We demonstrate the full functionality of a circuit that generates single microwave photons on demand, with a wave packet that can be modulated with a near-arbitrary shape. We achieve such a high ...tunability by coupling a superconducting qubit near the end of a semi-infinite transmission line. A dc superconducting quantum interference device shunts the line to ground and is employed to modify the spatial dependence of the electromagnetic mode structure in the transmission line. This control allows us to couple and decouple the qubit from the line, shaping its emission rate on fast time scales. Our decoupling scheme is applicable to all types of superconducting qubits and other solid-state systems and can be generalized to multiple qubits as well as to resonators.
Peer Reviewed
Carboxylated/oxidized diamond nanoparticles (nominal size 100 nm) exhibit exceptionally high affinity for proteins through both hydrophilic and hydrophobic forces. The affinity is so high that ...proteins in dilute solution can be easily captured by diamonds, simply separated by centrifugation, and directly analyzed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS). No preseparation of the adsorbed molecules from diamonds is required for the mass spectrometric analysis. Compared to conventional MALDI-TOF-MS, an enhancement in detection sensitivity by more than 2 orders of magnitude is achieved for dilute solution containing cytochrome c, myoglobin, and albumin because of preconcentration of the probed molecules. The lowest concentration detectable is 100 pM for a 1-mL solution. Aside from the enhanced sensitivity, the overall performance of this technique does not show any sign of deterioration for highly contaminated protein solutions, and furthermore, no significant peak broadening and band shift were observed in the mass spectra. The promise of this new method for clinical proteomics research is demonstrated with an application to human blood serum.
Recent studies suggest that some serous ovarian carcinomas (SOCs) arise from the fallopian tube (FT) epithelium rather than the ovarian surface epithelium. This hypothesis places emphasis on the FT ...secretory epithelial cell as a cell-of-origin. Herein, we report the development of a novel ex vivo primary human FT epithelium culture system that faithfully recapitulates the in vivo epithelium, as shown by morphological, ultrastructural and immunophenotypic analyses. Mass spectrometry-based proteomics reveal that these cultures secrete proteins previously identified as biomarkers for ovarian cancer. We also use this culture system to study the response of the FT epithelium to genotoxic stress and find that the secretory cells exhibit a distinct response to DNA damage when compared with neighboring ciliated cells. The secretory cells show a limited ability to resolve the damage over time, potentially leaving them more susceptible to accumulation of additional mutagenic injury. This divergent response is confirmed with in situ studies using tissue samples, further supporting the use of this ex vivo culture system to investigate FT epithelial pathobiology. We anticipate that this novel culture system will facilitate the study of SOC pathogenesis, and propose that similar culture systems could be developed for other organ site-specific epithelia.
Chang H‐H, Chang M‐C, Huang G‐F, Wang Y‐L, Chan C‐P, Wang T‐M, Lin P‐S, Jeng J‐H. Effect of triethylene glycol dimethacrylate on the cytotoxicity, cyclooxygenase‐2 expression and prostanoids ...production in human dental pulp cells. International Endodontic Journal, 45, 848–858, 2012.
Aim To evaluate the effect of TEGDMA on cell cycle progression as well as alterations of cell cycle‐related gene and protein expression.
Methodology Human dental pulp cells were exposed to 0–5 mmol L−1 TEGDMA for 24 h. Cytotoxicity was evaluated by 3‐(4, 5‐dimethyl‐ thiazol‐2‐yl)‐2,5‐diphenyl ‐tetrazolium bromide assay. Cell cycle progression was analysed by propidium iodide (PI) flow cytometry. Cell death pathway was surveyed by annexin V/PI dual‐staining flow cytometry. The mRNA expression of cell cycle‐related genes (cdc2, cyclinB1 and p21) and COX‐2 was evaluated by reverse transcriptase‐polymerase chain reaction, and their protein expression was evaluated by Western blotting. The production of PGE2 and PGF2α in the culture medium was determined by enzyme‐linked immunosorbent assay.
Results Triethylene glycol dimethacrylate inhibited cellular growth and induced cell cycle deregulation in dental pulp cells. High‐dose exposure provoked both necrotic and apoptotic cell death. The gene and protein expression of cdc2, cyclin B1 and cdc25C declined obviously whilst cells treated with 2.5 mmol L−1 TEGDMA concurrent with the elevated expression of p21. The mRNA and protein expression of COX‐2, along with production of PGE2 and PGF2α, are drastically raised by 2.5–5 mmol L−1 TEGDMA.
Conclusions Triethylene glycol dimethacrylate induced cytotoxicity, cell cycle arrest and apoptosis in dental pulp cells, which was associated with the decline of cdc2, cyclin B1, cdc25C expression and elevation of p21 expression. Concomitantly, COX‐2 expression, PGE2 and PGF2α production increased. These effects may contribute to explain the pulpal damage and inflammation induced by TEGDMA after operative procedures.
Background Amoxicillin‐resistant Helicobacter pylori with minimal inhibitory concentration (MIC) ≥ 256 mg L−1 was isolated from a gastritis patient. The aims were to investigate the mechanism of ...high‐level amoxicillin resistance in H. pylori.
