Conductor development for a wide bore 10 T Nb3Sn model dipole magnet

An 87.8 mm bore single aperture 10 T Nb3Sn model dipole magnet is under development as a next step in the realization of high-field Nb3Sn dipole magnets. The magnet is a 2 layer cos(&thetas;)-dipole model as an alternative for the proposed NbTi D1 beam separator magnets for the LHC. After completion of the general magnetic and mechanical design, all attention is focused on the manufacturing and cabling of a novel powder-in-tube Nb3Sn conductor. This Nb3Sn conductor is characterized by a high non-Cu Jc of 2680 A/mm2 at 10 T with an effective filament size of about 20 ¿m. Cabling should result in a Rutherford type of cable exhibiting a moderate Jc degradation due to the cabling process itself, a low transverse stress sensitivity and a controllable minimum value of Rc. The conductor development program is presented and the results are evaluated. Progress on the actual realization of the coils is briefly describe

Coding of multivariate stimuli and contextual interactions in the visual cortex

The primary visual cortex (V1) has long been considered the main low level visual analysis area of the brain. The classical view is of a feedfoward system functioning as an edge detector, in which each cell has a receptive field (RF) and a preferred orientation. Whilst intuitive, this view is not the whole story. Although stimuli outside a neuron’s RF do not result in an increased response by themselves, they do modulate a neuron’s response to what’s inside its RF. We will refer to such extra-RF effects as contextual modulation. Contextual modulation is thought to underlie several perceptual phenomena, such as various orientation illusions and saliency of specific features (such as a contour or differing element). This gives a view of V1 as more than a collection of edge detectors, with neurons collectively extracting information beyond their RFs. However, many of the accounts linking psychophysics and physiology explain only a small subset of the illusions and saliency effects: we would like to find a common principle. So first, we assume the contextual modulations experienced by V1 neurons is determined by the elastica model, which describes the shape of the smoothest curve between two points. This single assumption gives rise to a wide range of known contextual modulation and psychophysical effects. Next, we consider the more general problem of encoding and decoding multi-variate stimuli (such as center surround gratings) in neurons, and how well the stimuli can be decoded under substantial noise levels with a maximum likelihood decoder. Although the maximum likelihood decoder is widely considered optimal and unbiased in the limit of no noise, under higher noise levels it is poorly understood. We show how higher noise levels lead to highly complex decoding distributions even for simple encoding models, which provides several psychophysical predictions. We next incorporate more updated experimental knowledge of contextual modulations. Perhaps the most common form of contextual modulations is center surround modulation. Here, the response to a center grating in the RF is modulated by the presence of a surrounding grating (the surround). Classically this modulation is considered strongest when the surround is aligned with the preferred orientation, but several studies have shown how many neurons instead experience strongest modulation whenever center and surround are aligned. We show how the latter type of modulation gives rise to stronger saliency effects and unbiased encoding of the center. Finally, we take an experimental perspective. Recently, both the presence and the underlying mechanisms of contextual modulations has been increasingly studied in mice using calcium imaging. However, cell signals extracted with calcium imaging are often highly contaminated by other sources. As contextual effects beyond center surround modulation can be subtle, a method is needed to remove the contamination. We present an analysis toolbox to de-contaminate calcium signals with blind source separation. This thesis thus expands our understanding of contextual modulation, predicts several new experimental results, and presents a toolbox to extract signals from calcium imaging data which should allow for more in depth studies of contextual modulation

Physical mixing effects on iron biogeochemical cycling: FeCycle experiment

The effects of physical processes on the distribution, speciation, and sources/sinks for Fe in a high-nutrient low-chlorophyll (HNLC) region were assessed during FeCycle, a mesoscale SF6 tracer release during February 2003 (austral summer) to the SE of New Zealand. Physical mixing processes were prevalent during FeCycle with rapid patch growth (strain rate γ = 0.17–0.20 d−1) from a circular shape (50 km2) into a long filament of ∼400 km2 by day 10. Slippage between layers saw the patch-head overlying noninfused waters while the tail was capped by adjacent surface waters resulting in a SF6 maximum at depth. As the patch developed it entrained adjacent waters containing higher chlorophyll concentrations, but similar dissolved iron (DFe) levels, than the initial infused patch. DFe was low ∼60 pmol L−1 in surface waters during FeCycle and was dominated by organic complexation. Nighttime measurements of Fe(II) ∼20 pmol L−1 suggest the presence of Fe(II) organic complexes in the absence of an identifiable fast Fe(III) reduction process. Combining residence times and phytoplankton uptake fluxes for DFe it is cycled through the biota 140–280 times before leaving the winter mixed layer (WML). This strong Fe demand throughout the euphotic zone coupled with the low Fe:NO3 − (11.9 μmol:mol) below the ferricline suggests that vertical diffusion of Fe is insufficient to relieve chronic iron limitation, indicating the importance of atmospheric inputs of Fe to this region

