Coherent population oscillations with nitrogen-vacancy color centers in diamond

We present results of our research on two-field (two-frequency) microwave spectroscopy in nitrogen-vacancy (NV-) color centers in a diamond. Both fields are tuned to transitions between the spin sublevels of the NV- ensemble in the 3A2 ground state (one field has a fixed frequency while the second one is scanned). Particular attention is focused on the case where two microwaves fields drive the same transition between two NV- ground state sublevels (ms=0 -> ms=+1). In this case, the observed spectra exhibit a complex narrow structure composed of three Lorentzian resonances positioned at the pump-field frequency. The resonance widths and amplitudes depend on the lifetimes of the levels involved in the transition. We attribute the spectra to coherent population oscillations induced by the two nearly degenerate microwave fields, which we have also observed in real time. The observations agree well with a theoretical model and can be useful for investigation of the NV relaxation mechanisms.Comment: 17 page

Continuous-flow IRMS technique for determining the 17O excess of CO2 using complete oxygen isotope exchange with cerium oxide

This paper presents an analytical system for analysis of all single substituted isotopologues (¹²C¹⁶O¹⁷O, ¹²C¹⁶O¹⁸O, ¹³C¹⁶O¹⁶O) in nanomolar quantities of CO₂ extracted from stratospheric air samples. CO₂ is separated from bulk air by gas chromatography and CO₂ isotope ratio measurements (ion masses 45 / 44 and 46 / 44) are performed using isotope ratio mass spectrometry (IRMS). The ¹⁷O excess (Δ¹⁷O) is derived from isotope measurements on two different CO₂ aliquots: unmodified CO₂ and CO₂ after complete oxygen isotope exchange with cerium oxide (CeO₂) at 700 °C. Thus, a single measurement of Δ¹⁷O requires two injections of 1 mL of air with a CO₂ mole fraction of 390 μmol mol⁻¹ at 293 K and 1 bar pressure (corresponding to 16 nmol CO₂ each). The required sample size (including flushing) is 2.7 mL of air. A single analysis (one pair of injections) takes 15 minutes. The analytical system is fully automated for unattended measurements over several days. The standard deviation of the ¹⁷O excess analysis is 1.7‰. Multiple measurements on an air sample reduce the measurement uncertainty, as expected for the statistical standard error. Thus, the uncertainty for a group of 10 measurements is 0.58‰ for Δ ¹⁷O in 2.5 h of analysis. 100 repeat analyses of one air sample decrease the standard error to 0.20‰. The instrument performance was demonstrated by measuring CO₂ on stratospheric air samples obtained during the EU project RECONCILE with the high-altitude aircraft Geophysica. The precision for RECONCILE data is 0.03‰ (1σ) for δ¹³C, 0.07‰ (1σ) for δ¹⁸O and 0.55‰ (1σ) for δ¹⁷O for a sample of 10 measurements. This is sufficient to examine stratospheric enrichments, which at altitude 33 km go up to 12‰ for δ¹⁷O and up to 8‰ for δ¹⁸O with respect to tropospheric CO₂ : δ¹⁷O ~ 21‰ Vienna Standard Mean Ocean Water (VSMOW), δ¹⁸O ~ 41‰ VSMOW (Lämmerzahl et al., 2002). The samples measured with our analytical technique agree with available data for stratospheric CO₂

What is the impact of physical effort on the diagnosis of concussion?

Objective: Sport-related concussion commonly occurs in contact sports such as rugby. To date, diagnosis is based on the realization of clinical tests conducted pitch-side. Yet, the potential effect of prior physical effort on the results of these tests remains poorly understood. The purpose of this study was to determine whether preceding physical effort can influence the outcome of concussion assessments. Design: Prospective observational study. Setting: University Medicine Center Patients: A cohort of 40 subjects (20 rugby players and 20 athletes from a range of sports). Intervention: A concussion assessment was performed immediately following physical activity. Following a period of 6 months and under the same experimental conditions, the same cohort performed the same tests in resting conditions. Main outcome measure: Results of concussion tests. Results: In both cohorts, the comparison for post-exercise and rest assessments demonstrated a most likely moderate-to-very large increase in the number of symptoms, severity of symptoms and BESS score. In the rugby cohort, scores for concentration, delayed memory and SAC, likely-to-most likely decreased following completion of physical activity compared to baseline values. The between-cohort comparison showed a greater impact post-exercise in the rugby players for delayed recall (0.73±0.61, 93/7/1) and SAC score (0.75±0.41, 98/2/0). Conclusion: Physical activity altered the results of concussion diagnostic tests in athletes from a range of sports and notably in rugby players. Therefore, physical efforts prior to the concussion incident should be accounted for during pitch-side assessments and particularly during rugby competition and training

