Search

A practicable method is described for the synthesis of 3‐acyl‐pyrazolo[1,5‐a]pyridines from N‐aminopyridines and easily available enaminones via a [3+2] cycloaddition. The reactions proceed well with a broad scope, without using additive (base or oxidant). [ABSTRACT FROM AUTHOR]

Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a systematic review of literature following the PRISMA statement guidelines to obtain a description of these syndromes (population, context of occurrence, antipsychotic agents implicated) and draw conclusions about their links. We searched Medline and Web of science databases from January 1951 to May 2019 (further restricted from 2000 to 2019) using search terms including "catatonia", "neuroleptic malignant syndrome" and "antipsychotic agents" for case reports, case series and analytic studies. After screening 4082 records, 410 full-text articles (describing 555 events) were assessed for eligibility. We included events of AIC and/or NMS according to Diagnostic and Statistical Manual (DSM) criteria and extracted data about patients' characteristics, context of occurrence, antipsychotic agent(s) involved and treatment outcomes. We included 165 events (16 AIC, 129 NMS and 20 AIC + NMS) from 144 case reports and case series. The most reported diagnosis was schizophrenia. Comorbid pre-existing conditions such as central nervous system diseases and acute medical events were common. Most of the events (63.3 %) occurred during antipsychotic monotherapy. Second-generation antipsychotics (SGAs, 63.8 %) were overall more implicated than first-generation antipsychotics (FGAs, 36.2 %). Our findings highlight that any antipsychotic medication, even SGA monotherapy prescribed at recommended dose, is at risk for these side effects. FGAs and polypharmacy seem to represent risk factors for malignant catatonia in AIC. The clinical overlap observed between AIC and NMS events in our review suggests a clinical continuum between catatonia and NMS. [ABSTRACT FROM AUTHOR]

Keywords: sulfinate; sulfenylation; iodine; microwave heating; heterocycles; thiolation EN sulfinate sulfenylation iodine microwave heating heterocycles thiolation 1723 1726 4 08/18/23 20230901 NES 230901 Graph Organic sulfur compounds, especially thioethers, are prominent structural motifs in many bioactive natural products, pharmaceuticals, materials, and agrochemicals. [7] In 2018, the Song group developed a difunctionalization of an imidazopyridine by using a sodium sulfinate and iodine (Scheme 1)..[8] With the base and iodine, they obtained the sulfonylated product exclusively, whereas with iodine and a reducing agent (PPh SB 3 sb ), they obtained the sulfenylated product exclusively. However, the reaction of B 1a b with B 2a b in Et SB 2 sb O as a solvent under basic conditions at 100 °C for 20 hours gave the 3-phenylsulfonylated product B 4a b in only 50% conversion, along with 50% of the 3-iodo compound B 5 b (Table 1, entry 1). [Extracted from the article]

Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients. [ABSTRACT FROM AUTHOR]

The first nucleophilic selenocyanation from selenium dioxide and malononitrile is described. This methodology produced a wide variety of selenocyanates from halides in moderate to excellent yields under mild conditions, highlighting the versatility and usefulness of this new source of nucleophilic selenocyanation. [ABSTRACT FROM AUTHOR]

The article presents recent discoveries made by the French Archaeological Mission to the Eastern Desert of Egypt in two Ptolemaic forts occupied in the second half of the 3rd century b.c., Bir Samut and Abbad, located along the road leading from Edfu to Berenike on the Red Sea Coast at the southern fringes of the Ptolemaic Empire. These artifacts, three copper-alloy arrowheads marked with the monogram BE and four Ptolemaic coins minted in Joppa, were recovered in contexts securely dated to the last decades of the 3rd century b.c. Due to the sealed stratigraphy and the discovery of thousands of ostraca and dozens of coins in the same deposits, it is clear that the forts and these objects were abandoned on the eve of the Great Theban Revolt in Egypt, around 207–206 b.c. These discoveries offer an occasion to reassess the corpus of similar arrowheads and coins found in the Eastern Mediterranean. The catalog presented here includes 45 BE arrowheads and 18 Joppa coins and a careful reassessment of the corpus suggests that they were probably produced by the Ptolemaic regime in direct association with the Fourth Syrian War, which ended with the Battle of Raphia in 217 b.c. The geographic distribution of the arrowheads and coins discussed in the article demonstrates the mobility of the Ptolemaic troops after this intense period of conflict. [ABSTRACT FROM AUTHOR]

