Liouville-space R-matrix-Floquet description of atomic radiative processes involving autoionizing states in the presence of intense electromagnetic fields

A reduced-density-operator description is developed for coherent optical phenomena in many-electron atomic systems, utilizing a Liouville-space, multiple-mode Floquet–Fourier representation. The Liouville-space formulation provides a natural generalization of the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method, which has been developed for multi-photon transitions and laser-assisted electron–atom collision processes. In these applications, the R-matrix-Floquet method has been demonstrated to be capable of providing an accurate representation of the complex, multi-level structure of many-electron atomic systems in bound, continuum, and autoionizing states. The ordinary Hilbert-space (Hamiltonian) formulation of the R-matrix-Floquet method has been implemented in highly developed computer programs, which can provide a non-perturbative treatment of the interaction of a classical, multiple-mode electromagnetic field with a quantum system. This quantum system may correspond to a many-electron, bound atomic system and a single continuum electron. However, including pseudo-states in the expansion of the many-electron atomic wave function can provide a representation of multiple continuum electrons. The 'dressed' many-electron atomic states thereby obtained can be used in a realistic non-perturbative evaluation of the transition probabilities for an extensive class of atomic collision and radiation processes in the presence of intense electromagnetic fields. In order to incorporate environmental relaxation and decoherence phenomena, we propose to utilize the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method as a starting-point for a Liouville-space (reduced-density-operator) formulation. To illustrate how the Liouville-space R-matrix-Floquet formulation can be implemented for coherent atomic radiative processes, we discuss applications to electromagnetically induced transparency, as well as to related pump–probe optical phenomena, and also to the unified description of radiative and dielectronic recombination in electron–ion beam interactions and high-temperature plasmas

Robust Multi-Image HDR Reconstruction for the Modulo Camera

Photographing scenes with high dynamic range (HDR) poses great challenges to consumer cameras with their limited sensor bit depth. To address this, Zhao et al. recently proposed a novel sensor concept - the modulo camera - which captures the least significant bits of the recorded scene instead of going into saturation. Similar to conventional pipelines, HDR images can be reconstructed from multiple exposures, but significantly fewer images are needed than with a typical saturating sensor. While the concept is appealing, we show that the original reconstruction approach assumes noise-free measurements and quickly breaks down otherwise. To address this, we propose a novel reconstruction algorithm that is robust to image noise and produces significantly fewer artifacts. We theoretically analyze correctness as well as limitations, and show that our approach significantly outperforms the baseline on real data.Comment: to appear at the 39th German Conference on Pattern Recognition (GCPR) 201

Cluster J Mycobacteriophages: Intron Splicing in Capsid and Tail Genes

Bacteriophages isolated on Mycobacterium smegmatis mc2155 represent many distinct genomes sharing little or no DNA sequence similarity. The genomes are architecturally mosaic and are replete with genes of unknown function. A new group of genomes sharing substantial nucleotide sequences constitute Cluster J. The six mycobacteriophages forming Cluster J are morphologically members of the Siphoviridae, but have unusually long genomes ranging from 106.3 to 117 kbp. Reconstruction of the capsid by cryo-electron microscopy of mycobacteriophage BAKA reveals an icosahedral structure with a triangulation number of 13. All six phages are temperate and homoimmune, and prophage establishment involves integration into a tRNA-Leu gene not previously identified as a mycobacterial attB site for phage integration. The Cluster J genomes provide two examples of intron splicing within the virion structural genes, one in a major capsid subunit gene, and one in a tail gene. These genomes also contain numerous free-standing HNH homing endonuclease, and comparative analysis reveals how these could contribute to genome mosaicism. The unusual Cluster J genomes provide new insights into phage genome architecture, gene function, capsid structure, gene mobility, intron splicing, and evolution. © 2013 Pope et al

High incidence of diabetes after stroke in young adults and risk of recurrent vascular events: the FUTURE study

BACKGROUND: Diabetes diagnosed prior to stroke in young adults is strongly associated with recurrent vascular events. The relevance of impaired fasting glucose (IFG) and incidence of diabetes after young stroke is unknown. We investigated the long-term incidence of diabetes after young stroke and evaluated the association of diabetes and impaired fasting glucose with recurrent vascular events. METHODS: This study was part of the FUTURE study. All consecutive patients between January 1, 1980, and November 1, 2010 with TIA or ischemic stroke, aged 18-50, were recruited. A follow-up assessment was performed in survivors between November 1, 2009 and January 1, 2012 and included an evaluation for diabetes, fasting venous plasma glucose and recurrent vascular events. The association of diabetes and IFG with recurrent vascular events was assessed by logistic regression analysis, adjusted for age, sex and follow-up duration. RESULTS: 427 survivors without a medical history of diabetes were included in the present analysis (mean follow-up of 10.1 (SD 8.4) years; age 40.3 (SD 7.9) years). The incidence rate of diabetes was 7.9 per 1000 person-years and the prevalence of IFG was 21.1%. Patients with diabetes and IFG were more likely to have experienced any vascular event than those with normal fasting glucose values (OR 3.5 (95%CI 1.5-8.4) for diabetes and OR 2.5 (95%CI 1.3-4.8) for IFG). CONCLUSIONS: Diabetes or IFG in young stroke survivors is frequent and is associated with recurrent vascular events. Regular screening for IFG and diabetes in this population, yields potential for secondary prevention

Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus

A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules

At the crossroads of biomacromolecular research: highlighting the interdisciplinary nature of the field

