1,721,693 research outputs found
Endemic-Epidemic Modeling: Bridging Routine Infectious Disease Surveillance and Non-Traditional Data
No full textnot availabl
Endemic-Epidemic Modeling: Bridging Routine Infectious Disease Surveillance and Non-Traditional Data
No full textnot availabl
Discrete Approximations and Optimality Conditions for Controlled Free-Time Sweeping Processes
No full textThe paper is devoted to the study of a new class of optimal control problems governed
by discontinuous constrained differential inclusions of the sweeping type involving
the duration of the dynamic process into optimization. We develop a novel version
of the method of discrete approximations of its own qualitative and numerical values
with establishing its well-posedness and strong convergence to optimal solutions of
the controlled sweeping process. Using advanced tools of first-order and second-order
variational analysis and generalized differentiation allows us to derive new necessary
conditions for optimal solutions of the discrete-time problems and then, by passing
to the limit in the discretization procedure, for designated local minimizers in the
original problem of sweeping optimal control. The obtained results are illustrated by
a numerical example
An allosteric pocket for inhibition of bacterial Enzyme I identified by NMR-based fragment screening
Full text linkEnzyme I (EI), which is the key enzyme to activate the bacterial phosphotransferase system, plays an important role in the regulation of several metabolic pathways and controls the biology of bacterial cells at multiple levels. The conservation and ubiquity of EI among different types of bacteria makes the enzyme a potential target for antimicrobial research. Here, we use NMR-based fragment screening to identify novel inhibitors of EI. We identify three molecular fragments that allosterically inhibit the phosphoryl transfer reaction catalyzed by EI by interacting with the enzyme at a surface pocket located more than 10 Å away from the substrate binding site. Interestingly, although the three molecules share the same binding pocket, we observe that two of the discovered EI ligands act as competitive inhibitors while the third ligand acts as a mixed inhibitor. Characterization of the EI-inhibitor complexes by NMR and Molecular Dynamics simulations reveals key interactions that perturb the fold of the active site and provides structural foundation for the different inhibitory activity of the identified molecular fragments. In particular, we show that contacts between the inhibitor and the side-chain of V292 are crucial to destabilize binding of the substrate to EI. In contrast, mixed inhibition is caused by additional contacts between the inhibitor and ⍺-helix 2 that perturb the active site structure and turnover in an allosteric manner. We expect our results to provide the basis for the development of second generation allosteric inhibitors of increased potency and to suggest novel molecular strategies to combat drug-resistant infections.This article is published as Nguyen, Trang T., and Vincenzo Venditti. "An allosteric pocket for inhibition of bacterial Enzyme I identified by NMR-based fragment screening." Journal of Structural Biology: X (2020): 100034. DOI: 10.1016/j.yjsbx.2020.100034. Posted with permission.</p
Measles epidemic in Southern Vietnam: an age-stratified spatio-temporal model for infectious disease counts
No full textMeasles resurged in Vietnam between 2018 and 2020, especially in the Southern region. The proportion of children with measles infection showed quite some variation at the provincial level. We applied a spatio-temporal endemic-epidemic modelling framework for age-stratified infectious disease counts using measles surveillance data collected in Southern Vietnam between 1 January 2018 and 30 June 2020. We found that disease transmission within age groups was greatest in young children aged 0-4 years whereas a relatively high between-group transmission was observed in older age groups (5-14 years, 15-24 years and 25+ years groups). At the provincial level, spatial transmission followed an age-dependent distance decay with measles spread mainly depending on local and neighbouring transmission. Our study helped to clarify the measles transmission dynamics in a more detailed fashion with respect to age strata, time and space. Findings from this study may help determine proper strategies in measles outbreak control including promotion of age-targeted intervention programmes in specific areas.sponsorship: We are grateful to the VLIR-UOS for awarding THTN a scholarship to study the Master of Epidemiology at the University of Antwerp, Belgium. We acknowledge support from the board of directors and colleagues at the Pasteur Institute in Ho Chi Minh City in providing surveillance data for analysis. (VLIR-UOS)status: Publishe
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The oligomerization state of bacterial enzyme I (EI) determines EI's allosteric stimulation or competitive inhibition by α-ketoglutarate
Full text linkThe bacterial phosphotransferase system (PTS) is a signal transduction pathway that couples phosphoryl transfer to active sugar transport across the cell membrane. The PTS is initiated by phosphorylation of enzyme I (EI) by phosphoenolpyruvate (PEP). The EI phosphorylation state determines the phosphorylation states of all other PTS components and is thought to play a central role in the regulation of several metabolic pathways and to control the biology of bacterial cells at multiple levels, for example, affecting virulence and biofilm formation. Given the pivotal role of EI in bacterial metabolism, an improved understanding of the mechanisms controlling its activity could inform future strategies for bioengineering and antimicrobial design. Here, we report an enzymatic assay, based on Selective Optimized Flip Angle Short Transient (SOFAST) NMR experiments, to investigate the effect of the small-molecule metabolite α-ketoglutarate (αKG) on the kinetics of the EI-catalyzed phosphoryl transfer reaction. We show that at experimental conditions favoring the monomeric form of EI, αKG promotes dimerization and acts as an allosteric stimulator of the enzyme. However, when the oligomerization state of EI is shifted toward the dimeric species, αKG functions as a competitive inhibitor of EI. We developed a kinetic model that fully accounted for the experimental data and indicated that bacterial cells might use the observed interplay between allosteric stimulation and competitive inhibition of EI by αKG to respond to physiological fluctuations in the intracellular environment. We expect that the mechanism for regulating EI activity revealed here is common to several other oligomeric enzymes.This article is published as Nguyen, Trang T., Rodolfo Ghirlando, and Vincenzo Venditti. "The oligomerization state of bacterial enzyme I (EI) determines EI’s allosteric stimulation or competitive inhibition by α-ketoglutarate." Journal of Biological Chemistry 293, no. 7 (2018): 2631. DOI: 10.1074/jbc.RA117.001466.</p
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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