Measurement of the Electron Magnetic Moment.

The electron magnetic moment, -µ/µ_{B}=g/2=1.001 159 652 180 59 (13) [0.13 ppt], is determined 2.2 times more accurately than the value that stood for fourteen years. The most precisely determined property of an elementary particle tests the most precise prediction of the standard model (SM) to 1 part in 10^{12}. The test would improve an order of magnitude if the uncertainty from discrepant measurements of the fine structure constant α is eliminated since the SM prediction is a function of α. The new measurement and SM theory together predict α^{-1}=137.035 999 166 (15) [0.11 ppb] with an uncertainty 10 times smaller than the current disagreement between measured α values.

BMI is dead; long live waist-circumference indices: But which index should we choose to predict cardio-metabolic risk?

BACKGROUND AND AIMS: There is growing evidence that Body Mass Index (BMI) is unfit for purpose. Waist circumference (WC) indices appear to be the preferred alternative, although it is not clear which WC index is optimal at predicting cardio-metabolic risk (CMR) and associated health outcomes. METHODS AND RESULTS: We obtained a stratified random probability sample of 53,390 participants from the Health Survey for England (HSE), 2008-2018. The four available CMR factors were; high-density lipoproteins (HDL) cholesterol, glycated haemoglobin (HbA1c), systolic (SBP) and diastolic blood pressure (DBP). Strength of association between the four cardio-metabolic risk factors and competing anthropometric indicators of weight status [BMI, Waist-to-height ratio (WHTR), unadjusted WC, and a new WC index independent of height, WHT·5R = WC/height0.5] was assessed separately, using simple correlations and ANCOVAs, and together (combined) using MANCOVA, controlling for age, sex and ethnicity. Centile curves for the new index WHT·5R = WC/height0.5were also provided. CONCLUSIONS: Waist-circumference indices were superior to BMI when explaining/predicting our CMR factors, before and after controlling for age, sex and ethnicity. No single WC index was consistently superior. Results suggest that WHTR is the strongest predictor of HbA1c, confirming that shorter individuals are at great risk of diabetes. The most appropriate WC index associated with blood pressure was WHT·5R for DBP, or unadjusted WC for SBP. Given HDL cholesterol is independent of height, the best predictor of HDL was WHT.5R. Clearly, "no one size fits all!". MANCOVA identified WHT·5R to be the best single WC index associated with a composite of all four CMR factors.

Shallow and Deep States of Beryllium Acceptor in GaN: Why Photoluminescence Experiments Do Not Reveal Small Polarons for Defects in Semiconductors.

Currently, only one shallow acceptor (Mg) has been discovered in GaN. Here, using photoluminescence (PL) measurements combined with hybrid density functional theory, we demonstrate that a shallow effective-mass state also exists for the Be_{Ga} acceptor. A PL band with a maximum at 3.38 eV reveals a shallow Be_{Ga} acceptor level at 113±5 meV above the valence band, which is the lowest value among any dopants in GaN reported to date. Calculations suggest that the Be_{Ga} is a dual-nature acceptor with the "bright" shallow state responsible for the 3.38 eV PL band, and the "dark," strongly localized small polaronic state with a significantly lower hole capture efficiency.

In-situ measurement of pyrolysis and combustion gases from biomass burning using swept wavelength external cavity quantum cascade lasers.

Broadband high-speed absorption spectroscopy using swept-wavelength external cavity quantum cascade lasers (ECQCLs) is applied to measure multiple pyrolysis and combustion gases in biomass burning experiments. Two broadly-tunable swept-ECQCL systems were used, with the first tuned over a range of 2089-2262 cm-1 (4.42-4.79 µm) to measure spectra of CO2, H2O, and CO. The second was tuned over a range of 920-1150 cm-1 (8.70-10.9 µm) to measure spectra of ammonia (NH3), ethene (C2H4), and methanol (MeOH). Absorption spectra were measured continuously at a 100 Hz rate throughout the burn process, including inhomogeneous flame regions, and analyzed to determine time-resolved gas concentrations and temperature. The results provide in-situ, dynamic information regarding gas-phase species as they are generated, close to the biomass fuel source.

Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis.

OBJECTIVE: We previously found in our embryonic studies that proper regulation of the chemokine CCL12 through its sole receptor CCR2, is critical for joint and growth plate development. In the present study, we examined the role of CCR2 in injury-induced-osteoarthritis (OA). METHOD: We used a murine model of injury-induced-OA (destabilization of medial meniscus, DMM), and systemically blocked CCR2 using a specific antagonist (RS504393) at different times during disease progression. We examined joint degeneration by assessing cartilage (cartilage loss, chondrocyte hypertrophy, MMP-13 expression) and bone lesions (bone sclerosis, osteophytes formation) with or without the CCR2 antagonist. We also performed pain behavioral studies by assessing the weight distribution between the normal and arthritic hind paws using the IITS incapacitance meter. RESULTS: Testing early vs delayed administration of the CCR2 antagonist demonstrated differential effects on joint damage. We found that OA changes in articular cartilage and bone were ameliorated by pharmacological CCR2 blockade, if given early in OA development: specifically, pharmacological targeting of CCR2 during the first 4 weeks (wks) following injury, reduced OA cartilage and bone damage, with less effectiveness with later treatments. Importantly, our pain-related behavioral studies showed that blockade of CCR2 signaling during early, 1-4 wks post-surgery or moderate, 4-8 wks post-surgery, OA was sufficient to decrease pain measures, with sustained improvement at later stages, after treatment was stopped. CONCLUSIONS: Our data highlight the potential efficacy of antagonizing CCR2 at early stages to slow the progression of post-injury OA and, in addition, improve pain symptoms.

Dysregulation of interleukin 5 expression in familial eosinophilia.

BACKGROUND: Familial eosinophilia (FE) is a rare autosomal dominant inherited disorder characterized by the presence of lifelong peripheral eosinophilia (>1500/µL). Mapped to chromosome 5q31-q33, the genetic cause of FE is unknown, and prior studies have failed to demonstrate a primary abnormality in the eosinophil lineage. OBJECTIVE: The aim of this study was to identify the cells driving the eosinophilia in FE. METHODS: Microarray analysis and real-time PCR were used to examine transcriptional differences in peripheral blood mononuclear cells (PBMC), and in purified cell subsets from affected and unaffected family members belonging to a single large kindred. Cytokine levels in serum and PBMC culture supernatants were assessed by suspension array multiplexed immunoassays. RESULTS: Whereas IL-5 mRNA expression was significantly increased in freshly isolated PBMC from affected family members, this was not accompanied by increased mRNA expression of other Th2 cytokines (IL-4 or IL-13). Serum levels of IL-5 and IL-5 receptor α, but not IgE, were similarly increased in affected family members. Of note, IL-5 mRNA expression was significantly increased in purified CD3+ CD4+, CD14+, CD19+, and ILC2 cells from affected family members, as were IL-5 protein levels in supernatants from both stimulated PBMC and ILC2 cultures. CONCLUSIONS: These data are consistent with the hypothesis that the eosinophilia in FE is secondary to dysregulation of IL-5 production in PBMC (and their component subsets).

Prevalence and correlates of HIV infection and sexually transmitted infections in female sex workers (FSWs) in Shanghai, China.

In 2009, we examined HIV and sexually transmitted infections (STIs) in 750 female sex workers (FSWs) in Shanghai using a cross-sectional survey. Participants (mean age 27 years) were interviewed and tested for HIV and selected STIs. Prevalence was: HIV 0·13%, chlamydia 14·7%, gonorrhoea 3·5% and syphilis 1·3%. In a demographic multivariate model, younger age, higher income and originating from provinces other than Zhejiang and Shanghai were independently associated with STI. In a social and sexual behavioural model, women working in small venues with fewer clients per week, use of drugs, and higher price charged per sex act indicated a greater risk for STI. Although HIV appears rare in Shanghai FSWs, chlamydial infection is common, especially in women aged <25 years (prevalence 19·6%). Since STI and HIV share similar risk factors, preventive intervention measures should be implemented immediately based on the venues and characteristics of FSWs to prevent future spread of HIV.

