Search

Accumulating evidence suggests that individuals with autism spectrum disorder (ASD) show impairments in using contextual priors to predict others' actions and make intention inference. Yet less is known about whether and how children with ASD acquire contextual priors during action observation and how contextual priors relate to their action prediction and intention inference. To form proper contextual priors, individuals need to observe the social scenes in a reliable manner and focus on socially relevant information. By employing a data‐driven scan path method and areas of interest (AOI)‐based analysis, the current study investigated how contextual priors would relate to action prediction and intention understanding in 4‐to‐9‐year‐old children with ASD (N = 56) and typically developing (TD) children (N = 50) during free viewing of dynamic social scenes with different intentions. Results showed that children with ASD exhibited higher intra‐subject variability when scanning social scenes and reduced attention to socially relevant areas. Moreover, children with high‐level action prediction and intention understanding showed lower intra‐subject variability and increased attention to socially relevant areas. These findings suggest that altered fixation patterns might restrain children with ASD from acquiring proper contextual priors, which has cascading downstream effects on their action prediction and intention understanding. Lay Summary: Skilled social interactions require individuals to infer others' intentions and predict others' actions based on prior experiences, which is impaired in children with ASD. The present study investigated whether and how children with ASD acquire prior knowledge and how their prior knowledge would influence action prediction and intention understanding during viewing dynamic social scenes. We found that children with ASD viewed social scenes in an unpredictable way and showed decreased attention to socially relevant areas as compared with typically developing children. Moreover, children with high‐level action prediction and intention understanding observed the social scenes in a more predictable way and exhibited increased attention to socially relevant areas. These findings suggest that children with ASD may acquire unreliable prior knowledge, which has adverse effects on their action prediction and intention understanding. [ABSTRACT FROM AUTHOR]

Exploration of new electron‐withdrawing building blocks plays a key role in the development of n‐type organic semiconductors. Herein, a strong electron‐withdrawing building block, dipyridyl‐fused quinoxalineimide (DPQI), was successfully designed and synthesized. Single‐crystal structure reveals that DPQI molecule possesses a completely planar backbone, which is beneficial for charge transport. For comparison, dibenzo‐fused quinoxalineimide (DBQI) was also synthesized. The frontier molecular orbital (FMO) energy levels downshift with the incorporation of nitrogen atoms onto the π‐conjugated backbone of quinoxalineimide. Two acceptor‐acceptor (or all‐acceptor) polymers P(BTI‐DBQI) and P(BTI‐DPQI) based on DBQI and DPQI were synthesized, respectively. Two polymers exhibit deep lowest‐unoccupied molecular orbital (LUMO) levels (~−3.5 eV). Additionally, P(BTI‐DPQI) exhibits unipolar n‐type charge transport with μe of 1.4×10−4 cm2 V−1 s−1 in the organic field‐effect transistors (OFET), which render them highly attractive for developing n‐type semiconductors device. This work demonstrates that DPQI is a promising building block for constructing n‐type polymer semiconductors. [ABSTRACT FROM AUTHOR]

Objective: A systematic review and meta‐analysis were conducted to evaluate the efficacy and safety of ablative laser combined with pulsed dye laser to treat pathological scars. Methods: A systematic literature review was conducted to identify all blind, randomized, controlled trials of ablative laser and pulsed dye laser for treating pathological scars. The databases PubMed, Embase, and Cochrane were used. All research on ablative laser combined with PDL in treating pathological scars with ablative laser or no treatment as controls were included in the meta‐analysis. The retrieved studies' reference lists were thoroughly examined. Results: POSAS and VSS were used as evaluation criteria in seven studies involving 189 patients. Effect of combined laser group therapy (−1.259 95% confidence interval, −1.515 to −1.003; p < 0.0001). The difference between the combined treatment and control groups was (−1.375; 95% CI, −1.727 to −1.023; p < 0.0001) and (−1.150; 95% CI, −1.523 to −0.777; p < 0.0001). Conclusions: Ablative laser combined with PDL is more effective and safer than ablative laser or PDL alone in the treatment of pathological scars. [ABSTRACT FROM AUTHOR]

Background: Striae Distensae (SD) is a common dermatological lesion. The mechanism of formation is unclear, the prevailing theory is mechanical pulling of the skin and hormonal changes. Traditional SD treatment methods include topical drugs, photoelectric therapy, stripping and others, but each has limitations. Stromal vascular fraction gel (SVF‐gel) is a filler physically prepared from granular fat, enriched with adipose‐derived stem cells (ADSCs) and extracellular matrix (ECM). A good effect in the treatment of neck lines, wounds, acne, and other aspects. SD formation and treatment goals are comparable to those of neck lines. In this study, SVF‐gel filling will be used to treat mature SD, and its effectiveness and safety will be discussed in detail. Methods: From December 2019 to June 2022, recruit patients who want to treat SD caused by obesity or pregnancy among those who have "autologous fat aspiration" to change their body shape. Preoperatively, the area to be treated for SD was marked, autologous fat aspiration was performed, and the aspirated fat was prepared as SVF‐gel and filled into the preoperatively marked SD. All patients had preoperative and postoperative follow‐up with planar photographs and VISIA skin analyzer photographs to assess surgical results and safety from subjective and objective perspectives. Results: A total of 36 patients were enrolled, with 31 of them successfully followed up on. The mean Global Aesthetic Improvement Scale (GAIS) score six months after surgery was 1.87 ± 0.03. At six months postoperatively, the overall patient satisfaction rate was 90%. The depth, area, and color of SD improved six months after surgery, and no serious complications occurred in any of the patients. Conclusions: SVF‐gel is a safe and effective method of improving mature SD and can be used as a clinical treatment option. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by amyloid‐β (Aβ) deposition and neurofibrillary tangles. Although the NAD+‐dependent deacetylases SIRT1 and SIRT2 play pivotal roles in age‐related diseases, their cooperative effects in AD have not yet been elucidated. Here, we report that the SIRT2:SIRT1 ratio is elevated in the brains of aging mice and in the AD mouse models. In HT22 mouse hippocampal neuronal cells, Aβ challenge correlates with decreased SIRT1 expression, while SIRT2 expression is increased. Overexpression of SIRT1 prevents Aβ‐induced neurotoxicity. We find that SIRT1 impedes SIRT2‐mediated APP deacetylation by inhibiting the binding of SIRT2 to APP. Deletion of SIRT1 reduces APP recycling back to the cell surface and promotes APP transiting toward the endosome, thus contributing to the amyloidogenic processing of APP. Our findings define a mechanism for neuroprotection by SIRT1 through suppression of SIRT2 deacetylation, and provide a promising avenue for therapeutic intervention of AD. [ABSTRACT FROM AUTHOR]

