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Magnetic topological insulators are narrow-gap semiconductor materials that combine non-trivial band topology and magnetic order1. Unlike their nonmagnetic counterparts, magnetic topological insulators may have some of the surfaces gapped, which enables a number of exotic phenomena that have potential applications in spintronics1, such as the quantum anomalous Hall effect2 and chiral Majorana fermions3. So far, magnetic topological insulators have only been created by means of doping nonmagnetic topological insulators with 3d transition-metal elements; however, such an approach leads to strongly inhomogeneous magnetic4 and electronic5 properties of these materials, restricting the observation of important effects to very low temperatures2,3. An intrinsic magnetic topological insulator-a stoichiometric well ordered magnetic compound-could be an ideal solution to these problems, but no such material has been observed so far. Here we predict by ab initio calculations and further confirm using various experimental techniques the realization of an antiferromagnetic topological insulator in the layered van der Waals compound MnBi2Te4. The antiferromagnetic ordering that MnBi2Te4 shows makes it invariant with respect to the combination of the time-reversal and primitive-lattice translation symmetries, giving rise to a â¤2 topological classification; â¤2 = 1 for MnBi2Te4, confirming its topologically nontrivial nature. Our experiments indicate that the symmetry-breaking (0001) surface of MnBi2Te4 exhibits a large bandgap in the topological surface state. We expect this property to eventually enable the observation of a number of fundamental phenomena, among them quantized magnetoelectric coupling6-8 and axion electrodynamics9,10. Other exotic phenomena could become accessible at much higher temperatures than those reached so far, such as the quantum anomalous Hall effect2 and chiral Majorana fermions3.
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CONTEXT: With two northern white rhinos (NWR) remaining, the continued existence of this species relies on studying their relative, the southern white rhino (SWR). AIMS: (1) Characterise gene expression in granulosa cells (GC) from SWR cumulus oocyte complexes (COCs) prior to (Pre-) and after (Post-) in vitro maturation (IVM), comparing culture media and oocytes from donors treated with or without gonadotropin stimulation prior to ovum recovery; and (2) evaluate COC glucose consumption in spent media. METHODS: COCs were retrieved from four SWRs. Granulosa cells were collected before and after IVM in SDZ or IZW medium. Total RNA was evaluated by qPCR. KEY RESULTS: Oocyte maturation was greater in SDZ than IZW media. Expression of genes associated with follicle development increased in Pre-IVM GC. Six genes were differentially expressed in Post-IVM GC from stimulated compared to unstimulated donors. COCs from stimulated animals consumed more glucose. Fifty seven percent of oocytes in SDZ medium consumed all available glucose. CONCLUSIONS: Gene expression changed upon in vitro maturation and gonadotropin stimulation. Higher glucose availability might be needed during IVM. IMPLICATIONS: This is the first study examining GC gene expression and COC metabolic requirements in rhinoceros, which are critical aspects to optimise IVM of rhinoceros oocytes.
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Células del Cúmulo , Técnicas de Maduración In Vitro de los Oocitos , Animales , Células del Cúmulo/metabolismo , Femenino , Expresión Génica , Glucosa/metabolismo , Gonadotropinas , Células de la Granulosa/metabolismo , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/metabolismo , Perisodáctilos/genéticaRESUMEN
OBJECTIVE: To describe the immediate impact of the COVID-19 pandemic on cervical screening, colposcopy and treatment volumes in Ontario, Canada. DESIGN: Population-based retrospective observational study. SETTING: Ontario, Canada. POPULATION: People with a cervix age of 21-69 years who completed at least one cervical screening cytology test, colposcopy or treatment procedure for cervical dysplasia between January 2019 and August 2020. METHODS: Administrative databases were used to compare cervical screening cytology, colposcopy and treatment procedure volumes before (historical comparator) and during the first 6 months of the COVID-19 pandemic (March-August 2020). MAIN OUTCOME MEASURES: Changes in cervical screening cytology, colposcopy and treatment volumes; individuals with high-grade cytology awaiting colposcopy. RESULTS: During the first 6 months of the COVID-19 pandemic, the monthly average number of cervical screening cytology tests, colposcopies and treatments decreased by 63.8% (range: -92.3 to -41.0%), 39.7% (range: -75.1 to -14.3%) and 31.1% (range: -43.5 to -23.6%), respectively, when compared with the corresponding months in 2019. Between March and August 2020, on average 292 (-51.0%) fewer high-grade cytological abnormalities were detected through screening each month. As of August 2020, 1159 (29.2%) individuals with high-grade screening cytology were awaiting follow-up colposcopy. CONCLUSIONS: The COVID-19 pandemic has had a substantial impact on key cervical screening and follow-up services in Ontario. As the pandemic continues, ongoing monitoring of service utilisation to inform system response and recovery is required. Future efforts to understand the impact of COVID-19-related disruptions on cervical cancer outcomes will be needed. TWEETABLE ABSTRACT: COVID-19 has had a substantial impact on cervical screening and follow-up services in Ontario, Canada.