Systematic variation in gene expression patterns in human cancer cell lines.

We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo.

A gene expression database for the molecular pharmacology of cancer.

We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology.

Effect of music-movement synchrony on exercise oxygen consumption.

AIM: Past research indicates that endurance is improved when exercise movements are synchronised with a musical beat, however it is unclear whether such benefits are associated with reduced metabolic cost. We compared oxygen consumption (.VO2) and related physiological effects of exercise conducted synchronously and asynchronously with music. METHODS: Three music tracks, each recorded at three different tempi (123, 130, and 137 beats.min-1), accompanied cycle ergometry at 65 pedal revolutions.min-1. Thus three randomly-assigned experimental conditions were administered: slow tempo asynchronous, synchronous, and fast tempo asynchronous. Exercise response of .VO2, HR, and ratings of perceived exertion (RPE), to each condition was monitored in 10 untrained male participants aged 21.7±0.8 years (mean±SD) who cycled for 12 min at 70% maximal heart rate (HR). RESULTS: Mean .VO2 differed among conditions (P=0.008), being lower in the synchronous (1.80±0.22 L.min-1) compared to the slow tempo asynchronous condition (1.94±0.21 L.min-1; P<0.05). There was no difference in HR or RPE among conditions, although HR showed a similar trend to .VO2. CONCLUSION: The present results indicate that exercise is more efficient when performed synchronously with music than when musical tempo is slightly slower than the rate of cyclical movement.

Effects of epidermal growth factor and erythropoietin on Müller glial activation and phenotypic plasticity in the adult mammalian retina.

Retinal Müller glia have received considerable attention with regard to their potential to function as quiescent retinal precursors. Various activation strategies induce characteristic features of retinal progenitor cells in Müller glia; however, these are often accompanied by hallmark features of reactive gliosis. We investigated the effects of an intravitreal injection of epidermal growth factor (EGF), a known mitogen, and erythropoietin (EPO) on activation and expression of developmental phenotypes within the adult retina. Using thymidine-analogue labeling as well as immunocytochemical and confocal analyses, we assayed the responses of retinal cells exposed to intravitreal administration of either EGF or EPO. We report that adult Müller glia incorporate bromodeoxyuridine (BrdU) and undergo a process of nuclear translocation to ectopic retinal layers following exposure to EGF. These cells survive within the retina for at least 23 days and express the developmental markers Pax6 and Chx10 as well as nestin and glial fibrillary acidic protein. Furthermore, we demonstrate that cotreatment with EGF and EPO suppresses aspects of EGF-induced glial reactivity, alters the retinal distribution of BrdU-positive nuclei, and serves to regulate the expression of developmental phenotypes seen in these cells. These data further our understanding of Müller cell responsiveness to intravitral, combinatorial growth factor treatments.

Changes in Musashi-1 subcellular localization correlate with cell cycle exit during postnatal retinal development.

RNA-binding proteins, and in particular, the Musashi genes, function as essential regulators of progenitor functioning in both the developing and adult organism. In this report, we characterize the differential subcellular distribution of Musashi-1 in cells engaged in either proliferating or differentiating contexts in the developing mouse retina, and in cultured Müller glia. During retinal cell differentiation, Musashi-1 immunoreactivity shifts from exclusively cytoplasmic in retinal progenitor cells, to predominantly nuclear localization in differentiating neurons. This nuclear shift is transient, with localization in the adult retina becoming predominantly perinuclear and cytoplasmic in Müller glia and photoreceptors. A correlation between cell cycle progression and subcellular distribution of Musashi-1 is observed in passageable, adult Müller glial cells in vitro. Furthermore, treatment of Müller cultures with neuron-promoting differentiation media induces asymmetric cytoplasmic Musashi-1 immunoreactivity in dividing daughter cells. The observed shifts in subcellular Musashi-1 localization are consistent with contrasting roles for Musashi-1 during cell proliferation and differentiation. These data provide evidence that nuclear, and cytoplasmic sequestering of Musashi-1 in retinal cells is context-specific, and may contribute to downstream functioning of Musashi-1.

