Upcoming surveys will map the growth of large-scale structure with unprecented precision, improving our understanding of the dark sector of the Universe. Unfortunately, much of the cosmological ...information is encoded on small scales, where the clustering of dark matter and the effects of astrophysical feedback processes are not fully understood. This can bias the estimates of cosmological parameters, which we study here for a joint analysis of mock
Euclid
cosmic shear and
Planck
cosmic microwave background data. We use different implementations for the modelling of the signal on small scales and find that they result in significantly different predictions. Moreover, the different non-linear corrections lead to biased parameter estimates, especially when the analysis is extended into the highly non-linear regime, with the Hubble constant,
H
0
, and the clustering amplitude,
σ
8
, affected the most. Improvements in the modelling of non-linear scales will therefore be needed if we are to resolve the current tension with more and better data. For a given prescription for the non-linear power spectrum, using different corrections for baryon physics does not significantly impact the precision of
Euclid
, but neglecting these correction does lead to large biases in the cosmological parameters. In order to extract precise and unbiased constraints on cosmological parameters from
Euclid
cosmic shear data, it is therefore essential to improve the accuracy of the recipes that account for non-linear structure formation, as well as the modelling of the impact of astrophysical processes that redistribute the baryons.
Noted theologian Samuel Escobar offers a magisterial survey and study of Christology in Latin America. Presented for the first time in English, this rich resource starts with the first Spanish ...influence and moves through popular religiosity and liberationist themes in Catholic and Protestant thought of the twentieth and twenty-first centuries, culminating in an important description of the work of the Latin American Theological Fraternity.
Different alternatives for the effective integration of desalination technologies in the cooling of concentrating solar power (CSP) plants in the Mediterranean area are discussed and evaluated. Two ...cases are considered where a low temperature multi-effect distillation (LT-MED) plant is integrated into a CSP plant replacing the condenser of the power cycle. In one case, a LT-MED plant is fed by steam at the outlet of the turbine expanded to 70 °C. In the other case a LT-MED is fed by the steam obtained from a thermal vapour compressor (TVC) which uses the exhaust steam of the CSP plant (at 37 °C, 0.063 bar) together with some from the high pressure turbine extraction (17 bar). The two cases are compared with that of a reverse osmosis (RO) unit powered by the electricity produced by the CSP plant. In this case, two different wet cooling technologies, once-through and evaporative water cooling, and a dry air cooling are considered for the CSP plant. Thermodynamic simulations are presented for all cases, together with an economic analysis.
► The combination of desalination technologies into CSP plants is evaluated. ► Integration of LT-MED into a CSP plant is more efficient than a LT-MED-TVC. ► Connecting a RO unit to a CSP plant results more efficient than CSP + MED coupling. ► Evaporative cooling is the most efficient and economical for electricity production. ► Electricity costs for once-through and dry cooling are higher than CSP + MED coupling.
〈 We report on an infant with Opitz trigonocephaly C syndrome (OTCS), who also had manifestations of ciliopathy, including short ribs (non‐asphyxiating), trident acetabular roofs, postaxial ...polydactyly cone‐shaped epiphyses, and dysplasia of the renal, hepatic and pancreatic tissues. To investigate the molecular cause, we used an exome sequencing strategy followed by Sanger sequencing. Two rare variants, both predicted to result in loss of functional protein, were identified in the IFT140 gene; a substitution at the splice donor site of exon 24 (c.723 + 1 G > T) and a 17 bp deletion, impacting the first coding exon (c.‐11_6del). The variants were confirmed as being biallelic using Sanger sequencing, showing that the splice variant was inherited from the propositus mother and the deletion from the father. To date, Mainzer–Saldino syndrome, Jeune syndrome, and a form of nonsyndromic retinal dystrophy, have been identified as ciliopathies caused by IFT140 mutations. We provide the first description of an OTCS phenotype that appears to result from IFT140 mutations. The presentation of this patient is consistent with previous reports showing that OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy.
Background
Although patients with melanoma of unknown primary (MUP) have a better prognosis than similar-staged melanoma patients with known primary, the occurrence of brain metastases (BM) entails a ...serious complication. This study provides an overview of the incidence, treatment patterns, and overall survival (OS) of adult patients with BM-MUP in the Netherlands.
Methods
BM-MUP cases were retrieved from the Netherlands Cancer Registry. Patient, disease and treatment-related characteristics were summarised using descriptive statistics. Overall survival (OS) was calculated by the Kaplan–Meier method, and the impact of prognostic factors on OS was assessed using Cox proportional hazard regression analyses.
Results
Among 1779 MUP patients, 450 were identified as BM-MUP (25.3%). Of these patients, 381 (84.7%) presented with BM along with other metastases, while 69 (15.3%) had BM only. BM-MUP patients were predominantly male (68.2%), and had a median age of 64 years at diagnosis (interquartile range 54–71 years). Over time, the proportion of BM along other metastatic sites increased, and the occurrence of BM decreased (p = 0.01). 1-Year OS improved for the total population, from 30.0% (95% confidence interval (CI): 19.8–40.9%) in 2011–2012 to 43.6% (95%CI: 34.5–52.3%) in 2019–2020, and median OS more than doubled from 4.2 months (95%CI: 3.3–6.2 months) to 9.8 months (95%CI: 7.0–13.2 months). Patient’s age, localisation of BM, presence of synchronous liver metastasis and treatment were identified as independent predictors of OS.
Conclusion
Notwithstanding the progress made in OS for patients with BM-MUP in the past decade, their overall prognosis remains poor, and further efforts are needed to improve outcomes.
There is much interest in understanding the influence of the immune system on bone healing, including a number of reports suggesting a beneficial effect of FK506 (tacrolimus) in this regard. The ...influence of FK506 in a rat, femoral, critical size defect was examined using locally implanted, recombinant, human (rh) BMP-2 and adenovirally-transduced, autologous, adipose-derived mesenchymal stromal cells (AD-MSCs) expressing BMP-2. FK506 was delivered systemically using an implanted osmotic pump. Empty defects and those implanted with unmodified AD-MSCs did not heal in the presence or absence of FK506. Defects treated with rhBMP-2 healed with a large callus containing thin cortices and wispy trabeculae; this, too, was unaffected by FK506. A third of defects implanted with adenovirally-transduced AD-MSCs healed, but this improved to 100 % in the presence of FK506. New bone formed in response to BMP-2 synthesised endogenously by the genetically modified cells had a slimmer callus than those healed by rhBMP-2, with improved cortication and advanced reconstitution of marrow. These results suggest that FK506 may have had little effect on the intrinsic biology of bone healing, but improved healing in response to adenovirally-transduced cells by inhibiting immune responses to the first-generation adenovirus used here. Because the genetically modified cells produced bone of higher quality at far lower doses of BMP-2, this approach should be explored in subsequent research.
The aim of the present study was to define the role of Trx and Grx on metabolic thiol redox regulation and identify their protein and metabolite targets. The hepatocarcinoma-derived HepG2 cell line ...under both normal and oxidative/nitrosative conditions by overexpression of NO synthase (NOS3) was used as experimental model. Grx1 or Trx1 silencing caused conspicuous changes in the redox proteome reflected by significant changes in the reduced/oxidized ratios of specific Cys's including several glycolytic enzymes. Cys
of peroxiredoxin-6 (PRDX6) and Cys
of phosphoglycerate mutase-1 (PGAM1), that are known to be involved in progression of tumor growth, are reported here for the first time as specific targets of Grx1. A group of proteins increased their Cys
/Cys
ratio upon Trx1 and/or Grx1 silencing, including caspase-3 Cys
, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Cys
and triose-phosphate isomerase (TPI) Cys
likely by enhancement of NOS3 auto-oxidation. The activities of several glycolytic enzymes were also significantly affected. Glycolysis metabolic flux increased upon Trx1 silencing, whereas silencing of Grx1 had the opposite effect. Diversion of metabolic fluxes toward synthesis of fatty acids and phospholipids was observed in siRNA-Grx1 treated cells, while siRNA-Trx1 treated cells showed elevated levels of various sphingomyelins and ceramides and signs of increased protein degradation. Glutathione synthesis was stimulated by both treatments. These data indicate that Trx and Grx have both, common and specific protein Cys redox targets and that down regulation of either redoxin has markedly different metabolic outcomes. They reflect the delicate sensitivity of redox equilibrium to changes in any of the elements involved and the difficulty of forecasting metabolic responses to redox environmental changes.