Background: The treatment of patients with headache represents an important part of a neurologist's activity. It requires sufficient training for neurology residents. In France, residents in neurology can complete this training by attending specialized consultations or by participating in a postgraduate training program called "Diplôme Inter‐Universitaire Migraine et Céphalées" (DIUMC). Objective: The objective of this cross‐sectional study was to investigate the French residents' knowledge in headache medicine and the impact of different types of training in headache medicine that are available in France. Methods: An anonymous survey was carried out among 548 French residents in neurology. Results: The questionnaires of 121 residents (22.1%) were analyzed. Among them, 54.5% (66/121) had no complementary training apart from the internship (Group 1), 21.5% (26/121) had attended only specialized consultations (Group 2), and 24% (29/121) had participated in the DIUMC (Group 3). There was no difference between all groups regarding the knowledge of the prevalence of primary or chronic headaches. There was almost no difference between the groups in the management of episodic migraine. In contrast, the management of tension‐type headache and chronic headache was better known by residents of Group 3 than residents of Group 1. In these two diseases, residents of Group 3 offered prophylactic treatment more often. Almost 29% of the residents (35/121) had read the French guidelines for the diagnosis and management of migraine. In Group 3, residents had read them significantly more often (1.6% in Group 1, 38.5% in Group 2 and 62.1% in Group 3, p < 0.001). Conclusion: This study shows the lack of knowledge among French neurology residents regarding headache medicine. It highlights the interest of specific training programs that could improve the practical and theoretical knowledge of future neurologists. [ABSTRACT FROM AUTHOR]

The article presents a case study reporting two instances of severe and transient pain at recent bone fracture sites following subcutaneous sumatriptan (SS) injection in patients with cluster headaches. Topics include the unusual adverse reaction of bone site pain associated with SS injection, the patients' clinical histories, and the proposed hypotheses regarding the pathophysiology, including SS-induced allodynic pain and the stimulation of 5-HT1B and 5-HT1D receptors at the fracture site.

A new method of deborylative selanylation using arylboronic acids and arylseleninic acids gave diaryl selenoethers and diarylselenoxide. The present approach requires only equimolar arylseleninic acid and led selectively to selenoethers or selenoxides depending on the solvent. The method is metal-free, base- or oxidant-free, efficient, and environmentally friendly. [ABSTRACT FROM AUTHOR]

In this paper, a numerical process is presented for predicting the response of vibrating structures excited by a non-homogeneous turbulent boundary layer. This one is based on the synthesis of different realizations of the random pressure fluctuations that can be introduced as loading of a vibroacoustic model. The vibratory response is finally deduced by averaging together the responses of the different loads. As a first approach, the pressure fluctuations of the non-homogeneous turbulent boundary layer can be generated separately for different sub-areas of the structure by using the uncorrelated wall plane waves technique and mean boundary layer parameters. An extension of this basic approach consists in taking into account the interaction between the sub-areas and a refinement of the sub-area decomposition. Wall pressure fluctuations related to a continuous evolution of the boundary layer can then be generated and introduced in the vibroacoustic model. The accuracy of the proposed approach is studied on a rectangular panel excited on one side by a growing fully turbulent boundary layer triggered at one edge of the plate. Comparisons with the spatial approach and the wavenumber approach using the sub-area decomposition technique are proposed. Interests of the proposed approach in terms of accuracy and computing times are discussed. [ABSTRACT FROM AUTHOR]

Alienation is an extremely complex category, difficult to understand, especially when studied from certain works of Marx, such as the Economic--Philosophical Manuscripts of 1844, fragmented and incomplete. Although this notion was not created in the midst of Marxian theory, it is in this aspect that it acquires an understanding more aligned with social reality, with roots in the economic sphere. Using a literature review centered on the theme, this article aims to approach the term, a contribution to its understanding, whose determinants that frame it find their nexus of objectivity under the structural configurations of bourgeois society, dominated by capital. [ABSTRACT FROM AUTHOR]

Background: Indomethacin (IMC) as a prophylactic treatment is considered to be ineffective in cluster headache (CH). However, small series suggested the interest of IMC in CH. Some authors support that an IMC test is useful in all trigeminal autonomic cephalalgias. We described clinical features of IMC responders in a retrospective cohort of chronic cluster headache (CCH). Methods: This single-center and retrospective study was conducted in a tertiary care specialist headache center in France. Patients were selected between January 2007 and December 2008. We included all patients fulfilling CCH criteria (ICHD-3-beta). Data were collected from medical records. We recorded all the prescriptions of IMC as a prophylactic treatment. Responders were defined by 50% reduction in attack frequency; complete response was defined by disappearance of the attacks. The non-responders must have received at least 100 mg daily during 7 days. Results: The study consisted of 324 CCH, 121 female (37%) and 203 males (63%) with an average age at onset of 33.93 (± 14.71) years. Of the patients, 105 were treated with IMC. Thirty patients (29%) were responders. Thirty-four patients (32%) were non-responders. Responding status was undefined for 41 patients (39%). Twelve patients (11%) had a complete response. Responders were composed by 18 women (60%) and 12 men (40%) and had on average 44.89 (± 12.88) years. The minimal effective dose was 86.11 mg daily (± 48.72). Discussion: This study shows the interest of IMC in CCH patients. We recommend an IMC test as a third-line treatment in CCH. [ABSTRACT FROM AUTHOR]

