Upper‐level midlatitude troughs in boreal winter have an amplified low‐latitude linkage over Africa

In boreal winter, strong upper-level midlatitude troughs across the Atlantic–Africa–southwestern Asia sector generate substantial tropical–extratropical interaction and have become recognized as important factors in some extreme weather events. As such, they represent important dynamic features to understand and capture in weather forecasts, as well as in climate models for projections on longer timescales. Here, we empirically study the 20% of winter days with strongest trough signatures during 1982–2020 at each longitude across the sector, and show that the trough impact over northern Africa, most notably in central parts, is particularly strong in magnitude, low-latitude extent and persistence, leading to the characterization of a northern Africa mode of several-days weather fluctuation. Weather conditions that follow strong troughs from the eastern Atlantic to the Central Mediterranean include: (i) a warming tendency across much of northern Africa, generally of several Celsius magnitude ahead of the trough, and >1°C even extending to the south of 10° N in central parts and continuing eastward until the Ethiopian Highlands; (ii) precipitation development further north than normal across northern tropical Africa, especially strong over longitudes corresponding to a northward extension of the main Congo rain belt. The intertropical discontinuity and low-level heat low are also shifted significantly north, with the complex of anomalies persisting for several days, beyond the timescale of the trough. For context, at all other trough longitudes across the sector, a warming signal does emerge (statistically significant), but with much shorter persistence (2–3 days), smaller magnitude and extending southward clearly only to 15–20° N. Mid-level tropical plumes of moisture are also typically present for strong troughs from the eastern Atlantic to southwestern Asia, and these alone can lead to weather extremes. However, low-level warming and mid-level moistening are uniquely juxtaposed at low latitudes over central Africa, where a near-equatorial signature develops

Localized magnetoplasmon modes arising from broken translational symmetry in semiconductor superlattices

The electromagnetic propagator associated with the localized collective magnetoplasmon excitations in a semiconductor superlattice with broken translational symmetry, is calculated analytically within linear response theory. We discuss the properties of these collective excitations in both radiative and non-radiative regimes of the electromagnetic spectra. We find that low frequency retarded modes arise when the surface density of carriers at the symmetry breaking layer is lower than the density at the remaining layers. Otherwise a doublet of localized, high-frequency magnetoplasmon-like modes occurs.Comment: Revtex file + separate pdf figure

First Accuracy Evaluation of NIST-F2

We report the first accuracy evaluation of NIST-F2, a second-generation laser-cooled Cesium fountain primary standard developed at the National Institute of Standards and Technology (NIST) with a cryogenic (Liquid Nitrogen) microwave cavity and flight region. The 80 K atom interrogation environment reduces the uncertainty due to the Blackbody Radiation (BBR) shift by more than a factor of 50. Also, the Ramsey microwave cavity exhibits a high Q (>50,000) at this low temperature, resulting in a reduced distributed cavity phase shift. NIST-F2 has undergone many tests and improvements since we first began operation in 2008. In the last few years NIST-F2 has been compared against a NIST maser time scale and NIST-F1 (the US primary frequency standard) as part of in-house accuracy evaluations. We report the results of nine in-house comparisons since 2010 with a focus on the most recent accuracy evaluation. This paper discusses the design of the physics package, the laser and optics systems, and the accuracy evaluation methods. The Type B fractional uncertainty of NIST-F2 is shown to be 0.11 × 10-15 and is dominated by microwave amplitude dependent effects. The most recent evaluation (August 2013) had a statistical (Type A) fractional uncertainty of 0.44 × 10-15

Measuring proteins in H2O using 2D-IR spectroscopy; pre-processing steps and applications towards a protein library

