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Assessing root sources of three uncertainties – parameterization of soil hydraulic characteristics, boundary conditions, and estimation of source/sink terms – is a significant challenge in soil water transport modeling. This study aims to evaluate the uncertainty of three each widely-used parameter estimation methods affecting plot-scale water dynamics. The study employs HYDRUS, a process-based hydrologic model, to incorporate these uncertainties and compare model predictions to measured values in a semiarid Inner Mongolia steppe, China. Soil hydraulic parameters are determined using two direct methods (laboratory-derived approach and evaporation method) and one indirect method (neural network). While each hydraulic parameter method generally simulates soil moisture dynamics, the evaporation method performed better, especially under dry conditions. This suggests that measuring the intensity properties, such as unsaturated hydraulic conductivity, with the evaporation method is crucial for reasonable soil moisture simulation. The study also demonstrates the impact of different applied boundary conditions on simulated soil moisture, specifically the partitioning of reference FAO evapotranspiration via one direct method (soil fraction cover) and two indirect methods (leaf area index and crop height). The partitioning via soil fraction cover reflected a better simulation. Additionally, the study compares the uncertainties of root water uptake function with root growth parameters and constant root depth referenced to grass and pasture, and finds no significant difference among them. Comparing three sources of uncertainty in predicting soil moisture, the study concludes that the input soil hydraulic parameter is more sensitive than evapotranspiration partitioning or representation of root water uptake function. Our study highlights that measuring soil intensity properties can better reflect the effects of land use change, such as compaction, on field water transports.

Abstract The influenza A virus (IAV) polymerase is a multifunctional machine that can adopt alternative configurations to perform transcription and replication of the viral RNA genome in a temporally ordered manner. Although the structure of polymerase is well understood, our knowledge of its regulation by phosphorylation is still incomplete. The heterotrimeric polymerase can be regulated by posttranslational modifications, but the endogenously occurring phosphorylations at the PA and PB2 subunits of the IAV polymerase have not been studied. Mutation of phosphosites in PB2 and PA subunits revealed that PA mutants resembling constitutive phosphorylation have a partial (S395) or complete (Y393) defect in the ability to synthesize mRNA and cRNA. As PA phosphorylation at Y393 prevents binding of the 5′ promoter of the genomic RNA, recombinant viruses harboring such a mutation could not be rescued. These data show the functional relevance of PA phosphorylations to control the activity of viral polymerase during the influenza infectious cycle.

Abstract Exchange of viral segments between one or more influenza virus subtypes can contribute to a shift in virulence and adaptation to new hosts. Among several influenza subtypes, H9N2 is widely circulating in poultry populations worldwide and has the ability to infect humans. Here, we studied the reassortant compatibility between chicken H9N2 with N1–N9 gene segments of wild bird origin, either with an intact or truncated stalk. Naturally occurring amino acid deletions in the NA stalk of the influenza virus can lead to increased virulence in both mallard ducks and chickens. Our findings show extended genetic compatibility between chicken H9Nx gene segments and the wild-bird NA with and without 20 amino acid stalk deletion. Replication kinetics in avian, mammalian and human cell lines revealed that parental chH9N2 and rH9N6 viruses with intact NA-stalk replicated significantly better in avian DF1 cells compared to human A549 cells. After introducing a stalk deletion, an enhanced preference for replication in mammalian and human cell lines could be observed for rH9N2Δ(H6), rH9N6Δ and rH9N9Δ compared to the parental chH9N2 virus. This highlights the potential emergence of novel viruses with variable phenotypic traits, warranting the continuous monitoring of H9N2 and co-circulating subtypes in avian hosts.

Background: In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude. Aim: We hypothesized that hypobaric–hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500 m and 4500 m equivalent altitude would cause significant oxidative stress in healthy individuals. Methods: Twelve healthy, COVID-19-vaccinated (third portion of vaccination 15 months before study onset) subjects (six male, six female, mean age 35.7 years) from a larger cohort were selected to perform a 3 h flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO2, via venturi valve-equipped face mask), switching back and forth between simulated altitudes of 2500 m and 4500 m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both altitudes were centrifuged inside the chamber and the serum was frozen instantly at −21 °C for later analysis of the oxidative stress markers malondialdehyde low-density lipoprotein (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test. Results: Eleven subjects finished the study without adverse events. Whereas the partial pressure of oxygen (PO2) levels increased in the mean with increasing oxygen levels from baseline 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% FiO2 and 113.2 mmHg at 4500 m altitude and 60% FiO2, there was no significant increase in both oxidative markers from baseline to 60% FiO2 at these simulated altitudes. Some individuals had a slight increase, whereas some showed no increase at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0.55) existed between subject age and glutathione peroxidase levels at 60% FiO2 at 4500 m altitude. Conclusion: Supplemental oxygen of 60% FiO2 in a flight simulation, compared to flying in cabin pressure levels equivalent to 2500 m–4500 m altitude, does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GPX1 in the serum of arterial blood.

Evidence suggests that tart cherry (TC) supplementation has beneficial effects on health indices and recovery following strenuous exercise. However, little is known about the mechanisms and how TC might modulate the human metabolome. The aim of this study was to evaluate the influence of an acute high- and low-dose of Vistula TC supplementation on the metabolomic profile in humans. In a randomised, double-blind, placebo controlled, cross-over design, 12 healthy participants (nine male and three female; mean ± SD age, stature, and mass were 29 ± 7 years old, 1.75 ± 0.1 m, and 77.3 ± 10.5 kg, respectively) visited the laboratory on three separate occasions (high dose; HI, low dose; LO, or placebo), separated by at least seven days. After an overnight fast, a baseline venous blood sample was taken, followed by consumption of a standardised breakfast and dose conditions (HI, LO, or placebo). Subsequent blood draws were taken 1, 2, 3, 5, and 8 h post consumption. Following sample preparation, an untargeted metabolomics approach was adopted, and the extracts analysed by LCMS/MS. When all time points were collated, a principal component analysis showed a significant difference between the conditions (p < 0.05), such that the placebo trial had homogeneity, and HI showed greater heterogeneity. In a sub-group analysis, cyanidine-3-O-glucoside (C3G), cyanidine-3-O-rutinoside (C3R), and vanillic acid (VA) were detected in plasma and showed significant differences (p < 0.05) following acute consumption of Vistula TC, compared to the placebo group. These results provide evidence that phenolics are bioavailable in plasma and induce shifts in the metabolome following acute Vistula TC consumption. These data could be used to inform future intervention studies where changes in physiological outcomes could be influenced by metabolomic shifts following acute supplementation.

