560 research outputs found
Antarctic intermediate water circulation in the South Atlantic over the past 25,000years
Antarctic Intermediate Water is an essential limb of the Atlantic meridional overturning circulation that redistributes heat and nutrients within the Atlantic Ocean. Existing reconstructions have yielded conflicting results on the history of Antarctic Intermediate Water penetration into the Atlantic across the most recent glacial termination. In this study we present leachate, foraminiferal, and detrital neodymium isotope data from three intermediate-depth cores collected from the southern Brazil margin in the South Atlantic covering the past 25kyr. These results reveal that strong chemical leaching following decarbonation does not extract past seawater neodymium composition in this location. The new foraminiferal records reveal no changes in seawater Nd isotopes during abrupt Northern Hemisphere cold events at these sites. We therefore conclude that there is no evidence for greater incursion of Antarctic Intermediate Water into the South Atlantic during either the Younger Dryas or Heinrich Stadial 1. We do, however, observe more radiogenic Nd isotope values in the intermediate-depth South Atlantic during the mid-Holocene. This radiogenic excursion coincides with evidence for a southward shift in the Southern Hemisphere westerlies that may have resulted in a greater entrainment of radiogenic Pacific-sourced water during intermediate water production in the Atlantic sector of the Southern Ocean. Our intermediate-depth records show similar values to a deglacial foraminiferal Nd isotope record from the deep South Atlantic during the Younger Dryas but are clearly distinct during the Last Glacial Maximum and Heinrich Stadial 1, demonstrating that the South Atlantic remained chemically stratified during Heinrich Stadial 1.Natural Environment Research Council (Grant IDs: NE/K005235/1, NE/F006047/1), National Science Foundation (Grant ID: OCE -1335191), Rutherford Memorial Scholarship, DFG Research Center/Cluster of Excellence âThe Ocean in the Earth Systemâ, FAPESP (Grant ID: 2012/17517-3), CAPES (Grant IDs: 1976/2014, 564/2015
BPMN task instance streaming for efficient micro-task crowdsourcing processes
The Business Process Model and Notation (BPMN) is a standard for modeling and executing business processes with human or machine tasks. The semantics of tasks is usually discrete: a task has exactly one start event and one end event; for multi-instance tasks, all instances must complete before an end event is emitted. We propose a new task type and streaming connector for crowdsourcing able to run hundreds or thousands of micro-task instances in parallel. The two constructs provide for task streaming semantics that is new to BPMN, enable the modeling and efficient enactment of complex crowdsourcing scenarios, and are applicable also beyond the special case of crowdsourcing. We implement the necessary design and runtime support on top of Crowd- Flower, demonstrate the viability of the approach via a case study, and report on a set of runtime performance experiments
Translations equations to compare ActiGraph GT3X and Actical accelerometers activity counts
Background: This study aimed to develop a translation equation to enable comparison between Actical and ActiGraph GT3X accelerometer counts recorded minute by minute. Methods: Five males and five females of variable height, weight, body mass index and age participated in this investigation. Participants simultaneously wore an Actical and an ActiGraph accelerometer for two days. Conversion algorithms and R2 were calculated day by day for each subject between the omnidirectional Actical and three different ActiGraph (three-dimensional) outputs: 1) vertical direction, 2) combined vector, and 3) a custom vector. Three conversion algorithms suitable for minute/minute conversions were then calculated from the full data set. Results: The vertical ActiGraph activity counts demonstrated the closest relationship with the Actical, with consistent moderate to strong conversions using the algorithm: y = 0.905x, in the day by day data (R2 range: 0.514 to 0.989 and average: 0.822) and full data set (R2 = 0.865). Conclusions: The Actical is most sensitive to accelerations in the vertical direction, and does not closely correlate with three-dimensional ActiGraph output. Minute by minute conversions between the Actical and ActiGraphvertical component can be confidently performed between data sets and might allow further synthesis of information between studies
Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism
BACKGROUND: The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. METHODS: This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done. RESULTS: Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. CONCLUSION: Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice
Ethological principles predict the neuropeptides co-opted to influence parenting
Ethologists predicted that parental care evolves by modifying behavioural precursors in the asocial ancestor. As a corollary, we predict that the evolved mechanistic changes reside in genetic pathways underlying these traits. Here we test our hypothesis in female burying beetles, Nicrophorus vespilloides, an insect where caring adults regurgitate food to begging, dependent offspring. We quantify neuropeptide abundance in brains collected from three behavioural states: solitary virgins, individuals actively parenting or post-parenting solitary adults and quantify 133 peptides belonging to 18 neuropeptides. Eight neuropeptides differ in abundance in one or more states, with increased abundance during parenting in seven. None of these eight neuropeptides have been associated with parental care previously, but all have roles in predicted behavioural precursors for parenting. Our study supports the hypothesis that predictable traits and pathways are targets of selection during the evolution of parenting and suggests additional candidate neuropeptides to study in the context of parenting
Immune-Mobilizing Monoclonal T Cell Receptors Mediate Specific and Rapid Elimination of Hepatitis B-Infected Cells
Background and Aims:
Therapies for chronic hepatitis B virus (HBV) infection are urgently needed because of viral integration, persistence of viral antigen expression, inadequate HBVâspecific immune responses, and treatment regimens that require lifelong adherence to suppress the virus. Immune mobilizing monoclonal T Cell receptors against virus (ImmTAV) molecules represent a therapeutic strategy combining an affinityâenhanced T Cell receptor with an antiâCD3 T Cellâactivating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virusâderived peptides presented by human leukocyte antigen (HLA).
