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Intercropping is an agricultural technique where many crops are grown together on the same field, and it is becoming more widely acknowledged for its ability to improve productivity in food and forage production. This farming method allows for the strategic integration of a profitable crop with cover or non-profitable crops to achieve reciprocal benefits, while also spreading advantages across different agricultural systems. Intercropping designs differ to attain greater crop yields, reduce the use of chemicals and fertilizers, and enhance water-use efficiency, especially in the demanding circumstances of arid and semi-arid countries. This study examines new mechanisms via which intercropping enhances sustainable agriculture, including recent progress in ecological, genetic, and microbial interactions that enhance plant growth and resilience. The adaptability of the Mediterranean region, for varied agricultural methods is also assessed, with a particular focus on the possibilities for implementing intercropping systems. This study provides a thorough analysis of existing research, emphasizing the many advantages of intercropping and its contribution to the progress of sustainable agriculture.

Abstract Wastewater based epidemiology has become a widely used tool for monitoring trends of concentrations of different pathogens, most notably and widespread of SARS-CoV-2. Therefore, in 2022, also in Rhineland–Palatinate, the Ministry of Science and Health has included 16 wastewater treatment sites in a surveillance program providing biweekly samples. However, the mere viral load data is subject to strong fluctuations and has limited value for political deciders on its own. Therefore, the state of Rhineland–Palatinate has commissioned the University Medical Center at Johannes Gutenberg University Mainz to conduct a representative cohort study called SentiSurv, in which an increasing number of up to 12,000 participants have been using sensitive antigen self-tests once or twice a week to test themselves for SARS-CoV-2 and report their status. This puts the state of Rhineland–Palatinate in the fortunate position of having time series of both, the viral load in wastewater and the prevalence of SARS-CoV-2 in the population. Our main contribution is a calibration study based on the data from 2023-01-08 until 2023-10-01 where we identified a scaling factor ( $$0.208 \pm 0.031$$ 0.208 ± 0.031 ) and a delay ( $$5.07 \pm 2.30$$ 5.07 ± 2.30 days) between the virus load in wastewater, normalized by the pepper mild mottle virus (PMMoV), and the prevalence recorded in the SentiSurv study. The relation is established by fitting an epidemiological model to both time series. We show how that can be used to estimate the prevalence when the cohort data is no longer available and how to use it as a forecasting instrument several weeks ahead of time. We show that the calibration and forecasting quality and the resulting factors depend strongly on how wastewater samples are normalized.

Abstract Axions and axion-like particles emerge in many models for physics beyond the Standard Model. Thus, they have gained increasing research interest in both experimental and theoretical physics apart from their original proposition as a solution to the strong CP-problem. Among other aspects it has recently been shown that ALPs can potentially provide a solution to the long-lasting discrepancy between theory and experiment of the anomalous magnetic moment of the muon. Provided that the ALP has flavor-violating couplings to leptons, they can also mediate flavor-violating decays like $$\mu \rightarrow e\gamma $$ μ → e γ . Both processes are mediated through related form factors that we compute to two-loop order. We further show numerical implications of our calculations and how they might affect constraints on ALP couplings derived from experiments.

Abstract Smoking has multiple detrimental effects on health, and is a major preventable cause of premature death and chronic disease. Despite the well-described effect of inhaled substances from tobacco smoke on cell toxicity, the association between smoking and suicidal erythrocyte death, termed eryptosis, is virtually unknown. Therefore, the blood samples of 2023 participants of the German National Cohort Study (NAKO) were analyzed using flow cytometry analysis to determine eryptosis from fluorescent annexin V-FITC-binding to phosphatidylserine-exposing erythrocytes. Blood analyses were complemented by the measurement of hematologic parameters including red blood cell count, hematocrit, hemoglobin, mean corpuscular cell volume (MCV) and mean corpuscular hemoglobin (MCH). Eryptosis was higher in smokers than in non- and ex-smokers, and positively associated with the number of cigarettes smoked daily (r = 0.08, 95% CI [0.03, 0.12]). Interestingly, despite increased eryptosis, smokers had higher red blood cell indices than non-smokers. To conclude, smokers were characterized by higher eryptosis than non-smokers, without showing any obvious detrimental effect on classic hematological parameters.

