Ultra-low phase noise all-optical microwave generation setup based on commercial devices

In this paper, we present a very simple design based on commercial devices for the all-optical generation of ultra-low phase noise microwave signals. A commercial, fibered femtosecond laser is locked to a laser that is stabilized to a commercial ULE Fabry-Perot cavity. The 10 GHz microwave signal extracted from the femtosecond laser output exhibits a single sideband phase noise $\mathcal{L}(f)=-104 \ \mathrm{dBc}/\mathrm{Hz}$ at 1 Hz Fourier frequency, at the level of the best value obtained with such "microwave photonics" laboratory experiments \cite{Fortier2011}. Close-to-the-carrier ultra-low phase noise microwave signals will now be available in laboratories outside the frequency metrology field, opening up new possibilities in various domains.Comment: 8 pages, 3 figures. To be published in Applied Optics, early posting version available at http://www.opticsinfobase.org/ao/upcoming_pdf.cfm?id=23114

Neuropsychological and information processing deficits following mild traumatic brain injury

Neuroradiological and neuropathological investigations have found evidence of diffuse brain damage in the frontal and temporal lobes, corpus callosum, and fornices in patients who have sustained a mild traumatic brain injury (TBI). However, neuropsychological assessments of these patients do not typically target many of the subtle information processing deficits that may arise from diffuse damage involving the frontotemporal regions of the brain as well as white matter pathology, including the corpus callosum. Consequently, we have a limited understanding of the deficits that may be attributable to temporary or permanent disruptions to these functional pathways. This study assessed a group of mild TBI patients (N = 40) and a matched control group (N = 40) on a number of standard neuropsychological tests of selective and sustained attention, verbal and non-verbal fluency, and verbal memory. In addition, reaction time (RT) tasks, requiring both the inter- and intra-hemispheric processing of visual and tactile information, were used to assess the functional integrity of the tracts that are likely to be affected by diffuse damage. In the 1st month after sustaining their injury, the mild TBI group demonstrated deficits in attention, non-verbal fluency, and verbal memory. They also demonstrated slower visual and tactile RTs, with the visual RTs of mild TBI patients being more affected by increased task difficulty and the need to transfer information across the corpus callosum, than did their matched controls.Jane L. Mathias, Jaqcui A. Beall and Erin D. Bigle

The Carrington event not observed in most ice core nitrate records

The Carrington Event of 1859 is considered to be among the largest space weather events of the last 150 years. We show that only one out of 14 well-resolved ice core records from Greenland and Antarctica has a nitrate spike dated to 1859. No sharp spikes are observed in the Antarctic cores studied here. In Greenland numerous spikes are observed in the 40 years surrounding 1859, but where other chemistry was measured, all large spikes have the unequivocal signal, including co-located spikes in ammonium, formate, black carbon and vanillic acid, of biomass burning plumes. It seems certain that most spikes in an earlier core, including that claimed for 1859, are also due to biomass burning plumes, and not to solar energetic particle (SEP) events. We conclude that an event as large as the Carrington Event did not leave an observable, widespread imprint in nitrate in polar ice. Nitrate spikes cannot be used to derive the statistics of SEPs

Comment on “Low time resolution analysis of ice cores cannot detect impulsive nitrate events” by D. F. Smart et al.

Smart et al. (2014) suggested that the detection of nitrate spikes in polar ice cores from solar energetic particle (SEP) events could be achieved if an analytical system with sufficiently high resolution was used. Here we show that the spikes they associate with SEP events are not reliably recorded in cores from the same location, even when the resolution is clearly adequate. We explain the processes that limit the effective resolution of ice cores. Liquid conductivity data suggest that the observed spikes are associated with sodium or another nonacidic cation, making it likely that they result from deposition of sea salt or similar aerosol that has scavenged nitrate, rather than from a primary input of nitrate in the troposphere. We consider that there is no evidence at present to support the identification of any spikes in nitrate as representing SEP events. Although such events undoubtedly create nitrate in the atmosphere, we see no plausible route to using nitrate spikes to document the statistics of such events

Quantification of glucocorticoid and progestogen metabolites in bovine plasma, skimmed milk and saliva by UHPLC-HR-MS with polarity switching

Steroid metabolites are increasingly in focus when searching for novel biomarkers in physiological mechanisms and their disorders. While major steroids such as progesterone and cortisol are well-researched and routinely determined to assess the health, particularly the reproductive status of mammals, the function of potentially biologically active progestogen and glucocorticoid metabolites is widely unexplored. One of the main reasons for this is the lack of comprehensive, sensitive, and specific analytical methods. This is particularly the case when analyzing matrices like milk or saliva obtained by non-invasive sampling with steroid concentrations often below those present in plasma. Therefore, a new UHPLC-HR-MS method based on an Ultimate UHPLC system equipped with an Acquity HSS T3 reversed-phase column and a Q Exactive™ mass spectrometer was developed, enabling the simultaneous chromatographic separation, detection and quantification of eleven isobaric glucocorticoids (11-dehydrocorticosterone (A), corticosterone (B), cortisol (F), cortisone (E), the tetrahydrocortisols (THF): 3α,5α-THF, 3α,5β-THF, 3β,5α-THF, 3β,5β-THF, and the tetrahydrocortisones (THE): 3α,5α-THE, 3α,5β-THE, 3β,5α-THE) and twelve progestogens (progesterone (P4), pregnenolone (P5), the dihydroprogesterones (DHP): 20α-DHP, 20β-DHP, 3α-DHP, 3β-DHP, 5α-DHP, 5β-DHP, and the tetrahydroprogesterones (THP): 3α,5α-THP, 3α,5β-THP, 3β,5α-THP, 3β,5β-THP) in bovine plasma, skimmed milk, and saliva. A simple liquid-liquid extraction (LLE) with MTBE (methyl tert-butyl ether) was used for sample preparation of 500 μL plasma, skimmed milk, and saliva. Heated electrospray ionization (HESI) with polarity switching was applied to analyze steroids in high-resolution full scan mode (HR-FS). The method validation covered the investigation of sensitivity, selectivity, curve fitting, carry-over, accuracy, precision, recovery, matrix effects and applicability. A high sensitivity in the range of pg mL−1 was achieved for all steroids suitable for the analysis of authentic samples

