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Curcumin, derived from the rhizome Curcuma longa, has been scientifically proven to possess anti-inflammatory activity but is of limited clinical and veterinary use owing to its low bioavailability and poor solubility. Hence, analogs of curcuminoids with improved biological properties have been synthesized to overcome these limitations. This study aims to provide the pharmacological basis for the use of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a synthetic curcuminoid analog, as an anti-edematogenic and anti-granuloma agent. The carrageenan-induced paw edema and the cotton pellet-induced granuloma assays were used to assess the anti-inflammatory activity of DHHPD in mice. The effects of DHHPD on the histaminergic, serotonergic, and bradykininergic systems were determined by the histamine-, serotonin-, and bradykinin-induced paw edema tests, respectively. DHHPD (0.1, 0.3, 1, and 3 mg/kg, intraperitoneal) evoked significant reductions (p < 0.05) in carrageenan-induced paw edema at different time intervals and granuloma formation (p < 0.0001) by 22.08, 32.57, 37.20, and 49.25%, respectively. Furthermore, DHHPD significantly reduced paw edema (p < 0.05) induced by histamine, serotonin, and bradykinin. The present study suggests that DHHPD exerts anti-edematogenic activity, possibly by inhibiting the synthesis or release of autacoid mediators of inflammation through the histaminergic, serotonergic, and bradykininergic systems. The anti-granuloma effect may be attributed to the suppression of transudative, exudative, and proliferative activities associated with inflammation.

Nowadays, many countries have implemented carbon pricing policies. Hence, the industry adapts to this policy while striving for its main goal of maximizing financial benefits. Here, we study a single manufacturer–retailer inventory decision considering carbon emission cost and item deterioration for an imperfect production system. This study examines two models considering two cases of quality inspection. The first is when the buyer performs the quality inspection, and the second is when the quality inspection becomes the vendor’s responsibility so that no defective products are passed to the buyer. Carbon emission costs are incorporated under a carbon tax policy, and we consider the carbon footprint from transporting and warehousing the items. The objective is to jointly optimize the delivery quantity and number of deliveries per production cycle that minimize the total cost and reduce the total carbon emissions. This study provides solution procedures to solve the models, as well as two numerical examples.

A method is presented for dynamic model updating of on-load tap changer (OLTC). Based on a sensitivity-based optimization method, the initial simplified finite element (FE) model of OLTC component is updated using the analytical results of the FE super-model. The objective of model updating is to reduce the frequency difference between the simplified FE model and the super-model, and to make the simplified model accurately represent dynamic characteristics of the super-model. The updated simplified models can be further used in the modeling and analysis of the whole OLTC model. The results, taking the base of OLTC as example, indicate that the dynamic behavior of the updated simplified model match well with that of the super-model. Subsequently, the dynamic behavior of OLTC assembled with the updated parts is further predicted by modal analysis. The presented method improves the calculation efficiency, as well as accuracy, which has broad application prospects for dynamic prediction of complex structures in engineering.

Abstract Blood vessels are highly dynamic and complex structures with a variety of physiological functions, including the transport of oxygen, nutrients, and metabolic wastes. Their normal functioning involves the close and coordinated cooperation of a variety of cells. However, adverse internal and external environmental factors can lead to vascular damage and the induction of various vascular diseases, including atherosclerosis and thrombosis. This can have serious consequences for patients, and there is an urgent need for innovative techniques to repair damaged blood vessels. Polyesters have been extensively researched and used in the treatment of vascular disease and repair of blood vessels due to their excellent mechanical properties, adjustable biodegradation time, and excellent biocompatibility. Given the high complexity of vascular tissues, it is still challenging to optimize the utilization of polyesters for repairing damaged blood vessels. Nevertheless, they have considerable potential for vascular tissue engineering in a range of applications. This summary reviews the physicochemical properties of polyhydroxyalkanoate (PHA), polycaprolactone (PCL), poly-lactic acid (PLA), and poly(lactide-co-glycolide) (PLGA), focusing on their unique applications in vascular tissue engineering. Polyesters can be prepared not only as 3D scaffolds to repair damage as an alternative to vascular grafts, but also in various forms such as microspheres, fibrous membranes, and nanoparticles to deliver drugs or bioactive ingredients to damaged vessels. Finally, it is anticipated that further developments in polyesters will occur in the near future, with the potential to facilitate the wider application of these materials in vascular tissue engineering.

