Direct Vicinity Research Articles

The Valley of Rapha? A New Suggestion for the Identification of the Rephaim Valley

ABSTRACT The Valley of Rephaim is usually located in the direct vicinity of Jerusalem. However, a fresh look at the history of research reveals the uncertainty surrounding this identification and shows that the displayed geography rather points to a setting east of the Elah Valley. At this location, the Rephaim Valley was of utmost interest to the communities of the lowlands, who were during the 10th and 9th centuries BCE under the control of Philistine Gath, which is significantly featured in the books of Samuel. This paper highlights the relationship between the city and the Rephaim Valley accounts and further suggests, that the place owes its name to the local Gittite elite and not to an association with past mythical giants.

Safety of non-invasive brain stimulation in patients with implants: a computational risk assessment.

Non-invasive brain stimulation (NIBS) methodologies, such as transcranial electric (tES) are increasingly employed for therapeutic, diagnostic, or research purposes. The concurrent presence of active/passive implants can pose safety risks, affect the NIBS delivery, or generate confounding signals. A systematic investigation is required to understand the interaction mechanisms, quantify exposure, assess risks, and establish guidance for NIBS applications. We used measurements, simplified generic, and detailed anatomical modeling to: (i) systematically analyze exposure conditions with passive and active implants, considering local field enhancement, exposure dosimetry, tissue heating and neuromodulation, capacitive lead current injection, low-impedance pathways between electrode contacts, and insulation damage; (ii) identify risk metrics and efficient prediction strategies; (iii) quantify these metrics in relevant exposure cases and (iv) identify worst case conditions. Various aspects including implant design, positioning, scar tissue formation, anisotropy, and frequency were investigated. At typical tES frequencies, local enhancement of dosimetric exposure quantities can reach up to one order of magnitude for deep brain stimulation (DBS) and stereoelectroencephalography implants (more for elongated passive implants), potentially resulting in unwanted neuromodulation that can confound results but is still 2-3 orders of magnitude lower than active DBS. Under worst-case conditions, capacitive current injection in the active implants' lead can produce local exposures of similar magnitude as the passive field enhancement, while capacitive pathways between contacts are negligible. Above 10 kHz, applied current magnitudes increase, necessitating consideration of tissue heating. Furthermore, capacitive effects become more prominent, leading to current injection that can reach DBS-like levels. Adverse effects from abandoned/damaged leads in direct electrode vicinity cannot be excluded. Safety related concerns of tES application in the presence of implants are systematically identified and explored, resulting in specific and quantitative guidance and establishing basis for safety standards. Furthermore,several methods for reducing risks are suggested while acknowledging the limitations(see Sec. 4.5).

Drivers of nest site selection and breeding success in an Alpine ground-nesting songbird

AbstractBirds breeding in high-Alpine habitats must select a suitable breeding site and achieve successful reproduction within a restricted time. During four breeding seasons, we monitored nest sites of the Northern Wheatear (Oenanthe oenanthe), a high-Alpine long-distance migrant. We investigated how ecological factors predicted the selection of a site for nesting within the home range, using conditional logistic regression. Birds preferred south-exposed productive pastures on gentle slopes, interspersed with non-vegetated ground and human-made rockpiles. The direct vicinity of conspecific nests was avoided, as were shrubby or north-exposed areas. We investigated if habitat also influenced breeding success. We analysed the impact of environmental factors on breeding success, which was primarily driven by predation. The probability of the brood fledging successfully decreased on north-exposed slopes or on areas with low coverage of non-vegetated ground. The vicinity of conspecific nests did not have a clear effect. Further, we describe how breeding success varied within and between years. Within years, replacement broods had a higher breeding success. The apparent absence of variation in breeding success between years and a delay of the breeding period in the year with late spring onset suggest a high level of tolerance with respect to inter-annual variation of meteorological conditions. Since the preferred habitat is still widely available in the Alps and given the negative population trends in Western Europe, the Alpine range might serve as a refuge for the Northern Wheatear, as long as low-intensity management and heterogenous habitats are maintained.

