710 research outputs found
Nanowire-based very-high-frequency electromechanical resonator
Fabrication and readout of devices with progressively smaller size, ultimately down to the molecular scale, is critical for the development of very-high-frequency nanoelectromechanical systems (NEMS). Nanomaterials, such as carbon nanotubes or nanowires, offer immense prospects as active elements for these applications. We report the fabrication and measurement of a platinum nanowire resonator, 43 nm in diameter and 1.3 µm in length. This device, among the smallest NEMS reported, has a fundamental vibration frequency of 105.3 MHz, with a quality factor of 8500 at 4 K. Its resonant motion is transduced by a technique that is well suited to ultrasmall mechanical structures
Characterization of mouse neuro-urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation
Aim: To develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro-like access with in vivo-like neural connectivity. Methods: Adult male mice were decerebrated and arterially perfused with a carbogenated, Ringer’s solution to establish the DAPM. To allow distinction between central and peripheral actions of interventions, experiments were conducted in both the DAPM and in a “pithed” DAPM which has no brainstem or spinal cord control. Results: Functional micturition cycles were observed in response to bladder filling. During each void, the bladder showed strong contractions and the external urethral sphincter (EUS) showed bursting activity. Both the frequency and amplitude of non-voiding contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the LUT resulting in retention in DAPM as it increased tonic EUS activity and basal bladder pressure in a dose-dependent manner (basal pressure increase also noted in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion blockade (hexamethonium), initially caused incomplete voiding, and both drugs eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed bladder distention-induced activity in the non-noxious range which was associated with pMM. Conclusions: This study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice
Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neurons
Micturition requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. This involves a spino-bulbospinal control circuit incorporating Barrington’s nucleus in the pons (Barr). Ponto-spinal glutamatergic neurons that express corticotrophin-releasing hormone (CRH) form one of the largest Barr cell populations. BarrCRH neurons can generate bladder contractions, but it is unknown whether they act as a simple switch or provide a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with multisite extracellular recordings in urethane anaesthetised CRHCre mice show that BarrCRH neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. CRH itself provides negative feedback regulation of this process. These findings inform a new inferential model of autonomous micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding
The clinical outcomes of imaging modalities for surgical management Cushing’s disease – A systematic review and meta-analysis
Introduction: Cushing’s disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing’s disease. Methods: Searches of PubMed and EMBASE were conducted. Studies reporting on imaging modalities and clinical outcomes after surgical management of Cushing’s disease were included. Multilevel multivariable meta-regressions identified predictors of outcomes, adjusting for confounders and heterogeneity prior to investigating the effects of imaging. Results: 166 non-controlled single-arm studies were included, comprising 13181 patients over 44 years. The overall remission rate was 77.0% [CI: 74.9%-79.0%]. Cavernous sinus invasion (OR: 0.21 [CI: 0.07-0.66]; p=0.010), radiologically undetectable lesions (OR: 0.50 [CI: 0.37–0.69]; p<0.0001), previous surgery (OR=0.48 [CI: 0.28–0.81]; p=0.008), and lesions ≥10mm (OR: 0.63 [CI: 0.35–1.14]; p=0.12) were associated with lower remission. Less stringent thresholds for remission was associated with higher reported remission (OR: 1.37 [CI: 1.1–1.72]; p=0.007). After adjusting for this heterogeneity, no imaging modality showed significant differences in remission compared to standard preoperative MRI. The overall recurrence rate was 14.5% [CI: 12.1%-17.1%]. Lesion ≥10mm was associated with greater recurrence (OR: 1.83 [CI: 1.13–2.96]; p=0.015), as was greater duration of follow-up (OR: 1.53 (CI: 1.17–2.01); p=0.002). No imaging modality was associated with significant differences in recurrence. Despite significant improvements in detection rates over four decades, there were no significant changes in the reported remission or recurrence rates. Conclusion: A lack of controlled comparative studies makes it difficult to draw definitive conclusions. Within this limitation, the results suggest that despite improvements in radiological detection rates of Cushing’s disease over the last four decades, there were no changes in clinical outcomes. Advances in imaging alone may be insufficient to improve surgical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020187751
Astrobiological Complexity with Probabilistic Cellular Automata
Search for extraterrestrial life and intelligence constitutes one of the
major endeavors in science, but has yet been quantitatively modeled only rarely
and in a cursory and superficial fashion. We argue that probabilistic cellular
automata (PCA) represent the best quantitative framework for modeling
