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Quantification of land surface-atmosphere fluxes of carbon dioxide (CO2) fluxes and their trends and uncertainties is essential for monitoring progress of the EU27+UK bloc as it strives to meet ambitious targets determined by both international agreements and internal regulation. This study provides a consolidated synthesis of fossil sources (CO2 fossil) and natural sources and sinks over land (CO2 land) using bottom-up (BU) and top-down (TD) approaches for the European Union and United Kingdom (EU27+UK), updating earlier syntheses (Petrescu et al., 2020, 2021b). Given the wide scope of the work and the variety of approaches involved, this study aims to answer essential questions identified in the previous syntheses and understand the differences between datasets, particularly for poorly characterized fluxes from managed ecosystems. The work integrates updated emission inventory data, process-based model results, data-driven sectoral model results, and inverse modeling estimates, extending the previous period 1990–2018 to the year 2020 to the extent possible. BU and TD products are compared with European National Greenhouse Gas Inventories (NGHGIs) reported by Parties including the year 2019 under the United Nations Framework Convention on Climate Change (UNFCCC). The uncertainties of the EU27+UK NGHGI were evaluated using the standard deviation reported by the EU Member States following the guidelines of the Intergovernmental Panel on Climate Change (IPCC) and harmonized by gap-filling procedures. Variation in estimates produced with other methods, such as atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), originate from within-model uncertainty related to parameterization as well as structural differences between models. By comparing NGHGIs with other approaches, key sources of differences between estimates arise primarily in activities. System boundaries and emission categories create differences in CO2 fossil datasets, while different land use definitions for reporting emissions from Land Use, Land Use Change and Forestry (LULUCF) activities result in differences for CO2 land. The latter has important consequences for atmospheric inversions, leading to inversions reporting stronger sinks in vegetation and soils than are reported by the NGHGI. For CO2 fossil emissions, after harmonizing estimates based on common activities and selecting the most recent year available for all datasets, the UNFCCC NGHGI for the EU27+UK accounts for 3392 ± 49 Tg CO2 yr-1 (926 ± 13 Tg C yr-1), while eight other BU sources report a mean value of 3340 [3238,3401] [25th,75th percentile] Tg CO2 yr-1 (948 [937,961] Tg C yr-1). The sole top-down inversion of fossil emissions currently available accounts for 3800 Tg CO2 yr-1 (1038 Tg C yr-1), a value close to that of the NGHGI, but for which uncertainty estimates are not yet available. For the net CO2 land fluxes, during the most recent five-year period including the NGHGI estimates, the NGHGI accounted for -91 ± 32 Tg C yr-1 while six other BU approaches reported a mean sink of -62 [-117,-49] Tg C yr-1 and a 15-member ensemble of dynamic global vegetation models (DGVMs) reported -69 [-152,-5] Tg C yr-1. The five-year mean of three TD regional ensembles combined with one non-ensemble inversion of -73 Tg C yr-1 has a slightly smaller spread (0th–100th percentile of [-135,45] Tg C yr-1), and was calculated after removing land-atmosphere CO2 fluxes caused by lateral transport of carbon (crops, wood trade and inland waters) resulting in increased agreement with the the NGHGI and bottom-up approaches. Results at the sub-sector level (Forestland, Cropland, Grassland) show generally good agreement between the NGHGI and sub-sector-specific models, but results for a DGVM are mixed. Overall, for both CO2 fossil and net CO2 land fluxes, we find current independent approaches are consistent with the NGHGI at the scale of the EU27+UK. We conclude that CO2 emissions from fossil sources have decreased over the past 30 years in the EU27+UK, while large uncertainties on net uptake of CO2 by the land surface prevent trend identification. In addition, a gap on the order of 1000 Tg C yr-1 between CO2 fossil emissions and net CO2 uptake by the land exists regardless of the type of approach (NGHGI, TD, BU), falling well outside all available estimates of uncertainties. However, uncertainties in top-down approaches to estimate CO2 fossil emissions remain uncharacterized and are likely substantial. The data used to plot the figures are available at https://doi.org/10.5281/zenodo.7365863.

