Blik is an extensible 3D visualisation tool for the annotation and analysis of cryo-electron tomography data.

Powerful, workflow-agnostic and interactive visualisation is essential for the ad hoc, human-in-the-loop workflows typical of cryo-electron tomography (cryo-ET). While several tools exist for visualisation and annotation of cryo-ET data, they are often integrated as part of monolithic processing pipelines, or focused on a specific task and offering limited reusability and extensibility. With each software suite presenting its own pros and cons and tools tailored to address specific challenges, seamless integration between available pipelines is often a difficult task. As part of the effort to enable such flexibility and move the software ecosystem towards a more collaborative and modular approach, we developed blik, an open-source napari plugin for visualisation and annotation of cryo-ET data (source code: https://github.com/brisvag/blik). blik offers fast, interactive, and user-friendly 3D visualisation thanks to napari, and is built with extensibility and modularity at the core. Data is handled and exposed through well-established scientific Python libraries such as numpy arrays and pandas dataframes. Reusable components (such as data structures, file read/write, and annotation tools) are developed as independent Python libraries to encourage reuse and community contribution. By easily integrating with established image analysis tools-even outside of the cryo-ET world-blik provides a versatile platform for interacting with cryo-ET data. On top of core visualisation features-interactive and simultaneous visualisation of tomograms, particle picks, and segmentations-blik provides an interface for interactive tools such as manual, surface-based and filament-based particle picking, and image segmentation, as well as simple filtering tools. Additional self-contained napari plugins developed as part of this work also implement interactive plotting and selection based on particle features, and label interpolation for easier segmentation. Finally, we highlight the differences with existing software and showcase blik's applicability in biological research.

Multidisciplinary optimization of automotive mega-castings merging classical structural optimization with response-surface-based optimization enhanced by machine learning.

Large high pressure die castings (HPDC), recently referred to as mega-castings, can replace plenty of steel metal sheets usually employed for body-in-white (BIW) structures. They can save manufacturing expense and unleash additional lightweight potential thanks to additional design freedom and material properties. The BIW plays a major role in automotive design since it must fulfill numerous structural targets ranging from stiffness for vehicle dynamics, dynamic responses for NVH (noise, vibration, harshness), driving comfort standards and several passive safety requirements. The use of mega-casting structures leads to additional requirements with respect to castability and material quality. Achieving a lightweight design considering requirements related to crash or castability is a challenge on its own, due to the high computational cost of related simulation techniques. Considering multiple requirements simultaneously, therefore often leads to non-weight-optimal structures. To exploit the full lightweight potential, we present a generative multidisciplinary optimization pipeline for the structural design of automotive mega-casting parts in this paper. The approach combines established methods in automotive industry such as topology optimization and response-surface-based (RSM) optimization and enhances the latter by machine learning (ML) based clustering and classification. In a first step topology optimization is employed to derive optimal load-paths for multidisciplinary loading conditions. For this purpose, casting manufacturing constraints as well as more than hundred linearized loads are used to incorporate NVH and passive safety requirements. In a next step the optimal thickness distribution and rib orientation of the structure is achieved using RSM optimization algorithms for the computationally expensive nonlinear crash and casting simulations. Performance indicators are treated by unsupervised learning based on clustering. This enables classification constraints based on simulation field results from hundreds of samples to be included into RSM optimization. It resolves a typical risk of pure scalar, regression-type targets, where supposed optimal results fail when domain experts examine the full field result of the corresponding simulation. It is shown how this approach is superior in achieving a weight-optimal design and turnaround time compared to a design workflow classically used for BIW structures.

Extension of the Medial Approach to the Tibial Plateau via an Osteotomy of the Tibial Insertion of the Superficial Medial Collateral Ligament.