Transient sensor malfunction, improper replacement measures, and large non‐Gaussian noise can cause data outliers in real‐world scenarios. In this article, an outlier‐robust zonotope set‐membership filter is proposed for uncertain nonlinear systems susceptible to outliers. In order to linearize nonlinear systems, a linearization method based on Stirling's interpolation formula is proposed. Then, an outlier detector utilizing the linearization error bounds, the prediction domain, and the output feasible domain is constructed. Based on the linearized system, a tight strip construction method is given to reduce the conservatism of the estimated enclosure. Moreover, a prediction‐correction‐backward reconstruction filter structure is designed to improve estimation accuracy and reduce conservatism. The proposed structure fuses historical data to attenuate the impact of uncertainty on the system. The robustness, guarantee, and convergence of the proposed filter are investigated. Finally, the effectiveness of the proposed approach is evaluated by two simulation examples. [ABSTRACT FROM AUTHOR]

In this study, the blank hydrogels and the niosomal hydrogels loading coenzyme Q10 (CoQ10) were prepared by carbomer (CBM) and scleroglucan (SCL), and their physicochemical properties were characterized in terms of rheological and texture measurement, FTIR, SEM, DSC, and DLS. First, the blank hydrogels CBM‐SCL‐Gel were prepared. With the increase of SCL concentration, the viscosity and modulus increased, displaying better shear thinning behavior of pseudoplastic fluid. A dense network structure was formed in CBM‐SCL‐Gel, especially for CBM/SCL at 5/4 and 5/5, due to hydrogen bonding between CBM and SCL. The swelling behaviors of the composite gels conformed to pseudo‐second‐order kinetics, and CBM/SCL at 5/1 exhibited the highest swelling capability. The addition of SCL made the water absorption mechanism tend to a non‐Fickian diffusion mode. Then, the niosomal hydrogel was prepared by the optimized gel formulation with the CoQ10‐loaded niosome. It was found that the gel properties were insignificantly affected by the CoQ10 niosomes. The particle sizes of the niosomes in the gel were a little larger than that in aqueous suspension. After storage for 30 days, the CoQ10 retention rate in the niosomal gel remained at 92% (4°C, N‐Gel), representing high stability of CoQ10. [ABSTRACT FROM AUTHOR]

Autophagy is one of the underlying causes of resistance to many antitumor drugs, including cisplatin (DDP). The low‐density lipoprotein receptor (LDLR) is a regulator of ovarian cancer (OC) progression. However, whether LDLR regulates DDP resistance in OC via autophagy‐related pathways remains unclear. LDLR expression was measured by quantitative real‐time PCR, western blot (WB) and IHC staining. A Cell Counting Kit 8 assay was employed to evaluate DDP resistance and cell viability, and flow cytometry was used to assess apoptosis. WB analysis was employed to evaluate the expression of autophagy‐related proteins and PI3K/AKT/mTOR signaling pathway proteins. The autophagolysosomes and the fluorescence intensity of LC3 were observed by transmission electron microscopy and immunofluorescence staining, respectively. A xenograft tumor model was established to explore the role of LDLR in vivo. LDLR was highly expressed in OC cells, which was correlated with disease progression. In DDP‐resistant OC cells, high LDLR expression was related to DDP resistance and autophagy. Downregulation of LDLR repressed autophagy and growth in DDP‐resistant OC cell lines by activating the PI3K/AKT/mTOR pathway, and these effects were eliminated by an mTOR inhibitor. In addition, LDLR knockdown also reduced OC tumor growth by suppressing autophagy associated with the PI3K/AKT/mTOR pathway. LDLR promoted autophagy‐mediated DDP resistance in OC associated with the PI3K/AKT/mTOR pathway, indicating that LDLR might be a new target to prevent DDP resistance in OC patients. [ABSTRACT FROM AUTHOR]

Benzyl butyl phthalate (BBP) is a chemical softener and plasticizer commonly used in toys, food packaging, wallpaper, detergents and shampoos. The estrogenic actions of BBP have detrimental effects on humans and animals. In this study, the specific influence of BBP on mouse oocyte maturation was investigated using in vivo and in vitro models. The experiment first verified that BBP exposure significantly affected the rate of oocyte exclusion of the first polar body, although it did not affect germinal vesicle breakdown (GVBD) through in vitro oocyte culture system. Results of in vitro fertilization show that BBP exposure affects blastocyst rate. Subsequently, the results obtained by immunofluorescence staining technology showed that oocyte spindle organization, chromosomal arrangement and the distribution of cortical actin were disrupted by BBP exposure, and led to the failure of oocyte meiotic maturation and the subsequent early embryo development. Singe‐cell transcriptome analysis found that BBP exposure altered the expression levels of 588 genes, most associated with mitochondria‐related oxidative stress. Further analysis demonstrated that the detrimental effects of BBP involved the disruption of mitochondrial function and oxidative stress‐induced early apoptosis. Nicotinamide mononucleotide (NMN) supplementation reduced the adverse effects of BBP. Collectively, these findings revealed a mechanism of BBP‐induced toxicity on female reproduction and showed that NMN provides an effective treatment for BBP actions. [ABSTRACT FROM AUTHOR]