Comparative proteomic analysis of metronidazole-sensitive and resistant Trichomonas vaginalis suggests a novel mode of metronidazole action and resistance

The microaerophilic parasite Trichomonas vaginalis occurs worldwide and causes inflammation of the urogenital tract, especially in women. With 156 million infections annually, trichomoniasis is the most prevalent non-viral sexually transmitted disease. Trichomoniasis is treated with 5-nitroimidazoles, especially metronidazole, which are prodrugs that have to be reduced at their nitro group to be activated. Resistance rates to metronidazole have remained comparably low, but they can be higher in certain areas leading to an increase of refractory cases. Metronidazole resistance in T. vaginalis can develop in vivo in clinical isolates, or it can be induced in the laboratory. Both types of resistance share certain characteristics but differ with regard to the dependence of ambient oxygen to become manifest. Although several candidate factors for metronidazole resistance have been described in the past, e.g. pyruvate:ferredoxin oxidoreductase and ferredoxin or thioredoxin reductase, open questions regarding their role in resistance have remained.In order to address these questions, we performed a proteomic study with metronidazole-sensitive and –resistant laboratory strains, as well as with clinical strains, in order to identify factors causative for resistance. The list of proteins consistently associated with resistance was surprisingly short. Resistant laboratory and clinical strains only shared the downregulation of flavin reductase 1 (FR1), an enzyme previously identified to be involved in resistance. Originally, FR1 was believed to be an oxygen scavenging enzyme, but here we identified it as a ferric iron reductase which produces ferrous iron. Based on this finding and on further experimental evidence as presented herein, we propose a novel mechanism of metronidazole activation which is based on ferrous iron binding to proteins, thereby rendering them susceptible to complex formation with metronidazole. Upon resolution of iron-protein-metronidazole complexes, metronidazole radicals are formed which quickly react with thiols or proteins in the direct vicinity, leading to breaks in the peptide backbone.

3D characterization of kinematic fields and poroelastic swelling near the tip of a propagating crack in a hydrogel

AbstractIn fracture mechanics, polyacrylamide hydrogel has been widely used as a model material in experiments due to its optical transparency, the brittle nature of its failure, and low Rayleigh wave velocity. Indeed, linear elastic fracture mechanics has been used successfully to model the fracture of polyacrylamide hydrogels. However, in soft materials such as hydrogels, the crack opening can be extremely large, leading to substantial geometric and material nonlinearity at the crack tip. Furthermore, poroelasticity may also modify the local mechanical state within the polymer network due to solvent migration. Direct characterization of the kinematic fields and the poroelastic response at the crack tip is lacking. Here we use a hybrid digital image correlation—particle tracking technique to retrieve high-resolution 3D particle trajectories near the tip of a slowly propagating crack, and measure the near-tip 3D kinematic fields in-situ. With this method, we charactherize the displacement fields, rotation fields, stretch fields, strain fields, and swelling fields. These measurements confirm the complex multi-axial stretching near the crack tip and the substantial geometric nonlinearity, particularly in the wake of the crack, where material rotation exceeds $$30^{\circ }$$ 30 ∘ . Comparison between the measured fields and the corresponding prediction from linear elastic fracture mechanics highlights an increasing disagreement in the direct vicinity of the crack tip, particularly for displacement component $$u_x$$ u x and the through-thickness strain component $$\varepsilon _{zz}$$ ε zz . Significant swelling occurs due to solvent migration, with a strong correlation to the local stretch.

Persistent carriage of subpatent Plasmodium falciparum parasites associated with clinical malaria in a low transmission area in Senegal

ObjectivesIn low malaria transmission areas, the elimination of the disease has been hampered partly by the existence of a reservoir of subpatent Plasmodium falciparum infections within communities. This reservoir, often undetected, serves as a source of parasites and contributes to ongoing transmission and clinical malaria cases. MethodsThis study, spanning a period of 9 years from June 2014 to December 2022, examined individual variations and long-term subpatent P. falciparum carriage in two matched cohorts of 44 individuals each living in Dielmo village in the Sudanian area of Senegal. Biannual blood samples, collected in June/July and December of each year, underwent P. falciparum diagnosis by quantitative polymerase chain reaction. QGIS and R analytical tools were used to map infections, assess the occurrence and clustering of subpatent and clinical P. falciparum infections, and determine the risk of infection in the vicinity of asymptomatic P. falciparum carriers. ResultsThe point frequency and long-term P. falciparum carriage were significantly higher among the quantitative polymerase chain reaction (qPCR) positive cohort compared to the negative cohort across the 16 cross-sectional surveys analyzed in this study (19.76% vs 10.99%, P-value <0.001). Asymptomatic carriage events in qPCR-positive group were 18.86 ± 1.72% and significantly greater (P-value = 0.001) than in the qPCR-negative group (11.32 ± 1.32%). The relative risk of P. falciparum infection or clinical malaria calculated with a 95% confidence interval significantly increased in the vicinity of infected individuals and was 1.44 (P-value = 0.53) and 2.64 (P-value = 0.04) when at least one individual in the direct (household) or indirect (block of households) vicinity is infected, respectively. The risk increased to 3.64 (P-value <0.001) if at least 1/5 of individuals in the indirect vicinity were P. falciparum-infected. ConclusionsThe study provides a detailed qualitative and quantitative analysis of the asymptomatic P. falciparum reservoir and its temporal and spatial dynamics within two subgroups of P. falciparum-infected and non-infected individuals in Dielmo village. It identified high-risk populations known as “hotpops” and hotspots that could be targeted by innovative interventions to accelerate the elimination of malaria in Dielmo village.