The ability of two-dimensional infrared (2D-IR) spectroscopy to measure the amide I band of proteins in H2O rather than D2O-based solvents by evading the interfering water signals has enabled in-vivo studies of proteins under physiological conditions and in biofluids. Future exploitation of 2D-IR in analytical settings, from diagnostics to protein screening, will however require comparisons between multiple datasets, necessitating control of data collection protocols to minimise measurement-to-measurement inconsistencies. Inspired by analytical spectroscopy applications in other disciplines, we describe a workflow for pre-processing 2D-IR data that aims to simplify spectral cross-comparisons. Our approach exploits the thermal water signal that is collected simultaneously with, but is temporally separated from the amide I response to guide custom baseline correction and spectral normalisation strategies before combining them with Principal Component noise reduction tools. Case studies show that application of elements of the pre-processing workflow to previously-published data enables improvements in quantification accuracy and detection limits. We subsequently apply the complete workflow in a new pilot study, testing the ability of a prototype library of 2D-IR spectra to quantify the four major protein constituents of blood serum in a single, label-free measurement.  These advances show progress towards the robust data handling strategies that will be necessary for future applications of 2D-IR for pharmaceutical or biomedical applications

UNMASC: Tumor-only variant calling with unmatched normal controls

Despite years of progress, mutation detection in cancer samples continues to require significant manual review as a final step. Expert review is particularly challenging in cases where tumors are sequenced without matched normal control DNA. Attempts have been made to call somatic point mutations without a matched normal sample by removing well-known germline variants, utilizing unmatched normal controls, and constructing decision rules to classify sequencing errors and private germline variants. With budgetary constraints related to computational and sequencing costs, finding the appropriate number of controls is a crucial step to identifying somatic variants. Our approach utilizes public databases for canonical somatic variants as well as germline variants and leverages information gathered about nearby positions in the normal controls. Drawing from our cohort of targeted capture panel sequencing of tumor and normal samples with varying tumortypes and demographics, these served as a benchmark for our tumor-only variant calling pipeline to observe the relationship between our ability to correctly classify variants against a number of unmatched normals. With our benchmarked samples, approximately ten normal controls were needed to maintain 94% sensitivity, 99% specificity and 76% positive predictive value, far outperforming comparable methods. Our approach, called UNMASC, also serves as a supplement to traditional tumor with matched normal variant calling workflows and can potentially extend to other concerns arising from analyzing next generation sequencing data

Sensing of bacterial spores with 2D-IR spectroscopy

Ultrafast 2D-IR spectroscopy has proved to be a powerful analytical tool for the detection and differentiation of Bacillus spores as dry films on surfaces. Here, we expand on these findings by employing 2D-IR spectroscopy to study spores from B. atrophaeus (BG) in aqueous solution. Specific vibrational modes attributable to the calcium dipicolinate trihydrate biomarker for spore formation were observed alongside distinctive off-diagonal spectral features that can be used to differentiate spores from different Bacillus species, indicating that 2D-IR has potential for use as a sensing platform with both solid and liquid phase samples. The ability of 2D-IR to enhance the protein amide I band relative to the overlapping water bending vibration was exploited to compare the nature of the protein component of spores to that of solution phase protein molecules. The vibrational lifetime for the amide I band of the BG spore in H2O was 1.4 ± 0.1 ps, longer than those reported for the proteins in H2O solution. The nature of a band at 1710 cm-1 was also investigated. Collectively these results show the potential advantages of 2D-IR spectroscopy, with successful detection and classification of spores under different conditions being based on detailed molecular understanding of the spore state

Germline Analysis from Tumor–Germline Sequencing Dyads to Identify Clinically Actionable Secondary Findings

To evaluate germline variants in hereditary cancer susceptibility genes among unselected cancer patients undergoing tumor-germline sequencing

Sodium alginate decreases the permeability of intestinal mucus

In the small intestine the nature of the environment leads to a highly heterogeneous mucus layer primarily composed of the MUC2 mucin. We set out to investigate whether the soluble dietary fibre sodium alginate could alter the permeability of the mucus layer. The alginate was shown to freely diffuse into the mucus and to have minimal effect on the bulk rheology when added at concentrations below 0.1%. Despite this lack of interaction between the mucin and alginate, the addition of alginate had a marked effect on the diffusion of 500 nm probe particles, which decreased as a function of increasing alginate concentration. Finally, we passed a protein stabilised emulsion through a simulation of oral, gastric and small intestinal digestion. We subsequently showed that the addition of 0.1% alginate to porcine intestinal mucus decreased the diffusion of fluorescently labelled lipid present in the emulsion digesta. This reduction may be sufficient to reduce problems associated with high rates of lipid absorption such as hyperlipidaemia

Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays

Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care