A single biomaterial is disadvantageous for constructing skin in vitro, so a mixed biomaterial is more conducive to skin research. In this study, agarose–chitosan scaffolds with a final concentration of 4% were constructed by freeze‐drying, in which the concentration ratios of agarose to chitosan were 1:3, 2:2, and 3:1. The scaffolds were coated with a 3 mg/ml collagen solution, and the mechanical properties were evaluated by studying density, porosity, swelling rate, and degradation rate. The results demonstrated that the agarose–chitosan scaffolds were porous, with porosity reaching 93%. Their densities ranged from 0.1 to 0.16 g/cm3. Analysis of Young's modulus showed that the mechanical properties of the agarose–chitosan scaffolds were significantly enhanced when the agarose content in the agarose–chitosan scaffolds was increased. Moreover, the density and Young's modulus of the agarose–chitosan scaffolds of different concentration ratios were significantly different (p < 0.01). These scaffolds can withstand a certain amount of external pressure, such as that of human skin, making them more suitable for further skin replacement research. In addition, the results of thiazolyl blue tetrazolium bromide (MTT) cell assay and immunofluorescence staining showed that the collagen‐coated agarose–chitosan scaffolds were conducive to keratinocyte proliferation and differentiation. The MTT results revealed significant differences between the agarose–chitosan scaffolds coated with collagen and the agarose–chitosan scaffolds without collagen (p < 0.05). This study provides the potential for in vitro skin research and applications. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Alzheimer's disease (AD) is the most common form of dementia with a complex genetic background. The cause of sporadic AD (sAD) remains largely unknown. Increasing evidence shows that genetic variations play a crucial role in sAD. P75 neurotrophin receptor (p75NTR, encoded by NGFR) plays a critical role in the pathogenesis of AD. Yet, the relationship between NGFR gene polymorphisms and AD was less studied. This study aims to analyze the relationship of NGFR gene polymorphism with the risk of AD in the Chinese Han population and amyloid‐β deposition in the ADNI cohort. Methods: This case–control association study was conducted in a Chinese Han cohort consisting of 366 sporadic AD (sAD) patients and 390 age‐ and sex‐matched controls. Twelve tag‐SNPs were selected and genotyped with a multiplex polymerase chain reaction‐ligase detection reaction (PCR‐LDR) method. The associations between tag‐SNPs and the risk of AD were analyzed by logistic regression. Moreover, another cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database was included to examine the association of one tag‐SNP (rs2072446) with indicators of amyloid deposition. Kaplan–Meier survival analysis and Cox proportional hazards models were used to test the predictive abilities of rs2072446 genotypes for AD progression. The mediation effects of Aβ deposition on this association were subsequently tested by mediation analyses. Results: After multiple testing corrections, one tag‐SNP, rs2072446, was associated with an increased risk of sAD (additive model, OR = 1.79, Padjustment = 0.0144). Analyses of the ADNI cohort showed that the minor allele (T) of rs2072446 was significantly associated with the heavier Aβ burden, which further contributed to an increased risk of AD progression in APOE ε4 non‐carrier. Conclusion: Our study found that rs2072446 in NGFR is associated with both the risk of sAD in the Chinese Han population and the amyloid burden in the ADNI cohort, which reveals the role of p75NTR in AD from a genetic perspective. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this study the potential of liposomes as a vitamin E (VE) and β‐carotene (βC) delivery system was examined. The co‐encapsulated liposomes of βC and VE (L‐VE‐βC) were prepared and characterized. Their antioxidant properties were evaluated by free radical scavenging activities of 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS), hydroxyl radical and lipid peroxidation assay. The in vitro sustained release behaviour was then investigated and discussed. RESULTS: VE and βC were co‐encapsulated in liposomes with high encapsulation efficiency, up to 92.49% and 86.16% for βC and VE, respectively. The antioxidant activities of L‐VE‐βC samples were significantly higher than that of single loaded liposome. Among different ratios of VE/βC, L‐VE‐βC at 5:3 exhibited the highest radical scavenging rates, with 66.80%, 56.58% and 34.39% for DPPH, ABTS and OH radical, respectively. L‐VE‐βC samples also had a good ability to inhibit lipid peroxidation, especially the sample with ratios of VE/βC at 5:3 and 3:1. In simulated gastrointestinal release, L‐VE‐βC exhibited an excellent sustained release behaviour in SGF with the accumulated rate at about 20%, while the release rate in SIF increased to over 80%, where they should be absorbed. The release kinetics analysis indicated that βC was released in the Higuchi model in stomach, and the Korsmeyr–Peppas model in intestine. CONCLUSION: Compared to single loaded liposomes, the combined‐loaded liposomes exhibited higher antioxidant activity and bioavailability, suggesting the potential applications in functional foods. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The role of α1 adrenergic receptors (α1‐ARs) signaling pathway in the pathogenesis of Alzheimer's disease (AD) has rarely been investigated. Clarifying the pathophysiological functions of α1‐ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic targets of AD. This study included 2 arms of in vivo investigations: 1) 6‐month‐old female APPswe/PS1 mice were intravenously treated with AAV‐PHP.eB‐shRNA (α1‐ARs)‐GFP or AAV‐PHP.eB‐GFP for 3 months. 2) 3‐month‐old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or an equal volume of saline for 6 months. SH‐SY5Y cell lines bearing human amyloid precursor protein were treated with terazosin or saline for investigating possible mechanisms. α1‐ARs knockdown mice exhibited improved behavioral performances in comparison with control mice. α1‐ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aβ species, compact and total Aβ plaques, than control mice. α1‐ARs inhibitor terazosin substantially reduced Aβ deposition, attenuated downstream pathologies including tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction et al., and rescued behavioral deficits in APPswe/PS1 mice. In vitro investigation demonstrated that α1‐ARs inhibition down‐regulated BACE1 expression, and promoted ser9 phosphorylation of GSK‐3β, thus reducing Aβ production. This study indicates that inhibition of α1‐ARs signaling pathway might represent a promising therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Background: A previous study demonstrated that nearly 40%–60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aβ in the periphery. Methods: We investigated the physiological clearance of Aβ by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice. Results: We found that Aβ levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aβ is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aβ directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aβ burden and AD‐related pathologies in AD mice. Conclusion: Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aβ in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD. [ABSTRACT FROM AUTHOR]

