Lorentz transmission electron microscopy and magnetic force microscopy characterization of NiFe/Al-oxide/Co films

Magnetization reversal process of NiFe/Al-oxide/Co junction films was observed directly using Lorentztransmission electron microscopy (LTEM) and magnetic force microscopy(MFM).In situmagnetizing experiments performed in both LTEM and MFM were facilitated by a pair of electromagnets, which were mounted on the sample stages. A two-stage magnetization reversal process for the junction film was clearly observed in LTEM with NiFe magnetization reversed first via domain wall motion followed by Co magnetization reversal via moment rotation and domain wall motion. Reversal mechanism and domain characteristics of the NiFe and Co layers showed very distinctive features. The magnetization curve of the junction filmmeasured using alternating gradient force magnetometry showed a nonzero slope at the antiparallel magnetization configuration region, which implies that magnetization directions of the NiFe and Co layers were not exactly antiparallel due to Co moment rotation existed in that region. After the magnetization reversal of the Co was complete, MFM images revealed some magnetic contrast, which suggests that an out-of-plane magnetization component remained in the Co layer. Such magnetic contrast disappeared at higher magnetic fields when the Co moments further rotated and aligned parallel to the applied field direction

A feasibility study into the production of a mussel matrix reference material for the cyanobacterial toxins microcystins and nodularins.

Microcystins and nodularins, produced naturally by certain species of cyanobacteria, have been found to accumulate in aquatic foodstuffs such as fish and shellfish, resulting in a risk to the health of the seafood consumer. Monitoring of toxins in such organisms for risk management purposes requires the availability of certified matrix reference materials to aid method development, validation and routine quality assurance. This study consequently targeted the preparation of a mussel tissue reference material incurred with a range of microcystin analogues and nodularins. Nine targeted analogues were incorporated into the material as confirmed through liquid chromatography with tandem mass spectrometry (LC-MS/MS), with an additional 15 analogues detected using LC coupled to non-targeted high resolution mass spectrometry (LC-HRMS). Toxins in the reference material and additional source tissues were quantified using LC-MS/MS, two different enzyme-linked immunosorbent assay (ELISA) methods and with an oxidative-cleavage method quantifying 3-methoxy-2-methyl-4-phenylbutyric acid (MMPB). Correlations between the concentrations quantified using the different methods were variable, likely relating to differences in assay cross-reactivities and differences in the abilities of each method to detect bound toxins. A consensus concentration of total soluble toxins determined from the four independent test methods was 2425 ± 575 µg/kg wet weight. A mean 43 ± 9% of bound toxins were present in addition to the freely extractable soluble form (57 ± 9%). The reference material produced was homogenous and stable when stored in the freezer for six months without any post-production stabilization applied. Consequently, a cyanotoxin shellfish reference material has been produced which demonstrates the feasibility of developing certified seafood matrix reference materials for a large range of cyanotoxins and could provide a valuable future resource for cyanotoxin risk monitoring, management and mitigation

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Diagnosing Microcystin Intoxication of Canines: Clinicopathological Indications, Pathological Characteristics, and Analytical Detection in Postmortem and Antemortem Samples

In the summer of 2018, six dogs exposed to a harmful algal bloom (HAB) of Microcystis in Martin County Florida (USA) developed clinicopathological signs of microcystin (MC) intoxication (i.e., acute vomiting, diarrhea, severe thrombocytopenia, elevated alanine aminotransferase, hemorrhage). Successful supportive veterinary care was provided and led to survival of all but one patient. Confirmation of MC intoxication was made through interpretation of clinicopathological abnormalities, pathological examination of tissues, microscopy (vomitus), and analytical MC testing of antemortem/postmortem samples (vomitus, blood, urine, bile, liver, kidney, hair). Gross and microscopic examination of the deceased patient confirmed massive hepatic necrosis, mild multifocal renal tubular necrosis, and hemorrhage within multiple organ systems. Microscopy of a vomitus sample confirmed the presence of Microcystis. Three analytical MC testing approaches were used, including the MMPB (2-methyl-3-methoxy-4-phenylbutyric acid) technique, targeted congener analysis (e.g., liquid chromatography tandem-mass spectrometry of MC-LR), and enzyme-linked immunosorbent assay (ELISA). Total Adda MCs (as MMPB) were confirmed in the liver, bile, kidney, urine, and blood of the deceased dog. Urinalysis (MMPB) of one surviving dog showed a high level of MCs (32,000 ng mL&minus;1) 1-day post exposure, with MCs detectable &gt;2 months post exposure. Furthermore, hair from a surviving dog was positive for MMPB, illustrating another testable route of MC elimination in canines. The described cases represent the first use of urine as an antemortem, non-invasive specimen to diagnose microcystin toxicosis. Antemortem diagnostic testing to confirm MC intoxication cases, whether acute or chronic, is crucial for providing optimal supportive care and mitigating MC exposure

