To assess if SARS-CoV-2 (COVID-19) systemic disease can be determined by available nucleoprotein assays, we compared the performance of three commercial SARS-CoV-2 nucleoprotein (N) assays in plasma. ...A total of 272 plasma samples collected in the period November-December 2021 were analyzed by the methods Simoa SARS CoV-2 N Protein Advantage Kit Quanterix Simoa, Solsten SARS-CoV-2 Antigen enzyme immunosorbent assay (ELISA) Solsten ELISA, and Elecsys SARS-CoV-2 Antigen electrochemiluminescence immunoassay Elecsys ECLIA. Additionally, a dilution series of inactivated virus culture was analyzed by the three assays. The SARS CoV-2 PCR-status was not known for the patients. Linear correlation in the pairwise correlation between assays as well as linearity of dilution series of inactivated virus culture was estimated by Spearman score. Sensitivity and specificity were estimated by pairwise comparison. The three assays showed poor agreement on patient samples with regards to concentration. Performance on virus culture was excellent but with different level of detection (LOD). Positive vs negative results show comparable sensitivity and specificity of Quanterix Simoa and Solsten ELISA, with a higher LOD in Elecsys ECLIA and thus lower sensitivity and high specificity. N by all tested assays can be used as a marker for systemic COVID-19 disease.
Anatomy of STEM teaching in North American universities Stains, M; Harshman, J; Barker, M K ...
Science (American Association for the Advancement of Science),
2018-Mar-30, 2018-03-30, 20180330, Letnik:
359, Številka:
6383
Journal Article
Recenzirano
Odprti dostop
Lecture is prominent, but practices vary
A large body of evidence demonstrates that strategies that promote student interactions and cognitively engage students with content (
1
) lead to gains in ...learning and attitudinal outcomes for students in science, technology, engineering, and mathematics (STEM) courses (
1
,
2
). Many educational and governmental bodies have called for and supported adoption of these student-centered strategies throughout the undergraduate STEM curriculum. But to the extent that we have pictures of the STEM undergraduate instructional landscape, it has mostly been provided through self-report surveys of faculty members, within a particular STEM discipline e.g., (
3
–
6
). Such surveys are prone to reliability threats and can underestimate the complexity of classroom environments, and few are implemented nationally to provide valid and reliable data (
7
). Reflecting the limited state of these data, a report from the U.S. National Academies of Sciences, Engineering, and Medicine called for improved data collection to understand the use of evidence-based instructional practices (
8
). We report here a major step toward a characterization of STEM teaching practices in North American universities based on classroom observations from over 2000 classes taught by more than 500 STEM faculty members across 25 institutions.
Oxidative stress is proposed as an important factor in osteoarthritis (OA).
To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA.
SOD expression was ...determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin-Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression.
All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin-Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression.
This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function.
Extracellular adenosine (ADO), present in high concentrations in the tumor microenvironment (TME), suppresses immune function via inhibition of T cell and NK cell activation. Intratumoral generation ...of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases, CD39 (ATP → AMP) and CD73 (AMP → ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression. Extensive interrogation of structure–activity relationships (SARs), structure-based drug design, and optimization of pharmacokinetic properties culminated in the discovery of AB680, a highly potent (K i = 5 pM), reversible, and selective inhibitor of CD73. AB680 is further characterized by very low clearance and long half-lives across preclinical species, resulting in a PK profile suitable for long-acting parenteral administration. AB680 is currently being evaluated in phase 1 clinical trials. Initial data show AB680 is well tolerated and exhibits a pharmacokinetic profile suitable for biweekly (Q2W) iv-administration in human.
Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC ...has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab.
The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety.
Single-arm, multicenter, phase 2 clinical trial with two-stage design.
Comprehensive cancer center.
Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy.
Nivolumab (240 mg) IV every 2 weeks.
Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia.
Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.
The recent focus on topological insulators is due to the scientific interest in the new state of quantum matter as well as the technology potential for a new generation of THz optoelectronics, ...spintronics and quantum computations. It is important to elucidate the dynamics of the Dirac fermions in the topologically protected surface state. Hence we utilized a novel ultrafast optical pump mid-infrared probe to explore the dynamics of Dirac fermions near the Dirac point. The femtosecond snapshots of the relaxation process were revealed by the ultrafast optics. Specifically, the Dirac fermion-phonon coupling strength in the Dirac cone was found to increase from 0.08 to 0.19 while Dirac fermions were away from the Dirac point into higher energy states. Further, the energy-resolved transient reflectivity spectra disclosed the energy loss rate of Dirac fermions at room temperature was about 1 meV/ps. These results are crucial to the design of Dirac fermion devices.
Recent laboratory and field studies have indicated that glyoxal is a potentially large contributor to secondary organic aerosol mass. We present in situ glyoxal measurements acquired with a recently ...developed, high sensitivity spectroscopic instrument during the CalNex 2010 field campaign in Pasadena, California. We use three methods to quantify the production and loss of glyoxal in Los Angeles and its contribution to organic aerosol. First, we calculate the difference between steady state sources and sinks of glyoxal at the Pasadena site, assuming that the remainder is available for aerosol uptake. Second, we use the Master Chemical Mechanism to construct a two‐dimensional model for gas‐phase glyoxal chemistry in Los Angeles, assuming that the difference between the modeled and measured glyoxal concentration is available for aerosol uptake. Third, we examine the nighttime loss of glyoxal in the absence of its photochemical sources and sinks. Using these methods we constrain the glyoxal loss to aerosol to be 0–5 × 10−5 s−1 during clear days and (1 ± 0.3) × 10−5 s−1 at night. Between 07:00–15:00 local time, the diurnally averaged secondary organic aerosol mass increases from 3.2 μg m−3 to a maximum of 8.8 μg m−3. The constraints on the glyoxal budget from this analysis indicate that it contributes 0–0.2 μg m−3 or 0–4% of the secondary organic aerosol mass.
Key Points
We used a new field instrument to measure glyoxal in Los Angeles during 2010
We constrain glyoxal contribution to aerosol using three methods
During daytime, glyoxal contributes 0–4% of secondary organic aerosol mass
Resolving Mismatches in U.S. Ocean Governance Crowder, L. B.; Osherenko, G.; Young, O. R. ...
Science (American Association for the Advancement of Science),
08/2006, Letnik:
313, Številka:
5787
Journal Article
Recenzirano
Problems in ocean resource management derive from governance, not science. Ocean zoning would replace mismatched and fragmented approaches with integrated regulatory domains.
Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative ...performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics.
Summary
Desulfatibacillum alkenivorans AK‐01 serves as a model organism for anaerobic alkane biodegradation because of its distinctive biochemistry and metabolic versatility. The D. alkenivorans ...genome provides a blueprint for understanding the genetic systems involved in alkane metabolism including substrate activation, CoA ligation, carbon‐skeleton rearrangement and decarboxylation. Genomic analysis suggested a route to regenerate the fumarate needed for alkane activation via methylmalonyl‐CoA and predicted the capability for syntrophic alkane metabolism, which was experimentally verified. Pathways involved in the oxidation of alkanes, alcohols, organic acids and n‐saturated fatty acids coupled to sulfate reduction and the ability to grow chemolithoautotrophically were predicted. A complement of genes for motility and oxygen detoxification suggests that D. alkenivorans may be physiologically adapted to a wide range of environmental conditions. The D. alkenivorans genome serves as a platform for further study of anaerobic, hydrocarbon‐oxidizing microorganisms and their roles in bioremediation, energy recovery and global carbon cycling.
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