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COVID-19/prevención & control , Colposcopía/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapia , Frotis Vaginal/estadística & datos numéricos , Adulto , Anciano , Bases de Datos Factuales , Atención a la Salud/estadística & datos numéricos , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Ontario , SARS-CoV-2 , Adulto JovenRESUMEN
Consumption of seafood contaminated with ciguatoxins (CTXs) leads to a foodborne disease known as ciguatera. Primary producers of CTXs are epibenthic dinoflagellates of the genera Gambierdiscus and Fukuyoa. In this study, thirteen Gambierdiscus and Fukuyoa strains were cultured, harvested at exponential phase, and CTXs were extracted with an implemented rapid protocol. Microalgal extracts were obtained from pellets with a low cell abundance (20,000 cell/mL) and were then analyzed with magnetic bead (MB)-based immunosensing tools (colorimetric immunoassay and electrochemical immunosensor). It is the first time that these approaches are used to screen Gambierdiscus and Fukuyoa strains, providing not only a global indication of the presence of CTXs, but also the ability to discriminate between two series of congeners (CTX1B and CTX3C). Analysis of the microalgal extracts revealed the presence of CTXs in 11 out of 13 strains and provided new information about Gambierdiscus and Fukuyoa toxin profiles. The use of immunosensing tools in the analysis of microalgal extracts facilitates the elucidation of further knowledge regarding these dinoflagellate genera and can contribute to improved ciguatera risk assessment and management.
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Ciguatoxinas/aislamiento & purificación , Colorimetría/métodos , Dinoflagelados/química , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Ciguatoxinas/clasificación , Especificidad de la EspecieRESUMEN
Using density functional theory and Monte Carlo calculations, we study the thickness dependence of the magnetic and electronic properties of a van der Waals interlayer antiferromagnet in the two-dimensional limit. Considering MnBi_{2}Te_{4} as a model material, we find it to demonstrate a remarkable set of thickness-dependent magnetic and topological transitions. While a single septuple layer block of MnBi_{2}Te_{4} is a topologically trivial ferromagnet, the thicker films made of an odd (even) number of blocks are uncompensated (compensated) interlayer antiferromagnets, which show wide band gap quantum anomalous Hall (zero plateau quantum anomalous Hall) states. Thus, MnBi_{2}Te_{4} is the first stoichiometric material predicted to realize the zero plateau quantum anomalous Hall state intrinsically. This state has been theoretically shown to host the exotic axion insulator phase.
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INTRODUCTION: Insomnia is considered to be a serious public health issue affecting approximately 10% of adults. Chronic insomnia may increase the risk of health problem, psychological vulnerability and proneness to accidents. Cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first line of treatment. Even though CBT-I is widely considered as an effective therapy, 20 to 30% of patients do not respond to this treatment. Mindfulness therapy, known to reduce rumination and stress, could be an interesting complement to enhance CBT-I. The aim of this study is to evaluate the efficacy of therapy combining mindfulness meditation and CBT-I for the treatment of chronic insomnia. METHODS: Thirty-three patients, diagnosed with chronic insomnia, aged 18 to 75 years (51±15 years) were recruited between October 2015 and June 2016 at the Sleep Center of Marseille. The patients were then divided into two groups according to their psychotherapy method: group CBT-I alone (17 patients) or a group therapy combining CBT-I and Mindfulness (16 patients). All participants were given five sessions of standard CBT during eight weeks. The patient-reported outcome measures were sleep onset latency, wake after sleep onset (WASO), total wake time, total sleep time, time in bed, sleep efficiency and number of awakening from sleep diaries before treatment (T0) and six weeks later (T1). Assessments were done using Pittsburgh Sleep quality index (PSQI), Insomnia severity Index (ISI), the Epworth sleepiness scale, the hospital anxiety and depression scale (HAD), the dysfunctional beliefs and attitude about sleep (DBAS-16); further, the use of sleeping pills was also recorded at T0 and T1. RESULTS: Out of the 33 participants who began the treatment, 29 completed all sessions and were included in the analyses (4 dropouts in the group CBT-I alone). The data shows that each treatment yielded significant improvements over time in sleep variables from the diary, PSQI, ISI, anxiety (P=0.004), DBAS 16, sleeping pill use and vitality measured by SF36 health survey (P=0.004). Comparing the results of the two therapy groups, the meditation associated to CBT-I shows significantly greater rates of reduction in WASO relative to CBT-I group (P=0.009). CONCLUSIONS: This study confirms the beneficial effects of CBT for patients suffering from insomnia on sleep parameters, anxiety symptoms and quality of life. Furthermore, this study suggests, for the first time, that combining CBT and mindfulness is a superior approach compared to that of only conventional CBT-I in improving sleep.
