467 research outputs found
Foolproof quick-release locking pin
Locking pin can be withdrawn only when stress on the joint is negligible. Pin consists of a forward-pointing sleeve, a spring-loaded sliding handle, and a sliding plunger. Plunger movement controls installation and withdrawal of pin
A novel 18F-labelled high affinity agent for PET imaging of the translocator protein
The translocator protein (TSPO) is an important target for imaging focal neuroinflammation in diseases such as brain cancer, stroke and neurodegeneration, but current tracers for non-invasive imaging of TSPO have important limitations. We present the synthesis and evaluation of a novel 3-fluoromethylquinoline-2-carboxamide, AB5186, which was prepared in eight steps using a one-pot two component indium(III)-catalysed reaction for the rapid and efficient assembly of the 4-phenylquinoline core. Biological assessment and the implementation of a physicochemical study showed AB5186 to have low nanomolar affinity for TSPO, as well as optimal plasma protein binding and membrane permeability properties. Generation of [18F]-AB5186 through 18F incorporation was achieved in good radiochemical yield and subsequent in vitro and ex vivo autoradiography revealed the ability of this compound to bind with specificity to TSPO in mouse glioblastoma xenografts. Initial positron emission tomography imaging of a glioma bearing mouse and a healthy baboon support the potential for [18F]-AB5186 use as a radiotracer for non-invasive TSPO imaging in vivo
Synthesis and evaluation of a radioiodinated tracer with specificity for poly(ADP-ribose) polymerase-1 (PARP-1) in vivo
Interest in nuclear imaging of poly(ADP-ribose) polymerase-1 (PARP-1) has grown in recent years due to the ability of PARP-1 to act as a biomarker for glioblastoma and increased clinical use of PARP-1 inhibitors. This study reports the identification of a lead iodinated analog 5 of the clinical PARP-1 inhibitor olaparib as a potential single-photon emission computed tomography (SPECT) imaging agent. Compound 5 was shown to be a potent PARP-1 inhibitor in cell-free and cellular assays, and it exhibited mouse plasma stability but approximately 3-fold greater intrinsic clearance when compared to olaparib. An (123)I-labeled version of 5 was generated using solid state halogen exchange methodology. Ex vivo biodistribution studies of [(123)I]-5 in mice bearing subcutaneous glioblastoma xenografts revealed that the tracer had the ability to be retained in tumour tissue and bind to PARP-1 with specificity. These findings support further investigations of [(123)I]-5 as a non-invasive PARP-1 SPECT imaging agent
Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families
Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension
An 18F-labeled poly(ADP-ribose) polymerase positron emission tomography imaging agent
Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks
and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for
positron emission tomography (PET) and single photon emission computed tomography
imaging. Consequently, over the past decade, there has been a drive to develop nuclear
imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based
on the potent PARP inhibitor olaparib (1). Our lead PET tracer candidate, [18F]20, was
synthesized and evaluated as a potential PARP PET radiotracer in mice bearing
subcutaneous glioblastoma xenografts using ex vivo biodistribution and PETâmagnetic
resonance imaging techniques. Results showed that [18F]20 could be produced in a good
radioactivity yield and exhibited specific PARP binding allowing visualization of tumors overexpressing
PARP. [18F]20 is therefore a potential candidate radiotracer for in vivo PARP
PET imaging
Multi-center evaluation of analytical performance of the Beckman Coulter AU5822 chemistry analyzer
Objectives
Our three academic institutions, Indiana University, Northwestern Memorial Hospital, and Wake Forest, were among the first in the United States to implement the Beckman Coulter AU5822 series chemistry analyzers. We undertook this post-hoc multi-center study by merging our data to determine performance characteristics and the impact of methodology changes on analyte measurement.
Design and methods
We independently completed performance validation studies including precision, linearity/analytical measurement range, method comparison, and reference range verification. Complete data sets were available from at least one institution for 66 analytes with the following groups: 51 from all three institutions, and 15 from 1 or 2 institutions for a total sample size of 12,064.
Results
Precision was similar among institutions. Coefficients of variation (CV) were 10% included direct bilirubin and digoxin. All analytes exhibited linearity over the analytical measurement range. Method comparison data showed slopes between 0.900-1.100 for 87.9% of the analytes. Slopes for amylase, tobramycin and urine amylase were 1.5, due to known methodology or standardization differences. Consequently, reference ranges of amylase, urine amylase and lipase required only minor or no modification.
Conclusion
The four AU5822 analyzers independently evaluated at three sites showed consistent precision, linearity, and correlation results. Since installations, the test results had been well received by clinicians from all three institutions
Underground operation of the ICARUS T600 LAr-TPC: first results
Open questions are still present in fundamental Physics and Cosmology, like
the nature of Dark Matter, the matter-antimatter asymmetry and the validity of
the particle interaction Standard Model. Addressing these questions requires a
new generation of massive particle detectors exploring the subatomic and
astrophysical worlds. ICARUS T600 is the first large mass (760 ton) example of
a novel detector generation able to combine the imaging capabilities of the old
famous "bubble chamber" with an excellent energy measurement in huge electronic
detectors. ICARUS T600 now operates at the Gran Sasso underground laboratory,
studying cosmic rays, neutrino oscillation and proton decay. Physical
potentialities of this novel telescope are presented through few examples of
neutrino interactions reconstructed with unprecedented details. Detector design
and early operation are also reported.Comment: 14 pages, 8 figures, 2 tables. Submitted to Jins
First E region observations of mesoscale neutral wind interaction with auroral arcs
We report the first observations of E region neutral wind fields and their interaction with auroral arcs at mesoscale spatial resolution during geomagnetically quiet conditions at Mawson, Antarctica. This was achieved by using a scanning Doppler imager, which can observe thermospheric neutral line-of-sight winds and temperatures simultaneously over a wide field of view. In two cases, the background E region wind field was perpendicular to an auroral arc, which when it appeared caused the wind direction within âŒ50 km of the arc to rotate parallel along the arc, reverting to the background flow direction when the arc disappeared. This was observed under both westward and eastward plasma convection. The wind rotations occurred within 7â16 min. In one case, as an auroral arc propagated from the horizon toward the local zenith, the background E region wind field became significantly weaker but remained unaffected where the arc had not passed through. We demonstrate through modeling that these effects cannot be explained by height changes in the emission layer. The most likely explanation seems to be the greatly enhanced ion drag associated with the increased plasma density and localized ionospheric electric field associated with auroral arcs. In all cases, the F region neutral wind appeared less affected by the auroral arc, although its presence is clear in the data
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
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