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Controlling the stress in glass after laser exposure is of prime importance not only for photonics applications, but also for preserving the mechanical integrity of glass components in general. The sub-surface exposure of fused silica to femtosecond laser pulses can induce a permanent and localized modification to the glass structure. In this work, we present evidence that femtosecond laser exposure can be used to continuously tailor the stress in the material, from a tensile to compressivedoi:10.1364/optica.3.001285 fatcat:bubx2nw6rvb53hllrgvhskvapm
more »... e, as the laser pulse energy is changed. In addition, we demonstrate that this effect can not only be obtained while transitioning between different laser-induced microstructures, but also at low pulse energy, in the laser exposure regime particularly relevant for fabricating waveguides. These results demonstrate that femtosecond laser exposure is a versatile tool for fully controlling the stress landscape in a volume of silica, opening up new technological opportunities, like for instance, direct write stress-free waveguides, direct-write stress-induced birefringence state or mechanically reinforced parts, by locally preloading it. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. OCIS codes: (160.2750) Glass and other amorphous materials; (160.6030) Silica; (320.2250) Femtosecond phenomena; (320.7130) Ultrafast processes in condensed matter, including semiconductors. http://dx.
JAMA Network Open
The majority of US states have passed mandates requiring the use of electronic prescribing of controlled substances (EPCS) as a tool to reduce rates of opioid prescribing. It is not known whether increasing use of EPCS will have the intended effect. To assess the association between use of EPCS and trends in opioid prescribing. In this retrospective, longitudinal cohort study of all patients and prescribers in the 50 US states and the District of Columbia from 2010 to 2018, changes indoi:10.1001/jamanetworkopen.2020.27951 pmid:33346845 pmcid:PMC7753903 fatcat:iorfdoo67ff6pi64tkqhxyco54
more »... l use of EPCS and concurrent changes in opioid prescribing in each state are described. Then the association between changes in the use of EPCS and opioid prescribing are estimated using state and year fixed-effects models that include covariates for policy change and state demographic change. Data Analysis was performed on May 5, 2020. The proportion of controlled substances in each state prescribed using EPCS based on opioid prescriptions per 100 persons and morphine milligram equivalents (MME) of opioids. In 2018, the population-weighted percent of opioids prescribed using EPCS was 27%, up from 0% as of 2013. National rates of opioid prescriptions decreased from 78 prescriptions per 100 persons in 2013 to 53 in 2018. Over the same period, there was a decrease from 64 071 MME per 100 persons in 2013 to 40 906 MME per 100 persons in 2018, representing 36% of the 2013 level. By 2018, EPCS increased to 69.4% in states with mandates for its use and 23.6% in states without mandates. In multivariable models, a 10 percentage-point increase in the use of EPCS was associated with an additional 2 prescriptions per 100 persons (95% CI, 1.3-2.8) and a 0.8% (95% CI, 0.06%-1.5%) increase in MME per 100 persons. These data suggest that an increased use of EPCS was not associated with decreased opioid prescribing or a decrease in the amount prescribed and may have been associated with a small increase in opioid prescribing. Opioid prescribing is associated with a variety of social and public health factors, and thus, despite the appeal, EPCS adoption alone may be insufficient to reduce opioid prescribing. Policy makers should consider levers to ensure that EPCS is integrated with outside data and that information is actively used to inform prescribing decisions.
Gerard, Cheng-Hai Zhang, Min-Sheng Zhu, Kristine E. Kamm, James T. Stull. ... reveals that secondary, adaptational processes, triggered by the fHCM-related mutation, can obscure primary effects. 2464-Pos Board B450 Zipper-Interacting Protein Kinase Phosphorylates Cardiac Myosin Audrey ...doi:10.1016/j.bpj.2010.12.2676 fatcat:ifdx4d6lhbcbvcwjh7u4gqyzey
With recent advances in technology, deep sequencing data will be widely used to further the understanding of genetic influence on traits of interest. Therefore not only common variants but also rare variants need to be better used to exploit the new information provided by deep sequencing data. Recently, statistical approaches for analyzing rare variants in genetic association studies have been proposed, but many of them were designed only for dichotomous outcomes. We compare the type I errordoi:10.1186/1753-6561-5-s9-s113 pmid:22373209 pmcid:PMC3287837 fatcat:pvpep4bb55dqhj2ueagyk6ynu4
more »... d power of several statistical approaches applicable to quantitative traits for collapsing and analyzing rare variant data within a defined gene region. In addition to comparing methods that consider only rare variants, such as indicator, count, and data-adaptive collapsing methods, we also compare methods that incorporate the analysis of common variants along with rare variants, such as CMC and LASSO regression. We find that the three methods used to collapse rare variants perform similarly in this simulation setting where all risk variants were simulated to have effects in the same direction. Further, we find that incorporating common variants is beneficial and using a LASSO regression to choose which common variants to include is most useful when there is are few common risk variants compared to the total number of risk variants.