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Terapia Cognitivo-Conductual/métodos , Meditación/métodos , Atención Plena/métodos , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Adolescente , Adulto , Anciano , Ansiedad/etiología , Ansiedad/terapia , Enfermedad Crónica , Femenino , Humanos , Hipnóticos y Sedantes/uso terapéutico , Masculino , Persona de Mediana Edad , Calidad de Vida , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Resultado del Tratamiento , Adulto JovenRESUMEN
Ferrierite zeolites with nanosized crystals and external surface areas higher than 250â m2 g-1 have been prepared at relatively low synthesis temperature (120 °C) by means of the collaborative effect of two organic structure directing agents (OSDA). In this way, hierarchical porosity is achieved without the use of post-synthesis treatments that usually involve leaching of Tâ atoms and solid loss. Adjusting the synthesis conditions it is possible to decrease the crystallite size in the directions of the 8- and 10-ring channels, [010] and [001] respectively, reducing their average pore length to 10-30â nm and increasing the number of pores accessible. The small crystal size of the nano-ferrierites results in an improved accessibility of reactants to the catalytic active centers and enhanced product diffusion, leading to higher conversion and selectivity with lower deactivation rates for the oligomerization of 1-pentene into longer-chain olefins.
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Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro. In the current preclinical study, the mechanistic efficacy and gene specificity of these selected constructs delivered by an AAV serotype 5 (AAV5) vector was addressed using an acute HD rat model. Our data demonstrated suppression of mutant HTT messenger RNA, which almost completely prevented mutant HTT aggregate formation, and ultimately resulted in suppression of DARPP-32-associated neuronal dysfunction. The AAV5-miHTT construct was found to be the most efficient, although AAV5-miSNP50T demonstrated the anticipated mutant HTT allele selectivity and no passenger strand expression. Ultimately, AAV5-delivered-miRNA-mediated HTT lowering did not cause activation of microglia or astrocytes suggesting no immune response to the AAV5 vector or therapeutic precursor sequences. These preclinical results suggest that using gene therapy to knock-down HTT may provide important therapeutic benefit for HD patients and raised no safety concerns, which supports our ongoing efforts for the development of an RNA interference-based gene therapy product for HD.
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Enfermedad de Huntington/terapia , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Tratamiento con ARN de Interferencia/métodos , Animales , Dependovirus/genética , Vectores Genéticos/genética , Humanos , Proteína Huntingtina , Enfermedad de Huntington/genética , Masculino , Microglía/metabolismo , Mutación , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Neuronas/patología , Proteínas Nucleares/metabolismo , Tratamiento con ARN de Interferencia/efectos adversos , Ratas , Ratas Sprague-DawleyRESUMEN
Materials that exhibit ferromagnetism, interfacial stability, and tunability are highly desired for the realization of emerging magnetoelectronic phenomena in heterostructures. Here we present the GdAg2 monolayer alloy, which possesses all such qualities. By combining X-ray absorption, Kerr effect, and angle-resolved photoemission with ab initio calculations, we have investigated the ferromagnetic nature of this class of Gd-based alloys. The Curie temperature can increase from 19 K in GdAu2 to a remarkably high 85 K in GdAg2. We find that the exchange coupling between Gd atoms is barely affected by their full coordination with noble metal atoms, and instead, magnetic coupling is effectively mediated by noble metal-Gd hybrid s,p-d bands. The direct comparison between isostructural GdAu2 and GdAg2 monolayers explains how the higher degree of surface confinement and electron occupation of such hybrid s,p-d bands promote the high Curie temperature in the latter. Finally, the chemical composition and structural robustness of the GdAg2 alloy has been demonstrated by interfacing them with organic semiconductors or magnetic nanodots. These results encourage systematic investigations of rare-earth/noble metal surface alloys and interfaces, in order to exploit them in magnetoelectronic applications.