•We proposed and tested an irrigation scheduling approach for olive orchards under regulated deficit irrigation.•Our approach is based on leaf turgor pressure related measurements made with ZIM ...probes.•We show evidence of our approach being suitable for olive trees of different age growing under a wide range of water conditions.•A comparison with the crop coefficient approach shows that our approach led to greater water savings for the same crop performance.•Our approach is suitable for commercial orchards and users with low training.
Regulated deficit irrigation (RDI) has been proposed as one of the most promising irrigation strategies for hedgerow fruit orchards with high plant densities. Scheduling a RDI strategy, however, is highly demanding, since the targeted water savings must be achieved at the same time that episodes of excessive water stress are avoided when the crop is most sensitive to drought. Here we tested an approach to schedule a RDI strategy supplying 45% of the crop irrigation needs, specially designed for hedgerow olive orchards. Our approach is based on the use of a water stress indicator derived from the shape of the daily curves recorded with ZIM sensors, which are related to the leaf turgor pressure. We worked in a mature, fully productive ‘Arbequina’ olive orchard with 1667 trees ha−1, under both a daily irrigated (FI) treatment and the mentioned RDI strategy. We found that the relation between the shape of the curves and the tree water stress levels holds for olive trees of different age under a wide range of growing conditions. We were able to schedule irrigation just from the visual analysis of the curves derived from the ZIM outputs, without any further data processing. A comparison with the crop coefficient approach showed that, with our approach, we achieved greater water savings without affecting neither the trees water status nor the crop performance. Still, further studies are required to confirm whether empirical aspects of our approach are limiting and, if so, to derive suitable alternatives.
Purpose
Cancers of an unknown primary site (CUPs) have a dismal prognosis, and the situation is even worse for CUPs patients with brain metastases (BM-CUPs). This study aims to give better insight ...into the occurrence and survival of BM-CUPs patients.
Methods
Cases were selected from the Netherlands Cancer Registry (1,430 BM-CUPs/17,140 CUPs). Baseline characteristics between CUPs patients with and without BM were tested using chi-square tests and Mann–Whitney U tests. Patients’ overall survival (OS) times were estimated by the Kaplan–Meier method and prognostic factors on OS was assessed using Cox proportional hazards regression analyses.
Results
The proportion of BM-CUPs patients among CUPs increased from 8% in 2009–2010 to 10% in 2017–2018 (
p
< 0.001). Most patients presented with multiple brain lesions (53%). Survival of BM-CUPs improved over time: one-year OS increased from 10% for patients diagnosed in 2009–2010 to 17% (2017- 2018) (
p
< 0.01), and median survival times increased from 1.8 months to 2.2 months. Independent predictors of poor survival were multiple (HR 1.25;
p
< 0.01) or unknown (HR 1.48;
p
< 0.01) locations of BM, unknown/poorly/undifferentiated carcinoma histology (HR 1.53;
p
< 0.01), or clinical symptoms of BM (HR 1.74;
p
< 0.01), accompanying liver metastasis (HR 1.43;
p
< 0.01) and more than one metastatic site outside the brain compared to none (HR 1.52;
p
< 0.01).
Conclusion
The incidence of patients with BM-CUPs is steadily increasing over time and overall prognosis remains dismal. Our results, however, show distinct patient subgroups that exhibit comparatively better outcomes, and more predictors may likely still be identified.
PDF
