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Given stationary time series data, we study the problem of finding the best linear combination of a set of lag window spectral density estimators with respect to the mean squared risk. We present an aggregation procedure and prove a sharp oracle inequality for its risk. We also provide simulations demonstrating the performance of our aggregation procedure, given Bartlett and other estimators of varying bandwidths as input. This extends work by P. Rigollet and A. Tsybakov on aggregation of density estimators. © 2014 Elsevier B.V. 94 204 213 Cited By :1

The one airway, one disease hypothesis proposes that the upper and lower airways share the same physiology and histomorphology. Epidemiological clinical studies support a link between rhinosinusitis and asthma. The relationship can occur in both directions, with nasal allergen challenge leading to inflammatory changes in the lower airway and bronchoprovocation studies of the lower airway leading to inflammatory changes in the upper airway. In addition, both similarities and differences exist in the pathogenesis of nasal polyps and asthma. The mechanism for the connection between the upper and lower airways is a matter of great debate. It has been proposed that inflammatory changes in the lower airway may lead to systemic inflammatory effects that play a role in increased bronchial hyperresponsiveness. Similarly, lower airway inflammatory changes may affect nasal airway patency via systemic effects. Moreover, nasopharyngeal-bronchial reflexes may play a non-immunologic role in the interaction between the lower and upper airways. An example of the connection between the upper and lower airways is found in aspirin-exacerbated respiratory disease whereby leukotrienes play a role in the pathology of chronic rhinosinusitis with polyps and asthma. It is also been observed that the treatment of asthma is hindered by untreated rhinosinusitis.

Acute rhinosinusitis is a commonly seen disease that is frequently diagnosed based on clinical symptomatology without any objective evidence. The most common form of treatment is antibiotics, even though many cases may not have a bacterial etiology. The most common bacterial organisms in childhood sinusitis belong to the group that cause many childhood upper respiratory and lower respiratory infections and include Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Besides antibiotics, other treatments are aimed at assisting with drainage, and this can be accomplished by reducing the inflammation and edema that prevents venting of the sinus structures. These medications can include antihistamines, decongestants, intranasal steroids, nasal saline irrigation, and, in some countries, mucolytics. Complementary and alternative medicine (CAM) techniques including Chinese herbal medications are often used, but there is little scientific evidence to support their use. The use of immunotherapy has not been found to be effective in the management of acute rhinosinusitis in children or adults.

The Genome in a Bottle Consortium hosted by the National Institute of Standards and Technology, (NIST), is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Asian ancestry. The data described come from 11 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCodeTM WGS, and Illumina paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available and highly characterized. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly.

Diabetes is characterized by several poorly understood phenomena including dysfunctional wound healing and impaired vasculogenesis. p53, a master cell cycle regulator, is upregulated in diabetic wounds and has recently been shown to play a regulatory roles in vasculogenic pathways. We have previously described a novel method to topically silence target genes in a wound bed with small interfering (si)RNA. We hypothesized that silencing p53 results in improved diabetic wound healing and augmentation of vasculogenic mediators. Paired 4-mm stented wounds were created on diabetic db/db mice. Topically applied p53 siRNA, evenly distributed in an agarose matrix, was applied to wounds at postwound day 1 and 7 (matrix alone and nonsense siRNA served as controls). Animals were sacrificed at postwound days 10 and 24. Wound time to closure was photometrically assessed, and wounds were harvested for histology, immunohistochemistry, and immunofluorescence. Vasculogenic cytokine expression was evaluated via Western blot, reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. The ANOVA/t-test was used to determine significance (p≤ 0.05). Local p53 silencing resulted in faster wound healing with wound closure at 18±1.3 d in the treated group vs. 28±1.0 d in controls. The treated group demonstrated improved wound architecture at each time point while demonstrating near-complete local p53 knockdown. Moreover, treated wounds showed a 1.92-fold increase in CD31 endothelial cell staining over controls. Western blot analysis confirmed near-complete p53 knockdown in treated wounds. At day 10, VEGF secretion (enzyme-linked immunosorbent assay) was significantly increased in treated wounds (109.3±13.9 pg/mL) vs. controls (33.0±3.8 pg/mL) while reverse transcription-polymerase chain reaction demonstrated a 1.86-fold increase in SDF-1 expression in treated wounds vs. controls. This profile was reversed after the treated wounds healed and before closure of controls (day 24). Augmented vasculogenic cytokine profile and endothelial cell markers are associated with improved diabetic wound healing in topical gene therapy with p53 siRNA.

RNA binding proteins regulate gene expression at the posttranscriptional level and play important roles in embryonic development. Here, we report the cloning and expression of Samba, a Xenopus hnRNP that is maternally expressed and persists at least until tail bud stages. During gastrula stages, Samba is enriched in the dorsal regions. Subsequently, its expression is elevated only in neural and neural crest tissues. In the latter, Samba expression overlaps with that of Slug in migratory neural crest cells. Thereafter, Samba is maintained in the neural crest derivatives, as well as other neural tissues, including the anterior and posterior neural tube and the eyes. Overexpression of Samba in the animal pole leads to defects in neural crest migration and cranial cartilage development. Thus, Samba encodes a Xenopus hnRNP that is expressed early in neural and neural crest derivatives and may regulate crest cells migratory behavior. Developmental Dynamics 238:204 –209, 2009. © 2008 Wiley-Liss, Inc.