Retinitis pigmentosa (RP) is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium (RPE) cells. Its main clinical manifestations include night blindness and progressive loss of peripheral vision, making it a prevalent debilitating eye disease that significantly impacts patients' quality of life. RP exhibits significant phenotypic and genetic heterogeneity. For instance, numerous abnormal genes are implicated in RP, resulting in varying clinical presentations, disease progression rates, and pathological characteristics among different patients. Consequently, gene therapy for RP poses challenges due to these complexities. However, stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem cells. In recent years, a large number of animal experiments and clinical trials based on stem cell transplantation attempts, especially cord blood mesenchymal stem cell (MSC) transplantation and bone marrow-derived MSC transplantation, have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected eye. However, stem cell therapy also has certain limitations, such as the fact that RP patients may involve multiple types of retinal cytopathia, which brings great challenges to stem cell transplantation therapy, and further research is needed to solve various problems faced by this approach in the clinic. Through comprehensive analysis of the etiology and histopathological changes associated with RP, this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials, while also highlighting the existing limitations that warrant further investigation.

The purpose of these comments is to serve as a revision to the article by Khan, Jaber, & Bonney [2011, An economic order quantity (EOQ) for items with imperfect quality and inspection errors, International Journal of Production Economics, 133: 113–118]. This commenting paper first suggests that the revenue function derived in Khan et al. (2011) is unrealistic, and then offers revisions to complement the shortcomings.

In this paper, a multi products single machine economic order quantity model with discrete delivery is developed. A unique cycle length is considered for all produced items with an assumption that all products are manufactured on a single machine with a limited capacity. The proposed model considers different items such as production, setup, holding, and transportation costs. The resulted model is formulated as a mixed integer nonlinear programming model. Harmony search algorithm, extended cutting plane and particle swarm optimization methods are used to solve the proposed model. Two numerical examples are used to analyze and to evaluate the performance of the proposed model.

Curcuminoids derived from turmeric rhizome have been reported to exhibit antinociceptive, antioxidant and anti-inflammatory activities. We evaluated the peripheral and central antinociceptive activities of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a novel synthetic curcuminoid analogue at 0.1, 0.3, 1 and 3 mg/kg (intraperitoneal), through chemical and thermal models of nociception. The effects of DHHPD on the vanilloid and glutamatergic systems were evaluated through the capsaicin- and glutamate-induced paw licking tests. Results showed that DHHPD significantly (p < 0.05) attenuated the writhing response produced by the 0.8% acetic acid injection. In addition, 1 and 3 mg/kg of DHHPD significantly (p < 0.05) reduced the licking time spent by each mouse in both phases of the 2.5% formalin test and increased the response latency of mice on the hot-plate. However, the effect produced in the latter was not reversed by naloxone, a non-selective opioid receptor antagonist. Despite this, DHHPD decreased the licking latency of mice in the capsaicin- and glutamate-induced paw licking tests in a dose response manner. In conclusion, DHHPD showed excellent peripheral and central antinociceptive activities possibly by attenuation of the synthesis and/or release of pro-inflammatory mediators in addition to modulation of the vanilloid and glutamatergic systems without an apparent effect on the opioidergic system.

