Single-neutron and single-proton removal cross sections have been measured for medium-mass neutron-rich nuclei around Z=50 and energies around 1000A MeV using the FRagment Separator (FRS) at GSI. The ...measured cross sections confirm the relative low values of the proton-removal cross sections, observed since a long time ago and not yet understood. Model calculations considering the knock-out process together with initial- and final-state interactions describe the measured neutron-removal cross sections. Proton-removal cross sections are, however, significantly over-predicted by the same calculations. The observed difference can be explained to a large extent by the knock-out of short-range correlated nucleons from dominant neutron-proton pairs in neutron-rich nuclei.
Maytansinol is a valuable precursor for the preparation of maytansine derivatives (known as maytansinoids). Inspired by the intriguing structure of the macrocycle and the success in targeted cancer ...therapy of the derivatives, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives with novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation, and by determination of their crystal structures in complex with tubulin. The results shed further light on the intriguing chemical behavior of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.
Exploring the maytansinol acylation reaction, we have discovered previously unreported structural modifications of the maytansine scaffold. This permitted the synthesis and full characterization of a series of novel maytansinoids. A comprehensive biochemical evaluation and X‐ray crystallography structure determinations of tubulin‐maytansinoids identified potent tubulin binders. Moreover, our investigation allowed us to evaluate the impact of the structural modifications described.
to evaluate validity and concordance of Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) and Screening Tool for Risk On Nutritional status and Growth (STRONGkids) screening ...tools for assessment of nutritional risk in pediatric inpatients.
Prospective longitudinal observational multicenter study in children aged 1 month or older admitted as inpatients. Weight, height, cause of admission, demographic data, length of stay, and nutritional interventions were recorded. STAMP and STRONGkids were applied within the first 72 h of admission. Anthropometric measurements were recorded again 12-18 months after admission.
Eighty-one patients with median age of 4.1 years completed the study. Agreement between tools was moderate (κ = 0.47). STAMP had a greater tendency to classify patients as high risk (12.3% vs. 2.5%). Both tools showed very weak correlation with height for age. All undernourished patients at the beginning and the end of the study were classified as medium or high risk by STAMP and STRONGkids (100% sensitivity), although specificity was below 50% in all cases. There were no differences in length of stay based on nutritional risk with any of the tools.
STAMP and STRONGkids demonstrated moderate agreement, with high sensitivity but low specificity for the diagnosis of undernutrition. Further studies are required to analyze cost-effectiveness of these tools and nutritional interventions derived from them.
Display omitted
The study of controlled release and drug release devices has been dominated by considerations of the bulk or average properties of material or devices. Yet the outermost surface atoms ...play a central role in their performance. The objective of this article has been to characterize the surface of hydrophilic matrix tablets using the contact angle (CA) method to ascertain the surface free energy, and atomic force microscopy (AFM) and confocal microscopy (CM) for the physical characterization of the surface of the hydrophilic matrix. The surface free energy results obtained show that hydroxypropylmethylcellulose K15M hinders the spreading of water on the surface of the tablet, such that the concentration of HPMC K15M increases the reaction rate of the hydrophobic interactions between the chains of HPMC K15M which increases with respect to the rate of penetration of water into the tablet. In this study, we developed a new method to characterize the swelling of the tablets and established a relationship between the new method based on microswelling and the swelling ratio parameter. The surface texture parameters have been determined and the morphology of the tablets of the different formulations and the evolution of the surface morphology after interacting with the water, swelling and forming a gel layer were characterized. This work represents significant progress in the characterization of matrix tablets.
The aim of this current and innovative work is the numerical thermal analysis of multi-holed lightweight concrete blocks for external and non-habitable floors by the finite element method (FEM). ...Twelve different block designs with the same external dimensions 0.57
×
0.45
×
0.20
m were built varying the number of the horizontal intermediate bulkheads, from 3 to 12. Besides, five different compositions of the lightweight aggregate concrete (LWAC) and five different bulk temperatures have been taken into account, giving place to a total of 600 different floor configurations, 300 cases per each heat flow direction: upward and downward heat flows. A nonlinear thermal problem is solved for all cases analysed and then, it is possible to choose the best candidate block from the standard rule requirements. Mathematically, the nonlinearity due to the radiation boundary condition inside the inner recesses of the blocks is tackled by the matrix radiation method. Once the nonlinear thermal problem is solved, the temperature distribution is obtained and the thermal characteristic values of the floors, both for downward and upward heat flows, are calculated. From the numerical results, we can conclude that the main variables in the thermal performance are the total number of recesses and the material conductivities. Therefore, increasing the number of horizontal intermediate bulkheads and decreasing the material conductivities, the best thermal efficiency is obtained. The selection of the best candidate block of external floors and floors in contact with non-habitable spaces is carried out through the following parameters: the average mass overall thermal efficiency and the equivalent thermal conductivity. Finally, detailed instructions are provided in order to select the appropriate floor satisfying the standard rule requirements and conclusions of this work are exposed.