Background: Genetic risk factors have been explored extensively for late onset Alzheimer's Disease (LOAD). The largest meta‐analysis GWAS studies to date (Bellenguez et al., 2022) identified 83 single nucleotide polymorphisms (SNPs) associated with LOAD in the general population. The Long Life Family Study (LLFS) is aimed to identify factors associated with familial longevity and healthy aging by examining US and Danish families. Our earlier studies have shown that LLFS families are at lower risk of several age‐related diseases, including LOAD. Here, we will: (1) compare allele frequencies and effect sizes of the identified meta‐GWAS variants against those in LLFS; and (2) assess whether a polygenic risk score (PRS) based on meta‐GWAS variants differs between LOAD vs. cognitively healthy in LLFS. Method: We examined LLFS participants who were Non‐Hispanic Whites, had available cognitive and whole genome sequencing (WGS) (n = 4,220). Allele frequencies were estimated based on founders only. Association analyses were performed via logistic regression using Wald test and adjusting for sex, age, site, education, first principal components, and the genetic relationship matrix. PRS was calculated using a weighted formula, and to account for family structure, means for each status per family were obtained. Result: Independent of LOAD status, 13 SNPs had significantly different allele frequencies between the two studies. Minor allele frequencies of 10 of the SNPs were lower in LLFS when compared with Bellenguez et al. When examining the relations between LOAD and the 77 available SNPs, only five variants appeared to be associated in LLFS. The direction of association differed for two of the SNPs. Lastly, estimated PRS scores did not differ by LOAD status (affected vs unaffected: ‐0.059 vs. ‐0.054, respectively). Conclusion: Here we show that variants associated with LOAD in the general population were not necessarily associated with LOAD in in the LLFS cohort, a cohort ascertained for familial healthy aging. When estimating disease risk using genetic markers, as expected, ascertainment needs to be taken into consideration. [ABSTRACT FROM AUTHOR]

A record high zT of 2.2 at 740 K is reported in Ge0.92Sb0.08Te single crystals, with an optimal hole carrier concentration ≈4 × 1020 cm−3 that simultaneously maximizes the power factor (PF) ≈56 µW cm−1 K−2 and minimizes the thermal conductivity ≈1.9 Wm−1 K−1. In addition to the presence of herringbone domains and stacking faults, the Ge0.92Sb0.08Te exhibits significant modification to phonon dispersion with an extra phonon excitation around ≈5–6 meV at Γ point of the Brillouin zone as confirmed through inelastic neutron scattering (INS) measurements. Density functional theory (DFT) confirmed this phonon excitation, and predicted another higher energy phonon excitation ≈12–13 meV at W point. These phonon excitations collectively increase the number of phonon decay channels leading to softening of phonon frequencies such that a three‐phonon process is dominant in Ge0.92Sb0.08Te, in contrast to a dominant four‐phonon process in pristine GeTe, highlighting the importance of phonon engineering approaches to improving thermoelectric (TE) performance. [ABSTRACT FROM AUTHOR]

In this paper, we study the existence of multiple nontrivial solutions for the following semilinear Schrödinger equation: 1−Δu+V(x)u=f(x,u),x∈ℝN,u∈H1(ℝN), where the potential V is continuous and allowed to be sign‐changing and f(x,u) satisfies more general sublinear growth conditions than those in previous studies. The first result of this paper obtains the existence of a nontrivial solution of (1). The second establishes an existent result on infinitely many nontrivial solutions of (1) by using a variant fountain theorems. [ABSTRACT FROM AUTHOR]

Uranium is a key resource for the development of the nuclear industry, and extracting uranium from the natural seawater is one of the most promising ways to address the shortage of uranium resources. Herein, a semiconducting covalent organic framework (named NDA‐TN‐AO) with excellent photocatalytic and photoelectric activities was synthesized. The excellent photocatalytic effect endowed NDA‐TN‐AO with a high anti‐biofouling activity by generating biotoxic reactive oxygen species and promoting photoelectrons to reduce the adsorbed UVI to insoluble UIV, thereby increasing the uranium extraction capacity. Owing to the photoinduced effect, the adsorption capacity of NDA‐TN‐AO to uranium in seawater reaches 6.07 mg g−1, which is 1.33 times of that in dark. The NDA‐TN‐AO with enhanced adsorption capacity is a promising material for extracting uranium from the natural seawater. [ABSTRACT FROM AUTHOR]

In the magnetic levitation planar motor which can achieve six degrees‐of‐freedom motion, decoupling control is realised by coil array commutation algorithm, due to the limitation of the sampling period of the real‐time system, a high‐dynamic coil array commutation algorithm is needed to achieve higher computational efficiency, but this will lead to the coil array not accurately providing the force/torque required for the trajectory movement, and generate a certain torque ripple error. In this study, the cause of this torque ripple error is analysed, and a feedforward compensation method is proposed. The results of simulation and experiment show that the proposed feedforward compensation method of high‐dynamic coil array commutation algorithm can reduce torque ripple error by 88%, and achieve higher trajectory tracking accuracy while satisfying high computational efficiency. [ABSTRACT FROM AUTHOR]

