Eight infants with SCID-X1 had multilineage immune reconstitution after autologous hematopoietic stem-cell transplantation of marrow stem cells transfected with a lentiviral vector containing
IL2RG
...cDNA after busulfan conditioning. Previous infections cleared and functional T cells developed in all eight infants, IgM levels normalized in seven, and three had a response to vaccines.
Oriented external electric fields (OEEFs) have been shown to have great potential in being able to provide unprecedented control of chemical reactions, catalysis, and selectivity with applications ...ranging from H
storage to molecular machines. We report a theoretical study of the atomic origins of molecular changes because of OEEFs since understanding the characteristics of OEEF-induced couplings between atomic and molecular properties is an important step toward comprehensive understanding of the effects of strong external fields on the molecular structure, stability, and reactivity. We focus on the atomic and molecular (bond) properties of a set of homo- (H
, N
, O
, F
, and Cl
) and heterodiatomic (HF, HCl, CO, and NO) molecules under intense external electric fields in the context of quantum theory of atoms in molecules (QTAIM). It is shown that the atomic properties (atomic charges, energies, and localization indices) correlate linearly with the field strengths, but molecular properties (bond length, electron density at the bond critical point, and electron delocalization index) exhibit nonlinear responses to the imposed fields. In particular, the changes in the electron density distribution alter the shapes and locations of the zero-flux surfaces, atomic volumes, atomic electron population, and localization/delocalization indices. The topography and topology of the molecular electrostatic potential undergo dramatic changes. External fields also perturb the covalent-polar-ionic characteristic of the studied chemical bonds, hallmarking the impact of electric fields on the stability and reactivity of chemical compounds. The findings are well-rationalized within the framework of the QTAIM and form a coherent conceptual understanding of these effects in prototypical diatomic molecules.
This article compares molecular properties and atomic properties defined by the quantum theory of atoms in molecules (QTAIM) obtained from three underlying levels of theory: MP2(full), density ...functional theory (DFT) (B3LYP), and Hartree-Fock (H-F). The same basis set (6-311++G(d,p)) has been used throughout the study. The calculations and comparisons were applied to a set of 30 small molecules representing common fragments of biological molecules. The molecular properties investigated are the energies and the electrostatic moments (up to and including the quadrupoles), and the atomic properties include electron populations (and atomic charge), atomic dipolar and quadrupolar polarizations, atomic volumes, and corrected and raw atomic energies. The Cartesian distance between dipole vectors and the Frobenius distance between the quadrupole tensors calculated at the three levels of theory provide a measure of their correlation (or lack thereof). With the exception of energies (atomic and molecular), it is found that both DFT and H-F are in excellent agreement with MP2, especially with regards to the electrostatic mutipoles up to the quadrupoles, but DFT and MP2 agree better in almost all studied properties (with the exception of molecular geometries). QTAIM properties whether obtained from H-F, DFT(B3LYP), or MP2 calculations when used in the construction of empirical correlations with experiment such as quantitative structure-activity-(or property)-relationships (QSAR/QSPR) are equivalent (because the properties calculated at the three levels are very highly correlated among themselves with r² typically >0.95, and therefore preserving trends). These results suggest that the massive volume of results that were published in the older literature at the H-F level is valid especially when used to study trends or in QSAR or QSPR studies, and, as long as our test set of molecules is representative, there is no pressing need to re-evaluate them at other levels of theory except when inadequate basis sets were used by today's standards. Extensive tabulation of molecular and atomic properties at the three theoretical levels is available in the Supporting Information, including optimized geometries, molecular energies, virial ratios, molecular electrostatic moments up to and including hexadecapoles, atomic populations, atomic volumes, atomic electrostatic moments up to and including the quadrupoles, and atomic energies.
