Two-divisibility of the coefficients of certain weakly holomorphic modular forms

We study a canonical basis for spaces of weakly holomorphic modular forms of weights 12, 16, 18, 20, 22, and 26 on the full modular group. We prove a relation between the Fourier coefficients of modular forms in this canonical basis and a generalized Ramanujan tau-function, and use this to prove that these Fourier coefficients are often highly divisible by 2.Comment: Corrected typos. To appear in the Ramanujan Journa

Multi-decadal improvement in US Lake water clarity

Across the globe, recent work examining the state of freshwater resources paints an increasingly dire picture of degraded water quality. However, much of this work either focuses on a small subset of large waterbodies or uses in situ water quality datasets that contain biases in when and where sampling occurred. Using these unrepresentative samples limits our understanding of landscape level changes in aquatic systems. In lakes, overall water clarity provides a strong proxy for water quality because it responds to surrounding atmospheric and terrestrial processes. Here, we use satellite remote sensing of over 14 000 lakes to show that lake water clarity in the U.S. has increased by an average of 0.52 cm yr-1 since 1984. The largest increases occurred prior to 2000 in densely populated catchments and within smaller waterbodies. This is consistent with observed improvements in water quality in U.S. streams and lakes stemming from sweeping environmental reforms in the 1970s and 1980s that prioritized point-source pollution in largely urban areas. The comprehensive, long-term trends presented here emphasize the need for representative sampling of freshwater resources when examining macroscale trends and are consistent with the idea that extensive U.S. freshwater pollution abatement measures have been effective and enduring, at least for point-source pollution controls

PPARgamma in complex with an antagonist and inverse agonist: a tumble and trap mechanism of the activation helix

Peroxisome proliferator activated receptor γ (PPARγ) is a nuclear receptor and target for antidiabetics that increase insulin sensitivity. Owing to the side effects of PPARγ full agonists, research has recently focused on non-activating ligands of PPARγ, which increase insulin sensitivity with decreased side effects. Here, we present the crystal structures of inverse agonist SR10171 and a chemically related antagonist SR11023 bound to the PPARγ ligand-binding domain, revealing an allosteric switch in the activation helix, helix 12 (H12), forming an antagonist conformation in the receptor. H12 interacts with the antagonists to become fixed in an alternative location. Native mass spectrometry indicates that this prevents contacts with coactivator peptides and allows binding of corepressor peptides. Antagonists of related nuclear receptors act to sterically prevent the active configuration of H12, whereas these antagonists of PPARγ alternatively trap H12 in an inactive configuration, which we have termed the tumble and trap mechanism.Rebecca L. Frkic, Andrew C. Marshall, Anne-Laure Blayo, Tara L. Pukala, Theodore M. Kamenecka, Patrick R. Griffin, and John B. Brunin

Structural and dynamic elucidation of a non-acid PPARγ partial agonist: SR1988

Targeting peroxisome proliferator-activated receptor γ (PPARγ) by synthetic compounds has been shown to elicit insulin sensitising properties in type 2 diabetics. Treatment with a class of these compounds, the thiazolidinediones (TZDs), has shown adverse side effects such as weight gain, fluid retention, and congestive heart failure. This is due to their full agonist properties on the receptor, where a number of genes are upregulated beyond normal physiological levels. Lessened transactivation of PPARγ by partial agonists has proved beneficial in terms of reducing side effects, while still maintaining insulin sensitising properties. However, some partial agonists have been associated with unfavourable pharmacokinetic profiles due to their acidic moieties, often causing partitioning to the liver. Here we present SR1988, a new partial agonist with favourable non-acid chemical properties. We used a combination of X-ray crystallography and hydrogen/deuterium exchange (HDX) to elucidate the structural basis for reduced activation of PPARγ by SR1988. This structural analysis reveals a mechanism that decreases stabilisation of the AF2 coactivator binding surface by the ligand.Rebecca L. Frkic, Benjamin S. Chua, Youseung Shin, Bruce D. Pasca, Scott J. Novick, Theodore M. Kamenecka, Patrick R. Griffin, and John B. Brunin