We hypothesized that feeding 25-hydroxyvitamin D3 [25-(OH)D3] during lactation and prepartum in conjunction with negative dietary cation-anion difference diets would improve milk production, increase the probability of pregnancy, and reduce the incidence of postcalving diseases. Cows from 4 dairies with prepartum transition diets negative in dietary cation-anion difference were used in 2 randomized cohort experiments. In Experiment 1 (Exp. 1), cows were assigned to control [CON; n = 645; no 25-(OH)D3] or treatment [TRT; n = 537; 2 mg/d of 25-(OH)D3 from ∼21 d prepartum to parturition and 1 mg/d in lactation] groups at ∼21 d prepartum. Cows were monitored for weekly milk yield, milk composition every 60 d, and health and reproductive measures. In Experiment 2 (Exp. 2), cows (n = 2,064; median 147 d in milk) were assigned to 4 groups and monitored for the same measures as in Exp. 1 to the end of that lactation (L1), the subsequent transition (∼21 d prepartum to parturition), and the next lactation (L2). Groups were as follows, with the amount of 25-(OH)D3 fed (mg/d) indicated in parentheses for L1, transition, and L2, respectively: (A) control-control (CON-CON; 0-0-0), (B) treatment-treatment (TRT-TRT; 1-2-1), (C) control-treatment (CON-TRT; 0-2-1), and (D) treatment-control (TRT-CON; 1-0-0). For L1, a total of 1,032 cows entered the control groups A or C and a total of 1,032 cows in groups B or D. The number of cows in groups A to D that entered L2 was 521, 523, 273, and 248, respectively. Blood calcium, phosphorus, and 25-(OH)D3 concentrations were measured from 17 cows/group at 5 times. In Exp. 1, TRT cows had 0.2 lower log somatic cell count than CON cows (4.21 ± 0.045 vs. 4.01 ± 0.050, respectively) and multiparous TRT cows had 41 ± 23% higher probability of pregnancy/day than multiparous CON cows, resulting in a 22-d median decrease in time to pregnancy. Primiparous TRT cows had 1.67 ± 0.40 times greater odds of mastitis/day than primiparous CON cows. In Exp. 2 TRT-TRT cows had between 16 and 29% lower probability to be bred/day than other groups. Multiparous CON-CON and TRT-CON cows had 20 ± 8% and 30 ± 17% greater probability of pregnancy, respectively, than multiparous TRT-TRT cows. Serum calcium concentrations were not affected by group, but phosphorus and 25-(OH)D3 concentrations were highest in the TRT-TRT cows. The study provides further insights into the use of 25(OH)D3 in transition and lactation.

This review examines the role of nutritional strategies to improve lifetime performance in ruminants. Strategies to increase ruminants' productive longevity by means of nutritional interventions provide the opportunity not only to increase their lifetime performances and their welfare, but also to decrease their environmental impact. This paper will also address how such nutritional interventions can increase herd efficiency and farm profitability. The key competencies reviewed in this article are redox balance, skeletal development and health, nutrient utilization and sustainability, which includes rearing ruminants without antibiotics and methane mitigation. While the relationships between these areas are extremely complex, a multidisciplinary approach is needed to develop nutritional strategies that would allow ruminants to become more resilient to the environmental and physiological challenges that they will have to endure during their productive career. As the demand of ruminant products from the rapidly growing human world population is ever-increasing, the aim of this review is to present animal and veterinary scientists as well as nutritionists a multidisciplinary approach towards a sustainable ruminant production, while improving their nutrient utilization, health and welfare, and mitigation of their carbon footprint at the same time.

The objective of this study was to evaluate the safety of 25-OH-D3 addition to the diet of bovine calves. The investigation was conducted as a feeding experiment for 90 days. 40 calves were allotted to four groups: T1 - control group which received 30 IU vitamin D3/kg feed, and three experimental groups, which received 25-OH-D3 in increasing dosages: T2 - 25-OH-D3 at 1.7 μg/kg, T3 - 25-OH-D3 at 5.1 μg/kg and T4 - 25-OH-D3 at 8.5 μg/kg. All calves in the four groups gained weight continually: no growth depression was observed. No adverse effects of 25- OH-D3 were observed for any of the hematology and serum chemistry parameters measured or during the routine clinical examinations. Plasma 25-OH-D3 concentration was higher (p

The objective of this study was to evaluate the safety of 25-OH-D

Vanadium oxides were hydrothermally grown on opal glass substrates at 95 °C. The deposition period was observed to affect the structure of the oxides and the voids filling of the opal surfaces. V6O13 grown on opal for 50 h presented satisfactory electrochemical performance and electrochromic response with a contrast ratio of 2. The specific capacitance of this composite reached a value of 192 F g−1, which was stable up to 500 continuous charge intercalation/deintercalation scans. The importance of achieving crystalline V6O13 and high opal surface coverage towards the enhancement of the electrochemical properties is presented.