The treatment of medial tibial plateau fractures can be challenging due to poor exposure of the articular surface. Therefore, a medial epicondyle osteotomy may be needed. Current methods describe osteotomy of the medial femoral epicondyle. However, this method requires additional detachment of the medial meniscus in order to ensure proper visualization. The aim of this study is to present a new technique using distal osteotomy of the superficial medial collateral ligament and to analyze the area of the exposed articular surface area. On each of eight fresh-frozen human cadaveric knees (mean age: 79.4 ± 9.4 years), an osteotomy and proximal reflection of the distal insertion of the superficial medial collateral ligament combined with a submeniscal arthrotomy was performed, followed by a medial epicondyle osteotomy. Using a three-dimensional measurement arm (Absolute Arm 8320-7, Hexagon Metrology GmbH), the exposed area was analyzed and compared to the entire medial articular surface using ANOVA (p < 0.05). Through the medial epicondyle osteotomy, 39.9 ± 9.7% of the anteromedial articular surface was seen. This area was significantly smaller compared to the osteotomy of the distal insertion of the superficial collateral ligament with an exposed articular surface of 77.2 ± 16.9% (p = 0.004). Thus, the distal osteotomy exposed 37.3% more of the articular surface compared to the medial epicondyle osteotomy. None of these techniques were able to adequately expose the posteromedial- and medial-most aspects of the tibial plateau. A distal superficial collateral ligament osteotomy may be superior to a medial epicondyle osteotomy when an extension of the anteromedial approach to the tibial plateau is required. A distal superficial medial collateral ligament osteotomy combines the advantages of better exposure of the medial articular surface with preservation of the blood supply to the medial meniscus. However, surgeons should carefully consider whether such an extended approach is necessary, as it significantly increases invasiveness.

Increasing the payload capacity of soft robot arms by localized stiffening.

Soft robot arms offer safety and adaptability due to their passive compliance, but this compliance typically limits their payload capacity and prevents them from performing many tasks. This paper presents a model-based design approach to effectively increase the payload capacity of soft robot arms. The proposed approach uses localized body stiffening to decrease the compliance at the end effector without sacrificing the robot's range of motion. This approach is validated on both a simulated and a real soft robot arm, where experiments show that increasing the stiffness of localized regions of their bodies reduces the compliance at the end effector and increases the height to which the arm can lift a payload. By increasing the payload capacity of soft robot arms, this approach has the potential to improve their efficacy in a variety of tasks including object manipulation and exploration of cluttered environments.

A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity.

Type 1 conventional dendritic cells (cDC1) can support T cell responses within tumors but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8+ T cell clustering as a unique feature of protective anti-cancer immunity. These clusters form selectively in stromal tumor regions and constitute niches in which cDC1 activate TCF1+ stem-like CD8+ T cells. We identify a distinct population of immunostimulatory CCR7neg cDC1 that produce CXCL9 to promote cluster formation and cross-present tumor antigens within these niches, which is required for intratumoral CD8+ T cell differentiation and expansion and promotes cancer immune control. Similarly, in human cancers, CCR7neg cDC1 interact with CD8+ T cells in clusters and are associated with patient survival. Our findings reveal an intratumoral phase of the anti-cancer T cell response orchestrated by tumor-residing cDC1 that determines protective versus ineffective immunity and could be exploited for cancer therapy.

Effects of Feed Solution pH on Polyelectrolyte Multilayer Nanofiltration Membranes.

Over the past decade polyelectrolyte multilayer (PEM)-based membranes have gained a lot of interest in the field of nanofiltration (NF) as an alternative to conventional polyamide-based thin film composite membranes. With great variety in fabrication conditions, these membranes can achieve superior properties such as high chemical resistance and excellent filtration performance. Some of the most common polyelectrolytes used to prepare NF membranes are weak, meaning that their charge density depends on pH within the normal window of operation relevant for potential applications (pH 0-14). This might cause a dependency of membrane properties on the pH of filtered solutions, as indicated by other applications of PEMs. In this work, the susceptibility of membrane structure (swelling and surface charge) and performance (permeability, molecular weight cutoff, and salt retention) toward the pH of the filtration solution was studied for four fundamentally different PEM systems: poly(diallyldimethylammonium chloride) (PDADMAC)/poly(sodium-4-styrenesulfonate) (PSS) (strong/strong), poly(allylamine hydrochloric acid) (PAH)/poly(acrylic acid) (PAA) (weak/weak), and PAH/PSS (weak/strong) and PAH/PSS+PAH/PAA (asymmetric). Slight variations in structure and performance of the PDADMAC/PSS-based membranes were observed. On the contrary, structure and performance of PAH/PAA-based membranes are very susceptible to feed solution pH. A continuous change in charge density with variation in pH significantly affects salt retention. An increased swelling at pH 9 translates to variation in permeability and molecular weight cutoff of the membrane. The susceptibility of PAH/PSS-based membranes to pH is less pronounced compared to the PAH/PAA-based membranes since only one of the polyelectrolytes involved is weak. No structural changes were observed, indicating additional specific interactions between the polyelectrolytes other than electrostatic forces that stabilize film structure. A combination of the PAH/PSS and PAH/PAA system (8 + 2 bilayers) also displays a clear dependency of both membrane structure and performance on solution pH, where PAH/PSS is dominating due to a higher bilayer number.