In order to identify the optimal structure of an electricity power network under the main assumption of a price dependent demand of electrical energy, we presented an optimization model that aims at analyzing the effect of price-dependent demand on the sustainable electrical supply chain system (SESCS). The system included a power generation system, transmission and distribution substations, and many customers. The electrical energy was generated and transmitted through multiple substations to our customers, and the demand for electricity by the customers is dependent on the price of electricity. In the study, we considered the transmission and the distribution costs which depend on the capacities of power generation, transmission rates and distances between stations. We utilized the inventory theory to develop our model and proposed a procedure to derive an optimal solution for this problem. Finally, numerical examples and sensitivity analysis are provided to illustrate our study and consolidate managerial insights.

The economic production quantity (EPQ) model is widely employed in reality and is also being intensively developed in the research area. This research tries to develop more realistic EPQ models for deteriorating items by considering stochastic machine unavailability time (uniformly and exponentially distributed) and price-dependent demand. Lost sales will occur when machine unavailability time is longer than the non production time. Since the closed form solution cannot be derived, we use Genetic Algorithm (GA) to solve the models. A numerical example and sensitivity analysis is shown to illustrate the models. The sensitivity analyses show that a management can use price policy to minimize the profit loss due to machine unavailability time under a price- dependent demand situation

Many researches on deteriorating inventory model have been developed in recent years. This paper develops deteriorating inventory model with price-dependent demand and uses markdown policy to increase profit. Two examples are used to explain the model and some interesting results are derived. Markdown policy can increase total profit, but the best markdown time and price depend are case dependent.

Changes in tumor DNA mutation status during chemotherapy can provide insights into tumor biology and drug resistance. The purpose of this study is to analyse the presence or absence of mutations in cancer-related genes using baseline breast tumor samples and those obtained after exposure to one cycle of chemotherapy to determine if any differences exist, and to correlate these differences with clinical and pathological features.Paired breast tumor core biopsies obtained pre- and post-first cycle doxorubicin (n = 18) or docetaxel (n = 22) in treatment-naïve breast cancer patients were analysed for 238 mutations in 19 cancer-related genes by the Sequenom Oncocarta assay.Median age of patients was 48 years (range 32-64); 55% had estrogen receptor-positive tumors, and 60% had tumor reduction ≥25% after cycle 1. Mutations were detected in 10/40 (25%) pre-treatment and 11/40 (28%) post-treatment samples. Four mutation pattern categories were identified based on tumor mutation status pre- → post-treatment: wildtype (WT)→WT, n = 24; mutant (MT)→MT, n = 5; MT→WT, n = 5; WT→MT, n = 6. Overall, the majority of tumors were WT at baseline (30/40, 75%), of which 6/30 (20%) acquired new mutations after chemotherapy. Pre-treatment mutations were predominantly in PIK3CA (8/10, 80%), while post-treatment mutations were distributed in PIK3CA, EGFR, PDGFRA, ABL1 and MET. All 6 WT→MT cases were treated with docetaxel. Higher mutant allele frequency in baseline MT tumors (n = 10; PIK3CA mutations n = 8) correlated with less tumor reduction after cycle 1 chemotherapy (R = -0.667, p = 0.035). No other associations were observed between mutation pattern category with treatment, clinicopathological features, and tumor response or survival.Tumor mutational profiles can change as quickly as after one cycle of chemotherapy in breast cancer. Understanding of these changes can provide insights on potential therapeutic options in residual resistant tumors.ClinicalTrials.gov NCT00212082.

Summary: Vertical mammaplasty for breast reduction has been widely popularized by Lejour. In her planning for the new nipple-areolar complex, she did not specify a method of drawing the periareolar curve, leaving it to the surgeon’s creativity. We have designed a simple method using mathematics to draw the new periareolar curve consistently and reliably, not requiring any additional or complex devices. This method is easy for those who are accustomed to the Wise pattern to adopt and targets those who prefer formulated preplanned operative markings.

In a hospital setting, it is common to encounter certain haematological emergencies irrespective of whether or not the patient has an underlying haematological condition or if the hospital has a well-established haematology service. This article aims to define and illustrate common and less common haematological emergencies that a physician may encounter on the wards and the appropriate initial management for the patient prior to a formal hematological consult.