Abstract Aim Stillage, the main residue from cereal-based bioethanol production, offers a great potential for the recovery of pentosan-type carbohydrates. Therefore, potential process options for the recovery of pentosans from bioethanol thin stillage are investigated and their basic feasibility is demonstrated on a laboratory scale. Findings The main result of this work is the development of a three-stage process for pentosan recovery, including solid–liquid separation, pentosan solubilisation and purification. The pentosan content of the thin stillage used here was determined to be about 14% related to dry matter (DM). By means of solid–liquid separation, these pentosans accumulate in the liquid phase (up to 80%), while the remainder (about 20%) is found in the solid phase. Solubilisation of these insoluble pentosans was achieved by using either a hydrothermal, an alkaline or an enzymatic treatment. Here, the results indicate a maximum solubilisation yield of 90% with a hydrothermal treatment using liquid hot water at 180 °C. Ultrafiltration and precipitation are investigated for purification. The most promising process option in this study is solid–liquid separation followed by ultrafiltration. In this case, the total pentosan yield is assessed to be about 48% (based on thin stillage) with a final pentosan concentration of about 30%DM. Graphical Abstract

Abstract We derive a factorization theorem for the Higgs-boson production amplitude in gluon-gluon fusion induced by a light-quark loop, working at next-to-leading power in soft-collinear effective theory. The factorization is structurally similar to that obtained for the h → γγ decay amplitude induced by a light-quark loop, but additional complications arise because of external color charges. We show how the refactorization-based subtraction scheme developed in previous work leads to a factorization theorem free of endpoint divergences. We use renormalization-group techniques to predict the logarithmically enhanced terms in the three-loop gg → h form factor of order α s 3 ln k − M h 2 / m b 2 $$ {\alpha}_s^3{\ln}^k\left(-{M}_h^2/{m}_b^2\right) $$ with k = 6, 5, 4, 3. We also resum the first three towers of leading logarithms, α s n ln 2 n − k − M h 2 / m b 2 $$ {\alpha}_s^n{\ln}^{2n-k}\left(-{M}_h^2/{m}_b^2\right) $$ with k = 0, 1, 2, to all orders of perturbation theory.

IntroductionChildren and youth at risk for mental health disorders, such as eating disorders (ED), were particularly affected by the COVID-19 pandemic, yet evidence for the most seriously affected and thus hospitalized youth in Germany is scarce.MethodsThis crosssectional study investigated anonymized routine hospital data (demographic information, diagnoses, treatment modalities) of patients admitted (n = 2,849) to the Department of Child and Adolescence Psychiatry, Psychosomatics and Psychotherapy (DCAPPP) of a German University Hospital between 01/2016 and 02/2022. Absolute and relative number of inpatients with or without ED prior to (01/2016–02/2020) and during the COVID-19 pandemic (03/2020–02/2022) were compared. The effect of school closures as part of social lockdown measures for COVID-19 mitigation on inpatient admission rate was explored as it has been discussed as a potential risk factor for mental health problems in youth.ResultsDuring the COVID-19 pandemic, ED inpatient admission rate increased from 10.5 to 16.7%, primarily driven by Anorexia Nervosa (AN). In contrast to previous reports, we found no change in somatic and mental disorder comorbidity, age or sexratio for hospitalized youth with ED. However, we did observe a shortened length of hospital stay (LOS) for hospitalized youth with and without ED. In addition, non-ED admissions presented with an increased number of mental disorder comorbidities. In contrast to our hypothesis, school closures were not related to the observed increase in ED.DiscussionIn summary, the COVID-19 pandemic was associated with an increased rate of inpatient treatment for youth suffering from AN, and of youth affected by multiple mental disorders. Accordingly, we assume that inpatient admission was prioritized for individuals with a higher burden of disease during the COVID-19 pandemic. Our findings pinpoint the need for adequate inpatient mental health treatment capacities during environmental crises, and a further strengthening of child and adolescence psychiatry services in Germany.

Abstract Axions and axion-like particles (ALPs) are well-motivated low-energy relics of high-energy extensions of the Standard Model (SM). We investigate the phenomenology of an ALP with flavor-changing couplings, and present a comprehensive analysis of quark and lepton flavor-changing observables within a general ALP effective field theory. Observables studied include rare meson decays, flavor oscillations of neutral mesons, rare lepton decays, and dipole moments. We derive bounds on the general ALP couplings as a function of its mass, consistently taking into account the ALP lifetime and branching ratios. We further calculate quark flavor-changing effects that are unavoidably induced by running and matching between the new physics scale and the scale of the measurements. This allows us to derive bounds on benchmark ALP models in which only a single (flavorless or flavor-universal) ALP coupling to SM particles is present at the new physics scale, and in this context we highlight the complementarity and competitiveness of flavor bounds with constraints derived from collider, beam dump and astrophysical measurements. We find that searches for ALPs produced in meson decays provide some of the strongest constraints in the MeV-GeV mass range, even for the most flavorless of ALP models. Likewise, we discuss the interplay of flavor-conserving and flavor-violating couplings of the ALP to leptons, finding that constraints from lepton flavor-violating observables generally depend strongly on both. Additionally, we analyze whether an ALP can provide an explanation for various experimental anomalies including those observed in rare B-meson decays, measurements at the ATOMKI and KTeV experiments, and in the anomalous magnetic moments of the muon and the electron.

