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Global biodiversity is rapidly declining, and goals to halt biodiversity loss, such as the Aichi Biodiversity Targets, have not been achieved. To avoid further biodiversity loss, area-based protection will form part of new biodiversity targets. We use a state-of-the-art global land-use model, the Land System Modular Model, to explore global and regional human health and food security outcomes under strictly enforced 30% and 50% land protection scenarios. We find protection scenarios cause additional human mortality due to diet- and weight-related changes. Low-income regions such as South Asia and sub-Saharan Africa experience the highest levels of underweight-related mortality, causing an additional 200,000 deaths related to malnutrition in these regions alone. High-income regions, by contrast, are less affected by protection measures. Our results highlight that radical measures to protect areas of biodiversity value may jeopardize food security and human health in the most vulnerable regions of the world.

Machine learning approaches are increasingly used to extract patterns and insights from the ever-increasing stream of geospatial data, but current approaches may not be optimal when system behaviour is dominated by spatial or temporal context. Here, rather than amending classical machine learning, we argue that these contextual cues should be used as part of deep learning (an approach that is able to extract spatio-temporal features automatically) to gain further process understanding of Earth system science problems, improving the predictive ability of seasonal forecasting and modelling of long-range spatial connections across multiple timescales, for example. The next step will be a hybrid modelling approach, coupling physical process models with the versatility of data-driven machine learning.

Two of the elements of the Cabibbo–Kobayashi–Maskawa quark mixing matrix, $$|V_{ub}|$$ | V ub | and $$|V_{cb}|$$ | V cb | , are extracted from semileptonic B decays. The results of the B factories, analysed in the light of the most recent theoretical calculations, remain puzzling, because for both $$|V_{ub}|$$ | V ub | and $$|V_{cb}|$$ | V cb | the exclusive and inclusive determinations are in clear tension. Further, measurements in the $$\tau $$ τ channels at Belle, Babar, and LHCb show discrepancies with the Standard Model predictions, pointing to a possible violation of lepton flavor universality. LHCb and Belle II have the potential to resolve these issues in the next few years. This article summarizes the discussions and results obtained at the MITP workshop held on April 9–13, 2018, in Mainz, Germany, with the goal to develop a medium-term strategy of analyses and calculations aimed at solving the puzzles. Lattice and continuum theorists working together with experimentalists have discussed how to reshape the semileptonic analyses in view of the much higher luminosity expected at Belle II, searching for ways to systematically validate the theoretical predictions in both exclusive and inclusive B decays, and to exploit the rich possibilities at LHCb.

We provide updated predictions for the hadronic decays $$\bar{B}_s^0\rightarrow D_s^{(*)+} \pi ^-$$ B ¯ s 0 → D s ( ∗ ) + π - and $$\bar{B}^0\rightarrow D^{(*)+} K^-$$ B ¯ 0 → D ( ∗ ) + K - . They are based on $${\mathcal {O}}(\alpha _s^2)$$ O ( α s 2 ) results for the QCD factorization amplitudes at leading power and on recent results for the $$\bar{B}_{(s)} \rightarrow D_{(s)}^{(*)}$$ B ¯ ( s ) → D ( s ) ( ∗ ) form factors up to order $$\mathcal{O}(\Lambda _\mathrm{QCD}^2/m_c^2)$$ O ( Λ QCD 2 / m c 2 ) in the heavy-quark expansion. We give quantitative estimates of the matrix elements entering the hadronic decay amplitudes at order $$\mathcal{O}(\Lambda _\mathrm{QCD}/m_b)$$ O ( Λ QCD / m b ) for the first time. Our results are very precise, and uncover a substantial discrepancy between the theory predictions and the experimental measurements. We explore two possibilities for this discrepancy: non-factorizable contributions larger than predicted by the QCD factorization power counting, and contributions beyond the Standard Model. We determine the $$f_s/f_d$$ f s / f d fragmentation fraction for the CDF, D0 and LHCb experiments for both scenarios.

