The detection of ensembles of spins under ambient conditions has revolutionized the biological, chemical and physical sciences through magnetic resonance imaging1 and nuclear magnetic resonance2, 3. ...Pushing sensing capabilities to the individual-spin level would enable unprecedented applications such as single-molecule structural imaging; however, the weak magnetic fields from single spins are undetectable by conventional far-field resonance techniques4. In recent years, there has been a considerable effort to develop nanoscale scanning magnetometers5, 6, 7, 8, which are able to measure fewer spins by bringing the sensor in close proximity to its target. The most sensitive of these magnetometers generally require low temperatures for operation, but the ability to measure under ambient conditions (standard temperature and pressure) is critical for many imaging applications, particularly in biological systems. Here we demonstrate detection and nanoscale imaging of the magnetic field from an initialized single electron spin under ambient conditions using a scanning nitrogen-vacancy magnetometer. Real-space, quantitative magnetic-field images are obtained by deterministically scanning our nitrogen-vacancy magnetometer 50 nm above a target electron spin, while measuring the local magnetic field using dynamically decoupled magnetometry protocols. We discuss how this single-spin detection enables the study of a variety of room-temperature phenomena in condensed-matter physics with an unprecedented combination of spatial resolution and spin sensitivity.
As the first purely multi-decadal satellite-based soil moisture product that spans over 35 years (from November 1978 to December 2013) on a daily basis designed for climate application, the ...applicability of the European Space Agency (ESA) soil moisture product, including the hydrological consistency between the product and the observed precipitation and the product continuity on the Tibetan Plateau (TP) were investigated. The results show that there is significant degree between the ESA soil moisture product and the observed precipitation. The positive anomaly of the ESA soil moisture product can reflect the occurrences of precipitation, but the precipitation may not definitely lead to soil moisture anomaly, which largely depends on the precipitation amounts. For climate application, large number of missing gaps was shown on the west of the TP, where it is considered that the retrieval algorithms are largely affected by the permafrost covered in this region, leaving the ESA soil moisture product for further improvement. In application, the ESA soil moisture product was used to study the response of surface soil moisture to climate change on the TP. With the rapid warming and the overall wetting of the TP, soil moisture increases on the central of the TP with the increase of precipitation, and decreases in the southeast TP with the precipitation deduction. However, it decreases in the west TP, where it was probably influenced by both the insignificant precipitation changes and the significant increase of evaporation.
Background
Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab‐associated colitis (Ipi‐AC), an immune‐mediated colitis that mimics inflammatory bowel disease.
...Objective
We sought to characterize the histopathologic and immunophenotypic features of Ipi‐AC and to directly compare these features to ulcerative colitis (UC).
Methods
This is a retrospective cohort study of 22 patients with Ipi‐AC, 12 patients with treatment‐naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3.
Results
Endoscopic findings in both the Ipi‐AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi‐AC. As compared to UC, a smaller proportion of Ipi‐AC biopsies had basal plasmacytosis (14% for Ipi‐AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi‐AC vs. 75% for UC, P = 0.003), whereas Ipi‐AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi‐AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi‐AC had a lower density of CD20‐positive lymphocytes than UC (275.8 ± 253.3 cells mm−2 for Ipi‐AC vs. 1173.3 ± 1158.2 cells mm−2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3‐positive cells.
Conclusions
Ipi‐AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune‐related adverse events (iAEs) from ipilimumab therapy.
Objective
Observational studies point to an inverse correlation between low‐density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether ...this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.
Methods
We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high‐density lipoprotein HDL, and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses.
Results
We identified 410, 339, 393, and 317 lipid‐related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10‐100). While one SD increase in the PRSs for total cholesterol (odds ratio OR = 0.92; 95% confidence interval CI = 0.85–0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81–0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65–0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42–0.82; p = 0.002), respectively.
Interpretation
Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56–66
Background
Continuous welded rails (CWR) are subjected to thermal effects that may lead to buckling or fracture during warm or cold seasons, respectively. The modal characteristics (frequency and ...mode shapes) of CWR may reveal important information about the thermal stress that can be used to prevent rail failures.
Objective
The primary objective of this study is to prove a contactless method to monitor the vibration and to extract the modal characteristics of rails using a high-speed camera and advanced image processing. This study is the first step towards a general noninvasive monitoring paradigm aimed at measuring axial stress in CWR.
Methods
To prove the principles of the proposed paradigm, a finite element model of an unrestrained rail segment under varying length, boundary conditions, and axial stresses was formulated. The results of the model were then used to interpret the experimental results relative to a 2.4 m-long rail subjected to compressive loading–unloading cycles. During the experiment, the rail was subjected to the impact of an instrumented hammer and the triggered vibration was recorded with a high-speed camera. The videos were then processed using the phase-based displacement extraction, motion magnification, as well as dynamic mode decomposition techniques to extract the modal characteristics of the specimen.
Results
The results show that the frequencies extracted from the images matched well those obtained with two conventional accelerometers bonded to the rail while the mode shapes extracted from the videos matched those predicted numerically. Additionally, the numerical analysis enabled the interpretation of some unexpected experimental results.