Around one million metric ton of plastics is produced worldwide daily. Plastic contamination is aggravated when the particles reach sizes between 5 mm and 1 μm, giving rise to microplastics, which ...are omnipresent in the environment, especially in agroecosystems. To appreciate the magnitude of this problem, this review analyzes 177 scientific works to focus on the occurrence and effects of microplastics in agricultural soils. Firstly, the sources, behavior and fate of microplastics in agroecosystems are evaluated. Then, in the absence of a standard methodology for the study of microplastics in farmland soils, the procedures which have been employed for microplastic separation (density and floatation in 73% of the discussed works), identification and quantification (stereomicroscopy, 77%; infrared analysis, 62%) are addressed to provide a practical work guideline. Finally, we highlight the interaction between microplastics and soil microbiota, fauna and vegetation (negative effects reported in 83% of cases), including crop production (decrease in growth parameters in 63% of the reports). From this review, it can be inferred that microplastics may disrupt the biophysical environment of farmland soil, potentially leading to economic losses and to their entrance into the trophic food chain, affecting human feeding and health.
We consider
C
r
(
r
⩾
1
) diffeomorphisms
f
defined on manifolds of dimension
⩾
3
with homoclinic tangencies associated to saddles. Under generic properties, we show that if the saddle is ...homoclinically related to a blender then the diffeomorphism
f
can be
C
r
approximated by diffeomorphisms with
C
1
robust heterodimensional cycles. As an application, we show that the classic Simon–Asaoka’s examples of diffeomorphisms with
C
1
robust homoclinic tangencies also display
C
1
robust heterodimensional cycles. In a second application, we consider homoclinic tangencies associated to hyperbolic sets. When the entropy of these sets is large enough we obtain
C
1
robust cycles after
C
1
perturbations.
We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is ...(E)-3-(3''-amino-4''-methoxyphenyl)-1-(5'-methoxy-3',4'-methylendioxyphenyl)-2-methylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and therefore prevent the curved-to-straight structural transition of tubulin, which is required for microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. In addition, TUB091 displayed vascular disrupting effects in vitro and in the chicken chorioallantoic membrane (CAM) assay at low nanomolar concentrations. A water-soluble L-Lys-L-Pro derivative of TUB091 (i.e. TUB099) showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic activity similar to that of combretastatin A4-phosphate. Our data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, we provide evidence that our prodrug approach may be valuable for the development of anti-cancer drugs.
SARS-CoV-2 infection can associate diverse neurological manifestations. Several studies have provided proof to support the theory of neurotropic involvement of SARS-CoV-2. Alpha-synuclein has been ...described as a native antiviral factor within neurons, and upregulation of this protein can be seen in animals that suffered other neuroinvasive infections. To assess if increased expression of this protein takes place in COVID-19 patients with neurological symptoms, we analyzed serum total alpha-synuclein levels in three groups: seven COVID-19 patients with myoclonus, Parkinsonism and/or encephalopathy; thirteen age- and sex-matched COVID-19 patients without neurological involvement and eight age- and sex-matched healthy controls. We did not find differences among them. In a subset of four patients, the change in serum alpha-synuclein before and after the onset of neurological symptoms was not significant either. Cerebrospinal fluid alpha-synuclein levels were also similar between neurological COVID-19 and healthy controls. Overall, these results cannot support the hypothesis of alpha-synuclein upregulation in humans with neurological symptoms in COVID-19. Further research taking into account a larger group of COVID-19 patients including the whole spectrum of neurological manifestations and disease severity is needed.
Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder clinically defined by chronic and benign lymphoproliferation, autoimmunity and an increased risk of lymphoma due ...to a genetic defect in the FAS-FASL apoptotic pathway. Genetic defects associated with ALPS are germinal and somatic mutations in
gene, in addition to germinal mutations in
and
genes. The accumulation of CD3+TCRαβ+CD4-CD8- double negative T-cells (DNT) is a hallmark of the disease and 20-25% of ALPS patients show heterozygous somatic mutations restricted to DNT in the
gene (ALPS-sFAS patients). Nowadays, somatic mutations in the
gene are detected through Sanger sequencing in isolated DNT. In this study, we report an ALPS-sFAS patient fulfilling clinical and laboratory ALPS criteria, who was diagnosed through NGS with a targeted gene panel using DNA from whole blood. Data analysis was carried out with Torrent Suite Software and variant detection was performed by both germinal and somatic variant caller plugin. The somatic variant caller correctly detected other six ALPS-sFAS patients previously diagnosed in the authors' laboratories. In summary, this approach allows the detection of both germline and somatic mutations related to ALPS by NGS, avoiding the isolation of DNT as the first step. The reads of the somatic variants could be detected even in patients with DNT in the cut off limit. Thus, custom-designed NGS panel testing may be a faster and more reliable method for the diagnosis of new ALPS patients, including those with somatic
mutations (ALPS-sFAS).
PDF
