228 research outputs found

    Serum glutamine and hospital-acquired infections after aneurysmal subarachnoid hemorrhage

    Get PDF
    OBJECTIVE: To understand nutritional and inflammatory factors contributing to serum glutamine levels and their relationship to hospital-acquired infections (HAIs) after aneurysmal subarachnoid hemorrhage (SAH). METHODS: A prospective observational study of patients with SAH who had measurements of daily caloric intake and C-reactive protein, transthyretin, tumor necrosis factor α receptor 1a (TNFαR1a), glutamine, and nitrogen balance performed within 4 preset time periods during the 14 days after SAH. Factors associated with glutamine levels and HAIs were analyzed with multivariable regression. HAIs were tracked daily for time-to-event analyses. Outcome 3 months after SAH was assessed by the Telephone Interview for Cognitive Status and modified Rankin Scale. RESULTS: There were 77 patients with an average age of 55 ± 15 years. HAIs developed in 18 (23%) on mean SAH day 8 ± 3. In a multivariable linear regression model, negative nitrogen balance ( CONCLUSIONS: Declining glutamine levels in the first 14 days after SAH are influenced by inflammation and associated with an increased risk of HAI

    Exploiting Symmetries When Proving Equivalence Properties for Security Protocols

    Get PDF
    International audienceVerification of privacy-type properties for cryptographic protocols in an active adversarial environment, modelled as a behavioural equivalence in concurrent-process calculi, exhibits a high computational complexity. While undecidable in general, for some classes of common cryptographic primitives the problem is coNEXP-complete when the number of honest participants is bounded.In this paper we develop optimisation techniques for verifying equivalences, exploiting symmetries between the two processes under study. We demonstrate that they provide a significant (several orders of magnitude) speed-up in practice, thus increasing the size of the protocols that can be analysed fully automatically

    Are Zinc-Finger Domains of Protein Kinase C Dynamic Structures That Unfold by Lipid or Redox Activation?

    Full text link
    Protein kinase C (PKC) is activated by lipid second messengers or redox action, raising the question whether these activation modes involve the same or alternate mechanisms. Here we show that both lipid activators and oxidation target the zinc-finger domains of PKC, suggesting a unifying activation mechanism. We found that lipid agonist-binding or redox action leads to zinc release and disassembly of zinc fingers, thus triggering large-scale unfolding that underlies conversion to the active enzyme. These results suggest that PKC zinc fingers, originally considered purely structural devices, are in fact redox-sensitive flexible hinges, whose conformation is controlled both by redox conditions and lipid agonists. Antioxid. Redox Signal. 14, 757-766.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90473/1/ars-2E2010-2E3773.pd

    Subcritical multiplicative chaos for regularized counting statistics from random matrix theory

    Get PDF
    For an N×N random unitary matrix U_N, we consider the random field defined by counting the number of eigenvalues of U_N in a mesoscopic arc of the unit circle, regularized at an N-dependent scale Ɛ_N>0. We prove that the renormalized exponential of this field converges as N → ∞ to a Gaussian multiplicative chaos measure in the whole subcritical phase. In addition, we show that the moments of the total mass converge to a Selberg-like integral and by taking a further limit as the size of the arc diverges, we establish part of the conjectures in [55]. By an analogous construction, we prove that the multiplicative chaos measure coming from the sine process has the same distribution, which strongly suggests that this limiting object should be universal. The proofs are based on the asymptotic analysis of certain Toeplitz or Fredholm determinants using the Borodin-Okounkov formula or a Riemann-Hilbert problem for integrable operators. Our approach to the LÂč-phase is based on a generalization of the construction in Berestycki [5] to random fields which are only asymptotically Gaussian. In particular, our method could have applications to other random fields coming from either random matrix theory or a different context

    The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers

    Get PDF
    Objective: To evaluate the additive value of the prostate cancer gene 3 (PCA3) urine test to serum prostate-specific antigen (PSA) in prostate cancer (PC) screening among breast cancer, early-onset gene (BRCA) mutation carriers. This study was performed among the Dutch participants of IMPACT, a large international study on the effectiveness of PSA screening among BRCA mutation carriers. Materials and methods: Urinary PCA3 was measured in 191 BRCA1 mutation carriers, 75 BRCA2 mutation carriers, and 308 noncarriers. The physicians and participants were blinded for the results. Serum PSA level≄3.0. ng/ml was used to indicate prostate biopsies. PCA3 was evaluated (1) as an independent indicator for prostate biopsies and (2) as an indicator for prostate biopsies among men with an elevated

    Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy

    Get PDF
    Exome sequencing revealed a homozygous missense mutation (c.317C>G [p.Arg106Pro]) in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations (c.199_201del [p.Gln67del] and c.810+1G>T) in an unrelated person with cone-rod dystrophy. Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.Gln67del variant forms of POC1B. Morpholino-oligonucleotide-induced knockdown of poc1b translation in zebrafish resulted in a dose-dependent small-eye phenotype, impaired optokinetic responses, and decreased length of photoreceptor outer segments. These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs. Yeast two-hybrid screening of a human retinal cDNA library revealed FAM161A as a binary interaction partner of POC1B. This was confirmed in coimmunoprecipitation and colocalization assays, which both showed loss of FAM161A interaction with p.Arg106Pro and p.Gln67del variant forms of POC1B. FAM161A was previously implicated in autosomal-recessive retinitis pigmentosa and shown to be located at the base of the photoreceptor connecting cilium, where it interacts with several other ciliopathy-associated proteins. Altogether, this study demonstrates that POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors

    Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer

    Get PDF
    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 × 10(-6)]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r(2) = 0.999), which showed associations with both the splicing anomalies (P = 6.5 × 10(-32)) and with protection against prostate cancer (OR = 0.91, P = 3.8 × 10(-7)).National Cancer Research Institute (NCRI) G0500966/75466 Department of Health, Medical Research Council Cancer Research UK University of Cambridge NIHR Department of Health Anniversary Fund of the Austrian National Bank 15079 Medical and Scientific Fund of the Mayor of the City of Vienna 10077 Common Fund of the Office of the Director of the National Institutes of Health NCI NHGRI NHLBI NIDA NIMH NINDS NCI\SAIC-Frederick, Inc. (SAIC-F) 10XS170 Roswell Park Cancer Institute 10XS171 Science Care, Inc. X10S172 SAIC-F 10ST1035 HHSN261200800001E deCODE genetics/AMGEN HHSN268201000029C DA006227 DA033684 N01MH000028 MH090941 MH101814 MH090951 MH090937 MH101820 MH101825 MH090936 MH101819 MH090948 MH101782 MH101810 MH10182
    • 

    corecore