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged \u3e/=60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P \u3c 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P \u3c 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P \u3c 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival

GAS6 expression identifies high-risk adult AML patients: potential implications for therapy

Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged \u3c60 \u3eyears; n=199 aged \u3e= 60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged \u3e= 60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6-). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), shorter DFS (P=0.004) and OS (P=0.04). To gain further biological insights, we derived a GAS6-associated gene-expression signature (

Prognostic and Biologic Relevance of Clinically Applicable Long Noncoding RNA Profiling in Older Patients with Cytogenetically Normal Acute Myeloid Leukemia

We have previously shown that expression levels of 48 long noncoding RNAs (lncRNA) can generate a prognostic lncRNA score that independently associates with outcome of older patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the techniques used to identify and measure prognostic lncRNAs (i.e., RNA sequencing and microarrays) are not tailored for clinical testing. Herein, we report on an assay (based on the nCounter platform) that is designed to produce targeted measurements of prognostic lncRNAs in a clinically applicable manner. We analyzed a new cohort of 76 older patients with CN-AML and found that the nCounter assay yielded reproducible measurements and that the lncRNA score retained its prognostic value; patients with high lncRNA scores had lower complete remission (CR) rates (P = 0.009; 58% vs. 87%), shorter disease-free (P = 0.05; 3-year rates: 0% vs. 21%), overall (OS; P = 0.02, 3-year rates: 10% vs. 29%), and event-free survival (EFS; P = 0.002, 3-year rates: 0% vs. 18%) than patients with low lncRNA scores. In multivariable analyses, the lncRNA score independently associated with CR rates (P = 0.02), OS (P = 0.02), and EFS (P = 0.02). To gain biological insights, we examined our initial cohort of 71 older patients with CN-AML, previously analyzed with RNA sequencing. Genes involved in immune response and B-cell receptor signaling were enriched in patients with high lncRNA scores. We conclude that clinically applicable lncRNA profiling is feasible and potentially useful for risk stratification of older patients with CN-AML. Furthermore, we identify potentially targetable molecular pathways that are active in the high-risk patients with high lncRNA scores

Genomic insights into the rapid emergence and evolution of MDR in Staphylococcus pseudintermedius.

OBJECTIVES: MDR methicillin-resistant Staphylococcus pseudintermedius (MRSP) strains have emerged rapidly as major canine pathogens and present serious treatment issues and concerns to public health due to their, albeit low, zoonotic potential. A further understanding of the genetics of resistance arising from a broadly susceptible background of S. pseudintermedius is needed. METHODS: We sequenced the genomes of 12 S. pseudintermedius isolates of varied STs and resistance phenotypes. RESULTS: Nine distinct clonal lineages had acquired either staphylococcal cassette chromosome (SCC) mec elements and/or Tn5405-like elements carrying up to five resistance genes [aphA3, sat, aadE, erm(B), dfrG] to generate MRSP, MDR methicillin-susceptible S. pseudintermedius and MDR MRSP populations. The most successful and clinically problematic MDR MRSP clones, ST68 SCCmecV(T) and ST71 SCCmecII-III, have further accumulated mutations in gyrA and grlA conferring resistance to fluoroquinolones. The carriage of additional mobile genetic elements (MGEs) was highly variable, suggesting that horizontal gene transfer is frequent in S. pseudintermedius populations. CONCLUSIONS: Importantly, the data suggest that MDR MRSP evolved rapidly by the acquisition of a very limited number of MGEs and mutations, and that the use of many classes of antimicrobials may co-select for the spread and emergence of MDR and XDR strains. Antimicrobial stewardship will need to be comprehensive, encompassing human medicine and veterinary disciplines to successfully preserve antimicrobial efficacy