Embryonic stem (ES) cells derived from the inner cell mass (ICM) of blastocysts are characterised by their ability to self-renew and their potential to differentiate into many different cell types. Recent studies have shown that zinc finger proteins are crucial for maintaining pluripotent ES cells. Mouse zinc finger protein 322a (Zfp322a) is expressed in the ICM of early mouse embryos. However, little is known regarding the role of Zfp322a in the pluripotency maintenance of mouse ES cells. Here, we report that Zfp322a is required for mES cell identity since depletion of Zfp322a directs mES cells towards differentiation. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription. These data along with the results obtained from our ChIP-seq experiment showed that Zfp322a is an essential component of mES cell transcription regulatory network. Targets which are directly regulated by Zfp322a were identified by correlating the gene expression profile of Zfp322a RNAi-treated mES cells with the ChIP-seq results. These experiments revealed that Zfp322a inhibits mES cell differentiation by suppressing MAPK pathway. Additionally, Zfp322a is found to be a novel reprogramming factor that can replace Sox2 in the classical Yamanaka's factors (OSKM). It can be even used in combination with Yamanaka's factors and that addition leads to a higher reprogramming efficiency and to acceleration of the onset of the reprogramming process. Together, our results demonstrate that Zfp322a is a novel essential component of the transcription factor network which maintains the identity of mouse ES cells.

We discuss a new type of fully coupled forward-backward stochastic differential equations (FBSDEs) whose coefficients depend on the states of the solution processes as well as their expected values, and we call them fully coupled mean-field forward-backward stochastic differential equations (mean-field FBSDEs). We first prove the existence and the uniqueness theorem of such mean-field FBSDEs under some certain monotonicity conditions and show the continuity property of the solutions with respect to the parameters. Then we discuss the stochastic optimal control problems of mean-field FBSDEs. The stochastic maximum principles are derived and the related mean-field linear quadratic optimal control problems are also discussed.

BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66). CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

For the sake of environmental protection and circular economy, cement reduction and cement substitutes have become popular research topics, and the application of green materials has become an important issue in the development of building materials. This study developed green pervious concrete using water-quenched blast-furnace slag (BFS) and co-fired fly ash (CFFA) to replace cement. The objectives of this study were to gauge the feasibility of using a non-cement binder in pervious concrete and identify the optimal binder mix design in terms of compressive strength, permeability, and durability. For filled percentage of voids by cement paste (FPVs) of 70%, 80%, and 90%, which mixed with CFFA and BFS as the binder (40 + 60%, 50 + 50%, and 60 + 40%) to create pervious concrete with no cement. The results indicate that the complete (100%) replacement of cement with CFFA and BFS with no alkaline activator could induce hydration, setting, and hardening. After a curing period of 28 days, the compressive strength with different FPVs could reach approximately 90% that of the control cement specimens. The cementless pervious concrete specimens with BFS:CFFA = 7:3 and FPV = 90% presented better engineering properties and permeability. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of adding circulating fluidized bed combustion (CFBC) ash, desulfurization slag, air-cooled blast-furnace slag and coal bottom ash to the controlled low-strength material (CLSM). Test methods include slump flow test, ball drop test, water soluble chloride ion content measurement, compressive strength and length change measurement. The results show that (1) the use of CFBC hydration ash with desulfurization slag of slump flow is the best, and the use of CFBC hydration ash with coal bottom ash and slump flow is the worst; (2) CFBC hydration ash with desulfurization slag and chloride ion content is the highest; (3) 24 h ball drop test (diameter ≤ 76 mm), and test results are 70 mm to 76 mm; (4) CFBC hydration ash with desulfurization slag and compression strength is the highest, with the coal bottom ash being the lowest; increase of CFBC hydration ash can reduce compressive strength; and (5) the water-quenched blast furnace slag and CFBC hydration ash would expand, which results in length changes of CLSM specimens. [ABSTRACT FROM AUTHOR]

We investigate global dynamics for a system of delay differential equations which describes a virus-immune interaction in vivo. The model has two time delays describing time needed for infection of cell and CTLs generation. Our model admits three possible equilibria: infection-free equilibrium, CTL-absent infection equilibrium, and CTL-present infection equilibrium. The effect of time delay on stability of the equilibria of the CTL immune response model has been studied.