Abstract Factorization theorems in soft-collinear effective theory at subleading order in power counting involve “radiative jet functions”, defined in terms of matrix elements of hard-collinear fields with a soft momentum emitted from inside the jet. Of particular importance are the radiative quark jet functions with an external photon or gluon, which arise e.g. in the factorization theorems for the Higgs-boson amplitudes h → γγ, h → gg and gg → h induced by light-quark loops. While the photon case has been studied extensively in previous work, we present here a detailed study of the radiative jet function with an external gluon. We calculate this jet function at one- and two-loop order, derive its one-loop anomalous dimension and study its renormalization-group evolution.

We describe a new species of the genus Conraua from the Fouta Djallon Highlands in Guinea. The species is recognised as distinct from nominotypical C. alleni, based on morphological evidence and is supported by a recent species delimitation analysis, based on DNA sequence data. The new species is distinguished from its congeners by the unique combination of the following characters: medium body size, robust limbs, only one instead of two palmar tubercles, the first finger webbed to below the first subarticular tubercle, presence of a lateral line system, indistinct tympanum, two subarticular tubercles on fingers III and IV, venter in adults white with dark brown spots or dark brown with grey or whitish spots. The new species differs from all congeners by more than 6% in the DNA sequence of mitochondrial ribosomal 16S. We discuss isolation in Pliocene and Pleistocene forest refugia as a potential driver of speciation in the C. alleni complex. We also emphasise the importance of conserving the remaining forest fragments in the Fouta Djallon Region for the preservation of both its unique biodiversity and its valuable water sources for local people.

Photoacoustic (PA) imaging enables the detection of tumors with ultrasound sensors. A laser Doppler vibrometer (LDV) measures sound waves without contact and may enable non-contact PA imaging (PAI). A successful acquisition with LDV of the PA-signals generated by a tumor irradiated by a pulsed laser depends on several factors: the metrological characteristics of the LDV, the characteristics of the laser pulse as well as the properties of the tumor and of the tissue. In this work, we prove with experiments on tissue-mimicking phantoms the validity of a simulation model based on prior work. We use the validated model to simulate the photoacoustic tumor detection with LDV. Subsequently, we estimate the photoacoustic tumor detection capabilities of a self-designed LDV with the validated model. We derive the limits for the minimal detectable size of tumors for a given depth in tissue. The smallest inclusion detected with our LDV-system on a tissue-mimicking phantom was a sphere with a radius of 200 μm at a depth of 14 mm. With our experimentally validated model, we have predicted the possibility to detect an inclusion in breast tissue with a radius up to approximately 300 μm at a depth of 22 mm.

The heat transition is a central pillar of the energy transition, aiming to decarbonize and improve the energy efficiency of the heat supply in both the private and industrial sectors. On the one hand, this is achieved by substituting fossil fuels with renewable energy. On the other hand, it involves reducing overall heat consumption and associated transmission and ventilation losses. In addition to refurbishment, digitalization contributes significantly. Despite substantial research on Digital Twins (DTs) for heat transition at different scales, a cross-scale perspective on heat optimization still needs to be developed. In response to this research gap, the present study examines four instances of applied DTs across various scales: building, campus, neighborhood, and urban. The study compares their objectives and conceptual frameworks while also identifying common challenges and potential synergies. The study’s findings indicate that all DT scales face similar data-related challenges, such as gathering, ownership, connectivity, and reliability. Also, hierarchical synergy is identified among the DTs, implying the need for collaboration and exchange. In response to this, the “Wärmewende” data platform, whose objectives and concepts are presented in the paper, promotes research data and knowledge exchange with internal and external stakeholders.