Conclusions
The results presented here proved that the proposed method to infer axial stress in CWR requires proper modeling in order to link the modal characteristics of the rails to the axial stress. In the future, the finite element formulation presented here will be expanded to model CWR under given cross-ties and fasteners conditions in order to link the modal characteristics of the rail of interest to its axial stress.
Hematopoietic myeloblasts give rise to macrophages, dendritic cells, and neutrophils. Circulating myeloid cells detect invading microbes using pattern recognition receptors and subsequently ...orchestrate an innate immune response to contain and kill the pathogens. This innate immune response establishes an inflammatory niche characterized by hypoxia due to host and pathogen factors. Hypoxia-inducible factor (HIF) transcription factors are the primary regulators of the myeloid response to hypoxia. In particular, HIF-1α is a critical hub that integrates hypoxic and immunogenic signals during infection or inflammation. Hypoxia induces HIF-1α stabilization, which drives metabolic and phenotypic reprogramming of myeloid cells to maximize antimicrobial potential. HIF-1α activity in myeloid-derived cells enhances the host response to infection, but may also play a role in pathogenic inflammatory processes, such as atherosclerosis. In this review, we summarize recent advances that have elucidated the mechanism by which myeloid cells regulate HIF-1α activity and, in turn, how HIF-1α shapes myeloid cell function.
Background
The DIC Challenge 2.0 follows on from the work accomplished in the first Digital Image Correlation (DIC) Challenge Reu et al. (Experimental Mechanics 58(7):1067,
1
). The second challenge ...was required to better quantify the spatial resolution of 2D-DIC codes.
Objective
The goal of this paper is to outline the methods and images for the 2D-DIC community to use to evaluate the performance of their codes and improve the implementation of 2D-DIC.
Methods
This paper covers the creation of the new challenge images and the analysis and discussion of the results. It proposes a method of unambiguously defining spatial resolution for 2D-DIC and explores the tradeoff between displacement and strain noise (or measurement noise) and spatial resolution for a wide variety of DIC codes by a combination of the images presented here and a performance factor called Metrological Efficiency Indicator (MEI).
Results
The performance of the 2D codes generally followed the expected theoretical performance, particularly in the measurement of the displacement. The comparison did however show that even with fairly uniform displacement performance, the calculation of the strain spatial resolution varied widely.
Conclusions
This work provides a useful framework for understanding the tradeoff and analyzing the performance of the DIC software using the provided images. It details some of the unique errors associated with the analysis of these images, such as the Pattern Induced Bias (PIB) and imprecision introduced through the strain calculation method. Future authors claiming improvements in 2D accuracy are encouraged to use these images for an unambiguous comparison.
Late‐onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R–) despite the use of antiviral prophylaxis. We studied ...clinical efficacy of 6‐month low‐dose valganciclovir (VGCV) prophylaxis, risk factors for late‐onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R– kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow‐up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively. The use of an induction agent with rabbit antithymocyte globulin and older donor age were factors associated with the risk of late‐onset CMV disease (AHR 2.91, 95% CI 1.18–7.20, p = 0.021 and AHR 1.03, 95% CI 1.01–1.06, p = 0.016, respectively). Late‐onset CMV disease was associated with increased risk for death‐uncensored graft loss (AHR 2.95, 95% CI 1.15–7.61, p = 0.025). In conclusion, late‐onset CMV disease continues to negatively impact kidney transplant outcome despite 6‐month low‐dose VGCV prophylaxis. Investigations focusing on novel preventive approaches should be emphasized.
Late‐onset cytomegalovirus disease negatively affects kidney graft survival despite 6 months of valganciclovir prophylaxis.
Flavonoids are one of the predominant groups of plant polyphenols, and these compounds have significant effects on human health and nutrition. Sulfated flavonoids have more favorable attributes ...compared to their parent compounds such as increased solubility, stability, and bioavailability. In this research, we developed a microbial system to produce sulfated naringenin using
expressing a sulfotransferase (ST) from
(At2g03770). This wild-type strain was used as a model system for testing clustered regularly interspaced short palindromic repeats (CRISPR) interference (CRISPRi) metabolic engineering strategies. Using synthetic sgRNA to mediate transcriptional repression of
, a gene encoding 3'-phosphoadenosine-5'-phosphosulfate (PAPS) ST, which is involved in sulfur metabolism, resulted in an increase in intracellular PAPS accumulation by over 3.28-fold without impairing cell growth. Moreover, naringenin 7-sulfate production by engineering
with its
gene repressed in the open reading frame through CRISPRi was enhanced by 2.83-fold in compared with the wild-type control. To improve the efficiency of biotransformation, the concentration of
, glucose, and substrate were optimized. The bioproductivity of naringenin 7-sulfate was 135.49 μM ∼143.1 mg (47.7 mg L
) in a 3-L fermenter at 36 h. These results demonstrated that the CRISPRi system was successfully applied for the first time in
to develop an efficient microbial strain for production of a sulfated flavonoid. In addition, antibacterial and anticancer activities of naringenin 7-sulfate were investigated and found to be higher than the parent compound.
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