Abstract: Taking account of the effect of the driver's memory, an extended car‐following model is proposed in this paper. A control signal including the velocity contrast of considered car and the following car is taken into account in this extended model. Numerical simulations are implemented to prove that the application of the model can suppress the traffic congestion successfully. [ABSTRACT FROM AUTHOR]

Toxicity assessment of nitration/ultrafiltration/reverse osmosis (nitration/UF/RO) project, which has recently been widely used as an efficient process with applications in practical leachate treatment, was very limited. In the present study, DNA damage of leachates was investigated before and after the nitration/UF/RO process by a battery of assays with human hepatoma cells. Methyletrazolium assay showed a high cytotoxicity of 97.1% after being exposed to the highest concentration of raw leachate for 24 h, and a cytotoxicity of 26% in effluent at a concentration of 30% ( v/v). Both comet assay (24 h) and γH2AX flow cytometer assay (3 h) showed increased levels of DNA damage in cells exposed to raw leachate and after nitration/UF-treated leachate followed by a significant increase of 7-ethoxyresorufin- O-deethylase activity. However, the effluent after nitration/UF/RO treatment showed no significant difference compared to negative control for γH2AX flow cytometer assay but slight DNA damage at concentrations of 20% and 30% ( v/v) as well as increase of 7-ethoxyresorufin- O-deethylase. Analysis showed that nitration/UF/RO process exhibited high removal of physicochemical indexes and significant reduction of toxic and genotoxic effects of leachate, but still demands an improvement to reduce all possible negative risks to the environment and humans. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Based upon the classical car-following theory, an extended car-following model considering variable safety distance (VSD) and time-delay effect is constructed to improve driving efficiency and safety. Considering multiple preceding cars' speed differences and the difference between headway and safety distance, a new control signal is designed from the viewpoint of multiple information feedback control strategy. Stability criterion for the modified model is acquired by applying control theory. Several numerical simulations are used to show the effects of multiple preceding cars' speed changes and variable safety distance on car-following phenomena, and the outcomes prove that the presented model can enhance traffic safety and suppress traffic jams. [ABSTRACT FROM AUTHOR]

Introduction We performed linkage analyses in Caribbean Hispanic families with multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may contain disease causative variants. Methods We selected 67 LOAD families to perform genome-wide linkage scan. Analysis of the linked regions was repeated using the entire sample of 282 families. Validated chromosomal regions were analyzed using joint linkage and association. Results We identified 26 regions linked to LOAD (HLOD ≥3.6). We validated 13 of the regions (HLOD ≥2.5) using the entire family sample. The strongest signal was at 11q12.3 (rs2232932: HLOD max = 4.7, P joint = 6.6 × 10 −6 ), a locus located ∼2 Mb upstream of the membrane-spanning 4A gene cluster. We additionally identified a locus at 7p14.3 (rs10255835: HLOD max = 4.9, P joint = 1.2 × 10 −5 ), a region harboring genes associated with the nervous system ( GARS , GHRHR, and NEUROD6 ). Discussion Future sequencing efforts should focus on these regions because they may harbor familial LOAD causative mutations. [ABSTRACT FROM AUTHOR]

Objective To detect rare coding variants underlying loci detected by genome-wide association studies (GWAS) of late onset Alzheimer disease (LOAD). Methods We conducted targeted sequencing of ABCA7, BIN1, CD2AP, CLU, CR1, EPHA1, MS4A4A/MS4A6A, and PICALM in 3 independent LOAD cohorts: 176 patients from 124 Caribbean Hispanics families, 120 patients and 33 unaffected individuals from the 129 National Institute on Aging LOAD Family Study; and 263 unrelated Canadian individuals of European ancestry (210 sporadic patients and 53 controls). Rare coding variants found in at least 2 data sets were genotyped in independent groups of ancestry-matched controls. Additionally, the Exome Aggregation Consortium was used as a reference data set for population-based allele frequencies. Results Overall we detected a statistically significant 3.1-fold enrichment of the nonsynonymous mutations in the Caucasian LOAD cases compared with controls ( p = 0.002) and no difference in synonymous variants. A stop-gain mutation in ABCA7 (E1679X) and missense mutation in CD2AP (K633R) were highly significant in Caucasian LOAD cases, and mutations in EPHA1 (P460L) and BIN1 (K358R) were significant in Caribbean Hispanic families with LOAD. The EPHA1 variant segregated completely in an extended Caribbean Hispanic family and was also nominally significant in the Caucasians. Additionally, BIN1 (K358R) segregated in 2 of the 6 Caribbean Hispanic families where the mutations were discovered. Interpretation Targeted sequencing of confirmed GWAS loci revealed an excess burden of deleterious coding mutations in LOAD, with the greatest burden observed in ABCA7 and BIN1. Identifying coding variants in LOAD will facilitate the creation of tractable models for investigation of disease-related mechanisms and potential therapies. Ann Neurol 2015;78:487-498 [ABSTRACT FROM AUTHOR]

Objective In the context of late-onset Alzheimer's disease ( LOAD) over 20 genes have been identified but, aside APOE, all show small effect sizes, leaving a large part of the genetic component unexplained. Admixed populations, such as Caribbean Hispanics, can provide a valuable contribution because of their unique genetic profile and higher incidence of the disease. We aimed to identify novel loci associated with LOAD. Methods About 4514 unrelated Caribbean Hispanics (2451 cases and 2063 controls) were selected for genome-wide association analysis. Significant loci were further tested in the expanded cohort that also included related family members ( n = 5300). Two AD-like transgenic mice models (J20 and rTg4510) were used to study gene expression. Independent data sets of non-Hispanic Whites and African Americans were used to further validate findings, along with publicly available brain expression data sets. Results A novel locus, rs75002042 in FBXL7 (5p15.1), was found genome-wide significant in the case-control cohort (odd ratio [ OR] = 0.61, P = 6.19E-09) and confirmed in the related members cohorts ( OR = 0.63, P = 4.7E-08). Fbxl7 protein was overexpressed in both AD-like transgenic mice compared to wild-type littermates. Publicly available microarray studies also showed significant overexpression of Fbxl7 in LOAD brains compared to nondemented controls. single-nucleotide polymorphism ( SNP) rs75002042 was in complete linkage disequilibrium with other variants in two independent non-Hispanic White and African American data sets (0.0005 < P < 0.02) used for replication. Interpretation FBXL7, encodes a subcellular protein involved in phosphorylation-dependent ubiquitination processes and displays proapoptotic activity. F-box proteins also modulate inflammation and innate immunity, which may be important in LOAD pathogenesis. Further investigations are needed to validate and understand its role in this and other populations. [ABSTRACT FROM AUTHOR]