Presenilins are components of the gamma-secretase protein complex that mediates intramembranous cleavage of betaAPP and Notch proteins. A C. elegans genetic screen revealed two genes, aph-1 and pen-2, encoding multipass transmembrane proteins, that interact strongly with sel-12/presenilin and aph-2/nicastrin. Human aph-1 and pen-2 partially rescue the C. elegans mutant phenotypes, demonstrating conserved functions. The human genes must be provided together to rescue the mutant phenotypes, and the inclusion of presenilin-1 improves rescue, suggesting that they interact closely with each other and with presenilin. RNAi-mediated inactivation of aph-1, pen-2, or nicastrin in cultured Drosophila cells reduces gamma-secretase cleavage of betaAPP and Notch substrates and reduces the levels of processed presenilin. aph-1 and pen-2, like nicastrin, are required for the activity and accumulation of gamma-secretase.

A polymer waveguide is fabricated on top of an inverted opal photonic crystal structure to demonstrate an air clad functioning waveguide for the first time to the best of our knowledge. An optically thick layer with a refractive index (n = 1.01) close to air was realized on a silicon wafer by first co-forming a self-assembled 3-D photonic crystal structure with PMMA spheres and a silica backbone. Following the fabrication of polyimide waveguides on this surface by micro-molding, the PMMA spheres were removed to leave behind an inverted opal structure underneath the waveguides with refractive index close to air. Broadband, polarization independent fundamental mode optical waveguiding from 1300 nm to 1600 nm wavelengths was obtained. This original approach overcomes some of the drawbacks associated with conventional polymer waveguides and can be the basis for a range of optical interconnection and sensing applications.

The articles discussed in working group 3 dealt with specific aspects of clinical research. In this context, the literature reporting on survival and complication rates of implant-supported or implant-tooth supported restorations in longitudinal studies of at least 5 years were discussed. The second aspect dealt with the evaluation of aesthetic outcomes in clinical studies and the related index systems available. Finally, the third aspect discussed dealt with patient-reported outcome measures (PROMs). A detailed appraisal of the available methodology was presented.

BackgroundMany proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition.Methodology/principal findingsTo address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines.Conclusions/significanceOur analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations.

The US Army Research Development and Engineering Command (RDECOM), Natick Soldier Research, Development and Engineering Center (NSRDEC) have teamed with all Department of Defense (DoD) services and organizations with interest in programs and investments in Joint Precision Airdrop System (JPADS) technology and systems. These organizations include: Office of the Secretary of Defense (OSD) to include: Joint Staff (JS); Acquisition, Logistics and Technology (ALT); Director of Defense Research and Engineering (DDR&E), Advanced Systems and Concepts (AS&C), Joint Forces Command (JFCOM), US Air Force Air Mobility Command (USAF AMC), USAF Air Mobility Warfare Center (AMWC), the US Army Product Manager Force Sustainment Systems (PM-FSS), US Marine Corps (USMC), US Transportation Command (TRANSCOM), US Special Operations Command (USSOCOM) and many other government agencies and contractors to plan and execute JPADS programs. This paper will provide an overview of some of the DoD JPADS programs to include: Results of the JPADS Advanced Concept Technology Demonstration (ACTD), recent Joint Military Utility Assessment (JMUA) # 2, The US Army Formal Program of Record (PoR) for the JPADS Extra Light (700-2200lb capability), Rapid Combat Fielding (RCFs) Initiatives for JPADS 2,200lb systems and early results and lessons learned from Combat Operations, the recently started Wireless Gate Release System (WGRS), and related precision airdrop activities within NATO.

