A family of single-stage-switched-capacitor-inductor converters with different voltage conversion features and similar structures is presented in this paper. Unlike conventional ...switched-capacitor/switched-inductor converters that are produced by cascade operation, all of the proposed converters are operated in single-stage mode. Though each of the proposed converters employs two energy transfer components, i.e., one switched capacitor and one inductor, energy flowing though the two components both directly come from the input power sources and then is directly released to output terminal. This design can meet the high efficiency requirement and simple structure. A small resonant inductor is also used in these converters to limit the current peak caused by switched capacitors and to improve efficiency. The detailed analysis of circuit operation and design consideration is given. Simulation and experimental results are also provided to verify the performance of the new family of converters.
C. difficile forms biofilms in vitro Biofilm formation by C. difficile was first reported by Donelli and colleagues where they identified the role of polymicrobial biofilms in clogging of biliary ...stents using confocal and field emission scanning electron microscopy 4. Mutants deficient in stress-related proteins including the SOS response regulator, LexA, the RNA chaperone, Hfq, and the heat stress-associated chaperone, DnaK, have been associated with increased biofilm formation 8–10. In a recent global gene expression analysis of microfermentor biofilms, several genes controlled by the SinR-like regulators CD2214 and CD2215, including pilA1, were differentially expressed in biofilms, although pilA1 appeared to contribute to biofilm/aggregate formation only in c-di-GMP overexpressing strains 12. ...C. difficile forms complex biofilms in vitro which involves multiple regulatory pathways and several virulence-associated proteins. Paradoxically, subinhibitory concentrations of metronidazole and vancomycin induced biofilm formation and seemingly reduced antibiotic susceptibility 5,18. ...it is possible that low levels of antibiotics could induce C. difficile biofilm production, thus promoting persistence and recurrence of infection.
Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the ...mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we developed and tested a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored the Dmd reading frame in myofibers, cardiomyocytes, and muscle stem cells after local or systemic delivery. AAV-Dmd CRISPR treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.
Purpose
Despite advances in personalizing the efficacy of cancer therapy, our ability to identify patients at risk of severe treatment side effects and provide individualized supportive care is ...limited. This is particularly the case for mucositis (oral and gastrointestinal), with no comprehensive risk evaluation strategies to identify high-risk patients. We, the Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) Mucositis Study Group, therefore aimed to systematically review current evidence on that factors that influence mucositis risk to provide a foundation upon which future risk prediction studies can be based.
Methods
We identified 11,018 papers from PubMed and Web of Science, with 197 records extracted for full review and 113 meeting final eligibility criteria. Data were then synthesized into tables to highlight the level of evidence for each risk predictor.
Results
The strongest level of evidence supported dosimetric parameters as key predictors of mucositis risk. Genetic variants in drug-metabolizing pathways, immune signaling, and cell injury/repair mechanisms were also identified to impact mucositis risk. Factors relating to the individual were variably linked to mucositis outcomes, although female sex and smoking status showed some association with mucositis risk.
Conclusion
Mucositis risk reflects the complex interplay between the host, tumor microenvironment, and treatment specifications, yet the large majority of studies rely on hypothesis-driven, single-candidate approaches. For significant advances in the provision of personalized supportive care, coordinated research efforts with robust multiplexed approaches are strongly advised.
The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of ...cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type–specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions.
Aim
Increasing evidence demonstrates that circadian clock proteins are important regulators of physiological functions including blood pressure. An established risk factor for developing ...cardiovascular disease is the absence of a blood pressure dip during the inactive period. The goal of the present study was to determine the effects of a high salt diet plus mineralocorticoid on PER1‐mediated blood pressure regulation in a salt‐resistant, normotensive mouse model, C57BL/6J.
Methods
Blood pressure was measured using radiotelemetry. After control diet, wild‐type (WT) and Per1 (KO) knockout mice were given a high salt diet (4% NaCl) and the long‐acting mineralocorticoid deoxycorticosterone pivalate. Blood pressure and activity rhythms were analysed to evaluate changes over time.