We provide a global, spatially explicit characterization of 47 terrestrial habitat types, as defined in the International Union for Conservation of Nature (IUCN) habitat classification scheme, which is widely used in ecological analyses, including for quantifying species’ Area of Habitat. We produced this novel habitat map for the year 2015 by creating a global decision tree that intersects the best currently available global data on land cover, climate and land use. We independently validated the map using occurrence data for 828 species of vertebrates (35152 point plus 8181 polygonal occurrences) and 6026 sampling sites. Across datasets and mapped classes we found on average a balanced accuracy of 0.77 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\bar{+}$$\end{document}+¯0.14 SD) at Level 1 and 0.71 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\bar{+}$$\end{document}+¯0.15 SD) at Level 2, while noting potential issues of using occurrence records for validation. The maps broaden our understanding of habitats globally, assist in constructing area of habitat refinements and are relevant for broad-scale ecological studies and future IUCN Red List assessments. Periodic updates are planned as better or more recent data becomes available., Measurement(s) IUCN habitat/species management area Technology Type(s) Geographic Information System • digital curation • computational modeling technique Sample Characteristic - Environment terrestrial natural environment • anthropogenic terrestrial biome Sample Characteristic - Location Earth (planet) Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12619283

We carry out a comprehensive analysis of the full set of $\bar{B}_q \to D_q^{(*)}$ form factors for spectator quarks $q=u,d,s$ within the framework of the Heavy-Quark Expansion (HQE) to order $\mathcal{O}(\alpha_s, 1/m_b, 1/m_c^2)$. In addition to the available lattice QCD calculations we make use of two new sets of theoretical constraints: we produce for the first time numerical predictions for the full set of $\bar{B}_s \to D_s^{(*)}$ form factors using Light-Cone Sum Rules with $B_s$-meson distribution amplitudes. Furthermore, we reassess the QCD three-point sum rule results for the Isgur-Wise functions entering all our form factors for both $q=u,d$ and $q=s$ spectator quarks. These additional constraints allow us to go beyond the commonly used assumption of $SU(3)_F$ symmetry for the $\bar B_s\to D_s^{(*)}$ form factors, especially in the unitarity constraints which we impose throughout our analysis. We find the coefficients of the IW functions emerging at $\mathcal{O}(1/m_c^2)$ to be consistent with the naive $\mathcal{O}(1)$ expectation, indicating a good convergence of the HQE. While we do not find significant $SU(3)$ breaking, the explicit treatment of $q=s$ as compared to a simple symmetry assumption renders the unitarity constraints more effective. We find that the (pseudo)scalar bounds are saturated to a large degree, which affects our theory predictions. We analyze the phenomenological consequences of our improved form factors by extracting $|V_{cb}|$ from $\bar B\to D^{(*)}\ell\nu$ decays and producing theoretical predictions for the lepton-flavour universality ratios $R(D)$, $R(D^*)$, $R(D_s)$ and $R(D_s^*)$, as well as the $\tau$- and $D_q^*$ polarization fractions for the $\bar B_q\to D_q^{(*)}\tau\nu$ modes., Comment: 16 pages, 3 figures, 7 tables, includes ancillary files; v2: minor changes to the text, conclusions unchanged, 2 missing files added, as accepted for publication in EPJC

We carry out an analysis of the full set of ten $$\bar{B}\rightarrow D^{(*)}$$B¯→D(∗) form factors within the framework of the Heavy-Quark Expansion (HQE) to order $$\mathcal {O}\left( \alpha _s,\,1/m_b,\,1/m_c^2\right) $$Oαs,1/mb,1/mc2, both with and without the use of experimental data. This becomes possible due to a recent calculation of these form factors at and beyond the maximal physical recoil using QCD light-cone sum rules, in combination with constraints from lattice QCD, QCD three-point sum rules and unitarity. We find good agreement amongst the various theoretical results, as well as between the theoretical results and the kinematical distributions in $$\bar{B}\rightarrow D^{(*)}\lbrace e^-,\mu ^-\rbrace \bar{\nu }$$B¯→D(∗){e-,μ-}ν¯ measurements. The coefficients entering at the $$1/m_c^2$$1/mc2 level are found to be of $$\mathcal {O}(1)$$O(1), indicating convergence of the HQE. The phenomenological implications of our study include an updated exclusive determination of $$|V_{cb}|$$|Vcb| in the HQE, which is compatible with both the exclusive determination using the BGL parametrization and with the inclusive determination. We also revisit predictions for the lepton-flavour universality ratios $$R_{D^{(*)}}$$RD(∗), the $$\tau $$τ polarization observables $$P_\tau ^{D^{(*)}}$$PτD(∗), and the longitudinal polarization fraction $$F_L$$FL. Posterior samples for the HQE parameters are provided as ancillary files, allowing for their use in subsequent studies.