Most relevant to predicting the behavior of shape-memory-alloy (SMA)-based actuator-sensor applications activated by Joule heating are the electro-mechanical characteristics of the material under consideration. For a comprehensive characterization, a single setup that is able to provide all relevant data and information is desirable. This work covers the design, implementation and validation of such a high-end test bench for the holistic characterization of SMA micro-wires. In addition, the setup provides the possibility of application simulation experiments. Key elements of the design are the clamping mechanism guided on air bearings, a linear direct drive, a high-resolution load cell, a high-precision constant current source and a stress-controlled in-line wire sample installation. All measurements take place inside an isolated, temperature-controlled chamber. With the presented setup, the electro-mechanical and thermal characteristics of SMA wire samples with diameters from 20 µm to 100 µm can be determined. Via hardware-in-the-loop (HiL) implementation, the outputs with different biasing mechanisms and additional end-stops can be simulated even at high ambient temperatures. The generated results facilitate the prediction of the exact characteristics of SMA-driven actuator-sensor systems in a variety of applications and lead to a better general understanding of the alloy’s properties. All functionalities and features of the setup are presented by discussing the results of exemplary experiments.

Abstract Axions and axion-like particles (ALPs) are well-motivated low-energy relics of high-energy extensions of the Standard Model, which interact with the known particles through higher-dimensional operators suppressed by the mass scale Λ of the new-physics sector. Starting from the most general dimension-5 interactions, we discuss in detail the evolution of the ALP couplings from the new-physics scale to energies at and below the scale of electroweak symmetry breaking. We derive the relevant anomalous dimensions at two-loop order in gauge couplings and one-loop order in Yukawa interactions, carefully considering the treatment of a redundant operator involving an ALP coupling to the Higgs current. We account for one-loop (and partially two-loop) matching contributions at the weak scale, including in particular flavor-changing effects. The relations between different equivalent forms of the effective Lagrangian are discussed in detail. We also construct the effective chiral Lagrangian for an ALP interacting with photons and light pseudoscalar mesons, pointing out important differences with the corresponding Lagrangian for the QCD axion.

Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.

Targeting RNA methyltransferases with small molecules as inhibitors or tool compounds is an emerging field of interest in epitranscriptomics and medicinal chemistry. For two challenging RNA methyltransferases that introduce the 5-methylcytosine (m5C) modification in different tRNAs, namely DNMT2 and NSUN6, an ultra-large commercially available chemical space was virtually screened by physicochemical property filtering, molecular docking, and clustering to identify new ligands for those enzymes. Novel chemotypes binding to DNMT2 and NSUN6 with affinities down to KD,app = 37 µM and KD,app = 12 µM, respectively, were identified using a microscale thermophoresis (MST) binding assay. These compounds represent the first molecules with a distinct structure from the cofactor SAM and have the potential to be developed into activity-based probes for these enzymes. Additionally, the challenges and strategies of chemical space docking screens with special emphasis on library focusing and diversification are discussed.

Abstract Background Bacterial biofilms adhere to all tissues and surfaces in the oral cavity. Oral biofilms are responsible for the decay of human dental structures and the inflammatory degeneration of the alveolar bone. Moreover, oral biofilms on artificial materials influence the lifespan of dental prostheses and restoratives. Methods To investigate in vivo oral biofilm formation and growth, five different dental restorative materials were analyzed and compared to human enamel. The roughness of the materials and the human enamel control probe were measured at the start of the study. The dental restorative materials and the human enamel control probe were placed in dental splints and worn for 3 h, 24 h and 72 h. Results Scanning electron microscopy (SEM) revealed major differences between oral biofilm formation and growth on the materials compared to those on human enamel. Microbiological analyses showed that bacterial strains differed between the materials. Significant differences were observed in the roughness of the dental materials. Conclusions It can be concluded that material roughness affects biofilm formation on dental surfaces and restoratives, but other factors, such as surface charge, surface energy and material composition, may also have an influence.

Traffic monitoring technologies have become crucial for modern manned and autonomous vehicles. They aim to ensure the maximum level of safety and dependability. The commonly used monitoring technologies based on conventional LIDAR (laser imaging, detection, and ranging), vision and ultrasound sensors are effective if there is a clear line of sight for the surrounding traffic field. However, some potential accidents and traffic hazards beyond the line of sight cannot be detected by the aforementioned sensors. Thus, dedicated sensors require means to detect other traffic participants even if they are not visible due to obstacles. In this paper, a new traffic monitoring concept for detecting nearby traffic activities occurring beyond the line of sight is introduced. The principle is based on a portable laser Doppler vibrometer (LDV), which is mounted on the vehicle to measure the roadway’s vibration noise induced by nearby traffic activities. First proof-of-concept field tests were conducted using a commercial LDV and realistic public traffic conditions. A statistical classification method based on the frequency features of pavement vibration measurements showed quite good performance for identifying traffic conditions.