In this article, a dataset is described which combines wind turbine supervisory control and data acquisition (SCADA), meteorological and acoustical data and thus gives a detailed description of a wind farm and its atmospheric and acoustic environment. The data were collected during different seasons for several weeks at a time, such that a multitude of environmental and operational conditions are covered. In five measurement campaigns, in total three different locations with similar surroundings were captured. The raw data were enhanced with derived values such as atmospheric stability or direction of sound propagation. Data of one month including all time series measurements as well as monophonic audio recordings are now published. The dataset also contains three exemplary use cases along with documents that describe the data pre-processing.

Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the ωB97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48 ×10−13 cm3 molecules−1s−1 for adenine, 1.02 ×10−11 cm3 molecules−1s−1 for guanine, 5.52 ×10−13 cm3 molecules−1s−1 for thymine, 1.47 ×10−13 cm3 molecules−1s−1 for cytosine and 7.59 ×10−14 cm3 molecules−1s−1 for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics.

Case summary A 7-year-old female spayed domestic shorthair cat was presented with a history of progressive pelvic limb ataxia. A CT scan of the thoracic spine identified an extradural, left lateralised and compressive soft tissue mass at the level of T9. A decompressive hemilaminectomy at the level of T8–T10 and tissue sampling of the mass were performed. Histopathological examination revealed a parasite granuloma caused by Toxoplasma gondii infection. Postoperatively, the cat improved consistently, but mild left pelvic limb lameness remained. At 5 weeks, a recheck CT scan showed a small, enhancing soft tissue lesion in the left epidural space at T9, causing a mild left lateral compression of the spinal cord. After 9 months, the cat acutely deteriorated neurologically and was euthanased without postmortem examination. Relevance and novel information To our knowledge, this is the first report of a T gondii spinal granuloma in a cat. Such a granuloma should be considered as a differential in cats with evidence of an extradural soft tissue mass.

IntroductionDuring the first months of the COVID pandemic it emerged that facilities where people gather or live together in cohorts, such as nursing homes or schools, were particularly at high risk for becoming hotspots of virus transmission. German political and health institutions responded with far-reaching interventions and preventive strategies to protect the population from infection with SARS-CoV-2. In this context, it remains unclear whether boarding schools for sports particularly pose a risk of infection to their residents.MethodsIn a single-center prospective cohort study, numbers of SARS-CoV-2 infections of students in sports boarding schools (n = 11) vs. students attending regular day schools (n = 22) in the region Freiburg/Hochschwarzwald in Germany were investigated over a period from October 2020 to January 2021 via regular virus and antibody screening (German Clinical Trials Register; Study ID: DRKS00021909). In addition, individual and behavioral risk factors for infection were stratified via questionnaire, which provide an indication of cohort specific risk factors for infection and the success of the implementation of hygiene concepts, as well as other infection prevention strategies, within the respective facilities.ResultsRegarding SARS-CoV-2 infection numbers, the screening detected no significant group difference between sports boarding schools vs. day schools.DiscussionThe study results provide indications that sports boarding schools did not pose an increased risk of infection, assuming that the facilities prevent virus transmissions with appropriate preventive strategies and hygiene measures. In future pandemic scenarios larger-scale and multicenter studies are necessary to achieve more comprehensive epidemiological data in this field.

Noninvasive imaging of soils with X-ray CT has proven to be a useful method to assess soil structure from a pore space perspective. In contrast, methods like cone penetration tests reflect soil structure from the perspective of the soil matrix as assessed by its mechanical strength. Because both the gray value (GV) obtained with X-ray CT and the penetration resistance (PR) obtained with a cone penetration test depend on soil density there should be a relationship between the two. To the best of our knowledge, no studies attempted so far to investigate the nature of the PR ∼ GV relationship and to understand how well PR and GV are correlated. We aimed at bridging that gap and carried out a combined analysis of local GV and PR with undisturbed soil cores sampled in two soil textures, i.e., loam and sand. To carry out the GV measurements, we developed a new approach which considers an adaptive volume of the zone of influence of the penetrometer tip as a function of soil density. For sand and when looking at samples individually, the correlation between PR and GV was best when the soil microscale heterogeneity was high, i.e., when dense and loose zones of soil were present on the course of the penetrometer tip. For loam, the correlation between PR and GV was not dependent on soil heterogeneity. When looking at the whole dataset, the agreement between PR and GV was better in loam than in sand, with a distance correlation metric of 0.66 for loam and 0.34 for sand, respectively. For loam, the relationship PR ∼ GV had a trend which was similar to that of a hyperbola, i.e., with escalating PR values in a narrow GV range. For sand, no particular model could be recognized. In order to provide a proof-of-concept on how to generate 3D PR maps, the co-located measurements of GV and PR were used to establish an empirical relationship and X-ray CT was used to extrapolate it in 3D. This was carried out with the loam dataset by fitting a hyperbolic function to the PR ∼ GV data pairs. This model was then used to convert GVs into PR values, at a spatial resolution equal to that of the shaft diameter of the penetrometer tip we have used. Notwithstanding the fact that the suggested approach is dependent on numerous experimental conditions and edaphic factors, we advocate for the use of 3D PR maps. These maps could be used in root-soil interactions research, for which the study and breeding of cultivars that could show plastic response in their root systems under mechanical stress is becoming more and more important. This is particularly relevant in the context of mechanized modern agriculture.

Summary: Background: Ultra-low-dose CT (ULDCT) examinations of the chest at only twice the radiation dose of a chest X-ray (CXR) now offer a valuable imaging alternative to CXR. This trial prospectively compares ULDCT and CXR for the detection rate of diagnoses and their clinical relevance in a low-prevalence cohort of non-traumatic emergency department patients. Methods: In this prospective crossover cohort trial, 294 non-traumatic emergency department patients with a clinically indicated CXR were included between May 2nd and November 26th of 2019 (www.clinicaltrials.gov: NCT03922516). All participants received both CXR and ULDCT, and were randomized into two arms with inverse reporting order. The detection rate of CXR was calculated from ‘arm CXR’ (n = 147; CXR first), and of ULDCT from ‘arm ULDCT’ (n = 147; ULDCT first). Additional information reported by the second exam in each arm was documented. From all available clinical and imaging data, expert radiologists and emergency physicians built a compound reference standard, including radiologically undetectable diagnoses, and assigned each finding to one of five clinical relevance categories for the respective patient. Findings: Detection rates for main diagnoses by CXR and ULDCT (mean effective dose: 0.22 mSv) were 9.1% (CI [5.2, 15.5]; 11/121) and 20.1% (CI [14.2, 27.7]; 27/134; P = 0.016), respectively. As an additional imaging modality, ULDCT added 9.1% (CI [5.2, 15.5]; 11/121) of main diagnoses to prior CXRs, whereas CXRs did not add a single main diagnosis (0/134; P

