Stress, a prevalent experience in modern society, is a major risk factor for many psychiatric disorders. Although sensorimotor abnormalities are often present in these disorders, little is known ...about how stress affects the sensory cortex. Combining behavioral analyses with in vivo synaptic imaging, we show that stressful experiences lead to progressive, clustered loss of dendritic spines along the apical dendrites of layer (L) 5 pyramidal neurons (PNs) in the mouse barrel cortex, and such spine loss closely associates with deteriorated performance in a whisker-dependent texture discrimination task. Furthermore, the activity of parvalbumin-expressing inhibitory interneurons (PV+ INs) decreases in the stressed mouse due to reduced excitability of these neurons. Importantly, both behavioral defects and structural changes of L5 PNs are prevented by selective pharmacogenetic activation of PV+INs in the barrel cortex during stress. Finally, stressed mice raised under environmental enrichment (EE) maintain normal activation of PV+ INs, normal texture discrimination, and L5 PN spine dynamics similar to unstressed EE mice. Our findings suggest that the PV+ inhibitory circuit is crucial for normal synaptic dynamics in the mouse barrel cortex and sensory function. Pharmacological, pharmacogenetic and environmental approaches to prevent stress-induced maladaptive behaviors and synaptic malfunctions converge on the regulation of PV+ IN activity, pointing to a potential therapeutic target for stress-related disorders.
For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream ...analyses. Here we present SUITOR (Selecting the nUmber of mutatIonal signaTures thrOugh cRoss-validation), an unsupervised cross-validation method that requires little assumptions and no numerical approximations to select the optimal number of signatures without overfitting the data. In vitro studies and in silico simulations demonstrated that SUITOR can correctly identify signatures, some of which were missed by other widely used methods. Applied to 2,540 whole-genome sequenced tumors across 22 cancer types, SUITOR selected signatures with the smallest prediction errors and almost all signatures of breast cancer selected by SUITOR were validated in an independent breast cancer study. SUITOR is a powerful tool to select the optimal number of mutational signatures, facilitating downstream analyses with etiological or therapeutic importance.
Al2O3 and TiO2 atomic layer deposition (ALD) were employed to develop an ultrathin barrier film on copper to prevent water corrosion. The strategy was to utilize Al2O3 ALD as a pinhole-free barrier ...and to protect the Al2O3 ALD using TiO2 ALD. An initial set of experiments was performed at 177 °C to establish that Al2O3 ALD could nucleate on copper and produce a high-quality Al2O3 film. In situ quartz crystal microbalance (QCM) measurements verified that Al2O3 ALD nucleated and grew efficiently on copper-plated quartz crystals at 177 °C using trimethylaluminum (TMA) and water as the reactants. An electroplating technique also established that the Al2O3 ALD films had a low defect density. A second set of experiments was performed for ALD at 120 °C to study the ability of ALD films to prevent copper corrosion. These experiments revealed that an Al2O3 ALD film alone was insufficient to prevent copper corrosion because of the dissolution of the Al2O3 film in water. Subsequently, TiO2 ALD was explored on copper at 120 °C using TiCl4 and water as the reactants. The resulting TiO2 films also did not prevent the water corrosion of copper. Fortunately, Al2O3 films with a TiO2 capping layer were much more resilient to dissolution in water and prevented the water corrosion of copper. Optical microscopy images revealed that TiO2 capping layers as thin as 200 Å on Al2O3 adhesion layers could prevent copper corrosion in water at 90 °C for ∼80 days. In contrast, the copper corroded almost immediately in water at 90 °C for Al2O3 and ZnO films by themselves on copper. Ellipsometer measurements revealed that Al2O3 films with a thickness of ∼200 Å and ZnO films with a thickness of ∼250 Å dissolved in water at 90 °C in ∼10 days. In contrast, the ellipsometer measurements confirmed that the TiO2 capping layers with thicknesses of ∼200 Å on the Al2O3 adhesion layers protected the copper for ∼80 days in water at 90 °C. The TiO2 ALD coatings were also hydrophilic and facilitated H2O wetting to copper wire mesh substrates.