Approach and Results:
ImmTAV molecules specific for HLAâA*02:01ârestricted epitopes from HBV envelope, polymerase, and core antigens were engineered. The ability of ImmTAVâEnv to activate and redirect polyclonal T cells toward cells containing integrated HBV and cells infected with HBV was assessed using cytokine secretion assays and imagingâbased killing assays. Elimination of infected cells was further quantified using a modified fluorescent hybridization of viral RNA assay. Here, we demonstrate that picomolar concentrations of ImmTAVâEnv can redirect T cells from healthy and HBVâinfected donors toward hepatocellular carcinoma (HCC) cells containing integrated HBV DNA resulting in cytokine release, which could be suppressed by the addition of a corticosteroid in vitro. Importantly, ImmTAVâEnv redirection of T cells induced cytolysis of antigenâpositive HCC cells and cells infected with HBV in vitro, causing a reduction of hepatitis B e antigen and specific loss of cells expressing viral RNA.
Conclusions:
The ImmTAV platform has the potential to enable the elimination of infected cells by redirecting endogenous nonâHBVâspecific T cells, bypassing exhausted HBVâspecific T cells. This represents a promising therapeutic option in the treatment of chronic hepatitis B, with our lead candidate now entering trials
Methods to study splicing from high-throughput RNA Sequencing data
The development of novel high-throughput sequencing (HTS) methods for RNA
(RNA-Seq) has provided a very powerful mean to study splicing under multiple
conditions at unprecedented depth. However, the complexity of the information
to be analyzed has turned this into a challenging task. In the last few years,
a plethora of tools have been developed, allowing researchers to process
RNA-Seq data to study the expression of isoforms and splicing events, and their
relative changes under different conditions. We provide an overview of the
methods available to study splicing from short RNA-Seq data. We group the
methods according to the different questions they address: 1) Assignment of the
sequencing reads to their likely gene of origin. This is addressed by methods
that map reads to the genome and/or to the available gene annotations. 2)
Recovering the sequence of splicing events and isoforms. This is addressed by
transcript reconstruction and de novo assembly methods. 3) Quantification of
events and isoforms. Either after reconstructing transcripts or using an
annotation, many methods estimate the expression level or the relative usage of
isoforms and/or events. 4) Providing an isoform or event view of differential
splicing or expression. These include methods that compare relative
event/isoform abundance or isoform expression across two or more conditions. 5)
Visualizing splicing regulation. Various tools facilitate the visualization of
the RNA-Seq data in the context of alternative splicing. In this review, we do
not describe the specific mathematical models behind each method. Our aim is
rather to provide an overview that could serve as an entry point for users who
need to decide on a suitable tool for a specific analysis. We also attempt to
propose a classification of the tools according to the operations they do, to
facilitate the comparison and choice of methods.Comment: 31 pages, 1 figure, 9 tables. Small corrections adde
Comparison of uniaxial and triaxial accelerometry in the assessment of physical activity among adolescents under free-living conditions: the HELENA study
<p>Abstract</p> <p>Background</p> <p>Different types of devices are available and the choice about which to use depends on various factors: cost, physical characteristics, performance, and the validity and intra- and interinstrument reliability. Given the large number of studies that have used uniaxial or triaxial devices, it is of interest to know whether the different devices give similar information about PA levels and patterns. The aim of this study was to compare physical activity (PA) levels and patterns obtained simultaneously by triaxial accelerometry and uniaxial accelerometry in adolescents in free-living conditions.</p> <p>Methods</p> <p>Sixty-two participants, aged 13-16 years, were recruited in this ancillary study, which is a part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA). All participants wore a uniaxial accelerometer (ActiGraph GT1M<sup>Âź</sup>, Pensacola, FL) and a triaxial accelerometer (RT3<sup>Âź</sup>, Stayhealthy, Monrovia, CA) simultaneously for 7 days. The patterns were calculated by converting accelerometer data output as a percentage of time spent at sedentary, light, moderate, and vigorous PA per day. Analysis of output data from the two accelerometers were assessed by two different tests: Equivalence Test and Bland & Altman method.</p> <p>Results</p> <p>The concordance correlation coefficient between the data from the triaxial accelerometer and uniaxial accelerometer at each intensity level was superior to 0.95. The ANOVA test showed a significant difference for the first three lower intensities while no significant difference was found for vigorous intensity. The difference between data obtained with the triaxial accelerometer and the uniaxial monitor never exceeded 2.1% and decreased as PA level increased. The Bland & Altman method showed good agreement between data obtained between the both accelerometers (<it>p </it>< 0.05).</p> <p>Conclusions</p> <p>Uniaxial and triaxial accelerometers do not differ in their measurement of PA in population studies, and either could be used in such studies.</p
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