Live Cell Monitoring of Phosphodiesterase Inhibition by Sulfonylurea Drugs.

Sulfonylureas (SUs) are a class of antidiabetic drugs widely used in the management of diabetes mellitus type 2. They promote insulin secretion by inhibiting the ATP-sensitive potassium channel in pancreatic β-cells. Recently, the exchange protein directly activated by cAMP (Epac) was identified as a new class of target proteins of SUs that might contribute to their antidiabetic effect, through the activation of the Ras-like guanosine triphosphatase Rap1, which has been controversially discussed. We used human embryonic kidney (HEK) 293 cells expressing genetic constructs of various Förster resonance energy transfer (FRET)-based biosensors containing different versions of Epac1 and Epac2 isoforms, alone or fused to different phosphodiesterases (PDEs), to monitor SU-induced conformational changes in Epac or direct PDE inhibition in real time. We show that SUs can both induce conformational changes in the Epac2 protein but not in Epac1, and directly inhibit the PDE3 and PDE4 families, thereby increasing cAMP levels in the direct vicinity of these PDEs. Furthermore, we demonstrate that the binding site of SUs in Epac2 is distinct from that of cAMP and is located between the amino acids E443 and E460. Using biochemical assays, we could also show that tolbutamide can inhibit PDE activity through an allosteric mechanism. Therefore, the cAMP-elevating capacity due to allosteric PDE inhibition in addition to direct Epac activation may contribute to the therapeutic effects of SU drugs.

Assessing neural markers of attention during exposure to construction noise using machine learning classification of electroencephalogram data

Construction noise is one of the leading causes of attention impairment both for workers within construction sites and individuals in their direct vicinity. Distraction caused by construction noise can significantly affect productivity of people in the surrounding area. In addition, lack of adequate attention by workers in construction sites can increase the risk of mistakes potentially increasing work-related accidents. This study highlights the feasibility of using electroencephalogram (EEG) data for detecting distractions caused by construction noise. EEG data were collected from 23 participants while they completed a standard attention test (Go-NoGo) during exposure to construction noise. Both frequency-based features and non-linear features were extracted from the EEG signal and subject-independent machine learning models were applied. The results showed that channel FC5, with an F1 score of 68.41 % and an accuracy score of 70.28 % presented the best performance among all channels and the defined channel clusters. These findings will help inform the best features and channels to select for developing new purpose-built EEG devices with a smaller number of channels that are suited for distraction detection due to noise exposure in construction sites.

Agropastoral and dietary practices of the northern Levant facing Late Holocene climate and environmental change: Isotopic analysis of plants, animals and humans from Bronze to Iron Age Tell Tweini.