astrobiological history of the Milky Way and its Galactic Habitable Zone. The
relevant astrobiological parameters are to be modeled as the elements of the
input probability matrix for the PCA kernel. With the underlying simplicity of
the cellular automata constructs, this approach enables a quick analysis of
large and ambiguous input parameters' space. We perform a simple clustering
analysis of typical astrobiological histories and discuss the relevant boundary
conditions of practical importance for planning and guiding actual empirical
astrobiological and SETI projects. In addition to showing how the present
framework is adaptable to more complex situations and updated observational
databases from current and near-future space missions, we demonstrate how
numerical results could offer a cautious rationale for continuation of
practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo
What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017
Introduction: Storage phase bladder activity is a counter-intuitive observation of spontaneous contractions. They are potentially an intrinsic feature of the smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as well as other muscular elements in the mucosa may substantially influence them. They are identified in several models explaining lower urinary tract dysfunction. Methods: A consensus meeting at the International Consultation on Incontinence Research Society (ICI-RS) 2017 congress considered the origins and relevance of spontaneous bladder contractions by debating which cell type(s) modulate bladder spontaneous activity, whether the methodologies are sufficiently robust, and implications for healthy and abnormal lower urinary tract function. Results: The identified research priorities reflect a wide range of unknown aspects. Cellular contributions to spontaneous contractions in detrusor smooth muscle are still uncertain. Accordingly, insight into the cellular physiology of the bladder wall, particularly smooth muscle cells, interstitial cells, and urothelium, remains important. Upstream influences, such as innervation, endocrine, and paracrine factors, are particularly important. The cellular interactions represent the key understanding to derive the integrative physiology of organ function, notably the nature of signalling between mucosa and detrusor layers. Indeed, it is still not clear to what extent spontaneous contractions generated in isolated preparations mirror their normal and pathological counterparts in the intact bladder. Improved models of how spontaneous contractions influence pressure generation and sensory nerve function are also needed. Conclusions: Deriving approaches to robust evaluation of spontaneous contractions and their influences for experimental and clinical use could yield considerable progress in functional urology
Nuclear Charge Radii of Be-7,9,10 and the one-neutron halo nucleus Be-11
Nuclear charge radii of Be have been determined by
high-precision laser spectroscopy. On-line measurements were performed with
collinear laser spectroscopy in the transition on a
beam of Be ions. Collinear and anticollinear laser beams were used
simultaneously and the absolute frequency determination using a frequency comb
yielded an accuracy in the isotope-shift measurements of about
1 MHz. Combination with accurate calculations of the mass-dependent isotope
shifts yield nuclear charge radii. The charge radius decreases from Be to
Be and then increases for the halo nucleus Be. When comparing our
results with predictions of {\it ab initio} nuclear structure calculations we
find good agreement. Additionally, the nuclear magnetic moment of Be was
determined to be and that of Be from a previous
-NMR measurement was confirmed.Comment: 4 pages, 2 figures calculated mass shift values have been
re-evaluated with the latest mass values for the beryllium isotopes and the
nuclear polarization contribution for Be-11, published by K. Pachucki et al.
ater submission of our manuscript, is also included no
A scalable machine-learning approach to recognize chemical names within large text databases
MOTIVATION: The use or study of chemical compounds permeates almost every scientific field and in each of them, the amount of textual information is growing rapidly. There is a need to accurately identify chemical names within text for a number of informatics efforts such as database curation, report summarization, tagging of named entities and keywords, or the development/curation of reference databases. RESULTS: A first-order Markov Model (MM) was evaluated for its ability to distinguish chemical names from words, yielding ~93% recall in recognizing chemical terms and ~99% precision in rejecting non-chemical terms on smaller test sets. However, because total false-positive events increase with the number of words analyzed, the scalability of name recognition was measured by processing 13.1 million MEDLINE records. The method yielded precision ranges from 54.7% to 100%, depending upon the cutoff score used, averaging 82.7% for approximately 1.05 million putative chemical terms extracted. Extracted chemical terms were analyzed to estimate the number of spelling variants per term, which correlated with the total number of times the chemical name appeared in MEDLINE. This variability in term construction was found to affect both information retrieval and term mapping when using PubMed and Ovid
DNA topoisomerases participate in fragility of the oncogene RET
Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
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