Simple Bronsted acid catalyzed C-H functionalization: efficient access to poly-substituted pyridines

An exceptionally simple and environmentally friendly methodology has been developed for directly functionalizing the benzylic C-H bond of the poly-substituted pyridines with aromatic imines. Simple Bronsted acid catalysts including salicylic acid and TsOH were successfully employed. Different types of poly-substituted pyridines could be efficiently obtained with moderate yields. Traditional ways to such types of pyridines involved the aromatization of the corresponding Hantzsch 1,4-dihydropyridines, while this method greatly simplified the synthetic procedures. (C) 2016 Elsevier Ltd. All rights reserved

Impact of the Kuroshio intrusion on the nutrient inventory in the upper northern South China Sea: insights from an isopycnal mixing model

Based on four cruises covering a seasonal cycle in 2009-2011, we examined the impact of the Kuroshio intrusion, featured by extremely oligotrophic waters, on the nutrient inventory in the central northern South China Sea (NSCS). The nutrient inventory in the upper 100m of the water column in the study area ranged from similar to 200 to similar to 290 mmol m(-2) for N+N (nitrate plus nitrite), from similar to 13 to similar to 24 mmol m(-2) for soluble reactive phosphate and from similar to 210 to similar to 430 mmol m(-2) for silicic acid. The nutrient inventory showed a clear seasonal pattern with the highest value appearing in summer, while the N+N inventory in spring and winter had a reduction of similar to 13 and similar to 30 %, respectively, relative to that in summer. To quantify the extent of the Kuroshio intrusion, an isopycnal mixing model was adopted to derive the proportional contribution of water masses from the SCS proper and the Kuroshio along individual isopycnal surfaces. The derived mixing ratio along the isopycnal plane was then employed to predict the genuine gradients of nutrients under the assumption of no biogeochemical alteration. These predicted nutrient concentrations, denoted as N-m, are solely determined by water mass mixing. Results showed that the nutrient inventory in the upper 100m of the NSCS was overall negatively correlated to the Kuroshio water fraction, suggesting that the Kuroshio intrusion significantly influenced the nutrient distribution in the SCS and its seasonal variation. The difference between the observed nutrient concentrations and their corresponding Nm allowed us to further quantify the nutrient removal/addition associated with the biogeochemical processes on top of the water mass mixing. We revealed that the nutrients in the upper 100m of the water column had a net consumption in both winter and spring but a net addition in fall.Based on four cruises covering a seasonal cycle in 2009-2011, we examined the impact of the Kuroshio intrusion, featured by extremely oligotrophic waters, on the nutrient inventory in the central northern South China Sea (NSCS). The nutrient inventory in the upper 100m of the water column in the study area ranged from similar to 200 to similar to 290 mmol m(-2) for N+N (nitrate plus nitrite), from similar to 13 to similar to 24 mmol m(-2) for soluble reactive phosphate and from similar to 210 to similar to 430 mmol m(-2) for silicic acid. The nutrient inventory showed a clear seasonal pattern with the highest value appearing in summer, while the N+N inventory in spring and winter had a reduction of similar to 13 and similar to 30 %, respectively, relative to that in summer. To quantify the extent of the Kuroshio intrusion, an isopycnal mixing model was adopted to derive the proportional contribution of water masses from the SCS proper and the Kuroshio along individual isopycnal surfaces. The derived mixing ratio along the isopycnal plane was then employed to predict the genuine gradients of nutrients under the assumption of no biogeochemical alteration. These predicted nutrient concentrations, denoted as N-m, are solely determined by water mass mixing. Results showed that the nutrient inventory in the upper 100m of the NSCS was overall negatively correlated to the Kuroshio water fraction, suggesting that the Kuroshio intrusion significantly influenced the nutrient distribution in the SCS and its seasonal variation. The difference between the observed nutrient concentrations and their corresponding Nm allowed us to further quantify the nutrient removal/addition associated with the biogeochemical processes on top of the water mass mixing. We revealed that the nutrients in the upper 100m of the water column had a net consumption in both winter and spring but a net addition in fall

Differential regulation of morphology and stemness of mouse embryonic stem cells by substrate stiffness and topography