Copper oxides have been of considerable interest as electrocatalysts for CO2 reduction (CO2R) in aqueous electrolytes. However, their role as an active catalyst in reducing the required overpotential ...and improving the selectivity of reaction compared with that of polycrystalline copper remains controversial. Here, we introduce the use of selected-ion flow tube mass spectrometry, in concert with chronopotentiometry, in situ Raman spectroscopy, and computational modeling, to investigate CO2R on Cu2O nanoneedles, Cu2O nanocrystals, and Cu2O nanoparticles. We show experimentally that the selective formation of gaseous C2 products (i.e., ethylene) in CO2R is preceded by the reduction of the copper oxide (Cu2OR) surface to metallic copper. On the basis of density functional theory modeling, CO2R products are not formed as long as Cu2O is present at the surface because Cu2OR is kinetically and energetically more favorable than CO2R.
Additive manufacturing technique is a promising approach for fabricating cellular bone substitutes such as trabecular and cortical bones because of the ability to adjust process parameters to ...fabricate different shapes and inner structures. Considering the long term safe application in human body, the metallic cellular implants are expected to exhibit superior fatigue property. The objective of the study was to study the influence of cell shape on the compressive fatigue behavior of Ti-6Al-4V mesh arrays fabricated by electron beam melting. The results indicated that the underlying fatigue mechanism for the three kinds of meshes (cubic, G7 and rhombic dodecahedron) is the interaction of cyclic ratcheting and fatigue crack growth on the struts, which is closely related to cumulative effect of buckling and bending deformation of the strut. By increasing the buckling deformation on the struts through cell shape design, the cyclic ratcheting rate of the meshes during cyclic deformation was decreased and accordingly, the compressive fatigue strength was increased. With increasing bending deformation of struts, fatigue crack growth in struts contributed more to the fatigue damage of meshes. Rough surface and pores contained in the struts significantly deteriorated the compressive fatigue strength of the struts. By optimizing the buckling and bending deformation through cell shape design, Ti-6Al-4V alloy cellular solids with high fatigue strength and low modulus can be fabricated by the EBM technique.
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•Ti-6Al-4V meshes with different cell shapes were fabricated by EBM technique.•The fatigue behavior of these meshes was strongly influenced by the cell shapes.•The fatigue mechanism is the interaction of cyclic ratcheting and crack growth.•Cyclic ratcheting dominated the compressive fatigue processes of these meshes.•Fatigue properties can be improved by optimizing buckling and bending deformations.
We report multistate trajectory simulations, including coherence, decoherence, and multidimensional tunneling, of phenol photodissociation dynamics. The calculations are based on full-dimensional ...anchor-points reactive potential surfaces and state couplings fit to electronic structure calculations including dynamical correlation with an augmented correlation-consistent polarized valence double-ζ basis set. The calculations successfully reproduce the experimentally observed bimodal character of the total kinetic energy release spectra and confirm the interpretation of the most recent experiments that the photodissociation process is dominated by tunneling. Analysis of the trajectories uncovers an unexpected dissociation pathway for one quantum excitation of the O–H stretching mode of the S1 state, namely, tunneling in a coherent mixture of states starting in a smaller R OH (∼0.9–1.0 Å) region than has previously been invoked. The simulations also show that most trajectories do not pass close to the S1–S2 conical intersection (they have a minimum gap greater than 0.6 eV), they provide statistics on the out-of-plane angles at the locations of the minimum energy adiabatic gap, and they reveal information about which vibrational modes are most highly activated in the products.