Comparative efficacy of tannin-free grain sorghum varieties for the control of necrotic enteritis caused by Clostridium perfringens in broiler chickens.

A 28-day battery cage study was conducted to test the efficacy of tannin-free grain sorghum varieties fed to Cobb 500 male broiler chickens (n = 512) and challenged with Eimeria maxima (EM) and Clostridium perfringens (CP). Birds were fed 1 of 8 treatments (corn, red/bronze, white/tan, or U.S. No. 2 sorghum) and were grouped by challenge method (challenged with EM/CP or unchallenged). On d 14, birds in the challenge group were orally inoculated with ∼5,000 oocysts of EM, and on d 19, 20, and 21, birds were given a broth culture of CP with ∼108 CFU/mL once daily. On d 21, three birds were scored for the degree/presence of necrotic enteritis (NE) lesions. Birds and feed were group weighed (d 0, 14, 21, and 28) to calculate average feed intake (FI), body weight gain (BWG), and adjusted feed conversion ratio (AdjFCR). Intestinal integrity was assessed through histological analysis of intestinal tissues, and change in transcriptome was determined using mRNA-sequencing on intestinal mucosa. Relative concentrations of secondary metabolites in grain sorghum were determined by LC-MS/MS analysis. Data were analyzed as a 2-way ANOVA with factors of treatment, challenge and their interaction. Regardless of challenge from 14 to 21 d, birds on the corn, white/tan, and U.S. No. 2 treatments were more efficient than those fed red/bronze treatment (P = 0.0026). From 14 to 28 d, BWG was significantly higher for the white/tan treatment (P = 0.024) compared to the red/bronze treatment. At 21 d, a significant interaction was observed for lesion score (P = 0.0001) in which, challenged birds fed red/bronze and white/tan treatments had reduced intestinal lesions compared to U.S. No. 2 and corn treatments. No differences among treatments were observed in jejunum morphology, but differential expression analysis showed an upregulation in defense response to bacteria and biotic stress in the challenged red/bronze treatment compared to the challenged corn. This study demonstrated improved gut health and minimal impact on growth and efficiency of broilers fed select grain sorghum varieties when challenged with EM/CP.

Feeling the heat: variation in thermal sensitivity within and among populations.

Physiology defines individual responses to global climate change and species distributions across environments. Physiological responses are driven by temperature on three time scales: acute, acclimatory and evolutionary. Acutely, passive temperature effects often dictate an expected 2-fold increase in metabolic processes for every 10°C change in temperature (Q10). Yet, these acute responses often are mitigated through acclimation within an individual or evolutionary adaptation within populations over time. Natural selection can influence both responses and often reduces interindividual variation towards an optimum. However, this interindividual physiological variation is not well characterized. Here, we quantified responses to a 16°C temperature difference in six physiological traits across nine thermally distinct Fundulus heteroclitus populations. These traits included whole-animal metabolism (WAM), critical thermal maximum (CTmax) and substrate-specific cardiac metabolism measured in approximately 350 individuals. These traits exhibited high variation among both individuals and populations. Thermal sensitivity (Q10) was determined, specifically as the acclimated Q10, in which individuals were both acclimated and assayed at each temperature. The interindividual variation in Q10 was unexpectedly large: ranging from 0.6 to 5.4 for WAM. Thus, with a 16°C difference, metabolic rates were unchanged in some individuals, while in others they were 15-fold higher. Furthermore, a significant portion of variation was related to habitat temperature. Warmer populations had a significantly lower Q10 for WAM and CTmax after acclimation. These data suggest that individual variation in thermal sensitivity reflects different physiological strategies to respond to temperature variation, providing many different adaptive responses to changing environments.

Nano-scale collinear multi-Q states driven by higher-order interactions.