Alterations in both the expression and function of the non-receptor tyrosine kinase Zap70 are associated with numerous human diseases including immunodeficiency, autoimmunity, and leukemia. Zap70 propagates the TCR signal by phosphorylating two important adaptor molecules, LAT and SLP76, which orchestrate the assembly of the signaling complex, leading to the activation of PLCγ1 and further downstream pathways. These events are crucial to drive T-cell development and T-cell activation. Recently, it has been proposed that C564, located in the kinase domain of Zap70, is palmitoylated. A non-palmitoylable C564R Zap70 mutant, which has been reported in a patient suffering from immunodeficiency, is incapable of propagating TCR signaling and activating T cells. The lack of palmitoylation was suggested as the cause of this human disease. Here, we confirm that Zap70C564R is signaling defective, but surprisingly, the defective Zap70 function does not appear to be due to a loss in palmitoylation. We engineered a C564A mutant of Zap70 which, similarly to Zap70C564R, is non-palmitoylatable. However, this mutant was capable of propagating TCR signaling. Moreover, Zap70C564A enhanced the activity of Lck and increased its proximity to the TCR. Accordingly, Zap70-deficient P116 T cells expressing Zap70C564A displayed the hyperphosphorylation of TCR-ζ and Zap70 (Y319), two well-known Lck substrates. Collectively, these data indicate that C564 is important for the regulation of Lck activity and proximal TCR signaling, but not for the palmitoylation of Zap70.

In order to overcome several obstacles when using lignocellulosic biomass as solid fuel, different heat induced pre-treatment techniques are available. Such a pre-treatment can be realized either within a gaseous or within a hydrothermal or vapothermal atmosphere. Below, the main reactions, occurring in the respective atmosphere at temperatures below 300°C, typical for such a pre-treatment, are discussed. Different pre-treatment techniques realized at this temperature range were introduced, characterized and compared with each other. This comparison included the current state of research, the market proximity, the process parameters as well as applicable educts and product properties.

In industrial-scale biogas production from cereal straw, large quantities of solid fiber-rich digestate are produced as residual material. These residues usually contain high amounts of cellulose, hemicellulose and lignin and thus have potential for further utilization. However, they also contain impurities such as ammonia and minerals, which could negatively affect further utilization. Against this background, the present study investigates how this fibrous straw digestate can be fractionated by a combined hydrothermal and enzymatic treatment and what influence the impurities have in this process. Therefore, it is analyzed how the fractions cellulose, hemicellulose and lignin are modified by this two-stage treatment, using either raw digestate (including all impurities) or washed digestate (containing only purified fibers) as the substrate. For both substrates, around 50% of the hemicellulose is solubilized to xylans after 50 min of hydrothermal treatment using steam at 180 ∘C. Furthermore, by subsequent enzymatic treatment, around 90% and 92% of the cellulose and hemicellulose still contained in the solids are hydrolyzed to glucose and xylose, respectively. Lignin accumulates in the remaining solid but structurally degrades during the hydrothermal treatment, which is indicated by decreasing ether and ester bond contents with increasing treatment times. Impurities contained within the raw digestate do not hinder this fractionation; they even seem to positively affect hemicellulose and cellulose valorization, but apparently lead to a slightly higher lignin degradation.

The Higgs-boson production channel $gg\to h$ mediated by light-quark loops receives large logarithmic corrections in QCD, which can be resummed using factorization formulae derived in soft-collinear effective theory. In these factorization formulae the radiative gluon jet function appears, which is a central object in the study of factorization beyond the leading order in scale ratios. We calculate this function at two-loop order for the first time and present the subtleties that come along with this.

3D printing is a technology which has recently found its way into the fi eld of textile fabrics, from fashion design to technical textiles. By combining both technologies with their advantages, new composites with novel physical properties can be created. Increasing adhesion between both components, however, still remains challenging. This paper suggests a new method to improve the adhesion of a 3D printed object on a textile fabric by previously coating the latter with a polymer layer. In this way, adhesion can be substantially enhanced without signifi cantly changing the bending stiffness and haptic properties of a fabric. In this study, this procedure worked especially well for printing PLA (poly(lactic acid)) on PMMA (poly(methyl methacrylate)) or PLA coatings, while for printing ABS (acrylonitrile butadiene styrene), the best textile coatings were ABS and PLA.

