The triphosphorus complex Mo2Cp2(μ-η3:η3-P3)(μ-P t Bu2) was prepared in 83% yield by reacting the methyl complex Mo2Cp2(μ-κ1:η2-CH3)(μ-P t Bu2)(μ-CO) with P4 at 333 K, a process also giving small ...amounts of the methyldiphosphenyl complex Mo2Cp2(μ-η2:η2-P2Me)(μ-P t Bu2)(CO)2. The latter could be better prepared by first reacting the anionic complex NaMo2Cp2(μ-P t Bu2)(μ-CO)2 with P4 to give the diphosphorus derivative NaMo2Cp2(μ-η2:η2-P2)(μ-P t Bu2)(CO)2 and further reaction of the latter with MeI. Density functional theory calculations on the title complex revealed that its triphosphorus group can be viewed as an allylic-like P3 – ligand acting as a six-electron donor via the external P atoms, while coordination of the internal P atom involves donation from the π orbital of the ligand and back-donation to its π* orbital, both interactions having a weakening effect on the Mo–Mo and P–P connections. The reactivity of the title compound is dominated by the electron-donor ability associated with the lone pairs located at the P atoms. Its reaction with CF3SO3Me gave Mo2Cp2(μ-η3:η3-P3Me)(μ-P t Bu2)(CF3SO3) as a result of methylation at an external atom of the P3 ligand, while its reaction with Fe2(CO)9 enabled the addition of one, two, or three Fe(CO)4 fragments at these P atoms, but only the diiron derivative Mo2Fe2Cp2(μ-η3:η3:κ1:κ1-P3)(μ-P t Bu2)(CO)8 could be isolated. This complex bears a Fe(CO)4 fragment at each of the external atoms of the P3 ligand, and the central P atom of the latter displays the lowest 31P chemical shift reported to date (δP −721.8 ppm). The related complexes Mo2M2Cp2(μ-η3:η3:κ1:κ1-P3)(μ-P t Bu2)(CO)10 (M = Mo, W) were prepared by reacting the title compound with the corresponding M(CO)5(THF) complexes in toluene, while reaction with Mo(CO)4(THF)2 also enabled the formation of the heptanuclear derivative Mo7Cp4(μ-η3:η3:κ1:κ1-P3)2(μ-P t Bu2)2(CO)14. The interatomic distances in the above compounds indicate that the central Mo2P3 skeleton of these molecules is little modified by the attachment of 16-electron M(CO) n fragments at the external atoms of the P3 ligand.
Tuberculous meningitis (TB meningitis) is the most severe form of tuberculosis (TB), requiring 12 months of multidrug treatment for cure, and is associated with high morbidity and mortality. ...High-dose rifampin (35 mg/kg/d) is safe and improves the bactericidal activity of the standard-dose (10 mg/kg/d) rifampin-containing TB regimen in pulmonary TB. However, there are conflicting clinical data regarding its benefit for TB meningitis, where outcomes may also be associated with intracerebral inflammation. We conducted cross-species studies in mice and rabbits, demonstrating that an intensified high-dose rifampin-containing regimen has significantly improved bactericidal activity for TB meningitis over the first-line, standard-dose rifampin regimen, without an increase in intracerebral inflammation. Positron emission tomography in live animals demonstrated spatially compartmentalized, lesion-specific pathology, with postmortem analyses showing discordant brain tissue and cerebrospinal fluid rifampin levels and inflammatory markers. Longitudinal multimodal imaging in the same cohort of animals during TB treatment as well as imaging studies in two cohorts of TB patients demonstrated that spatiotemporal changes in localized blood-brain barrier disruption in TB meningitis are an important driver of rifampin brain exposure. These data provide unique insights into the mechanisms underlying high-dose rifampin in TB meningitis with important implications for developing new antibiotic treatments for infections.
With heavy crude oil refining on the rise, upgrading strategies are fundamental to yield high-value products. Hydroconversion and thermal cracking are well-established and widely used upgrading ...processes for heavy oils’ distillation cuts and residues. Recognizing molecular changes in these fractions after upgrading, particularly of asphaltenic compounds, is fundamental to understand and optimize the processes. In this work, we follow compositional changes in the asphaltene fraction of a Colombian heavy crude, after hydroconversion and thermal cracking, using high-resolution mass spectrometry. The liquid products from the upgrading processes were fractionated into maltenes and residual asphaltenes, with yields between 33% and 38% in maltenes from the original asphaltene feedstock. Contoured plots of double bond equivalents versus carbon number and van Krevelen diagrams show maltenic fractions exhibiting lower aromaticity, smaller molecular size, fewer heteroatomic species, and higher content of alkyl side chains than the starting asphaltenic material. Residual asphaltenes, on the other hand, consist of compounds with lower H/C ratios and reduced content of alkyl groups than the feedstock. In addition, structural information about the feedstock, such as archipelago or island structures, can be derived from the plots. This information is useful to establish trends between compound class reactivity and the suitability to produce valuable maltenic compounds through upgrading technologies.