AbstractIt is known that the effectiveness of tuned mass dampers (TMDs) decreases as the input duration shortens. As a result, their use is commonly discouraged against short-duration, pulse-like ...ground motions, such as those occurring in near-field (NF) zones in the presence of forward directivity or fling-step effects. Yet a systematic assessment of such control impairment is still missing. In this paper, a recent analytical model of ground motion pulses is applied to the design and evaluation of TMDs against impulsive earthquakes. Based on this model, first, a new optimization method is introduced as an alternative to the classical H∞ approach. Then, the two strategies are tested on single- and multi- degrees-of-freedom linear structures subject both to analytical pulses and to a large set of NF records possessing pulse-like features. The resulting statistical evaluation, expressed by percentile response spectra, shows the pros and cons of a pulse-oriented TMD design and improves the general understanding of TMD performance under impulsive ground motions.
Celotno besedilo
Dostopno za:
DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This article provides critical engagement with cultural heritage‐making processes conducted by stakeholders and interest groups within the UNESCO's intangible heritage paradigm. By tracking the road ...of Peru's cuisine to the Representative List of Intangible Cultural Heritage (the ICH List) and focusing on the turning points during food's shift from culinary to heritage status, the aim is to shed light on the political and economic forces that shape the meanings of food heritage. This article draws on recent research conducted at the intersection of globalisation with cultural and food politics in Peru. The empirical evidence, collected between 2011 and 2014 from individuals directly implicated in Peru's food heritage‐making, allows for a discussion of how, despite a discursive emphasis on cultural continuity and intercultural dialogue, food incursions into the UNESCO intangible cultural paradigm operate more as an elite‐driven competitive global concept than as a tool for cultural safeguarding and inclusive development. To do so, a description of the backgrounds that led to the rise of food heritage awareness in Peru and an account of the evolution of the candidature of Peruvian cuisine to the UNESCO's ICH List are provided.
Incursions alimentaires dans le patrimoine global: le difficile parcours de la cuisine péruvienne vers l'UNESCO
Cet article développe un regard critique sur les processus du patrimonialisation au sein du paradigme du patrimoine immatériel établi par l'UNESCO. En retraçant le parcours de la cuisine péruvienne vers la Liste Représentative du Patrimoine Culturel Immatériel, il met en lumière les forces politiques et économiques qui façonnent les significations multiples du patrimoine alimentaire. Les données empiriques qui servent de base à cet article ont été recueillies auprès d'individus directement impliqués dans la construction du patrimoine alimentaire péruvien. Elles permettent une discussion sur comment, en dépit d'un discours axé sur la continuité culturelle et le dialogue interculturel, les patrimoines alimentaires dans le cadre de l'UNESCO s'imposent plus comme des concepts de concurrence au niveau global que comme des outils de sauvegarde culturelle et de développement inclusif.
Abstract
We investigate the micro-connectivity drivers of network change in an underperforming industrial cluster in Argentina. Our analysis is based on data collected in two consecutive surveys, ...conducted in 2005 and 2012, of entrepreneurs in the electronics cluster in Córdoba. We find that social and institutional factors influence micro-connectivity choices at the local level, while firms that are more open to non-local knowledge have the tendency to behave like external stars, potentially limiting the flow of non-locally generated knowledge into the cluster network as it grows. We interpret these results using the intuitions from strain theory and suggest that strain may engender an ‘everyone for themselves’ mentality in the most open cluster firms as they seek to escape from a condition of underperformance. We posit, also, that local social and institutional ties are relevant for most cluster firms to survive, but are not sufficient for the cluster to thrive.