The presence of endolymphatic hydrops has been studied in many neurological disorders. The pathophysiological mechanisms may involve CSF pressure variations, transmitted to the innear ear. This hydrops could play a role in vestibular or cochlear symptoms. For the ENT specialist, the etiological diagnosis of endolymphatic hydrops is a challenge, and neurological etiologies must be known. The treatment of these neurological causes could be effective on cochleo-vestibular symptoms. The knowledge of endolymphatic hydrops could also be a target for noninvasive tests, able to estimate CSF pressure variations. For the neurologist, this could represent a useful tool for the diagnosis and follow-up, in some of these neurological disorders, related to a CSF pressure imbalance. The purpose of this paper is to summarize literature data on endolymphatic hydrops in neurological disorders. We define some neurological conditions, for which there is a particular interest in noninvasive investigations of endolymphatic hydrops. [ABSTRACT FROM AUTHOR]

The cell cycle is modulated by ubiquitin ligases, including CRL4, which facilitate degradation of the chromatin-bound substrates involved in DNA replication and chromosome segregation. One of the members of the CRL4 complex, RepID (DCAF14/PHIP), recognizes kinetochore-localizing BUB3, known as the CRL4 substrate, and recruits CRL4 to the chromatin/chromosome using the WD40 domain. Here, we show that the RepID WD40 domain provides different platforms to CRL4 and BUB3. Deletion of the H-box or exon 8 located in the RepID WD40 domain compromises the interaction between RepID and CRL4, whereas BUB3 interacts with the exon 1–2 region. Moreover, deletion mutants of other exons in the WD40 domain lost chromatin binding affinity. Structure prediction revealed that the RepID WD40 domain has two beta-propeller folds, linked by loops, which are possibly crucial for chromatin binding. These findings provide mechanistic insights into the space occupancy of the RepID WD40 domain to form a complex with CRL4, BUB3, or chromatin. • RepID WD40 domain is crucial for binding to chromatin and proteins. • WD40 domain of RepID forms a two-β propeller configuration connected by a loop. • RepID WD40 domain provides different platforms for proteins and chromatin. [ABSTRACT FROM AUTHOR]

Resulting from a university extension action, the article presents elements and characteristics of Xapuri, State of Acre, Brazil, birthplace of the rubber tapper leader, Francisco Alves Mendes Filho, best known as Chico Mendes, from a historical and cultural trail conducted during the Vale do Acre Operation, part of the Rondon Project, coordinated by the Ministry of Defense. The town comprises a series of historic-cultural, identity and social particularities, which, at first, may go unnoticed by its visitors or even by natives. Considering the potential of Xapuri regarding tourism, the trail can be an attractive proposal for the sector and a tool for heritage education, as it is a hiking path that allows participants to identify and interpret the landscapes and the material and immaterial elements of the visited route, which contribute to its visibility, preservation and memory. [ABSTRACT FROM AUTHOR]

Deciphering how DCAFs (DDB1‐CUL4 Associated Factors) modulate a broad spectrum of cellular processes, including cell cycle progression and maintenance of genomic integrity is critical to better understand cellular homeostasis and diseases. Cells contain more than 100 DCAFs that associate with the Cullin‐Ring Ubiquitin Ligase 4 (CRL4) complex that target specific protein substrates for degradation. DCAFs are thought to act as substrate receptors that dictate the specificity of the ubiquitination machinery ("catalytic DCAFs"). However, recent studies have suggested that some DCAFs might play a different role by targeting CRL4 complexes to distinct cellular compartments ("structural DCAFs"). Once localized to their correct cellular domains, these CRLs dissociate from the structural DCAFs prior to their association with other, substrate‐specific catalytic DCAFs. Thus, we propose that DCAF switches can provide a mechanistic basis for the degradation of proteins that regulate cell growth and proliferation at precise points in space and time. [ABSTRACT FROM AUTHOR]

Susceptibility to breast cancer is significantly increased in individuals with germ line mutations in RECQ1 (also known as RECQL or RECQL1), a gene encoding a DNA helicase essential for genome maintenance. We previously reported that RECQ1 expression predicts clinical outcomes for sporadic breast cancer patients stratified by estrogen receptor (ER) status. Here, we utilized an unbiased integrative genomics approach to delineate a cross talk between RECQ1 and ERa, a known master regulatory transcription factor in breast cancer. We found that expression of ESR1, the gene encoding ERa, is directly activated by RECQ1. More than 35% of RECQ1 binding sites were cobound by ERa genome-wide. Mechanistically, RECQ1 cooperates with FOXA1, the pioneer transcription factor for ERa, to enhance chromatin accessibility at the ESR1 regulatory regions in a helicase activity-dependent manner. In clinical ERapositive breast cancers treated with endocrine therapy, high RECQ1 and high FOXA1 coexpressing tumors were associated with better survival. Collectively, these results identify RECQ1 as a novel cofactor for ERa and uncover a previously unknown mechanism by which RECQ1 regulates disease-driving gene expression in ER-positive breast cancer cells. [ABSTRACT FROM AUTHOR]

