230 research outputs found

    High-concentration Er:YAG single-crystal fibers grown by laser-heated pedestal growth technique

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    High-concentration Er:YAG single-crystal fibers have been grown using the laser-heated pedestal growth technique. Instability in the melt and concomitant opacity of fibers were observed at source concentrations higher than 15 mol.%. Spectroscopic examination shows that broadening of the linewidth of the I<sub>13/2</sub>4→I<sub>15/2</sub>4 transition is strongly dependent on Er<sup>3+</sup> concentration

    Spatial and temporal variation in long-term sediment accumulation in a back-barrier salt marsh

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    In situ persistence of salt marshes in the face of sea-level rise relies on their ability to maintain substrate elevation through sufficient vertical accretion of sediment. However, sedimentation rates in salt marshes vary spatially and temporally, which complicates the assessment of their ability to keep up with sea-level rise. Here, we explore the spatial and temporal variation in sediment accumulation in a single back-barrier salt marsh site. Using one-time in situ measurements at the landscape scale, we obtained synoptic information of elevation and sediment thickness over the entire salt marsh in a chronosequence over centuries. Repeated measurements along short elevation transects (0.3–0.9 m +MHT) revealed decadal changes, complementing the broader marsh data with detailed information on elevation, thickness of the marsh deposits and accumulation rates. Thickness of the deposits was largely related to the elevation gradient: the sediment layer was thinner at the higher marsh (near the dunes and far away from the intertidal flats), and thicker at the lower marsh (near the intertidal flats). Moreover, the thickness of the layer increased with salt marsh age along the chronosequence, and age accounted for 72 % of variability in sediment accumulation. The rate of sediment accumulation was higher than the local rate of sea-level rise in the younger marsh, whereas it was equal to the rate of sea-level rise in the older marsh. In the older salt marsh, sediment accumulation was lower, possibly due to autocompaction in the thicker, older layers. Both at the landscape scale and along short elevation transects within individual drainage basins, sediment accumulation decreased with distance to sediment supply routes. However, their relative importance depended on the scale of observation. Distance to creeks accounted for 17 % of the variability in sediment accumulation at the landscape scale, compared to 4 % at the smaller scale. Similarly, the influence of distance to intertidal flats varied from 1 % at the landscape scale to 13 % at the smaller scale. Our main findings indicate that lower-elevation older marshes and higher-elevation younger marshes far away from sediment sources are at risk of not keeping pace with the local rate of sea-level rise and are potentially vulnerable to increased flooding.</p

    Breathlessness is associated with urinary incontinence in men: A community-based study

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    <p>Abstract</p> <p>Background</p> <p>Urinary incontinence (UI) is a distressing problem for older people. To investigate the relationship between UI and respiratory symptoms among middle-aged and older men, a community-based study was conducted in Japan.</p> <p>Methods</p> <p>A convenience sample of 668 community-dwelling men aged 40 years or above was recruited from middle and southern Japan. The International Consultation on Incontinence Questionnaire-Short Form, the Medical Research Council's dyspnoea scale and the Australian Lung Foundation's Feeling Short of Breath scale, were administered by face-to-face interviews to ascertain their UI status and respiratory symptoms.</p> <p>Results</p> <p>The overall prevalence of UI was 7.6%, with urge-type leakage (59%) being most common among the 51 incontinent men. The presence of respiratory symptoms was significantly higher among incontinent men than those without the condition, especially for breathlessness (45% versus 30%, <it>p </it>= 0.025). The odds of UI for breathlessness was 2.11 (95% confidence interval 1.10-4.06) after accounting for age, body mass index, smoking and alcohol drinking status of each individual.</p> <p>Conclusions</p> <p>The findings suggested a significant association between UI and breathlessness in middle-aged and older men.</p

    Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane

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    Rif1 is involved in telomere homeostasis, DNA replication timing, and DNA double-strand break (DSB) repair pathway choice from yeast to human. The molecular mechanisms that enable Rif1 to fulfill its diverse roles remain to be determined. Here, we demonstrate that Rif1 is S-acylated within its conserved N-terminal domain at cysteine residues C466 and C473 by the DHHC family palmitoyl acyltransferase Pfa4. Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, the attenuation of DNA end-resection, and DSB repair by non-homologous end-joining (NHEJ). These findings identify S-acylation as a posttranslational modification regulating DNA repair. S-acylated Rif1 mounts a localized DNA-damage response proximal to the inner nuclear membrane, revealing a mechanism of compartmentalized DSB repair pathway choice by sequestration of a fatty acylated repair factor at the inner nuclear membrane

    Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability

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    Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA polymerase II, causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions. However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR-Cas9 screen, we identified the elongation factor ELOF1 as an important factor in the transcription stress response following DNA damage. We show that ELOF1 has an evolutionarily conserved role in transcription-coupled nucleotide excision repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair transcription-blocking lesions and resume transcription. Additionally, ELOF1 modulates transcription to protect cells against transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms

    A high-order FEM formulation for free and forced vibration analysis of a nonlocal nonlinear graded Timoshenko nanobeam based on the weak form quadrature element method

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    The purpose of this paper is to provide a high-order finite element method (FEM) formulation of nonlocal nonlinear nonlocal graded Timoshenko based on the weak form quadrature element method (WQEM). This formulation offers the advantages and flexibility of the FEM without its limiting low-order accuracy. The nanobeam theory accounts for the von Kármán geometric nonlinearity in addition to Eringen’s nonlocal constitutive models. For the sake of generality, a nonlinear foundation is included in the formulation. The proposed formulation generates high-order derivative terms that cannot be accounted for using regular first- or second-order interpolation functions. Hamilton’s principle is used to derive the variational statement which is discretized using WQEM. The results of a WQEM free vibration study are assessed using data obtained from a similar problem solved by the differential quadrature method (DQM). The study shows that WQEM can offer the same accuracy as DQM with a reduced computational cost. Currently the literature describes a small number of high-order numerical forced vibration problems, the majority of which are limited to DQM. To obtain forced vibration solutions using WQEM, the authors propose two different methods to obtain frequency response curves. The obtained results indicate that the frequency response curves generated by either method closely match their DQM counterparts obtained from the literature, and this is despite the low mesh density used for the WQEM systems

    Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends

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    In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ∼125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an α-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer. Engagement of the Rif1-NTD with telomeres proved essential for checkpoint control and telomere length regulation. Unexpectedly, Rif1-NTD also promoted NHEJ at DNA breaks in yeast, revealing a conserved role of Rif1 in DNA repair. We propose that tight associations between the Rif1-NTD and DNA gate access of processing factors to DNA ends, enabling Rif1 to mediate diverse telomere maintenance and DNA repair functions

    The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS

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    Background The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Methods and analysis Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care. . .'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. Conclusions This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. Copyright
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