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OBJECTIVES: To evaluate the prevalence of obstructive sleep apnoea syndrome (OSAS) in a population of patients treated for an advanced oropharyngeal cancer (AJCC Stage III or IV), depending on treatment strategy, and to evaluate its impact on quality of life. DESIGN: Prospective cohort study. SETTING: University Teaching Hospital of La Conception, Marseille, France. PARTICIPANTS: Fifty-one disease-free patients were included. Forty-one patients received a combined chemoradiotherapy, while 10 patients were treated by surgery followed by chemoradiotherapy. MAIN OUTCOME MEASURES: Every patient underwent a formal sleep consultation and was asked to complete the Epworth Sleepiness Scale and EORTC QLQ C-30 and the EORTC H&N 35 questionnaires. A home overnight respiratory polygraphy was performed in every subject. RESULTS: The mean time between the end of cancer treatment and the OSAS analysis was 54.04 months [20; 84]. An OSAS was found in 25.49% of our patients. There was no significant difference between patients treated with either surgery (30%) or CRT (24.39%), P=.79. The EORTC QLQ C-30 questionnaire showed a significant difference between positive and negative OSAS groups in the Global Health Status Scale (50.64 vs 67.11, P=.02) and in the fatigue item (35.04 vs 17.25, P=.03). CONCLUSIONS: Our population with advanced oropharyngeal cancer, whatever the treatment strategy it may be, was at risk of developing OSAS with negative impact on quality of life. A routine screening and treatment of OSAS seems necessary to improve the quality of life of patients treated for advanced oropharyngeal cancer.
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Quimioradioterapia , Neoplasias Orofaríngeas/terapia , Faringectomía , Apnea Obstructiva del Sueño/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/complicaciones , Neoplasias Orofaríngeas/patología , Polisomnografía , Prevalencia , Calidad de Vida , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/terapia , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Cassava is an important food security crop in Sub-Saharan Africa. Two episomal begomovirus-associated sequences, named Sequences Enhancing Geminivirus Symptoms (SEGS1 and SEGS2), were identified in field cassava affected by the devastating cassava mosaic disease (CMD). The sequences reportedly exacerbated CMD symptoms in the tolerant cassava landrace TME3, and the model plants Arabidopsis thaliana and Nicotiana benthamiana, when biolistically co-inoculated with African cassava mosaic virus-Cameroon (ACMV-CM) or East African cassava mosaic virus-UG2 (EACMV-UG2). Following the identification of small SEGS fragments in the cassava EST database, the intention of this study was to confirm their presence in the genome, and investigate a possible role for these sequences in CMD. We report that multiple copies of varying lengths of both SEGS1 and SEGS2 are widely distributed in the sequenced cassava genome and are present in several other cassava accessions screened by PCR. The endogenous SEGS1 and SEGS2 are in close proximity or overlapping with cassava genes, suggesting a possible role in regulation of specific biological processes. We confirm the expression of SEGS in planta using EST data and RT-PCR. The sequence features of endogenous SEGS (iSEGS) are unique but resemble non-autonomous transposable elements (TEs) such as MITEs and helitrons. Furthermore, many SEGS-associated genes, some involved in virus-host interactions, are differentially expressed in susceptible (T200) and tolerant TME3) cassava landraces infected by South African cassava mosaic virus (SACMV) of susceptible (T200) and tolerant (TME3) cassava landraces. Abundant SEGS-derived small RNAs were also present in mock-inoculated and SACMV-infected T200 and TME3 leaves. Given the known role of TEs and associated genes in gene regulation and plant immune responses, our observations are consistent with a role of these DNA elements in the host's regulatory response to geminiviruses.
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ADN de Plantas/genética , Manihot/genética , Begomovirus/fisiología , Elementos Transponibles de ADN , Regulación de la Expresión Génica de las Plantas , Manihot/virología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/virología , Análisis de Secuencia de ADNRESUMEN
During the Pleistocene, Australia and New Guinea supported a rich assemblage of large vertebrates. Why these animals disappeared has been debated for more than a century and remains controversial. Previous synthetic reviews of this problem have typically focused heavily on particular types of evidence, such as the dating of extinction and human arrival, and have frequently ignored uncertainties and biases that can lead to misinterpretation of this evidence. Here, we review diverse evidence bearing on this issue and conclude that, although many knowledge gaps remain, multiple independent lines of evidence point to direct human impact as the most likely cause of extinction.