With the rapid development of cloud computing, more and more data are being centralized into cloud server for sharing. It is a challenge problem on how to keep them both private and accessible. Re-encryption function is a useful tool to fulfill secure cloud computing. Cloud data owners store their encrypted data on the cloud server. When other cloud users want to share the cloud data, cloud server can re-encrypt the encrypted data for them. So data on the cloud server can be both accessible and private. Secure obfuscation for re-encryption function can hide all the private information in the re-encryption function, so the obfuscated program can be directly outsourced to cloud server without leaking anything about the computation task. In this paper, we study on secure obfuscation for three kinds of new re-encryption functions: multi-use re-encryption, conditional re-encryption with keyword search, and broadcast re-encryption. We utilize the obfuscated results as tools to fulfill secure cloud computing. Cloud-computing schemes based on obfuscation have better security compared with other tools. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

It has been reported that NKD1 was an antagonist of the canonical Wnt/β-catenin pathway. While there is little information regarding NKD1 expression pattern in human hepatocellular carcinoma ( HCC). The aim of this study was to investigate the clinicopathologic significance and expression pattern of NKD1 in HCC. NKD1 protein expressions in 69 paired HCC cancer/adjacent non-cancerous tissues were detected by Western blot. Immunohistochemical studies were performed on 58 cases of HCC with integrated clinical information. NKD1 protein expression was divided into normal and low expression group and correlations between NKD1 protein expression and clinicopathologic factors were then evaluated. Western blot results showed that NKD1 protein levels were significantly lower in cancerous tissues compared with corresponding normal tissue (p < 0.05). In addition, we found that the level of NKD1 protein expression in HCC was significantly associated with tumor size (p = 0.011), intra or extra-hepatic metastasis (p = 0.010) and differentiation (p = 0.003). This is to our knowledge the first report investigating NKD1 protein expression pattern in HCC. Our data show that decreased NKD1 protein expression is associated with clinicopathologic factors, and suggest that NKD1 may play an important role in the development of HCC and could serve as a novel biomarker for HCC after further investigation. [ABSTRACT FROM AUTHOR]

Objective: Common single nucleotide polymorphisms in the SORL1 gene have been associated with late onset Alzheimer disease (LOAD), but causal variants have not been fully characterized nor has the mechanism been established. The study was undertaken to identify functional SORL1 mutations in patients with LOAD.Methods: This was a family- and cohort-based genetic association study. Caribbean Hispanics with familial and sporadic LOAD and similarly aged controls were recruited from the United States and the Dominican Republic, and patients with sporadic disease of Northern European origin were recruited from Canada. Prioritized coding variants in SORL1 were detected by targeted resequencing and validated by genotyping in additional family members and unrelated healthy controls. Variants transfected into human embryonic kidney 293 cell lines were tested for Aβ40 and Aβ42 secretion, and the amount of the amyloid precursor protein (APP) secreted at the cell surface was determined.Results: Seventeen coding exonic variants were significantly associated with disease. Two rare variants (rs117260922-E270K and rs143571823-T947M) with minor allele frequency (MAF) < 1% and 1 common variant (rs2298813-A528T) with MAF = 14.9% segregated within families and were deemed deleterious to the coding protein. Transfected cell lines showed increased Aβ40 and Aβ42 secretion for the rare variants (E270K and T947M) and increased Aβ42 secretion for the common variant (A528T). All mutants increased the amount of APP at the cell surface, although in slightly different ways, thereby failing to direct full-length APP into the retromer-recycling endosome pathway.Interpretation: Common and rare variants in SORL1 elevate the risk of LOAD by directly affecting APP processing, which in turn can result in increased Aβ40 and Aβ42 secretion. [ABSTRACT FROM AUTHOR]

Objective Common single nucleotide polymorphisms in the SORL1 gene have been associated with late onset Alzheimer disease (LOAD), but causal variants have not been fully characterized nor has the mechanism been established. The study was undertaken to identify functional SORL1 mutations in patients with LOAD. Methods This was a family- and cohort-based genetic association study. Caribbean Hispanics with familial and sporadic LOAD and similarly aged controls were recruited from the United States and the Dominican Republic, and patients with sporadic disease of Northern European origin were recruited from Canada. Prioritized coding variants in SORL1 were detected by targeted resequencing and validated by genotyping in additional family members and unrelated healthy controls. Variants transfected into human embryonic kidney 293 cell lines were tested for Aβ40 and Aβ42 secretion, and the amount of the amyloid precursor protein (APP) secreted at the cell surface was determined. Results Seventeen coding exonic variants were significantly associated with disease. Two rare variants (rs117260922-E270K and rs143571823-T947M) with minor allele frequency (MAF) < 1% and 1 common variant (rs2298813-A528T) with MAF = 14.9% segregated within families and were deemed deleterious to the coding protein. Transfected cell lines showed increased Aβ40 and Aβ42 secretion for the rare variants (E270K and T947M) and increased Aβ42 secretion for the common variant (A528T). All mutants increased the amount of APP at the cell surface, although in slightly different ways, thereby failing to direct full-length APP into the retromer-recycling endosome pathway. Interpretation Common and rare variants in SORL1 elevate the risk of LOAD by directly affecting APP processing, which in turn can result in increased Aβ40 and Aβ42 secretion. Ann Neurol 2015;77:215-227 [ABSTRACT FROM AUTHOR]

