Homogenization of weakly coupled systems of Hamilton--Jacobi equations with fast switching rates

We consider homogenization for weakly coupled systems of Hamilton--Jacobi equations with fast switching rates. The fast switching rate terms force the solutions converge to the same limit, which is a solution of the effective equation. We discover the appearance of the initial layers, which appear naturally when we consider the systems with different initial data and analyze them rigorously. In particular, we obtain matched asymptotic solutions of the systems and rate of convergence. We also investigate properties of the effective Hamiltonian of weakly coupled systems and show some examples which do not appear in the context of single equations.Comment: final version, to appear in Arch. Ration. Mech. Ana

Optimal stent design for high bleeding risk patients: Evidence from a network meta-analysis

Objective. To determine the best stent design for high bleeding risk (HBR) patients. Background. Polymer-free (PF) drug eluting stent (DES) devices have a proven benefit over bare-metal stent (BMS) devices in previous trials. It is unknown, however, whether polymer-based (PB)-DES devices are as safe as PF-DES devices. Methods. A network meta-analysis including all randomized controlled trials (RCTs) that compared different stent technology in HBR patients with a 1-month course of dual-antiplatelet therapy (DAPT) was performed. The main efficacy outcome was major adverse cardiac event (MACE) rate, defined as the composite of all-cause mortality, myocardial infarction (MI), and target-lesion revascularization (TLR). Secondary efficacy events included all-cause and cardiac mortality, MI, stroke, TLR, and target-vessel revascularization (TVR). Safety outcomes included all bleeding, major bleeding, and stent thrombosis (ST). Results. A total of 4 RCTs with 6456 patients were included. PF-DES and PB-DES yielded a reduced rate of MACE, MI, TLR, and TVR events compared with BMS (all P<.05). ST events were reduced in PB-DES compared with BMS (P=.01). No differences were found in all-cause death, cardiac death, or stroke events in PF-DES and PB-DES compared with BMS. Furthermore, no differences were found between PF-DES and PB-DES regarding any of the outcomes. Conclusion. DES devices were associated with lower MACE and TVR rates compared with BMS, whereas there were no statistical differences in other efficacy endpoints. Also, PB-DES were associated with fewer ST events compared with BMS. There were no statistical differences between PB-DES and PF-DES with regard to any of the endpoints. t 2021 HMP Comm Personal Use Onl

Impact of the Deepwater Horizon oil spill on a deep-water coral community in the Gulf of Mexico

To assess the potential impact of the Deepwater Horizon oil spill on offshore ecosystems, 11 sites hosting deep-water coral communities were examined 3 to 4 mo after the well was capped. Healthy coral communities were observed at all sites \u3e20 km from the Macondo well, including seven sites previously visited in September 2009, where the corals and communities appeared unchanged. However, at one site 11 km southwest of the Macondo well, coral colonies presented widespread signs of stress, including varying degrees of tissue loss, sclerite enlargement, excessmucous production, bleached commensal ophiuroids, and covering by brown flocculent material (floc). On the basis of these criteria the level of impact to individual colonies was ranked from 0 (least impact) to 4 (greatest impact). Of the 43 corals imaged at that site, 46% exhibited evidence of impact onmore than half of the colony,whereas nearly a quarter of all of the corals showed impact to \u3e90% of the colony. Additionally, 53% of these corals\u27 ophiuroid associates displayed abnormal color and/or attachment posture. Analysis of hopanoid petroleumbiomarkers isolated from the floc provides strong evidence that this material contained oil fromtheMacondowell. The presence of recently damaged and deceased corals beneath the path of a previously documented plume emanating from the Macondo well provides compelling evidence that the oil impacted deep-water ecosystems. Our findings underscore the unprecedented nature of the spill in terms of its magnitude, release at depth, and impact to deep-water ecosystems

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Membrane fission by dynamin: what we know and what we need to know

The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis. We present the two current models for fission, essentially diverging in how GTP energy is spent. We further discuss how future research might solve the remaining open questions presently under discussion

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

Experimental discovery of sRNAs in Vibrio cholerae by direct cloning, 5S/tRNA depletion and parallel sequencing

Direct cloning and parallel sequencing, an extremely powerful method for microRNA (miRNA) discovery, has not yet been applied to bacterial transcriptomes. Here we present sRNA-Seq, an unbiased method that allows for interrogation of the entire small, non-coding RNA (sRNA) repertoire in any prokaryotic or eukaryotic organism. This method includes a novel treatment that depletes total RNA fractions of highly abundant tRNAs and small subunit rRNA, thereby enriching the starting pool for sRNA transcripts with novel functionality. As a proof-of-principle, we applied sRNA-Seq to the human pathogen Vibrio cholerae. Our results provide information, at unprecedented depth, on the complexity of the sRNA component of a bacterial transcriptome. From 407 039 sequence reads, all 20 known V. cholerae sRNAs, 500 new, putative intergenic sRNAs and 127 putative antisense sRNAs were identified in a limited number of growth conditions examined. In addition, characterization of a subset of the newly identified transcripts led to the identification of a novel sRNA regulator of carbon metabolism. Collectively, these results strongly suggest that the number of sRNAs in bacteria has been greatly underestimated and that future efforts to analyze bacterial transcriptomes will benefit from direct cloning and parallel sequencing experiments aided by 5S/tRNA depletion

Amount and timing of group-based childcare from birth and cognitive development at 51 months: a UK study

This study investigated whether the amount and timing of group-based childcare between birth and 51 months were predictive of cognitive development at 51 months, taking into account: other non-parental childcare; demographic characteristics; cognitive development at 18 months, sensitive parenting and a stimulating home environment. Children’s (N=978) cognitive development was assessed at 51 months with four subscales of the British Ability Scales, two verbal and two non-verbal. Mothers were interviewed and observed at 3, 10, 18, and 36 months and the quality of group care was assessed at 10, 18 and 36 months (N=239) if it was used for ≥12 hours per week. Age of starting in group care and amount were highly associated (r=-.75). Multiple regressions indicated that, controlling for other factors, higher cognitive development and particularly non-verbal ability was associated with more hours per week in group care from 0 to 51 months, or an earlier start, or group care before age 2. Nevertheless, the majority of variance was explained by other predictors: sex (girl), higher cognitive development at 18 months, older mother, first language English, mother of white ethnic background, with more qualifications, higher family social class, more maternal responsivity at 10 months and a more stimulating home learning environment (HLE) at 36 months. Hours per week in relative care or home-based care were not significant predictors of cognitive scores. For the smaller relatively advantaged sample who had group care quality information (N=239), quality was a marginal predictor of better cognitive development but age of starting group care was not. Most variance was explained by 18 month cognitive development, maternal education and family social class

Mycobacterium tuberculosis phagosome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75241/1/j.1365-2958.1999.01279.x.pd