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Untraceable
Jennifer Marsh is an FBI secret service agent who gets caught up in a very personal and deadly cat-and-mouse game with a serial killer. The killer knows that people are drawn to the curious and the dark side of things. They will log onto an 'untraceable' website where the killer conducts violent and painful murders live on the internet. The more people who log on and enter the website, the quicker and more violently the victim dies.
DVD
Online Monitoring of Catalytic Processes by Fiber-Enhanced Raman Spectroscopy
An innovative solution for real-time monitoring of reactions within confined spaces, optimized for Raman spectroscopy applications, is presented. This approach involves the utilization of a hollow-core waveguide configured as a compact flow cell, serving both as a conduit for Raman excitation and scattering and seamlessly integrating into the effluent stream of a cracking catalytic reactor. The analytical technique, encompassing device and optical design, ensures robustness, compactness, and cost-effectiveness for implementation into process facilities. Notably, the modularity of the approach empowers customization for diverse gas monitoring needs, as it readily adapts to the specific requirements of various sensing scenarios. As a proof of concept, the efficacy of a spectroscopic approach is shown by monitoring two catalytic processes: CO2 methanation (CO2 + 4H2 → CH4 + 2H2O) and ammonia cracking (2NH3 → N2 + 3H2). Leveraging chemometric data processing techniques, spectral signatures of the individual components involved in these reactions are effectively disentangled and the results are compared to mass spectrometry data. This robust methodology underscores the versatility and reliability of this monitoring system in complex chemical environments.
Journal Article
Development of a clinical polygenic risk score assay and reporting workflow
Implementation of polygenic risk scores (PRS) may improve disease prevention and management but poses several challenges: the construction of clinically valid assays, interpretation for individual patients, and the development of clinical workflows and resources to support their use in patient care. For the ongoing Veterans Affairs Genomic Medicine at Veterans Affairs (GenoVA) Study we developed a clinical genotype array-based assay for six published PRS. We used data from 36,423 Mass General Brigham Biobank participants and adjustment for population structure to replicate known PRS–disease associations and published PRS thresholds for a disease odds ratio (OR) of 2 (ranging from 1.75 (95% CI: 1.57–1.95) for type 2 diabetes to 2.38 (95% CI: 2.07–2.73) for breast cancer). After confirming the high performance and robustness of the pipeline for use as a clinical assay for individual patients, we analyzed the first 227 prospective samples from the GenoVA Study and found that the frequency of PRS corresponding to published OR > 2 ranged from 13/227 (5.7%) for colorectal cancer to 23/150 (15.3%) for prostate cancer. In addition to the PRS laboratory report, we developed physician- and patient-oriented informational materials to support decision-making about PRS results. Our work illustrates the generalizable development of a clinical PRS assay for multiple conditions and the technical, reporting and clinical workflow challenges for implementing PRS information in the clinic.
The first report from the prospective GenoVA Study provides preliminary insights into the development of a polygenic risk score assay in a clinical setting and discusses the challenges of generating, interpreting and reporting results.
Journal Article
Rapid serum clot tubes reduce haemolysis due to pneumatic tube transport
AimsPneumatic tube systems (PTSs) are critical for modern hospital operations, allowing for rapid sample transport. Despite widespread use, PTSs can compromise specimen integrity and affect laboratory values. Our objective was to prove that rapid serum clot tubes (RST) provide protective benefits over plasma during PTS transport and can be a practical solution for certain PTS routes.MethodsIn this study, we compared the effects of PTS transport on cell lysis indicators: h-index, lactate dehydrogenase (LDH) and potassium (K+), in RST versus lithium heparin gel separator tubes using 10 volunteers.ResultsIn comparison with plasma, RST showed a median reduction in PTS-induced haemolysis of 80.4% (p=0.0049), with a reduction in post-PTS median LDH concentration (49.7%, p=0.04) and K+ concentration (50.0%, p=0.0273).ConclusionThis study demonstrates RST tubes can significantly reduce PTS-induced haemolysis and can be recommended for poor PTS routes.
Journal Article
Exosites in Hypervariable Loops of ADAMTS Spacer Domains control Substrate Recognition and Proteolysis
ADAMTS (A Disintegrin-like and Metalloproteinase domain with Thrombospondin type 1 Motif)-1, -4 and -5 share the abilities to cleave large aggregating proteoglycans including versican and aggrecan. These activities are highly relevant to cardiovascular disease and osteoarthritis and during development. Here, using purified recombinant ADAMTS-1, -4 and -5, we quantify, compare, and define the molecular basis of their versicanase activity. A novel sandwich-ELISA detecting the major versican cleavage fragment was used to determine, for the first time, kinetic constants for versican proteolysis. ADAMTS-5 (
k
cat
/
K
m
35 × 10
5
M
−1
s
−1
) is a more potent (~18-fold) versicanase than ADAMTS-4 (
k
cat
/
K
m
1.86 × 10
5
M
−1
sec
−1
), whereas ADAMTS-1 versicanase activity is comparatively low. Deletion of the spacer domain reduced versicanase activity of ADAMTS-5 19-fold and that of ADAMTS-4 167-fold. Co-deletion of the ADAMTS-5 cysteine-rich domain further reduced versicanase activity to a total 153-fold reduction. Substitution of two hypervariable loops in the spacer domain of ADAMTS-5 (residues 739–744 and 837–844) and ADAMTS-4 (residues 717–724 and 788–795) with those of ADAMTS-13, which does not cleave proteoglycans, caused spacer-dependent reductions in versicanase activities. Our results demonstrate that these loops contain exosites critical for interaction with and processing of versican. The hypervariable loops of ADAMTS-5 are shown to be important also for its aggrecanase activity. Together with previous work on ADAMTS-13 our results suggest that the spacer domain hypervariable loops may exercise significant control of ADAMTS proteolytic activity as a general principle. Identification of specific exosites also provides targets for selective inhibitors.
Journal Article
RuKY Catalyst‐Packed Permeation Membrane for Quantitative Ammonia and d3‐Ammonia Dehydrogenation to Ultrapure Hydrogen
Ammonia is a promising carbon‐free hydrogen carrier, but incomplete ammonia dehydrogenation (cracking) generates atmospheric emissions of NOx, a potent greenhouse gas. Additionally, incomplete cracking of ammonia leads to regulatory challenges in nuclear and fusion power, where tritiated ammonia (NT3) emissions are strictly controlled. Therefore, we report the use of low‐temperature ammonia dehydrogenation catalysts (3%Ru/1%Y/12%K/Al2O3) in a palladium alloy H2 permeation membrane for quantitative conversion of ammonia into hydrogen and nitrogen at industry‐relevant conditions. This catalytic membrane reactor system achieved an astonishing effluent concentration of <1 ppm at 450°C under a 100% NH3 stream, which is far beyond the 99.6% conversion target required for the adoption of ammonia as a vehicle fuel. The low‐temperature ammonia dehydrogenation catalyst was tested in a packed bed reactor with NH3 and ND3 to both elucidate the reaction mechanism and to quantify the kinetic isotope effect of the membrane reactor. The rate‐limiting step at temperatures relevant to the palladium membrane are isotope independent, indicating that the isotopologue content will not modify the desired reaction kinetics. By reducing emissions to below‐trace levels with no additional separation, this work provides a path to greatly simplified and miniaturized ammonia cracking processes. The removal of ammonia in gas effluent streams is an important, albeit energy intensive, step in a variety of industrial applications. However, a palladium‐silver permeation membrane reactor greatly increases the performance of the system, allowing for near quantitative conversion of ammonia into nitrogen and hydrogen.
Journal Article
