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To improve crowd evacuation efficiency in large building spaces during fires, a spatial layout optimization method using PyroSim and Pathfinder software was proposed. Disaster-causing factors that hinder safe evacuation - such as smoke spread, fire scene temperature, CO concentration, and visibility - were compared. The arrival time of danger in fire environments was analysed, the time required for crowd evacuation was calculated, structural characteristics of building space affecting evacuation efficiency were identified, and evacuation bottlenecks in large-scale buildings were revealed. Taking the super-large building of Silk Clothing City in Jiangsu Province, China as an example, a spatial layout optimization scheme focused on evacuation efficiency was proposed and its effectiveness was verified. Results show that before spatial layout optimization, the available safe evacuation time is 145 seconds, which is shorter than the required safe evacuation time of 197.8 seconds, indicating high safety risks during evacuation in a fire. After optimizing the layout of smoke exhaust equipment, the available safe evacuation time is increased to 205 seconds, substantially enhancing crowd evacuation safety. [ABSTRACT FROM AUTHOR]

We consider the evolution of a spatially periodic, perturbed vortex sheet for small times after the formation of a curvature singularity at time t = tc as demonstrated by Moore (Proc. R. Soc. Lond. A, vol. 365, issue 1720, 1979, pp. 105-119). The Moore analysis is extended to provide the small-amplitude, full-sheet structure at t = tc for a general single-mode initial condition in terms of polylogarithmic functions, from which its asymptotic form near the singular point is determined. This defines an intermediate evolution problem for which the leading-order, and most singular, approximation is solved as a Taylor-series expansion in τ = t - tc, where coefficients are calculated by repeated differentiation of the defining Birkhoff-Rott (BR) equation. The first few terms are in good agreement with numerical calculation based on the full-sheet solution. The series is summed, providing an analytic continuation which shows sheet rupture at circulation r = 0+, τ > 0+, but with non-physical features owing to the absence of end-tip sheet roll up. This is corrected by constructing an inner solution with r < τ, as a perturbed similarity form with small parameter τ1/2. Numerical solutions of both the inner, nonlinear zeroth-order and first-order linear BR equations are obtained whose outer limits match the intermediate solution. The composite solution shows sheet tearing at τ = 0+ into two separate, rolled up algebraic spirals near the central singular point. Branch separation distance scales as T with a non-local, τ3/2 correction. Properties of the intermediate and inner solutions are discussed. [ABSTRACT FROM AUTHOR]

Shear instabilities at the interface of two fluids, such as classical Kelvin-Helmholtz instability (KHI), is the precursor of interface destabilization, leading to fluid fragmentation critical in a wide range of applications. While many insights into such instabilities are derived for steady background forcing flow, unsteady impulse flows are ubiquitous in environmental and physiological processes. Yet, little is understood on how unsteadiness shapes the initial interface amplification necessary for the onset of its topological change enabling subsequent fragmentation. In this combined theoretical, numerical and experimental study, we focus on an air-on-liquid interface exposed to canonical unsteady shear flow profiles. Evolution of the perturbed interface is formulated theoretically as an impulse-driven initial value problem using both linearized potential flow and nonlinear boundary integral methods. We show that the unsteady airflow forcing can amplify the interface's inherent gravity-capillary wave, up to wave-breaking transition, even if the configuration is classically KH stable. For impulses much shorter than the gravity-capillary wave period, it is the cumulative action, akin to total energy, that determines amplification, independent of the details of the impulse profile. However, for longer impulses, the details of the impulse profile become important. In this limit, akin to a resonance, it is the entangled history of the interaction of the forcing, i.e. the impulse, that changes rapidly in amplitude, and the response of the oscillating interface that matters. The insights gained are discussed and experimentally illustrated in the context of interface distortion and destabilization relevant for upper respiratory mucosalivary fluid fragmentation in violent exhalations. [ABSTRACT FROM AUTHOR]

Blood vessel formation is an important initial step for bone formation during development as well as during remodelling and repair in the adult skeleton. This results in a heavily vascularized tissue where endothelial cells and skeletal cells are constantly in crosstalk to facilitate homeostasis, a process that is mediated by numerous environmental signals, including mechanical loading. Breakdown in this communication can lead to disease and/or poor fracture repair. Therefore, this study aimed to determine the role of mature bone cells in regulating angiogenesis, how this is influenced by a dynamic mechanical environment, and understand the mechanism by which this could occur. Herein, we demonstrate that both osteoblasts and osteocytes coordinate endothelial cell proliferation, migration, and blood vessel formation via a mechanically dependent paracrine mechanism. Moreover, we identified that this process is mediated via the secretion of extracellular vesicles (EVs), as isolated EVs from mechanically stimulated bone cells elicited the same response as seen with the full secretome, while the EV-depleted secretome did not elicit any effect. Despite mechanically activated bone cell-derived EVs (MA-EVs) driving a similar response to VEGF treatment, MA-EVs contain minimal quantities of this angiogenic factor. Lastly, a miRNA screen identified mechanoresponsive miRNAs packaged within MA-EVs which are linked with angiogenesis. Taken together, this study has highlighted an important mechanism in osteogenic-angiogenic coupling in bone and has identified the mechanically activated bone cell-derived EVs as a therapeutic to promote angiogenesis and potentially bone repair. [ABSTRACT FROM AUTHOR]

Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1·EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription. [ABSTRACT FROM AUTHOR]

Plants produce a wide variety of secondary metabolites, which often are of interest to pharmaceutical and nutraceutical industry. Plant-cell cultures allow producing these metabolites in a standardised manner, independently from various biotic and abiotic factors difficult to control during conventional cultivation. However, plant-cell fermentation proves to be very difficult, since these chemically complex compounds often result from the interaction of different biosynthetic pathways operating in different cell types. To simulate such interactions in cultured cells is a challenge. Here, we present a microfluidic bioreactor for plant-cell cultivation to mimic the cell–cell interactions occurring in real plant tissues. In a modular set-up of several microfluidic bioreactors, different cell types can connect through a flow that transports signals or metabolites from module to module. The fabrication of the chip includes hot embossing of a polycarbonate housing and subsequent integration of a porous membrane and in-plane tube fittings in a two-step ultrasonic welding process. The resulting microfluidic chip is biocompatible and transparent. Simulation of mass transfer for the nutrient sucrose predicts a sufficient nutrient supply through the membrane. We demonstrate the potential of this chip for plant cell biology in three proof-of-concept applications. First, we use the chip to show that tobacco BY-2 cells in suspension divide depending on a "quorum-sensing factor" secreted by proliferating cells. Second, we show that a combination of two Catharanthus roseus cell strains with complementary metabolic potency allows obtaining vindoline, a precursor of the anti-tumour compound vincristine. Third, we extend the approach to operationalise secretion of phytotoxins by the fungus Neofusicoccum parvum as a step towards systems to screen for interorganismal chemical signalling. [ABSTRACT FROM AUTHOR]

This work aims at investigating the effect of the progressive damage interphase on the global bulk behavior of spherical particulate composites by proposing a nonlinear stress-strain relationship. To this end, first, the modeling of a damage interphase as a damage imperfect interface is briefly presented in a mathematically rigorous manner. The relationship between the proposed interface model and the classical cohesive model is also discussed and depicted by taking the example of the bilinear shape cohesive model. Second, the elastic fields of the problem where an infinite body made of a matrix containing a spherical particle with a damage interface under a remote uniform isotropic strain boundary condition are then provided in the framework of a Cartesian coordinate system, and the critical macroscopic strain boundary associated to the initial softening of the damage interface is determined. Third, with the aid of these results, the equivalent elastic properties of a perfectly bonded spherical particle related to an imperfectly damage bonded one in an infinite matrix are derived by the replacement procedure of equivalent inclusion with the requirement of energy equality. Finally, the effective bulk of the isotropic particulate composite is obtained by using the classical generalized self-consistent scheme; its global strength is also given, and their features are discussed through some numerical examples. [ABSTRACT FROM AUTHOR]

We consider the evolution of a shock wave generated by an impulsively accelerated, two-dimensional, almost planar piston with a sinusoidally corrugated surface of amplitude $\epsilon$. We develop a complex-variable formulation for a nonlinear theory of generalized geometrical shock dynamics (GGSD) (Best, Shock Waves, vol. 1, issue 4, 1991, pp. 251–273; Best, Proc. R. Soc. Lond. A, vol. 442, 1993, pp. 585–598) as a hierarchical expansion of the Euler equations that can be closed at any order. The zeroth-order truncation of GGSD is related to the equations of Whitham's geometrical shock dynamics (GSD), while higher-order corrections incorporate non-uniformity of the flow immediately behind the piston-driven shock. Numerical solutions to GGSD systems up to second order are coupled to an edge-detection algorithm in order to investigate the hypothesized development of a shock-shape curvature singularity as the rippled shock evolves. This singular behaviour, together with the simultaneous development of a Mach-number discontinuity, is found at all orders of the GGSD hierarchy for both weak and strong shocks. The critical time at which a curvature singularity occurs converges as the order of the GGSD system increases at fixed $\epsilon$ , and follows a scaling inversely proportional to $\epsilon$ at sufficiently small values. This result agrees with the weakly nonlinear GSD analysis of Mostert et al. (J. Fluid Mech., vol. 846, 2018, pp. 536–562) for a general Mach-number perturbation on a planar shock, and suggests that this represents the universal behaviour of a slightly perturbed, planar shock. [ABSTRACT FROM AUTHOR]

Carbon isotope composition of the tissue of several mollusc species gathered from the Huaxi river, in China, a typical karst river, was analysed to determine their potential food sources. The results showed that δ13Ctissues values of gastropod species Cipangopaludina chinensis are about 3%o heavier than the values of bivalve species Corbicula fluminea and Anodonta woodiana, which indicates the different food and nutrition sources between species. According to the δ13C values of mollusc's tissues and the potential food, bivalve species C. fluminea and A. woodiana mainly assimilate phytoplankton and terrestrial plant detritus as food, while gastropod species C. chinensis also utilize sediment organic matter as a food source excluding the phytoplankton and terrestrial plant detritus. Moreover, the preferential food selection behavior and varied metabolic intensity between different ages and individuals may lead to some variation of δ13Ctissues values of C. fluminea. This study will be helpful in defining the role of molluscs in the energy flow of the karst river ecosystem, and to protect and manage those molluscs' resources. [ABSTRACT FROM AUTHOR]

The article discusses the usage of next- generation sequencing (NGS) in the genetic diagnosis of inherited bleeding disorders. It mentions the information on the mutation screening for large deletions and duplications in Haemophilia A (HA). It also mentions the information on the Multiples ligation- dependent probe amplification.

Presents a study that examined the effect of hydrogen insertion into rare earth-iron compounds. Methodology; Analysis of the location of hydrogen in the rare earth-iron hydrides; Evaluation of the nuclear magnetic resonance spectra of the samples.

While porcine reproductive and respiratory syndrome ( PRRS) causes great economic losses in southern and central China, systematic studies on the epidemiology of PRRS virus ( PRRSV) in Heilongjiang Province had not been performed. Therefore, we conducted a preliminary study to estimate the prevalence and risk factors associated with PRRSV infection, as well as characterize the PRRSV in registered pig farms in Heilongjiang Province, China in 2011. A total of 1237 blood samples were collected from 72 farms and tested by reverse transcription polymerase chain reaction ( RT- PCR) for PRRSV. Risk factors associated to PRRSV infection were analysed using logistic regression models. Genes of non-structural protein-2 (Nsp2) and glycoprotein 5 ( GP5) from 22 isolates were sequenced for phylogenetic analysis. The results showed that the herd apparent prevalence was 9.7% (95% CI: 6.3, 13.1) in Heilongjiang Province. An increased risk of PRRSV infection on farms was associated with unrestricted movement of external people ( OR = 14.1, 95% CI: 1.68, 119.07), close proximity (<1 km) to the nearest house, road or neighbouring farm ( OR = 16.2, 95% CI: 1.52, 171.80), and selling farm products at both local and provincial markets ( OR = 20.6, 95% CI: 2.02, 210.56). Phylogenetic analysis based on partial amino acid sequences of GP5 and Nsp2 showed that all the 22 PRRSV isolates in Heilongjiang are closely related to the highly pathogenic PRRSV strain JXA1 and belong to the Genotype 2 (American genotype). The prevalence, determination of risk factors and phylogenetic characterization will provide information for future epidemiological studies and a reference for developing surveillance and control strategies in this region. [ABSTRACT FROM AUTHOR]

The mechanisms by which AML1/ETO (A/E) fusion protein induces leukemogenesis in acute myeloid leukemia (AML) without mutagenic events remain elusive. Here we show that interactions between A/E and hypoxia-inducible factor 1α (HIF1α) are sufficient to prime leukemia cells for subsequent aggressive growth. In agreement with this, HIF1α is highly expressed in A/E-positive AML patients and strongly predicts inferior outcomes, regardless of gene mutations. Co-expression of A/E and HIF1α in leukemia cells causes a higher cell proliferation rate in vitro and more serious leukemic status in mice. Mechanistically, A/E and HIF1α form a positive regulatory circuit and cooperate to transactivate DNMT3a gene leading to DNA hypermethylation. Pharmacological or genetic interventions in the A/E-HIF1α loop results in DNA hypomethylation, a re-expression of hypermethylated tumor-suppressor p15INK4b and the blockage of leukemia growth. Thus high HIF1α expression serves as a reliable marker, which identifies patients with a poor prognosis in an otherwise prognostically favorable AML group and represents an innovative therapeutic target in high-risk A/E-driven leukemia. [ABSTRACT FROM AUTHOR]

The potential of using corn steep liquor powder ( CSLP), peanut meal ( PM), soybean meal ( SM), cotton meal ( CM) and urea as the substitute of yeast extract ( YE) as the nitrogen source was investigated for producing succinic acid ( SA). Actinobacillus succinogenes GXAS137 was used as the fermenting bacterium and sugarcane molasses was used as the main substrate. None of these materials were able to produce SA as high as YE did. The CSLP could still be considered as a feasible and inexpensive alternate for YE as the yield of SA produced using CSLP was second only to the yield of SA obtained by YE. The use of CSLP-PM mixed formulation ( CSLP to PM ratio = 2·6) as nitrogen source produced SA up to 59·2 g l−1 with a productivity of 1·2 g l−1 h−1. A batch fermentation using a stirred bioreactor produced up to 60·7 g l−1 of SA at the same formulation. Fed-batch fermentation that minimized the substrate inhibition produced 64·7 g l−1 SA. These results suggest that sugarcane molasses supplemented with a mixture of CSLP and PM as the nitrogen source could be used to produce SA more economically using A. succinogenes. Significance and Impact of the Study Succinic acid (SA) is commonly used as a platform chemical to produce a number of high value derivatives. Yeast extract (YE) is used as a nitrogen source to produce SA. The high cost of YE is currently the limiting factor for industrial production of SA. This study reports the use of a mixture of corn steep liquor powder (CSLP) and peanut meal (PM) as an inexpensive nitrogen source to substitute YE. The results showed that this CSLP-PM mixed formulation can be used as an effective and economic nitrogen source for the production of SA. [ABSTRACT FROM AUTHOR]

Background:Chinese women tend to have small and dense breasts and ultrasound is a common method for breast cancer screening in China. However, its efficacy and cost comparing with mammography has not been evaluated in randomised trials.Methods:At 14 breast centres across China during 2008-2010, 13 339 high-risk women aged 30-65 years were randomised to be screened by mammography alone, ultrasound alone, or by both methods at enrolment and 1-year follow-up.Results:A total of 12 519 and 8692 women underwent the initial and second screenings, respectively. Among the 30 cancers (of which 15 were stage 0/I) detected, 5 (0.72/1000) were in the mammography group, 11 (1.51/1000) in the ultrasound group, and 14 (2.02/1000) in the combined group (P=0.12). In the combined group, ultrasound detected all the 14 cancers, whereas mammography detected 8, making ultrasound more sensitive (100 vs 57.1%, P=0.04) with a better diagnostic accuracy (0.999 vs 0.766, P=0.01). There was no difference between mammography and ultrasound in specificity (100 vs 99.9%, P=0.51) and positive predictive value (72.7 vs 70.0%; P=0.87). To detect one cancer, the costs of ultrasound, mammography, and combined modality were $7876, $45 253, and $21 599, respectively.Conclusions:Ultrasound is superior to mammography for breast cancer screening in high-risk Chinese women. [ABSTRACT FROM AUTHOR]

In order to enhance pristinamycin production, six homologous ptr genes from high pristinamycin-producing strains of Streptomyces pristinaespiralis were selected for DNA shuffling, and the reason for the altered activities of the shuffled ptr gene was speculated by sequence alignment. The highest pristinamycin yield of 0.12 g/L was achieved with a sixfold increase in strain sps16 obtained by DNA shuffling when compared to ancestral strain ATCC 25486. Sequence analysis of the ptr gene variant from the sps16 strain indicated that five mutations (H16P, N63D, T75P, Q107R, and P435A) were introduced into the gene, two of them (N63D and T75P) located in the second of the 14 transmembrane segments (TMS). Prediction of the secondary structure of the gene product indicated that mutations at the N-terminus resulted in the shortening of the corresponding α-helix, while the mutation at the C-terminus lengthened the helix. In conclusion, combination of DNA shuffling with genome shuffling is an effective breeding strategy for increasing the antibiotic yield by directed evolution of target genes. [ABSTRACT FROM AUTHOR]

Background: Chinese women tend to have small and dense breasts and ultrasound is a common method for breast cancer screening in China. However, its efficacy and cost comparing with mammography has not been evaluated in randomised trials.Methods: At 14 breast centres across China during 2008-2010, 13 339 high-risk women aged 30-65 years were randomised to be screened by mammography alone, ultrasound alone, or by both methods at enrollment and 1-year follow-up.Results: A total of 12 519 and 8692 women underwent the initial and second screenings, respectively. Among the 30 cancers (of which 15 were stage 0/I) detected, 5 (0.72/1000) were in the mammography group, 11 (1.51/1000) in the ultrasound group, and 14 (2.02/1000) in the combined group (P=0.12). In the combined group, ultrasound detected all the 14 cancers, whereas mammography detected 8, making ultrasound more sensitive (100 vs 57.1%, P=0.04) with a better diagnostic accuracy (0.999 vs 0.766, P=0.01). There was no difference between mammography and ultrasound in specificity (100 vs 99.9%, P=0.51) and positive predictive value (72.7 vs 70.0%; P=0.87). To detect one cancer, the costs of ultrasound, mammography, and combined modality were $7876, $45 253, and $21 599, respectively.Conclusions: Ultrasound is superior to mammography for breast cancer screening in high-risk Chinese women. [ABSTRACT FROM AUTHOR]

The grindability of titanium alloys that are classified as hard-to-machine materials is studied in high-speed cylindrical grinding using a cubic boron nitride (CBN) wheel. The investigation is concerned with residual surface stresses, including the construction of its empirical model, orthogonal experiments with a CBN grinding wheel at a speed of 45-150 m/s, and prediction with the back propagation (BP) network. The results of residual surface stress measurements obtained in grinding experiments and simulation analysis for five sets of grinding conditions are compared, it can be seen that the empirical model is partially applicable to a Ti-6Al-4V titanium alloy (TC4) under examined grinding conditions. Generally, the calculation results with the empirical model exhibit a significant deviation from the data of actual measurements in some cases. The BP network possesses the function of complex nonlinear mapping and adaptive learning. So the BP network is adopted to predict the relation between residual surface stresses and three key grinding conditions accurately enough. The accuracy of the network is verified, which lays the foundation for its in practical application. [ABSTRACT FROM AUTHOR]

An inexact stochastic fuzzy programming (ISFP) approach has been developed for the optimization of the industrial structure in resource-based city subjected to water resources under uncertainty in present study. The ISFP method incorporates the techniques of inexact stochastic programming and inexact fuzzy chance-constrained programming, where the uncertainties are expressed as interval, fuzzy sets, and probability distribution, respectively. Moreover, it can also examine the risk of violating fuzzy tolerance constraints. The developed method is subsequently employed in a realistic case for industrial development in the Jinchang city, Gansu province, China. The result can help to analyze whether the water resources carrying capacity of Jinchang can meet the need of local economic development plan under uncertainty and help decision maker to optimize the industry structure under water resource constraints to meet the maximum economic efficiency. [ABSTRACT FROM AUTHOR]

This paper reviews the progress of the vertical top-down nanowire technology platform developed to explore novel device architectures and integration schemes for green electronics and clean energy applications. Under electronics domain, besides having ultimate scaling potential, the vertical wire offers (1) CMOS circuits with much smaller foot print as compared to planar transistor at the same technology node, (2) a natural platform for tunneling FETs, and (3) a route to fabricate stacked nonvolatile memory cells.Under clean energy harvesting area, vertical wires could provide (1) cost reduction in photovoltaic energy conversion through enhanced light trapping and (2) a fully CMOS compatible thermoelectric engine converting waste-heat into electricity. In addition to progress review, we discuss the challenges and future prospects with vertical nanowires platform. [ABSTRACT FROM AUTHOR]

Fas is ubiquitously expressed on a variety of cells and triggers apoptosis, which have critical roles in the immune system. MicroRNAs (miRNAs) have been recently identified as regulators that modulate target gene expression and are involved in diverse biological processes, such as cell proliferation and apoptosis. This study was undertaken to investigate the contribution of miRNA in the regulation of Fas expression and Fas-mediated apoptosis. Bioinformatics analysis indicated that Fas was a potential target of let-7/miR-98 family. Indeed ectopic expression of let-7/miR-98 reduced, whereas knockdown of endogenous let-7/miR-98 increased the expression of Fas at both mRNA and protein levels. Let-7/miR-98 was verified to target Fas 3′ untranslated region directly by site-directed gene mutagenesis and reporter gene assay. More importantly, introduction of let-7/miR-98 could decrease the sensitivity to Fas-induced apoptosis. Furthermore, let-7/miR-98 expression was reduced in activation-induced cell death process, accompanied by increased expression of Fas. In conclusion, our study first demonstrated that let-7/miR-98 regulated Fas expression and the sensitivity of Fas-mediated apoptosis. [ABSTRACT FROM AUTHOR]

The genetic components in systemic lupus erythematosus (SLE) have long been established, however, it has been unclear for many years whether the same genetic risk factors for SLE are shared across different ethnic groups. Over the past few years, a number of genetic and genomic studies have been conducted in Asian populations to address this question. These studies have demonstrated that genetic heterogeneity does exist in SLE across different ethnic groups. With these studies, it has been established that a number of genes associated with SLE in Caucasians are also risk factors in Asians: HLA class II genes, STAT4, BANK1, BLK, IRF5, TNFSF4, ITGAM, etc., while there are also novel genetic risk factors identified by these studies in Asians, for instance, the ETS1 and WDFY4 in Chinese. For the genomic studies, the interferon signature has been confirmed as a major lupus molecular phenotype in Asians the same as in Caucasians; microRNA expression profiling and its novel role in regulating the interferon pathway has been first revealed in Asians. Further understanding of the function of lupus disease genes and delineating the key molecular pathway(s) will enhance the development of novel therapeutic targets and biomarkers for individualized clinical management for lupus patients. [ABSTRACT FROM PUBLISHER]

Recent theoretical work suggests that the conversion efficiency from laser to protons in laser irradiated thin foil experiments increases if the atomic mass of nonhydrogen atoms on the foil rear surface increases. Experiments were performed at the Lawrence Livermore National Laboratory Jupiter Laser Facility to observe the effect of thin foils coated with erbium hydride on the conversion efficiency from laser to protons. Gold foils with and without the rear surface coated with ErH3 were irradiated using the ultrashort pulse, 40 TW Callisto laser. An argon-ion etching system was used to remove naturally occurring nanometer thick surface layer contaminants from the hydride. With the etcher, gold with ErH3 showed a 25% increase in the conversion efficiency to protons above 3.4 MeV relative to contaminants, where C+4 and H+ were the dominant ion species. No difference in the ion signal was observed without first cleaning the hydrides. Simulations using the hybrid PIC code, LSP, revealed that the increase due to erbium hydride versus contaminants is 37% for protons above 3 MeV. [ABSTRACT FROM AUTHOR]

Several studies by microarray analysis and real-time polymerase chain reaction (RT-PCR) reveal that type I interferon-inducible genes (IFIGs) are implicated in systemic lupus erythematosus (SLE). To find a potential clinical biomarker capable of monitoring lupus disease activity clinically, quantitative RT-PCR was used to identify transcript expression levels of 13 type I IFIGs in peripheral blood cells in 144 patients with SLE, 27 non-SLE patients and 60 healthy controls and then analyse connections between gene expression and disease activity. The expression levels of five type I lFlGs (LY6E, OAS3, lFlT4, OASI and OAS2) were significantly higher in the SLE group than in the healthy and non-SLE controls. LY6E gene that had highest expression was chosen to analyse the association of expression level with clinical features. Compared to low LY6E expression group, SLE patients with high LY6E expression had higher SLEDAI-2K score, increased 24 h urine protein and lower blood C3 complement. Active SLE patients had more elevated LY6E expression than stable patients. And LY6E expression levels in patients with SLE were strongly correlated with their SLEDAI-2K scores. Our results indicate that increased expression of LY6E gene in peripheral blood cells in patients with SLE is correlated with lupus activity and may be a useful, noninvasive biomarker for assessing SLE disease activity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore whether there are extrinsic factors that impair the suppressive function of CD4+,CD25+ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE). METHODS: We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4+,CD25+,FoxP3+ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-alpha (IFNalpha) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay. RESULTS: The percentage of CD4+,CD25+, FoxP3+ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean +/- SEM 9.11 +/- 0.73% versus 4.78 +/- 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4+,CD25+ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4+,CD25+ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFNalpha derived from SLE patient APCs. CONCLUSION: We suggest that blockade of Treg cell-mediated suppression by IFNalpha-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease. [ABSTRACT FROM AUTHOR]

Interferon (IFN)-α is involved in the pathogenesis of systemic lupus erythematosus. Studies in murine lupus models have revealed that type I IFN exerts either a protective effect in MRL/lpr, or can detrimentally impact disease progression, as in NZB/W mice. To understand this paradox, we examined the kinetic global gene expression in pre-autoimmune NZB/W-, MRL/lpr- and normal BALB/c-derived splenic mononuclear cells following ex vivo IFN-α treatment. Analysis of IFN-α-induced gene expression patterns revealed genes associated with antiproliferative activity of IFN-α including CDKN1A, GADD45B, pituitary tumor-transforming 1, SCOTIN, ataxia telangiectasia-mutated homolog and calcyclin-binding protein were upregulated in MRL/lpr and/or BALB/c mice. Of IFN-α-induced genes differentially expressed in NZB/W vs BALB/c and MRL/lpr mice at 3 h time point, enhanced expression of CCND1, cyclin D2, matrix metalloproteinase 13 and a panel of cytokines and chemokines and impaired expression of negative inflammatory regulators CD69 and an Src family kinase hemopoietic cell kinase were notable. Interestingly, the splenic mononuclear cells from the NZB/W not MRL/lpr lupus-prone mice at the pre-autoimmune stage before ex vivo IFN-α treatment, have increased expression of many known IFN-regulated genes. These results provide a unique genomic view of ex vivo IFN-α response in two lupus-prone models, and help to have an insight into the role of IFN-α in lupus pathogenesisGenes and Immunity (2007) 8, 590–603; doi:10.1038/sj.gene.6364421; published online 30 August 2007 [ABSTRACT FROM AUTHOR]

Rapamycin and several analogs, such as CCI-779 and RAD001, are currently undergoing clinical evaluation as anticancer agents. In this study, we show that inhibition of mammalian target of rapamycin (mTOR) signaling by rapamycin leads to an increase of Akt phosphorylation in Rh30 and RD human rhabdomyosarcoma cell lines and xenografts, and insulin-like growth factor (IGF)-II-treated C2C12 mouse myoblasts and IGF-II-overexpressing Chinese hamster ovary cells. RNA interference-mediated knockdown of S6K1 also results in an increase of Akt phosphorylation. These data suggest that mTOR/S6K1 inhibition either by rapamycin or small interfering RNA (siRNA) triggers a negative feedback loop, resulting in the activation of Akt signaling. We next sought to investigate the mechanism of this negative feedback regulation from mTOR to Akt. Suppression of insulin receptor substrate (IRS)-1 and tuberous sclerosis complex-1 by siRNAs failed to abrogate rapamycin-induced upregulation of Akt phosphorylation in both Rh30 and RD cells. However, pretreatment with h7C10 antibody directed against insulin-like growth factor-1 receptor (IGF-1R) led to a blockade of rapamycin-induced Akt activation. Combined mTOR and IGF-1R inhibition with rapamycin and h7C10 antibody, respectively, resulted in additive inhibition of cell growth and survival. These data suggest that rapamycin mediates Akt activation through an IGF-1R-dependent mechanism. Thus, combining an mTOR inhibitor and an IGF-1R antibody/inhibitor may be an appropriate strategy to enhance mTOR-targeted anticancer therapy.Oncogene (2007) 26, 1932–1940. doi:10.1038/sj.onc.1209990; published online 25 September 2006 [ABSTRACT FROM AUTHOR]

The emergence of high temporal resolution satellite data such as MODIS enables timely monitoring of locust outbreaks from space. This monitoring is hampered by the effect of random atmospheric variations on satellite imagery, which may be suppressed through temporal filtering. This paper aims to evaluate the utility of temporally filtering successive MODIS data in monitoring an outbreak in East China. Of the eight vegetation indices examined, the commonly used NDVI was the most indicative of varying vegetation conditions caused by locust infestation inside the study area. The averaging of three successive days of satellite data improves the R 2 value of NDVI regression models by 0.227 over single-day data. It also outperforms the data averaged from two successive days (a broader window size was not attempted due to the short span of the study period). Temporally, NDVI changed at varying rates daily during the outbreak. Early in the outbreak it increased at a reduced pace until 7.5 days. Afterwards it started to decrease at an accelerated rate. If temporally filtered with a proper window size, successive MODIS data allow the outbreak to be monitored accurately ( R 2 = 0.696). [ABSTRACT FROM AUTHOR]

The Triaxial Attitude Control Testbed has been developed as part of a research program at the University of Michigan on multibody rotational dynamics and control. In this paper, equations of motion are derived and presented in various forms. Actuation mechanisms are incorporated into the models; these include fan actuators, reaction wheel actuators and proof mass actuators that are fixed to the triaxial base body. The models also allow incorporation of unactuated auxiliary bodies that are constrained to move relative to the triaxial base body. The models expose the dynamic coupling between the rotational motion of the triaxial base body, the relative or shape motion of the unactuated auxiliary degrees of freedom, and dynamics associated with actuation mechanisms. Many different model simplications and approximations are developed. Control models for the triaxial attitude control testbed are formulated that reflect specific assumptions. [ABSTRACT FROM AUTHOR]

Epidemiologic studies suggest a strong genetic component for susceptibility to systemic lupus erythematosus (SLE). To investigate the genetic mechanism of pathogenesis of SLE, we studied the difference in gene expression of peripheral blood cells between 10 SLE patients and 18 healthy controls using oligonucleotide microarray. When gene expression for patients was compared to the mean of normal controls, among the 3002 target genes, 61 genes were identified with greater than a two-fold change difference in expression level. Of these genes, 24 were upregulated and 37 downregulated in at least half of the patients. By the Welch's ANOVA/Welch's t-test, all these 61 genes were significantly different (P`0.05) between SLE patients and normal controls. Among these genes with differential expression, IFN-? and Ly6E (TSA-1/Sca-2) may play an important role in the mechanism of SLE pathogenesis. TSA-1 antigens may represent an important alternative pathway for T-cell activation that may be involved in IFN-mediated immunomodulation. Hierarchical clustering showed that patient samples were clearly separated from controls based on their gene expression profile. These results demonstrate that high-density oligonucleotide microarray has the potential to explore the mechanism of pathogenesis of systemic lupus erythematosus.Genes and Immunity (2003) 4, 177-186. doi:10.1038/sj.gene.6363966 [ABSTRACT FROM AUTHOR]

We have sequenced the promoter region of the murine asparagine synthetase gene and examined its methylation profile in the CpG islands of L-asparaginase-sensitive 6C3HED cells (asparagine auxotrophs) and resistant variants (prototrophs). In the former, complete methylation of the CpG island is correlated with failure of expression of mRNA: cells of the latter possess both methylated and unmethylated alleles, as do cells of the intrinsically asparagine-independent lines L1210 and EL4. A similar phenomenon was seen in normal splenic cells of adult mice. This was age related: no methylation was found in weanlings, but up to 45% of gene copies in animals 18 weeks or older were methylated. It was also tissue related, with methylation occurring rarely in liver cells. The relationship of these changes to oncogenesis is considered. [ABSTRACT FROM AUTHOR]

Intramuscular injection of plasmid DNA results in myofiber cell expression of proteins encoded by the DNA. The preferred vehicle for plasmid DNA injections has been saline (154 mM sodium chloride) or PBS (154 mM NaCI plus 10 mM sodium phosphate). Here, it is shown that injection of luciferase or β-galactosidase encoding plasmid DNA in a 150 mM sodium phosphate vehicle into murine muscle resulted in a two- to seven-fold increase in transgene expression compared with DNA injected in saline or PBS. When the DNA encoded secreted alkaline phosphatase, preproinsulin or interferon, sodium phosphate vehicle increased their serum levels by two- to four-fold. When the DNA encoded mouse erythropoietin, sodium phosphate vehicle increased hematocrits by two-fold compared with DNA injected in saline. When the DNA encoded influenza nucleoprotein, sodium phosphate increased anti-nucleoprotein antibody titers by two-fold. The expression of luciferase from plasmid DNA instilled into lung was increased five-fold compared with that in vehicle without sodium phosphate. Incubation of plasmid DNA with muscle extract or serum showed that sodium phosphate protected the DNA from degradation. Thus, a change from sodium chloride to sodium phosphate vehicle can enhance the expression of plasmid DNA in a tissue, possibly by inhibiting DNA degradation. [ABSTRACT FROM AUTHOR]

This project was designed to evaluate the oxidative stability of corn oils with increased total saturated fatty acid composition and to test the feasibility of using the AromaScan, an “electronic nose,” to detect the odors/aromas produced by oxidation. Corn oils with traditional (13.1%) and elevated (14.7 to 17.1%) total saturated fatty acid percentages were evaluated for their oxidative quality. Oils from five corn genotypes were extracted, refined, bleached, and deodorized (RBD) in the laboratory. Two replications, separated at the point of extraction, were evaluated for each genotype. The RBD corn oils (18.0 g) were stored in 50-mL beakers at 60°C in the dark, and peroxide values were measured every other day for 8 d. Corn oils with elevated saturated fatty acid compositions were more stable ( P<0.05) than the traditional corn oil. Aroma intensity of the oils was measured with an AromaScan at days 0, 4, and 8. The AromaScan provided a useful tool to detect odors/aromas produced by oxidation during an oxidative stability study; this tool might be used to partly replace human sensory panel evaluation of oxidized samples. [ABSTRACT FROM AUTHOR]