Two-dimensional (2D) materials have been studied extensively as monolayers, vertical or lateral heterostructures. To achieve functionalization, monolayers are often patterned using soft lithography ...and selectively decorated with molecules. Here we demonstrate the growth of a family of 2D materials that are intrinsically patterned. We demonstrate that a monolayer of PtSe
can be grown on a Pt substrate in the form of a triangular pattern of alternating 1T and 1H phases. Moreover, we show that, in a monolayer of CuSe grown on a Cu substrate, strain relaxation leads to periodic patterns of triangular nanopores with uniform size. Adsorption of different species at preferred pattern sites is also achieved, demonstrating that these materials can serve as templates for selective self-assembly of molecules or nanoclusters, as well as for the functionalization of the same substrate with two different species.
Single-layer transition-metal dichalcogenides (TMDs) receive significant attention due to their intriguing physical properties for both fundamental research and potential applications in electronics, ...optoelectronics, spintronics, catalysis, and so on. Here, we demonstrate the epitaxial growth of high-quality single-crystal, monolayer platinum diselenide (PtSe2), a new member of the layered TMDs family, by a single step of direct selenization of a Pt(111) substrate. A combination of atomic-resolution experimental characterizations and first-principle theoretic calculations reveals the atomic structure of the monolayer PtSe2/Pt(111). Angle-resolved photoemission spectroscopy measurements confirm for the first time the semiconducting electronic structure of monolayer PtSe2 (in contrast to its semimetallic bulk counterpart). The photocatalytic activity of monolayer PtSe2 film is evaluated by a methylene-blue photodegradation experiment, demonstrating its practical application as a promising photocatalyst. Moreover, circular polarization calculations predict that monolayer PtSe2 has also potential applications in valleytronics.
ABSTRACT
During the first three observing runs of the Advanced gravitational-wave detector network, the LIGO/Virgo collaboration detected several black hole binary (BHBH) mergers. As the population ...of detected BHBH mergers grows, it will become possible to constrain different channels for their formation. Here we consider the chemically homogeneous evolution (CHE) channel in close binaries, by performing population synthesis simulations that combine realistic binary models with detailed cosmological calculations of the chemical and star-formation history of the Universe. This allows us to constrain population properties, as well as cosmological and aLIGO/aVirgo detection rates of BHBH mergers formed through this pathway. We predict a BHBH merger rate at redshift zero of $5.8 \textrm {Gpc}^{-3} \textrm {yr}^{-1}$ through the CHE channel, to be compared with aLIGO/aVirgo’s measured rate of ${53.2}_{-28.2}^{+55.8} \text{Gpc}^{-3}\text{yr}^{-1}$, and find that eventual merger systems have BH masses in the range $17{-}43 \,\textrm {M}_{\odot }$ below the pair-instability supernova (PISN) gap, and ${\gt}124 \textrm {M}_{\odot }$ above the PISN gap. We investigate effects of momentum kicks during black hole formation, and calculate cosmological and magnitude limited PISN rates. We also study the effects of high-redshift deviations in the star formation rate. We find that momentum kicks tend to increase delay times of BHBH systems, and our magnitude limited PISN rate estimates indicate that current deep surveys should be able to detect such events. Lastly, we find that our cosmological merger rate estimates change by at most ${\sim}8{{\ \rm per\ cent}}$ for mild deviations of the star formation rate in the early Universe, and by up to ${\sim}40\,\text{per cent}$ for extreme deviations.
Background
Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models. A phase I clinical trial was performed to ...establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma.
Design
Nine subjects received twice-weekly intravenous ascorbate (15–125 g) employing Simon’s accelerated titration design to achieve a targeted post-infusion plasma level of ≥350 mg/dL (≥20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic laboratories, time to progression and overall survival were monitored.
Results
Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 ± 0.02 vs. 0.78 ± 0.09 mg/dL, i.e., 83 vs. 44 μM,
p
< 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (
n
= 4) and dry mouth (
n
= 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least two cycles (8 weeks) of therapy was 13 ± 2 months.
Conclusions
Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.
Aims/hypothesis
In previous studies we have shown that extravasated, modified LDL is associated with pericyte loss, an early feature of diabetic retinopathy (DR). Here we sought to determine detailed ...mechanisms of this LDL-induced pericyte loss.
Methods
Human retinal capillary pericytes (HRCP) were exposed to ‘highly-oxidised glycated’ LDL (HOG-LDL) (a model of extravasated and modified LDL) and to 4-hydroxynonenal or 7-ketocholesterol (components of oxidised LDL), or to native LDL for 1 to 24 h with or without 1 h of pretreatment with inhibitors of the following: (1) the scavenger receptor (polyinosinic acid); (2) oxidative stress (
N
-acetyl cysteine); (3) endoplasmic reticulum (ER) stress (4-phenyl butyric acid); and (4) mitochondrial dysfunction (cyclosporin A). Oxidative stress, ER stress, mitochondrial dysfunction, apoptosis and autophagy were assessed using techniques including western blotting, immunofluorescence, RT-PCR, flow cytometry and TUNEL assay. To assess the relevance of the results in vivo, immunohistochemistry was used to detect the ER stress chaperon, 78 kDa glucose-regulated protein, and the ER sensor, activating transcription factor 6, in retinas from a mouse model of DR that mimics exposure of the retina to elevated glucose and elevated LDL levels, and in retinas from human participants with and without diabetes and DR.