Direct hits to the head during amateur boxing is associated with a rise in serum biomarkers for brain injury.

Boxing exposes participants to the physiological response to high intensity exercise and also to direct body and brain trauma. Amateur boxing is increasing and females have also been included in the Olympics. The aim of this study is to assess the stress response and possible brain injury incurred during a match by measuring serum biomarkers associated with stress and cellular brain injury before and after combat. Sixteen male amateur boxers were studied retrospectively. The study population was divided into two groups: (a) a group that received predominantly punches to the head (PTH) and (b) a group that received predominantly punches to the body (PTB). Blood samples were taken before and five minutes after each contest. They were analysed for S-100B, neuron-specific enolase (NSE), creatine kinase (CK) and cortisol. The PTH group received direct contacts to the head (not blocked, parried or avoided) and to the body (n=8, age: 17.6 ± 5.3, years; height: 1.68 ± 0.13, meters; mass: 65.4 ± 20.3, kg). The PTB group received punches to the body including blocked and parried punches, but received no direct punches to the head, (n=8, mean ± SD, age: 19.1 ± 3.2 years; height: 1.70 ± 0.75, meters; mass: 68.5 ± 15 kg). Significant increases (P<0.05) were observed between pre- and post-combat serum concentrations in serum concentrations in PTH of S-100B (0.35 ± 0.61 vs. 0.54 ± 0.73, µg.L-1) NSE (19.7 ± 14 vs.31.1 ± 26.6, ng.ml-1) and cortisol (373 ± 202 vs. 756 ± 93, nmol.L-1). Significant increases (P<0.05) of creatine kinase were recorded in both groups. This study demonstrates significant elevations in neurochemical biomarkers in boxers who received direct blows to the head. However, further work is required to quantify this volumetric brain damage and long term clinical sequelae.

Switchable damping for a one-particle oscillator.

The possibility to switch the damping rate for a one-electron oscillator is demonstrated for an electron that oscillates along the magnetic field axis in a Penning trap. Strong axial damping can be switched on to allow this oscillation to be used for quantum nondemolition detection of the cyclotron and spin quantum state of the electron. Weak axial damping can be switched on to circumvent the backaction of the detection motion that has limited past measurements. The newly developed switch will reduce the linewidth of the cyclotron transition of one-electron by two orders of magnitude.

Cyclization of the phosphate side chain of adenosine triphosphate: formation of monoadenosine 5'-trimetaphosphate.

Monoadenosine 5'-trimetaphosphate has been prepared from adeno-sine 5'-triphosphate by a carbodiimide-mediated condensation. The molecule was characterized by (3l)P nuclear magnetic resonance, and its (31)P spectrum was simulated through the assumption of a three-phosphorus spin system. The molecule is highly reactive and is rapidly converted to adenosine triphosphate upon contact with water.

2-aminoethylphosphonic Acid metabolism during embryonic development of the planorbid snail helisoma.

In freshly laid egg masses of Helisoma sp., more than 95 percent of the phosphorus is found in alkylphosphonic acids, as determined by phosphorus-31 nuclear magnetic resonance spectroscopy. These compounds are metabolized during embryonic development, as shown by differential acid hydrolysis and experiments with phosphorus-33-labeled phosphoric acid. Further, nuclear magnetic resonance spectroscopy indicates phosphonic acid involvement in related snail families, including the schistosomal vector Biomphalaria glabrata.

Biological phosphonates: determination by phosphorus-31 nuclear magnetic resonance.

Advanced methods of phosphorus-31 nuclear magnetic resonance spectroscopy provided a method whereby biological phosphonates and phosphates can be determined on simple lipid fractions of biological origin. The spectra consist of two easily distinguished resonance bands; one corresponds to families of phosphonates, and the other corresponds to families of orthophosphates.

An information-intensive approach to the molecular pharmacology of cancer.

Since 1990, the National Cancer Institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI50) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI50 values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.