BACKGROUND: The Hedgehog (HH) signaling pathway is critical for embryonic development and adult homeostasis. Recent studies have identified regulatory roles for this pathway in certain cancers with mutations in the HH pathway genes. The extent to which mutations of the HH pathway genes are involved in the pathogenesis of malignant mesothelioma (MMe) is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Real-time PCR analysis of HH pathway genes PTCH1, GLI1 and GLI2 were performed on 7 human MMe cell lines. Exon sequencing of 13 HH pathway genes was also performed in cell lines and human MMe tumors. In silico programs were used to predict the likelihood that an amino-acid substitution would have a functional effect. GLI1, GLI2 and PTCH1 were highly expressed in MMe cells, indicative of active HH signaling. PTCH1, SMO and SUFU mutations were found in 2 of 11 MMe cell lines examined. A non-synonymous missense SUFU mutation (p.T411M) was identified in LO68 cells. In silico characterization of the SUFU mutant suggested that the p.T411M mutation might alter protein function. However, we were unable to demonstrate any functional effect of this mutation on Gli activity. Deletion of exons of the PTCH1 gene was found in JU77 cells, resulting in loss of one of two extracellular loops implicated in HH ligand binding and the intracellular C-terminal domain. A 3-bp insertion (69_70insCTG) in SMO, predicting an additional leucine residue in the signal peptide segment of SMO protein was also identified in LO68 cells and a MMe tumour. CONCLUSIONS/SIGNIFICANCE: We identified the first novel mutations in PTCH1, SUFU and SMO associated with MMe. Although HH pathway mutations are relatively rare in MMe, these data suggest a possible role for dysfunctional HH pathway in the pathogenesis of a subgroup of MMe and help rationalize the exploration of HH pathway inhibitors for MMe therapy.

Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used “off-label” to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

During tumor progression, EphA2 receptor can gain ligand-independent pro-oncogenic functions due to Akt activation and reduced ephrin-A ligand engagement. The effects can be reversed by ligand stimulation, which triggers the intrinsic tumor suppressive signaling pathways of EphA2 including inhibition of PI3/Akt and Ras/ERK pathways. These observations argue for development of small molecule agonists for EphA2 as potential tumor intervention agents. Through virtual screening and cell-based assays, we report here the identification and characterization of doxazosin as a novel small molecule agonist for EphA2 and EphA4, but not for other Eph receptors tested. NMR studies revealed extensive contacts of doxazosin with EphA2/A4, recapitulating both hydrophobic and electrostatic interactions recently found in the EphA2/ephrin-A1 complex. Clinically used as an α1-adrenoreceptor antagonist (Cardura®) for treating hypertension and benign prostate hyperplasia, doxazosin activated EphA2 independent of α1-adrenoreceptor. Similar to ephrin-A1, doxazosin inhibited Akt and ERK kinase activities in an EphA2-dependent manner. Treatment with doxazosin triggered EphA2 receptor internalization, and suppressed haptotactic and chemotactic migration of prostate cancer, breast cancer, and glioma cells. Moreover, in an orthotopic xenograft model, doxazosin reduced distal metastasis of human prostate cancer cells and prolonged survival in recipient mice. To our knowledge, doxazosin is the first small molecule agonist of a receptor tyrosine kinase that is capable of inhibiting malignant behaviors in vitro and in vivo.

A close reading of feminism and patriarchy within obsession_inc's Concession (2010).

