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We study the problem of maximizing the probability that (i) an electric component or financial institution $X$ does not default before another component or institution $Y$ and (ii) that $X$ and $Y$ default jointly within the class of all random variables $X,Y$ with given univariate continuous distribution functions $F$ and $G$, respectively, and show that the maximization problems correspond to finding copulas maximizing the mass of the endograph $\Gamma^\leq(T)$ and the graph $\Gamma(T)$ of $T=G \circ F^-$, respectively. After providing simple, copula-based proofs for the existence of copulas attaining the two maxima $\overline{m}_T$ and $\overline{w}_T$ we generalize the obtained results to the case of general (not necessarily monotonic) transformations $T:[0,1] \rightarrow [0,1]$ and derive simple and easily calculable formulas for $\overline{m}_T$ and $\overline{w}_T$ involving the distribution function $F_T$ of $T$ (interpreted as random variable on $[0,1]$). The latter are then used to charac\-terize all non-decreasing transformations $T:[0,1] \rightarrow [0,1]$ for which $\overline{m}_T$ and $\overline{w}_T$ coincide. A strongly consistent estimator for the maximum probability that $X$ does not default before $Y$ is derived and proven to be asymptotically normal under very mild regularity conditions. Several examples and graphics illustrate the main results and falsify some seemingly natural conjectures., Comment: 27 pages, 4 figures

Staat-Interessengruppen-Beziehungen (SIB) sind von maßgeblicher Bedeutung für Policy-Stabilität oder -Variationen. Als Beitrag zur policy-analytischen Forschung wie zur Interessengruppenforschung stellt das Papier einen Mechanismus der Reproduktion und Veränderung der SIB vor. Dieser besteht aus unterschiedlichen Elementen der Perzeption, der Interaktion und der unilateralen Handlung. Der Mehrwert dieses Mechanismus besteht nicht allein in der Dynamisierung der Analyse von politischem Einfluss durch Interessengruppen, sondern auch darin, die Auswirkungen auf die zukünftigen Beziehungen zwischen Politik und organisierten Interessen in den Blick zu nehmen. Anhand eines fall-kontrastierenden Vergleichs wird die Tauglichkeit des Mechanismus für die Forschung geprüft. Die Fälle sind die Krisenmaßnahmen 2020/21, die Allianzbildung beim Fachkräftemangel im Handwerk und die Gesetzgebung zu menschenrechtlichen Sorgfaltspflichten in transnationalen Lieferketten. Im Ergebnis wird die Reproduktion der SIB durch drei immanente Restriktionen beeinträchtigt, nämlich durch divergierende Problemperzeptionen, Niederlagenerfahrungen und Mitgliederschwund. Zudem sind zwei exogene Kontingenzen feststellbar: Die Grenzen politischer Steuerungsmöglichkeiten und eine exogene politische Mobilisierung.

European ash dieback caused by the alien, invasive ascomycete species Hymenoscyphus fraxineus currently represents, along with its side effects, the greatest threat to common ash (Fraxinus excelsior) trees in Europe. The disease is widely distributed in Germany and present in all regions where common ash is growing. In order to study European ash dieback in Germany and to develop management strategies to conserve common ash as a forest tree species, the concerted, interdisciplinary research project FraxForFuture was initiated. FraxForFuture consist of an association of five sub-networks: FraxConnect, FraxMon, FraxGen, FraxPath, and FraxSilva. In total, 27 individual projects conduct research on the epidemiology of the disease, the pathogen and the preservation of ash, including various control, breeding, and silvicultural strategies. The main goals of the FraxForFuture network and the sub-networks as well as essential information about the network of common research plots are provided.

In recent decades the vitality and physical stability of European ash trees in Germany have been reduced by European ash dieback, especially when associated with stem collar necroses and rots. This study was carried out to investigate the composition of the fungal communities associated with stem collar necroses. Filamentous fungi were isolated from 58 ash trees out of nine forest stands in northern, eastern, and central Germany. Obtained isolates were identified to a genus or species level by means of morphological and molecular analyses. In total 162 morphotypes including endophytic, saprotrophic and pathogenic fungi were isolated. For 33 species found no prior reports from Fraxinus excelsior were recognised, including Cryptostroma corticale and Diplodia sapinea. None of the identified species were found at all studied sites, though Diplodia fraxini was the most common fungi with regard to frequency within all isolates, occurring at seven sample sites. This species is followed by Hymenoscyphus fraxineus, Armillaria spp., Neonectria punicea, Diaporthe cf. eres, Fusarium cf. lateritium, and Paracucurbitaria sp. in order of frequency within all isolates. The aforementioned species are characterised and analysed in respect to their occurrence in stem collar necroses and at sample sites. The influence of site conditions on the fungal composition was described for five intensively sampled sites with a minimum of five studied trees (Schwansee, Rhüden, Berggießhübel, Satrup, and Schlangen). The sampling site of Schlangen was further subdivided into four subplots with different positions in the terrain. In the remaining four extensive sample sites either one or two trees, respectively, were sampled and analysed (Oranienbaumer Heide, Woltershausen, Wolfenbüttel, and Neuhege). Over all sample sites fungal communities of symptomatic stem tissue are similar concerning the most frequent fungi, but vary greatly according to singularly isolated fungi.

Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in key clinical parameters: the arterial partial pressure of oxygen, the quantity and viscosity of tracheal mucus, and neutrophilic inflammatory cells in the respiratory tracts of the severe equine asthmatic subjects. At the immunological level, an upregulation of the regulatory antiallergic and anti-inflammatory cytokine IL-10 as well as a downregulation of the proallergic IL-4 and proinflammatory IFN-γ in the respiratory tracts of the severe equine asthmatic patients were identified in the treatment groups. CD4

Altered composition of the B cell compartment in the pathogenesis of systemic lupus erythematosus (SLE) is characterized by expanded plasmablast and IgD-CD27- double-negative B cell populations. Previous studies showed that double-negative B cells represent a heterogeneous subset, and further characterization is needed.We analyzed 2 independent cohorts of healthy donors and SLE patients, using a combined approach of flow cytometry (for 16 healthy donors and 28 SLE patients) and mass cytometry (for 18 healthy donors and 24 SLE patients) and targeted RNA-Seq analysis. To compare B cell subset formation during the acute immune response versus that during autoimmune disease, we investigated healthy donors at various time points after receipt of the BNT162b2 messenger RNA COVID-19 vaccine and patients with acute SARS-CoV-2 infection, using flow cytometry.We found that IgD-CD27+ switched and atypical IgD-CD27- memory B cells, the levels of which were increased in SLE patients, represented heterogeneous populations composed of 3 different subsets each. CXCR5+CD19Our data suggest that CXCR5-CD19

Looking at bivariate copulas from the perspective of conditional distributions and considering weak convergence of almost all conditional distributions yields the notion of weak conditional convergence. At first glance, this notion of convergence for copulas might seem far too restrictive to be of any practical importance - in fact, given samples of a copula $C$ the corresponding empirical copulas do not converge weakly conditional to $C$ with probability one in general. Within the class of Archimedean copulas and the class of Extreme Value copulas, however, standard pointwise convergence and weak conditional convergence can even be proved to be equivalent. Moreover, it can be shown that every copula $C$ is the weak conditional limit of a sequence of checkerboard copulas. After proving these three main results and pointing out some consequences we sketch some implications for two recently introduced dependence measures and for the nonparametric estimation of Archimedean and Extreme Value copulas., Comment: 23 pages, 9 figures

Conditional Value-at-Risk (CoVaR) is defined as the Value-at-Risk of a certain risk given that the related risk equals a given threshold (CoVaR=) or is smaller/larger than a given threshold (CoVaR

We have investigated a locality very well known to mineral collectors, the Yates U-Th prospect near Otter Lake, Québec. There, dikes of orange to pink calcite enclose euhedral prisms of fluorapatite, locally aligned. Early investigators pointed out the importance of micro-inclusions in the prisms. We describe and image the micro-inclusions in two polished sections of fluorapatite prisms, one of them with a millimetric globule of orange calcite similar to that in the matrix. We interpret the globule to have been an inclusion of melt trapped during growth. Micro-globules disseminated in the fluorapatite are interpreted to have crystallized in situ from aliquots of the boundary-layer melt enriched in constituents rejected by the fluorapatite; the micro-globules contain a complex jigsawed assemblage of carbonate, silicate, and sulfate minerals. Early minerals to crystallize are commonly partly dissolved and partly replaced by lower-temperature phases. Such jigsawed assemblages seem to be absent in the carbonate matrix sampled away from the fluorapatite prisms. The pressure and temperature attained at the Rigolet stage of the Grenville collisional orogeny were conducive to the anatexis of marble in the presence of H2O. The carbonate melt is considered to have become silicocarbonatitic by assimilation of the enclosing gneisses, which were also close to their melting point. Degassing was important, and the melt froze quickly. The evidence points to a magmatic origin for the carbonate dikes and the associated clinopyroxenite, rather than a skarn-related association.

