Purpose Macroscopic magnetic field inhomogeneities adversely affect different aspects of MRI images. In quantitative MRI when the goal is to quantify biological tissue parameters, they bias and often corrupt such measurements. The goal of this paper is to develop a method for correction of macroscopic field inhomogeneities that can be applied to a variety of quantitative gradient-echo-based MRI techniques. Methods We have re-analyzed a basic theory of gradient echo (GE) MRI signal formation in the presence of background field inhomogeneities and derived equations that allow for correction of magnetic field inhomogeneity effects based on the phase and magnitude of GE data. We verified our theory by mapping R2* relaxation rate in computer simulated, phantom, and in vivo human data collected with multi-GE sequences. Results The proposed technique takes into account voxel spread function (VSF) effects and allowed obtaining virtually free from artifacts R2* maps for all simulated, phantom and in vivo data except of the edge areas with very steep field gradients. Conclusion The VSF method, allowing quantification of tissue specific R2*-related tissue properties, has a potential to breed new MRI biomarkers serving as surrogates for tissue biological properties similar to R1 and R2 relaxation rate constants widely used in clinical and research MRI.

We present an unprecedented set of high-resolution climate simulations, consisting of a 500-year pre-industrial control simulation and a 250-year historical and future climate simulation from 1850 to 2100. A high-resolution configuration of the Community Earth System Model version 1.3 (CESM1.3) is used for the simulations with a nominal horizontal resolution of 0.25°for the atmosphere and land models and 0.1°for the ocean and sea-ice models. At these resolutions, the model permits tropical cyclones and ocean mesoscale eddies, allowing interactions between these synoptic and mesoscale phenomena with large-scale circulations. An overview of the results from these simulations is provided with a focus on model drift, mean climate, internal modes of variability, representation of the historical and future climates, and extreme events. Comparisons are made to solutions from an identical set of simulations using the standard resolution (nominal 1°) CESM1.3 and to available observations for the historical period to address some key scientific questions concerning the impact and benefit of increasing model horizontal resolution in climate simulations. An emerging prominent feature of the high-resolution pre-industrial simulation is the intermittent occurrence of polynyas in the Weddell Sea and its interaction with an Interdecadal Pacific Oscillation. Overall, high-resolution simulations show significant improvements in representing global mean temperature changes, seasonal cycle of sea-surface temperature and mixed layer depth, extreme events and in relationships between extreme events and climate modes. Plain Language Summary Although the current generation of climate models has demonstrated high fidelity in simulating and projecting global temperature change, these models show large uncertainties when it comes to questions concerning how rising global temperatures will impact local weather conditions. This is because the resolution (~100 km) at which the majority of climate models simulate the climate is not fine enough to resolve these small-scale regional features. Conducting long-term (multi-centuries) high-resolution (~10 km) climate simulations has been a great challenge for the research community due to the extremely high computational demands. Through international

Little is known about the role of specific delta GST genes in the detoxification of lambda-cyhalothrin in the global quarantine fruit pest codling moth, Cydia pomonella (L.). Real-time quantitative PCR shows that CpGSTd3 was ubiquitously expressed at all developmental stages and is most abundant in the larval stage and lowest in the egg stage; the mRNA level of CpGSTd3 is higher in the midgut and Malpighian tubules of fourth-instar larvae and abdomens of adults than in other tissues. Exposure of fourth-instar larvae to an LD10 dosage of lambda-cyhalothrin significantly induced the transcript of CpGSTd3 at 3 h, but the mRNA level was down-regulated after 12 h of treatment. Recombinant CpGSTd3 expressed in Escherichia coli was able to catalyze the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and with an IC50 value of 0.65 mM for lambda-cyhalothrin. Metabolism assays indicate that recombinant CpGSTd3 could metabolize lambda-cyhalothrin. These results suggest that CpGSTd3 is probably a lambda-cyhalothrin metabolizing GST in C. pomonella.