Electrochemically based technologies are rapidly moving from the laboratory to bedside applications and wearable devices, like in the field of cardiovascular disease. Major efforts have focused on the biosensor component in contrast with those employed in creating more suitable detection algorithms for long-term real-world monitoring solutions. The calibration curve procedure presents major limitations in this context. The objective is to propose a new algorithm, compliant with current clinical guidelines, which can overcome these limitations and contribute to the development of trustworthy wearable or telemonitoring solutions for home-based care. A total of 123 samples of phosphate buffer solution were spiked with different concentrations of troponin, the gold standard method for the diagnosis of the acute coronary syndrome. These were classified as normal or abnormal according to established clinical cut-off values. Off-the-shelf screen-printed electrochemical sensors and cyclic voltammetry measurements (sweep between -1 and 1 V in a 5 mV step) was performed to characterize the changes on the surface of the biosensor and to measure the concentration of troponin in each sample. A logistic regression model was developed to accurately classify these samples as normal or abnormal. The model presents high predictive performance according to specificity (94%), sensitivity (92%), precision (92%), recall (92%), negative predictive value (94%) and F-score (92%). The area under the curve of the precision-recall curve is 97% and the positive and negative likelihood ratios are 16.38 and 0.082, respectively. Moreover, high discriminative power is observed from the discriminate odd ratio (201) and the Youden index (0.866) values. The promising performance of the proposed algorithm suggests its capability to overcome the limitations of the calibration curve procedure and therefore its suitability for the development of trustworthy home-based care solutions. [ABSTRACT FROM AUTHOR]

the poverty is an inescapable condition in a society ruled by capital, being the weakest link in the relationship with wealth, its dialectical pair. In addition to its production, centered on the structure of society (in a Marxian approach), and its representation in the objective living conditions of the majority of the world population, poverty is the target of political efforts to alleviate it, as well as theorizations bourgeois about their origin and validity, all detached from social reality. This article aims to analyze the World Bank's conception of poverty over the decades, considering its centralizing and radiating role of measures to confront it in developing countries, highlighting its strong political presence in these locations. We made use of a literature review on the relevant topic and also of documentary research, having as main source the World Bank Reports, the study evidenced the neoliberal influence in the referred institution and, therefore, its importance and functionality on the topic for the bourgeois order. [ABSTRACT FROM AUTHOR]

The Town Energy Balance (TEB) urban climate model has recently been improved to more realistically address the radiative effects of trees within the urban canopy. These processes necessarily have an impact on the energy balance that needs to be taken into account. This is why a new method for calculating the turbulent fluxes for sensible and latent heat has been implemented. This method remains consistent with the "bigleaf" approach of the Interaction Soil–Biosphere–Atmosphere (ISBA) model, which deals with energy exchanges between vegetation and atmosphere within TEB. Nonetheless, the turbulent fluxes can now be dissociated between ground-based natural covers and the tree stratum above (knowing the vertical leaf density profile), which can modify the vertical profile in air temperature and humidity in the urban canopy. In addition, the aeraulic effect of trees is added, parameterized as a drag term and an energy dissipation term in the evolution equations of momentum and turbulent kinetic energy, respectively. This set of modifications relating to the explicit representation of the tree stratum in TEB is evaluated on an experimental case study. The model results are compared to micrometeorological and surface temperature measurements collected in a semi-open courtyard with trees and bordered by buildings. The new parameterizations improve the modeling of surface temperatures of walls and pavements, thanks to taking into account radiation absorption by trees, and of air temperature. The effect of wind speed being strongly slowed down by trees is also much more realistic. The universal thermal climate index diagnosed in TEB from inside-canyon environmental variables is highly dependent and sensitive to these variations in wind speed and radiation. This demonstrates the importance of properly modeling interactions between buildings and trees in urban environments, especially for climate-sensitive design issues. [ABSTRACT FROM AUTHOR]

This speculative opinion is based on an apparent dream caused by Donald Trump's decision to withdraw the U.S. from the Paris Agreement. The account includes a comparison between arguments against the abolition of slavery and those against ending a fossil-fuel based economy in favor of sustainability through a green approach. Recent social disturbance in France shows that a carbon tax has not been persuasively advocated. But it should be clear that unchanged laissez-faire economics will produce disaster in light of the facts about global heating and climate change. This account is based on historical and contemporary quotations from American political figures from both the XIX and XXI centuries. The parallels raise fundamental issues of human rights. [ABSTRACT FROM AUTHOR]

The first ipso -selenocyanation of arylboronic acids is achieved using selenium dioxide and malononitrile under mild conditions. The reaction is successful even without metal or base in DMSO. The major advantages of this new method are an easy set-up, excellent yields, and the use of odorless and inexpensive selenium reagents. Basic conditions subsequently afford new access to diaryldiselenides in good yields without isolating the organoselenocyanate intermediates. [ABSTRACT FROM AUTHOR]

