Lung adenocarcinoma promotion by air pollutants

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden

ENERGY STORAGE AND MANAGEMENT FOR A SMALL SERIES PLUG-IN HYBRID ELECTRIC VEHICLE

Plug-in hybrid electric vehicles (PHEVs) are gaining increasing interest for both residential and commercial transportation applications. In PHEV design, energy storage system (EES) is a critical component which will impact the overall design efficiency, performance, cost and etc. This dissertation aims to design an advanced energy storage system for a small plug-in hybrid electric vehicle, whose performance will approach very closely to the optimal possible, in terms of energy efficiency and acceleration, for passenger road vehicles application. Moreover, practical automotive requirements are considered during ESS design, such as cost, life time, safety and volume. This dissertation utilizes ultracapacitors in conjunction with Lithium-ion batteries to combine the power performance ability of the former with the greater energy storage capability of the latter. This combination can improve vehicle performance, battery life time and safety issue with appropriate design. This dissertation describes the entire ESS design, from energy storage size optimization (determination of power and capacity), multi-source control strategy, to associated power electronics design and testing. An economical 16-phase interleaved bidirectional DC/DC converter connected between ultracapacitors and batteries, is presented featuring smaller input/output filters, faster dynamic response and lower device stress advantages, which are highly preferable in high power applications. Discontinuous conduction mode (DCM) methodology is applied in the proposed converter to reduce imbalance current between phases so that the current control loop in each phase can be removed. The high current ripples associated with DCM operation are then alleviated by interleaving. The design, construction and testing of hardware prototype are presented with experimental results. Moreover, a novel ZVS/ZCS soft switch is proposed for the DC/DC converter based on DCM operation to improve efficiency, reduce spike voltage between MOSFET, and reduce Electromagnetic Interference (EMI). Both simulation model and experiment circuit have been built for one stage DC/DC converter to verify the proposed method. In addition, a battery charger for residential application with power factor correction (PFC) capability is designed. A single stage of boost converter is proposed to achieve both PFC and battery charging control simultaneously. A modified charger system is proposed by utilizing ultracapacitor combined with bidirectional DC/DC converter, to remove large filtering capacitor requirement in traditional charger system, due to the fact that the power absorbed from the single phase AC supply has a large 120 Hz component

Moment redistribution in continuous profiled steel-concrete composite slabs

10.1680/macr.53.5.301.39454Magazine of Concrete Research535301-309MCOR

Gene transfer by microinjection in the zebra fish Brachydanio rerio.

Methods in molecular biology (Clifton, N.J.)1887-9

Distinctions between critical illness polyneuropathy and axonal Guillain-Barre sybdrome

In this letter we comment on the publication of Yuki and Hirata who postulate a possible relation between critical illness polyneuropathy and axonal Guillain-Barré syndrome.1 The authors mentioned a nosological relation, which at that time still had to be demonstrated by the presence of antiganglioside antibodies in the serum of patients with critical illness polyneuropathy. Critical illness polyneuropathy is a neuromuscular disorder that has been recognised in critically ill patients.2 The clinical picture consists of difficulty in weaning from the artificial respirator, tetraparesis, and muscle wasting of the limbs. The tendon reflexes are mostly decreased or absent. The neurophysiological examination shows an axonal polyneuropathy and sometimes myopathic altered motor unit potentials. The morphological features in the nerve point to a primarily distal axonal degeneration of motor and sensory fibres. Muscle biopsy shows scattered atrophic fibres in acute denervation and grouped atrophy in chronic denervation. Also, necrotic muscle fibres .........

Improvement on lithography pattern profile by plasma treatment

Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films1741526-1530JVTA

Enhancement or reduction of catalytic dissolution reaction in chemically amplified resists by substrate contaminants

10.1109/66.806124IEEE Transactions on Semiconductor Manufacturing124462-469ITSM

Expansion and Differentiation of Human Embryonic Stem Cells to Endoderm Progeny in a Microcarrier Stirred-Suspension Culture

Embryonic stem cells (ESCs) with their abilities for extensive proliferation and multi-lineage differentiation can serve as a renewable source of cellular material in regenerative medicine. However, the development of processes for large-scale generation of human ESCs (hESCs) or their progeny will be necessary before hESC-based therapies become a reality. We hypothesized that microcarrier stirred-suspension bioreactors characterized by scalability, straightforward operation, and tight control of the culture environment can be used for hESC culture and directed differentiation. Under appropriate conditions, the concentration of hESCs cultured in a microcarrier bioreactor increased 34- to 45-fold over 8 days. The cells retained the expression of pluripotency markers such as OCT3/4A, NANOG, and SSEA4, as assessed by quantitative PCR, immunocytochemistry, and flow cytometry. We further hypothesized that hESCs on microcarriers can be induced to definitive endoderm (DE) when incubated with physiologically relevant factors. In contrast to embryoid body cultures, all hESCs on microcarriers are exposed to soluble stimuli in the bulk medium facilitating efficient transition to DE. After reaching a peak concentration, hESCs in microcarrier cultures were incubated in medium containing activin A, Wnt3a, and low concentration of serum. More than 80% of differentiated hESCs coexpressed FOXA2 and SOX17 in addition to other DE markers, whereas the expression of non-DE genes was either absent or minimal. We also demonstrate that the hESC-to-DE induction in microcarrier cultures is scalable. Our findings support the use of microcarrier bioreactors for the generation of endoderm progeny from hESCs including pancreatic islets and liver cells in therapeutically useful quantities