The merit of high-frequency data in portfolio allocation

This paper addresses the open debate about the usefulness of high-frequency (HF) data in large-scale portfolio allocation. Daily covariances are estimated based on HF data of the S&P 500 universe employing a blocked realized kernel estimator. We propose forecasting covariance matrices using a multi-scale spectral decomposition where volatilities, correlation eigenvalues and eigenvectors evolve on different frequencies. In an extensive out-of-sample forecasting study, we show that the proposed approach yields less risky and more diversified portfolio allocations as prevailing methods employing daily data. These performance gains hold over longer horizons than previous studies have shown

Long-Read Sequencing to Unravel Complex Structural Variants of CEP78 Leading to Cone-Rod Dystrophy and Hearing Loss

Inactivating variants as well as a missense variant in the centrosomal CEP78 gene have been identified in autosomal recessive cone-rod dystrophy with hearing loss (CRDHL), a rare syndromic inherited retinal disease distinct from Usher syndrome. Apart from this, a complex structural variant (SV) implicating CEP78 has been reported in CRDHL. Here we aimed to expand the genetic architecture of typical CRDHL by the identification of complex SVs of the CEP78 region and characterization of their underlying mechanisms. Approaches used for the identification of the SVs are shallow whole-genome sequencing (sWGS) combined with quantitative polymerase chain reaction (PCR) and long-range PCR, or ExomeDepth analysis on whole-exome sequencing (WES) data. Targeted or whole-genome nanopore long-read sequencing (LRS) was used to delineate breakpoint junctions at the nucleotide level. For all SVs cases, the effect of the SVs on CEP78 expression was assessed using quantitative PCR on patient-derived RNA. Apart from two novel canonical CEP78 splice variants and a frameshifting single-nucleotide variant (SNV), two SVs affecting CEP78 were identified in three unrelated individuals with CRDHL: a heterozygous total gene deletion of 235 kb and a partial gene deletion of 15 kb in a heterozygous and homozygous state, respectively. Assessment of the molecular consequences of the SVs on patient’s materials displayed a loss-of-function effect. Delineation and characterization of the 15-kb deletion using targeted LRS revealed the previously described complex CEP78 SV, suggestive of a recurrent genomic rearrangement. A founder haplotype was demonstrated for the latter SV in cases of Belgian and British origin, respectively. The novel 235-kb deletion was delineated using whole-genome LRS. Breakpoint analysis showed microhomology and pointed to a replication-based underlying mechanism. Moreover, data mining of bulk and single-cell human and mouse transcriptional datasets, together with CEP78 immunostaining on human retina, linked the CEP78 expression domain with its phenotypic manifestations. Overall, this study supports that the CEP78 locus is prone to distinct SVs and that SV analysis should be considered in a genetic workup of CRDHL. Finally, it demonstrated the power of sWGS and both targeted and whole-genome LRS in identifying and characterizing complex SVs in patients with ocular diseases

Evidence from Individual Inference for High-Dimensional Coexistence: Long-Term Experiments on Recruitment Response

Background: For competing species to coexist, individuals must compete more with others of the same species than with those of other species. Ecologists search for tradeoffs in how species might partition the environment. The negative correlations among competing species that would be indicative of tradeoffs are rarely observed. A recent analysis showed that evidence for partitioning the environment is available when responses are disaggregated to the individual scale, in terms of the covariance structure of responses to environmental variation. That study did not relate that variation to the variables to which individuals were responding. To understand how this pattern of variation is related to niche variables, we analyzed responses to canopy gaps, long viewed as a key variable responsible for species coexistence. Methodology/Principal Findings: A longitudinal intervention analysis of individual responses to experimental canopy gaps with 12 yr of pre-treatment and 8 yr post-treatment responses showed that species-level responses are positively correlated – species that grow fast on average in the understory also grow fast on average in response to gap formation. In other words, there is no tradeoff. However, the joint distribution of individual responses to understory and gap showed a negative correlation – species having individuals that respond most to gaps when previously growing slowly also have individuals that respond least to gaps when previously growing rapidly (e.g., Morus rubra), and vice versa (e.g., Quercus prinus). Conclusions/Significance: Because competition occurs at the individual scale, not the species scale, aggregated speciesleve

Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation

To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation

Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1:A multicentre cohort follow-up study

Objective: High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1). Methods: 117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months. Results: Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score. Conclusions: Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting

Global burned area and biomass burning emissions from small fires

[1] In several biomes, including croplands, wooded savannas, and tropical forests, many small fires occur each year that are well below the detection limit of the current generation of global burned area products derived from moderate resolution surface reflectance imagery. Although these fires often generate thermal anomalies that can be detected by satellites, their contributions to burned area and carbon fluxes have not been systematically quantified across different regions and continents. Here we developed a preliminary method for combining 1-km thermal anomalies (active fires) and 500 m burned area observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) to estimate the influence of these fires. In our approach, we calculated the number of active fires inside and outside of 500 m burn scars derived from reflectance data. We estimated small fire burned area by computing the difference normalized burn ratio (dNBR) for these two sets of active fires and then combining these observations with other information. In a final step, we used the Global Fire Emissions Database version 3 (GFED3) biogeochemical model to estimate the impact of these fires on biomass burning emissions. We found that the spatial distribution of active fires and 500 m burned areas were in close agreement in ecosystems that experience large fires, including savannas across southern Africa and Australia and boreal forests in North America and Eurasia. In other areas, however, we observed many active fires outside of burned area perimeters. Fire radiative power was lower for this class of active fires. Small fires substantially increased burned area in several continental-scale regions, including Equatorial Asia (157%), Central America (143%), and Southeast Asia (90%) during 2001–2010. Globally, accounting for small fires increased total burned area by approximately by 35%, from 345 Mha/yr to 464 Mha/yr. A formal quantification of uncertainties was not possible, but sensitivity analyses of key model parameters caused estimates of global burned area increases from small fires to vary between 24% and 54%. Biomass burning carbon emissions increased by 35% at a global scale when small fires were included in GFED3, from 1.9 Pg C/yr to 2.5 Pg C/yr. The contribution of tropical forest fires to year-to-year variability in carbon fluxes increased because small fires amplified emissions from Central America, South America and Southeast Asia—regions where drought stress and burned area varied considerably from year to year in response to El Nino-Southern Oscillation and other climate modes