Background Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to nuclear factor κB, c-Jun N-terminal kinase, and mechanistic target of rapamycin complex 1. Germline CARD11 mutations cause several distinct primary immune disorders in human subjects, including severe combined immune deficiency (biallelic null mutations), B-cell expansion with nuclear factor κB and T-cell anergy (heterozygous, gain-of-function mutations), and severe atopic disease (loss-of-function, heterozygous, dominant interfering mutations), which has focused attention on CARD11 mutations discovered by using whole-exome sequencing. Objectives We sought to determine the molecular actions of an extended allelic series of CARD11 and to characterize the expanding range of clinical phenotypes associated with heterozygous CARD11 loss-of-function alleles. Methods Cell transfections and primary T-cell assays were used to evaluate signaling and function of CARD11 variants. Results Here we report on an expanded cohort of patients harboring novel heterozygous CARD11 mutations that extend beyond atopy to include other immunologic phenotypes not previously associated with CARD11 mutations. In addition to (and sometimes excluding) severe atopy, heterozygous missense and indel mutations in CARD11 presented with immunologic phenotypes similar to those observed in signal transducer and activator of transcription 3 loss of function, dedicator of cytokinesis 8 deficiency, common variable immunodeficiency, neutropenia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked–like syndrome. Pathogenic variants exhibited dominant negative activity and were largely confined to the CARD or coiled-coil domains of the CARD11 protein. Conclusion These results illuminate a broader phenotypic spectrum associated with CARD11 mutations in human subjects and underscore the need for functional studies to demonstrate that rare gene variants encountered in expected and unexpected phenotypes must nonetheless be validated for pathogenic activity.

Collective emission behavior is usually described by the decay dynamics of the completely symmetric Dicke states. To study a more realistic scenario, we investigate alternative initial states inducing a more complex time evolution. Superposition states of the fully inverted Dicke state and the Dicke ground state with unequal mutual weights are studied as examples as well as superradiance stemming from atoms in clusters separated by more than one wavelength. The Monte Carlo wave function method serves as framework to study the dynamics of quantum states, which is determined by quantum jumps on the one hand and continuous evolution dynamics on the other hand. We compare this method with the classical picture of a system of rate equations written for the diagonal components of the density matrix., Comment: 11 pages, 5 figures

Motivated by the increasing popularity and the seemingly broad applicability of pair-copula constructions underlined by numerous publications in the last decade, in this contribution we tackle the unavoidable question on how flexible and simplifying the commonly used `simplifying assumption' is from an analytic perspective and provide answers to two related open questions posed by Nagler and Czado in 2016. Aiming at a simplest possible setup for deriving the main results we first focus on the three-dimensional setting. We prove that the family of simplified copulas is flexible in the sense that it is dense in the set of all three-dimensional co\-pulas with respect to the uniform metric $d_\infty$ - considering stronger notions of convergence like the one induced by the metric $D_1$, by weak conditional convergence, by total variation, or by Kullback-Leibler divergence, however, the family even turn out to be nowhere dense and hence insufficient for any kind of flexible approximation. Furthermore, returning to $d_\infty$ we show that the partial vine copula is never the optimal simplified copula approximation of a given, non-simplified copula $C$, and derive examples illustrating that the corresponding approximation error can be strikingly large and extend to more than 28\% of the diameter of the metric space. Moreover, the mapping $\psi$ assigning each three-dimensional copula its unique partial vine copula turns out to be discontinuous with respect to $d_\infty$ (but continuous with respect to $D_1$ and to weak conditional convergence), implying a surprising sensitivity of partial vine copula approximations. The afore-mentioned main results concerning $d_\infty$ are then extended to the general multivariate setting., Comment: 36 pages, 3 figures

Nowadays building works, especially of historic buildings with facades out of natural stone, require continuous maintenance, repair and retrofit works. In order to fulfill the needs for a completely digitized natural stone retrofit process, works are to be projected, planned, conducted and cleared with instrumentation of Building Information Modeling (BIM). Due to this need, a novel knowledge-based stone damage identification system focused on natural stone damage on the basis of BIM is developed, which will present implicitly existing knowledge and information from the building survey explicitly and objectively by using semantic data structures. BIM-SIS is an adaptive damage identification system for natural stone, which allows to virtually merge different natural stone damages, recorded by different information systems and with different procedures, into a holistic damage model. This model is used to assess the damages integrative and in detail, supported by knowledge-based methods, and to develop a uniform and cost-stable remediation strategy. Therefore, the BIM-SIS methodology consists of BIMification for information processes, Ontologies for knowledge representation and Multimodels for data interoperability. The so formed continuous interoperable digital construction representation consists of separate but interlinked domain models. This model structure is then extended for remediation execution management and allows to simply incorporate subsequently detected defects during execution. The complete damage profile is the basis for all further retrofit-creation and calculation processes in BIM-SIS which will automatically lead to user customized retrofit variants presented in VR and AR.

