Nowhere minimal CR submanifolds and Levi-flat hypersurfaces

A local uniqueness property of holomorphic functions on real-analytic nowhere minimal CR submanifolds of higher codimension is investigated. A sufficient condition called almost minimality is given and studied. A weaker necessary condition, being contained a possibly singular real-analytic Levi-flat hypersurface is studied and characterized. This question is completely resolved for algebraic submanifolds of codimension 2 and a sufficient condition for noncontainment is given for non algebraic submanifolds. As a consequence, an example of a submanifold of codimension 2, not biholomorphically equivalent to an algebraic one, is given. We also investigate the structure of singularities of Levi-flat hypersurfaces.Comment: 21 pages; conjecture 2.8 was removed in proof; to appear in J. Geom. Ana

Treatment Burden of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Randomized Study

Context: Somatrogon is a long-acting recombinant human growth hormone treatment developed as a once-weekly treatment for pediatric patients with growth hormone deficiency (GHD). / Objective: Evaluate patient and caregiver perceptions of the treatment burden associated with the once-weekly somatrogon injection regimen vs a once-daily Somatropin injection regimen. / Methods: Pediatric patients (≥3 to <18 years) with GHD receiving once-daily somatropin at enrollment were randomized 1:1 to Sequence 1 (12 weeks of once-daily Somatropin, then 12 weeks of once-weekly somatrogon) or Sequence 2 (12 weeks of once-weekly somatrogon, then 12 weeks of once-daily Somatropin). Treatment burden was assessed using validated questionnaires completed by patients and caregivers. The primary endpoint was the difference in mean overall life interference (LI) total scores after each 12-week treatment period (somatrogon vs Somatropin), as assessed by questionnaires. / Results: Of 87 patients randomized to Sequence 1 (n = 43) or 2 (n = 44), 85 completed the study. Once-weekly somatrogon had a significantly lower treatment burden than once-daily Somatropin, based on mean overall LI total scores after somatrogon (8.63) vs Somatropin (24.13) treatment (mean difference -15.49; 2-sided 95% CI -19.71, -11.27; P < .0001). Once-weekly somatrogon was associated with greater convenience, higher satisfaction with treatment experience, and less LI. The incidence of treatment-emergent adverse events (TEAEs) for Somatropin and somatrogon was 44.2% and 54.0%, respectively. No severe or serious AEs were reported. / Conclusion: In pediatric patients with GHD, once-weekly somatrogon had a lower treatment burden and was associated with a more favorable treatment experience than once-daily Somatropin

Dirofilaria spp. And angiostrongylus vasorum: Current risk of spreading in central and northern europe

In the past few decades, the relevance of Dirofilaria immitis and Dirofilaria repens, causing cardiopulmonary and subcutaneous dirofilariosis in dogs and cats, and of Angiostrongylus vasorum, causing canine angiostrongylosis, has steadily increased in Central and Northern Europe. In this review, a summary of published articles and additional reports dealing with imported or autoch-thonous cases of these parasites is provided for Central (Austria, Czechia, Germany, Hungary, Lux-emburg, Poland, Slovakia, Slovenia, and Switzerland) and Northern (Denmark, Finland, Iceland, Norway, and Sweden) Europe. Research efforts focusing on Dirofilaria spp. and A. vasorum have varied by country, and cross-border studies are few. The housing conditions of dogs, pet move-ments, the spread of competent vectors, and climate change are important factors in the spread of these nematodes. Dogs kept outside overnight are a major factor for the establishment of Dirofilaria spp. However, the establishment of invasive, diurnal, synanthropic, competent mosquito vectors such as Aedes albopictus may also influence the establishment of Dirofilaria spp. The drivers of the spread of A. vasorum remain not fully understood, but it seems to be influenced by habitats shared with wild canids, dog relocation, and possibly climatic changes; its pattern of spreading appears to be similar in different countries. Both Dirofilaria spp. and A. vasorum merit further monitoring and research focus in Europe

Detection of crenosoma spp., angiostrongylus vasorum and aelurostrongylus abstrusus in gastropods in Eastern Austria

Canine and feline cardiorespiratory parasites are of utmost relevance in veterinary medicine. Key epizootiological information on major pet metastrongyloids, i.e., Angiostrongylus vasorum and Crenosoma vulpis infecting dogs, and Aelurostrongylus abstrusus and Troglostrongylus brevior infecting cats, is missing from Austria. This study investigated their occurrence in 1320 gastropods collected in the Austrian provinces of Styria, Burgenland, Lower Austria, and in metropolitan Vienna. Metastrongyloid larvae were microscopically detected in 25 samples, and sequence analysis confirmed the presence of metastrongyloids in nine samples, i.e., A. vasorum in one slug (Arion vulgaris) (0.07%), C. vulpis in five slugs (one Limax maximus and four A. vulgaris) (0.4%), A. abstrusus in two A. vulgaris (0.17%), and the hedgehog lungworm Crenosoma striatum was detected in one A. vulgaris. The present study confirms the enzooticity of major cardiorespiratory nematodes in Austria and that canine and feline populations are at risk of infection

