Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the endoplasmic reticulum (ER) to mitochondria. Transfer is thought to occur at regions of close contact of ...these organelles and to be nonvesicular, but the mechanism is not known. Here we used a novel genetic screen in S. cerevisiae to identify mutants with defects in lipid exchange between the ER and mitochondria. We show that a strain missing multiple components of the conserved ER membrane protein complex (EMC) has decreased phosphatidylserine (PS) transfer from the ER to mitochondria. Mitochondria from this strain have significantly reduced levels of PS and its derivative phosphatidylethanolamine (PE). Cells lacking EMC proteins and the ER-mitochondria tethering complex called ERMES (the ER-mitochondria encounter structure) are inviable, suggesting that the EMC also functions as a tether. These defects are corrected by expression of an engineered ER-mitochondrial tethering protein that artificially tethers the ER to mitochondria. EMC mutants have a significant reduction in the amount of ER tethered to mitochondria even though ERMES remained intact in these mutants, suggesting that the EMC performs an additional tethering function to ERMES. We find that all Emc proteins interact with the mitochondrial translocase of the outer membrane (TOM) complex protein Tom5 and this interaction is important for PS transfer and cell growth, suggesting that the EMC forms a tether by associating with the TOM complex. Together, our findings support that the EMC tethers ER to mitochondria, which is required for phospholipid synthesis and cell growth.
Tumor vasculature is characterized by a variety of abnormalities including irregular architecture, poor lymphatic drainage, and the upregulation of factors that increase the paracellular ...permeability. The increased permeability is important in mediating the uptake of an intravenously administered drug in a solid tumor and is known as the enhanced permeation and retention (EPR) effect. Studies in animal models have demonstrated a cut-off size of 500 nm - 1 µm for molecules or nanoparticles to extravasate into a tumor, however, surprisingly little is known about the kinetics of the EPR effect. Here we present a pharmacokinetic model to quantitatively assess the influence of the EPR effect on the uptake of a drug into a solid tumor. We use pharmacokinetic data for Doxil and doxorubicin from human clinical trials to illustrate how the EPR effect influences tumor uptake. This model provides a quantitative framework to guide preclinical trials of new chemotherapies and ultimately to develop design rules that can increase targeting efficiency and decrease unwanted side effects in normal tissue.
Highly uniform single crystal ultrathin CsPbBr3 nanowires (NWs) with diameter of 2.2 ± 0.2 nm and length up to several microns were successfully synthesized and purified using a catalyst-free ...colloidal synthesis method followed by a stepwise purification strategy. The NWs have bright photoluminescence (PL) with a photoluminescence quantum yield (PLQY) of about 30% after surface treatment. Large blue-shifted UV–vis absorption and PL spectra have been observed due to strong two-dimensional quantum confinement effects. A small angle X-ray scattering (SAXS) pattern shows the periodic packing of the ultrathin NWs along the radial direction, demonstrates the narrow radial distribution of the wires, and emphasizes the deep intercalation of the surfactants. Despite the extreme aspect ratios of the ultrathin NWs, their composition and the resulting optical properties can be readily tuned by an anion-exchange reaction with good morphology preservation. These bright ultrathin NWs may be used as a model system to study strong quantum confinement effects in a one-dimensional halide perovskite system.
The rapidly growing field of nanoscale lasers can be advanced through the discovery of new, tunable light sources. The emission wavelength tunability demonstrated in perovskite materials is an ...attractive property for nanoscale lasers. Whereas organic–inorganic lead halide perovskite materials are known for their instability, cesium lead halides offer a robust alternative without sacrificing emission tunability or ease of synthesis. Here, we report the low-temperature, solution-phase growth of cesium lead halide nanowires exhibiting low-threshold lasing and high stability. The as-grown nanowires are single crystalline with well-formed facets, and act as high-quality laser cavities. The nanowires display excellent stability while stored and handled under ambient conditions over the course of weeks. Upon optical excitation, Fabry–Pérot lasing occurs in CsPbBr₃ nanowires with an onset of 5 μJ cm−2 with the nanowire cavity displaying a maximum quality factor of 1,009 ± 5. Lasing under constant, pulsed excitation can be maintained for over 1 h, the equivalent of 10⁹ excitation cycles, and lasing persists upon exposure to ambient atmosphere. Wavelength tunability in the green and blue regions of the spectrum in conjunction with excellent stability makes these nanowire lasers attractive for device fabrication.
Cerebral infarction is a commonly observed radiological finding in the absence of corresponding, clinical symptomatology, the so-called silent brain infarction (SBI). SBIs are a relatively new ...consideration as improved imaging has facilitated recognition of their occurrence. However, the true incidence, prevalence and risk factors associated with SBI remain controversial.
Systematic searches of the Medline and EMBASE databases from 1946 to December 2013 were performed to identify original studies of population-based adult cohorts derived from community surveys and routine health screening that reported the incidence and prevalence of magnetic resonance imaging (MRI)-determined SBI.
The prevalence of SBI ranges from 5% to 62% with most studies reported in the 10% to 20% range. Longitudinal studies suggest an annual incidence of between 2% and 4%. A strong association was seen to exist between epidemiological estimates of SBI and age of the population assessed. Hypertension, carotid stenosis, chronic kidney disease and metabolic syndrome all showed a strong association with SBI. Heart failure, coronary artery disease, hyperhomocysteinemia and obstructive sleep apnea are also likely of significance. However, any association between SBI and gender, ethnicity, tobacco or alcohol consumption, obesity, dyslipidemia, atrial fibrillation and diabetes mellitus remains unclear.