Introduction: Hypoglycaemia is an important complication of type 2 diabetes mellitus treatment, because it causes recurrent physical and psycho-social morbidity, and it is sometimes fatal. Achieving target glycaemic goals while avoiding hypoglycaemia is a major challenge in the management of patients with type 2 diabetes mellitus. Awareness of hypoglycaemia is a function of the knowledge and experience of an individual, as well as the physiological responses to low glucose concentrations. Our team conducted an audit to identify the prevalence and underlying causes of hypoglycaemic symptoms among type 2 diabetes mellitus patients seen in SingHealth Polyclinics. This data was collected as part of our efforts to improve diabetes care and increase awareness. Methods: Audit in the form of nurse-administered interviews were carried out on 120 type 2 diabetic patients seen in the Family Physician Clinic; they were 20 consecutive patients seen in each of 6 polyclinics. The questionnaire included both patient and nurse components, identifying hypoglycaemic symptoms, causes, related hospital admissions, self-management, current treatment and control. Results: Of the 120 patients audited, 31 (26%) reported hypoglycaemic symptoms. These patients with hypoglycaemic symptoms were more likely to be on insulin treatment than those without symptoms (p=0.000). Majority of patients with symptoms did not use the glucometer when they experienced these symptoms (19/31). The cause of hypoglycaemic symptoms was often meal-related. For patients not on insulin, those with hypoglycaemic symptoms were more likely to own a glucometer than those without symptoms (p=0.033). Conclusion: Hypoglycaemia is a common complication of diabetic treatment, and efforts should be focused especially on insulin-treated patients to prevent hypoglycaemia, including education on hypoglycaemia awareness, self-monitoring of blood glucose and dietary advice.

In the title complex, [Cd(C14H9N5)(NO3)(H2O)2]NO3, the CdII ion is coordinated in a distorted pentagonal-bipyramidal geometry. The equatorial sites are occupied by a 2-(1H-1,2,4-triazol-1-yl)-1,10-phenanthroline ligand in a tridentate coordination mode and a bis-chelating nitrate ligand. Two aqua ligands are coordinated at the axial sites. All non-H atoms in the equatorial plane are co-planar within 0.0673 Å. In the crystal, intermolecular O—H...O and O—H...N hydrogen bonds connect the components into a two-dimensional network parallel to (001). In addition, there is a π–π stacking interaction between symmetry-related benzene rings, with a centroid–centroid distance of 3.598 (3) Å.

Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age.

Steel furnace slag containing heavy metal components is covered by asphalt cement when it is used to replace natural aggregates in road paving. When such a pavement deteriorates as a result of wear by people and vehicles as well as washing by rain, the aggregates are worn away and the heavy metal components within can overflow on the road’s surface, forming rust spots. This phenomenon has been observed on many roads, leading the general public to question the validity of using steel furnace slag and whether this is in violation of a contract with the contractor. However, it is known from literature that such rust spots on a road surface may also be caused by natural minerals such as pyrite that are contained in natural aggregates. Unlike cement concrete, the slag cannot be separated from the mixture after hardening; however, the asphalt cement can be separated from the aggregates by using a solvent. In this study, separated aggregates are tested for pH value, magnetic attraction, and elemental composition in order to assess the usability of slag. Based on the findings and the characteristics of steel furnace slag, this paper proposes a method for detection of steel furnace slag in asphalt concrete, which is divided into two stages. In the first stage, core samples of asphalt concrete are obtained from the road site. The asphalt cement is separated from the aggregates according to AASHTO T164 and then the separated aggregates are analyzed in pH value and magnetic attraction tests. When one or both of the tests indicate steel furnace slag characteristics, that is, alkalinity or magnetism, then it is possible that the asphalt concrete sample contains steel furnace slag, and should be tested in the second stage for further confirmation. In the second stage, the separated aggregates are grinded to less than 0.075 mm (No. 200) and their elemental composition is analyzed. Based on the composition of steel furnace slag, when the analysis results indicate ≥30 % CaO and ≥10 % Fe2O3, it can be regarded that steel furnace slag has been used in the asphalt concrete.

