In this review we investigate the use of complex ester fragment couplings within natural product total synthesis campaigns. We first outline the different biosynthetic and chemical strategies for ...performing complex ester couplings and on this mechanistic background we then present and discuss a collection of successful examples from the literature.
Understanding the motion of magnetic skyrmions is essential if they are to be used as information carriers in devices. It is now shown that topological confinement endows the skyrmions with an ...unexpectedly large mass, which plays a key role in their dynamics.
The onset of alcoholic liver disease （ALD） is initiated by different cell types in the liver and a number of different factors including： products derived from ethanol-induced inflammation, ethanol ...metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide （LPS） has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflammation and fibrosis, and play a role in the development and/or progression of ALD.
Microsomal glutathione transferase （MGST1, EC 2.5.1.18） is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic ...electrophile intermediates and lipophilic hydroperoxides through its glutathione dependent transferase and peroxidase activities. It is expressed in high amounts in the liver, located both in the endoplasmic reticulum and the inner and outer mitochondrial membranes. This enzyme is activated by oxidative stress. Binding of GSH and modification of cysteine 49 （the oxidative stress sensor） has been shown to increase activation and induce conformational changes in the enzyme. These changes have either been shown to enhance the protective effect ascribed to this enzyme or have been shown to contribute to cell death through mitochondrial permeability transition pore formation. The purpose of this review is to elucidate how one enzyme found in two places in the cell subjected to the same conditions of oxidative stress could both help protect against and contribute to reactive oxygen species-induced liver injury.
During ultrafast demagnetization of a magnetically ordered solid, angular momentum has to be transferred between the spins, electrons, and phonons in the system on femto- and picosecond timescales. ...Although the intrinsic spin-transfer mechanisms are intensely debated, additional extrinsic mechanisms arising due to nanoscale heterogeneity have only recently entered the discussion. Here we use femtosecond X-ray pulses from a free-electron laser to study thin film samples with magnetic domain patterns. We observe an infrared-pump-induced change of the spin structure within the domain walls on the sub-picosecond timescale. This domain-topography-dependent contribution connects the intrinsic demagnetization process in each domain with spin-transport processes across the domain walls, demonstrating the importance of spin-dependent electron transport between differently magnetized regions as an ultrafast demagnetization channel. This pathway exists independent from structural inhomogeneities such as chemical interfaces, and gives rise to an ultrafast spatially varying response to optical pump pulses.
The influence on ultrafast demagnetization dynamics of metallic nano-structured gratings deposited on thin films of magnetic Co/Pt multilayers is investigated by the time-resolved optical Kerr ...effect. Depending on the polarization of the pump pulse, a pronounced enhancement of the demagnetization amplitude is found. Calculation of the inhomogeneous optical field distribution due to plasmon interaction and time-dependent solutions of the coupled electron, lattice, and spin temperatures in two dimensions show good agreement with the experimental data, as well as giving evidence of non-local demagnetization dynamics due to electron diffusion.
The use of insecticide-treated nets has lately attracted scientific interest for the management of mosquitoes and related species, as well as for crop pest control and the protection of stored ...agricultural commodities. In our study, the effect of Carifend
®
, an alpha-cypermethrin-coated polyester net, on adults of the two most important stored-tobacco insect pests,
Lasioderma serricorne
and
Ephestia elutella,
was evaluated in laboratory bioassays. Carifend
®
was applied to the bottom of plastic Petri dishes, whereas an additional series of dishes with net material without insecticide was also prepared and served as control. Twenty beetles or moths of mixed sex were placed in each dish. Insects were exposed to the substrates for 1, 5, 15, 30, 60, 90, 120 and 240 min and for 12 and 24 h. Immediate mortality and knockdown effect were measured after each exposure. Afterward, all surviving individuals were placed in untreated plastic dishes and delayed mortality, as well as percentage of knocked down insects, were counted after 1, 3, 5 and 7 days. Immediate mortality was very low for both species tested, even after 24 h of exposure. In contrast, immediate knockdown was high, especially for exposure intervals longer than 60 min. After insect removal from dishes with Carifend
®
, the high knockdown percentages were gradually transformed in most cases to delayed mortality. Based on our results, Carifend
®
can provide a satisfactory level of protection for stored tobacco against these two major tobacco insect pests, at least at the conditions tested here.
Sensor networks are gaining a central role in the research community. This paper addresses some of the issues arising from the use of sensor networks in control applications. Classical control theory ...proves to be insufficient in modeling distributed control problems where issues of communication delay, jitter, and time synchronization between components are not negligible. After discussing our hardware and software platform and our target application, we review useful models of computation and then suggest a mixed model for design, analysis, and synthesis of control algorithms within sensor networks. We present a hierarchical model composed of continuous time-trigger components at the low level and discrete event-triggered components at the high level.
Single‐cell flow cytometric techniques have been indispensable to improving our understanding of the phenotype and function of immune cell subsets that are important in both rejection and tolerance ...after transplant. Mass cytometry, or cytometry by time of flight, is a single‐cell–based platform that utilizes antibodies conjugated to rare heavy metal ions for analysis of cellular proteins by a time‐of‐flight mass spectrometer. This new technology allows for the evaluation of >40 simultaneous cellular parameters in a single sample because the limitation of spectral overlap, seen in conventional flow cytometry, is eliminated. In this review, we discuss the current state of mass cytometry, describe the advantages and disadvantages compared with multiparameter flow cytometry, introduce novel methods of high‐dimensional data analysis and visualization, and review some recent studies using mass cytometry to profile the immune systems of healthy people and transplant recipients.
This review discusses the current state of mass cytometry, the methods of data analysis, and potential applications of this technology to both basic science and clinical studies in transplantation.
Epstein–Barr virus (EBV) is a γ‐herpesvirus that is linked to the development of posttransplant lymphoproliferative disorder (PTLD) in solid organ recipients. We previously demonstrated that EBV+ B ...cell lymphoma cell lines isolated from patients with PTLD produce human IL‐10 as an autocrine growth factor. However, little is known regarding IL‐10 regulation in B cells. Here we show that EBV infection markedly alters the expression of host B cell microRNA, a class of small noncoding RNA that is an important regulator of transcriptional and posttranscriptional gene expression. Gene arrays reveal unique microRNA profiles in EBV+ B cell lymphoma lines from patients with PTLD, compared to normal B cells or in vitro generated EBV+ lymphoblastoid cell lines. We show that microRNA‐194 expression is uniquely suppressed in EBV+ B cell lines from PTLD patients and that the 3'untranslated region of IL‐10 is targeted by microRNA‐194. Overexpression of microRNA‐194 attenuates IL‐10 production and increases apoptosis of EBV+ B cell lymphoma lines. Together, these data indicate that EBV co‐opts the host B cell microRNA network and specifically suppresses microRNA‐194 to override control of IL‐10 expression. Thus, modulation of microRNA‐194 may constitute a novel approach to inhibiting proliferation of EBV+ B cell lymphomas in PTLD.
Epstein‐Barr virus modulates B cell microRNA‐194 expression during latent infection to promote the production of IL‐10, an important autocrine growth factor for EBV+ B cell lymphomas in posttransplant lymphoproliferative disorder.
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