Impacts of Ti content and annealing temperature on electrical properties of Si MOS capacitors with HfTiON gate dielectric

Proceedings of the IEEE International Conference of Electron Devices and Solid-State Circuits, 2009, p. 221-224HfTiON gate dielectric is fabricated by reactive co-sputtering method followed by annealing in N 2 ambient. The effects of Ti content and annealing temperature on the performances of HfTiON gate-dielectric Si MOS devices are investigated. Experimental results indicate that gate capacitance is increased with increasing Ti content. However, when the Ti/Hf ratio exceeds -1.75, increase of the gate capacitance becomes small. Surface roughness of the samples annealed at different temperatures is analyzed by AFM, and results show that high annealing temperature (e.g. 700 °C for 30 s) can produce smooth surface, thus resulting in low gate leakage current. ©2009 IEEE.published_or_final_versio

Lipid profiling of complex biological mixtures by liquid chromatography/mass spectrometry using a novel scanning quadrupole data-independent acquisition strategy

Rationale A novel data-independent acquisition method is detailed that incorporates a scanning quadrupole in front of an orthogonal acceleration time-of-flight (TOF) mass analyser. This approach is described and the attributes are compared and contrasted to other DIA approaches. Methods Specific application of the method to both targeted and untargeted lipidomic identification strategies is discussed, with data from both shotgun and LC separated lipidomics experiments presented. Results The benefits of the fast quadrupole scanning technique are highlighted, and include improvements in speed and specificity for complex mixtures providing high quality qualitative and quantitative data. Conclusions In particular the high specificity afforded by the scanning quadrupole improves qualitative information for lipid identification

Population-level effects of parasitism on a freshwater ecosystem engineer, the unionid mussel Anodonta anatina

Funder: Woolf Fisher TrustAbstract: Parasites can negatively affect hosts at individual, population, and species‐level scales. However, the link between individual‐ and population‐level impacts is often poorly understood. In particular, the population‐level response to parasitism may alter wider ecosystem dynamics if animals with ecosystem engineering capabilities are infected. Here, we examine the effects of parasitism on a freshwater ecosystem engineer, the unionid mussel Anodonta anatina, at two different sites. We study three common parasites: the digenean trematode Rhipidocotyle campanula; the unionicolid mite Unionicola intermedia; and the ectoparasitic invasive zebra mussel Dreissena polymorpha. As well as demonstrating the individual‐level effects of parasitism on the native host mussel, we construct a simple model to estimate the reduction in population‐level reproductive output caused by parasites. We show that both infection prevalence and intensity were population‐specific, with one site having more than three times as many native mussels infected by trematodes and mites than the other, but more than four times fewer mussels afflicted by invasive zebra mussels. Negative reproductive consequences for individual host mussels were documented as a result of parasitism, with trematodes causing castration at both sites. Mites were also correlated with a reduction in the viability of larval offspring (glochidia) by more than 25%, but only at one site, suggesting some potential impacts of parasitism may be population specific. The population‐level model shows that parasitism alone reduces larval output of the two populations by 10% and 13%, respectively. Our study takes the important step of scaling individual‐level effects of parasitism to population‐level processes, and highlights the influence that parasites may have in the population dynamics of unionid mussels. Given the ecosystem engineering capabilities of A. anatina, such effects may have important impacts on the wider biota. Even at relatively low prevalences, the observed effects of parasites on native mussel populations suggests that parasitism must be considered in the conservation of freshwater mussels, one of the world's most globally imperilled faunal groups. Further, understanding how the effects of parasitism on individual hosts scales to the ecosystem level is a crucial and unaddressed question in freshwater biology

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.Comment: 40 pages, 13 PostScript figure

Proteomic responses reveal the differential effects induced by cadmium in mussels Mytilus galloprovincialis at early life stages

Cadmium (Cd) has become an important metal contaminant and posed severe risk on the organisms in the coastal environments of the Bohai Sea. Marine mussel Mytilus galloprovincialis is widely distributed along the Bohai coast and consumed as seafood by local residents. Evidences indicate that the early stages of marine organisms are more sensitive to metal contaminants. In this study, we applied two-dimensional electrophoresis-based proteomics to characterize the biological effects of Cd (50 mu g L-1) in the early life stages (D-shape larval and juvenile) of mussels. The different proteomic responses demonstrated the differential responsive mechanisms to Cd exposure in these two early life stages of mussels. In details, results indicated that Cd mainly induced immune and oxidative stresses in both D-shape larval and juvenile mussels via different pathways. In addition, the significant up-regulation of triosephosphate isomerase and metallothionein confirmed the enhanced energy demand and mobilized detoxification mechanism in D-shape larval mussels exposed to Cd. In juvenile mussels, Cd exposure also induced clear apoptosis. Overall, this work suggests that Cd is a potential immune toxicant to mussel M. galloprovincialis at early life stages. (C) 2016 Elsevier Ltd. All rights reserved

Effects of brodifacoum and diphacinone exposure on four species of reptiles: tissue residue levels and survivorship

