about what happens to these proteins in between these stages, or how they first attach to the membrane before anchoring to it. Electrostatic forces between oppositely charged molecules are known to be important for them to bind with each other. Here, electrostatic forces are less likely to occur because SNAP25 and SNAP23 are both mostly negatively charged, and should therefore be repelled from the cell membrane, which also typically has a negative charge. However, both SNAP25 and SNAP23 have a small cluster of positively charged amino acids (the building blocks of proteins) near the attachment site, and Weber et al. have now tested whether this charge is sufficient to overcome the predicted repulsion. The approach involved making mutant proteins with either more or less positively charged attachment regions. Mutant SNAP25 or SNAP23 proteins with more positive charges may stick more tightly but not necessarily more permanently to the membrane. However, when the number of positive charges was lowered, more of the proteins remained floating freely in the liquid inside the cell. These results suggest that even a small number of positively charged amino acids is sufficient to help a protein bind to a cell membrane for further processing. The findings of Weber et al. reveal an early step in the life cycle of SNAP25 and SNAP23 before they anchor to the cell membrane. They suggest that finely tuned protein electrostatics can regulate how long a protein spends at a specific site and thereby indirectly determine its fate. Such fine-tuned protein electrostatics are difficult to recognize and could represent an underestimated regulatory mechanism in all types of cells.

Adipose tissues were shown to host which is persisting inside mature adipocytes. It remains unknown whether this holds true for , a rare representative of the complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with and as a positive control. Both mycobacteria were able to infect 18-22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for ( = 0.02) and ( = 0.03). Further infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by and 17% of infected cells by ( = 0.001). Interestingly, replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for complex mycobacteria; and illustrate differential outcome of complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for , it is still an open question whether and could persist in brown adipose tissues.

Direct numerical simulations of the flow past an impulsively started cylinder at high Reynolds numbers (25k–100k) reveal an intriguing portrait of unsteady separation. Vorticity generation and vortex shedding entails a cascade of separation events on the cylinder surface that are reminiscent of Kelvin–Helmholtz instabilities. Primary vortices roll up along the cylinder surface as a result of instabilities of the initially attached vortex sheets, followed by vortex eruptions, creation of secondary vorticity and formation of dipole structures that are subsequently ejected from the surface of the cylinder. We analyse the vortical structures and their relationship to the forces experienced by the cylinder. This striking cascade of vortex instabilities may serve as reference for reduced-order models of flow separation and as guide for flow control of separated flows at high Reynolds numbers.

Direct numerical simulations of the flow past an impulsively started cylinder at high Reynolds numbers (25k–100k) reveal an intriguing portrait of unsteady separation. Vorticity generation and vortex shedding entails a cascade of separation events on the cylinder surface that are reminiscent of Kelvin–Helmholtz instabilities. Primary vortices roll up along the cylinder surface as a result of instabilities of the initially attached vortex sheets, followed by vortex eruptions, creation of secondary vorticity and formation of dipole structures that are subsequently ejected from the surface of the cylinder. We analyse the vortical structures and their relationship to the forces experienced by the cylinder. This striking cascade of vortex instabilities may serve as reference for reduced-order models of flow separation and as guide for flow control of separated flows at high Reynolds numbers.