We study the phenomenology of electric dipole moments (EDMs) induced in various scalar leptoquark models. We consider generic leptoquark couplings to quarks and leptons and match to Standard Model effective field theory. After evolving the resulting operators to low energies, we connect to EDM experiments by using up-to-date hadronic, nuclear, and atomic matrix elements. We show that current experimental limits set strong constraints on the possible CP-violating phases in leptoquark models. Depending on the quarks and leptons involved in the interaction, the existing searches for EDMs of leptons, nucleons, atoms, and molecules all play a role in constraining the CP-violating couplings. We discuss the impact of hadronic and nuclear uncertainties as well as the sensitivities that can be achieved with future EDM experiments. Finally, we study the impact of EDM constraints on a specific leptoquark model that can explain the recent $B$-physics anomalies., Published version

In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments(1). Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway(2) or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40)(3,4) and homologous yeast guided entry of tail-anchored proteins (GET)(5,6) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay(7,8). We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae(9,10), and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.

The purpose of this study was to examine the effect of subperiosteal injection of chondroinductive growth factors on the histological and biomechanical outcome of autologous osteoperiosteal grafts.Thirty six standardised osteochondral defects were created in the trochlear groove of 18 Göttinger Minipigs and evaluated after six, 12 and 52 weeks. Defects were treated with press-fit implantation of autologous osteoperiosteal cylindrical block-grafts with or without subperiosteal injection of a chondroinductive growth factor mixture (GFM).Histomorphological analysis showed complete osseointegration of all grafts from six weeks. The periosteum remained in place in 35 of 36 cases. Fibrocartilagineous repair tissue formation occurred at the cambium layer with a maximum at 12 weeks in both groups. Histomorphological grading and biomechanical testing showed highest values at 12 weeks, with signs of tissue degradation at one year. There was no significant difference between both groups.Transplantation of autologous osteoperiosteal grafts is an effective method to restore subchondral bone defects, but not the overlying cartilage as the repair tissue deteriorates in the long term. Subperiosteal growth factors injection did not stimulate tissue differentiation on a biomechanical and histomorphological level.

The purpose of this population analysis was to characterize the pharmacokinetic properties of robenacoxib in blood and stifle joint synovial fluid of dogs.Data were obtained from two studies: 1) 8 healthy Beagle dogs in which an acute inflammation was induced by injection of urate crystals into one joint; 2) 95 dogs from various breeds diagnosed with osteoarthritis (OA). Robenacoxib concentrations in blood and synovial fluid were measured using a validated HPLC-UV and LC-MS method. Non-linear mixed effects modeling was performed using NONMEM6.A two-compartment pharmacokinetic model with linear elimination was developed to describe blood concentrations of robenacoxib. Blood clearance in healthy animals was found to be 75% higher than in OA dogs. Synovial fluid concentrations were modeled using an effect-compartment-type model predicting longer residence times in OA dogs compared to healthy Beagles (e.g. concentrations above the IC(50) for COX-2, respectively, 16 h vs. 10 h at 1.5 mg/kg).Robenacoxib was found to reside longer at the effect site (inflamed joint) compared to blood in both healthy and OA dogs. These results may explain the good efficacy observed with once-daily dosing in clinical trials and the high safety index of robenacoxib in dogs.

