Multi-centre molecules driven by intense laser fields

In this dissertation we investigate the underlying mechanisms for double ionisation in atoms and frustrated double ionisation in multi-centre molecules. We first study the main mechanisms that underlie non-sequential double ionisation in atoms that are driven by near-single-cycle intense laser fields. Unlike long laser pulses, short ones allow for an easier comparison between theory and experiment. We compare several very recently measured experimental quantities for strongly-driven $Ar$ with our computational results and find good agreement. Next, we investigate double ionisation, frustrated double ionisation, frustrated single ionisation in two-electron triatomic molecules. We compare our computational results for the sum of the kinetic energies of the final ion fragments for double ionisation and for frustrated double ionisation with experimental results. We find very good agreement, particularly for frustrated double ionisation. Moreover, we find that, as for diatomic molecules, two pathways prevail in frustrated ionisation of two-electron triatomic molecules. Only in one of these pathways electron-electron correlation plays an important role. For non-sequential double ionisation, it is well established both theoretically and experimentally that electron-electron correlation plays an important role. However, this is not the case for frustrated double ionisation. We identify a scheme of two colour, orthogonally polarised laser fields that can control the strength of the electron-electron correlation in frustrated double ionisation as a function of the time delay between the two laser pulses. Therefore, based on our proposed combination of laser pulses future experiments can demonstrate the role of electron-electron correlation in frustrated double ionisation

Determination of dimethoxyphenethylamine derivatives in urine by deuterium labeled internal standards

The use of gas chromatography–mass spectrometry (GC–MS) in forensic analysis is increasing. To exploit fully the capabilities of MS, labeled standards, that can be used to improve the performance of the quantitative analysis, and to increase accuracy and precision, are required. A series of deuterated internal standards, corresponding to the 2C-series of phenethylamine derivatives, including 4-bromo-2,5-dimethoxyphenethylamine-d6 (2C-B), 4-chloro-2,5-dimethoxyphenethylamine-d6 (2C-C), 4-iodo-2,5-dimethoxy-phe¬nethyl-amine-d6 (2C-I), 4-ethylthio-2,5-dimethoxy-phenethylamine-d6 (2C-T-2) and 2,5-dimethoxy-4-n-propylthiophenethylamine-d6 (2C-T-7), were synthesized. These deuterated compounds were used to analyze for the corresponding unlabeled compounds in urine. The analysis was performed using GC–MS, with the selected ion monitoring (SIM) technique, whereby good results were achieved

The COP9 signalosome complex regulates fungal development and virulence in the wheat scab fungus Fusarium graminearum

The COP9 signalosome (Csn) complex is an evolutionarily conserved complex that regulates various important cellular processes. However, the function of the Csn complex in pathogenic fungi remains elusive. Here, the distribution of Csn subunits in the fungal kingdom was surveyed, and their biological functions were systematically characterized in the fungal pathogen Fusarium graminearum, which is among the top 10 plant fungal pathogens. The results obtained from bioinformatic analyses suggested that the F. graminearum Csn complex consisted of seven subunits (Csn1–Csn7) and that Csn5 was the most conserved subunit across the fungi kingdom. Yeast two-hybrid assays demonstrated that the seven Csn subunits formed a complex in F. graminearum. The Csn complex was localized to both the nucleus and cytoplasm and necessary for hyphal growth, asexual and sexual development and stress response. Transcriptome profiling revealed that the Csn complex regulated the transcription abundance of TRI genes necessary for mycotoxin deoxynivalenol (DON) biosynthesis, subsequently regulating DON production to control fungal virulence. Collectively, the roles of the Csn complex in F. graminearum were comprehensively analyzed, providing new insights into the functions of the Csn complex in fungal virulence and suggesting that the complex may be a potential target for combating fungal diseases

Component Interaction of ESCRT Complexes Is Essential for Endocytosis-Dependent Growth, Reproduction, DON Production and Full Virulence in Fusarium graminearum

Multivesicular bodies (MVBs) are critical intermediates in the trafficking of ubiquitinated endocytosed surface proteins to the lysosome/vacuole for destruction. Recognizing and packaging ubiquitin modified cargoes to the MVB pathway require ESCRT (Endosomal sorting complexes required for transport) machinery, which consists of four core subcomplexes, ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops. Our previous results showed that ESCRT-0 is essential for fungal development and pathogenicity in Fusarium graminearum. We then, in this study, systemically studied the protein-protein interactions within F. graminearum ESCRT-I, -II or -III complex, as well as between ESCRT-0 and ESCRT-I, ESCRT-I and ESCRT-II, and ESCRT-II and ESCRT-III complexes and found that loss of any ESCRT component resulted in abnormal function in endocytosis. In addition, ESCRT deletion mutants displayed severe defects in growth, deoxynivalenol (DON) production, virulence, sexual, and asexual reproduction. Importantly genetic complementation with corresponding ESCRT genes fully rescued all these defective phenotypes, indicating the essential role of ESCRT machinery in fungal development and plant infection in F. graminearum. Taken together, the protein-protein interactome and biological functions of the ESCRT machinery is first profoundly characterized in F. graminearum, providing a foundation for further exploration of ESCRT machinery in filamentous fungi