Circulating CD11c+ B cells are a key phenomenon in certain types of autoimmunity but have also been described in the context of regular immune responses (i.e., infections, vaccination). Using mass cytometry to profile 46 different markers on individual immune cells, we systematically initially confirmed the presence of increased CD11c+ B cells in the blood of systemic lupus erythematosus (SLE) patients. Notably, significant differences in the expression of CD21, CD27, and CD38 became apparent between CD11c− and CD11c+ B cells. We observed direct correlation of the frequency of CD21−CD27− B cells and CD21−CD38− B cells with CD11c+ B cells, which were most pronounced in SLE compared to primary Sjögren's syndrome patients (pSS) and healthy donors (HD). Thus, CD11c+ B cells resided mainly within memory subsets and were enriched in CD27−IgD−, CD21−CD27−, and CD21−CD38− B cell phenotypes. CD11c+ B cells from all donor groups (SLE, pSS, and HD) showed enhanced CD69, Ki-67, CD45RO, CD45RA, and CD19 expression, whereas the membrane expression of CXCR5 and CD21 were diminished. Notably, SLE CD11c+ B cells showed enhanced expression of the checkpoint molecules CD86, PD1, PDL1, CD137, VISTA, and CTLA-4 compared to HD. The substantial increase of CD11c+ B cells with a CD21− phenotype co-expressing distinct activation and checkpoint markers, points to a quantitative increased alternate (extrafollicular) B cell activation route possibly related to abnormal immune regulation as seen under the striking inflammatory conditions of SLE which shows a characteristic PD-1/PD-L1 upregulation.

Plant hydraulic traits are key for understanding and predicting tree drought responses. Information about the degree of the traits' intra-specific variability may guide the selection of drought-resistant genotypes and is crucial for trait-based modelling approaches. For the three temperate minor broadleaf tree species Acer platanoides, Carpinus betulus and Tilia cordata, we measured xylem embolism resistance (P50 ), leaf turgor loss point (PTLP ), specific hydraulic conductivity (KS ), Huber values (HVs), and hydraulic safety margins in adult trees across a precipitation gradient. We further quantified trait variability on different organizational levels (inter-specific to within-canopy variation), and analysed its relationship to climatic and soil water availability. Although we observed a certain intra-specific trait variability (ITV) in safety-related traits (P50 , PTLP ) with higher within-tree and between-tree than between populations variability, the magnitude was small compared to inter-specific differences, which explained 78.4% and 58.3% of the variance in P50 and PTLP , respectively. In contrast, efficiency-related traits (KS , HV) showed a high ITV both within populations and within the crowns of single trees. Surprisingly, the observed ITV of all traits was neither driven by climatic nor soil water availability. In conclusion, the high degree of conservatism in safety-related traits highlights their potential for trait-based modelling approaches.

Backgound The potential of a single progenitor cell to establish and maintain long-term protective T-cell immunity in humans is unknown. For genetic disorders disabling T-cell immunity, somatic reversion was shown to support limited T-cell development attenuating the clinical phenotype. However, the cases reported so far deteriorated over time leaving unanswered the important question of long-term activity of revertant precursors and the robustness of the resulting T-cell system. Methods We applied TCRβ-CDR3 sequencing and mass cytometry on serial samples of a now 18 year-old SCIDX1 patient with somatic reversion to analyse the longitudinal diversification and stability of a T-cell system emerging from somatic gene rescue. Findings We detected close to 105 individual CDR3β sequences in the patient. Blood samples of equal size contained about 10-fold fewer unique CDR3β sequences compared to healthy donors, indicating a surprisingly broad repertoire. Despite dramatic expansions and contractions of individual clonotypes representing up to 30% of the repertoire, stable diversity indices revealed that these transient clonal distortions did not cause long-term repertoire imbalance. Phenotypically, the T-cell system did not show evidence for progressive exhaustion. Combined with immunoglobulin substitution, the limited T-cell system in this patient supported an unremarkable clinical course over 18 years. Interpretation Genetic correction in the appropriate cell type, in our patient most likely in a T-cell biased self-renewing hematopoietic progenitor, can yield a diverse T-cell system that provides long-term repertoire stability, does not show evidence for progressive exhaustion and is capable of providing protective and regulated T-cell immunity for at least two decades. Funding DFG EH 145/9-1, DFG SCHW 432/4-1 and the German Research Foundation under Germany's Excellence Strategy–EXC-2189–Project ID: 390939984.

Úbeda-Flores showed that the range of multivariate Spearman’s footrule for copulas of dimension d ≥ 2 is contained in the interval [−1/d, 1], that the upper bound is attained exclusively by the upper Fréchet-Hoeffding bound, and that the lower bound is sharp in the case where d = 2. The present paper provides characterizations of the copulas attaining the lower bound of multivariate Spearman’s footrule in terms of the copula measure but also via the copula’s diagonal section.