•We obtain foams with tunable cell size between the nanometric and micrometric ranges.•We obtain both closed and open cell structures with similar cell sizes and densities.•We found that PMMA–block ...copolymer foams present an enhanced thermal stability.•We determine the role of the block copolymer on the CO2 sorption and desorption.•We propose one- and two-step foaming processes assuming heterogeneous nucleation.
Fabricated by high-pressure or supercritical CO2 gas dissolution foaming process, nanocellular and microcellular polymer foams based on poly(methyl methacrylate) (PMMA homopolymer) present a controlled nucleation mechanism by the addition of a methylmethacrylate–butylacrylate–methylmethacrylate block copolymer (MAM), leading to defined nanocellular morphologies templated by the nanostructuration of PMMA/MAM precursor blends. Influence of the CO2 saturation temperature on the foaming mechanism and on the foam structure has been studied in 90/10 PMMA/MAM blends and also in the neat (amorphous) PMMA or (nanostructured) MAM polymers, in order to understand the role of the MAM nanostructuration in the cell growth and coalescence phenomena. CO2 uptake and desorption measurements on series of block copolymer/homopolymer blend samples show a competitive behavior of the soft, rubbery, and CO2-philic block of PBA (poly(butyl acrylate)) domains: fast desorption kinetics but higher initial saturation. This competition nevertheless is strongly influenced by the type of dispersion of PBA (e.g. micellar or lamellar) and a very consequent influence on foaming.
CO2 sorption and desorption were characterized in order to provide a better understanding of the role of the block copolymer on the foaming stages. Poly(butyl acrylate) blocks are shown to have a faster CO2 diffusion rate than poly(methyl methacrylate) but are more CO2-philic. Thus gas saturation and cell nucleation (heterogeneous) are more affected by the PBA block while cell coalescence is more affected by the PMMA phases (in the copolymer blocks+in the matrix).
Highly anisotropic, beam-like neutron emission with peak flux of the order of 109 n/sr was obtained from light nuclei reactions in a pitcher-catcher scenario, by employing MeV ions driven by a ...sub-petawatt laser. The spatial profile of the neutron beam, fully captured for the first time by employing a CR39 nuclear track detector, shows a FWHM divergence angle of ∼ 70 ° , with a peak flux nearly an order of magnitude higher than the isotropic component elsewhere. The observed beamed flux of neutrons is highly favourable for a wide range of applications, and indeed for further transport and moderation to thermal energies. A systematic study employing various combinations of pitcher-catcher materials indicates the dominant reactions being d(p, n+p)1H and d(d,n)3He. Albeit insufficient cross-section data are available for modelling, the observed anisotropy in the neutrons' spatial and spectral profiles is most likely related to the directionality and high energy of the projectile ions.
Background and purpose
To evaluate the incidence and predictors of ischaemic recurrent stroke and the adverse events of antithrombotic therapy in patients with first intra‐ or extracranial vertebral ...artery dissection (VAD) who were treated with aspirin or oral anticoagulation (OA).
Methods
A 21‐year database of consecutive patients with confirmed diagnoses of VAD (n = 110, 63% men; mean age 37.9 ± 8.5 years) without intracerebral hemorrhage and who were treated with aspirin or OA were analyzed retrospectively. In all cases, the admission diagnosis was ischaemic stroke. Three groups were defined according to the site of the dissection: (i) extracranial, (ii) intracranial, and (iii) intra‐/extracranial. Clinical follow‐up was obtained by neurologic examination. Outcome measures were (i) recurrent ischaemic events (ischaemic stroke or transient ischaemic attack) and (ii) intra‐ and extracranial major bleeding.
Results
No difference in age, smoking, or hypertension was found between patients treated with OA (n = 49) and those treated with aspirin (n = 50). Extracranial artery dissection (49%) had preponderance over intracranial (27%) or intra‐/extracranial (23%) location. During the follow‐up, recurrent ischaemic events were rare (one case). There were no bleeding complications. The treatment that was used did not influence the functional outcome or recanalization. A good functional outcome (modified Rankin score ≤ 2) was observed in 82 patients.
Conclusions
Although this was a non‐randomized study, our data suggest that the frequency of recurrent ischaemic stroke in patients with intra‐ or extracranial VAD is low and most likely independent of the type of antithrombotic treatment.
NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 ...signaling launches a leukemia-prone chromatin landscape during T-ALL initiation is unknown. Here we demonstrate an essential role for the high-mobility-group transcription factor Tcf1 in orchestrating chromatin accessibility and topology, allowing aberrant Notch1 signaling to convey its oncogenic function. Although essential, Tcf1 is not sufficient to initiate leukemia. The formation of a leukemia-prone epigenetic landscape at the distal Notch1-regulated Myc enhancer, which is fundamental to this disease, is Tcf1-dependent and occurs within the earliest progenitor stage even before cells adopt a T lymphocyte or leukemic fate. Moreover, we discovered a unique evolutionarily conserved Tcf1-regulated enhancer element in the distal Myc-enhancer, which is important for the transition of preleukemic cells to full-blown disease.
•Tcf1 shapes a Notch1-induced T-ALL-prone chromatin landscape in early hematopoietic progenitors.•Tcf1 orchestrates chromatin accessibility within the Notch1-regulated Myc super-enhancer.
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Live fuel moisture content (LFMC) is an input factor in fire behavior simulation models highly contributing to fire ignition and propagation. Developing models capable of accurately estimating ...spatio-temporal changes of LFMC in different forest species is needed for wildfire risk assessment. In this paper, an empirical model based on multivariate linear regression was constructed for the forest cover classified as shrublands in the central part of the Valencian region in the Eastern Mediterranean of Spain in the fire season. A sample of 15 non-monospecific shrubland sites was used to obtain a spatial representation of this type of forest cover in that area. A prediction model was created by combining spectral indices and meteorological variables. This study demonstrates that the Normalized Difference Moisture Index (NDMI) extracted from Sentinel-2 images and meteorological variables (mean surface temperature and mean wind speed) are a promising combination to derive cost-effective LFMC estimation models. The relationships between LFMC and spectral indices for all sites improved after using an additive site-specific index based on satellite information, reaching a R2adj = 0.70, RMSE = 8.13%, and MAE = 6.33% when predicting the average of LFMC weighted by the canopy cover fraction of each species of all shrub species present in each sampling plot.
There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT), but this does not explain all cases. We study the role of the ...immunogenetic profile (HLA, KIRs and KIR-ligand binding) of mothers and children in HCV-MTCT and in chronicity in the children.
79 HCV-RNA (+) mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16. HLA-class-I and II and KIRs were determined by Luminex.
MTCT study: The presence of HLA-C1-ligand in mothers and/or their children reduces the risk of transmission (mothers: Pc = 0.011, children: P = 0.033), whereas the presence of HLA-C2C2-ligand in mothers increases it (Pc = 0.011). In children KIR2DL3-HLA-C1 is a protector factor (Pc = 0.011). Chronicity in children study: Maternal DQA1*01 allele (Pc = 0.027), KIR2DS1 (Pc = 0.011) or KIR3DS1 (Pc = 0.011) favours chronicity in the child. The presence of the DQB1*03 allele (Pc = 0.027) and KIR2DS3 (P = 0.056) in the child and homozygosity for KIR3DL1/3DL1 (Pc = 0.011) and for the HLA-Bw4/Bw4 ligand (P = 0.027) is associated with viral clearance, whereas the presence of HLA-Bw6 ligand (P = 0.027), the binding of KIR3DS1-HLA-Bw4 (P = 0.037) and heterozygosity for KIR3DL1/3DS1 (Pc = 0.011) favour viral chronicity. Mother/child allele matching: In the joint HLA analysis, matching was greater between mothers and children with chronic infection vs those who had cleared the virus (67%±4.1 vs 57%±1.2, P = 0.003).
The HLA-C1 ligand in the mother is related to MTCT, while several genetic factors of the mother or child are involved in the chronification or clearance of infection in the child. Matching allelic data is considered to be an indicator of HCV chronicity in the child and can be used as a potential prognostic test. This implies that NK cells may play a previously undocumented role in protecting against MTCT and that both NK cell immunity and adaptive T-cell responses may influence viral clearance in infected children.
The concept of a European super-grid for electricity presents clear advantages for a reliable and affordable renewable power production (photovoltaics and wind). Based on the mean-variance portfolio ...optimization analysis, we explore optimal scenarios for the allocation of new renewable capacity at national level in order to provide to energy decision-makers guidance about which regions should be mostly targeted to either maximize total production or reduce its day-to-day variability. The results show that the existing distribution of renewable generation capacity across Europe is far from optimal: i.e. a 'better' spatial distribution of resources could have been achieved with either a ~31% increase in mean power supply (for the same level of day-to-day variability) or a ~37.5% reduction in day-to-day variability (for the same level of mean productivity). Careful planning of additional increments in renewable capacity at the European level could, however, act to significantly ameliorate this deficiency. The choice of where to deploy resources depends, however, on the objective being pursued-if the goal is to maximize average output, then new capacity is best allocated in the countries with highest resources, whereas investment in additional capacity in a north/south dipole pattern across Europe would act to most reduce daily variations and thus decrease the day-to-day volatility of renewable power supply.
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