Geometric-Phase-Effect Tunnel-Splitting Oscillations in Single-Molecule Magnets with Fourth-Order Anisotropy Induced by Orthorhombic Distortion

We analyze the interference between tunneling paths that occurs for a spin system with both fourth-order and second-order transverse anisotropy. Using an instanton approach, we find that as the strength of the second-order transverse anisotropy is increased, the tunnel splitting is modulated, with zeros occurring periodically. This effect results from the interference of four tunneling paths connecting easy-axis spin orientations and occurs in the absence of any magnetic field.Comment: 6 pages, 5 eps figures. Version published in EPL. Expanded from v1: Appendix added, references added, 1 figure added, others modified cosmeticall

Dietary intakes of women with Type 1 diabetes before and during pregnancy: A pre‐specified secondary subgroup analysis among CONCEPTT participants

Aim To describe the dietary intakes of women with Type 1 diabetes before and during pregnancy. Methods This was a pre‐specified subgroup analysis of CONCEPTT involving 63 women planning pregnancy and 93 pregnant women from 14 sites in England, Scotland and Ireland. Two hundred and forty‐six 3‐day food diaries (104 planning pregnancy, 142 pregnant) were matched to data source and food reference codes, and analysed using dietary software. Participants were informed that food diaries would be de‐identified and used only for research purposes. Results Mean (sd) daily energy intake was 1588 (346) kcal and 1673 (384) kcal in women planning pregnancy and pregnant women respectively. Total carbohydrate intake was consistent with dietary guideline recommendations [180 (52) g planning pregnancy, 198 (54) g pregnant], but non‐recommended sources (e.g. sugars, preserves, confectionery, biscuits, cakes) contributed to 46% of total daily carbohydrate intake. Fat consumption exceeded guideline recommendations [70 (21) g planning pregnancy, 72 (21) g pregnant]. Fibre [15.5 (5.3) g planning pregnancy, 15.4 (5.1) g pregnant], fruit and vegetable intakes [3.5 (2.2) and 3.1 (1.8) serves/day] were inadequate. Twelve women planning pregnancy (19%) and 24 pregnant women (26%) did not meet micronutrient requirements. Conclusions The diets of pregnant women from England, Scotland and Ireland are characterized by high fat, low fibre and poor‐quality carbohydrate intakes. Fruit and vegetable consumption is inadequate, with one in four women at risk of micronutrient deficiencies. Further research is needed to optimize maternal nutrition for glycaemic control and for maternal and offspring health

CHARMM36m: An improved force field for folded and intrinsically disordered proteins.

The all-atom additive CHARMM36 protein force field is widely used in molecular modeling and simulations. We present its refinement, CHARMM36m (http://mackerell.umaryland.edu/charmm_ff.shtml), with improved accuracy in generating polypeptide backbone conformational ensembles for intrinsically disordered peptides and proteins

Reply: KRAS status analysis and anti-EGFR therapies: is comprehensiveness a biologist's fancy or a clinical necessity?

We thank Dr Lopez-Crapez et al 2010 to have taken cue fro

Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial

Aims: To examine the relationship between maternal glycaemic control and risk of neonatal hypoglycaemia using conventional and continuous glucose monitoring (CGM) metrics in the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT) participants. Methods: A secondary analysis of CONCEPTT involving 225 pregnant women and their liveborn infants. Antenatal glycaemia was assessed at 12, 24 and 34 weeks gestation. Intrapartum glycaemia was assessed by CGM measures 24 hours prior to delivery. The primary outcome was neonatal hypoglycaemia defined as glucose concentration 97.7th centile (63.2% vs 33.9%; p<0.0001) and skinfold thickness (p≤0.02). Intrapartum CGM was available for 33 participants, with no differences between mothers of neonates with and without hypoglycaemia. Conclusions: Modest increments in CGM time-in-target (5-7% increase) during the second and third trimesters are associated with reduced risk for neonatal hypoglycaemia. While more intrapartum CGM data are needed, the higher birthweight and skinfold measures associated with neonatal hypoglycaemia, suggest that risk is related to fetal hyperinsulinemia preceding the immediate intrapartum period

Evaluation of the LSA-SAF gross primary production product derived from SEVIRI/MSG data (MGPP)