BACKGROUND: Anticoagulant rodenticides are used worldwide to control pest rodent species. However, the risks posed to nontarget reptiles have not been well characterized. In this study, 46 giant ameivas (Ameiva ameiva), 39 boa constrictors (Boa constrictor), 33 wood turtles (Rhinoclemmys pulcherrima), and 47 green iguanas (Iguana iguana) were orally dosed with one of two levels of either diphacinone or brodifacoum anticoagulant in propylene glycol solutions. Dosages were derived using daily food intake (DFI) equations, converting DFI to an equivalent anticoagulant bait amount and gavaging the solution volume needed to deliver the quantity of anticoagulant in that amount of bait. Animals were dosed on days 0 and 7 and monitored for a further 7 days for signs of anticoagulant intoxication and differences in behaviors and postures. At necropsy on day 14, animals were examined for thoracic and abdominal bleeding, and both tissue and organ samples were taken for histology. Liver and wholebody anticoagulant residues were assessed. RESULTS: No turtles or boas died due to anticoagulant exposure. However, anticoagulant intoxication was suspected in one iguana dosed with brodifacoum. A few treated ameivas died but exhibited no hemorrhaging. Liver residue levels were higher than whole-body remainder residue levels for all species. Unlike the other species, turtles had higher diphacinone residue levels than brodifacoum. CONCLUSION: Turtles and boas exhibited a relative insensitivity to diphacinone and brodifacoum, while the lizards appeared to be somewhat more sensitive to these compounds. This study provides data for future assessments of the risks to these species associated with anticoagulant use

Costs associated with febrile neutropenia in solid tumor and lymphoma patients - an observational study in Singapore.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients

Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury

Background: Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.Results: We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia (DRG), 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour. The results show a set of genes, differentially regulated in the adult DRG, that are principally involved in immune system modulation. A functional consequence of this different immune response to injury is that resident macrophages cluster around the large A sensory neuron bodies in the adult DRG seven days post injury, whereas the macrophages in young DRG remain scattered evenly throughout the ganglion, as in controls.Conclusions: The results show, for the first time, a major difference in the neuroimmune response to nerve injury in the dorsal root ganglion of young and adult rats. Differential analysis reveals a new set of immune related genes in the ganglia, that are differentially regulated in adult neuropathic pain, and that are consistent with the selective activation of macrophages around adult, but not young large A sensory neurons post injury. These differences may contribute to the reduced incidence of neuropathic pain in infants

AZD8055 enhances in vivo efficacy of afatinib in chordomas

Chordomas are primary bone tumors that arise in the cranial base, mobile spine, and sacrococcygeal region, affecting patients of all ages. Currently, there are no approved agents for chordoma patients. Here, we evaluated the anti-tumor efficacy of small molecule inhibitors that target oncogenic pathways in chordoma, as single agents and in combination, to identify novel therapeutic approaches with the greatest translational potential. A panel of small molecule compounds was screened in vivo against patient-derived xenograft (PDX) models of chordoma, and potentially synergistic combinations were further evaluated using chordoma cell lines and xenograft models. Among the tested agents, inhibitors of EGFR (BIBX 1382, erlotinib, and afatinib), c-MET (crizotinib), and mTOR (AZD8055) significantly inhibited tumor growth in vivo but did not induce tumor regression. Co-inhibition of EGFR and c-MET using erlotinib and crizotinib synergistically reduced cell viability in chordoma cell lines but did not result in enhanced in vivo activity. Co-inhibition of EGFR and mTOR pathways using afatinib and AZD8055 synergistically reduced cell viability in chordoma cell lines. Importantly, this dual inhibition completely suppressed tumor growth in vivo, showing improved tumor control. Together, these data demonstrate that individual inhibitors of EGFR, c-MET, and mTOR pathways suppress chordoma growth both in vitro and in vivo. mTOR inhibition increased the efficacy of EGFR inhibition on chordoma growth in several preclinical models. The insights gained from our study potentially provide a novel combination therapeutic strategy for patients with chordoma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

One-dimensional Topological Edge States of Bismuth Bilayers

The hallmark of a time-reversal symmetry protected topologically insulating state of matter in two-dimensions (2D) is the existence of chiral edge modes propagating along the perimeter of the system. To date, evidence for such electronic modes has come from experiments on semiconducting heterostructures in the topological phase which showed approximately quantized values of the overall conductance as well as edge-dominated current flow. However, there have not been any spectroscopic measurements to demonstrate the one-dimensional (1D) nature of the edge modes. Among the first systems predicted to be a 2D topological insulator are bilayers of bismuth (Bi) and there have been recent experimental indications of possible topological boundary states at their edges. However, the experiments on such bilayers suffered from irregular structure of their edges or the coupling of the edge states to substrate's bulk states. Here we report scanning tunneling microscopy (STM) experiments which show that a subset of the predicted Bi-bilayers' edge states are decoupled from states of Bi substrate and provide direct spectroscopic evidence of their 1D nature. Moreover, by visualizing the quantum interference of edge mode quasi-particles in confined geometries, we demonstrate their remarkable coherent propagation along the edge with scattering properties that are consistent with strong suppression of backscattering as predicted for the propagating topological edge states.Comment: 15 pages, 5 figures, and supplementary materia