Ameloblastic Fibroma (AF) is a benign mixed odontogenic tumor that usually affects young patients and is characterized histopathologically by odontogenic epithelial strands in a myxoid cell-rich stroma with stellate-shaped fibroblasts resembling embryonic tooth pulp. Here we describe a rare cystic ameloblastic fibroma with conventional ameloblastic fibroma in the cyst wall. We discuss the clinical features of this odontogenic tumor and review similar cases reported in the English literature.

The intensity of the reflected measuring beam is greatly reduced for laser-Doppler vibrometer (LDV) measurements on rough surfaces since a considerable part of the light is scattered and cannot reach the photodetector (laser speckle effect). The low intensity of the reflected laser beam leads to a so-called signal dropout, which manifests as noise peaks in the demodulated velocity signal. In such cases, no light reaches the detector at a specific time and, therefore, no signal can be detected. Consequently, the overall quality of the signal decreases significantly. In the literature, first attempts and a practical implementation to reduce this effect by signal diversity can be found. In this article, a practical implementation with four measuring heads of a Multipoint Vibrometer (MPV) and an evaluation and optimization of an algorithm from the literature is presented. The limitations of the algorithm, which combines velocity signals, are shown by evaluating our measurements. We present a modified algorithm, which generates a combined detector signal from the raw signals of the individual channels, reducing the mean noise level in our measurement by more than 10 dB. By comparing the results of our new algorithm with the algorithms of the state-of-the-art, we can show an improvement of the noise reduction with our approach.

Frataxin is a highly conserved protein whose deficiency results in the neurodegenerative disease Friederich’s ataxia. Frataxin’s actual physiological function has been debated for a long time without reaching a general agreement; however, it is commonly accepted that the protein is involved in the biosynthetic iron-sulphur cluster (ISC) machinery, and several authors have pointed out that it also participates in iron homeostasis. In this work, we use site-directed spin labeling coupled to electron paramagnetic resonance (SDSL EPR) to add new information on the effects of ferric and ferrous iron binding on the properties of human frataxin in vitro. Using SDSL EPR and relating the results to fluorescence experiments commonly performed to study iron binding to FXN, we produced evidence that ferric iron causes reversible aggregation without preferred interfaces in a concentration-dependent fashion, starting at relatively low concentrations (micromolar range), whereas ferrous iron binds without inducing aggregation. Moreover, our experiments show that the ferrous binding does not lead to changes of protein conformation. The data reported in this study reveal that the currently reported binding stoichiometries should be taken with caution. The use of a spin label resistant to reduction, as well as the comparison of the binding effect of Fe2+ in wild type and in the pathological D122Y variant of frataxin, allowed us to characterize the Fe2+ binding properties of different protein sites and highlight the effect of the D122Y substitution on the surrounding residues. We suggest that both Fe2+ and Fe3+ might play a relevant role in the context of the proposed FXN physiological functions.

Inflammation is a key physiological phenomenon that can be pervasive when dysregulated. Persistent chronic inflammation precedes several pathophysiological conditions forming one of the critical cellular homeostatic checkpoints. With a steady global surge in inflammatory diseases, it is imperative to delineate underlying mechanisms and design suitable drug molecules targeting the cellular partners that mediate and regulate inflammation. Nicotinic acetylcholine receptors have a confirmed role in influencing inflammatory pathways and have been a subject of scientific scrutiny underlying drug development in recent years. Drugs designed to target allosteric sites on the nicotinic acetylcholine receptors present a unique opportunity to unravel the role of the cholinergic system in regulating and restoring inflammatory homeostasis. Such a therapeutic approach holds promise in treating several inflammatory conditions and diseases with inflammation as an underlying pathology. Here, we briefly describe the potential of cholinergic allosterism and some allosteric modulators as a promising therapeutic option for the treatment of neuroinflammation.

The exceptional reactivity of the azide group makes organic azides a highly versatile family of compounds in chemistry and the material sciences. One of the most prominent reactions employing organic azides is the regioselective copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition with alkynes yielding 1,2,3-triazoles. Other named reactions include the Staudinger reduction, the aza-Wittig reaction, and the Curtius rearrangement. The popularity of organic azides in material sciences is mostly based on their propensity to release nitrogen by thermal activation or photolysis. On the one hand, this scission reaction is accompanied with a considerable output of energy, making them interesting as highly energetic materials. On the other hand, it produces highly reactive nitrenes that show extraordinary efficiency in polymer crosslinking, a process used to alter the physical properties of polymers and to boost efficiencies of polymer-based devices such as membrane fuel cells, organic solar cells (OSCs), light-emitting diodes (LEDs), and organic field-effect transistors (OFETs). Thermosets are also suitable application areas. In most cases, organic azides with multiple azide functions are employed which can either be small molecules or oligo- and polymers. This review focuses on nitrene-based applications of multivalent organic azides in the material and life sciences.