In the present paper we study the problem of how to transform a copula for an arbitrary distribution function into a copula for its conditional distribution function where conditioning is meant with respect to a tail event in which the observations lie below some threshold. To this end, we consider conditioning of copulas as a map which transforms every copula into another one. Besides the general case, which refers to conditioning in all coordinates, we also pay attention to the special case of univariate conditioning, which refers to conditioning in a single coordinate. We investigate the behaviour of conditioning under composition and with respect to certain transformations of copulas, and we show that invariance of a copula under conditioning is equivalent to invariance of a copula under univariate conditioning in each coordinate. Finally, we apply conditioning of copulas to Sklar's Theorem and to measures of concordance.

All reported patients with hypomorphic X-linked severe combined immunodeficiency (X-SCID) due to c.664C>T (p.R222C) mutations in the gene (IL2RG) encoding the common γ chain (γc) have presented with opportunistic infections within the first year of life, despite the presence of nearly normal NK and T cell numbers. Reporting five children of one extended family with hemizygous mutations in IL2RG, we explore potential diagnostic clues and extend our comprehension of the functional impact of this mutation. Whole exome sequencing (WES); detailed immune phenotyping; cytokine-induced STAT phosphorylation; B, T, and NK cell activation; and quantification of sjTRECs in five Arab children with c.664C>T (p.R222C) IL2RG mutation. The mean age at clinical presentation with respiratory tract infection or diarrhea was 6.8 (range: 2–12) months. None of the children presented with opportunistic infections. Diagnostic clues were early onset in the first year of life, and a suggestive family history associated with reduced naive CD4 T cells and absent switched memory B cells. Number and phenotype of NK cells and innate-like lymphocytes were normal. The diagnosis was made by WES and corroborated by absent STAT phosphorylation and reduced functional response after IL-2 and IL-21 stimulation. Four patients underwent successful hematopoietic stem cell transplantation. As early diagnosis and treatment are important, a high index of suspicion in the diagnosis of c.664C>T (p.R222C) X-SCID is needed. This requires prompt genetic testing by next generation sequencing in order to avoid unnecessary delays in the definite diagnosis since immunological work up may not be discriminating. Assays directly testing cytokine signaling or cytokine-dependent functions are helpful in confirming the functional impact of the identified hypomorphic variants.

Kendall’s tau is one of the most popular measures of concordance, and even in the multivariate case exact upper and lower bounds of Kendall’s tau are known. The present paper provides characterizations of the copulas attaining the bounds of multivariate Kendall’s tau, mainly in terms of the copula measure, but also via Kendall’s distribution function and for shuffles of copulas.

Anthropogenic trace substances are residues from pharmaceuticals, detergents, care products and other areas of everyday use. Municipal wastewater treatment plants (WWTPs) are unable to remove these substances adequately and are therefore among the main emitters. The treatment of municipal wastewater with powdered activated carbon in combination with precoat filtration is a suitable downstream stage. Within the scope of this work, four powdered activated carbons (PACs) with different particle sizes in the range of 10–200 µm are compared (#1-#4). The sum parameters UV absorption at 254 nm (UVA254), dissolved organic carbon (DOC), chemical oxygen demand (COD), as well as the analysis of seven trace substances, characterize the removal performance of the activated carbons. As result, only the PAC #4 with the smallest particle size ( x 50.3 ≈ 10 µm) shows a target-oriented reduction of the parameters from a concentration of 30 mg∙l−1 and a contact time of 30 min. The other carbons with higher particle size do not achieve sufficient removal rates. Due to the selectivity of the activated carbons towards trace substances, a correlation of trace substance removal is not given for every PAC. Besides, investigations on a continuously operated pressurized filter cell (PFC) for filtration of an activated carbon show the separation performance. A precoat of cellulose supplies the filtration process and can improve the backwashing application.

IntroductionVertigo, dizziness and balance problems (VDB) as well as osteoarthritis (OA) are among the health conditions with the greatest impact on mobility and social participation in older adults. Patients with VDB and OA were shown to benefit from specialised care such as vestibular rehabilitation therapy or joint replacement. However, these effects are not permanent and seem to disappear over time. One important reason might be a decreasing adherence to therapy recommendations. Findings from behavioural economics (BE) can help to shed light on individual effects on adherence behaviour and long-term outcomes of VDB and OA.ObjectiveBased on insights from BE concepts (ie, self-efficacy, intention, and time and risk preferences), MobilE-TRA 2 investigates the determinants of functioning and health-related quality of life (HRQoL) 3 and 12 months after discharge from total hip replacement (THR)/total knee replacement (TKR) in patients with OA and after interdisciplinary evaluation for VDB.Methods and analysisMobilE-TRA 2 is a longitudinal observational study with data collection in two specialised tertiary care centres at the university hospital in Munich, Germany between 2020 and 2023. Patients aged 60 and older presenting for their first THR/TKR or interdisciplinary evaluation of VDB at Ludwig Maximilians University (LMU) hospital will be recruited for study participation. Three and twelve months after baseline assessment, all patients will receive a follow-up questionnaire. Mixed-effect regression models will be used to examine BE concepts as determinants of adherence, HRQoL and functioning.Ethics and disseminationThe study was approved by the ethics committee at the medical faculty of the LMU Munich under the number 20-727. Results will be published in scientific, peer-reviewed journals and at national and international conferences. Findings will also be disseminated via newsletters, the project website and a regional conference for representatives of local and national authorities.