Complex magnetic order arises due to the competition of different interactions between the magnetic moments. Recently, there has been an increased interest in such states not only to unravel the fundamental physics involved, but also with regards to applications exploiting their unique interplay with moving electrons. Whereas it is the Dzyaloshinskii-Moriya interaction (DMI) that has attracted much attention because of its nature to induce non-collinear magnetic order including magnetic-field stabilized skyrmions, it is the frustration of exchange interactions that can drive magnetic order down to the nano-scale. On top of that, interactions between multiple spins can stabilize two-dimensional magnetic textures as zero-field ground states, known as multi-Q states. Here, we introduce a two-dimensional itinerant magnet with various competing atomic-scale magnetic phases. Using spin-polarized scanning tunneling microscopy we observe several zero-field uniaxial or hexagonal nano-scale magnetic states. First-principles calculations together with an atomistic spin model reveal that these states are stabilized by the interplay of frustrated exchange and higher-order interactions while the DMI is weak. Unexpectedly, it is found that not only non-collinear magnetic states arise, but that higher-order interactions can also lead to collinear nano-scale multi-Q states.

Apparent metabolizable energy, growth performance and carcass traits of Japanese quail fed select modern grain sorghum varieties.

OBJECTIVE: This study was performed to determine the apparent metabolizable energy (AMEn) content of tannin-free red/bronze, white/tan and U.S. No. 2 varieties of grain sorghum for feeding Japanese quail and validate their nutrient profile by evaluating effects on performance and carcass traits with full-substitution of corn. METHODS: Experiment 1 determined the AMEn content of red/bronze, white/tan, and U.S. No. 2 grain sorghum varieties fed to mixed-sex Japanese quail (Coturnix japonica) (n = 314) at 3 and 6-weeks of age. Analyses were based on a 2×4 factorial treatment design with age and grain types defining the treatments, and a randomized complete block experiment design with cage and trials defining the block. AMEn values were validated by evaluating the performance and carcass traits of Japanese quail (n = 644) from 1 to 40 days of age in Experiment 2 with birds were fed 1 of 4 complete diets. Statistical analyses were conducted on performance data and select individual carcass trait measurements. RESULTS: Determined AMEn values at 3-weeks of age were 3,524±122.03 (red/bronze), 3,252±122.03 (white/tan), and 3,039±123.44 (U.S. No. 2) kcal/kg. At 6-weeks of age, determined AMEn were 3,373±297.35 (red/bronze), 3,279±297.35 (white/tan), and 2,966±298.64 (U.S. No. 2) kcal/kg. Carcass traits showed live body weight (p = 0.0409) and hot carcass weight (p = 0.0234) were greatest in U.S. No. 2; however, carcass yield (p<0.0001) was lowest. No significant differences were observed among treatments for feed intake, feed conversion ratio, breast weight and breast yield (p>0.05). CONCLUSION: These studies demonstrated that tannin-free grain sorghum varieties may be a potential alternative to corn in quail diets while maintaining growth performance and carcass parameters.

Pyridylpiperazine-based allosteric inhibitors of RND-type multidrug efflux pumps.

Efflux transporters of the RND family confer resistance to multiple antibiotics in Gram-negative bacteria. Here, we identify and chemically optimize pyridylpiperazine-based compounds that potentiate antibiotic activity in E. coli through inhibition of its primary RND transporter, AcrAB-TolC. Characterisation of resistant E. coli mutants and structural biology analyses indicate that the compounds bind to a unique site on the transmembrane domain of the AcrB L protomer, lined by key catalytic residues involved in proton relay. Molecular dynamics simulations suggest that the inhibitors access this binding pocket from the cytoplasm via a channel exclusively present in the AcrB L protomer. Thus, our work unveils a class of allosteric efflux-pump inhibitors that likely act by preventing the functional catalytic cycle of the RND pump.

Case Report: Deep brain stimulation improves tremor in FGF-14 associated spinocerebellar ataxia.