A Precious Bequest: Contemporary Research with the WPA-CCC Collections from Moundville, Alabama *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72459/1/j.1749-6632.1981.tb28184.x.pd

Biodiversity increases the resistance of ecosystem productivity to climate extremes

It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide1. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities2. However, subsequent experimental tests produced mixed results3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16–32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability14, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events

The provenance of Borneo's enigmatic alluvial diamonds:A case study from Cempaka, SE Kalimantan

Gem-quality diamonds have been found in several alluvial deposits across central and southern Borneo. Borneo has been a known source of diamonds for centuries, but the location of their primary igneous source remains enigmatic. Many geological models have been proposed to explain their distribution, including: the diamonds were derived from a local diatreme; they were brought to the surface through ophiolite obduction or exhumation of UHP metamorphic rocks; they were transported long distances southward via major Asian river systems; or, they were transported from the Australian continent before Borneo was rifted from its northwestern margin in the Late Jurassic. To assess these models, we conducted a study of the provenance of heavy minerals from Kalimantan's Cempaka alluvial diamond deposit. This involved collecting U–Pb isotopic data, fission track and trace element geochemistry of zircon as well as major element geochemical data of spinels and morphological descriptions of zircon and diamond. The results indicate that the Cempaka diamonds were likely derived from at least two sources, one which was relatively local and/or involved little reworking, and the other more distal which records several periods of reworking. The distal diamond source is interpreted to be diamond-bearing pipes that intruded the basement of a block that: (1) rifted from northwest Australia (East Java or SW Borneo) and the diamonds were recycled into its sedimentary cover, or: (2) were emplaced elsewhere (e.g. NW Australia) and transported to a block (e.g. East Java or SW Borneo). Both of these scenarios require the diamonds to be transported with the block when it rifted from NW Australia in the Late Jurassic. The local source could be diamondiferous diatremes associated with eroded Miocene high-K alkaline intrusions north of the Barito Basin, which would indicate that the lithosphere beneath SW Borneo is thick (~ 150 km or greater). The ‘local’ diamonds could also be associated with ophiolitic rocks that are exposed in the nearby Meratus Mountains

Current use of androgens in bone marrow failure disorders: a report from the Severe Aplastic Anemia Working Party of the European Society of Blood and Marrow Transplantation

Androgens have represented the historical therapeutic backbone of bone marrow failure (BMF) syndromes. However, their role has been rarely analyzed in prospective setting and systematic and long-term data are currently unavailable regarding their usage, effectiveness and toxicity in both acquired and inherited BMF. Here, taking advantage of a unique disease-specific international dataset, we retrospectively analyzed the so far largest cohort of BMF patients who received androgens before or in absence of an allogeneic hematopoietic cell transplantation (HCT), reappraising their current use in these disorders. We identified 274 patients across 82 EBMT affiliated centers, 193 with acquired (median age of 32) and 81 with inherited BMF (median age of 8 years). With a median duration of androgen treatment of 5.6 and 20 months respectively, complete/partial remission rates at 3 months were of 6%/29% in acquired and 8%/29% in inherited disorders. Five-year overall survival and failure free survival (FFS) were respectively 63% and 23% in acquired and 78% and 14% in inherited contexts. Androgen initiation after second line treatments for acquired, and after > 12 months post-diagnosis for inherited group were identified as factors associated with improved FFS in multivariable analysis. Androgen use was associated with a manageable incidence of organ-specific toxicity and low rates of solid and hematological malignancies. Sub-analysis of transplant-related outcomes after exposure to these compounds showed probabilities of survival and complications similar to other transplanted BMF cohorts. This study delivers a unique opportunity to track androgen use in BMF syndromes and represents the basis for general recommendations on their use on behalf of the SAAWP of the EBMT