Ubiquitin fold modifier 1 (UFM1) is an ubiquitin-like protein (Ubl) involved especially in endoplasmic stress response. Activation occurs via a three-step mechanism like other Ubls. Data obtained reveal that UFM1 regulates the oligomeric state of ubiquitin activating enzyme 5 (UBA5) to initiate the activation step. Mixtures of homodimers and heterotrimers are observed in solution at the equilibrium state, demonstrating that the UBA5-UFM1 complex undergoes several concentration dependent oligomeric translational states to form a final functional complex. The oligomerization state of unbound UBA5 is also concentration dependent and shifts from the monomeric to the dimeric state. Data describing different oligomeric states are complemented with binding studies that reveal a negative cooperativity for the complex formation and thereby provide more detailed insights into the complex formation mechanism.

There is a close spatial relation between high-grade gold mineralization in the Witwatersrand basin and carbonaceous nodules, veins and seams. Hydrocarbons thus may well have been essential in ore genesis. We have sampled four major gold-, uranium- and hydrocarbon-bearing ore horizons, namely the Carbon Leader, Vaal, B and Black reefs, to determine the role of hydrocarbons in the accumulation and hydrothermal fixation of gold. Our multipronged approach included high-resolution scanning and transmission electron microscopy (SEM, TEM), nanotomography with video clips, and geochemical modeling. Post-depositional hydrothermal activity at the peak of regional metamorphism produced an assemblage of quartz, phyllosilicates, brannerite, crandallite, florencite, monazite and gold in all four reefs. The gold, hydrocarbons and associated mineral assemblages are closely related on the micro to nano scale. Gold deposition occurred in interstices, as fracture fillings in detrital minerals, and on the surface of migrated solid hydrocarbon residues. The spherical to elliptical inclusions in the gold consist of an outer pyrobitumen phase and a central void space, partially associated with nanometric gold, uraninite, coffinite and silica. The hydrocarbon-bearing inclusion likely formed by the entrapment of a fossil liquid oil precursor during gold precipitation. The oil was subsequently thermally altered and converted into the final pyrobitumen and gaseous residues. Geochemical calculations to simulate the interaction of an invading hot hydrothermal fluid with the hydrocarbons in the reefs reveal that a very small amount of hydrocarbons will drastically decrease the aqueous solubility of gold and hence cause its instant precipitation. We extend our genetic model for the epigenetic formation of gold in the Witwatersrand. Regional metamorphism promoted the extensive and likely basin-wide circulation of hydrothermal fluids; these were capable of mobilizing substantial amounts of gold. The liquid, gaseous and solid hydrocarbons in the reefs acted as efficient chemical traps for the concentration of gold. Being strong chemical reductants, they caused the rapid precipitation and accumulation of gold on the surface of the fossil oil droplets and already solidified hydrocarbons. The release of the gases from accessible hydrocarbons into the sediments away from their source buffered the redox state of the hydrothermal solutions even at a considerable distance from the pyrobitumen seams and veins, likely resulting in the deposition of gold in the absence of visible hydrocarbons. Although our findings do not explain the ultimate origin and exceptional endowment of gold in the Witwatersrand, we do provide intriguing evidence for the large-scale hydrothermal mobilization, accumulation and fixation of gold mediated by hydrocarbons during post-depositional metamorphism.

