Modulation induced frequency shifts in a CPT-based atomic clock

We investigate systematic errors associated with a common modulation technique used for phase sensitive detection of a coherent population trapping (CPT) resonance. In particular, we show that modification of the CPT resonance lineshape due to the presence of off-resonant fields leads to frequency shifts which may limit the stability of CPT-based atomic clocks. We also demonstrate that an alternative demodulation technique greatly reduces these effects.Comment: 14 pages, 7 figure

Authorship Trends in the Journal of Orthopaedic Research: A Bibliometric Analysis

Publications are an important tool to measure one's success and achievement in academia. They can help propel a career forward and move one into a position of leadership. The overall purpose of this study was to investigate changes in bibliometric variables, authorship, and collaboration trends in the Journal of Orthopaedic Research (JOR®), since its inception in 1983. A bibliometric analysis was completed for all manuscripts meeting the inclusion criteria (638), which were published throughout the inaugural year plus one representative year of each decade. Several parameters were investigated including numbers of manuscripts, authors, collaborating institutions/countries, references, pages, and citations; region of origin and gender of authors over time and by region were main focuses. Significant increases over time were observed in all bibliometric variables analyzed except in the number of pages and citations. There was an approximate 27 percentage point increase for both female first and corresponding authors from 1983 to 2015. While this is most likely due to the increase in the number of women that have entered the field over time, similar increases in the percentage of women holding positions on the JOR editorial board or in leadership positions within in the field may have also contributed to improvements in gender parity. Understanding changes in publishing characteristics over time, by region, and by gender are critical, especially with the rising demands of publishing in academia. JOR has seen increase in most variables analyzed, including improvements in authorship by women in the field of orthopaedic research

Coherent instabilities in a semiconductor laser with fast gain recovery

We report the observation of a coherent multimode instability in quantum cascade lasers (QCLs), which is driven by the same fundamental mechanism of Rabi oscillations as the elusive Risken-Nummedal-Graham-Haken (RNGH) instability predicted 40 years ago for ring lasers. The threshold of the observed instability is significantly lower than in the original RNGH instability, which we attribute to saturable-absorption nonlinearity in the laser. Coherent effects, which cannot be reproduced by standard laser rate equations, can play therefore a key role in the multimode dynamics of QCLs, and in lasers with fast gain recovery in general.Comment: 5 pages, 4 figure

Regulation of Expression of Citrate Synthase by the Retinoic Acid Receptor-Related Orphan Receptor α (RORα)

The retinoic acid receptor-related orphan receptor α (RORα) is a member of the nuclear receptor superfamily of transcription factors that plays an important role in regulation of the circadian rhythm and metabolism. Mice lacking a functional RORα display a range of metabolic abnormalities including decreased serum cholesterol and plasma triglycerides. Citrate synthase (CS) is a key enzyme of the citric acid cycle that provides energy for cellular function. Additionally, CS plays a critical role in providing citrate derived acetyl-CoA for lipogenesis and cholesterologenesis. Here, we identified a functional RORα response element (RORE) in the promoter of the CS gene. ChIP analysis demonstrates RORα occupancy of the CS promoter and a putative RORE binds to RORα effectively in an electrophoretic mobility shift assay and confers RORα responsiveness to a reporter gene in a cotransfection assay. We also observed a decrease in CS gene expression and CS enzymatic activity in the staggerer mouse, which has a mutation of in the Rora gene resulting in nonfunctional RORα protein. Furthermore, we found that SR1001 a RORα inverse agonist eliminated the circadian pattern of expression of CS mRNA in mice. These data suggest that CS is a direct RORα target gene and one mechanism by which RORα regulates lipid metabolism is via regulation of CS expression

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

A comprehensive analysis of coherent rainfall patterns in China and potential drivers. Part II: intraseasonal variability

