423 research outputs found
Multiple electron trapping in the fragmentation of strongly driven molecules
We present a theoretical quasiclassical study of the formation, during
Coulomb explosion, of two highly excited neutral H atoms (double H) of
strongly driven H. In this process, after the laser field is turned off
each electron occupies a Rydberg state of an H atom. We show that two-electron
effects are important in order to correctly account for double H
formation. We find that the route to forming two H atoms is similar to
pathway B that was identified in Phys. Rev. A {\bf 85} 011402 (R) as one of the
two routes leading to single H formation. However, instead of one
ionization step being "frustrated" as is the case for pathway B, both
ionization steps are "frustrated" in double H formation. Moreover, we
compute the screened nuclear charge that drives the explosion of the nuclei
during double H formation.Comment: 4 pages, 6 figure
Molecular heat pump for rotational states
In this work we investigate the theory for three different uni-directional
population transfer schemes in trapped multilevel systems which can be utilized
to cool molecular ions. The approach we use exploits the laser-induced coupling
between the internal and motional degrees of freedom so that the internal state
of a molecule can be mapped onto the motion of that molecule in an external
trapping potential. By sympathetically cooling the translational motion back
into its ground state the mapping process can be employed as part of a cooling
scheme for molecular rotational levels. This step is achieved through a common
mode involving a laser-cooled atom trapped alongside the molecule. For the
coherent mapping we will focus on adiabatic passage techniques which may be
expected to provide robust and efficient population transfers. By applying
far-detuned chirped adiabatic rapid passage pulses we are able to achieve an
efficiency of better than 98% for realistic parameters and including
spontaneous emission. Even though our main focus is on cooling molecular
states, the analysis of the different adiabatic methods has general features
which can be applied to atomic systems
Provenance-Centered Dataset of Drug-Drug Interactions
Over the years several studies have demonstrated the ability to identify
potential drug-drug interactions via data mining from the literature (MEDLINE),
electronic health records, public databases (Drugbank), etc. While each one of
these approaches is properly statistically validated, they do not take into
consideration the overlap between them as one of their decision making
variables. In this paper we present LInked Drug-Drug Interactions (LIDDI), a
public nanopublication-based RDF dataset with trusty URIs that encompasses some
of the most cited prediction methods and sources to provide researchers a
resource for leveraging the work of others into their prediction methods. As
one of the main issues to overcome the usage of external resources is their
mappings between drug names and identifiers used, we also provide the set of
mappings we curated to be able to compare the multiple sources we aggregate in
our dataset.Comment: In Proceedings of the 14th International Semantic Web Conference
(ISWC) 201
Dietary and other lifestyle characteristics of Cypriot school children: results from the nationwide CYKIDS study
Dietary and lifestyle behaviors at young ages have been associated with the development of various chronic diseases. Schools are regarded as an excellent setting for lifestyle modification; there is a lack, however, of published dietary data in Cypriot school children. Thus, the objective of this work was to describe lifestyle characteristics of a representative segment of Cypriot school children and provide implications for school health education. Methods. The CYKIDS (Cyprus Kids Study) is a national, cross-sectional study conducted among 1140 school children (10.7 0.98 years). Sampling was stratified and multistage in 24 primary schools of Cyprus. Dietary assessment was based on a 154-item semi-quantitative food-frequency questionnaire and three supplementary questionnaires, assessing dietary patterns and behaviors. Adherence to the Mediterranean diet was evaluated by the KIDMED index (Mediterranean Diet Quality Index for children and adolescents). Physical activity was assessed by a 32-item, semi-quantitative questionnaire. Results. Analysis revealed that 6.7% of the children were classified as high adherers, whereas 37% as low adherers to the Mediterranean diet. About 20% of boys and 25% of girls reported "not having breakfast on most days of the week", while more than 80% of the children reported having meals with the family at least 5 times/week. Some food-related behaviors, such as intake of breakfast, were associated with socio-demographic factors, mostly with gender and the geomorphological characteristics of the living milieu. With respect to physical activity, boys reported higher levels compared to girls, however, one fourth of children did not report any kind of physical activity. Conclusion. A large percentage of Cypriot school children have a diet of low quality and inadequate physical activity. Public health policy makers should urgently focus their attention to primary school children and design school health education programs that target the areas that need attention in order to reduce the future burden of metabolic disorders and chronic diseases
A Halomethane thermochemical network from iPEPICO experiments and quantum chemical calculations