Cross-reactivity of B and T cells: desired in influenza vaccine responses, feared in autoimmune diseases

Innate immune mechanisms are very efficient at mounting rapid immune responses at the site of infection. Complete clearance of a pathogen and long-lasting protection through memory formation requires the adaptive immune system. To be able to cope with the large variety of pathogens we encounter, T and B cells acquire an almost infinite number of specificities by VDJ-recombination and somatic hypermutation. However, not all recombinations are equally likely to occur and the majority of lymphocyte clones will never be released from the thymus or bone marrow due to negative selection. T cells also need to recognize host HLA-proteins, adding further constraints. Therefore, immune cell diversity is more restricted than theoretically possible. A certain redundancy is induced by the fact that a T or B cell clone may recognize multiple epitopes, albeit with different affinities, a feature termed cross-reactivity. In a vaccine against a genetically diverse pathogen, cross-reactivity of vaccine-induced immune cells is desirable. An ideal vaccine enables the host to mount an immune response not only against the vaccine strain but also against naturally occurring variants that may be antigenically different. Influenza virus is one of the most prevalent human pathogens and of high economic relevance. The ‘success’ of influenza virus is tightly linked to its extraordinary ability to evolve – that is, evading the host’s immune system – while still maintaining its integrity and virulence. Annually updated influenza vaccines provide some protection against infection. However, vaccine efficacy is strongly reduced when there is an antigenic mismatch between vaccine strain and predominant circulating virus. We hypothesized that the cross-reactivity of the influenza vaccine response is affected by the individual B cell repertoire and wanted to test whether low cross-reactivity associates with a narrow repertoire. A narrow antibody repertoire could be related to the previous infection history or to repetitive vaccination with very similar influenza vaccine strains. Consequently, this may lead to higher susceptibility to emerging viral variants. The breadth and degree of antigen-specificity of the B cell receptor (BCR) repertoire can be assessed by sequencing the immunoglobulin heavy chains before and after vaccination. We tested this hypothesis by analyzing samples from a previous cohort of influenza-vaccinated healthy subjects and aimed to extend our findings by conducting a prospective clinical influenza vaccination study in individuals with known vaccination history. Since the composition of the influenza vaccine is an active debate in the field, our results could inform on both strain selection and better vaccination strategies. Cross-reactivity can be beneficial in the case of vaccination but may be harmful if cross-reactive lymphocytes target self-structures, as it is the case in autoimmunity. While B cells recognize native macromolecular structures, T cells mainly respond towards peptides displayed on MHC of antigen-presenting cells (APC). In Giant Cell Arteritis (GCA), a disease affecting medium-sized and large arteries, considerable infiltration of CD4+ T cells is found in the affected vessels. Several lines of evidence suggest that these T cells are not just merely attracted to a site of inflammation, but rather might recognize a specific antigen. Whether this is a primary response against a microbial or self-protein or infection-induced cross-reactivity to self-proteins is currently unknown. In order to investigate antigen involvement in GCA pathogenesis, we used an antigen-centered approach to screen for T cell reactivity against self- and candidate viral antigens. Complementary, we used a T cell receptor (TCR)-based approach in order to investigate expanded clones and enriched CDR3-motifs in the affected arteries. Finally, taking advantage of our prospective GCA cohort study at the University Hospital Basel, we tested the antibody reactivity in newly diagnosed GCA patients against a self-protein proposed by others to be important in GCA pathogenesis. These results will help us to better understand the (early) disease pathogenesis and to find possible druggable pathways

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

Screening of leaf extraction and storage conditions for eco‐metabolomics studies

Mass spectrometry‐based plant metabolomics is frequently used to identify novel natural products or study the effect of specific treatments on a plant's metabolism. Reliable sample handling is required to avoid artifacts, which is why most protocols mandate shock freezing of plant tissue in liquid nitrogen and an uninterrupted cooling chain. However, the logistical challenges of this approach make it infeasible for many ecological studies. Especially for research in the tropics, permanent cooling poses a challenge, which is why many of those studies use dried leaf tissue instead. We screened a total of 10 extraction and storage approaches for plant metabolites extracted from maize leaf tissue across two cropping seasons to develop a methodology for agroecological studies in logistically challenging tropical locations. All methods were evaluated based on changes in the metabolite profile across a 2‐month storage period at different temperatures with the goal of reproducing the metabolite profile of the living plant as closely as possible. We show that our newly developed on‐site liquid–liquid extraction protocol provides a good compromise between sample replicability, extraction efficiency, material logistics, and metabolite profile stability. We further discuss alternative methods which showed promising results and feasibility of on‐site sample handling for field studies