The viable but non culturable (VBNC) state is a condition in which bacterial cells are viable and metabolically active, but resistant to cultivation using a routine growth medium. We investigated the ...ability of V. parahaemolyticus to form VBNC cells, and to subsequently become resuscitated. The ability to control VBNC cell formation in the laboratory allowed us to selectively isolate VBNC cells using fluorescence activated cell sorting, and to differentiate subpopulations based on their metabolic activity, cell shape and the ability to cause disease in Galleria mellonella. Our results showed that two subpopulations (P1 and P2) of V. parahaemolyticus VBNC cells exist and can remain dormant in the VBNC state for long periods. VBNC subpopulation P2, had a better fitness for survival under stressful conditions and showed 100% revival under favourable conditions. Proteomic analysis of these subpopulations (at two different time points: 12 days (T12) and 50 days (T50) post VBNC) revealed that the proteome of P2 was more similar to that of the starting microcosm culture (T0) than the proteome of P1. Proteins that were significantly up or down-regulated between the different VBNC populations were identified and differentially regulated proteins were assigned into 23 functional groups, the majority being assigned to metabolism functional categories. A lactate dehydrogenase (lldD) protein, responsible for converting lactate to pyruvate, was significantly upregulated in all subpopulations of VBNC cells. Deletion of the lactate dehydrogenase (RIMD2210633:ΔlldD) gene caused cells to enter the VBNC state significantly more quickly compared to the wild-type, and adding lactate to VBNC cells aided their resuscitation and extended the resuscitation window. Addition of pyruvate to the RIMD2210633:ΔlldD strain restored the wild-type VBNC formation profile. This study suggests that lactate dehydrogenase may play a role in regulating the VBNC state.
The subunit vaccine SV1 (20 μg F1 + 10 μg rV270) has been identified as the optimal formulation in mice, which provided a good protection against plague in mice, guinea pigs and rabbits. To compare ...SV1 and SV2 (200 μg F1 + 100 μg rV270) with live attenuated vaccine EV76, antibody responses, protective efficacy, cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-10 and IL-12) production, CD4/CD8 ratio and CD69⁺ T-cell activation marker were determined in sera of the immunized Chinese-origin rhesus macaques, Macaca mulatta. The immunized animals with SV1 or SV2 developed higher anti-rV270 IgG titre, while those immunized with EV76 elicited a negligible IgG to V antigen, indicating that subunit vaccine (SV) had an advantage over EV76 in terms of the indispensable role of anti-V antibody against Yersinia pestis. There was no significant antibody titre difference between SV1 and SV2, suggesting that the immune response may have been saturated at the dose level of SV1. There were no statistical changes for CD4/CD8 ratios, IL-4 and CD69 levels between the three-vaccine immunized groups. However, a significant higher level of IL-12 was observed in the EV76 immunized animals, indicating that EV76 had an advantage over SV in respect of cellular immunity. Complete protection was observed for the immunized animals with SV and EV76, revealing that SV has a similar protective efficacy with EV76 against 6 x 10⁶ CFU of Y. pestis challenge by subcutaneous route in Chinese-origin rhesus macaques.
Chaotic Dirac Billiard in Graphene Quantum Dots Ponomarenko, L.A; Schedin, F; Katsnelson, M.I ...
Science (American Association for the Advancement of Science),
04/2008, Letnik:
320, Številka:
5874
Journal Article
Recenzirano
Odprti dostop
The exceptional electronic properties of graphene, with its charge carriers mimicking relativistic quantum particles and its formidable potential in various applications, have ensured a rapid growth ...of interest in this new material. We report on electron transport in quantum dot devices carved entirely from graphene. At large sizes (>100 nanometers), they behave as conventional single-electron transistors, exhibiting periodic Coulomb blockade peaks. For quantum dots smaller than 100 nanometers, the peaks become strongly nonperiodic, indicating a major contribution of quantum confinement. Random peak spacing and its statistics are well described by the theory of chaotic neutrino billiards. Short constrictions of only a few nanometers in width remain conductive and reveal a confinement gap of up to 0.5 electron volt, demonstrating the possibility of molecular-scale electronics based on graphene.
In recent years, cellular metallic materials have attracted significant interest for biomedical applications. However, mutually opposing requirements of porous architecture and mechanical strength in ...conjunction with the high energy absorption capability have restricted their use. Here, we illustrate that electron beam melting can fabricate functionally graded Ti-6Al-4V alloy interconnected mesh structures with a combination of low density (0.5–2 g/cm3), high fatigue strength (∼70 MPa) and energy absorption (∼50 MJ/mg), which is superior to the ordinary uniform cellular structures. The underlying fundamental mechanisms governing the compressive and fatigue behavior of the graded cellular structures are elucidated via in situ tomography experiments and digital volume correlation analyses. It is underscored that during cyclic deformation, the stress can be continuously redistributed because of inhomogeneous mechanical properties and crack formation in constituent meshes, thereby resulting in variation of cyclic ratcheting rate for the graded cellular structures.
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