Electron-hole symmetry in a semiconducting carbon nanotube quantum dot

Optical and electronic phenomena in solids arise from the behaviour of electrons and holes (unoccupied states in a filled electron sea). Electron-hole symmetry can often be invoked as a simplifying description, which states that electrons with energy above the Fermi sea behave the same as holes below the Fermi energy. In semiconductors, however, electron-hole symmetry is generally absent since the energy band structure of the conduction band differs from the valence band. Here we report on measurements of the discrete, quantized-energy spectrum of electrons and holes in a semiconducting carbon nanotube. Through a gate, an individual nanotube is filled controllably with a precise number of either electrons or holes, starting from one. The discrete excitation spectrum for a nanotube with N holes is strikingly similar to the corresponding spectrum for N electrons. This observation of near perfect electron-hole symmetry demonstrates for the first time that a semiconducting nanotube can be free of charged impurities, even in the limit of few-electrons or holes. We furthermore find an anomalously small Zeeman spin splitting and an excitation spectrum indicating strong electron-electron interactions.Comment: 12 pages, 4 figure

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Lipopolysaccharide does not alter small airway reactivity in mouse lung slices

The bacterial endotoxin, lipopolysaccharide (LPS) has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase contraction and impair relaxation of mouse small airways. Lung slices were prepared from naïve Balb/C mice and cultured in the absence or presence of LPS (10 µg/ml) for up to 48 h for measurement of TNFα levels in conditioned media. Alternatively, mice were challenged with PBS or LPS in vivo once a day for 4 days for preparation of lung slices or for harvest of lungs for Q-PCR analysis of gene expression of pro-inflammatory cytokines and receptors involved in airway contraction. Reactivity of small airways to contractile agonists, methacholine and serotonin, and bronchodilator agents, salbutamol, isoprenaline and rosiglitazone, were assessed using phase-contrast microscopy. In vitro LPS treatment of slices increased TNFα release 6-fold but did not alter contraction or relaxation to any agonists tested. In vivo LPS treatment increased lung gene expression of TNFα, IL-1β and ryanodine receptor isoform 2 more than 5-fold. However there were no changes in reactivity in lung slices from these mice, even when also incubated with LPS ex vivo. Despite evidence of LPS-induced inflammation, neither airway hyperresponsiveness or impaired dilator reactivity were evident. The increase in ryanodine receptor isoform 2, known to regulate calcium signaling in vascular smooth muscle, warrants investigation. Since LPS failed to elicit changes in small airway reactivity in mouse lung slices following in vitro or in vivo treatment, alternative approaches are required to define the potential contribution of this endotoxin to altered small airway reactivity in human lung diseases

Socio-economic factors, gender and smoking as determinants of COPD in a low-income country of sub-Saharan Africa: FRESH AIR Uganda.

In Uganda, biomass smoke seems to be the largest risk factor for the development of COPD, but socio-economic factors and gender may have a role. Therefore, more in-depth research is needed to understand the risk factors. The aim of this study was to investigate the impact of socio-economic factors and gender differences on the COPD prevalence in Uganda. The population comprised 588 randomly selected participants (>30 years) who previously completed the FRESH AIR Uganda study. In this post hoc analysis, the impact of several socio-economic characteristics, gender and smoking on the prevalence of COPD was assessed using a logistic regression model. The main risk factors associated with COPD were non-Bantu ethnicity (odds ratio (OR) 1.73, 95% confidence interval (CI) 1.06-2.82, P=0.030), biomass fuel use for heating (OR 1.76, 95% CI 1.03-3.00, P=0.038), former smoker (OR 1.87, 95% CI 0.97-3.60, P=0.063) and being unmarried (OR 0.087, 95% CI 0.93-2.95, P=0.087). A substantial difference in the prevalence of COPD was seen between the two ethnic groups: non-Bantu 20% and Bantu 12.9%. Additional analysis between these two groups showed significant differences in socio-economic circumstances: non-Bantu people smoked more (57.7% vs 10.7%), lived in tobacco-growing areas (72% vs 14.8%) and were less educated (28.5% vs 12.9% had no education). With regard to gender, men with COPD were unmarried (OR 3.09, 95% CI 1.25-7.61, P=0.015) and used more biomass fuel for heating (OR 2.15, 95% CI 1.02-4.54, P=0.045), and women with COPD were former smokers (OR 3.35, 95% CI 1.22-9.22, P=0.019). Only a few socio-economic factors (i.e., smoking, biomass fuel use for heating, marital status and non-Bantu ethnicity) have been found to be associated with COPD. This applied for gender differences as well (i.e., for men, marital status and biomass fuel for heating, and for women being a former smoker). More research is needed to clarify the complexity of the different risk factors

One Step Ahead in Realizing Pharmacogenetics in Low- and Middle-Income Countries: What Should We Do?

Yudisia Ausi,1,2 Melisa Intan Barliana,2,3 Maarten J Postma,3,4 Auliya A Suwantika3,5 1Doctor Program in Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 2Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 3Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 4Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; 5Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, IndonesiaCorrespondence: Auliya A Suwantika, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung Sumedang KM 21 Jatinangor, Sumedang, 45363, Indonesia, Tel +62 22 84288828, Email [email protected]: Pharmacogenetics is a promising approach in future personalized medicine. This field holds excellent prospects for healthcare quality acceleration. It promotes the transition to the precision medicine era, whereby a health treatment is driven by a deeper understanding of individual characteristics by interpreting the underlying genomic variation. Pharmacogenetics has been developing rapidly since the human genome project. Many pharmacogenetics studies have shown the association between genetic variants and therapy outcomes. Several pharmacogenetics working groups have recommended guidelines for the clinical application of pharmacogenetics. However, the development of pharmacogenetics in low- and middle-income countries (LMICs) is still retarded behind. The problems mainly include clinical evidence, technology, policy and regulation, and human resources. Currently, available genome and drug effect data in LMICs are scarce. Pharmacogenetics development should be escalated with evidence proof through research collaboration across countries. The challenges of pharmacogenetics implementation are discussed comprehensively in this article, along with the prospect of pharmacogenetics-guided personalized medicine in developed countries. Stepwise is expected to help the researchers and stakeholders define the problem that hindered the pharmacogenetics application.Keywords: pharmacogenetics, implementation, LMICs, personalized medicin