1,501 research outputs found
Selfies beyond self-representation: the (theoretical) f(r)ictions of a practice
Drawing on a wide corpus of ethnographic research pro- jects, including on photography practices, young film- makers and writers, and current research with young unemployed people, we argue that contemporary under- standings of selfies either in relation to a ‘‘documenting of the self’’ or as a neoliberal (narcissistic) identity affirmation are inherently problematic. Instead, we argue that selfies should be understood as a wider social, cultural, and media phenomenon that understands the selfie as far more than a representational image. This, in turn, necessarily redirects us away from the object ‘‘itself,’’ and in so doing seeks to understand selfies as a socio-technical phenomenon that momentarily and tentatively holds together a number of different elements of mediated digital communication
Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins
Background: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. Materials and Methods: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting. Ingenuity pathway analysis revealed metabolomic pathway changes. Results: A total of 189 proteins were identified with restricted criteria. Combined treatment targeting the proteasome-ubiquitin pathway resulted in re-sensitisation of drug-resistant cells. In addition, examination of five surgical biopsies of ovarian tissues revealed α-enolase (ENOA), elongation factor Tu, mitochondrial (EFTU), glyceraldehyde-3-phosphate dehydrogenase (G3P), stress-70 protein, mitochondrial (GRP75), apolipoprotein A-1 (APOA1), peroxiredoxin (PRDX2) and annexin A (ANXA) as candidate biomarkers of drug-resistant disease. Conclusion: Proteomics combined with pathway analysis provided information for an effective combined treatment approach overcoming drug resistance. Analysis of cell lines and tissues revealed potential prognostic biomarkers for ovarian cancer
Towards developing a Core Outcome Set for malnutrition intervention studies in older adults: a scoping review to identify frequently used research outcomes
Purpose: To conduct a scoping review to provide a systematic overview of outcomes used in nutritional intervention studies focused on the treatment of protein-energy malnutrition in older adults. // Methods: A systematic search of four electronic databases (Medline, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL) was performed to retrieve randomized controlled trials (RCTs), published until March 9, 2020, that evaluated the effect of nutritional interventions to treat protein-energy malnutrition in older adults and those at risk for malnutrition. Two authors screened titles, abstracts and full texts independently. One author extracted data that were cross-checked by another author. // Results: Sixty-three articles reporting 60 RCTs were identified. Most frequently used outcomes included body weight/body mass index (75.0% of RCTs), dietary intake (61.7%), functional limitations (48.3%), handgrip strength (46.7%), and body circumference (40.0%). The frequencies differed by setting (community, hospital and long-term care). For some outcomes there was a preferred assessment method (e.g., Barthel index for functional limitations), while for other outcomes (e.g., functional performance) a much greater variation was observed. // Conclusion: A large variation in outcomes, not only across but also within settings, was identified in nutritional intervention studies in malnourished older adults and those at risk. Furthermore, for many outcomes there was a large variation in the used assessment method. These results highlight the need for developing a Core Outcome Set for malnutrition intervention studies in older adults to facilitate future meta-analyses that may enhance our understanding on the effectiveness of treatment
A constitutive law for dense granular flows
A continuum description of granular flows would be of considerable help in
predicting natural geophysical hazards or in designing industrial processes.
However, the constitutive equations for dry granular flows, which govern how
the material moves under shear, are still a matter of debate. One difficulty is
that grains can behave like a solid (in a sand pile), a liquid (when poured
from a silo) or a gas (when strongly agitated). For the two extreme regimes,
constitutive equations have been proposed based on kinetic theory for
collisional rapid flows, and soil mechanics for slow plastic flows. However,
the intermediate dense regime, where the granular material flows like a liquid,
still lacks a unified view and has motivated many studies over the past decade.