One of the largest isotopic datasets of the ancient Eastern Mediterranean region is evaluated, based on plants (n = 410), animals (n = 210) and humans (n = 16) from Tell Tweini (Syria). Diachronic analysis of plant and faunal specimens from four main periods of occupation: Early Bronze Age (2600-2000 BC), Middle Bronze Age (2000-1600 BC), Late Bronze Age (1600-1200 BC) and Iron Age (1200-333 BC) were investigated. Mean Δ13C results from seven plant species reveal emmer and free threshing wheat, olives, bitter vetch, rye grass and barley were adequately or well-watered during all periods of occupation. The grape Δ13C results suggest excellent growing conditions and particular care for its cultivation. The δ15N results indicate that especially the emmer and free threshing wheats received some manure inputs throughout the occupation sequence, while these were likely further increased during the Iron Age, encompassing also the olive groves and grape vineyards. Generally, domestic animals (cattle, sheep, goats) had C3 terrestrial diets and were kept together in similar environments. However, some animals consumed significant amounts of marine or C4 plants, possibly from disturbed habitats due to land use pressure or salt tolerant grasses and shrubs from wetland environments, which were recorded in the direct vicinity of the site. Middle Bronze Age humans consumed a C3 terrestrial diet with no measurable input from C4, freshwater or marine protein sources. Interestingly, the human diet was relatively low in animal protein and appears comparable to what is considered today a typical Mediterranean diet consisting of bread (wheat/barley), olives, grapes, pulses, dairy products and small amounts of meat. The combined isotopic analysis of plants, animals and humans from Tell Tweini represents unbroken links in the food chain which create unparalleled opportunities to enhance our current understanding of environmental conditions, climate change and lifeways in past populations from the Eastern Mediterranean.

Use of electrical resistivity tomography measurements for investigation of different grouting materials for very shallow geothermal applications within varying seasonal conditions; Applied on a geothermal earth-air heat exchanger system

To achieve the current climate targets, heat pump systems like very shallow geothermal applications are gaining ground. However, the dimensioning of these ground coupled systems is soil-dependent and thus subject to significant differences in efficiency. Furthermore, the thermal properties of the grouting materials are essential for heat transfer in the direct vicinity of the geothermal application. To provide a non-invasive assessment of relevant soil and grouting characteristics, electrical resistivity tomography (ERT) measurements were performed.In this case, the surrounding of an Earth Air-Heat Exchanger – system (EAHE) with different grouting materials (fine sand and fine sand with bentonite) was investigated. For investigation the electrical resistivity (ER) of initial and modified soil conditions were measured regarding soil texture and moisture content. Thereby, the different grouting materials are clearly identified. Thus, based on the ERT measurements, a characterisation of key soil and grouting material properties for applications focusing on heat transfer in soil has been carried out.Furthermore, the depth of soil disturbance due to the EAHE installation could have been traced.Due to a monitoring over different season (February and May) changes in raw ER data could have been ascribed to temperature changes.

MINDS: JWST/NIRCam imaging of the protoplanetary disk PDS 70

Context. Two protoplanets have recently been discovered within the PDS 70 protoplanetary disk. JWST/NIRCam offers a unique opportunity to characterize them and their birth environment at wavelengths that are difficult to access from the ground. Aims. We image the circumstellar environment of PDS 70 at 1.87 μm and 4.83 μm, assess the presence of Pa-α emission due to accretion onto the protoplanets, and probe any IR excess indicative of heated circumplanetary material. Methods. We obtained noncoronagraphic JWST/NIRCam images of PDS 70 within the MIRI mid-INfrared Disk Survey (MINDS) program. We leveraged the Vortex Image Processing (VIP) package for data reduction, and we developed dedicated routines for optimal stellar point spread function subtraction, unbiased imaging of the disk, and protoplanet flux measurement in this type of dataset. A radiative transfer model of the disk was used to separate the contributions from the disk and the protoplanets. Results. We redetect both protoplanets and identify extended emission after subtracting a disk model, including a large-scale spiral-like feature. We interpret its signal in the direct vicinity of planet c as tracing the accretion stream that feeds its circumplanetary disk, while the outer part of the feature may rather reflect asymmetric illumination of the outer disk. We also report a bright signal that is consistent with a previously proposed protoplanet candidate enshrouded in dust near the 1:2:4 mean-motion resonance with planets b and c. The 1.87 μm flux of planet b is consistent with atmospheric model predictions, but the flux of planet c is not. We discuss potential origins for this discrepancy, including significant Pa-α line emission. The 4.83 μm fluxes of planets b and c suggest enshrouding dust or heated CO emission from their circumplanetary environment. Conclusions. The use of image-processing methods that are optimized for extended disk signals on high-sensitivity and high-stability from JWST can uniquely identify signatures of planet–disk interactions and enable accurate photometry of protoplanets at wavelengths that are difficult to probe from the ground. Our results indicate that more protoplanets can be identified and characterized in other JWST datasets.