Estimating Ixodes ricinus densities on the landscape scale

Background: The study describes the estimation of the spatial distribution of questing nymphal tick densities by investigating Ixodes ricinus in Southwest Germany as an example. The production of high-resolution maps of questing tick densities is an important key to quantify the risk of tick-borne diseases. Previous I. ricinus maps were based on quantitative as well as semi-quantitative categorisations of the tick density observed at study sites with different vegetation types or indices, all compiled on local scales. Here, a quantitative approach on the landscape scale is introduced. Methods: During 2 years, 2013 and 2014, host-seeking ticks were collected each month at 25 sampling sites by flagging an area of 100 square meters. All tick stages were identified to species level to select nymphal ticks of I. ricinus, which were used to develop and calibrate Poisson regression models. The environmental variables height above sea level, temperature, relative humidity, saturation deficit and land cover classification were used as explanatory variables. Results: The number of flagged nymphal tick densities range from zero (mountain site) to more than 1,000 nymphs/100 m$^{2}$. Calibrating the Poisson regression models with these nymphal densities results in an explained variance of 72 % and a prediction error of 110 nymphs/100 m$^{2}$ in 2013. Generally, nymphal densities (maximum 374 nymphs/100 m$^{2}$), explained variance (46 %) and prediction error (61 nymphs/100 m2) were lower in 2014. The models were used to compile high-resolution maps with 0.5 km$^{2}$ grid size for the study region of the German federal state Baden-Württemberg. The accuracy of the mapped tick densities was investigated by leave-one-out cross-validation resulting in root-mean-square-errors of 227 nymphs/100 m$^{2}$ for 2013 and 104 nymphs/100 m$^{2}$ for 2014. Conclusions: The methodology introduced here may be applied to further tick species or extended to other study regions. Finally, the study is a first step towards the spatial estimation of tick-borne diseases in Central Europe

Synthesis, characterization and optoelectronic properties of iridium complexes bearing nonconjugated six-membered chelating ligands

The authors thank the EPSRC UK National Mass Spectrometry Facility at Swansea University for analytical services. C.H. acknowledges the Région Bretagne, France for funding. D.J. acknowledges the European Research Council and the Région des Pays de la Loire for financial support in the framework of a Starting Grant (Marches - 278845) and the LUMOMAT RFI project, respectively. This research used resources of 1) the GENCI-CINES/IDRIS, 2) the CCIPL (Centre de Calcul Intensif des Pays de Loire), 3) a local Troy cluster. E.Z.-C. acknowledges the University of St. Andrews and EPSRC (EP/M02105X/1) for financial support.We report the synthesis, characterization and the optoelectronic properties of a series of four new luminescent iridium(III) complexes 1-4 , of the form [Ir(C^N)2(N^N)]PF6 [where C^N is the nonconjugated benzylpyridinato (bnpy) and N^N is a neutral diimine ancillary ligand] with the goal of investigating the impact of the methylene spacer between the coordination moieties of the C^N ligand on the optoelectronic properties of the complexes. The crystal structures of 1-3 illustrate two possible orientations of the methylene unit of the bnpy ligand. The formation of these two separate conformers is a result of the conformational flexibility of the bnpy ligand. In complexes 3 and 4 , mixtures of the two conformers were observed by 1H-NMR spectroscopy in CDCl3 at room temperature, whereas only a single conformer is detected for 1 and 2 . Detailed DFT calculations corroborate ROESY experiments, accounting for the presence and relative populations of the two conformers. The optoelectronic properties of all four complexes, rationalized by the theoretical study, demonstrate that the interruption of conjugation in the C^N ligands results in a reduced electrochemical gap but similar triplet state energies and lower photoluminescence quantum yields compared to the reference complexes R1-R4 . Depending on the nature of the N^N ligand, we observe (1) marked variations of the ratio of the conformers at ambient temperature and (2) phosphorescence ranging from yellow to red.PostprintPeer reviewe

Chemical genetics strategies for identification of molecular targets

Chemical genetics is an emerging field that can be used to study the interactions of chemical compounds, including natural products, with proteins. Usually, the identification of molecular targets is the starting point for studying a drug’s mechanism of action and this has been a crucial step in understanding many biological processes. While a great variety of target identification methods have been developed over the last several years, there are still many bioactive compounds whose target proteins have not yet been revealed because no routine protocols can be adopted. This review contains information concerning the most relevant principles of chemical genetics with special emphasis on the different genomic and proteomic approaches used in forward chemical genetics to identify the molecular targets of the bioactive compounds, the advantages and disadvantages of each and a detailed list of successful examples of molecular targets identified with these approaches

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C