To compare direct multi-slice CT arthrography (MSCT-AG) and direct MR arthrography (MR-AG) of the wrist with regard to the depiction of the triangular fibro-cartilage (TFC). Fifteen consecutive patients with ulnar-sided wrist pain suspicious for TFC tear underwent both MSCT-AG and MR-AG of the wrist. Images obtained were evaluated by two radiologists in a blinded fashion for the depiction of six anatomical areas (radial, central and ulnar portion on the proximal and distal side) of the TFC by means of a five-point scoring system (1 = excellent visibility to 5 = not visible). Scores for MSCT-AG and MR-AG were compared using the Student's t-test. Mean scores for MSCT-AG and MR-AG, respectively, were 2.5/2.0, 3.2/2.5 and 2.8/2.4 for the radial, central and ulnar portion of the TFC on its proximal side, and 2.7/2.0, 3.1/2.3 and 2.9/2.4 for the radial, central and ulnar portion on its distal side (n = 15). Paired Student's t-test showed no significant difference between MSCT-AG and MR-AG (P > 0.05). In a first, small series, depiction of the TFC with MSCT-AG is comparable to that of MR-AG. Further evaluation of direct multi-slice CT arthrography of the wrist in a larger patient population would be promising.

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.

Nature Cell Biology 18, 1173–1184 (2016); published online 17 October 2016; corrected after print 18 November 2016. In the version of this Article originally published, the name of co-author Eduardo Cebollero Presmanes was coded wrongly resulting in it being incorrect when exported to citation databases.

The rare multi-body decays $$ \overline{B}\to \overline{K}\pi \ell \ell $$ and $$ {\overline{B}}_s\ \to \overline{K}K\ell \ell $$ are both important as backgrounds to precision analyses in the benchmark modes $$ \overline{B}\to {\overline{K}}^{*}\ell \ell $$ and $$ {\overline{B}}_s\to \phi \ell \ell $$ as well as sensitive probes of flavor physics in and beyond the standard model. We work out non-resonant contributions to $$ \overline{B}\to \overline{K}\pi \ell \ell $$ and $$ {\overline{B}}_s\ \to \overline{K}K\ell \ell $$ amplitudes, where l = e,μ, at low hadronic recoil in a model-independent way. Using the operator product expansion in 1/m b , we present expressions for the full angular distribution. The latter allows to probe new combinations of |ΔB| = |ΔS| = 1 couplings and gives access to strong phases between non-resonant and resonant contributions. Exact endpoint relations between transversity amplitudes based on Lorentz invariance are obtained. Several phenomenological distri- butions including those from the angular projections to the S-, P-, D-waves are given. Standard model branching ratios for non-resonant $$ \overline{B}\to \overline{K}\pi \ell \ell $$ and $$ {\overline{B}}_s\ \to \overline{K}K\ell \ell $$ decays are found to be in the few 10−8 region, but drop significantly if cuts around the K * or ϕ mass are employed. Nevertheless, the non-resonant contributions to $$ \overline{B}\to \overline{K}\pi \ell \ell $$ provide the dominant background in the $$ \overline{B}\to {\overline{K}}^{*}\ell \ell $$ signal region with respect to the low mass scalars. In $$ {\overline{B}}_s\ \to \overline{K}K\ell \ell $$ , the narrowness of the ϕ allows for more efficient background control. We briefly discuss lepton-flavor non-universal effects, also in view of the recent data on R K .

The protein kinase CK2 is composed of two catalytic α-or α’- and two regulatory [β-subunits. In mammalian cells there is ample evidence for the presence of individual CK2 subunits beside the holoenzyme. By immunofluorescence studies using peptide antibodies which allow us to detect the CK2α-, α’- and β-subunits we found all three subunits to be co-localized with a 58 KDa Golgi protein which is specific for the Golgi complex. Subfractionation studies using dog pancreas cells revealed the presence of all three subunits of CK2 at the smooth endoplasmic reticulum (sER)/Golgi fraction whereas the rough endoplasmic reticulum (rER) harboured only the catalytic α-and α’-subunits. We found that the microsomal preparation from dog pancreas cells contained CK2 which phosphorylated a CK2 specific synthetic peptide and which was heparin sensitive. Furthermore, we could immunoprecipitate the CK2α-subunit that exhibited a kinase activity which phosphorylated a CK2 specific substrate and which was heparin sensitive. Protease digestion experiments revealed that the CK2 subunits were located on the cytosolic side of the rER and the sER/Golgi complex. Thus, we could demonstrate an asymmetric distribution of the CK2 subunits at the rER and sER/Golgi complex. Since the CK2α-and α’-subunits exhibit a substrate specificity which is different from the CK2 holoenzyme one might speculate that the asymmetric distribution of the CK2 holoenzyme and the CK2 catalytic subunits may have regulatory functions. (Mol Cell Biochem 227: 73-80, 2001)