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Aves/fisiología , Extinción Biológica , Mamíferos/fisiología , Reptiles/fisiología , Animales , Australia , Humanos , Nueva Guinea , PaleontologíaRESUMEN
INTRODUCTION: Molecular testing of Inherited bleeding coagulation disorders (IBCDs) not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and in certain cases genotype-phenotype correlations are important for predicting the clinical course of the disease and to allow tailor-made follow-up of individuals. Until recently, genotyping has been mainly performed by Sanger sequencing, a technique known to be time consuming and expensive. Currently, next-generation sequencing (NGS) offers a new potential approach that enables the simultaneous investigation of multiple genes at manageable cost. AIM: The aim of this study was to design and to analyse the applicability of a 23-gene NGS panel in the molecular diagnosis of patients with IBCDs. METHODS: A custom target enrichment library was designed to capture 31 genes known to be associated with IBCDs. Probes were generated for 296 targets to cover 86.3 kb regions (all exons and flanking regions) of these genes. Twenty patients with an IBCDs phenotype were studied using NGS technology. RESULTS: In all patients, our NGS approach detected causative mutations. Twenty-one pathogenic variants were found; while most of them were missense (18), three deletions were also identified. Six novel mutations affecting F8, FGA, F11, F10 and VWF genes, and 15 previously reported variants were detected. NGS and Sanger sequencing were 100% concordant. CONCLUSION: Our results demonstrate that this approach could be an accurate, reproducible and reliable tool in the rapid genetic diagnosis of IBCDs.
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Trastornos de la Coagulación Sanguínea Heredados/genética , Pruebas Genéticas/métodos , Adolescente , Adulto , Trastornos de la Coagulación Sanguínea Heredados/patología , Niño , Preescolar , ADN/química , ADN/aislamiento & purificación , ADN/metabolismo , Femenino , Mutación del Sistema de Lectura , Eliminación de Gen , Estudios de Asociación Genética , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación Missense , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Soft hydrogel particles show a rich structural and mechanical behaviour compared to hard particles, both in bulk and when confined in two dimensions at a fluid interface. Moreover, encapsulation into hydrogel shells makes it possible to transfer the tunability of soft steric interactions to hard nanoparticle cores, which bear interest for applications, e.g. in terms of optical, magnetic and reinforcement properties. In this work, we investigate the microstructures formed by hard core-soft shell particles at liquid-liquid interfaces upon compression. We produced model particles with the same silica core and systematically varied the shell-to-core ratio by synthesising shells with three different thicknesses. These particles were spread at an oil-water interface in a Langmuir-Blodgett trough and continuously transferred onto a solid support during compression. The transferred microstructures were analysed by atomic force and scanning electron microscopy. Quantitative image analysis provided information on the particle packing density, the inter-particle distance, and the degree of order of the monolayers. We discovered several essential differences compared to purely soft hydrogel particles, which shed light on the role played by the hard cores in the assembly and compression of these composite monolayers.
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Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthesized with the aim of investigating the in vitro antiproliferative activities of these nucleoside derivatives. A subset of the compounds was evaluated at a fixed concentration of 100µM against a small panel of tumor cell lines (HL-60, K-562, Jurkat, Caco-2 and HT-29). The entire set was also tested at varying concentrations against two human glioma lines (U373 and Hs683) to obtain GI50 values, with the best results being values of â¼25µM.