First‐principle calculations are still a challenge since they require a great amount of computational time. In this article, we introduce a new algorithm to perform orbital‐free density functional theory (OF‐DFT) calculations. Our new algorithm focuses computational efforts on important parts of the particle system, which, in the context of adaptively restrained particle simulations (ARPS) allows us to accelerate particle simulations. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of spontaneous or post‐traumatic intracranial hypotension mainly rely on clinical features and neuroimaging. In atypical presentations, other non‐invasive tests are missing to support the diagnosis of intracranial hypotension. The assessment of otoacoustic emissions (OAE) shown interest to monitor intracranial pressure mainly in cases of intracranial hypertension. This non‐invasive method was also assessed in response to pressure change after lumbar puncture. A few reports showed abnormal results of distortion product otoacoustic emissions (DPOAE) in cases of spontaneous or post‐traumatic intracranial hypotension. We describe additional results in a series of intracranial hypotension cases. We discuss the interest of DPOAE assessment in atypical presentations of intracranial hypotension. We review the other non‐invasive tests reported in literature. Methods: We studied 4 atypical or recurrent cases of spontaneous or post‐traumatic intracranial hypotension by recording OAE in sitting then supine position. Results: Unilateral or bilateral abnormal changes of DPOAE were recorded in all cases, in response to postural test. These changes were present even in the absence of vestibular symptoms. Conclusion: The study of OAE may be a non‐invasive tool for the diagnosis of spontaneous intracranial hypotension. [ABSTRACT FROM AUTHOR]

The TEB urban climate model has recently been improved to more realistically address the radiative effects of trees within the urban canopy. These processes necessarily have an impact on the energy balance that needs to be taken into account. This is why a new method for calculating the turbulent fluxes for sensible and latent heat has been implemented. This method remains consistent with the "bigleaf" approach of the ISBA model which deals with energy exchanges between vegetation and atmosphere within TEB. Nonetheless, the turbulent fluxes can now be dissociated between ground-based natural covers and tree stratum above (knowing the vertical leaf density profile), which can modify the vertical profile in air temperature and humidity in the urban canopy. In addition, the aeraulic effect of trees is added, parameterized as a drag term and an energy dissipation term in the evolution equations of momentum and of turbulent kinetic energy, respectively. This set of modifications relating to the explicit representation of tree stratum in TEB is evaluated on an experimental case study. The model results are compared to micrometeorological and surface temperature measurements collected in a semi-open courtyard with trees and bordered by buildings. The new parameterizations improve the modelling of surface temperatures of walls and pavements thanks to taking into account radiation absorption by trees, and of air temperature. The wind speed is strongly slowed down by trees that is also much more realistic. The universal thermal climate index diagnosed in TEB from inside-canyon environmental variables is highly dependent and sensitive to these variations in wind speed and radiation. This demonstrates the importance of properly modelling interactions between buildings and trees in urban environments, especially for climate-sensitive design issues. [ABSTRACT FROM AUTHOR]

Population stratification is a well-known confounding factor in both common and rare variant association analyses. Rare variants tend to be more geographically clustered than common variants, because of their more recent origin. However, it is not yet clear if population stratification at a very fine scale (neighboring administrative regions within a country) would lead to statistical bias in rare variant analyses. As the inclusion of convenience controls from external studies is indeed a common procedure, in order to increase the power to detect genetic associations, this problem is important. We studied through simulation the impact of a fine scale population structure on different rare variant association strategies, assessing type I error and power. We showed that principal component analysis (PCA) based methods of adjustment for population stratification adequately corrected type I error inflation at the largest geographical scales, but not at finest scales. We also showed in our simulations that adding controls obviously increased power, but at a considerably lower level when controls were drawn from another population. [ABSTRACT FROM AUTHOR]

Series of solid-state emitters based on the D-π-A dipolar structure and featuring various electron-donor and electron-acceptor groups were designed, and their spectroscopic properties studied. From weak emission in dilute solutions, intense emissions in aggregated state (AIE) and in the crystalline state were obtained. Analysis in light of crystal structures obtained by X-ray diffraction revealed specific crystal packing and presence of long chain of emitting aggregates. This simple molecular engineering around the D-π-A dipolar structure provides easy access to a wide range of effective solid-state emitters allowing modulation of emission wavelengths up to the near infrared ( λ em reaching 735 and 768 nm for compound 2f and 3f bearing the strongest electron-withdrawing group). [ABSTRACT FROM AUTHOR]

The computation of long‐range potentials is one of the demanding tasks in Molecular Dynamics. During the last decades, an inventive panoply of methods was developed to reduce the CPU time of this task. In this work, we propose a fast method dedicated to the computation of the electrostatic potential in adaptively restrained systems. We exploit the fact that, in such systems, only some particles are allowed to move at each timestep. We developed an incremental algorithm derived from a multigrid‐based alternative to traditional Fourier‐based methods. Our algorithm was implemented inside LAMMPS, a popular molecular dynamics simulation package. We evaluated the method on different systems. We showed that the new algorithm's computational complexity scales with the number of active particles in the simulated system, and is able to outperform the well‐established Particle Particle Particle Mesh (P3M) for adaptively restrained simulations. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Low socio-economic status, high exposure to health risk and poor access to basic treatment are the main determinants of high child mortality in sub-Saharan African rural regions. 50 to 80% of child deaths are caused by a triptych of infectious diseases. Early 2000's Inter Aide made the postulate that it was possible to act on under-five mortality through a strategy combining raising under five mothers awareness on major diseases, spreading of prevention means and local access to basic care. An operational model was thus defined, contributing in a few years to a frank, rapid and lasting reduction of under five mortality in all areas where the methodology could be applied. The importance of community-based care in relation to an institutional health system unable to provide early management of diarrhoea and malaria cases is fundamental. [ABSTRACT FROM AUTHOR]

Presents information pertaining to the physical aspects associated with the mechanism of exchange anisotropy and thermal stability within the ultrathin TbCo layers. Development of a modified spin-valve structure; How unshielded sensors were implemented; Information on the results.