Objectives: Spinocerebellar ataxia 27 (SCA 27) is a rare heredodegenerative disorder caused by mutations in the fibroblast growth factor 14 (FGF14) and characterized by early-onset tremor and progressive ataxia later during the disease course. We investigated the effect of deep brain stimulation (DBS) of the ventralis intermedius nucleus of the thalamus (VIM) and subthalamic projections on tremor and ataxia. Methods: At baseline, we studied the effects of high-frequency VIM stimulation and low-frequency stimulation of subthalamic projections on tremor and ataxia. The patient then adopted the best individual high-frequency stimulation programme at daytime and either 30 Hz-stimulation of the subthalamic contacts or StimOFF at night during two separate 5-weeks follow-up intervals. Both patient and rater were blinded to the stimulation settings. Results: High-frequency stimulation of the VIM effectively attenuated tremor. At follow-up, intermittent 30 Hz-stimulation at night resulted in a superior tremor response compared to StimOFF at night. Ataxia was not affected. Discussion: Stimulation of the VIM and adjacent subthalamic projections effectively attenuated tremor in a patient with confirmed SCA 27. Cycling between daytime high-frequency and night-time low-frequency stimulation led to a more sustained tremor response. This suggests to study in future if low-frequency stimulation of the subthalamic projection fibers may help overcome tolerance of tremor that is observed as a long-term limitation of VIM-DBS.

Pneumothorax in a persistent canine Angiostrongylus vasorum infection.

Canine angiostrongylosis is a gastropod-borne parasitosis caused by the cosmopolitan nematode Angiostrongylus vasorum. It is associated with cardiorespiratory disorders and eventually fatal coagulopathies. A 6-months-old female dog previously diagnosed with bronchopneumonia and pneumothorax, treated accordingly without success, was hospitalized for further treatment. Complementary diagnostics confirmed previous findings plus pneumomediastinum, thoracic exudate, leucocytosis, thrombocytosis, hypercoagulability, and hyperglobulinemia. Coprological analysis showed a severe patent A. vasorum infection. After the third daily fenbendazole administration, all A. vasorum larvae were found dead in follow-up coprological analyses while in intensive care. Upon release, the dog was monitored until full clinical recovery 3 months later. Up to date, A. vasorum infection-related pneumothorax was rarely described, particularly with full recovery of such a young patient. Thus, a parasitological aetiology should be considered for dogs with severe bronchopneumonia or pneumothorax, especially in Europe and South America where increasing numbers of canine angiostrongylosis cases call for enhanced awareness of veterinary practitioners.

Moral dilemmas and trust in leaders during a global health crisis.

Trust in leaders is central to citizen compliance with public policies. One potential determinant of trust is how leaders resolve conflicts between utilitarian and non-utilitarian ethical principles in moral dilemmas. Past research suggests that utilitarian responses to dilemmas can both erode and enhance trust in leaders: sacrificing some people to save many others ('instrumental harm') reduces trust, while maximizing the welfare of everyone equally ('impartial beneficence') may increase trust. In a multi-site experiment spanning 22 countries on six continents, participants (N = 23,929) completed self-report (N = 17,591) and behavioural (N = 12,638) measures of trust in leaders who endorsed utilitarian or non-utilitarian principles in dilemmas concerning the COVID-19 pandemic. Across both the self-report and behavioural measures, endorsement of instrumental harm decreased trust, while endorsement of impartial beneficence increased trust. These results show how support for different ethical principles can impact trust in leaders, and inform effective public communication during times of global crisis. PROTOCOL REGISTRATION STATEMENT: The Stage 1 protocol for this Registered Report was accepted in principle on 13 November 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13247315.v1 .

Interindividual plasticity in metabolic and thermal tolerance traits from populations subjected to recent anthropogenic heating.