To study the genetics of atopy systematically we established a mouse model that provides the general phenotype of atopy: the early response characteristic of IgE-dependent eczema or atopic dermatitis, and the diagnostic test of atopy, the skin-prick test. Using an immediate cutaneous hypersensitivity test (ICHS) against birch pollen extract we could classify A/J and C57BL/6 (B6) inbred mouse strains respectively as high responder and low responders. The F1 hybrids were found to be high responders with incomplete penetrance. Backcrossing F1 mice to the low responder B6 strain yielded three classes of responders, high, intermediate, and low. A genome-wide microsatellite screen of the backcross progeny disclosed suggestive linkage to a microsatellite marker on chromosome 6 close to the locus of the IL-5 receptor alpha chain. Its allelic variation in A/J and B6 strains was investigated and two major differences were detected. Firstly, a nucleotide exchange in the 5' untranslated region of B6 mRNA resulted in increased transcription/translation of a reporter construct. Higher expression of the receptor on the cell surface would be expected to favor an allergic immune response. Secondly, the two alleles are differentially spliced so as to yield two soluble isoforms in A/J mice versus one in B6 mice. Higher expression of soluble IL-5R would be expected to reduce the level of allergy through capture of IL-5. Thus both findings conform to the expectation based on susceptibility to atopy and thus identify the IL-5R alpha chain as a likely contributor to the genetics of atopy.

Papillon-Lefèvre syndrome is an autosomal recessively inherited palmoplantar keratoderma of unknown aetiology associated with severe periodontitis leading to premature loss of dentition. Three consanguineous families, two of Turkish and one of German origin, and three multiplex families, one of Ethiopian and two of German origin, with 11 affected and 6 unaffected siblings in all were studied. A targeted genome search was initially attempted to several candidate gene regions but failed to demonstrate linkage. Therefore a genome-wide linkage scan using a combination of homozygosity mapping and traditional linkage analysis was undertaken. Linkage was obtained with marker D11S937 with a maximum two-point lod score of Zmax = 6.1 at recombination fraction theta = 0.00 on chromosome 11q14-q21 near the metalloproteinase gene cluster. Multipoint likelihood calculations gave a maximum lod score of 7.35 between D11S901 and D11S1358. A 9.2-cM region homozygous by descent in the affected members of the three consanguineous families lies between markers D11S1989 and D11S4176 harbouring the as yet unknown Papillon-Lefèvre syndrome gene. Haplotype analyses in all the families studied support this localisation. This study has identified a further locus harbouring a gene for palmoplantar keratoderma and one possibly involved in periodontitis.

By inclusion gas chromatography on (2,6-di-O-methyl-3-O-perfluoroacyl)-β-cyclodextrins (perfluoroacyl=trifluoroacetyl or heptafluorobutanoyl), the aroma compound of hazelnuts,E-5-methyl-hept-2-en-4-one, filbertone, was quantitatively separated into its enantiomers without derivatization. The method is used for the screening of the enantiomeric composition of filbertone in foodstuffs.

Chemically bonded β-cyclodextrin (ChiraDex®) has been packed into 0.25 mm i.d. capillaries and used for the enantiomer separation of several pharmaceuticals by capillary HPLC with UV and electrospray ionization (ESI) MS detection. While having several advantages over conventional HPLC, capillary HPLC yielded comparable results, e.g. with respect to resolution and sensitivity. The good compatibility to ESI-MS was demonstrated.

Precision measurements of branching fractions and CP asymmetries in non-leptonic b -> s decays reveal certain "puzzles" when compared with Standard Model expectations based on a global fit of the CKM triangle and general theoretical expectations. Without reference to a particular model, we investigate to what extent the (small) discrepancies observed in (B -> J/psi K), (B -> phi K) and (B -> K pi) may constrain new physics in (b -> s q qbar) operators. In particular, we compare on a quantitative level the relative impact of different quark flavours q=c,s,u,d., Comment: 25 pages, 7 figures, some references added, brief discussion of B -> J/psi \pi included