Temporal contrast enhancement of a Ti:Sapphire laser by nonlinear Fourier filtering

Temporal cleaning of high-power infrared (IR) pulses generated by a Ti:Sapphire system is demonstrated by the use of the Nonlinear Fourier Filtering (NFF) method. In a proof-of-principle experiment suppression of up to 1000 is achieved for the temporal pedestal prior to the main pulse, with a moderate (20-25%) overall throughput. This includes the same suppression ratio for the picosecond coherent pedestal in the direct vicinity of the main pulse. Based on the instantaneous, intensity-dependent and high-order switching characteristics of NFF, excellent pulse cleaning performance is observed. The efficient, high-contrast removal of the coherent pedestal from the foot of the main pulse even if its duration is shorter than 100 fs is compared with the capability of the plasma mirror technique. Calculations are also performed, supporting the experimentally observed sharp intensity dependence of the switching process, pointing out the dominant role of the ionization-based refractive index change.

Long-term impact of wastewater effluent discharge on groundwater: Identification of contaminant plume by geochemical, isotopic, and organic tracers' approach

Infiltration of effluents from wastewater treatment plants (WWTP) into groundwater can be a source of Contaminants of Emerging Concern (CECs), such as pharmaceutical compounds, that are not fully removed during the treatment processes. A multi-tracer approach, based on hydrogeochemical, isotopic, and organic tracers, is applied in the Vistrenque Aquifer (Gard, France) to assess the dispersion of such unintentional plumes and its potential implication on groundwater quality for CECs in a small catchment area. In this area, a point source of WWTP effluent causes contaminant infiltration and unintentional transfer to the aquifer. This strong impact of an urban effluent was revealed from the Br/Cl ratio, boron concentrations and δ11B isotopic signature of the groundwater in the direct vicinity of the infiltration point. With increasing distance from that point, dilution with groundwater rapidly attenuates the urban signal from these hydrogeochemical and isotopic tracers. Nevertheless, a gadolinium anomaly, resulting from discharges of urban wastewater containing the contrast agents used for magnetic resonance imaging (MRI), highlights the presence of a wastewater plume further along the flow line, that comes with a series of organic molecules, including pharmaceutical residues. Monitoring persistent or reactive molecules along the plume provides a more detailed understanding of the transfer of CECs into groundwater bodies. This highlights the relevance of pharmaceutical compounds as co-tracers for WWTP plume delineation. The present multi-tracer approach for groundwater resource vulnerability towards CECs allows a more in-depth understanding of contaminant transfer and their fate in groundwater.

A comparative study on the linear scaling relations for the diffusion of S-vacancies on MoS2 and WS2.

This work uses density functional theory (DFT) calculations and kinetic Monte Carlo (kMC) simulations to compare the diffusion of S-vacancies on defective MoS2 and WS2, two structures that are often discussed as catalysts. Similar to what has been discussed for MoS2, the vacancy diffusion barriers on WS2 also follow Brønsted-Evans-Polanyi (BEP) type linear scaling relations. The vacancy diffusion kinetics is discussed at the example of a large vacancy cluster consisting of 37 unoccupied sites in direct vicinity and how its structure changes with time. Using barriers estimated via linear scaling relations as input for the kMC simulations yields results that qualitatively agree with results calculated self-consistently at DFT level. As the diffusion barriers for WS2 are significantly higher than those for MoS2, the vacancy diffusion on WS2 is poorly described by the linear scaling relations derived from MoS2 and vice versa. This work further shows that one needs DFT level barriers of about 40% of all S-vacancy diffusion processes on a material to derive sufficiently reliable linear scaling relations. This means that computational costs for future studies may be reduced by only explicitly computing one fraction of the diffusion barriers while estimating the remaining ones via linear scaling. However, in this case, one would lack information about the partition function of the transition states, which are needed for calculating the rate constants. Thus, we have also proposed a scheme to estimate the contribution of the partition functions based only on the initial state's vibrational modes.

Subcellular fractionation by differential centrifugation for mitochondrial studies.

In addition to fluorescence microscopy, the subcellular fractionation of eukaryotic cells remains one of the central methods for the basic characterization of proteins. Here we describe an optimized procedure for the subcellular fractionation of yeast cells, specifically for mitochondrial studies. Major recommendations are to separate the fractions immediately after each centrifugation step, to carefully discard a significant part of the supernatant fractions which is in the direct vicinity to the pellets and, in addition, to perform an extra homogenization step of the post nuclear supernatant fraction. These principles help to collect supernatant fractions with less cross-contaminations from the corresponding pellets. These approaches are scalable and adaptable for the fractionation of other cell types and are also useful for the characterization of other organelles.