SBI is a remarkably common phenomenon and endemic among older people. This systematic review supports the association of a number of traditional vascular risk factors, but also highlights disparities between clinically apparent and silent strokes, potentially suggesting important differences in pathophysiology and warranting further investigation.
The nano-TiO2 modified foamed wheat straw fiber/polypropylene (F-WSFs/PP) hierarchical composites were fabricated by a hot-extrusion process. To improve the dispersion of nano-TiO2 and increase the ...compatibility between WSFs and PP, the WSFs were immersed in 1–5 wt% unmodified and coupling agents (A171 or KH550)-modified nano-TiO2 suspensions by vacuum pressure. The size, crystallinity and composition of modified nano-TiO2 were analyzed by Laser particle size analyzer (LS), XRD and FT-IR. Moreover, the modification mechanism was clarified to understand interface interaction between WSFs and PP. SEM results showed that nano-TiO2 was deposited on the WSFs surfaces. UV–Vis showed that WSFs treated with modified-TiO2 exhibited excellent UV-shielding properties in the range of 100–200 nm. Mechanical testing indicated that WSFs treated with 4% KH550-modified nano-TiO2 exhibited the highest flexural (29.27 MPa), tensile (14.38 MPa), and impact (4.55 kJ/m2) strengths. Overall, the TiO2-KH550 modified F-WSFs/PP composites excellent UV-shielding properties and mechanical strengths.
Controlling the flow of thermal energy is crucial to numerous applications ranging from microelectronic devices to energy storage and energy conversion devices. Here, we report ultralow lattice ...thermal conductivities of solution-synthesized, single-crystalline all-inorganic halide perovskite nanowires composed of CsPbI₃ (0.45 ± 0.05 W·m−1·K−1), CsPbBr₃ (0.42 ± 0.04 W·m−1·K−1), and CsSnI₃ (0.38 ± 0.04 W·m−1·K−1). We attribute this ultralow thermal conductivity to the cluster rattling mechanism, wherein strong optical–acoustic phonon scatterings are driven by a mixture of 0D/1D/2D collective motions. Remarkably, CsSnI₃ possesses a rare combination of ultralow thermal conductivity, high electrical conductivity (282 S·cm−1), and high hole mobility (394 cm²·V−1·s−1). The unique thermal transport properties in all-inorganic halide perovskites hold promise for diverse applications such as phononic and thermoelectric devices. Furthermore, the insights obtained from this work suggest an opportunity to discover low thermal conductivity materials among unexplored inorganic crystals beyond caged and layered structures.
Classification of data with imbalanced class distribution has posed a significant drawback of the performance attainable by most standard classifier learning algorithms, which assume a relatively ...balanced class distribution and equal misclassification costs. The significant difficulty and frequent occurrence of the class imbalance problem indicate the need for extra research efforts. The objective of this paper is to investigate meta-techniques applicable to most classifier learning algorithms, with the aim to advance the classification of imbalanced data. The AdaBoost algorithm is reported as a successful meta-technique for improving classification accuracy. The insight gained from a comprehensive analysis of the AdaBoost algorithm in terms of its advantages and shortcomings in tacking the class imbalance problem leads to the exploration of three cost-sensitive boosting algorithms, which are developed by introducing cost items into the learning framework of AdaBoost. Further analysis shows that one of the proposed algorithms tallies with the stagewise additive modelling in statistics to minimize the cost exponential loss. These boosting algorithms are also studied with respect to their weighting strategies towards different types of samples, and their effectiveness in identifying rare cases through experiments on several real world medical data sets, where the class imbalance problem prevails.
Methods to visualize metastasis exist, but additional tools to better define the biologic and physical processes underlying invasion and intravasation are still needed. One difficulty in studying ...metastasis stems from the complexity of the interface between the tumor microenvironment and the vascular system. Here, we report the development of an investigational platform that positions tumor cells next to an artificial vessel embedded in an extracellular matrix. On this platform, we used live-cell fluorescence microscopy to analyze the complex interplay between metastatic cancer cells and a functional artificial microvessel that was lined with endothelial cells. The platform recapitulated known interactions, and its use demonstrated the capabilities for a systematic study of novel physical and biologic parameters involved in invasion and intravasation. In summary, our work offers an important new tool to advance knowledge about metastasis and candidate antimetastatic therapies.
Organic-inorganic hybrid perovskites, which have proved to be promising semiconductor materials for photovoltaic applications, have been made into atomically thin two-dimensional (2D) sheets. We ...report the solution-phase growth of single- and few-unit-cell-thick single-crystalline 2D hybrid perovskites of (C4H9NH3)2PbBr4 with well-defined square shape and large size. In contrast to other 2D materials, the hybrid perovskite sheets exhibit an unusual structural relaxation, and this structural change leads to a band gap shift as compared to the bulk crystal. The high-quality 2D crystals exhibit efficient photoluminescence, and color tuning could be achieved by changing sheet thickness as well as composition via the synthesis of related materials.
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