Introduction: XL184 (BMS-907351) produces balanced pharmacodynamic inhibition of MET, VEGFR2, and RET, as well as robust antiangiogenic and anti-tumor effects with oral dosing in preclinical models. Based on the encouraging preclinical activity, XL184 is being studied in multiple Phase 1 to 3 clinical studies of various tumor types. Methods: Biomarker studies from a Phase 1 trial (XL184-001, n=85) of XL184 in solid tumors enriched for a medullary thyroid carcinoma (MTC) population and from a Phase 2 trial (XL184-201, n=46) in recurrent or progressive glioblastoma multiforme (GBM) are reported here. Plasma samples were analyzed for pharmacodynamic, on-target effects of XL184 and biomarkers known to change in response to anti-angiogenic treatment. Surrogate tissue sections of skin or hair were analyzed for biomarkers of ontarget activity of XL184 using immunofluorescence. Genomic DNA isolated from archival tumor and/or fresh blood samples was analyzed for alterations in genes relevant to either GBM or MTC and/or the target profile of XL184, such as RET, MET, KIT, PTEN, and MGMT. Plasma and genotypic biomarkers were investigated for potential correlation with clinical benefit (durable stable disease or partial response). Results: Plasma biomarker data from patients (pts) in both groups receiving 175 mg oral XL184 once daily demonstrated statistically significant changes from baseline in sVEGFR2, PlGF, VEGF-A, EPO, and sKIT levels (XL184-001 n=28; XL184-201 n=22; all p Conclusion: Biomarker analyses in plasma and surrogate tissues confirm pharmacodynamic activity of XL184. Changes in plasma HGF may be a predictive biomarker of clinical benefit and will be further evaluated. The clinical benefit rates produced in GBM and MTC coupled with clear evidence of XL184 on-target activity, independent of tumor genotypes, suggests that the clinical benefits produced by this compound may be a result of its multitargeted profile which includes inhibition of MET, VEGFR2 and RET activity. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B269.

WOULD you or any of your readers kindly tell me where I may find an account of any of the latest methods of determining the back E. M. F. of the arc-light?

Understanding historical changes in gross primary productivity (GPP) is essential for better predicting the future global carbon cycle. However, the historical trends of terrestrial GPP, due to the CO2 fertilization effect, climate, and land-use change, remain largely uncertain. Using long-term satellite-based near-infrared radiance of vegetation (NIRv), a proxy for GPP, and multiple GPP datasets derived from satellite-based products, dynamic global vegetation model (DGVM) simulations, and an upscaled product from eddy covariance (EC) measurements, here we comprehensively investigated their trends and analyzed the causes for any discrepancies during 1982–2015. Although spatial patterns of climatological annual GPP from all products and NIRv are highly correlated (r>0.84), the spatial correlation coefficients of trends between DGVM GPP and NIRv significantly decreased (with the ensemble mean of r=0.49) and even the spatial correlation coefficients of trends between other GPP products and NIRv became negative. By separating the global land into the tropics plus extratropical Southern Hemisphere (Trop+SH) and extratropical Northern Hemisphere (NH), we found that, during 1982–2015, simulated GPP from most of the models showed a stronger increasing trend over Trop+SH than NH. In contrast, the satellite-based GPP products indicated a substantial increase over NH. Mechanistically, model sensitivity experiments indicated that the increase of annual global total GPP was dominated by the CO2 fertilization effect (83.9 % contribution), however, with the largest uncertainty in magnitude in individual simulations among the three drivers of CO2 fertilization, climate, and land-use change. Interestingly, the spatial distribution of inter-model spreads of GPP trends resulted mainly from climate and land-use change rather than CO2 fertilization effect. After 2000, trends from satellite-based GPP products were different from the full time series, suggesting weakened rising trends over NH and even significantly decreasing trends over Trop+SH, while the trends from DGVMs and NIRv kept increasing. The inconsistencies of GPP trends are very likely caused by the contrasting performance between satellite-derived and DGVM simulated vegetation structure parameter (leaf area index, LAI). Therefore, the uncertainty in satellite-based GPP products induced by highly uncertain LAI data in the tropics undermines their roles in assessing the performance of DGVM simulations and understanding the changes of global carbon sinks. The higher consistency between DGVM GPP and NIRv suggests that the trends from a DGVM ensemble might even have better performance than satellite-based GPP products.