Remodelling of cAMP dynamics within the SERCA2a microdomain in heart failure with preserved ejection fraction caused by obesity and type 2 diabetes.

Despite massive efforts, we remain far behind in our attempts to identify effective therapies to treat heart failure with preserved ejection fraction (HFpEF). Diastolic function is critically regulated by sarcoplasmic/endoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a), which forms a functional cardiomyocyte (CM) microdomain where 3',5'-cyclic adenosine monophosphate (cAMP) produced upon β-adrenergic receptor (β-AR) stimulation leads to phospholamban (PLN) phosphorylation and facilitated Ca2+ re-uptake. To visualize real-time cAMP dynamics in the direct vicinity of SERCA2a in healthy and diseased myocytes, we generated a novel mouse model on the leprdb background that stably expresses the Epac1-PLN Förster resonance energy transfer biosensor. Mice homozygous for the leprdb mutation (db/db) developed obesity and type 2 diabetes and presented with a HFpEF phenotype, evident by mild left ventricular hypertrophy and elevated left atria filling pressures. Live cell imaging uncovered a substantial β2-AR subtype stimulated cAMP response within the PLN/SERCA2a microdomain of db/db but not healthy control (db/+) CMs, which was accompanied by increased PLN phosphorylation and accelerated calcium re-uptake. Importantly, db/db CMs also exhibited a desensitization of β1-AR stimulated cAMP pools within the PLN/SERCA2a microdomain, which was accompanied by a blunted lusitropic effect, suggesting that the increased β2-AR control is an intrinsic compensatory mechanism to maintain PLN/SERCA2a-mediated calcium dynamics and cardiac relaxation. Mechanistically, this was due to a local loss of cAMP-degrading phosphodiesterase 4 associated specifically with the PLN/SERCA2a complex. These newly identified alterations of cAMP dynamics at the subcellular level in HFpEF should provide mechanistic understanding of microdomain remodelling and pave the way towards new therapies.

Why Hydrogen Dissociation Catalysts do not Work for Hydrogenation of Magnesium.

Provision of atomic hydrogen by hydrogen dissociation catalysts only moderately accelerates the hydrogenation rate of magnesium. They shed light on this well-known but technically challenging fact through a combined approach using an unconventional surface science technique together with Density Functional Theory (DFT) calculations. The calculations demonstrate the drastic electronic structure changes during transformation of Mg to MgH2 , which make fractional hydrogen coverage on the surface, as well as substoichiometric hydrogen content in the bulk energetically unfavorable. Reflecting Electron Energy Loss Spectroscopy (REELS) is used to measure the surface and bulk plasmon during hydrogen sorption in magnesium. The measurements show that the hydrogenation proceeds via the growth of magnesium hydride without the presence of chemisorbed hydrogen on the metallic magnesium surface exactly as indicated by the calculations. This is due to the low stability of sub-stoichiometric amounts of chemisorbed H correlating with the unfavorable charge state of Mg. They are merely bound to the unchanged adjacent Mg layers, thereby explaining the failure of classical hydrogenation catalysts, which effectively only hydrogenate Mg in their direct vicinity. The acceleration of hydrogen sorption kinetics in Mg must affect the polarization in the interface between Mg and MgH2 during hydrogenation.

Progressive alterations in lipid distribution and composition in a murine Alzheimer’s disease model visualized by label‐free Raman microscopy