Pore-forming toxins (PFTs) are by far the most abundant bacterial protein toxins and are important for the virulence of many important pathogens. As such, cellular responses to PFTs critically modulate host-pathogen interactions. Although many cellular responses to PFTs have been recorded, little is understood about their relevance to pathological or defensive outcomes. To shed light on this important question, we have turned to the only genetic system for studying PFT-hostdoi:10.1371/journal.ppat.1000689 pmid:20011506 pmcid:PMC2785477 fatcat:ogtu5vvnjjhudl33c5bkh3mtf4
more »... bditis elegans intoxication by Crystal (Cry) protein PFTs. We mutagenized and screened for C. elegans mutants resistant to a Cry PFT and recovered one mutant. Complementation, sequencing, transgenic rescue, and RNA interference data demonstrate that this mutant eliminates a gene normally involved in repression of the hypoxia (low oxygen response) pathway. We find that up-regulation of the C. elegans hypoxia pathway via the inactivation of three different genes that normally repress the pathway results in animals resistant to Cry PFTs. Conversely, mutation in the central activator of the hypoxia response, HIF-1, suppresses this resistance and can result in animals defective in PFT defenses. These results extend to a PFT that attacks mammals since up-regulation of the hypoxia pathway confers resistance to Vibrio cholerae cytolysin (VCC), whereas down-regulation confers hypersusceptibility. The hypoxia PFT defense pathway acts cell autonomously to protect the cells directly under attack and is different from other hypoxia pathway stress responses. Two of the downstream effectors of this pathway include the nuclear receptor nhr-57 and the unfolded protein response. In addition, the hypoxia pathway itself is induced by PFT, and low oxygen is protective against PFT intoxication. These results demonstrate that hypoxia and induction of the hypoxia response protect cells against PFTs, and that the cellular environment can be modulated via the hypoxia pathway to protect against the most prevalent class of weapons used by pathogenic bacteria. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Obesity is associated with a decrease in mortality in the intensive care unit (ICU) (the "obesity paradox"). We hypothesized that obesity may paradoxically improve diaphragmatic function. Methods Diaphragm contractility was prospectively recorded in vitro in adult male Zucker lean (control), fatty, and diabetic fatty rats, at rest, after 12h mechanical ventilation and after fatigue. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways.doi:10.1371/journal.pone.0174043 pmid:28328996 pmcid:PMC5362060 fatcat:odrczcygxfe4fbo45bjpitv2se
more »... lts Diaphragm active-force (AF) was higher in fatty (96±7mN.mm -2 ,P = 0.02) but not in diabetic fatty rats (90±17mN.mm -2 ) when compared with controls (84±8mN.mm -2 ). Recovery from fatigue was improved in fatty and diabetic fatty groups compared with controls. Ventilatorinduced diaphragmatic dysfunction was observed in each group, but AF remained higher in fatty (82±8mN.mm -2 ,P = 0.03) compared with controls (70±8mN.mm -2 ). There was neutral lipid droplet accumulation in fatty and diabetic fatty. There were shifts towards a higher cross-sectional-area (CSA) of myosin heavy chain isoforms (MyHC)-2A fibers in fatty and diabetic fatty compared with control rats (P = 0.002 and P<0.001, respectively) and a smaller CSA of MyHC-2X in fatty compared with diabetic fatty and control rats (P<0.001 and P<0.001, respectively). The phosphorylated total-protein-kinase-B (pAKT)/AKT ratio was higher in fatty (182±58%,P = 0.03), but not in diabetic fatty when compared with controls PLOS ONE | https://doi.
Angiopoietin-like proteins (angptls) are capable of ex vivo expansion of mouse and human hematopoietic stem and progenitor cells (HSPCs). Despite this intriguing ability, their mechanism is unknown. In this study, we show that angptl2 overexpression is sufficient to expand definitive HSPCs in zebrafish embryos. Angptl1/2 are required for definitive hematopoiesis and vascular specification of the hemogenic endothelium. The loss-of-function phenotype is reminiscent of the notch mutant mindbombdoi:10.7554/elife.05544 pmid:25714926 pmcid:PMC4371382 fatcat:mkqcsu2lyjcjxnp6fdcsyryfxm
more »... b), and a strong genetic interaction occurs between angptls and notch. Overexpressing angptl2 rescues mib while overexpressing notch rescues angptl1/2 morphants. Gene expression studies in ANGPTL2-stimulated CD34+ cells showed a strong MYC activation signature and myc overexpression in angptl1/2 morphants or mib restored HSPCs formation. ANGPTL2 can increase NOTCH activation in cultured cells and ANGPTL receptor interacted with NOTCH to regulate NOTCH cleavage. Together our data provide insight to the angptl-mediated notch activation through receptor interaction and subsequent activation of myc targets.
