Quantum Symmetries and Strong Haagerup Inequalities

In this paper, we consider families of operators $\{x_r\}_{r \in \Lambda}$ in a tracial C$^\ast$-probability space $(\mathcal A, \phi)$, whose joint $\ast$-distribution is invariant under free complexification and the action of the hyperoctahedral quantum groups $\{H_n^+\}_{n \in \N}$. We prove a strong form of Haagerup's inequality for the non-self-adjoint operator algebra $\mathcal B$ generated by $\{x_r\}_{r \in \Lambda}$, which generalizes the strong Haagerup inequalities for $\ast$-free R-diagonal families obtained by Kemp-Speicher \cite{KeSp}. As an application of our result, we show that $\mathcal B$ always has the metric approximation property (MAP). We also apply our techniques to study the reduced C$^\ast$-algebra of the free unitary quantum group $U_n^+$. We show that the non-self-adjoint subalgebra $\mathcal B_n$ generated by the matrix elements of the fundamental corepresentation of $U_n^+$ has the MAP. Additionally, we prove a strong Haagerup inequality for $\mathcal B_n$, which improves on the estimates given by Vergnioux's property RD \cite{Ve}

eClinic: increasing use of telehealth as a risk reduction strategy during the covid-19 pandemic

Prior to the covid-19 pandemic, telehealth was already being rapidly adopted nationally by healthcare systems. During the covid-19 pandemic, increased use of telehealth may be considered as a risk reduction strategy. Benefits of this strategy may be conferred to both patients and health providers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155565/1/Kemp_Williams_Alam_eClinic.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155565/4/DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID.pdfDescription of Kemp_Williams_Alam_eClinic.pdf : ArticleDescription of DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID.pdf : Deep Blue sharing agreemen

Trial Designs Likely to Meet Valid Long-Term Alzheimer's Disease Progression Effects: Learning from the Past, Preparing for the Future

The International Society for CNS Clinical Trials and Methodology (ISCTM) held its 4th Annual Autumn Conference in Toronto, Ontario, October 6-7, 2008. The purpose of the present report is to provide an overview of one of the sessions at the conference which focused on the designs and methodologies to be applied in clinical trials of new treatments for Alzheimer's disease (AD) with purported “disease-modifying” effects. The session began with a discussion of how neuroimaging has been applied in multiple sclerosis clinical trials (another condition for which disease modification claims have been achieved). The next two lectures provided a pharmaceutical industry perspective on some of the specific challenges and possible solutions for designing trials to measure disease progression and/or modification. The final lecture provided an academic viewpoint and the closing discussion included additional academic and regulatory perspectives on trial designs, methodologies, and statistical issues relevant to the disease modification concept

Red Galaxy Growth and the Halo Occupation Distribution

We have traced the past 7 Gyr of red galaxy stellar mass growth within dark matter halos. We have determined the halo occupation distribution, which describes how galaxies reside within dark matter halos, using the observed luminosity function and clustering of 40,696 0.2<z<1.0 red galaxies in Bootes. Half of 10^{11.9} Msun/h halos host a red central galaxy, and this fraction increases with increasing halo mass. We do not observe any evolution of the relationship between red galaxy stellar mass and host halo mass, although we expect both galaxy stellar masses and halo masses to evolve over cosmic time. We find that the stellar mass contained within the red population has doubled since z=1, with the stellar mass within red satellite galaxies tripling over this redshift range. In cluster mass halos most of the stellar mass resides within satellite galaxies and the intra-cluster light, with a minority of the stellar mass residing within central galaxies. The stellar masses of the most luminous red central galaxies are proportional to halo mass to the power of a third. We thus conclude that halo mergers do not always lead to rapid growth of central galaxies. While very massive halos often double in mass over the past 7 Gyr, the stellar masses of their central galaxies typically grow by only 30%.Comment: Accepted for publication in the ApJ. 34 pages, 22 Figures, 5 Table

Mechanism of Release and Fate of Excised Oligonucleotides during Nucleotide Excision Repair

A wide range of environmental and carcinogenic agents form bulky lesions on DNA that are removed from the human genome in the form of short, ∼30-nucleotide oligonucleotides by the process of nucleotide excision repair. Although significant insights have been made regarding the mechanisms of damage recognition, dual incisions, and repair resynthesis during nucleotide excision repair, the fate of the dual incision/excision product is unknown. Using excision assays with both mammalian cell-free extract and purified proteins, we unexpectedly discovered that lesion-containing oligonucleotides are released from duplex DNA in complex with the general transcription and repair factor, Transcription Factor IIH (TFIIH). Release of excision products from TFIIH requires ATP but not ATP hydrolysis, and release occurs slowly, with a t½ of 3.3 h. Excised oligonucleotides released from TFIIH then become bound by the single-stranded binding protein Replication Protein A or are targeted by cellular nucleases. These results provide a mechanism for release and an understanding of the initial fate of excised oligonucleotides during nucleotide excision repair

Coupling of Human DNA Excision Repair and the DNA Damage Checkpoint in a Defined in Vitro System

DNA repair and DNA damage checkpoints work in concert to help maintain genomic integrity. In vivo data suggest that these two global responses to DNA damage are coupled. It has been proposed that the canonical 30 nucleotide single-stranded DNA gap generated by nucleotide excision repair is the signal that activates the ATR-mediated DNA damage checkpoint response and that the signal is enhanced by gap enlargement by EXO1 (exonuclease 1) 5′ to 3′ exonuclease activity. Here we have used purified core nucleotide excision repair factors (RPA, XPA, XPC, TFIIH, XPG, and XPF-ERCC1), core DNA damage checkpoint proteins (ATR-ATRIP, TopBP1, RPA), and DNA damaged by a UV-mimetic agent to analyze the basic steps of DNA damage checkpoint response in a biochemically defined system. We find that checkpoint signaling as measured by phosphorylation of target proteins by the ATR kinase requires enlargement of the excision gap generated by the excision repair system by the 5′ to 3′ exonuclease activity of EXO1. We conclude that, in addition to damaged DNA, RPA, XPA, XPC, TFIIH, XPG, XPF-ERCC1, ATR-ATRIP, TopBP1, and EXO1 constitute the minimum essential set of factors for ATR-mediated DNA damage checkpoint response

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits

Synergistic malaria vaccine combinations identified by systematic antigen screening.

A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

Event-related alpha suppression in response to facial motion

This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al