Sap flow probes are routinely used in forest and horticulture hydrology for estimating tree water use. This requires unbiased measurements when upscaling from tree to stand level, but accuracy and comparability of different thermometric methods have been questioned. Three sap flow measuring techniques were compared against gravimetric flow measurement in cut stem segments: ‘Granier-type’ thermal dissipation probes (TDP; three different sensor types), the heat field deformation method (HFD), and the heat ratio method (HRM). For the empirical methods (TDP and HFD), new calibration parameters were estimated using a nonlinear hierarchical modelling approach. 66 stem segments from five temperate, diffuse-porous tree species (9–16 cm stem diameter, 100 cm stem length) were exposed to a wide range of flux densities by applying subatmospheric pressure (−50 to −650 hPa) analogous to natural flow conditions in the field. All TDP probes underestimated flux density by 23–45% when calculated with Granier's original calibration parameters, with the deviation increasing with flux rate. The accuracy was significantly improved by estimating new calibration parameters, especially for probes differing from Granier's original sensor design. Species-specific parameters further improved accuracy, although the species differences might partially be explained by variation in the observed ranges of sap flux. The HFD sensor overestimated gravimetric flow by ∼11%; empirical calibration did not improve its accuracy compared to the manufacturer's equation. At low to medium flow rates, the HRM system achieved higher accuracy than the other probes (0.8% underestimation), while performing poorly at high flux rates under our measurement settings (energy input of 25 J). Both for TDP and HFD sensors, we observed a surprisingly large variability in calibration parameters between different stems of the same species. We conclude that (i) TDP and HFD sensors require species-specific calibration to measure sap flux with high accuracy, (ii) the original Granier equation cannot be used for TDP probes with deviating design, and (iii), at low to medium flow rates, the highest accuracy can be achieved with HRM sensors. Our results help to increase the accuracy of tree sap flow measurements with thermal dissipation probes, and to assess various levels of errors related to the different thermometric methods. This is important when synthesizing forest transpiration data on regional and global scales.

The exchange and provision of interdisciplinary information is a key to leverage of sophisticated cross-domain BIM applications like project controlling, simulations, energy efficiency or building automation. Thereby existing data formats, domain applications and information processes must be retained as far as possible. As current interoperability methods cannot cope with this challenge satisfactorily, the multimodel method is presented here, which enables interdisciplinary construction information processes on the base of original data. A multimodel therefore combines heterogeneous models of different domains. The loose cross-model coupling of data elements is neutrally stored in external ID-based link models. As the single domain models remain unaffected, they can still be used by traditional applications. Because of the absence of a leading or integrating data scheme, no transformation processes are required, common established data formats can be reused and the linked domain models can be exchanged neutrally. The linked data in multimodels offers an additional value of information in contrast to the single domain models. Information belonging together can be automatically evaluated by the persistent links. Thus, a multimodel appears to a user as a single self-contained information space. While the method focuses on closed world data exchange scenarios, it is not intended to form a singular project information space.

A theoretical framework is presented for a (copula-based) notion of dissimilarity between continuous random vectors and its main properties are studied. The proposed dissimilarity assigns the smallest value to a pair of random vectors that are comonotonic. Various properties of this dissimilarity are studied, with special attention to those that are prone to the hierarchical agglomerative methods, such as reducibility. Some insights are provided for the use of such a measure in clustering algorithms and a simulation study is presented. Real case studies illustrate the main features of the whole methodology., Comment: 38 pages, 10 figures, 7 tables

Climate warming and a rise in evaporative demand expose forests to increasing stress, challenging silvicultural planning in many temperate forest regions. As some major timber species are drought susceptible, the choice of native broadleaf minor timbers with assumed higher drought tolerance is a promising alternative option. However, their growth performance and vitality in a warmer and drier climate are not well known. We studied tree-ring chronologies of the Central European minor timbers Acer platanoides L., Fraxinus excelsior L., and Tilia cordata Mill. in comparison to the widely planted Quercus petraea Matt. Liebl in different mixed stands along a precipitation gradient in Central Germany and analyzed the sensitivity of radial growth to climatic drivers and severe drought events with the aim to compare the species’ drought tolerance. While growth responded in all four species positively to summer (or spring) precipitation and negatively to higher summer temperature and climatic aridity, climate sensitivity of growth decreased in the period 1967–2016, proving non-stationarity. Superposed epoch analysis revealed larger growth reduction during severe drought in the diffuse-porous species (A. platanoides, T. cordata) than the ring-porous species (Q. petraea, F. excelsior), but resilience was high in all species. Moreover, none of the species showed negative growth trends with recent climate warming, and drought sensitivity was not higher at drier sites, suggesting a considerable acclimation and adaptation potential to increasing drought stress. As all four species proved to be fairly drought tolerant, they deserve broader consideration in silvicultural concepts targeted at adapting production forests to climate warming.