Abstract Background Activation of RNA-dependent stress kinase PKR, especially by viral double-stranded RNA, induces eukaryotic initiation factor 2 α-chain (eIF2α) phosphorylation, attenuating thereby translation. We report that this RNA-mediated negative control mechanism, considered a cornerstone of the cell’s antiviral response, positively regulates splicing of a viral mRNA. Results Excision of the large human immunodeficiency virus (HIV) rev/tat intron depends strictly on activation of PKR by the viral RNA and on eIF2α phosphorylation. Rev/tat mRNA splicing was blocked by viral PKR antagonists Vaccinia E3L and Ebola VP35, as well as by a trans-dominant negative mutant of PKR, yet enhanced by overexpressing PKR. Expression of non-phosphorylatable mutant eIF2αS51A, but not of wild type eIF2α, abrogated efficient splicing of rev/tat mRNA. By contrast, expression of eIF2αS51D, a phosphomimetic mutant of eIF2α, left rev/tat mRNA splicing intact. Unlike eIF2αS51A, eIF2αS51D does not inhibit eIF2α phosphorylation by activated PKR. All HIV mRNA species contain terminal trans-activation response (TAR) stem-loop sequences that potentially could activate PKR, yet even upon TAR deletion, HIV mRNA production remained sensitive to inhibitors of PKR activation. Bioinformatic and mutational analyses revealed a compact RNA pseudoknot upstream of 3′-terminal TAR that promotes splicing by activating PKR. Supporting its essential role in control of splicing, this pseudoknot is conserved among diverse HIV and nonhuman primate SIVcpz isolates. The pseudoknot and 3′-terminal TAR collaborate in mediating PKR-regulated splicing of rev/tat intron, the pseudoknot being dominant. Conclusions Our results on HIV provide the first example of a virus co-opting activation of PKR by its RNA, a cellular antiviral mechanism, to promote splicing. They raise the question whether other viruses may use local activation of host kinase PKR through RNA elements within their genome to achieve efficient splicing of their mRNA. Our experiments reveal an indispensable role for eIF2α phosphorylation in HIV rev/tat mRNA splicing that accounts for the need for PKR activation.

The exponentially growing demand for high-speed data necessitates more complex and versatile networks. Optimization and reliability assurance of such high-complexity networks is getting increasingly important. In this article, we experimentally validate our a machine learning-based framework that combines quality of transmission (QoT) estimation with soft-failure detection, identification, and localization based on the same latent space of a variational autoencoder running on optical spectra obtained by optical spectrum analyzers at high priority nodes in the network. We further investigate the advantages of a variational autoencoder-based soft-failure detection mechanism over a QoT metric-based approach. We use data acquired from optical transmission experiments involving different modulation formats and channel configurations. The results demonstrate that the proposed framework achieves reliable QoT estimation in real world scenarios. Additionally, it effectively detects soft-failures, identifies specific failure types and accurately localizes the occurrence of failures.

We experimentally investigate the problem of monitoring the Kerr-nonlinearity coefficient $\gamma$ from transmitted and received data for a single-mode fiber link of 1600 km length. We compare the accuracy and speed of three different approaches. First, a standard split-step Fourier method is used to predict the output at various $\gamma$ values, which are then compared to the measured output. Second, a recently proposed nonlinear Fourier transform (NFT)-based method, which matches solitonic eigenvalues in the transmitted and received signals for various $\gamma$ values. Third, a novel fast version of the NFT-based method, which only matches the highest few eigenvalues. Although the NFT-based methods do not scale with link length, we demonstrate that the SSFM-based method is significantly faster than the basic NFT-based method for the considered link of 1600 km, and outperforms even the faster version. However, for a simulated link of 8000 km, the fast NFT-based method is shown to be faster than the SSMF-based method, although at the cost of a small loss in accuracy.

An underwater optical wireless communication system concept based on optical phased array antennas is presented. With this optical phased array, a laser beam can be electronically steered to adjust not only the azimuth and elevation angles, but also the beamwidth.The proposed concept simplifies pointing and acquisition challenges between non-aligned transceivers. The performance (in terms of the trade-off between achievable range, bit error rate, and data rate) is explored for different numbers of antenna elements and water types. Also, a suitable scanning method is suggested.

Coronavirus disease-19 (COVID-19) is still affecting the lives of people round the globe and remains a major public health threat. The emergence of new variants more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity creates a long-term negative outlook for the management of the pandemic. The development of effective and viable prevention and treatment options to reduce viral transmission is of the utmost importance. The fruits of the European black elderberry and extracts thereof have been traditionally used to treat viral infections such as coughs, cold and flu. Specifically, its efficacy against the Influenza A virus has been shown in vitro as well as in human clinical trials. In the current project, we investigated the antiviral activity of a black elderberry extract, mainly containing anthocyanins and phenolic compounds, against SARS-CoV-2 and its variants of concern and explored the possible mode of action by performing time of addition experiments. The results revealed that the extract displayed a strong anti-SARS-CoV-2 activity against the Wuhan type as well as the variants of concern Alpha, Beta, Gamma, Delta and Omicron with a comparable antiviral activity. Based on cytotoxicity data, a 2-log theoretical therapeutic window was established. The data accumulated so far suggest that the viral replication cycle is inhibited at later stages, inasmuch as the replication process was affected after virus entry. Therefore, it would be legitimate to assume that black elderberry extract might have the potential to be an effective treatment option for SARS-CoV-2 infections.

Abstract Large-scale urban growth has modified the hydrological cycle of our cities, causing greater and faster runoff. Urban forests (UF), i.e. the stock of trees and shrubs, can substantially reduce runoff; still, how climate, tree functional types influence rainfall partitioning into uptake and runoff is mostly unknown. We analyzed 92 published studies to investigate: interception (I), transpiration (T), soil infiltration (IR) and the subsequent reduction in runoff. Trees showed the best runoff protection compared to other land uses. Within functional types, conifers provided better protection on an annual scale through higher I and T but broadleaved species provided better IR. Regarding tree traits, leaf area index (LAI) showed a positive influence for both I and T. For every unit of LAI increment, additional 5% rainfall partition through T (3%) and I (2%) can be predicted. Overall, runoff was significantly lower under mixed species stands. Increase of conifer stock to 30% in climate zones with significant winter precipitation and to 20% in areas of no dry season can reduce runoff to an additional 4%. The study presented an overview of UF potential to partition rainfall, which might help to select species and land uses in different climate zones for better storm-water management.