This study was aimed to characterize the spermatogenic process and its seasonal variation in Desmodus rotundus, in the Caatinga biome, a water-limited ecosystem, with marked water restriction during ...most of the year. Collections of adult animals were performed during the dry and rainy seasons, and after euthanasia, their testes were processed histologically to perform morphological, morphometric, ultrastructural and immunohistochemical analyzes. The percentage of seminiferous epithelium, number of Leydig cells per gram of testis, and population of Sertoli cells and A-type spermatogonia presented by D. rotundus were significantly higher in the rainy season, while the percentage of lumen, mitotic index, support capacity performed by Sertoli cells, and overall yield of spermatogenesis were higher in the dry season. The ultrastructure of spermatogenesis was similar to that described in other mammals, and the immunohistochemical analysis revealed activity of the aromatase enzyme in Sertoli cells, Leydig cells, spermatocytes and spermatids, as well as the presence of androgen receptors in Sertoli cells and Leydig cells. FGF2 activity was detected in primary spermatocytes in zygotene and pachytene, as well as secondary spermatocytes and rounded and elongated spermatids, while the BCL-2 protein was expressed in primary spermatocytes in zygotene and pachytene, secondary spermatocytes, and rounded spermatids. The activity of these molecules was similar in both seasons, and associated with the morphometric findings, indicates maintenance in the integrity of the seminiferous epithelium throughout the year. The seasonal study of D. rotundus spermatogenesis indicates a continuous spermatogenesis pattern and suggests a greater production of spermatozoa in the rainy season in the Caatinga biome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In cerebral cortex there is a developmental switch from NR2B- to NR2A-containing NMDA receptors (NMDARs) driven by activity and sensory experience. This subunit switch alters NMDAR function, ...influences synaptic plasticity, and its dysregulation is associated with neurological disorders. However, the mechanisms driving the subunit switch are not known. Here, we show in hippocampal CA1 pyramidal neurons that the NR2B to NR2A switch driven acutely by activity requires activation of NMDARs and mGluR5, involves PLC, Ca2+ release from IP3R-dependent stores, and PKC activity. In mGluR5 knockout mice the developmental NR2B-NR2A switch in CA1 is deficient. Moreover, in visual cortex of mGluR5 knockout mice, the NR2B-NR2A switch evoked in vivo by visual experience is absent. Thus, we establish that mGluR5 and NMDARs are required for the activity-dependent NR2B-NR2A switch and play a critical role in experience-dependent regulation of NMDAR subunit composition in vivo.
► The NR2B to 2A subunit switch at CA1 synapses requires NMDARs and mGluR5 ► The NR2 subunit switch requires PLC, IP3, and PKC signaling ► The acute NR2 subunit switch is absent in slices from mGluR5 KO mice ► mGluR5 KO mice exhibit a deficient experience-driven NR2 subunit switch
Nicotine exerts its behavioral and additive actions through a family of brain nicotinic acetylcholine receptors (nAChRs). Enhancing α7-type nAChR signaling improves symptoms in Alzheimer’s disease ...and schizophrenia. The pharmaceutical study of α7 receptors is hampered because these receptors do not form their functional pentameric structure in cell lines, and mechanisms that underlie α7 receptor assembly in neurons are not understood. Here, a genomic screening strategy solves this long-standing puzzle and identifies NACHO, a transmembrane protein of neuronal endoplasmic reticulum that mediates assembly of α7 receptors. NACHO promotes α7 protein folding, maturation through the Golgi complex, and expression at the cell surface. Knockdown of NACHO in cultured hippocampal neurons or knockout of NACHO in mice selectively and completely disrupts α7 receptor assembly and abolishes α7 channel function. This work identifies NACHO as an essential, client-specific chaperone for nAChRs and has implications for physiology and disease associated with these widely distributed neurotransmitter receptors.
•Genomic screening identifies NACHO as a mediator of α7 nAChR functional expression•NACHO promotes folding and surface expression of α7 nAChRs•NACHO is a neuronal ER-resident protein that enhances α7 nAChR biogenesis•Alpha7 nAChR assembly and function in brain require NACHO
Gu et al. used high-throughput screening to identify NACHO, a unique mediator of α7 nACh receptor assembly, biogenesis, and membrane insertion. Complete absence of functional α7 receptors in NACHO knockout mice establishes the essential role for this novel mechanism.
PDF