Tyrosine kinase 2 (TYK2) associates with interferon (IFN) alpha receptor, IL-10 receptor (IL-10R) beta and other cytokine receptor subunits for signal transduction, in response to various cytokines, including type-I and type-III IFNs, IL-6, IL-10, IL-12 and IL-23. Data on TYK2 dependence on cytokine responses and in vivo consequences of TYK2 deficiency are inconsistent. We investigated a TYK2 deficient patient, presenting with eczema, skin abscesses, respiratory infections and IgE levels >1000 U/mL, without viral or mycobacterial infections and a corresponding cellular model to analyze the role of TYK2 in type-III IFN mediated responses and NK-cell function. We established a novel simple diagnostic monocyte assay to show that the mutation completely abolishes the IFN-α mediated antiviral response. It also partly reduces IL-10 but not IL-6 mediated signaling associated with reduced IL-10Rβ expression. However, we found almost normal type-III IFN signaling associated with minimal impairment of virus control in a TYK2 deficient human cell line. Contrary to observations in TYK2 deficient mice, NK-cell phenotype and function, including IL-12/IL-18 mediated responses, were normal in the patient. Thus, preserved type-III IFN responses and normal NK-cell function may contribute to antiviral protection in TYK2 deficiency leading to a surprisingly mild human phenotype.

We study the problem of how to transform a copula for the distribution function of an arbitrary random vector into a copula for the distribution function of its order statistic. We thus extend results of Navarro and Spizzichino (2010).

Recently, gain-of-function (GOF) mutations in the gene encoding signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis (CMC). This case report describes a 10-year-old boy presenting with signs of common variable immunodeficiency (CVID), failure to thrive, impaired neurological development, and a history of recurrent mucocutaneous Candida infections. Sequencing of the STAT1 gene identified a heterozygous missense mutation in exon 7 encoding the STAT1 coiled-coil domain (c.514T>C, p.Phe172Leu). In addition to hypogammaglobulinemia with B-cell deficiency, and a low percentage of Th17 cells, immunological analysis of the patient revealed a marked depletion of forkhead-box P3(+)-expressing regulatory T cells (Tregs). In vitro stimulation of T cells from the patient with interferon-α (IFNα) and/or IFNɣ resulted in a significantly increased expression of STAT1-regulated target genes such as MIG1, IRF1, MX1, MCP1/CCL2, IFI-56K, and CXCL10 as compared to IFN-treated cells from a healthy control, while no IFNα/ɣ-mediated up-regulation of the FOXP3 gene was found. These data demonstrate that the STAT1 GOF mutation F172L, which results in impaired stability of the antiparallel STAT1 dimer conformation, is associated with inhibited Treg cell development and neurological symptoms.

Using Kendall’s tau for copulas, we compare the degree of concordance of random variables with that of their order statistics. We prove a general inequality and show that this inequality is strict for every copula from the Frechet family which is distinct from the upper Frechet–Hoeffding bound.

Sap flow measurements are a crucial tool for studies of plant water relations, but upscaling to tree or stand transpiration requires accounting for the radial distribution of sap flow across the stem. Because radial sap flow profiles cannot be measured with single-point measuring methods, predicting their shape based on easier to measure structural or functional traits is a potential route to cost-efficiently improve water-use estimates. We used heat field deformation (HFD) sensors to measure sap flux density at different sapwood depths on 38 trees of eight tropical tree species in secondary dry forest patches in north-west Costa Rica. Based on a Bayesian hierarchical modeling framework, we developed a flexible model for radial profiles that expresses the average profile depth and the spread of the profile around this depth as functions of tree height, wood density and stem growth rate, while allowing for random tree and species effects. From the model output, we scale up to approximate whole-tree daily water use (DWU). Our model revealed pronounced tree height effects, with taller trees having narrower sap flow profiles peaking closer to the cambium. While it explained 96% of the variance in the dataset, large fractions were attributed to random species and tree individual effects. Including functional traits as predictors improved the accuracy of predictions considerably both for new trees and new species. DWU responded positively to tree height, but not to annual stem increment and wood density. Extrapolating the average sap flux in the outermost 2 cm over the entire sapwood area overestimated DWU on average by 26% compared to estimates based on radial profiles. Our model provides a starting point for future studies aiming to improve landscape-scale water-use estimates integrating single-point sap flow measurements and radial profiles from a subset of trees.

Percutaneous biliary interventions (PBIs) can be associated with a high patient radiation dose, which can be reduced when national diagnostic reference levels (DRLs) are kept in mind. The aim of this multicentre study was to investigate patient radiation exposure in different percutaneous biliary interventions, in order to recommend national DRLs. A questionnaire asking for the dose area product (DAP) and the fluoroscopy time (FT) in different PBIs with ultrasound- or fluoroscopy-guided bile duct punctures was sent to 200 advanced care hospitals. Recommended national DRLs are set at the 75th percentile of all DAPs. Twenty-three facilities (9 interventional radiology depts. and 14 gastroenterology depts.) returned the questionnaire (12%). Five hundred sixty-five PBIs with 19 different interventions were included in the analysis. DAPs (range 4–21,510 cGy·cm2) and FTs (range 0.07–180.33 min) varied substantially depending on the centre and type of PBI. The DAPs of initial PBIs were significantly (p