This paper discusses the influence of material strain and strain rate on efficiency and temperature span of elastocaloric cooling processes. The elastocaloric material, a newly developed quaternary Ni-Ti-Cu-V alloy, is characterized at different maximum strains and strain rates. The experiments are performed with a specially designed test setup, which enables the measurement of mechanical and thermal process parameters. The material efficiency is compared to the efficiency of the Carnot process at equivalent thermal operation conditions. This method allows for a direct comparison of the investigated material with other caloric materials.

Computer-supported learning is an increasingly important form of study since it allows for independent learning and individualized instruction. In this paper, we discuss a novel approach to developing an intelligent tutoring system for teaching textbook-style mathematical proofs. We characterize the particularities of the domain and discuss common ITS design models. Our approach is motivated by phenomena found in a corpus of tutorial dialogs that were collected in a Wizard-of-Oz experiment. We show how an intelligent tutor for textbook-style mathematical proofs can be built on top of an adapted assertion-level proof assistant by reusing representations and proof search strategies originally developed for automated and interactive theorem proving. The resulting prototype was successfully evaluated on a corpus of tutorial dialogs and yields good results.

The development of temporomandibular joint implants has involved simplified mechanical tests that apply pure vertical forces or pure rotational movements to the implant. The aim of this study was to develop a biological based mastication mechanism and conduct preliminary testing of a novel temporomandibular joint implant. The mechanism was designed to mimic temporomandibular joint loads by performing compression and anterior/posterior translation. Pilot testing was performed on six implant/joint specimens for seven consecutive hours, completing approximately 22,000 cycles at a frequency of approximately 1 Hz. Each cycle had a joint compression phase (67.3 N over 0.15 s) followed by a translation phase (8.67 N over 0.43 s) that was similar to joint loads/motions that have been reported in vivo. This new mastication mechanism incorporates both anatomical and mechanical variability. The use of biological specimens is an important approach that can help bridge the gap between traditional synthetic implant materials/mechanical testing and in vivo testing.

Abstract The exploding number of computational models produced by Systems Biologists over the last years is an invitation to structure and exploit this new wealth of information. Researchers would like to trace models relevant to specific scientific questions, to explore their biological content, to align and combine them, and to match them with experimental data. To automate these processes, it is essential to consider semantic annotations, which describe their biological meaning. As a prerequisite for a wide range of computational methods, we propose general and flexible similarity measures for Systems Biology models computed from semantic annotations. By using these measures and a large extensible ontology, we implement a platform that can retrieve, cluster, and align Systems Biology models and experimental data sets. At present, its major application is the search for relevant models in the BioModels Database, starting from initial models, data sets, or lists of biological concepts. Beyond similarity searches, the representation of models by semantic feature vectors may pave the way for visualisation, exploration, and statistical analysis of large collections of models and corresponding data.