Results
Compared with native LDL, HOG-LDL activated oxidative and ER stress in HRCP, resulting in mitochondrial dysfunction, apoptosis and autophagy. In a mouse model of diabetes and hyperlipidaemia (vs mouse models of either condition alone), retinal ER stress was enhanced. ER stress was also enhanced in diabetic human retina and correlated with the severity of DR.
Conclusions/interpretation
Cell culture, animal, and human data suggest that oxidative stress and ER stress are induced by modified LDL, and are implicated in pericyte loss in DR.
Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 ...December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.
Background:
MicroRNAs (miRNAs) are known to regulate the inflammatory response in various cell types. However, the ability of miRNAs to modulate dendritic cells (DCs) function for allergen ...immunotherapy is unclear.
Objective:
To assess the role of miR‐23b in the regulation of ovalbumin (OVA)‐induced DC differentiation and function and to investigate the related molecular mechanisms.
Methods:
Bone marrow‐derived dendritic cells (BMDCs) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of miRNA expression. After transfection with miR‐23b reagents, DCs were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD4+ T‐cell differentiation. The possible roles of the Notch and NF‐κB signalling pathways were also evaluated. Human monocyte‐derived dendritic cells (MDDCs) were similarly evaluated as well.
Results:
Significant upregulation of miR‐23b was observed in BMDCs pulsed with OVA. Following miR‐23b transfection, BMDCs showed decreased OVA uptake, increased IL‐10 production, decreased IL‐12 production and an enhanced capacity to promote FoxP3+ CD4+ T regulatory cells (Tregs) differentiation. In addition, inactivation of the Notch1 and NF‐κB signalling pathways were observed. Conversely, inhibition of miR‐23b in BMDCs resulted in the opposite effects. In human MDDCs, miRNA23b transfection similarly increased IL‐10 and decreased IL‐12 production, and that treated human MDDCs induced increased FoxP3+ CD4+ T cells.
Conclusion:
Our findings provide evidence that miR‐23b is capable of inducing tolerogenic DC activity and Treg responses in vitro through the inhibition of the Notch1 and NF‐κB signalling pathways; thus, miR‐23b might represent a therapeutic target for the management of allergic diseases.
The combination of the BCL2 inhibitor venetoclax plus obinutuzumab was more effective in the treatment of older medically ill patients with untreated chronic lymphocytic leukemia than was ...chlorambucil plus obinutuzumab. Progression-free survival at 2 years was 88% with venetoclax and 64% with chlorambucil.
Few studies describe the sequence of morphological events that characterize spermiogenesis in birds. In this paper, the clearly observable steps of spermiogenesis are described and illustrated for ...the first time in a commercially important ratite, the ostrich, based on light microscopy of toluidine blue-stained plastic sections. Findings were supplemented and supported by ultrastructural observations, PNA labeling of acrosome development, and immunocytochemical labeling of isolated spermatogenic cells. Spermiogenesis in the ostrich followed the general pattern described in non-passerine birds. Eight steps were identified based on changes in nuclear shape and contents, positioning of the centriolar complex, and acrosome development. Only two steps could be recognized with certainty during development of the round spermatid which contributed to the fewer steps recorded for the ostrich compared to that described in some other bird species. The only lectin that displayed acrosome reactivity was PNA and only for the first three steps of spermiogenesis. This suggests that organizational and/or compositional changes may occur in the acrosome during development and merits further investigation. Immunological labeling provided additional evidence to support the finding of previous studies that the tip of the nucleus in the ostrich is shaped by the forming acrosome and not by the microtubular manchette. To our knowledge, this is the first complete description of spermiogenesis in ostrich and one of few in any avian species. In addition to comparative reproduction and animal science, this work has implications for evolutionary biology as the reported germ cell features provide a bridge between reptile and ratite-avian spermatogenesis.
Aims/hypothesis
Blood–retina barrier leakage in diabetes results in extravasation of plasma lipoproteins. Intra-retinal modified LDLs have been implicated in diabetic retinopathy (DR), but their ...effects on retinal pigment epithelial (RPE) cells and the added effects of extravasated modified HDLs are unknown.
Methods
In human retinas from individuals with and without diabetes and DR, immunohistochemistry was used to detect ApoB, ApoA1 and endoplasmic reticulum (ER) stress markers. In cell culture, human RPE cells were treated with native LDL (N-LDL) or heavily-oxidised glycated LDL (HOG-LDL) with or without pretreatment with native HDL (N-HDL) or heavily-oxidised glycated HDL (HOG-HDL). Cell viability, oxidative stress, ER stress, apoptosis and autophagy were assessed by Cell Counting Kit-8 assay, dichlorofluorescein assay, western blotting, immunofluorescence and TUNEL assay. In separate experiments, RPE cells were treated with lipid oxidation products, 7-ketocholesterol (7-KC, 5–40 μmol/l) or 4-hydroxynonenal (4-HNE, 5–80 μmol/l), with or without pretreatment with N-HDL or HOG-HDL.
Results
ApoB, ApoA1 staining and RPE ER stress were increased in the presence of DR. HOG-LDL but not N-LDL significantly decreased RPE cell viability and increased reactive oxygen species generation, ER stress, apoptosis and autophagy. Similarly, 4-HNE and 7-KC decreased viability and induced ER stress. Pretreatment with N-HDL mitigated these effects, whereas HOG-HDL was less effective by most, but not all, measures.
Conclusions/interpretation
In DR, extravascular modified LDL may promote RPE injury through oxidative stress, ER stress, autophagy and apoptosis. N-HDL has protective effects, but HOG-HDL is less effective. Extravasation and modification of HDL may modulate the injurious effects of extravasated modified LDL on the retinal pigment epithelium.
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