AbstractBackgroundAlzheimer’s disease (AD) is accompanied by severe alterations in the brain lipid profile, affecting both the type and the distribution of lipids in the tissue. Moreover, literature also suggests a close association of Aβ plaques and lipids, exacerbating amyloidogenesis and plaque deposition. Thus, a spatially resolved approach is eminently important to understand the chemical nature of the progressive relationship between Aβ plaques and surrounding lipids. In the here presented study, Raman microscopy, a label‐free, chemically selective technique, was used in combination with state‐of‐the‐art statistics to analyze Aβ plaques and the surrounding tissue in a murine Alzheimer’s disease model. By encompassing differently aged diseased and healthy mice, this study aimed to generate knowledge on the alterations of Aβ plaque surrounding lipids during disease progression, whilst advancing the application of Raman microscopy within a neurodegenerative context.MethodRegions of interest in brain sections of APP/PS1 (Amyloid‐Precursor‐Protein / Presenilin‐1) mice aged 50 days, 5 months, and 10 months, as well as healthy non‐transgenic mice were imaged using a confocal Raman microscope (WITec GmbH, Ulm, Germany). The hyperspectral Raman data sets were processed using Project 4 software (WITec GmbH, Ulm, Germany), in‐house written Matlab scripts (The Mathworks, Inc., Natick, USA) and the Matlab‐integrated RamanLight App.ResultUsing multivariate analysis, Raman signatures of the Aβ plaques, cell nuclei, mitochondria, and lipids were identified in the tissue, characterized, and compared to each other (Figure 1). Subsequently, the lipid signal was semi‐quantitatively analyzed. The results of this analysis indicate an increasing, massive abundance of lipids in the direct vicinity of the Aβ plaques with disease progression, and the biochemical Raman spectra also reveal the growing presence of long‐chained lipids around the Aβ plaque. Overall, a distinct shift of the lipid spectra and abundance, starting with disease manifestation, is observed in the proximity of the plaques.ConclusionThe presented study shows progressive alterations in the distribution and type of lipids surrounding Aβ plaques in an AD model, spatially resolving lipid alterations and providing valuable additional biochemical insight to more established imaging methods such as fluorescence microscopy.

The 2022 MW 6.0 Gölyaka–Düzce earthquake: an example of a medium-sized earthquake in a fault zone early in its seismic cycle

Abstract. On 23 November 2022, a MW 6.0 earthquake occurred in the direct vicinity of the MW 7.1 Düzce earthquake that ruptured a portion of the North Anatolian Fault in 1999. The Mw 6.0 event was attributed to a small portion of the Karadere fault off the main North Anatolian Fault that did not rupture during the 1999 sequence. We analyze the spatiotemporal evolution of the MW 6.0 Gölyaka–Düzce seismic sequence at various scales and resolve the source properties of the mainshock. Modeling the decade-long evolution of the background seismicity of the Karadere fault employing an Epistemic Type Aftershock Sequence model shows that this fault was almost seismically inactive before 1999, while a progressive increase in seismic activity is observed from 2000 onwards. A newly generated high-resolution seismicity catalog from 1 month before the mainshock until 6 d after was created using artificial-intelligence-aided techniques and shows only a few events occurring within the rupture area within the previous month, no spatiotemporal localization process and a lack of immediate foreshocks preceding the rupture. The aftershock hypocenter distribution suggests the activation of both the Karadere fault, which ruptured in this earthquake, and the Düzce fault that ruptured in 1999. First results on the source parameters and the duration of the first P-wave pulse from the mainshock suggest that the mainshock propagated eastwards, which is in agreement with predictions from a bimaterial interface model. The MW 6.0 Gölyaka–Düzce event represents a good example of an earthquake rupture with damaging potential within a fault zone that is in a relatively early stage of the seismic cycle.

Superconducting shield for the injection channel of the muEDM experiment at PSI

At the Paul Scherrer Institute (PSI), we are setting up an experiment to search for the electric dipole moment (EDM) of the muon using the frozen-spin technique. The discovery of a muon EDM would indicate violation of charge conjugation parity symmetry (CP-violation) and lepton flavor universality, beyond the Standard Model. The experiment aims to achieve a sensitivity of σ(dμ ) ≤ 6 × 10-23 e · cm.This study is taking place during the first phase of the experiment and it focuses on the off-axis injection of muons into a 3 T storage solenoid. Muons need to be transported from the exit of the PSI beamline, a low magnetic-field region, into the strong magnetic-field of the solenoid. For this purpose, two magnetically shielded channels are being developed. In the direct vicinity of the injection helix inside the solenoid bore, we will use superconducting (SC) shielding to avoid any hysteresis effect, while farther away in the fringe field we will use iron tubes. Three prototypes of SC injection tubes will be produced: the first will use a commercial high temperature superconducting (HTS) tape wrapped around a hollow copper tube, the second will utilize several Nb-Ti/Nb/Cu sheets obtained from CERN, wrapped and mechanically clamped around another hollow copper tube, while the third will consist of a commercial cast Bi-2223 superconducting tube coiled with HTS tape. To evaluate the effectiveness of the different SC-shields, we will measure their shielding factors and determine the muon injection efficiency from the beamline into the solenoid.