Adaptively restrained molecular dynamics (ARMD) allows users to perform more integration steps in wall‐clock time by switching on and off positional degrees of freedoms. This article presents new, single‐pass incremental force updates algorithms to efficiently simulate a system using ARMD. We assessed different algorithms for speedup measurements and implemented them in the LAMMPS MD package. We validated the single‐pass incremental force update algorithm on four different benchmarks using diverse pair potentials. The proposed algorithm allows us to perform simulation of a system faster than traditional MD in both NVE and NVT ensembles. Moreover, ARMD using the new single‐pass algorithm speeds up the convergence of observables in wall‐clock time. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Textile batteries are of utmost interest for the emerging field of electronic textiles. Several research groups work on this topic, developing either fiber-based batteries or planar alternatives, e.g. by coating textile fabrics with metallic electrodes and an electrolyte between them. Since usual non-toxic electrolytes are fluid, using them in a textile battery necessitates gelling them or embedding them in a sponge-like matrix to avoid diffusion through the textile electrodes. Here we report on measurements of textile batteries, prepared from different conductive woven fabrics with a nanofiber mat as an interlayer filled with iodine-triiodide solution. Firstly, the highest voltages were achieved combining metal electrodes with a carbon electrode, showing that the electrolyte in this system is part of the redox system. Second, the metal electrodes were destroyed after short times, suggesting that iodine-triiodide is not an ideal choice for an electrolyte, although this material is often used. Finally, we show that even without setting up the complete battery, the electrolyte slowly destroys the metal layers, while it is itself degraded by photo-oxidation, underlining the necessity to find non-toxic, environmentally-friendly alternatives for iodine-triiodide to enable long-term storage. Assuming non-solid state for electrolytes, the level of their confinement by different types of corrugated materials was tested. [ABSTRACT FROM AUTHOR]

The efficacy and safety of olmesartan medoxomil (OM) vs active control (AC) monotherapy among elderly patients aged 60-79 years (N = 4487) was evaluated by meta-analysis (25 studies). In all patients, change from baseline to end point in blood pressure (BP) was significantly greater with OM vs AC (-19.5/-11.9 vs -16.8/-10.7 mm Hg). Greater proportions of OM- vs AC-treated patients achieved BP goals. In patients with impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2 ), OM treatment resulted in a greater mean change from baseline in systolic BP vs AC (-21.2 vs -18.7 mm Hg, respectively) and a greater proportion of patients achieving BP goals. These parameters were similar in both groups for elderly patients with diabetes. OM was well tolerated with few adverse events. OM monotherapy can be used as an initial treatment for hypertension in elderly patients, including those with renal impairment or diabetes. [ABSTRACT FROM AUTHOR]

Objective: To report a case series of sneezing systematically occurring in two cases with migraine and cranial autonomic symptoms and two with cluster headache. Background: Sneezing occurring systematically during cluster headache or migraine is a rare condition. Sneezing has been described as a specific trigger for migraine. Methods: Case reports. Case series: We describe four patients with primary headaches, presenting systematic sneezing at a definite time of premonitory, postdromal, or headache phase. All of these headaches were associated with cranial autonomic symptoms. Conclusion: Sneezing is a symptom associated with primary headaches. The definite place of sneezing in these patients suggests a particular implication of hypothalamus in the pathophysiology of these cases. [ABSTRACT FROM AUTHOR]

Background and aims Angiopoietin-like 3 (ANGPTL3) has emerged as a key regulator of lipoprotein metabolism in humans. Homozygous loss of ANGPTL3 function causes familial combined hypolipidemia characterized by low plasma levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). While known effects of ANGPTL3 in inhibiting lipoprotein lipase and endothelial lipase contribute to the low TG and HDL-C, respectively, the basis of low LDL-C remains unclear. Our aim was to explore the role of ANGPTL3 in modulating plasma LDL-C. Methods We performed RNAi-mediated gene silencing of ANGPTL3 in five mouse models and in human hepatoma cells. We validated results by deleting ANGPTL3 gene using the CRISPR/Cas9 genome editing system. Results RNAi-mediated Angptl3 silencing in mouse livers resulted in very low TG, HDL-C and LDL-C, a pattern similar to the human phenotype. The effect was observed in wild-type and obese mice, while in hCETP/apolipoprotein (Apo) B-100 double transgenic mice, the silencing decreased LDL-C and TG, but not HDL-C. In a humanized mouse model ( Apobec1 −/− carrying human ApoB-100 transgene) deficient in the LDL receptor (LDLR), Angptl3 silencing had minimum effect on LDL-C, suggesting the effect being linked to LDLR. This observation is supported by an additive effect on LDL-C between ANGPTL3 and PCSK9 siRNAs. ANGPTL3 gene deletion induced cellular long-chain TG and ApoB-100 accumulation with elevated LDLR and LDLR-related protein (LRP) 1 expression. Consistent with this, ANGPTL3 deficiency by gene deletion or silencing reduced nascent ApoB-100 secretion and increased LDL/VLDL uptake. Conclusions Reduced secretion and increased uptake of ApoB-containing lipoproteins may contribute to the low LDL-C observed in mice and humans with genetic ANGPTL3 deficiency. [ABSTRACT FROM AUTHOR]