Results
Blood pressure in WT mice was not affected by a high salt diet plus mineralocorticoid. In contrast, Per1 KO mice exhibited significantly increased mean arterial pressure (MAP) in response to a high salt diet plus mineralocorticoid. The inactive/active phase ratio of MAP in WT mice was unchanged by high salt plus mineralocorticoid treatment. Importantly, this treatment caused Per1 KO mice to lose the expected decrease or ‘dip’ in blood pressure during the inactive compared to the active phase.
Conclusion
Loss of PER1 increased sensitivity to the high salt plus mineralocorticoid treatment. It also resulted in a non‐dipper phenotype in this model of salt‐sensitive hypertension and provides a unique model of non‐dipping. Together, these data support an important role for the circadian clock protein PER1 in the modulation of blood pressure in a high salt/mineralocorticoid model of hypertension.
Transcription activator-like effector nucleases (TALENs) are an approach for directed gene disruption and have been proved to be effective in various animal models. Here, we report that TALENs can ...induce somatic mutations in Xenopus embryos with reliably high efficiency and that such mutations are heritable through germ-line transmission. We modified the Golden Gate method for TALEN assembly to make the product suitable for RNA transcription and microinjection into Xenopus embryos. Eight pairs of TALENs were constructed to target eight Xenopu s genes, and all resulted in indel mutations with high efficiencies of up to 95.7% at the targeted loci. Furthermore, mutations induced by TALENs were highly efficiently passed through the germ line to F ₁ frogs. Together with simple and reliable PCR-based approaches for detecting TALEN-induced mutations, our results indicate that TALENs are an effective tool for targeted gene editing/knockout in Xenopus .
Summary Background Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in China, where the population is also exposed to high levels of passive smoking, yet little ...information exists on the effects of such exposure on COPD. We examined the relation between passive smoking and COPD and respiratory symptoms in an adult Chinese population. Methods We used baseline data from the Guangzhou Biobank Cohort Study. Of 20 430 men and women over the age of 50 recruited in 2003–06, 15 379 never smokers (6497 with valid spirometry) were included in this cross-sectional analysis. We measured passive smoking exposure at home and work by two self-reported measures (density and duration of exposure). Diagnosis of COPD was based on spirometry and defined according to the GOLD guidelines. Findings There was an association between risk of COPD and self-reported exposure to passive smoking at home and work (adjusted odds ratio 1·48, 95% CI 1·18–1·85 for high level exposure; equivalent to 40 h a week for more than 5 years). There were significant associations between reported respiratory symptoms and increasing passive smoking exposure (1·16, 1·07–1·25 for any symptom). Interpretation Exposure to passive smoking is associated with an increased prevalence of COPD and respiratory symptoms. If this association is causal, we estimate that 1·9 million excess deaths from COPD among never smokers could be attributable to passive smoking in the current population in China. Our findings provide strong evidence for urgent measures against passive smoking in China.
The increase of transmission frequency reveals more merits than low- or medium-frequency distribution among different kinds of power applications. High-frequency inverter serves as source side in ...high-frequency ac (HFAC) power distribution system (PDS). However, it is complicated to obtain a high-frequency inverter with both simple circuit topology and straightforward modulation strategy. A novel switched-capacitor-based cascaded multilevel inverter is proposed in this paper, which is constructed by a switched-capacitor frontend and H-Bridge backend. Through the conversion of series and parallel connections, the switched-capacitor frontend increases the number of voltage levels. The output harmonics and the component counter can be significantly reduced by the increasing number of voltage levels. A symmetrical triangular waveform modulation is proposed with a simple analog implementation and low modulation frequency comparing with traditional multicarrier modulation. The circuit topology, symmetrical modulation, operation cycles, Fourier analysis, parameter determination, and topology enhancement are examined. An experimental prototype with a rated output frequency of 25 kHz is implemented to compare with simulation results. The experimental results agreed very well with the simulation that confirms the feasibility of proposed multilevel inverter.
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