The main characteristics of granular liquids are: a yield criterion (a critical
shear stress below which flow is not possible) and a complex dependence on
shear rate when flowing. In this sense, granular matter shares similarities
with classical visco-plastic fluids such as Bingham fluids. Here we propose a
new constitutive relation for dense granular flows, inspired by this analogy
and recent numerical and experimental work. We then test our three-dimensional
(3D) model through experiments on granular flows on a pile between rough
sidewalls, in which a complex 3D flow pattern develops. We show that, without
any fitting parameter, the model gives quantitative predictions for the flow
shape and velocity profiles. Our results support the idea that a simple
visco-plastic approach can quantitatively capture granular flow properties, and
could serve as a basic tool for modelling more complex flows in geophysical or
industrial applications.Comment: http://www.nature.com/nature/journal/v441/n7094/abs/nature04801.htm
Magnesium lactate in the treatment of Gitelman syndrome: patient-reported outcomes.
BACKGROUND: Gitelman syndrome (GS) is a rare recessively inherited renal tubulopathy associated with renal potassium (K) and magnesium (Mg) loss. It requires lifelong K and Mg supplementation at high doses that are at best unpalatable and at worst, intolerable. In particular, gastrointestinal side effects often limit full therapeutic usage. METHODS: We report here the analysis of a cohort of 28 adult patients with genetically proven GS who attend our specialist tubular disorders clinic, in whom we initiated the use of a modified-release Mg preparation (slow-release Mg lactate) and who were surveyed by questionnaire. RESULTS: Twenty-five patients (89%) preferred the new treatment regimen. Of these 25, 17 (68%) regarded their symptom burden as improved and seven reported no worsening. Of the 25 who were not Mg-treatment naïve, 13 (59%) patients reported fewer side effects, 7 (32%) described them as the same and only 2 (9%) considered side effects to be worse. Five were able to increase their dose without ill-effect. Overall, biochemistry improved in 91% of the 23 patients switched from therapy with other preparations who chose to continue the modified-release Mg preparation. Eleven (48%) improved both their Mg and K mean levels, 3 (13%) improved Mg levels only and in 7 cases (30%), K levels alone rose. CONCLUSIONS: Patient-reported and biochemical outcomes using modified-release Mg supplements were very favourable, and patient choice should play a large part in choosing Mg supplements with GS patients.This work was supported by the Wellcome Trust and the NIHR Cambridge Biomedical Research Centre, and contains data that were presented in abstract form at ASN Kidney week 2014.This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/ndt/gfw01
FASTKIT: A Mobile Cable-Driven Parallel Robot for Logistics
International audienceThe subject of this paper is about the design, modeling, control and performance evaluation of a low cost and versatile robotic solution for logistics. The robot under study, named FASTKIT, is obtained from a combination of mobile robots and a Cable-Driven Parallel Robot (CDPR). FASTKIT addresses an industrial need for fast picking and kitting operations in existing storage facilities while being easy to install, keeping existing infrastructures and covering large areas. The FASTKIT prototype consists of two mobile bases that carry the exit points of the CDPR. The system can navigate autonomously to the area of interest. Once the desired position is attained, the system deploys the CDPR in such a way that its workspace corresponds to the current task specification. The system calculates the required mobile base position from the desired workspace and ensures the controllability of the platform during the deployment. Once the system is successfully deployed, the set of stabilizers are used to ensure the prototype structural stability. Then the prototype gripper is moved accurately by the CDPR at high velocity over a large area by controlling the cable tension
Simultaneous determination of natural and synthetic steroid estrogens and their conjugates in aqueous matrices by liquid chromatography / mass spectrometry
An analytical method for the simultaneous determination of nine free and conjugated steroid estrogens was developed with application to environmental aqueous matrices. Solid phase extraction (SPE) was employed for isolation and concentration, with detection by liquid chromatography/mass spectrometry (LC/MS) using electrospray ionisation (ESI) in the negative mode. Method recoveries for various aqueous matrices (wastewater, lake and drinking water) were determined, recoveries proving to be sample dependent. When spiked at 50 ng/l concentrations in sewage influent, recoveries ranged from 62-89 % with relative standard deviations (RSD) < 8.1 %. In comparison, drinking water spiked at the same concentrations had recoveries between 82-100 % with an RSD < 5%. Ion suppression is a known phenomenon when using ESI; hence its impact on method recovery was elucidated for raw sewage. Both ion suppression from matrix interferences and the extraction procedure has bearing on the overall method recovery. Analysis of municipal raw sewage identified several of the analytes of interest at ng/l concentrations, estriol (E3) being the most abundant. Only one conjugate, estrone 3-sulphate (E1-3S) was observe
Paediatric obsessive-compulsive disorder and depressive symptoms: clinical correlates and CBT treatment outcomes.
Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 - 18] years, 42 % female), using both dimensional (Beck Depression Inventory-youth; n = 261) and diagnostic (Development and Wellbeing Assessment; n = 127) measures of depression. The impact of depressive symptoms and suspected disorders on post-treatment OCD severity was examined in a sub-sample who received CBT, with or without SSRI medication (N = 100). Fifty-one per-cent of patients reported moderately or extremely elevated depressive symptoms and 26 % (95 % CI: 18 - 34) met criteria for a suspected depressive disorder. Depressive symptoms and depressive disorders were associated with worse OCD symptom severity and global functioning prior to CBT. Individuals with depression were more likely to be female, have had a psychiatric inpatient admission and less likely to be attending school (ps < 0.01). OCD and depressive symptom severity significantly decreased after CBT. Depressive symptoms and depressive disorders predicted worse post-treatment OCD severity (βs = 0.19 and 0.26, ps < 0.05) but became non-significant when controlling for pre-treatment OCD severity (βs = 0.05 and 0.13, ns). Depression is common in paediatric OCD and is associated with more severe OCD and poorer functioning. However, depression severity decreases over the course of CBT for OCD and is not independently associated with worse outcomes, supporting the recommendation for treatment as usual in the presence of depressive symptoms
Modifying the m6A brain methylome by ALKBH5-mediated demethylation: a new contender for synaptic tagging
Synaptic plasticity processes, which underlie learning and memory formation, require RNA to be translated local to synapses. The synaptic tagging hypothesis has previously been proposed to explain how mRNAs are available at specific activated synapses. However how RNA is regulated, and which transcripts are silenced or processed as part of the tagging process is still unknown. Modification of RNA by N6-methyladenosine (m6A/m) influences the cellular fate of mRNA. Here, by advanced microscopy, we showed that m6A demethylation by the eraser protein ALKBH5 occurs at active synaptic ribosomes and at synapses during short term plasticity. We demonstrated that at activated glutamatergic post-synaptic sites, both the YTHDF1 and YTHDF3 reader and the ALKBH5 eraser proteins increase in co-localisation to m6A-modified RNAs; but only the readers showed high co-localisation to modified RNAs during late-stage plasticity. The YTHDF1 and YTHFDF3 readers also exhibited differential roles during synaptic maturation suggesting that temporal and subcellular abundance may determine specific function. m6A-sequencing of human parahippocampus brain tissue revealed distinct white and grey matter m6A methylome profiles indicating that cellular context is a fundamental factor dictating regulated pathways. However, in both neuronal and glial cell-rich tissue, m6A effector proteins are themselves modified and m6A epitranscriptional and posttranslational modification processes coregulate protein cascades. We hypothesise that the availability m6A effector protein machinery in conjunction with RNA modification, may be important in the formation of condensed synaptic nanodomain assemblies through liquid-liquid phase separation. Our findings support that m6A demethylation by ALKBH5 is an intrinsic component of the synaptic tagging hypothesis and a molecular switch which leads to alterations in the RNA methylome, synaptic dysfunction and potentially reversible disease states
A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13
The size of von Willebrand factor (VWF), controlled by ADAMTS13-dependent proteolysis, is associated with its hemostatic activity. Many factors regulate ADAMTS13-dependent VWF proteolysis through their interaction with VWF. These include coagulation factor VIII, platelet glycoprotein 1bα, and heparin sulfate, which accelerate the cleavage of VWF. Conversely, thrombospondin-1 decreases the rate of VWF proteolysis by ADAMTS13 by competing with ADAMTS13 for the A3 domain of VWF. To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. Additionally, the epitope of anti-VWF mAb (SZ34) was mapped using recombinant proteins in combination with enzyme-linked immunosorbent assay and Western blot analysis. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. The binding epitope of SZ34 mAb is located between A1555 and G1595 in the central A2 domain of VWF. These data show that an anti-VWF mAb against the VWF-A2 domain (A1555-G1595) reduces the proteolytic cleavage of VWF by ADAMTS13 under shear stress, suggesting the role of this region in interaction with ADAMTS13
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