Materials and methods The β‐lactamase production was determined by means of nitrocefin sticks and the presence of gene encoding the β‐lactam antibiotic resistance enzyme TEM β‐lactamase was analysed by polymerase chain reaction (PCR), sequencing and dot‐blot hybridization. Sequencing analysis of pbp1A gene was performed and amoxicillin‐susceptible isolate was transformed with pbp1A PCR products from the resistant isolate. The expression of hefC efflux system was analysed using real‐time quantitative PCR.
Results Activity of β‐lactamase was detected. Sequence analysis showed that the PCR product derived from H. pylori 3778 was identical to the blaTEM‐1 (GenBank accession EU726527). Dot‐blot hybridization confirmed the presence of β‐lactamase gene blaTEM‐1. By transformation of PCR product of mutated pbp1A gene from H. pylori 3778 into amoxicillin‐susceptible strain showed that substitutions in Thr556→Ser, Lys648→Gln, Arg649→Lys and Arg656→Pro contribute to low‐level amoxicillin resistance. The MIC of amoxicillin for the transformants was 0·75 mg L−1. Over‐expression of hefC was not found.
Conclusions High‐level amoxicillin resistance is associated with β‐lactamase production in H. pylori. Low‐level amoxicillin resistance is linked to a point mutation on pbp1A. Because H. pylori can exchange DNA through natural transformation, spreading of blaTEM‐1 amoxicillin resistance gene among H. pylori is a potential threat when treating H. pylori infection.
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its ...stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD(+) genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.
To perform a quantitative review of the evidence on the diagnostic value of inflammatory markers in maternal serum or umbilical cord blood for the diagnosis of early-onset neonatal sepsis (EONS).
We ...searched multiple databases for studies published through March 2013 that evaluated the diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models.
Our search identified 3874 citations, of which 15 studies evaluating 2178 episodes of suspected neonatal infection were included for analysis. IL-6 in cord blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a valid rule-in test. IL-6 in cord blood with a LR- of 0.10 (0.05 to 0.21) and PCT in cord blood with a LR- of 0.20 (0.12-0.37) can be qualified as a useful rule-out test. Either CRP or WBC was inadequate for diagnosis of EONS.
For cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool. For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An interventional study may be needed to answer whether the addition of these tests will improve the outcome of patients with EONS.
The synthesis of a series of (formazanate)boron difluorides and their 1-electron reduction products is described. The neutral compounds are fluorescent with large Stokes shifts. DFT calculations ...suggest that a large structural reorganization accompanies photoexictation and accounts for the large Stokes shift. Reduction of the neutral boron difluorides occurs at the ligand and generates the corresponding radical anions. These complexes are non-fluorescent, allowing switching of the emission by changing the ligand oxidation state.
Managing the related but distinct processes of "product design and engineering" and manufacturing in an integrated way poses significant challenges for many industrial enterprises. This study ...presents a systematic review of the literature focused on the interface between these two areas. The review has identified six core themes based on 49 retrieved papers: (A) Integral Productivity, (B) Order Entry Points and Modularity, (C) Product Life Cycle Management, (D) Sourcing Decisions and Supplier Involvement, (E) Integrated Processes and Coordination, and (F) Enabling through Information and Communication Technology. Five of these themes, A-E, are discussed in the paper, using the retrieved works complemented by additional literature, case evidence from the literature as well as additional cases. A generic reference model is used to support the in-depth review of literature and cases. The study shows that tremendous progress during the past 20 years has been made in approaches for managing the interface by both researchers providing generic concepts and practitioners to overcome obstacles for implementation; at the same the paper also identifies gaps in the literature from both theoretical and practical perspectives. An extensive research agenda is proposed to address the gaps identified. It is argued that across all themes further research on this critical interface needs to consider the degree of novelty in new product development, engineering and manufacturing as mediating factor. However, it is also noted that companies seem to manage this interface effectively despite it being challenging, albeit sometimes very practically and intuitively.
Objectives
The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is ...stronger among those with HIV infection.
Methods
Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD‐9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)‐9 scores ≥ 10. The outcome was all‐cause mortality. Covariates were demographics, comorbid conditions and health behaviours.
Results
Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow‐up time of 11 years. The death rate was 25.3 95% confidence interval (CI) 25.0–25.6 deaths per 1000 person‐years. Major depressive disorder was associated with mortality hazard ratio (HR) 1.04; 95% CI 1.01, 1.07. This association was modified by HIV status (interaction P‐value = 0.02). In HIV‐stratified analyses, depression was significantly associated with mortality among HIV‐uninfected veterans but not among those with HIV infection. Among those with PHQ‐9 data (n = 7372), 50% had HIV infection, 22% had PHQ‐9 scores ≥ 10, and 28% died over a median follow‐up time of 12 years. The death rate was 27.3 (95% CI 26.1–28.5) per 1000 person‐years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P‐value = 0.05). In HIV‐stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection.
Conclusions
Depression was associated with all‐cause mortality. This association was modified by HIV status and method of depression ascertainment.
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