The maintenance of stem cell pluripotency or sternness is crucial to embryonic development and differentiation. The mechanical or physical microenvironment of stem cells, which includes extracellular matrix stiffness and topography, regulates cell morphology and stemness. Although a growing body of evidence has shown the importance of these factors in stem cell differentiation, the impact of these biophysical or biomechanical regulators remains insufficiently characterized. In the present study, we applied a micro-fabricated polyacrylamide hydrogel substrate with two elasticities and three topographies to systematically test the morphology, proliferation, and sternness of mESCs. The independent or combined impact of the two factors on specific cell functions was analyzed. Cells are able to grow effectively on both polystyrene and polyacrylamide substrates in the absence of feeder cells. Substrate stiffness is predominant in preserving stemness by enhancing Oct-4 and Nanog expression on a soft polyacrylamide substrate. Topography is also a critical factor for manipulating sternness via the formation of a relatively flattened colony on a groove or pillar substrate and a spheroid colony on a hexagonal substrate. Although topography is less effective on soft substrates, it plays a role in retaining cell sternness on stiff, hexagonal or pillar-shaped substrates. mESCs also form, in a timely manner, a 3D structure on groove or hexagonal substrates. These results further the understanding of stem cell morphology and stemness in a microenvironment that mimics physiological conditions. (C) 2014 Elsevier Ltd. All rights reserved

Observation of the induced pressure in a hybrid micro/nano-channel

This paper studies the flow characteristics in micro/nano-channels subjected to an applied electric field. The nano-channel flow was observed by means of the fluorescence Calcein. A Fluorescence Concentration Gradient Interface (FCGI) was observed across the nano-channel array. The front of the FCGI was shown to have an analogous parabolic shape. The propagation of this interface reflects indirectly the induced pressure at the micro/nano-channel junction, where the enrichment-depletion processes are known to take place. This induced pressure was predicted by numerical simulations, and this paper gives the first experimental evidence

Bone Marrow-Derived Microglia-Based Neurturin Delivery Protects Against Dopaminergic Neurodegeneration in a Mouse Model of Parkinson\u27s Disease

Although neurotrophic factors have long been recognized as potent agents for protecting against neuronal degeneration, clinical success in treating Parkinson\u27s disease and other neurodegenerative disorders has been hindered by difficulties in delivery of trophic factors across the blood brain barrier (BBB). Bone marrow hematopoietic stem cell-based gene therapy is emerging as a promising tool for overcoming drug delivery problems, as myeloid cells can cross the BBB and are recruited in large numbers to sites of neurodegeneration, where they become activated microglia that can secrete trophic factors. We tested the efficacy of bone marrow-derived microglial delivery of neurturin (NTN) in protecting dopaminergic neurons against neurotoxin-induced death in mice. Bone marrow cells were transduced ex vivo with lentivirus expressing the NTN gene driven by a synthetic macrophage-specific promoter. Infected bone marrow cells were then collected and transplanted into recipient animals. Eight weeks after transplantation, the mice were injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropuridine (MPTP) for seven days to induce dopaminergic neurodegeneration. Microglia-mediated NTN delivery dramatically ameliorated MPTP-induced degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and their terminals in the striatum. Microglia-mediated NTN delivery also induced significant recovery of synaptic marker staining in the striatum of MPTP-treated animals. Functionally, NTN treatment restored MPTP-induced decline in general activity, rearing behavior, and food intake. Thus, bone marrow-derived microglia can serve as cellular vehicles for sustained delivery of neurotrophic factors capable of mitigating dopaminergic injury

A physico-chemical model of seepage flows in reservoirs during alkaline flooding

In the present paper, we have established a physico-chemical model to describe seepage flows in reservoirs for enhancement of oil recovery (EOR) during alkaline flooding, focusing on the examination of rock /alkaline interation and scale formation. Numerical simulation shows that a few percent enhancement in oil recovery is possible when the alkaline flood technique is applied. However, the reduction of rock permeability for strong alkaline flood is more serious than that for weak alkaline flood. Therefore, the latter should be recommended as a candidate in alkaline flooding

Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells

The physiological microenvironment of the stem cell niche, including the three factors of stiffness, topography, and dimension, is crucial to stem cell proliferation and differentiation. Although a growing body of evidence is present to elucidate the importance of these factors individually, the interaction of the biophysical parameters of the factors remains insufficiently characterized, particularly for stem cells. To address this issue fully, we applied a micro-fabricated polyacrylamide hydrogel substrate with two elasticities, two topographies, and three dimensions to systematically test proliferation, morphology and spreading, differentiation, and cytoskeletal re-organization of rat bone marrow mesenchymal stem cells (rBMSCs) on twelve cases. An isolated but not combinatory impact of the factors was found regarding the specific functions. Substrate stiffness or dimension is predominant in regulating cell proliferation by fostering cell growth on stiff, unevenly dimensioned substrate. Topography is a key factor for manipulating cell morphology and spreading via the formation of a large spherical shape in a pillar substrate but not in a grooved substrate. Although stiffness leads to osteogenic or neuronal differentiation of rBMSCs on a stiff or soft substrate, respectively, topography or dimension also plays a lesser role in directing cell differentiation. Neither an isolated effect nor a combinatory effect was found for actin or tubulin expression, whereas a seemingly combinatory effect of topography and dimension was found in manipulating vimentin expression. These results further the understandings of stem cell proliferation, morphology, and differentiation in a physiologically mimicking microenvironment

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe