Complex regulation of neutrophil-derived MMP-9 secretion in central nervous system tuberculosis.

BACKGROUND: Central nervous system tuberculosis (CNS-TB) may be fatal even with treatment. Neutrophils are the key mediators of TB immunopathology, and raised CSF matrix metalloproteinase-9 (MMP-9) which correlates to neutrophil count in CNS-TB is associated with neurological deficit and death. The mechanisms by which neutrophils drive TB-associated CNS matrix destruction are not clearly defined. METHODS: Human brain biopsies with histologically proven CNS-TB were stained for neutrophils, neutrophil elastase, and MMP-9. Neutrophil MMP-9 secretion and gene expression were analyzed using Luminex and real-time PCR. Type IV collagen degradation was evaluated using confocal microscopy and quantitative fluorescent assays. Intracellular signaling pathways were investigated by immunoblotting and chemical inhibitors. RESULTS: MMP-9-expressing neutrophils were present in tuberculous granulomas in CNS-TB and neutrophil-derived MMP-9 secretion was upregulated by Mycobacterium tuberculosis (M.tb). Concurrent direct stimulation by M.tb and activation via monocyte-dependent networks had an additive effect on neutrophil MMP-9 secretion. Destruction of type IV collagen, a key component of the blood-brain barrier, was inhibited by neutralizing neutrophil MMP-9. Monocyte-neutrophil networks driving MMP-9 secretion in TB were regulated by MAP-kinase and Akt-PI3 kinase pathways and the transcription factor NF-kB. TNFα neutralization suppressed MMP-9 secretion to baseline while dexamethasone did not. CONCLUSIONS: Multiple signaling paths regulate neutrophil-derived MMP-9 secretion, which is increased in CNS-TB. These paths may be better targets for host-directed therapies than steroids currently used in CNS-TB

On Some Geometric Properties of Slice Regular Functions of a Quaternion Variable

The goal of this paper is to introduce and study some geometric properties of slice regular functions of quaternion variable like univalence, subordination, starlikeness, convexity and spirallikeness in the unit ball. We prove a number of results, among which an Area-type Theorem, Rogosinski inequality, and a Bieberbach-de Branges Theorem for a subclass of slice regular functions. We also discuss some geometric and algebraic interpretations of our results in terms of maps from $\mathbb R^4$ to itself. As a tool for subordination we define a suitable notion of composition of slice regular functions which is of independent interest

The underperformance of the growth enterprise market in Hong Kong

This paper examines the stock return performance of the IPO stocks which are listed on the Growth Enterprise Market (GEM) in Hong Kong. By using several benchmarks, over 3 years, this paper finds that the results produced are sensitive to the benchmark employed. The two factors causing the underperformance of GEM stocks are the `technology boom and `IPO effects. This suggests that appropriate benchmarks are very important for assessing the performance of newly issued stocks. The results of the cross-sectional analyses suggest that the Hong Kong GEM is a unique market. Since at least 70 percent of the IPO stocks listed on theGEMare technology stocks, the `technology factor outweighs the various hypotheses advocated by previous researchers to explain the poor performance of newly listed stocks

Utilization of engineered resistance to viruses in crops of the developing world, with emphasis on sub-Saharan Africa

Engineering for viral resistance • Viruses and CancerViral diseases in crop plants constitute a major obstacle to food security in the developing world. Subsistence crops, including cassava, sweetpotato, potato, banana, papaya, common bean, rice and maize are often infected with RNA and/or DNA viruses that cannot be controlled with pesticides. Hence, healthy planting materials and virus-resistant cultivars are essential for high yields of good quality. However, resistance genes are not available for all viral diseases of crop plants. Therefore, virus resistance engineered in plants using modern biotechnology methods is an important addition to the crop production toolbox.Peer reviewe

Pneumococcal Serotype-Specific Antibodies Persist through Early Childhood after Infant Immunization: Follow-Up from a Randomized Controlled Trial

Background: In a previous UK multi-center randomized study 278 children received three doses of 7-valent (PCV-7) or 13- valent (PCV-13) pneumococcal conjugate vaccine at 2, 4 and 12 months of age. At 13 months of age, most of these children had pneumococcal serotype-specific IgG concentrations $0.35 mg/ml and opsonophagocytic assay (OPA) titers$8. Methods: Children who had participated in the original study were enrolled again at 3.5 years of age. Persistence of immunity following infant immunization with either PCV-7 or PCV-13 and the immune response to a PCV-13 booster at preschool age were investigated. Results: In total, 108 children were followed-up to the age of 3.5 years and received a PCV-13 booster at this age. At least 76% of children who received PCV-7 or PCV-13 in infancy retained serotype-specific IgG concentrations $0.35 mg/ml against each of 5/7 shared serotypes. For serotypes 4 and 18C, persistence was lower at 22–42$0.35 mg/ml against each of 4/6 of the additional PCV-13 serotypes; for serotypes 1 and 3 this proportion was 45% and 52%. In the PCV-7 group these percentages were significantly lower for serotypes 1, 5 and 7F. A pre-school PCV-13 booster was highly immunogenic and resulted in low rates of local and systemic adverse effects. Conclusion: Despite some decline in antibody from 13 months of age, these data suggest that a majority of pre-school children maintain protective serotype-specific antibody concentrations following conjugate vaccination at 2, 4 and 12 months of age. Trial Registration: ClinicalTrials.gov NCT0109547

Determinants of sourcing flexibility and its impact on performance

© 2018 Elsevier B.V. Sourcing flexibility is an increasingly important building block of supply chain flexibility. Our study which is grounded in information processing theory argues that two mechanisms can support firms in building up sourcing flexibility. Based on a survey of 336 manufacturing firms from Europe and the U.S. and using partial least squares (PLS) modeling as well as hierarchical regression analysis, we show that supplier evaluation and selection, and the integration of information systems at the buyer-supplier interface are positively related to sourcing flexibility. Sourcing flexibility, in turn, is curvilinearly related to delivery performance. Finally, delivery performance positively influences the product's financial performance. The strong associations between sourcing flexibility, delivery performance, and product financial performance underscore that sourcing flexibility merits the attention of supply chain managers during supplier selection and purchasing decisions

Behavioural mediators of genetic life-history trade-offs: a test of the pace-of-life syndrome hypothesis in field crickets

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The pace-of-life syndrome (POLS) hypothesis predicts associations between life history and 'risky' behaviours. Individuals with 'fast' lifestyles should develop faster, reproduce earlier, exhibit more risk-prone behaviours, and die sooner than those with 'slow' lifestyles. While support for POLS has been equivocal to date, studies have relied on individual-level (phenotypic) patterns in which genetic trade-offs may be masked by environmental effects on phenotypes. We estimated genetic correlations between life history (development, lifespan, size) and risky behaviours (exploration, aggression) in a pedigreed population of Mediterranean field crickets (Gryllus bimaculatus). Path analyses showed that behaviours mediated some genetic relationships between life history traits, though not those involved in trade-offs. Thus, while specific predictions of POLS theory were not supported, genetic integration of behaviour and life history was present. This implies a major role for risky behaviours in life history evolution.F.S. and N.J.D. were supported by the Max Planck Society, F.S. by the International Max Planck Research School for Organismal Biology, A.J.W. by a BBSRC David Phillips Research Fellowship, and P.T.N. by a postdoctoral fellowship of the German Science Foundation (DFG)

Improved Charge-Trapping Properties of TiON/HfON Dual Charge Storage Layer by Tapered Band Structure

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A novel MONOS memory with high-κ HfLaON as charge-storage layer

MIS capacitors with a high-κ HfLaON or HfLaO gate dielectric are fabricated by using a reactive sputtering method to investigate the applicability of the films as a novel charge-storage layer in a metaloxidenitrideoxidesilicon nonvolatile memory device. Experimental results indicate that the MIS capacitor with a HfLaON gate dielectric exhibits a large memory window, high program/erase speed, excellent endurance property, and reasonable retention. The involved mechanisms for these promising characteristics with HfLaON are thought to be in part from nitrogen incorporation leading to higher density of traps with deeper levels and, thus, higher trapping efficiency, stronger HfN and LaN bonds, and more stable atomic structure and HfLaONSiO 2 interface, as compared to the HfLaO dielectric. © 2011 IEEE.published_or_final_versio

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