The causes of subseasonal precipitation variability in China are investigated using observations and reanalysis data for extended winter (November–April) and summer (May–October) seasons from 1982 to 2007. For each season, the three dominant regions of coherent intraseasonal variability are identified with Empirical Orthogonal Teleconnection (EOT) analysis. While previous studies have focused on particular causes for precipitation variability or on specific regions, here a comprehensive analysis is carried out with an objective method. Furthermore, the associated rainfall anomaly timeseries are tied to specific locations in China, which facilitates their interpretation. To understand the underlying processes associated with spatially coherent patterns of rainfall variability, fields from observations and reanalysis are regressed onto EOT timeseries. The three dominant patterns in winter together explain 43% of the total space–time variance and have their origins in midlatitude disturbances that appear two pentads in advance. Winter precipitation variability along the Yangtze River is associated with wave trains originating over the Atlantic and northern Europe, while precipitation variability in southeast China is connected to the Mediterranean storm track. In summer, all patterns have a strong relationship with the Boreal Summer Intraseasonal Oscillation and are modulated by the seasonal cycle of the East Asian summer monsoon. The wet and dry phases of the regional patterns can substantially modulate the frequency of daily rainfall across China. The discovered links between weather patterns, precursors, and effects on local and remote precipitation may provide a valuable basis for hydrological risk assessments and the evaluation of numerical weather prediction models

Helicobacter pylori Infection of Gastrointestinal Epithelial Cells in vitro Induces Mesenchymal Stem Cell Migration through an NF-κB-Dependent Pathway

The role of bone marrow-derived mesenchymal stem cells (MSC) in the physiology of the gastrointestinal tract epithelium is currently not well established. These cells can be recruited in response to inflammation due to epithelial damage, home, and participate in tissue repair. In addition, in the case of tissue repair failure, these cells could transform and be at the origin of carcinomas. However, the chemoattractant molecules responsible for MSC recruitment and migration in response to epithelial damage, and particularly to Helicobacter pylori infection, remain unknown although the role of some chemokines has been suggested. This work aimed to get insight into the mechanisms of mouse MSC migration during in vitro infection of mouse gastrointestinal epithelial cells by H. pylori. Using a cell culture insert system, we showed that infection of gastrointestinal epithelial cells by different H. pylori strains is able to stimulate the migration of MSC. This mechanism involves the secretion by infected epithelial cells of multiple cytokines, with a major role of TNFα, mainly via a Nuclear Factor-kappa B-dependent pathway. This study provides the first evidence of the role of H. pylori infection in MSC migration and paves the way to a better understanding of the role of bone marrow-derived stem cells in gastric pathophysiology and carcinogenesis

Nogo-B is associated with cytoskeletal structures in human monocyte-derived macrophages

<p>Abstract</p> <p>Background</p> <p>The reticulon Nogo-B participates in cellular and immunological processes in murine macrophages. Since leukocytes are an essential part of the immune system in health and disease, we decided to investigate the expression of Nogo-A, Nogo-B and Nogo-C in different human immune cell subpopulations. Furthermore, we analyzed the localization of Nogo-B in human monocyte-derived macrophages by indirect immunofluorescence stainings to gain further insight into its possible function.</p> <p>Findings</p> <p>We describe an association of Nogo-B with cytoskeletal structures and the base of filopodia, but not with focal or podosomal adhesion sites of monocyte-derived macrophages. Nogo-B positive structures are partially co-localized with RhoA staining and Rac1 positive membrane ruffles. Furthermore, Nogo-B is associated with the tubulin network, but not accumulated in the Golgi region. Although Nogo-B is present in the endoplasmic reticulum, it can also be translocated to large cell protrusions or the trailing end of migratory cells, where it is homogenously distributed.</p> <p>Conclusions</p> <p>Two different Nogo-B staining patterns can be distinguished in macrophages: firstly we observed ER-independent Nogo-B localization in cell protrusions and at the trailing end of migrating cells. Secondly, the localization of Nogo-B in actin/RhoA/Rac1 positive regions supports an influence on cytoskeletal organization. To our knowledge this is the first report on Nogo-B expression at the base of filopodia, thus providing further insight into the distribution of this protein.</p