To better understand temperature's role in the interaction between local evolutionary adaptation and physiological plasticity, we investigated acclimation effects on metabolic performance and thermal tolerance among natural Fundulus heteroclitus (small estuarine fish) populations from different thermal environments. Fundulus heteroclitus populations experience large daily and seasonal temperature variations, as well as local mean temperature differences across their large geographical cline. In this study, we use three populations: one locally heated (32°C) by thermal effluence (TE) from the Oyster Creek Nuclear Generating Station, NJ, and two nearby reference populations that do not experience local heating (28°C). After acclimation to 12 or 28°C, we quantified whole-animal metabolic (WAM) rate, critical thermal maximum (CTmax) and substrate-specific cardiac metabolic rate (CaM, substrates: glucose, fatty acids, lactate plus ketones plus ethanol, and endogenous (i.e. no added substrates)) in approximately 160 individuals from these three populations. Populations showed few significant differences due to large interindividual variation within populations. In general, for WAM and CTmax, the interindividual variation in acclimation response (log2 ratio 28/12°C) was a function of performance at 12°C and order of acclimation (12-28°C versus 28-12°C). CTmax and WAM were greater at 28°C than 12°C, although WAM had a small change (2.32-fold) compared with the expectation for a 16°C increase in temperature (expect 3- to 4.4-fold). By contrast, for CaM, the rates when acclimatized and assayed at 12 or 28°C were nearly identical. The small differences in CaM between 12 and 28°C temperature were partially explained by cardiac remodeling where individuals acclimatized to 12°C had larger hearts than individuals acclimatized to 28°C. Correlation among physiological traits was dependent on acclimation temperature. For example, WAM was negatively correlated with CTmax at 12°C but positively correlated at 28°C. Additionally, glucose substrate supported higher CaM than fatty acid, and fatty acid supported higher CaM than lactate, ketones and alcohol (LKA) or endogenous. However, these responses were highly variable with some individuals using much more FA than glucose. These findings suggest interindividual variation in physiological responses to temperature acclimation and indicate that additional research investigating interindividual may be relevant for global climate change responses in many species.

NADH Fluorescence Lifetime Imaging Microscopy Reveals Selective Mitochondrial Dysfunction in Neurons Overexpressing Alzheimer's Disease-Related Proteins.

Alzheimer's disease (AD), the most prevalent form of dementia, affects globally more than 30 million people suffering from cognitive deficits and neuropsychiatric symptoms. Substantial evidence for the involvement of mitochondrial dysfunction in the development and/or progression of AD has been shown in addition to the pathological hallmarks amyloid beta (Aß) and tau. Still, the selective vulnerability and associated selective mitochondrial dysfunction cannot even be resolved to date. We aimed at optically quantifying mitochondrial function on a single-cell level in primary hippocampal neuron models of AD, unraveling differential involvement of cell and mitochondrial populations in amyloid precursor protein (APP)-associated mitochondrial dysfunction. NADH lifetime imaging is a highly sensitive marker-free method with high spatial resolution. However, deciphering cellular bioenergetics of complex cells like primary neurons has still not succeeded yet. To achieve this, we combined highly sensitive NADH lifetime imaging with respiratory inhibitor treatment, allowing characterization of mitochondrial function down to even the subcellular level in primary neurons. Measuring NADH lifetime of the same neuron before and after respiratory treatment reveals the metabolic delta, which can be taken as a surrogate for cellular redox capacity. Correlating NADH lifetime delta with overexpression strength of Aß-related proteins on the single-cell level, we could verify the important role of intracellular Aß-mediated mitochondrial toxicity. Subcellularly, we could demonstrate a higher respiration in neuronal somata in general than dendrites, but a similar impairment of somatic and dendritic mitochondria in our AD models. This illustrates the power of NADH lifetime imaging in revealing mitochondrial function on a single and even subcellular level and its potential to shed light into bioenergetic alterations in neuropsychiatric diseases and beyond.

The Incidence of Mental Disorders Increases over Time in Patients with Cancer Pain: Data from a Retrospective Cohort Study.

Background: It is well known that cancer patients more seldom have a psychiatric disorder than noncancer patients with chronic pain. Conversely, earlier studies have suggested that, at the psychiatric level, long-term cancer survivors (LCSs) have more in common with noncancer patients affected by chronic pain. Materials and Methods: We investigated 89 cancer patients with acute pain (Acute Cancer Pain Patients, ACPPs) treated at a university outpatient chemotherapy department and compared these with 61 LCSs (living >5 yr after the first diagnosis) admitted by general practitioners for the treatment of noncancer pain. Upon administration, each patient was psychiatrically assessed by a liaison-psychiatrist conducting a semistructured interview. In a second step, we compared the LCS patients with hitherto treated noncancer patients suffering from chronic pain and ACPPs with data published by Derogatis in 1983. Results: In a comparison of LCSs with ACPPs, LCSs have more patients with brain organic disorders and more addictions. The largest cancer group within the LCSs is patients with urogenital (Uro) cancer (44.3%), while within the ACPPs, these are patients with cancer of the gastrointestinal (GI) tract (ACPP-GI, 57.2%). As far as the distribution of mental disorders is concerned, long-term cancer survivors show some similarities to noncancer patients. The data of ACPPs are similar to those of cancer patients, published by Derogatis. Discussion. The higher values of addiction and brain organic disorders, in particular, and the slight differences for psychic disorders in general of LCSs vs. ACPPs may result from the different cancer types and a longer survival time for urogenital tract cancer compared to GI cancer. In an additional examination, we compared patients with acute cancer of the GI tract (ACPP-GI, n = 50) with those of the urogenital tract (ACPP-Uro, n = 43). ACPP-Uro had the lowest percentage of patients with psychiatric disorders in general (ACPP-Uro 37.2%, ACPP-GI 50.0%, all LCSs 65.6%, and LCS-Uro 74.1%) and addiction, in particular (ACPP-Uro 2.3%, ACPP-GI 4.0%, and LCSs 13.1%). Conclusion: Cancer patients can develop a process of chronification with an increase in the prevalence of mental disorders. For urogenital cancer, an increase in the probability to develop mental disorders is a function of time.