Ischemic stroke is a leading cause of long-term disability and death worldwide. Current drug delivery vehicles for the treatment of ischemic stroke are less than satisfactory, in large part due to their short circulation lives, lack of specific targeting to the ischemic site, and poor controllability of drug release. In light of the upregulation of reactive oxygen species (ROS) in the ischemic neuron, we herein developed a bioengineered ROS-responsive nanocarrier for stroke-specific delivery of a neuroprotective agent, NR2B9C, against ischemic brain damage. The nanocarrier is composed of a dextran polymer core modified with ROS-responsive boronic ester and a red blood cell (RBC) membrane shell with stroke homing peptide (SHp) inserted. These targeted "core-shell" nanoparticles (designated as SHp-RBC-NP) could thus have controlled release of NR2B9C triggered by high intracellular ROS in ischemic neurons after homing to ischemic brain tissues. The potential of the SHp-RBC-NP for ischemic stroke therapy was systematically evaluated in vitro and in rat models of middle cerebral artery occlusion (MCAO). In vitro results showed that the SHp-RBC-NP had great protective effects on glutamate-induced cytotoxicity in PC-12 cells. In vivo pharmacokinetic (PK) and pharmacodynamic (PD) testing further demonstrated that the bioengineered nanoparticles can drastically prolong the systemic circulation of NR2B9C, enhance the active targeting of the ischemic area in the MCAO rats, and reduce ischemic brain damage.

Pancreatic cancer has the lowest survival rate among human cancers, and there are no effective markers for its screening and early diagnosis. To identify genetic susceptibility markers for this cancer, we carried out a genome-wide association study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free controls of Chinese descent using 666,141 autosomal SNPs. Promising associations were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls recruited from 25 hospitals in 16 provinces or cities in China. We identified five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11 (P = 2.24 × 10(-13) to P = 4.18 × 10(-10)) in addition to 13q22.1 previously reported in populations of European ancestry. These results advance our understanding of the development of pancreatic cancer and highlight potential targets for the prevention or treatment of this cancer.

Unsatisfying reversibility of zinc (Zn) metal anode seriously hinders its further practical applications. It corresponds to two major issues including the notorious dendrite growth and the exacerbated hydrogen evolution, resulting...

Ischemic stroke caused by a thrombus clog and ischemia is one of the most lethal and disabling cerebrovascular diseases. A sequentially targeted delivery system is highly desired to deliver thrombolytics and neuroprotectant to the site of the thrombus and ischemic penumbra, respectively, to pursue a maximized combinational effect. Inspired by the vital roles that platelets play in thrombus formation, herein, we develop a bioengineered "nanoplatelet" (tP-NP-rtPA/ZL006e) for sequentially site-specific delivery of recombinant tissue plasminogen activator (rtPA) and neuroprotectant (ZL006e) for ischemic stroke treatment. The tP-NP-rtPA/ZL006e consists of a ZL006e-loaded dextran derivative polymeric nanoparticle core and platelet membrane shell conjugated with thrombin-cleavable Tat-peptide-coupled rtPA. Mediated by the cloak of the platelet membrane, tP-NP-rtPA/ZL006e targets the thrombus site and rtPA is triggered to release by the upregulated thrombin. Subsequently, the in situ exposed Tat peptide enhanced penetration of the "nanoplatelet" across the blood−brain barrier into ischemic brain for ZL006e site-specific delivery. From the in vitro and in vivo evaluation, tP-NP-rtPA/ZL006e is demonstrated to significantly enhance the anti-ischemic stroke efficacy in the rat model with middle cerebral artery occlusion, showing a 63 and 72% decrease in ischemic area and reactive oxygen species level compared to that with free drug combination, respectively.

The hypothesis that marrow-derived cells, and specifically proinflammatory proteins in those cells, play a critical role in the development of diabetes-induced retinopathy and tactile allodynia was investigated. Abnormalities characteristic of the early stages of retinopathy and allodynia were measured in chimeric mice lacking inducible nitric oxide synthase (iNOS) or poly(ADP-ribosyl) polymerase (PARP1) in only their marrow-derived cells. Diabetes-induced capillary degeneration, proinflammatory changes, and superoxide production in the retina and allodynia were inhibited in diabetic animals in which iNOS or PARP1 was deleted from bone marrow cells only. Of the various marrow cells, neutrophils (and monocytes) play a major role in retinopathy development, because retinal capillary degeneration likewise was significantly inhibited in diabetic mice lacking the receptor for granulocyte colony-stimulating factor in their marrow-derived cells. Immunodepletion of neutrophils or monocytes inhibited the endothelial death otherwise observed when coculturing leukocytes from wild-type diabetic animals with retinal endothelium. iNOS and PARP1 are known to play a role in inflammatory processes, and we conclude that proinflammatory processes within marrow-derived cells play a central role in the development of diabetes complications in the retina and nerve.