Abstract Beyond the characteristics of a brain lesion, such as its etiology, size or location, lesion network mapping (LNM) has shown that similar symptoms after a lesion reflects similar dis-connectivity patterns, thereby linking symptoms to brain networks. Here, we extend LNM by using a multimodal strategy, combining functional and structural networks from 1000 healthy participants in the Human Connectome Project. We apply multimodal LNM to a cohort of 54 stroke patients with the aim of predicting sensorimotor behavior, as assessed through a combination of motor and sensory tests. Results are two-fold. First, multimodal LNM reveals that the functional modality contributes more than the structural one in the prediction of sensorimotor behavior. Second, when looking at each modality individually, the performance of the structural networks strongly depended on whether sensorimotor performance was corrected for lesion size, thereby eliminating the effect that larger lesions generally produce more severe sensorimotor impairment. In contrast, functional networks provided similar performance regardless of whether or not the effect of lesion size was removed. Overall, these results support the extension of LNM to its multimodal form, highlighting the synergistic and additive nature of different types of network modalities, and their corresponding influence on behavioral performance after brain injury.

Abstract Background During their lifetime, animals must adapt their behavior to survive in changing environments. This ability requires the nervous system to undergo adjustments at distinct temporal scales, from short-term dynamic changes in expression of neurotransmitters and receptors to longer-term growth, spatial and connectivity reorganization, while integrating external stimuli. The nematode Caenorhabditis elegans provides a model of nervous system plasticity, in particular its dauer exit decision. Under unfavorable conditions, larvae will enter the non-feeding and non-reproductive stress-resistant dauer stage and adapt their behavior to cope with the harsh new environment, with active reversal under improved conditions leading to resumption of reproductive development. However, how different environmental stimuli regulate the exit decision mechanism and thereby drive the larva’s behavioral change is unknown. To fill this gap and provide insights on behavioral changes over extended periods of time, we developed a new open hardware method for long-term imaging (12h) of C. elegans larvae. Results Our WormObserver platform comprises open hardware and software components for video acquisition, automated processing of large image data (> 80k images/experiment) and data analysis. We identified dauer-specific behavioral motifs and characterized the behavioral trajectory of dauer exit in different environments and genetic backgrounds to identify key decision points and stimuli promoting dauer exit. Combining long-term behavioral imaging with transcriptomics data, we find that bacterial ingestion triggers a change in neuropeptide gene expression to establish post-dauer behavior. Conclusions Taken together, we show how a developing nervous system can robustly integrate environmental changes activate a developmental switch and adapt the organism’s behavior to a new environment. WormObserver is generally applicable to other research questions within and beyond the C. elegans field, having a modular and customizable character and allowing assessment of behavioral plasticity over longer periods.

mRNA translation is tightly regulated to preserve cellular homeostasis. Here live-cell spectroscopy and single-particle tracking are combined to interrogate the binding dynamics of endogenous initiation factors to mRNAs 5’cap, revealing the sequence of translation initiation factors assembly and disassembly; and the clustering of translation in neurons.

Abstract Background Injectable biphasic ceramic bone substitutes (BCBSs) represent a modern alternative to conventional options for bone defect filling, as they further open the possibilities for percutaneous cavity reconstruction. Although recent studies have shown good surgical outcomes after treatment with BCBSs, mid-term follow-up data are still missing. Patients and methods Between 2013 and 2017, 18 patients were [1] treated with BCBS [2] for benign bone lesions and [3] had a complete set of retrospective information, including surgical protocols, imaging, patient dismission letters and outpatient clinic protocols, [4] with a minimum follow-up time of one year. Eleven patients received percutaneous surgery, while 7 patients had open curettage and BCBS filling. The median follow-up time was 36.5 (range 12–80) months. Results Local recurrence was reported in four patients. A distinctive bone remodelling pattern was noted on follow-up X-ray and magnetic resonance imaging showing a double-line phenomenon and continuously increasing cortical thickness one year after treatment in nine of thirteen patients. Regarding surgical complications, one patient suffered from a septic complication that required BCBS removal and lavage. One patient experienced superficial surgical site inflammation with redness and swelling, while two other patients had prolonged wound secretion. Conclusion In a limited case series, the studied BCBS demonstrated acceptable surgical outcomes. Initial wound leakage and recurrence seemed to be associated with percutaneous injection. Further studies are needed to compare recurrence and bone graft resorption after open and percutaneous bone cyst surgeries and to further evaluate postoperative surgical site inflammation, which appears self-limiting in most cases.

Abstract Background [18F] FDG PET-CT has an important role in the initial staging of lung cancer; however, accurate differentiation between activity in malignant and benign intrathoracic lymph nodes on PET-CT scans can be challenging. The purpose of the current study was to investigate the effect of incorporating primary tumour data and clinical features to differentiate between [18F] FDG-avid malignant and benign intrathoracic lymph nodes. Methods We retrospectively selected lung cancer patients who underwent PET-CT for initial staging in two centres in the Netherlands. The primary tumour and suspected lymph node metastases were annotated and cross-referenced with pathology results. Lymph nodes were classified as malignant or benign. From the image data, we extracted radiomic features and trained the classifier model using the extreme gradient boost (XGB) algorithm. Various scenarios were defined by selecting different combinations of data input and clinical features. Data from centre 1 were used for training and validation of the models using the XGB algorithm. To determine the performance of the model in a different hospital, the XGB model was tested using data from centre 2. Results Adding primary tumour data resulted in a significant gain in the performance of the trained classifier model. Adding the clinical information about distant metastases did not lead to significant improvement. The performance of the model in the test set (centre 2) was slightly but statistically significantly lower than in the validation set (centre 1). Conclusions Using the XGB algorithm potentially leads to an improved model for the classification of intrathoracic lymph nodes. The inclusion of primary tumour data improved the performance of the model, while additional knowledge of distant metastases did not. In patients in whom metastases are limited to lymph nodes in the thorax, this may reduce costly and invasive procedures such as endobronchial ultrasound or mediastinoscopy procedures.

Training spiking recurrent neural networks on neuronal recordings or behavioral tasks has become a popular way to study computations performed by the nervous system. As the size and complexity of neural recordings increase, there is a need for efficient algorithms that can train models in a short period of time using minimal resources. We present optimized CPU and GPU implementations of the recursive least-squares algorithm in spiking neural networks. The GPU implementation can train networks of one million neurons, with 100 million plastic synapses and a billion static synapses, about 1,000 times faster than an unoptimized reference CPU implementation. We demonstrate the code's utility by training a network, in less than an hour, to reproduce the activity of > 66, 000 recorded neurons of a mouse performing a decision-making task. The fast implementation enables a more interactive in-silico study of the dynamics and connectivity underlying multi-area computations. It also admits the possibility to train models as in-vivo experiments are being conducted, thus closing the loop between modeling and experiments.

Summary: Aging is associated with changes in the central nervous system and leads to reduced life quality. Here, we investigated the age-related differences in the CNS underlying motor performance deficits using magnetic resonance spectroscopy and diffusion MRI. MRS measured N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) concentrations in the sensorimotor and occipital cortex, whereas dMRI quantified apparent fiber density (FD) in the same voxels to evaluate white matter microstructural organization. We found that aging was associated with increased reaction time and reduced FD and NAA concentration in the sensorimotor voxel. Both FD and NAA mediated the association between age and reaction time. The NAA concentration was found to mediate the association between age and FD in the sensorimotor voxel. We propose that the age-related decrease in NAA concentration may result in reduced axonal fiber density in the sensorimotor cortex which may ultimately account for the response slowness of older participants.

Two test series were examined using nondestructive measuring methods by six independent laboratories before determining their compressive strength. The nondestructive test methods used were the rebound hammer and ultrasonic pulse velocity measurement. Two types of geometries were investigated: drilled cores and cubes. The measurement procedure for each of these datasets is conditioned to the geometry and is therefore different.The first series consists of 20 drilled cores (approximately diameter/height = 10 cm/20 cm) from the 55-year-old Lahntal Viaduct near Limburg, Germany. After preparation in the first laboratory, the lateral surface of the drilled cores was tested with the rebound hammer using a given pattern. Every laboratory tested every drilled core at different locations. Ultrasonic measurements in transmission were performed repeatedly at predefined points on the flat surfaces of the specimen.The second series consisted of 25 newly manufactured concrete cubes of a mix with a target concrete strength class of C30/37. The edge length was 15 cm. Each laboratory received five specimens of this test series. Thus, contrary to the first series, each specimen was tested by only one laboratory. Two side faces of each cube were tested with the rebound hammer. In addition, ultrasonic measurements were performed by one laboratory. The time of flight was measured between the tested side faces of the rebound hammer at different positions.For both series, rebound hammers were used to determine the R-value as well as the Q-value. The rebound hammer models within the laboratories were always the same, while they differed between the laboratories. The ultrasonic measurements took place with different measurement systems and couplants. Finally, both specimen series were tested destructively for compressive strength.The dataset contains the raw data summarized in tabular form. In addition, relevant calculated data are included in some cases. For the ultrasonic measurements, the time of flight has already been converted into the ultrasonic velocity. Besides, in addition to the raw data of the compressive strength test (force, weight, and geometry values), the calculated compressive strengths and densities are also provided.

This paper deals with the influence of microwaves on the hardening and curing of geopolymer binders synthesized from metakaolin or aluminum orthophosphate with sodium silicate solution as the activator. Pure geopolymer pastes as well as geopolymer mortars were considered. The variable parameters were the modulus of the sodium silicate solutions (molar ratio of SiO2 to Na2O: 1.5, 2.0 and 2.5) and the Si/Al ratio (3/1 and 2/1). Selected samples were cured in a microwave oven until hardening, so the curing time depended on the mixture. For comparison some samples were cured at ambient temperature. To investigate the influence of microwave radiation on the reaction kinetics, isothermal heat flow calorimetry, ultrasonic velocity measurements and rheological investigations into the variation of curing temperature were used. In addition, the mechanical properties of the cured samples were characterized. The results show that microwave curing only takes a few minutes, so it is the most time-saving method. Key factors influencing the geopolymer reaction under microwave radiation are the raw materials as well as the Si/Al ratio. Metakaolin-based geopolymer binders are more stable than those based on aluminum orthophosphate, especially regarding their salt efflorescence. Microwave radiation is an efficient method to accelerate the geopolymer reaction.

This vision paper covers the increased complexity of navigational environments and presents an innovative navigation system that can support the human in this task. Shipping in general also requires a mean to support navigators reduce the risk of accidents due to smaller passing distance or a shorter reaction time. An innovative approach called Velocity Obstacles might help the operator to avoid intruding into an object’s protected zone by visualizing the problem space in relation to the maneuvering potential of the Own Ship.

Urban environments are challenging places for urban greenspaces, especially for trees, which have the greatest impact on ecosystem service provisions [...]

Neil R Euliano,1 Paul Stephan,1 Konstantinos Michalopoulos,1 Michael A Gentile,2 A Joseph Layon,3 Andrea Gabrielli4 1Convergent Engineering, Inc, Gainesville, FL, USA; 2Department of Anesthesiology, Duke University, Durham, NC, USA; 3Department of Anesthesiology, College of Medicine, University of Central Florida, Orlando, FL, USA; 4Miller School of Medicine, University of Miami, Miami, FL, USACorrespondence: Neil R Euliano, Convergent Engineering, Inc, 100 SW 75th Street, STE 106, Gainesville, FL, 32607, USA, Tel +1 352 378 4899 x 107, Fax +1 352 378 9202, Email neil@conveng.comBackground: Mechanical ventilation (MV) is used to support patients with respiratory impairment. Evidence supports the use of lung-protective ventilation (LPV) during MV to improve outcomes. However, studies have demonstrated poor adherence to LPV guidelines. We hypothesized that an electronic platform adapted to a hand-held tablet receiving real-time ventilatory parameters could increase clinician awareness of key LPV parameters. Furthermore, we speculated that an electronic shift-change tool could improve the quality of clinician handoffs.Methods: Using a specially designed Wi-Fi dongle to transmit data from three ventilators and a respiratory monitor, we implemented a system that displays data from all ventilators under the care of a Respiratory Care Practitioner (RCP) on an electronic tablet. In addition, the tablet created a handoff checklist to improve shift-change communication. In a simulated ICU environment, we monitored the performance of eight RCPs at baseline and while using the system.Results: Using the system, the time above guideline Pplat decreased by 74% from control, and the time outside the VT range decreased by 60% from control, p = 0.007 and 0.015, respectively. The handoff scores improved quality significantly from 2.8 to 1.6 on a scale of 1 to 5 (1 being best), p = 0.03.Conclusion: In a simulated environment, an electronic RT tool can significantly improve shift-change communication and increase the RCP’s level of LPV adherence.Keywords: respiration, lung protective ventilation, handoff, respiratory therapy, clinical decision support software, health information technology

Background and purpose: The geometrical accuracy of auto-segmentation using convolutional neural networks (CNNs) has been demonstrated. This study aimed to investigate the dose-volume impact of differences between automatic and manual OARs for locally advanced (LA) and peripherally located early-stage (ES) non-small cell lung cancer (NSCLC). Material and methods: A single CNN was created for automatic delineation of the heart, lungs, main left and right bronchus, esophagus, spinal cord and trachea using 55/10/40 patients for training/validation/testing. Dice score coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were used for geometrical analysis. A new treatment plan based on the auto-segmented OARs was created for each test patient using 3D for ES-NSCLC (SBRT, 3–8 fractions) and IMRT for LA-NSCLC (24–35 fractions). The correlation between geometrical metrics and dose-volume differences was investigated. Results: The average (±1 SD) DSC and HD95 were 0.82 ± 0.07 and 16.2 ± 22.4 mm, while the average dose-volume differences were 0.5 ± 1.5 Gy (ES) and 1.5 ± 2.8 Gy (LA). The geometrical metrics did not correlate with the observed dose-volume differences (average Pearson for DSC: −0.27 ± 0.18 (ES) and −0.09 ± 0.12 (LA); HD95: 0.1 ± 0.3 mm (ES) and 0.2 ± 0.2 mm (LA)). Conclusions: After post-processing, manual adjustments of automatic contours are only needed for clinically relevant OARs situated close to the tumor or within an entry or exit beam e.g., the heart and the esophagus for LA-NSCLC and the bronchi for ES-NSCLC. The lungs do not need to be checked further in detail.

Background: As the awareness towards gender-specific therapies continues to increase among all fields of medicine, so does the need for gender-sensitive evaluations of established surgical techniques. With a higher likelihood of anterior cruciate ligament injury in women, a critical assessment of the functional outcome of anterior cruciate ligament reconstruction regarding patient sex is indispensable. Almost all pre-existing literature on this subject is based on anterior cruciate ligament reconstructions carried out before 2008, when ‘all-inside’ techniques did not exist. This implicates the need to investigate this technique towards its differences in outcome between male and female patients. Objectives: The purpose of this study was to determine whether there is a difference concerning the functional outcome of an ‘all-inside’ technique for anterior cruciate ligament reconstruction in female patients when compared to a cohort of male patients matched for body mass index and age. Design: Retrospective analysis. Methods: All female patients who underwent anterior cruciate ligament reconstruction using an all-inside technique between 2011 and 2012 were examined for inclusion. Functional outcome parameters investigated included the Lysholm Knee Score, International Knee Documentation Committee score, Visual Analogue Scale score and the Tegner Activity Scale. All parameters were documented before surgery and at 3-, 6-, 12- and >24 months follow-up. At 24-month follow-up, anterior–posterior knee laxity was tested using the KT-2000 arthrometer device. For comparison, an equivalent group of male patients who underwent the same procedure was matched. Results: 27 female patients were matched with 27 male patients. The average age was 29 years, and a mean follow-up of 90 months could be achieved with 27 of patients reaching a follow-up of > 10 years. The evaluated scores showed no significant difference between female and male patients. Women presented with poorer functional outcome at 3- as well as 6-month follow-ups compared to men, without reaching statistical significance. After 12 months, no further differences could be found. Conclusion: This study proved that an all-inside technique for anterior cruciate ligament reconstruction is able to produce the same functional outcome in female as in male patients at long-term follow-up. The results on short-term outcome indicate the need for further research towards gender-specific differences after anterior cruciate ligament reconstruction, their potential causes and potential of improvement. Level of evidence: Level III, retrospective comparative study.

The management of proximal tibial fractures has evolved significantly in recent years. While the main goals of treatment – stability, restoration of the mechanical axis, and smooth articular surfaces – remain the same, methods have advanced substantially. In diagnostics, technical progress in CT and MR imaging has led to a better three-dimensional understanding of the injury. Newly developed classification systems such as the three-column concept of Luo et al. and the 10-segment concept of Krause et al. take this into account. Accordingly, there is a trend towards tailored approaches for particular fracture localizations. Parallel to this development, there is increasing evidence of the advantages of arthroscopically assisted surgical procedures. This Current Concepts article reviews classifications, diagnostics, treatment options as well as complications in fractures of the proximal tibia.

An integrated analysis of GABA concentration, interhemispheric phase-based connectivity behavior and in healthy human participants revealed a task-specific association between GABA concentration and motor-cortical connectivity. These results shed light on how GABA is involved in neural oscillations and behavioral performance.

Abstract Cell migration plays an essential role in wound healing and inflammatory processes inside the human body. Peripheral blood neutrophils, a type of polymorphonuclear leukocyte (PMN), are the first cells to be activated during inflammation and subsequently migrate toward an injured tissue or infection site. This response is dependent on both biochemical signaling and the extracellular environment, one aspect of which includes increased temperature in the tissues surrounding the inflammation site. In our study, we analyzed temperature-dependent neutrophil migration using differentiated HL-60 cells. The migration speed of differentiated HL-60 cells was found to correlate positively with temperature from 30 to 42 °C, with higher temperatures inducing a concomitant increase in cell detachment. The migration persistence time of differentiated HL-60 cells was higher at lower temperatures (30–33 °C), while the migration persistence length stayed constant throughout the temperature range. Coupled with the increased speed observed at high temperatures, this suggests that neutrophils are primed to migrate more effectively at the elevated temperatures characteristic of inflammation. Temperature gradients exist on both cell and tissue scales. Taking this into consideration, we also investigated the ability of differentiated HL-60 cells to sense and react to the presence of temperature gradients, a process known as thermotaxis. Using a two-dimensional temperature gradient chamber with a range of 27–43 °C, we observed a migration bias parallel to the gradient, resulting in both positive and negative thermotaxis. To better mimic the extracellular matrix (ECM) environment in vivo, a three-dimensional collagen temperature gradient chamber was constructed, allowing observation of biased neutrophil-like differentiated HL-60 migration toward the heat source.

In this study, in operandi SAXS experiments were conducted on samples of human hair with a varying degree of strain (2% within the elastic region and 10% beyond). Four different features in the SAXS patterns were evaluated: The intermediate filament distance perpendicular to and the distance from the meridional arc in the load direction, as well as the distances of the lipid bilayer peak in and perpendicular to the load direction. From the literature, one concludes that polar lipids in the cuticle are the origin of the lipid peak in the SAXS pattern, and this study shows that the observed strain in the lipids is much lower than in the intermediate filaments. We support these findings with SEM micrographs, which show that the scales in the cuticle deform much less than the cortex. The observed deformation of the intermediate filaments is very high, about 70% of the macrostrain, and the ratio of the transverse strain to the longitudinal strain at the nanoscale gives a Poisson ratio of νnano = 0.44, which is typical for soft matter. This work also finds that by varying the time period between two strain cycles, the typical strain recovery time is about 1000 min, i.e., one day. After this period, the structure is nearly identical to the initial structure, which suggests an interpretation that this is the typical time for the self-healing of hair after mechanical treatment.