Pathogenic mutations in the three known genes - the amyloid precursor protein ( APP), presenilin 1 ( PSEN1), presenilin 2 ( PSEN2) - are known to cause familial Alzheimer's disease ( AD) and tend to be associated with early-onset AD. However, the frequency and risk associated with these mutations vary widely. In addition, mutations in the frontotemporal lobar degeneration ( FTLD) genes - the microtubule-associated protein tau ( MAPT), granulin ( GRN) - have also been found to be associated with clinical AD. Here, we conducted targeted resequencing of the exons in genes encoding APP, PSEN1, PSEN2, GRN, and MAPT in 183 individuals from families with four or more affected relatives, presumed to be AD, and living in the Dominican Republic and Puerto Rico. We then performed linkage and family-based association analyses in carrier families, and genotyped 498 similarly aged unrelated controls from the same ethnic background. Twelve potentially pathogenic mutations were found to be associated with disease in 53 individuals in the five genes. The most frequently observed mutation was the p.Gly206Ala variant in PSEN1 present in 30 (57%) of those sequenced. In the combined linkage and association analyses several rare variants were associated with dementia. In Caribbean Hispanics with familial AD, potentially pathogenic variants were present in 29.2%, four were novel mutations, while eight had been previously observed. In addition, some family members carried variants in the GRN and MAPT genes which are associated with FTLD. [ABSTRACT FROM AUTHOR]

ABSTRACT A blue fluorescent polymer based on poly(vinyl carbazole) (PVK) and terfluorene, combined to make a chemical hybrid at the carbazole unit (PVK-TF), is fully characterized in this study. PVK-TF shows useful emission features, such as peaks at 400, 420, 437, 460, and 496 nm, depending on the processing conditions. It possesses a relatively high triplet energy level (2.23 eV), electrochemical stability, good film-forming ability, and morphological stability. Based on this blue fluorescent material, highly efficient orange phosphorescent polymer light-emitting diodes (PLEDs) were fabricated with a maximum efficiency of 21.99 cd A−1, and a maximum luminance of 19552.3 cd m−2. Single-layer hybrid white PLEDs were developed, with a high color rendering index of 81.9 that emitted across the whole visible spectrum from 380 to 780 nm, corresponding to the Commission International de L'Eclairage coordinates x, y values of around (0.38, 0.40) and CCT = 3774, with a maximum current efficiency of 10.69 cd A−1, and a maximum brightness of 15723.3 cd m−2. © 2014 Wiley Periodicals, Inc. J. Polym. Sci. Part B: Polym. Phys. 2014, 52, 587-595 [ABSTRACT FROM AUTHOR]

A chemo-biochemical process for desulfurization of simulated natural gas containing hydrogen sulfide (H2S) was investigated. The results showed that using polyurethane foam as a support for immobilization of Acidithiobacillus ferrooxidans obtained good biological oxidation performance and the maximum oxidation rate of ferrous iron was 4.12 kg m−3 h−1. Moreover, a semi-empirical formula was set up for calculating theoretical ferrous oxidation rate as a function of influent Fe2+ and Fe2+ concentration in the bioreactor. The integrated chemical and biological process achieved removal efficiencies of about 80% when treating high concentrations of H2S (15 000 ± 100 ppmv). © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Compared with other T-helper subsets, Th17 cell numbers are very low in human blood but become elevated in chronic inflammatory diseases. In this study, we investigated mechanisms that may explain the frequent involvement of Th17 cells in autoimmune diseases such as uveitis. We compared Th17 and Th1 subsets and found that Th17 cells expressed lower IL-2 levels during Ag-priming and this correlated with their decreased susceptibility to activation-induced cell death (AICD). However, complete depletion of IL-2 with IL-2 neutralizing antibodies rendered Th17 cells as susceptible to apoptosis as Th1 cells, suggesting that the low levels of IL-2 produced by Th17 cells conferred survival advantages to this subset. We describe here a Th17 subtype that constitutively produces very low levels of IL-2 (Th17-DP). The Th17-DP population increased dramatically in the blood and retina of mice during experimental autoimmune uveitis, indicating their potential involvement in the etiology of uveitis. We further show that the majority of the memory Th17 cells in human blood are Th17-DP and are targets of daclizumab, an IL-2R antibody used in treating recalcitrant uveitis. Thus, Th17 cells may persist in tissues and contribute to chronic inflammation by limiting IL-2 production to levels that cannot provoke IL-2-induced AICD yet are sufficient to promote Th17 homeostatic expansion. [ABSTRACT FROM AUTHOR]

Neuronal or photoreceptor deficit observed in uveitis and multiple sclerosis derives in part from inability to control inflammatory responses in neuroretina or brain. Recently, IL-27 was found to play a role in suppressing experimental autoimmune uveitis and experimental autoimmune encephalomyelitis, two animal models that share essential pathological features of human uveitis and multiple sclerosis, respectively. However, the mechanism by which interleukin-27 (IL-27) inhibits central nervous system (CNS) inflammation is not clear. In this study we have investigated mechanisms that mitigate or curtail intraocular inflammation (uveitis) and examined whether inhibitory effects of IL-27 are mediated locally by neuroretinal cells or by regulatory T cells. We show here that microglia cells in the neuroretina constitutively secrete IL-27 and its expression is up-regulated during uveitis. We further show that photoreceptors constitutively express IL-27 receptor and respond to IL-27 signalling by producing anti-inflammatory molecules, IL-10 and suppressor of cytokine signalling 1 (SOCS1) through signal transducer and activator of transcription 1 (STAT1) -dependent mechanisms. Moreover, STAT1-deficient mice produced reduced amounts of IL-27, IL-10 and SOCS1 and developed more severe uveitis. Surprisingly, IL-10-producing regulatory T cells had marginal roles in suppressing uveitis. These results suggest that suppression of intraocular inflammation might be mediated through endogenous production of IL-27 and IL-10 by retinal cells, whereas SOCS proteins induced by IL-27 during uveitis may function to protect the neuroretinal cells from the toxic effects of pro-inflammatory cytokines. Targeted delivery of IL-27 into immune privileged tissues of the CNS may therefore be beneficial in the treatment of CNS inflammatory diseases, such as uveitis and multiple sclerosis. [ABSTRACT FROM AUTHOR]