Internal energy selected halomethane cations CH3Cl+, CH2Cl2+, CHCl3+, CH3F+, CH2F2+, CHClF2+ and CBrClF2+ were prepared by vacuum ultraviolet photoionization, and their lowest energy dissociation channel studied using imaging photoelectron photoion coincidence spectroscopy (iPEPICO). This channel involves hydrogen atom loss for CH3F+, CH2F2+ and CH3Cl+, chlorine atom loss for CH2Cl2+, CHCl3+ and CHClF2+, and bromine atom loss for CBrClF2+. Accurate 0 K appearance energies, in conjunction with ab initio isodesmic and halogen exchange reaction energies, establish a thermochemical network, which is optimized to update and confirm the enthalpies of formation of the sample molecules and their dissociative photoionization products. The ground electronic states of CHCl3+, CHClF2+ and CBrClF2+ do not confirm to the deep well assumption, and the experimental breakdown curve deviates from the deep well model at low energies. Breakdown curve analysis of such shallow well systems supplies a satisfactorily succinct route to the adiabatic ionization energy of the parent molecule, particularly if the threshold photoelectron spectrum is not resolved and a purely computational route is unfeasible. The ionization energies have been found to be 11.47 ± 0.01 eV, 12.30 ± 0.02 eV and 11.23 ± 0.03 eV for CHCl3, CHClF2 and CBrClF2, respectively. The updated 0 K enthalpies of formation, âfHo0K(g) for the ions CH2F+, CHF2+, CHCl2+, CCl3+, CCl2F+ and CClF2+ have been derived to be 844.4 ± 2.1, 601.6 ± 2.7, 890.3 ± 2.2, 849.8 ± 3.2, 701.2 ± 3.3 and 552.2 ± 3.4 kJ molâ1, respectively. The âfHo0K(g) values for the neutrals CCl4, CBrClF2, CClF3, CCl2F2 and CCl3F and have been determined to be â94.0 ± 3.2, â446.6 ± 2.7, â702.1 ± 3.5, â487.8 ± 3.4 and â285.2 ± 3.2 kJ molâ1, respectively
Geriatric pharmacotherapy : optimisation through integrated approach in the hospital setting
Since older patients are more vulnerable to adverse drug-related events, there is a need to ensure appropriate prescribing in these patients in order to prevent misuse, overuse and underuse of drugs. Different tools and strategies have been developed to reduce inappropriate prescribing; the available measures can be divided into medication assessment tools, and speciïŹc interventions to reduce inappropriate prescribing. Implicit criteria of inappropriate prescribing focus on appropriate dosing, search for drug-drug interactions, and increase adherence. Explicit criteria are consensus-based standards focusing on drugs and diseases and include lists of drugs to avoid in general or lists combining drugs with clinical data. These criteria take into consideration differences between patients, and stand for a medication review, by using a systematic approach. Different types of interventions exist in order to reduce inappropriate prescribing in older patients, such as: educational interventions, computerized decision support systems, pharmacist-based interventions, and geriatric assessment. The effects of these interventions have been studied, sometimes in a multifaceted approach combining different techniques, and all types seem to have positive effects on appropriateness of prescribing. Interdisciplinary teamwork within the integrative pharmaceutical care is important for improving of outcomes and safety of drug therapy. The pharmaceutical care process consists offour steps, which are cyclic for an individual patient. These steps are pharmaceutical anamnesis, medication review, design and follow-up of a pharmaceutical care plan. A standardized approach is necessary for the adequate detection and evaluation of drug-related problems. Furthermore, it is clear that drug therapy should be reviewed in-depth, by having full access to medical records, laboratory values and nursing notes. Although clinical pharmacists perform the pharmaceutical care process to manage the patientâs drug therapy in every day clinical practice, the physician takes the ultimate responsibility for the care of the patient in close collaboration with nurses
Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy
Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ÎΚm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control
HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa
The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells
Digital biomarker-based individualized prognosis for people at risk of dementia
Background: Research investigating treatments and interventions for cognitive decline fail due to difficulties in accurately recognizing behavioral signatures in the presymptomatic stages of the disease. For this validation study, we took our previously constructed digital biomarker-based prognostic models and focused on generalizability and robustness of the models. Method: We validated prognostic models characterizing subjects using digital biomarkers in a longitudinal, multi-site, 40-month prospective study collecting data in memory clinics, general practitioner offices, and home environments. Results: Our models were able to accurately discriminate between healthy subjects and individuals at risk to progress to dementia within 3 years. The model was also able to differentiate between people with or without amyloid neuropathology and classify fast and slow cognitive decliners with a very good diagnostic performance. Conclusion: Digital biomarker prognostic models can be a useful tool to assist large-scale population screening for the early detection of cognitive impairment and patient monitoring over time
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