Current induced resistance changes were investigated in magnetic tunnel junctions with ultrathin Al-Ox barriers. The nonuniformity of the insulator induced a strong coupling between the two magnetic electrodes and no magnetoresistance. However, the current-voltage (I–V) characteristics at low bias voltages were consistent with a tunnellike behavior. At larger bias voltages, they showed an abrupt change of slope that was reversible for an opposite voltage polarity. The resistance versus current (R–I) curves exhibited reversible resistance changes that reached over 100%. We interpret this as controlled electromigration in local nanoconstrictions of the barrier. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Experiments on the longitudinal biasing of microsized magnetic tunnel junctions have been conducted using permanent magnets partially overlapping the junction area. The tunneling magnetoresistance ratio showed a strong dependency on the overlap length, since even a 10% overlap of the sensor length resulted in a 25% drop from its initial value without overlap. Analytical and micromagnetic analyses have demonstrated that this decrease comes from extra current channels, located in the regions below the permanent magnets, that shorted a large amount of the sense current from the central active region in the antiparallel magnetization state. The high uniaxial anisotropy field, induced by the permanent magnets in the overlapped regions, created particular magnetic configurations responsible for these low resistance paths. Several alternatives, using antiferromagnetic material in place of the permanent magnets or a modified design of the magnetic tunnel junction structure, are presented and discussed to prevent this extra current channel effect. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: analyses from the FIGARO-DKD trial. Keywords: Finerenone; Type 2 diabetes; Chronic kidney disease; Heart failure; FIGARO-DKD EN Finerenone Type 2 diabetes Chronic kidney disease Heart failure FIGARO-DKD e36 e37 2 05/20/22 20220401 NES 220401 Diabetes is the main cause of chronic kidney disease (CKD) and a risk factor for their progression to end-stage renal disease. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. [Extracted from the article]

Objective To see how patients' clinical descriptions compare to the third classification of International Classification of Headache Disorders (ICHD-III beta). Background CVS is an episodic syndrome associated with migraine. It is a rare disorder of childhood and adulthood. New criteria are proposed in the third classification of International Classification of Headache Disorders. Methods This study describes children and adults' CVS characteristics at a French tertiary-care center, according to the ICHD-II and ICHD-III beta criteria. Clinical features, and results of paraclinical tests were characterized. Results Fifteen patients were included: 8 adults, 2 children, and 5 adolescents. Familial history of migraine or CVS was respectively noticed in 12 and 4 patients. The duration of premonitory, emetic, and postdromal phases was evaluated from hours to days. Some symptoms described in theses phases are also described in migrainous population, with a comparable frequency. Cranial or systemic autonomic symptoms were respectively reported in 47% and 93%. Nine patients described a circadian periodicity, and six patients described a circannual periodicity. The predictable periodicity was from 1 week to 12 months. A brain perfusion SPECT showed an increased hypothalamic perfusion during emetic phase in one patient. Conclusions CVS is a rare episodic syndrome associated with migraine. Some clinical features and paraclincal tests suggest a chronobiological disease. [ABSTRACT FROM AUTHOR]

We consider Adaptively Restrained Langevin dynamics, in which the kinetic energy function vanishes for small velocities. Properly parameterized, this dynamics makes it possible to reduce the computational complexity of updating inter-particle forces, and to accelerate the computation of ergodic averages of molecular simulations. In this paper, we analyze the influence of the method parameters on the total achievable speed-up. In particular, we estimate both the algorithmic speed-up, resulting from incremental force updates, and the influence of the change of the dynamics on the asymptotic variance. This allows us to propose a practical strategy for the parameterization of the method. We validate these theoretical results by representative numerical experiments. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that affects multiple organs. Currently, therapeutic molecules present adverse side effects and are only effective in some SLE patient subgroups. Extracellular vesicles (EV), including exosomes, microvesicles and apoptotic bodies, are released by most cell types, carry nucleic acids, proteins and lipids and play a crucial role in cell-to-cell communication. EVs can stimulate or suppress the immune responses depending on the context. In SLE, EVs can work as autoadjuvants, enhance immune complex formation and maintaining inflammation state. Over the last years, EVs derived from mesenchymal stem cells and antigen presenting cells have emerged as cell-free therapeutic agents to treat autoimmune and inflammatory diseases. In this review, we summarize the current therapeutic applications of extracellular vesicles to regulate immune responses and to ameliorate disease activity in SLE and other autoimmune disorders. [ABSTRACT FROM AUTHOR]