Fetal and neonatal alloimmune thromboctyopenia due to maternal human platelet antigen (HPA)-1a antibodies affects primigravidas. Immunization must occur early in pregnancy before fetal platelets enter maternal blood via fetomaternal hemorrhage. The HPA-1a antigen is located on platelet glycoprotein (GP)IIIa (CD61, β3 integrin), which is also present on the placental syncytiotrophoblast (ST) and in direct contact with maternal blood. Since ST debris is shed into maternal blood during pregnancy, this material might be immunogenic in vivo. For experimental purposes, we prepared and characterized ST microparticles (STMPs) in vitro from term placentas. Phenotype analysis by flow cytometry and Western blotting showed that STMP expressed more placental alkaline phosphatase (PLAP) than GPIIIa. Quantitative real-time PCR demonstrated expression of human placental lactogen (HPL), human chorionic gonadotrophin (HCG), and GPIIIa by STMP, in the order HPL > HCG > GPIIIa. PLAP, HPL, and HCG are trophoblast-specific proteins. These STMPs may be a useful model for studying the natural ST debris in plasma of pregnant women. [ABSTRACT FROM AUTHOR]

Previously, we reported an algorithm for scanning a large number of tightly linked single nucleotide polymorphisms (SNPs) for LD mapping of functional sites or regions from a family-based association design. In the present study, we extend our method to a case-control design. We first use the expectation maximization (EM) algorithm to estimate haplotype frequencies of multiple linked SNPs, and follow this by constructing a contingency table statisticSfor LD analysis, based on the estimated haplotype frequencies. An empiricalp-value is obtained based on the null distribution of the maximum ofS(S *) from a large number (e.g., 1,000 or more) of randomized permutations. The proposed algorithm has been implemented in a computer program in which window searching for functional SNP sites can cover any number of loci without limitation, except that of computer storage. Unlike other programs for a case-control design that always conduct tests at a fix window width, in our program after setting a maximum size of haplotype window width, for a given maximum window width all possible widths of haplotypes are utilized to find the maximum statisticS * for each locus under investigation. The sensitivity of the proposed algorithm has been examined with simulated and real genotyping datasets. Association analyses indicate that our program is powerful enough to detect most, if not all, functional SNPs simulated in the original model or identified in the original report. Moreover, the program is very flexible and can be used in either regional or genome-wide scanning for association analysis with SNP markers. [ABSTRACT FROM AUTHOR]

Background Numerous twin studies on smoking behavior have shown that genetic and environmental factors play significant and approximately equal roles in the determination of smoking initiation (SI) and smoking persistence (SP). However, estimates of heritability (h²), shared (c²) and unique environmental effects (e²) from the literature display considerable variability for SI and SP. due most probably to differences in statistical analysis models, age, gender, sample size, origin of cohorts and measurement of smoking behavior, Methods A systematic literature search identified six studies for SI and 10 studies for SP. Data from these studies were obtained and re-analysed by metaanalytical techniques. Results For SI, our results indicate that the parameters h², c² and e² are (mean ± SEM): 0.37 ± 0.04. 0.49 ± 0.04 and 0.17±0.03 in male adults, and 0,55 ± 0.04, 0.24 ± 0.06 and 0.16 ± 0.01 in female adults, respectively. These values were weighted by a combination of original estimates of variance from studies reporting variances plus estimated variances from studies where variances were not reported (called the combined variance method). Using the same approach for SP, we found that the parameters h², c² and e² weighted by the combined variance method for the phenotype are (mean ± SEM): 0,59 ± 0.02. 0.08 ± 0.04 and 0.37 ± 0.03 in male adults, and 0.46 ± 0.12, 0.28 ± 0.08 and 0.24 ± 0.07 in female adults, respectively, Conclusions Our results indicate that genetic factors play a more significant role for SI but a less significant role for SP in female adults compared to male adults. Significant gender difference was also detected in shared environmental factors for SI and SP. However, no significant gender difference was detected for e² for either phenotype. These findings suggest that genetic and environmental factors... [ABSTRACT FROM AUTHOR]

Abstract. It is widely accepted that oxidative stress (OS) is a major causative factor for many of the age-related dysfunctions and specific diseases. Since the oxidative stress state (OSS) of an individual depends on hereditary, dietary, and environmental factors, there is a large heterogeneity in the population that may be related to disease incidence and longevity. Hence there is a need to assess how well an individual is coping against OS. The Japan Institute for the Control of Aging (JaICA) and Genox have jointly developed a profiling technique to measure the "Oxidative Stress Profiles (JaICA-Genox OSP)" of individuals and laboratory test animals. The JaICA-Genox OSP consists of about 45 different assays measuring the levels of oxidative damage in lipids and nucleic acids, and the antioxidant defenses in the serum. In addition, several bio-markers for cardiovascular disease risk are also measured, and assays to measure specific age-and sex-related hormones in the serum and urine, and race elements in serum, urine, and drinking water are also undertaken. This overview discusses the designing of the JaICA-Genox OSP and its application in the testing of human subjects. [ABSTRACT FROM AUTHOR]