The root-colonizing endophytic fungus Piriformospora indica promotes the root and shoot growth of its host plants. We show that the growth promotion of Arabidopsis thaliana leaves is abolished when the seedlings are grown on media with nitrogen (N) limitation. The fungus neither stimulated the total N content nor did it promote 15NO3− uptake from agar plates to the leaves of the host under N-sufficient or N-limiting conditions. However, when the roots were co-cultivated with 15N-labelled P. indica, more labels were detected in the leaves of N-starved host plants but not in plants supplied with sufficient N. Amino acid and primary metabolite profiles, as well as the expression analyses of N metabolite transporter genes suggest that the fungus alleviates the adaptation of its host from the N limitation condition. P. indica alters the expression of transporter genes, which participate in the relocation of NO3−, NH4+ and N metabolites from the roots to the leaves under N limitation. We propose that P. indica participates in the plant’s metabolomic adaptation against N limitation by delivering reduced N metabolites to the host, thus alleviating metabolic N starvation responses and reprogramming the expression of N metabolism-related genes.

Abstract Objective White matter lesions (WML) in multiple sclerosis (MS) differ from vascular WML caused by Fabry disease (FD). However, in atypical cases the discrimination can be difficult and may vary between individual raters. The aim of this study was to evaluate interrater reliability of WML differentiation between MS and FD patients. Materials and methods Brain MRI scans of 21 patients with genetically confirmed FD were compared to 21 matched patients with MS. Pseudonymized axial FLAIR sequences were assessed by 6 blinded raters and attributed to either the MS or the FD group to investigate interrater reliability. Additionally, localization of WML was compared between the two groups. Results The median age of patients was 46 years (IQR 35–58). Interrater reliability was moderate with a Fleiss' Kappa of 0.45 (95%CI 0.3–0.59). Overall, 85% of all ratings in the MS group and 75% in the FD group were correct. However, only 38% of patients with MS and 33% of patients with FD were correctly identified by all 6 raters. WML involving the corpus callosum (p

Abstract Vitamin D is an important parameter, in serum/plasma based diagnostic analysis, for the determination of optimal regulation of calcium and phosphate homeostases in the human body, vital for the monitoring/progression of osteomalacia and rickets. Particularly, the quantification of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D in blood is an excellent indicator for the vitamin D status of a patient. For this purpose, LC–MS/MS methods, based on appropriate vitamin D reference standards, are considered to be ‘gold standard’ for such measurements. We have utilized quantitative NMR spectroscopy to determine the absolute content of these molecules, available as non-certified chemicals, and have determined the stability of these callibrators in borderline polar solvents at room temperature. We have observed significant isomerization of the analytes, which can play a big role in quantification of these analytes by hyphenated LC and GC analytical techniques. Appropriate explanations are given for the observation of new impurities with time in solution phase. The spin system selected for quantitation was determined using relevant 1D and 2D NMR pulse sequences. The advantage of the qNMR approach is that it is based on the quantification of atoms rather than molecular properties (e.g., quantitation by LC/UV, GC, etc.). Since the signals in an NMR spectrum are different nuclear spin-systems dispersed precisely in a magnetic environment, with the intensity being directly proportional to the amount of a particular type of nuclear spin, this technique delivers unparalleled information about the chemical structure and the absolute content.

Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, LRRC37A2, in clinical samples. LRRC37A2 expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced LRRC37A2 mRNA levels and increased LRRC37A2 exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, LRRC37A2 gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing LRRC37A2 expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy.Abbreviations: AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; B2M: beta-2-microglobulin; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; LRRC37A2: leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1

The systematic monitoring of glaciers is essential to both evaluate water resource availability and better understand the effects of climate change. The increased speed of glacier changes observed in the past few years requires a more frequent update of the glacier inventories than in the past; however, the high human supervision required by the state-of-the-art techniques is discouraging their systematic application over large areas. This article proposes a novel approach to exploit the large volume of data provided by Copernicus Sentinel missions for detecting glacier outlines, including debris-covered glaciers. In detail, our method exploits the Sentinel-1 and Sentinel-2 multitemporal images to build a composite image representing the glacier conditions during the yearly maximum ablation period. The Sentinel-2 multispectral images are classified with a support vector machine and composed to a mosaic that represents the information of the maximum glacier ablation. At the same time, the Sentinel-1 time series are exploited to build a multitemporal coherence composite that represents all the snow-covered and glaciated areas together with all the moving surfaces. This information is used together with the Sentinal-2 composite to detect the debris-covered part of the glaciers. The proposed method was tested in the Central East Alps and presented an overall accuracy of 92% with respect to a reference inventory over South Tyrol and an agreement of 90% with respect to the latest glacier inventory of the Alps from Sentinel-2. The proposed approach enables to assist glacier experts in identifying glacier outlines over large areas and in short time

Abstract Green infrastructure (GI) has emerged as a feasible strategy for promoting adaptive capacities of cities to climate change by alleviating urban heat island (UHI) and thus heat stress for humans. However, GI can also intensify the winter cold stress. To understand the extent of UHI within a city as well as the link between outdoor thermal stress both diurnally and seasonally, we carried out an empirical study in Würzburg, Germany from 2018 to 2020. At sub-urban sites, relative humidity and wind speed (WS) was considerably higher and air temperature (AT) lower compared to the inner city sites. Mean AT of inner city sites were higher by 1.3 °C during summer and 5 °C during winter compared to sub-urban sites. The magnitude followed the spatial land use patterns, in particular the amount of buildings. Consequently, out of 97 hot days (AT > 30 °C) in 3 years, 9 days above the extreme threshold of wet bulb globe temperature of 35 °C were recorded at a centre location compared to none at a sub-urban site. Extreme heat stress could be halved with 30–40% cover of greenspaces including grass lawns, green roofs, and green walls with little compromise in increasing winter cold stress.

In visible light communication systems, the ability to suppress interference caused by other light sources is a major benefit towards performance improvements. Especially for large transmitter arrays or even multi-cell arrangements, the interference problem needs to be handled. In previous work, we have presented a liquid crystal display (LCD) used as an adaptive interference-suppression filter mounted in front of each photodetector. The display elements are switched on and off in such a way that light emitted by unwanted light sources ideally is blocked, but light emitted by desired light sources reaches the detector. The pattern generated by the LC display has strong impact on the system performance. In this paper, we propose combined precoding in conjunction with LCD-based interference suppression in order to increase the signal-to-interference-plus-noise ratio and to ensure user fairness in massive MIMO scenarios. The suggested precoding strategy uses a new heuristic optimization approach based on the Santa Claus problem on unrelated machines known from computer sciences, and employs only binary entries in the weighting matrix. Corresponding results are compared with a genetic evolutionary optimization strategy and with conventional zero-forcing precoding. Regarding performance evaluation, we perform numerical ray-tracing simulations and present a room-scale VLC testbed for experimental verification.