The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development

Type I diabetes is caused by loss of insulin-secreting beta cells. To identify novel, pharmacologically-targetable histone-modifying proteins that enhance beta cell production from pancreatic progenitors, we performed a screen for histone modifications induced by signal transduction pathways at key pancreatic genes. The screen led us to investigate the temporal dynamics of ser-28 phosphorylated histone H3 (H3S28ph) and its upstream kinases, MSK1 and MSK2 (MSK1/2). H3S28ph and MSK1/2 were enriched at the key endocrine and acinar promoters in E12.5 multipotent pancreatic progenitors. Pharmacological inhibition of MSK1/2 in embryonic pancreatic explants promoted the specification of endocrine fates, including the beta-cell lineage, while depleting acinar fates. Germline knockout of both Msk isoforms caused enhancement of alpha cells and a reduction in acinar differentiation, while monoallelic loss of Msk1 promoted beta cell mass. Our screen of chromatin state dynamics can be applied to other developmental contexts to reveal new pathways and approaches to modulate cell fates

Insights Into the Biogeochemical Cycling of Iron, Nitrate, and Phosphate Across a 5,300 km South Pacific Zonal Section (153°E–150°W)

Iron, phosphate and nitrate are essential nutrients for phytoplankton growth and hence their supply into the surface ocean controls oceanic primary production. Here, we present a GEOTRACES zonal section (GP13; 30-33oS, 153oE-150oW) extending eastwards from Australia to the oligotrophic South Pacific Ocean gyre outlining the concentrations of these key nutrients. Surface dissolved iron concentrations are elevated at >0.4 nmol L-1 near continental Australia (west of 165°E) and decreased eastward to ≤0.2 nmol L-1 (170oW-150oW). The supply of dissolved iron into the upper ocean (<100m) from the atmosphere and vertical diffusivity averaged 11 ±10 nmol m-2 d-1. In the remote South Pacific Ocean (170oW-150oW) atmospherically sourced iron is a significant contributor to the surface dissolved iron pool with average supply contribution of 23 ± 17% (range 3% to 55%). Surface-water nitrate concentrations averaged 5 ±4 nmol L-1 between 170oW and 150oW whilst surface-water phosphate concentrations averaged 58 ±30 nmol L-1. The supply of nitrogen into the upper ocean is primarily from deeper waters (24-1647 μmol m-2 d-1) with atmospheric deposition and nitrogen fixation contributing <1% to the overall flux, in remote South Pacific waters. The deep water N:P ratio averaged 16 ±3 but declined to <1 above the deep chlorophyll maximum (DCM) indicating a high N:P assimilation ratio by phytoplankton leading to almost quantitative removal of nitrate. The supply stoichiometry for iron and nitrogen relative to phosphate at and above the DCM declines eastward leading to two biogeographical provinces: one with diazotroph production and the other without diazotroph production

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

State of wildfires 2023–24

Climate change is increasing the frequency and intensity of wildfires globally, with significant impacts on society and the environment. However, our understanding of the global distribution of extreme fires remains skewed, primarily influenced by media coverage and regional research concentration. This inaugural State of Wildfires report systematically analyses fire activity worldwide, identifying extreme events from the March 2023–February 2024 fire season. We assess the causes, predictability, and attribution of these events to climate change and land use, and forecast future risks under different climate scenarios. During the 2023–24 fire season, 3.9 million km2 burned globally, slightly below the average of previous seasons, but fire carbon (C) emissions were 16 % above average, totaling 2.4 Pg C. This was driven by record emissions in Canadian boreal forests (over 9 times the average) and dampened by reduced activity in African savannahs. Notable events included record-breaking wildfire extent and emissions in Canada, the largest recorded wildfire in the European Union (Greece), drought-driven fires in western Amazonia and northern parts of South America, and deadly fires in Hawai’i (100 deaths) and Chile (131 deaths). Over 232,000 people were evacuated in Canada alone, highlighting the severity of human impact. Our analyses revealed that multiple drivers were needed to cause areas of extreme fire activity. In Canada and Greece a combination of high fire weather and an abundance of dry fuels increased the probability of fires by 4.5-fold and 1.9–4.1-fold, respectively, whereas fuel load and direct human suppression often modulated areas with anomalous burned area. The fire season in Canada was predictable three months in advance based on the fire weather index, whereas events in Greece and Amazonia had shorter predictability horizons. Formal attribution analyses indicated that the probability of extreme events has increased significantly due to anthropogenic climate change, with a 2.9–3.6-fold increase in likelihood of high fire weather in Canada and a 20.0–28.5-fold increase in Amazonia. By the end of the century, events of similar magnitude are projected to occur 2.22–9.58 times more frequently in Canada under high emission scenarios. Without mitigation, regions like Western Amazonia could see up to a 2.9-fold increase in extreme fire events. For the 2024–25 fire season, seasonal forecasts highlight moderate positive anomalies in fire weather for parts of western Canada and South America, but no clear signal for extreme anomalies is present in the forecast. This report represents our first annual effort to catalogue extreme wildfire events, explain their occurrence, and predict future risks. By consolidating state-of-the-art wildfire science and delivering key insights relevant to policymakers, disaster management services, firefighting agencies, and land managers, we aim to enhance society’s resilience to wildfires and promote advances in preparedness, mitigation, and adaptation