The ends of eukaryotic chromosomes, known as telomeres, consist of repetitive DNA sequences, multiple proteins and noncoding RNAs. Telomeres are dynamic structures that play crucial roles as guardians of genome stability and tumor suppressors. Defects in telomere length or protein composition can accelerate aging and are seen in telomere syndromes, which affect various proliferative tissues such as the bone marrow or the lungs. One of the biggest challenges in the telomere field is to identify the molecular changes at telomeres that occur during normal development, in cancer and in telomere syndromes. To tackle this problem, our laboratory has established a quantitative telomeric chromatin isolation protocol (QTIP) for human cells, in which chromatin is cross-linked, immunopurified and analyzed by mass spectrometry. QTIP involves stable isotope labeling by amino acids in cell culture (SILAC) to compare and identify quantitative differences in telomere protein composition of cells from various states. [ABSTRACT FROM AUTHOR]

The Town Energy Balance (TEB) model has been refined and improved in order to explicitly represent street trees and their impacts on radiative transfer: a new vegetated stratum on the vertical plane, which can shade the road, the walls, and the low vegetation has been added. This modification led to more complex radiative calculations, but has been done with a concern to preserve a certain level of simplicity and to limit the number of new input parameters for TEB to the cover fraction of trees, the mean height of trunks and trees, their specific leaf area index, and albedo. Indeed, the model is designed to be run over whole cities, for which it can simulate the local climatic variability related to urban landscape heterogeneity at the neighborhood scale. This means that computing times must be acceptable, and that input urban data must be available or easy to define. This simplified characterization of high vegetation necessarily induces some uncertainties in terms of the solar radiative exchanges, as quantified by comparison of TEB with a high-spatial-resolution solar enlightenment model (SOLENE). On the basis of an idealized geometry of an urban canyon with various vegetation layouts, TEB is evaluated regarding the total shortwave radiation flux absorbed by the elements that compose the canyon. TEB simulations in summer gathered best scores for all configurations and surfaces considered, which is precisely the most relevant season to assess the cooling effect of deciduous trees under temperate climate. Mean absolute differences and biases of 6.03 and +3.50 W m−2 for road, respectively, and of 3.38 and +2.80 W m−2 for walls have been recorded in vegetationless canyons. In view of the important incident radiation flux, exceeding 1000 W m−2 at solar noon, the mean absolute percentage differences of 3 % for both surfaces remain moderate. Concerning the vegetated canyons, we noted a high variability of statistical scores depending on the vegetation layout. The greater uncertainties are found for the solar radiation fluxes received and absorbed by the high vegetation. The mean absolute differences averaged over the vegetation configurations during summertime are 21.12 ± 13.39 W m−2 or 20.92 ± 10.87 % of mean absolute percentage differences for the total shortwave absorption, but these scores are associated with acceptable biases: −15.96 ± 15.93 W m−2. [ABSTRACT FROM AUTHOR]

We consider Langevin dynamics associated with a modified kinetic energy vanishing for small momenta. This allows us to freeze slow particles, and hence avoid the re-computation of inter-particle forces, which leads to computational gains. On the other hand, the statistical error may increase since there are a priori more correlations in time. The aim of this work is first to prove the ergodicity of the modified Langevin dynamics (which fails to be hypoelliptic), and next to analyze how the asymptotic variance on ergodic averages depends on the parameters of the modified kinetic energy. Numerical results illustrate the approach, both for low-dimensional systems where we resort to a Galerkin approximation of the generator, and for more realistic systems using Monte Carlo simulations. [ABSTRACT FROM AUTHOR]

The TEB model has been refined and improved in order to explicitly represent street trees and their impacts on radiative transfers: a new vegetated stratum on the vertical plane, which can superimpose to road and low vegetation has been added. This modification has obviously complexified the radiative calculations, but has been done with a concern to preserve a certain level of simplicity and to limit the number of new input parameters for TEB to the cover fraction of trees, the mean height of trunks and trees, their specific Leaf Area Index and albedo. Indeed, the model is designed to be run over whole cities, for which it can simulate the local climatic variability related to urban landscape heterogeneity at the neighborhood scale. This means that computing times must be acceptable, and that input urban data must be available or quite easy to define. This simplified characterization of high vegetation necessarily induces some uncertainties on solar radiative exchanges, that were quantified through the comparison of TEB with a high spatial-resolution solar enlightenment model (SOLENE). On the basis of an idealized geometry of urban canyon with various vegetation layouts, TEB is evaluated regarding the direct and diffuse solar radiation received by the elements that compose the canyon, as well as the total shortwave radiation absorbed (after multiple reflections) by these elements. The cases of vegetationless canyons lead to root mean square errors less than 15?W?m-2 and biases less than 5?W?m-2. For the cases with high vegetation, the statistical scores are degraded (with a trend of underestimation of solar absorption by trees) but remain acceptable. It is interesting to emphasize that the summertime TEB simulations gave the best scores (∣bias∣ < 20?W?m-2) for all configurations and surfaces considered, which is precisely the most relevant season to assess the cooling effect of deciduous trees under temperate climate. [ABSTRACT FROM AUTHOR]