The social cost of contacts: Theory and evidence for the first wave of the COVID-19 pandemic in Germany.

Building on the epidemiological SIR model, we present an economic model with heterogeneous individuals deriving utility from social contacts creating infection risks. Focusing on social distancing of individuals susceptible to an infection we theoretically characterize the gap between private and social cost of contacts. Our main contribution is to quantify this gap by calibrating the model with unique survey data from Germany on social distancing and impure altruism from the beginning of the COVID-19 pandemic. The optimal policy is to drastically reduce contacts at the beginning to almost eradicate the epidemic and keep them at levels that contain the pandemic at a low prevalence level. We find that also in laissez faire, private protection efforts by forward-looking, risk averse individuals would have stabilized the epidemic, but at a much higher prevalence of infection than optimal. Altruistic motives increase individual protection efforts, but a substantial gap to the social optimum remains.

Charge Regulation at a Nanoporous Two-Dimensional Interface.

In this work, we have studied the pH-dependent surface charge nature of nanoporous graphene. This has been investigated by membrane potential and by streaming current measurements, both with varying pH. We observed a lowering of the membrane potential with decreasing pH for a fixed concentration gradient of potassium chloride (KCl) in the Donnan dominated regime. Interestingly, the potential reverses its sign close to pH 4. The fitted value of effective fixed ion concentration (C̅ R) in the membrane also follows the same trend. The streaming current measurements show a similar trend with sign reversal around pH 4.2. The zeta potential data from the streaming current measurement is further analyzed using a 1-pK model. The model is used to determine a representative pK (acid-base equilibrium constant) of 4.2 for the surface of these perforated graphene membranes. In addition, we have also theoretically investigated the effect of the PET support in our membrane potential measurement using numerical simulations. Our results indicate that the concentration drop inside the PET support can be a major contributor (up to 85%) for a significant deviation of the membrane potential from the ideal Nernst potential.

Polygenic Selection within a Single Generation Leads to Subtle Divergence among Ecological NichesINc.

Selection on standing genetic variation may be effective enough to allow for adaptation to distinct niche environments within a single generation. Minor allele frequency changes at multiple, redundant loci of small effect can produce remarkable phenotypic shifts. Yet, demonstrating rapid adaptation via polygenic selection in the wild remains challenging. Here we harness natural replicate populations that experience similar selection pressures and harbor high within-, yet negligible among-population genetic variation. Such populations can be found among the teleost Fundulus heteroclitus that inhabits marine estuaries characterized by high environmental heterogeneity. We identify 10,861 single nucleotide polymorphisms in F. heteroclitus that belong to a single, panmictic population yet reside in environmentally distinct niches (one coastal basin and three replicate tidal ponds). By sampling at two time points within a single generation, we quantify both allele frequency change within as well as spatial divergence among niche subpopulations. We observe few individually significant allele frequency changes yet find that the "number" of moderate changes exceeds the neutral expectation by 10-100%. We find allele frequency changes to be significantly concordant in both direction and magnitude among all niche subpopulations, suggestive of parallel selection. In addition, within-generation allele frequency changes generate subtle but significant divergence among niches, indicative of local adaptation. Although we cannot distinguish between selection and genotype-dependent migration as drivers of within-generation allele frequency changes, the trait/s determining fitness and/or migration likelihood appear to be polygenic. In heterogeneous environments, polygenic selection and polygenic, genotype-dependent migration offer conceivable mechanisms for within-generation, local adaptation to distinct niches.