Potential use of PCSK9 inhibitors as a secondary preventative measure for cardiovascular disease following acute coronary syndrome: a UK real-world study

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a major development in the prevention of cardiovascular disease (CVD) and is one of the most significant discoveries since the development of statin therapy. Administration of two human monoclonal antibodies to PCSK9 (alirocumab and evolocumab) can significantly reduce low-density lipoprotein cholesterol (LDL-c) concentrations, thus improving lipid management. Accordingly, guidelines on the specific indications for alirocumab and evolocumab usage have been released. This multicentre study aimed to estimate the proportion of patients treated for an acute myocardial infarction (MI) who could be considered for PCSK9 inhibitors under the current National Institute for Health and Care Excellence (NICE) lipid targets criteria. The records of 596 patients in two large hospitals in Liverpool, UK were analysed. Information was collected on lipid profiles during and after admission, lipid-lowering therapy and previous CVD. At least 2.2% of patients were eligible for PCSK9 inhibitors post-MI under the current NICE guidance. Additionally, 29% of patients failed to achieve LDL-c concentrations <2.0 mmol/L despite maximum statin therapy and failed to meet eligibility for PCSK9 inhibitors as per the NICE criteria. This cohort represents a group of patients 'in limbo', in which statin therapy alone is not sufficient to reduce LDL-c. PCSK9 inhibitors are expensive and so their use must be highly selective. At present, in a real-world setting with ezetimibe underprescribing, ~2% of patients are eligible and a further 30% are deprived of benefit and improved outcomes by lack of optimisation and/or potential use of PCSK9 inhibitors. [Abstract copyright: © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Retromer Is Essential for Autophagy-Dependent Plant Infection by the Rice Blast Fungus

We thank Dr. Yizhen Deng at the Temasek Life sciences Laboratory (TLL) for providing the RFP-MoAtg8 plasmid. We would like to thank Drs. Zhenbiao Yang (University of California, Riverside) and Xianying Dou (Fujian Agriculture and Forestry University) for helpful discussions.Author Summary The rice blast fungus Magnaporthe oryzae utilizes key infection structures, called appressoria, elaborated at the tips of the conidial germ tubes to gain entry into the host tissue. Development of the appressorium is accompanied with autophagy in the conidium leading to programmed cell death. This work highlights the significance of the Vps35/retromer membrane-trafficking machinery in the regulation of autophagy during appressorium-mediated host penetration, and thus sheds light on a novel molecular mechanism underlying autophagy-based membrane trafficking events during pathogen-host interaction in rice blast disease. Our findings provide the first genetic evidence that the retromer controls the initiation of autophagy in filamentous fungi.Yeshttp://www.plosgenetics.org/static/editorial#pee

Molecular rotation assisted non-sequential double ionization

A molecular rotation assisted non-sequential double ionization (MR-NSDI) mechanism is identified in the breakup of rotational H$_2$ molecules in a few-cycle intense laser pulse using a semi-classical trajectory Monte Carlo method. Applying a molecular source in an appropriate rotational state could intensively boost NSDI probability, and conclude with an additional small anti-correlated electron momentum distribution. It reveals the critical role of the continuous dynamics of molecular rotation, which assists the recollision process and subsequently releases the excited electron from the potential portal resulted from molecular rotation. Two underlying exit channels are found to contribute to MR-NSDI, i.e. tunneling ionization (dominated by enhanced ionization) and direct ionization. The two channels are confirmed to have different critical breakup internuclear distances. A prominent nuclear emission in $(-30^{\circ},30^{\circ})$ along the laser polarized direction is identified to be a signature of MR-NSDI.Comment: This article has been removed by arXiv administrators because the submitter did not have the authority to agree to the licens

A system-bath separation with Smolyak sparse grid scheme: application to an encapsulated molecule

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A Smolyak algorithm adapted to a system-bath separation: application to an encapsulated molecule with large amplitude motions

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A system-bath separation with Smolyak sparse grid scheme: application to an encapsulated molecule

International audienc