Optical channel decorrelation is a key aspect in designing a multi-user visible light communication system. As light-emitting diodes (LEDs) are commonly used for illumination and data transmission in such a system simultaneously, the interference between them is a major problem for suitable modulation schemes. We have proposed to position liquid-crystal (LC) matrix elements in front of the receivers in order to block unwanted light – so effectively acting as filter and reducing the interference. To do so, the appropriate pixels of the LC filter are switched either to a transmissive state or to an opaque state. The selection of the correct pixel patterns is a high-order optimization problem, which makes it challenging for classic algorithms. In this paper, we suggest applying a genetic optimization to find suitable pixel patterns. We combine this kind of receiver-side optimization with conventional convex precoding at the transmitter side in an iterative manner. The overall optimization goal is to maximize the sum rate over all users. To prove the effectiveness, we use a numeric ray-tracing simulation with different settings. Also we analyze the impact of the main parameters for the genetic algorithm.

ABSTRACT The influenza A virus (IAV)-encoded matrix protein 1 (M1) acts as a master regulator of virus replication and fulfills multiple structural and regulatory functions in different cell compartments. Therefore, the spatiotemporal regulation of M1 is achieved by different mechanisms, including its structural and pH-dependent flexibility, differential association with cellular factors, and posttranslational modifications. Here, we investigated the function of M1 phosphorylation at the evolutionarily conserved threonine 108 (T108) and found that its mutation to a nonphosphorylatable alanine prohibited virus replication. Absent T108, phosphorylation led to strongly increased self-association of M1 at the cell membrane and consequently prohibited its ability to enter the nucleus and to contribute to viral ribonucleoprotein nuclear export. M1 T108 phosphorylation also controls the binding affinity to the cellular STRIPAK (striatin-interacting phosphatases and kinases) complex, which contains different kinases and the phosphatase PP2A to shape phosphorylation-dependent signaling networks. IAV infection led to the redistribution of the STRIPAK scaffolding subunits STRN and STRN3 from the cell membrane to cytosolic and perinuclear clusters, where it colocalized with M1. Inactivation of the STRIPAK complex resulted in compromised M1 polymerization and IAV replication. IMPORTANCE Influenza viruses pose a major threat to human health and cause annual epidemics and occasional pandemics. Many virus-encoded proteins exert various functions in different subcellular compartments, as exemplified by the M1 protein, but the molecular mechanisms endowing the multiplicity of functions remain incompletely understood. Here, we report that phosphorylation of M1 at T108 is essential for virus replication and controls its propensity for self-association and nuclear localization. This phosphorylation also controls binding affinity of the M1 protein to the STRIPAK complex, which contributes to M1 polymerization and virus replication.

Global spread and regional endemicity of H5Nx Goose/Guangdong avian influenza viruses (AIV) pose a continuous threat for poultry production and zoonotic, potentially pre-pandemic, transmission to humans. Little is known about the role of mutations in the viral neuraminidase (NA) that accompanied bird-to-human transmission to support AIV infection of mammals. Here, after detailed analysis of the NA sequence of human H5N1 viruses, we studied the role of A46D, L204M, S319F and S430G mutations in virus fitness in vitro and in vivo. Although H5N1 AIV carrying avian- or human-like NAs had similar replication efficiency in avian cells, human-like NA enhanced virus replication in human airway epithelia. The L204M substitution consistently reduced NA activity of H5N1 and nine other influenza viruses carrying NA of groups 1 and 2, indicating a universal effect. Compared to the avian ancestor, human-like H5N1 virus has less NA incorporated in the virion, reduced levels of viral NA RNA replication and NA expression. We also demonstrate increased accumulation of NA at the plasma membrane, reduced virus release and enhanced cell-to-cell spread. Furthermore, NA mutations increased virus binding to human-type receptors. While not affecting high virulence of H5N1 in chickens, the studied NA mutations modulated virulence and replication of H5N1 AIV in mice and to a lesser extent in ferrets. Together, mutations in the NA of human H5N1 viruses play different roles in infection of mammals without affecting virulence or transmission in chickens. These results are important to understand the genetic determinants for replication of AIV in mammals and should assist in the prediction of AIV with zoonotic potential.

Aging is associated with alterations in the brain including structural and metabolic changes. Previous research has focused on neurometabolite level differences associated to age in a variety of brain regions, but the relationship among metabolites across the brain has been much less studied. Investigating these relationships can reveal underlying neurometabolic processes, their interdependency, and their progress throughout the lifespan. Using 1H-MRS, we investigated the relationship among metabolite concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-Inositol (mIns) and glutamate-glutamine complex (Glx) in seven voxel locations, i.e., bilateral sensorimotor cortex, bilateral striatum, pre-supplementary motor area, right inferior frontal gyrus and occipital cortex. These measurements were performed on 59 human participants divided in two age groups: young adults (YA: 23.2 ± 4.3; 18–34 years) and older adults (OA: 67.5 ± 3.9; 61–74 years). Our results showed age-related differences in NAA, Cho, and mIns across brain regions, suggesting the presence of neurodegeneration and altered gliosis. Moreover, associative patterns among NAA, Cho and Cr were observed across the selected brain regions, which differed between young and older adults. Whereas most of metabolite concentrations were inhomogeneous across different brain regions, Cho levels were shown to be strongly related across brain regions in both age groups. Finally, we found metabolic associations between homologous brain regions (SM1 and striatum) in the OA group, with NAA showing a significant correlation between bilateral sensorimotor cortices (SM1) and mIns levels being correlated between the bilateral striata. We posit that a network perspective provides important insights regarding the potential interactions among neurochemicals underlying metabolic processes at a local and global level and their relationship with aging.

Abstract Three-body semileptonic $$\tau $$ τ -decays offer a path to understand the properties of light hadronic systems and CP symmetry violations through searches for electric dipole moments. In studies of electro-weak physics, the hadronic part of the final states has traditionally been described using the language of form factors. Spectroscopic information, resolved in terms of orbital angular momentum quantum-numbers, is best being derived from an explicit decomposition of the hadronic current in the orbital angular momentum basis. Motivated by the upcoming large data samples from $$\mathrm {B}$$ B factories, we present the full description of the hadronic currents decomposed into quantum numbers of the hadronic final state using the isobar picture. We present formulas for orbital angular momenta up to three and apply the rules derived from hadron spectroscopy to formulate the decay chain of hadronic three-body systems of arbitrary mass. We also translate this formalism to the language of form factors and thereby correct insufficiencies found in previous analyses of three-body hadronic final states.