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Antineoplásicos/química , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Nucleósidos/química , Nucleósidos/farmacología , Antineoplásicos/síntesis química , Línea Celular Tumoral , Humanos , Neoplasias/tratamiento farmacológico , Nucleósidos/síntesis química , Relación Estructura-ActividadRESUMEN
Nine-dimensional potential energy surface (PES) and dipole moment surface (DMS) of the germane molecule are constructed using extended ab initio CCSD(T) calculations at 19â¯882 points. PES analytical representation is determined as an expansion in nonlinear symmetry adapted products of orthogonal and internal coordinates involving 340 parameters up to eighth order. Minor empirical refinement of the equilibrium geometry and of four quadratic parameters of the PES computed at the CCSD(T)/aug-cc-pVQZ-DK level of the theory yielded the accuracy below 1 cm-1 for all experimentally known vibrational band centers of five stable isotopologues of 70GeH4, 72GeH4, 73GeH4, 74GeH4, and 76GeH4 up to 8300 cm-1. The optimized equilibrium bond re = 1.517â¯594 Å is very close to best ab initio values. Rotational energies up to J = 15 are calculated using potential expansion in normal coordinate tensors with maximum errors of 0.004 and 0.0006 cm-1 for 74GeH4 and 76GeH4. The DMS analytical representation is determined through an expansion in symmetry-adapted products of internal nonlinear coordinates involving 967 parameters up to the sixth order. Vibration-rotation line intensities of five stable germane isotopologues were calculated from purely ab initio DMS using nuclear motion variational calculations with a full account of the tetrahedral symmetry of the molecules. For the first time a good overall agreement of main absorption features with experimental rotationally resolved Pacific Northwest National Laboratory spectra was achieved in the entire range of 700-5300 cm-1. It was found that very accurate description of state-dependent isotopic shifts is mandatory to correctly describe complex patterns of observed spectra at natural isotopic abundance resulting from the superposition of five stable isotopologues. The data obtained in this work will be made available through the TheoReTS information system.
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Cell-type-specific gene silencing is critical to understand cell functions in normal and pathological conditions, in particular in the brain where strong cellular heterogeneity exists. Molecular engineering of lentiviral vectors has been widely used to express genes of interest specifically in neurons or astrocytes. However, we show that these strategies are not suitable for astrocyte-specific gene silencing due to the processing of small hairpin RNA (shRNA) in a cell. Here we develop an indirect method based on a tetracycline-regulated system to fully restrict shRNA expression to astrocytes. The combination of Mokola-G envelope pseudotyping, glutamine synthetase promoter and two distinct microRNA target sequences provides a powerful tool for efficient and cell-type-specific gene silencing in the central nervous system. We anticipate our vector will be a potent and versatile system to improve the targeting of cell populations for fundamental as well as therapeutic applications.
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Astrocitos/fisiología , Técnicas de Transferencia de Gen , Vectores Genéticos , Lentivirus , ARN Interferente Pequeño , Animales , Sistema Nervioso Central/citología , Sistema Nervioso Central/fisiología , Regulación de la Expresión Génica , Silenciador del Gen , Ratones , Ratones Transgénicos , TetraciclinaRESUMEN
A simultaneous use of the full molecular symmetry and of an exact kinetic energy operator (KEO) is of key importance for accurate predictions of vibrational levels at a high energy range from a potential energy surface (PES). An efficient method that permits a fast convergence of variational calculations would allow iterative optimization of the PES parameters using experimental data. In this work, we propose such a method applied to tetrahedral AB4 molecules for which a use of high symmetry is crucial for vibrational calculations. A symmetry-adapted contracted angular basis set for six redundant angles is introduced. Simple formulas using this basis set for explicit calculation of the angular matrix elements of KEO and PES are reported. The symmetric form (six redundant angles) of vibrational KEO without the sin(q)(-2) type singularity is derived. The efficient recursive algorithm based on the tensorial formalism is used for the calculation of vibrational matrix elements. A good basis set convergence for the calculations of vibrational levels of the CH4 molecule is demonstrated.
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Past scanning tunneling microscopy (STM) experiments of H manipulation on Pd(111), at low temperature, have shown that it is possible to induce diffusion of surface species as well as of those deeply buried under the surface. Several questions remain open regarding the role of subsurface site occupancies. In the present work, the interaction potential of H atoms with Pd(111) under various H coverage conditions is determined by means of density functional theory calculations in order to provide an answer to two of these questions: (i) whether subsurface sites are the final locations for the H impurities that attempt to emerge from bulk regions, and (ii) whether penetration of the surface is a competing route of on-surface diffusion during depletion of surface H on densely covered Pd(111). We find that a high H coverage has the effect of blocking resurfacing of H atoms travelling from below, which would otherwise reach the surface fcc sites, but it hardly alters deeper diffusion energy barriers. Penetration is unlikely and restricted to high occupancies of hcp hollows. In agreement with experiments, the Pd lattice expands vertically as a consequence of H atoms being blocked at subsurface sites, and surface H enhances this expansion. STM tip effects are included in the calculations self-consistently as an external static electric field. The main contribution to the induced surface electric dipoles originates from the Pd substrate polarisability. We find that the electric field has a non-negligible effect on the H-Pd potential in the vicinity of the topmost Pd atomic layer, yet typical STM intensities of 1-2 VÅ(-1) are insufficient to invert the stabilities of the surface and subsurface equilibrium sites.