Comprehensive multi-technique approach reveals the high diversity of microcystins in field collections and an associated isolate of Microcystis aeruginosa from a Turkish lake

Microcystins (MCs) are hepatotoxic and potentially carcinogenic cyanotoxins. They exhibit high structural variability, with nearly 250 variants described to date. This variability can result in incomplete detection of MC variants during lake surveys due to the frequent use of targeted analytical methods and a lack of standards available for identification and quantitation. In this study, Lake Uluabat in Turkey was sampled during the summer of 2015. Phylogenetic analysis of the environmental mcyA sequences suggested Microcystis spp. were the major MC contributors. A combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS), liquid chromatography with UV detection and mass spectrometry (LC-UV-MS), and a novel liquid chromatography-high resolution mass spectrometry (LC-HRMS) method, together with thiol and periodate reactivity, revealed more than 36 MC variants in the lake samples and a strain of M. aeruginosa (AQUAMEB-24) isolated from Lake Uluabat. Only MCs containing arginine at position-4 were detected in the culture, while MC-LA, -LY, -LW and -LF were also detected in the lake samples, suggesting the presence of other MC producers in the lake. The previously unreported MCs MC-(H2)YR (dihydrotyrosine at position-2) (17), [epoxyAdda(5)]MC-LR, [DMAdda(5)]MC-RR (1) and [Mser(7)]MC-RR (8) were detected in the culture and/or field samples. This study is a good example of how commonly used targeted LC-MS methods can underestimate the diversity of MCs in freshwater lakes and cyanobacteria cultures and how untargeted LC-MS methods can be used to comprehensively assess MC diversity present in a new system

Implementation of a multidisciplinary medication refill protocol

Introduction:Primary care clinicians spend significant time managing nonvisit activities, including processing of requests for prescription renewal. Delays in processing refills may lead to patient dissatisfaction and impact provider productivity. Having nonclinicians process refills can be more efficient and time-saving. We aimed to evaluate the use of a multidisciplinary medication refill protocol to decrease the time to complete refill requests. Methods:We implemented nursing-driven management of refill requests within two family medicine residency clinics in Milwaukee, Wisconsin (Phase 1: single clinic implementation [March 2017-June 2019]; Phase 2: added second clinic prepandemic [June 2019-March 2020] and postpandemic [April 2020-December 2020]). The multidisciplinary refill protocol was created by faculty, residents, pharmacy, and nursing. Data were collected using electronic health record time stamps to determine when refill requests were initiated and filled by faculty, residents, and nurses. We used Mood\u27s median test to compare the median time for medication refill completion. We used Levene\u27s test to test for equal variance surrounding the median of each caregiver group. We used Fisher\u27s exact test or χ2 test with Yates\u27 correction for 2×2 contingency tables. Results:In both phases, we identified a significant reduction in median time to refill completion ( P\u3c.001) and variability of time to refill completion ( P\u3c.001). Notably, in Phase 1, reduction in median refill time was most apparent among residents (383 vs 79 min postimplementation); and in Phase 2, the percentage of refills completed within 48 hours significantly increased between the pre-COVID-19 and COVID-19 pandemic among faculty and nursing in Clinic 1 and residents and faculty in Clinic 2 (all P\u27s\u3c.001). Conclusions:Implementation of a multidisciplinary refill protocol significantly improved time and predictability of refill completion in both phases