Due to their complexity and wide-ranging utility, biomacromolecular research is an especially interdisciplinary branch of chemistry. It is my goal that the Biomacromolecules subject area of Chemistry Central Journal will parallel this richness and diversity. In this inaugural commentary, I attempt to set the stage for achieving this by highlighting several areas where biomacromolecular research overlaps more traditional chemistry sub-disciplines. Specifically, it is discussed how Materials Science and Biotechnology, Analytical Chemistry, Cell Biology and Chemical Theory are each integral to modern biomacromolecular research. Investigators with reports in any of these areas, or any other dealing with biomacromolecules, are encouraged to submit their research papers to Chemistry Central Journal

Baseline and follow-up assessment of regional left ventricular volume using 3-dimensional echocardiography: comparison with cardiac magnetic resonance

The assessment of regional volumes is an option for analysis of the response of LV segments to interventions such as revascularization or cell therapy. We sought to compare regional volumes from 3D-echocardiography (3DE) with cardiac magnetic resonance (CMR) over follow-up

Kidney Dysfunction Increases Mortality and Incident Events after Young Stroke: The FUTURE Study.

BACKGROUND: In about 30% of young stroke patients, no cause can be identified. In elderly patients, kidney dysfunction has been suggested as a contributing risk factor for mortality as well as stroke. There are hypotheses that novel non-traditional risk factors, like chronic inflammation and oxidative stress, are involved in chronic kidney disease, affecting the cerebral microvasculature that would in turn lead to stroke. Our objective is to investigate the influence of kidney dysfunction on long-term mortality and incident vascular events after stroke in young adults aged 18 through 50 and if this relationship would be independent of other cardiovascular risk factors. METHODS: We prospectively included 460 young stroke patients with an ischemic stroke or transient ischemic attack admitted to our department between January 1, 1980 and November 1, 2010. Follow-up was done between 2014 and 2015. Estimated glomerular filtration rate (eGFR) was calculated from baseline creatinine levels and was divided in 3 subgroups: eGFR 120 ml/min/1.73 m2. Cox proportional hazard models were used to determine the effect of kidney dysfunction on mortality and incident vascular events, adjusting for cardiovascular risk factors. RESULTS: An eGFR <60 (HR 4.6; 95% CI 2.6-8.2) was associated with an increased risk of death and an increased risk of incident stroke (HR 4.1; 95% CI 1.9-9.0) independent of cardiovascular risk factors, but it was not associated with other vascular events. The point estimate for the 15-year cumulative mortality was 70% (95% CI 46-94) for patients with a low eGFR, 24% (95% CI 18-30) for patients with a normal eGFR and 30% (95% CI 12-48) for patients with a high eGFR. The point estimate for the 15-year cumulative risk of incident stroke was 45% (95% CI 16-74) for patients with a low eGFR, 13% (95% CI 9-17) for patients with a normal eGFR and 8% (95% CI 0-18) for patients with a high eGFR. CONCLUSIONS: Kidney dysfunction is related to long-term mortality and stroke recurrence, but not to incident cardiovascular disease, on average 11 years after young stroke. This warrants a more intensive follow-up of young stroke patients with signs of kidney dysfunction in the early phase. In addition, the clear association between kidney dysfunction and incident stroke seen in our young stroke population might be a first step in the recognition of kidney dysfunction as a new risk factor for the development of stroke at young age. Also, it can lead to new insights in the etiological differences between cardiovascular and cerebrovascular disease.This study was funded by the Dutch Epilepsy Fund (grant number 10-18)

Hydrogen bond networks determine emergent mechanical and thermodynamic properties across a protein family

<p>Abstract</p> <p>Background</p> <p>Gram-negative bacteria use periplasmic-binding proteins (bPBP) to transport nutrients through the periplasm. Despite immense diversity within the recognized substrates, all members of the family share a common fold that includes two domains that are separated by a conserved hinge. The hinge allows the protein to cycle between open (apo) and closed (ligated) conformations. Conformational changes within the proteins depend on a complex interplay of mechanical and thermodynamic response, which is manifested as an increase in thermal stability and decrease of flexibility upon ligand binding.</p> <p>Results</p> <p>We use a distance constraint model (DCM) to quantify the give and take between thermodynamic stability and mechanical flexibility across the bPBP family. Quantitative stability/flexibility relationships (QSFR) are readily evaluated because the DCM links mechanical and thermodynamic properties. We have previously demonstrated that QSFR is moderately conserved across a mesophilic/thermophilic RNase H pair, whereas the observed variance indicated that different enthalpy-entropy mechanisms allow similar mechanical response at their respective melting temperatures. Our predictions of heat capacity and free energy show marked diversity across the bPBP family. While backbone flexibility metrics are mostly conserved, cooperativity correlation (long-range couplings) also demonstrate considerable amount of variation. Upon ligand removal, heat capacity, melting point, and mechanical rigidity are, as expected, lowered. Nevertheless, significant differences are found in molecular cooperativity correlations that can be explained by the detailed nature of the hydrogen bond network.</p> <p>Conclusion</p> <p>Non-trivial mechanical and thermodynamic variation across the family is explained by differences within the underlying H-bond networks. The mechanism is simple; variation within the H-bond networks result in altered mechanical linkage properties that directly affect intrinsic flexibility. Moreover, varying numbers of H-bonds and their strengths control the likelihood for energetic fluctuations as H-bonds break and reform, thus directly affecting thermodynamic properties. Consequently, these results demonstrate how unexpected large differences, especially within cooperativity correlation, emerge from subtle differences within the underlying H-bond network. This inference is consistent with well-known results that show allosteric response within a family generally varies significantly. Identifying the hydrogen bond network as a critical determining factor for these large variances may lead to new methods that can predict such effects.</p

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results