Background The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma. Methods All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total ofdoi:10.1186/s13014-021-01835-0 pmid:34158078 pmcid:PMC8220779 fatcat:cjvyrrrnmfgghpe6rxcask3euy
more »... 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy. Results Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall. Conclusions There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.
Leber congenital amaurosis (LCA) encompasses a set of early-onset blinding diseases that are characterized by vision loss, involuntary eye movement, and nonrecordable electroretinogram (ERG). At least 19 genes are associated with LCA, which is typically recessive; however, mutations in homeodomain transcription factor CRX lead to an autosomal dominant form of LCA. The mechanism of CRX-associated LCA is not understood. Here, we identified a spontaneous mouse mutant with a frameshift mutation indoi:10.1172/jci72722 pmid:24382353 pmcid:PMC3904630 fatcat:3vtemhoeazc4dm4tqnibg52xhm
more »... rx (Crx Rip ). We determined that Crx Rip is a dominant mutation that results in congenital blindness with nonrecordable response by ERG and arrested photoreceptor differentiation with no associated degeneration. Expression of LCA-associated dominant CRX frameshift mutations in mouse retina mimicked the Crx Rip phenotype, which was rescued by overexpression of WT CRX. Whole-transcriptome profiling using deep RNA sequencing revealed progressive and complete loss of rod differentiation factor NRL in Crx Rip retinas. Expression of NRL partially restored rod development in Crx Rip/+ mice. We show that the binding of homeobox transcription factor OTX2 at the Nrl promoter was obliterated in Crx Rip mice and ectopic expression of OTX2 rescued the rod differentiation defect. Together, our data indicate that OTX2 maintains Nrl expression in developing rods to consolidate rod fate. Our studies provide insights into CRX mutation-associated congenital blindness and should assist in therapeutic design.
Metagenomic DNA sequencing is a powerful tool to characterize microbial communities but is sensitive to environmental DNA contamination, in particular when applied to samples with low microbial biomass. Here, we present contamination-free metagenomic DNA sequencing (Coffee-seq), a metagenomic sequencing assay that is robust against environmental contamination. The core idea of Coffee-seq is to tag the DNA in the sample prior to DNA isolation and library preparation with a label that can bedoi:10.1101/2021.11.22.469599 pmid:34845444 pmcid:PMC8629186 fatcat:trh6nrf4vfb7hjuwwgozid745u
more »... ded by DNA sequencing. Any contaminating DNA that is introduced in the sample after tagging can then be bioinformatically identified and removed. We applied Coffee-seq to screen for infections from microorganisms with low burden in blood and urine, to identify COVID-19 co-infection, to characterize the urinary microbiome, and to identify microbial DNA signatures of inflammatory bowel disease in blood.
27%; P =0.043, P =0.031 Forskolin 3 ,5 - 1 - 2 - - Zucker - Zucker 1 - 2 - - de la voie de la stimulation des récepteurs -adrénergiques dans le myocarde des rats Zucker obèses et obèses diabétiques Par Cheng ...doi:10.1097/ccm.0000000000000999 pmid:26079096 fatcat:jk4x5owejjgodesckmaxrrl2p4
Collective migration of epithelial cells is essential for morphogenesis, wound repair, and the spread of many cancers, yet how individual cells signal to one another to coordinate their movements is largely unknown. Here, we introduce a tissue-autonomous paradigm for semaphorin-based regulation of collective cell migration. Semaphorins typically regulate the motility of neuronal growth cones and other migrating cell types by acting as repulsive cues within the migratory environment. Studyingdoi:10.1016/j.cub.2019.01.049 pmid:30827914 pmcid:PMC6424623 fatcat:wa4k2rm7rngxhgvnibbazusa6i
more »... follicular epithelial cells of Drosophila, we discovered that the transmembrane semaphorin, Sema-5c, promotes collective cell migration by acting within the migrating cells themselves, not the surrounding environment. Sema-5c is planar polarized at the basal epithelial surface such that it is enriched at the leading edge of each cell. This location places it in a prime position to send a repulsive signal to the trailing edge of the cell ahead to communicate directional information between neighboring cells. Our data show that Sema-5c can signal across cell-cell boundaries to suppress protrusions in neighboring cells and that Plexin A is the receptor that transduces this signal. Finally, we present evidence that Sema-5c antagonizes the activity of Lar, another transmembrane guidance cue that operates along leading-trailing cell-cell interfaces in this tissue, via a mechanism that appears to be independent of Plexin A. Together, our results suggest that multiple transmembrane guidance cues can be deployed in a planar-polarized manner across an epithelium and work in concert to coordinate individual cell movements for collective migration.
Crispness and crunchiness are important factors in the enjoyment of many foods, but they are defined differently among dictionaries, consumers, and researchers. Sensory, mechanical, and acoustic methods have been used to provide data on crispness and crunchiness. Sensory measurements include biting force and sound intensity. Mechanical techniques resemble mastication and include flex, shear, and compression. Acoustical techniques measure frequency, intensity, and number of sound events. Waterdoi:10.1080/10942912.2011.573116 fatcat:glsczu43ybarvgin6j75cpkkly
more »... d oil content contribute to crispness and crunchiness, which also have temporal aspects. Information in the literature is compared in this article to develop definitions of crispness and crunchiness. A dense-textured food which, when chewed with the molars, undergoes a series of fractures while emitting relatively loud, low-pitched sounds. CONCLUSIONS Further work on differentiating and defining crispy and crunchy textures is needed so that universal standards can be obtained. Such definitions could be translated into any Downloaded by [DigiTop -USDA's Digital Desktop Library] at 12:09 12 April 2013 960 TUNICK ET AL. language and would be applicable to fruits, vegetables, baked foods, extruded foods, etc. Research in our laboratory, described in a subsequent article,  represents a step in that direction.
Phthalates are commonly used in plastic products in daily life. The endocrine-disrupting effects of phthalates have been widely reported. Accumulating evidence from human cohorts and lab animals indicate exposure to phthalates might impair neurodevelopment. However, the direct causal relationship and mechanism between phthalates with neurodevelopment and neurotoxicity have not been firmly established. We found that phthalates (i.e. DBP, DINP, BBP) disrupted the expression of estrogen receptorsdoi:10.1016/j.aquatox.2020.105469 pmid:32179334 fatcat:khsqdvm7dnas3lmqqyo75o2rr4
more »... esr1, esr2a, esr2b), and impaired neurogenesis in the brain of zebrafish during embryonic development. Moreover, the abnormal expression of estrogen receptors, especially esr2a, was partly rescued in zebrafish which exposed to phthalates, with the estrogen receptor antagonist tamoxifen. Hence, impaired neurogenesis of zebrafish exposed to phthalates was partly reversed by tamoxifen treatment. Moreover, our results show that induced pluripotent stem cells (iPSC)-derived human neurons exposed to phthalates triggered double-strand DNA breaks in vitro. Overall, this study demonstrates that exposure to phthalates affects neurodevelopment in zebrafish embryos and induces neurotoxicity in human neurons partly through disrupting the expression of estrogen receptors.
Chronic venous insufficiency is a chronic disease of the venous system with a prevalence of 25% to 40% in females and 10% to 20% in males. Venous leg ulcers (VLUs) result from venous insufficiency. VLUs have a prevalence of 0.18% to 1% with a 1-year recurrence of 25% to 50%, bearing significant socioeconomic burden. It is therefore important for regular assessment and monitoring of VLUs to prevent worsening. Our study aims to assess the intra- and inter-rater reliability of a machinedoi:10.1111/iwj.13644 pmid:34121320 pmcid:PMC8762571 fatcat:v567am3am5fe7lffjrsqma5rse
more »... sed handheld 3-dimensional infrared wound imaging device (WoundAide [WA] imaging system, Konica Minolta Inc, Tokyo, Japan) compared with traditional measurements by trained wound nurse. This is a prospective cross-sectional study on 52 patients with VLUs from September 2019 to January 2021 using three WA imaging systems. Baseline patient profile and clinical demographics were collected. Basic wound parameters (length, width and area) were collected for both traditional measurements and measurements taken by the WA imaging systems. Intra- and inter-rater reliability was analysed using intra-class correlation statistics. A total of 222 wound images from 52 patients were assessed. There is excellent intra-rater reliability of the WA imaging system on three different image captures of the same wound (intra-rater reliability ranging 0.978-0.992). In addition, there is excellent inter-rater reliability between the three WA imaging systems for length (0.987), width (0.990) and area (0.995). Good inter-rater reliability for length and width (range 0.875-0.900) and excellent inter-rater reliability (range 0.932-0.950) were obtained between wound nurse measurement and each of the WA imaging system. In conclusion, high intra- and inter-rater reliability was obtained for the WA imaging systems. We also obtained high inter-rater reliability of WA measurements against traditional wound measurement. The WA imaging system is a useful clinical adjunct in the monitoring of VLU wound documentation.
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