Decreased upright cerebral blood flow (CBF) with hyperpnea and hypocapnia is seen in a minority of patients with postural tachycardia syndrome (POTS). More often, CBF is not decreased despite upright neurocognitive dysfunction. This may result from time-dependent changes in CBF. We hypothesized that increased oscillations in CBF occurs in POTS (N=12) compared to healthy controls (N=9), and tested by measuring CBF velocity (CBFv) by transcranial Doppler ultrasound of the middle cerebral artery, mean arterial pressure (MAP) and related parameters, supine and during 70o upright tilt. Autospectra for mean CBFv and MAP, and transfer function analysis were obtained over the frequency range of 0.0078 to 0.4 Hz. Upright HR was increased in POTS (125±8 vs 86±2 bpm), as was diastolic BP (74±3 vs 65±3 mmHg) compared to control, while peripheral resistance, cardiac output, and mean CBFv increased similarly with tilt. Upright BP variability (BPV), low frequency (LF) power (.04 - 0.13 Hz) , and peak frequency of BPV were increased in POTS (24.3±4.1, and 18.4±4.1 mmHg2/Hz at .091 Hz vs 11.8±3.3, and 8.8 ± 2 mmHg2/Hz c at 0.071 Hz), as was upright overall CBFv variability, low frequency power and peak frequency of CBFv variability (29.3±4.7, and 22.1±2.7 [cm/s]2/Hz at .092 Hz vs 14.7±2.6, and 6.7 ± 1.2 [cm/s]2/Hz at 0.077Hz). Autospectra were sharply peaked in POTS. LF phase was decreased in POTS (-14 ± 4 vs -25 ± 10 degrees) while upright. LF gain was increased (1.51 ± 0.09 vs 0.86 ± 0.12 [cm/s]/ mmHg) while coherence was increased (0.96 ± 0.01 vs 0.80 ± 0.04). Increased oscillatory BP in upright POTS patients is closely coupled to oscillatory CBFv over a narrow bandwidth corresponding to the Mayer wave frequency. Therefore combined increased oscillatory BP and increased LF gain markedly increases CBFv oscillations in a narrow bandwidth. This close coupling of CBF to MAP indicates impaired cerebral autoregulation that may underlie upright neurocognitive dysfunction in POTS.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system of unknown etiology with both genetic and environmental factors playing a role in susceptibility. To date, the HLA DR15/DQ6 haplotype within the major histocompatibility complex on chromosome 6p, is the strongest genetic risk factor associated with MS susceptibility. Additional alleles of IL7 and IL2 have been identified as risk factors for MS with small effect. Here we present two independent studies supporting an allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12 and encoding ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1. The initial association was made in a single three-generation family where a single-nucleotide polymorphism (SNP) rs4762896, was segregating together with HLA DR15/DQ6 in MS patients. A study of 274 family trios (affected child and both unaffected parents) from Australia validated the association of ST8SIA1 in individuals with MS, showing transmission disequilibrium of the paternal alleles for three additional SNPs, namely rs704219, rs2041906, and rs1558793, with p = 0.001, p = 0.01 and p = 0.01 respectively. These findings implicate ST8SIA1 as a possible novel susceptibility gene for MS.

Objective: To assess the effect of pharmacist screening for osteoporosis risk with increased bone mineral density (BMD) testing., Design: Prospective, quasi-experiment., Setting: Veterans Affairs medical center Community Living Centers (CLC), home-based primary care, and outpatient geriatric clinic., Participants: Patients with a routine pharmacist interaction were included. Exclusion criteria included hospice, dialysis, and respite care., Interventions: Risk assessment with recommendations communicated by progress notes to consider BMD testing or interventions in the settings described. A second phase of the project was conducted in CLC patients to evaluate the effect of an interdisciplinary team with the inclusion of a physician to assess clinical appropriateness of interventions., Main Outcome Measure(s): Proportion of patients meeting guidelines for BMD testing and change in proportion of patients with BMD testing ordered after intervention. Secondary measures included response to recommendations and initiation of osteoporosis pharmacotherapies., Results: A total of 219 patients were included in the first phase of the project, with 120 (54.8%) identified as candidates for BMD testing with recommendations documented. Of this population, 5 patients without previous dual-energy absorptiometry results had BMD testing ordered (P = 0.6). In the second phase, 22 high-risk patients in the CLC met criteria for BMD testing, with 14 determined to have reasons for not pursuing BMD testing., Conclusion: Most patients in the settings described met guidelines for BMD testing. Pharmacist recommendations to consider BMD testing did not increase the rate of testing. Including a physician on an interdisciplinary team appeared to help determine appropriateness and improve the rate of testing, though the increase in testing was not statistically significant.

Serum concentrations of oestrogen stimulated neurophysin (ESN) were measured throughout pregnancy in thirty-one women and until 6 weeks post-partum in a further twenty-three. During pregnancy ESN rose progressively and values during labour were similar to those immediately before delivery. There were significant correlations (P less than 0.05) between serum ESN and oestradiol values measured in samples from four patients. After delivery the concentration of ESN fell rapidly to the range for non-pregnant women by 5 days post-partum, whether the mothers lactated or not, and remained fairly constant for the next 6 weeks. Bromocriptine or metoclopramide, drugs which affect prolactin secretion, were without effect on ESN values. At 8 days post-partum in sixteen of the eighteen patients studied there was an increase in ESN concentration 30 min after suckling commenced. At 6 weeks similar changes occurred in five of the ten subjects studied. In contrast, at 8 days there was no significant change in ESN in four mothers who bottle fed their babies over the 90 min studied. The relationship between ESN and hormonal changes during pregnancy and lactation is discussed in the light of these results.