The objective of this study is to describe a completely new 10-day gross primary production (GPP) product (MGPP LSA-411) based on data from the geostationary SEVIRI/MSG satellite within the LSA SAF (Land Surface Analysis SAF) as part of the SAF (Satellite Application Facility) network of EUMETSAT. The methodology relies on the Monteith approach. It considers that GPP is proportional to the absorbed photosynthetically active radiation APAR and the proportionality factor is known as the light use efficiency ε. A parameterization of this factor is proposed as the product of a εmax, corresponding to the canopy functioning under optimal conditions, and a coefficient quantifying the reduction of photosynthesis as a consequence of water stress. A three years data record (2015–2017) was used in an assessment against site-level eddy covariance (EC) tower GPP estimates and against other Earth Observation (EO) based GPP products. The site-level comparison indicated that the MGPP product performed better than the other EO based GPP products with 48% of the observations being below the optimal accuracy (absolute error < 1.0 g m−2 day−1) and 75% of these data being below the user requirement threshold (absolute error < 3.0 g m−2 day−1). The largest discrepancies between the MGPP product and the other GPP products were found for forests whereas small differences were observed for the other land cover types. The integration of this GPP product with the ensemble of LSA-SAF MSG products is conducive to meet user needs for a better understanding of ecosystem processes and for improved understanding of anthropogenic impact on ecosystem services.The objective of this study is to describe a completely new 10-day gross primary production (GPP) product (MGPP LSA-411) based on data from the geostationary SEVIRI/MSG satellite within the LSA SAF (Land Surface Analysis SAF) as part of the SAF (Satellite Application Facility) network of EUMETSAT. The methodology relies on the Monteith approach. It considers that GPP is proportional to the absorbed photosynthetically active radiation APAR and the proportionality factor is known as the light use efficiency epsilon. A parameterization of this factor is proposed as the product of a epsilon(max), corresponding to the canopy functioning under optimal conditions, and a coefficient quantifying the reduction of photosynthesis as a consequence of water stress. A three years data record (2015-2017) was used in an assessment against site-level eddy covariance (EC) tower GPP estimates and against other Earth Observation (EO) based GPP products. The site-level comparison indicated that the MGPP product performed better than the other EO based GPP products with 48% of the observations being below the optimal accuracy (absolute error <1.0 g m(-2) day(-1)) and 75% of these data being below the user requirement threshold (absolute error <3.0 g m(-2) day(-1)). The largest discrepancies between the MGPP product and the other GPP products were found for forests whereas small differences were observed for the other land cover types. The integration of this GPP product with the ensemble of LSA-SAF MSG products is conducive to meet user needs for a better understanding of ecosystem processes and for improved understanding of anthropogenic impact on ecosystem services.Peer reviewe

Attraction between DNA molecules mediated by multivalent ions

The effective force between two parallel DNA molecules is calculated as a function of their mutual separation for different valencies of counter- and salt ions and different salt concentrations. Computer simulations of the primitive model are used and the shape of the DNA molecules is accurately modelled using different geometrical shapes. We find that multivalent ions induce a significant attraction between the DNA molecules whose strength can be tuned by the averaged valency of the ions. The physical origin of the attraction is traced back either to electrostatics or to entropic contributions. For multivalent counter- and monovalent salt ions, we find a salt-induced stabilization effect: the force is first attractive but gets repulsive for increasing salt concentration. Furthermore, we show that the multivalent-ion-induced attraction does not necessarily correlate with DNA overcharging.Comment: 51 pages and 13 figure

Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer

An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the analysis of why immunotherapy is ineffective in this human disease. Despite finding that PDA-bearing mice had cancer cell-specific CD8+ T cells, the mice, like human patients with PDA, did not respond to two immunological checkpoint antagonists that promote the function of T cells: anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) and α-programmed cell death 1 ligand 1 (α-PD-L1). Immune control of PDA growth was achieved, however, by depleting carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). The depletion of the FAP+ stromal cell also uncovered the antitumor effects of α-CTLA-4 and α-PD-L1, indicating that its immune suppressive activity accounts for the failure of these T-cell checkpoint antagonists. Three findings suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) explained the overriding immunosuppression by the FAP+ cell: T cells were absent from regions of the tumor containing cancer cells, cancer cells were coated with the chemokine, CXCL12, and the FAP+ CAF was the principal source of CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor chemokine (C-X-C motif) receptor 4 inhibitor, induced rapid T-cell accumulation among cancer cells and acted synergistically with α-PD-L1 to greatly diminish cancer cells, which were identified by their loss of heterozygosity of Trp53 gene. The residual tumor was composed only of premalignant epithelial cells and in flammatory cells. Thus, a single protein, CXCL12, from a single stromal cell type, the FAP+ CAF, may direct tumor immune evasion in a model of human PDA