Food-grade methyl cinnamate as an acyl donor was used to enzymatically acylate cyanidin-3-O-glucoside (C3G) under reduced pressure, which has the advantages of safety, high efficiency and single acylation product. After being purified by semi-preparative high-performance liquid chromatography (SP-HPLC), the acylation product was evaluated for its thermal stability and antioxidant activity. The results showed that the acylation rate was 80%, and the purity of the purified acylated C3G was as high as 98.3%. Mass spectral analysis showed that the acylated product was cyanidin-3-(6-cinnamoyl)-glucoside (C3(6C)G). Acylation modification significantly improved the lipid solubility and thermal stability of C3G. C3G and C3(6C)G had weaker scavenging capacity against 2,2-amino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation but similar 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, ferric reducing and antioxidant power (FRAP) and hydroxyl radical scavenging capacity compared with vitamin C (VC) at the same concentration. At 200 μmol/L, the hydroxyl and DPPH radical scavenging capacity of C3(6C)G was significantly enhanced compared with C3G (P 0.05), which showed that cinnamyl modification did not impair the antioxidant capacity of anthocyanins, but instead improved the scavenging capacity against hydroxyl radicals.

Habitat degradation and fragmentation are crucial factors which result in biodiversity loss among the world. Understanding how species respond to the habitat change is helpful and essential for the conservation of the endangered ones. Therefore, the aim of current study is to explore how to carry out biodiversity conservation from the perspective of the habitat selection of species. We studied the microhabitat selection of blue eared pheasant (Crossoptilon auritum) during its breeding time (including mating, incubation, and feeding periods). The field research was carried out from April to August in 2014 at Helan Mountains, China. Six nests of blue eared pheasants were found; 323 used plots and 171 control plots were recorded. Results indicated that blue eared pheasants prefer mountainous coniferous forest at shady slope with domination of Picea crassifolia, and its habitat selection was mainly influenced by shrub density, tree density, altitude, slope degree, hiding cover, water resource, and human disturbance. However, there were slight differences among the three periods. Our study firstly compared factors that affect the microhabitat selection of blue eared pheasants among the three periods of its breeding time. Meanwhile, combining the current study with the previous ones, specific strategies could be applied on the works of endangered species and biodiversity conservation. [ABSTRACT FROM AUTHOR]

Concrete is porous; the partial pores in the internal structure of concrete are generated by hydration products, such as calcium hydroxide, dissolved in water. External harmful substances in the form of gases or aqueous solutions can penetrate concrete. The destruction of the internal structure of concrete leads to problems such as shortening of the service life of concrete as well as the corrosion and poor durability of steel. To improve the pore structure of concrete, a material can be added to concrete mixtures to cause the secondary hydration of the hydration products of cement. This reaction is expected to reduce the pore volume and increase the density of concrete. For existing concrete structures, inorganic crystalline materials can be used to protect the surface and reduce the intrusion of external harmful substances. In this study, the water–binder ratio was 0.4 and 0.6. Three inorganic crystalline materials and recycled fine aggregates (0%, 10%, 20%, and 30% replacement of natural aggregates by weight) were used in the same cement-based composites. The results indicated that all specimens had a high total charge-passed value, and inorganic crystalline material C provided superior protection for green cement-based composites.

Green concrete (GC) was developed for realizing sustainable development, recycling waste materials, and reducing environmental pollution. For the practical use of GC, various harmful materials must blocked from entering its cracks and pores; and its strength and durability must be improved. The use of an inorganic coating material (ICM) for GC effectively prevents the intrusion of harmful materials and repairs the concrete. ICMs can reduce the permeability and increase the durability of concrete. This study investigated GC, construction waste, and ICMs and used recycled sand and gravel as well as construction waste as substitutes for cement. The results indicate that the coarse aggregate substitution, water-binder ratio, and recycled fine aggregate substitution must be controlled suitably in GC. Furthermore, the coating layer, fine aggregate substitution, and aging of the ICM mut be controlled suitably. GC with an ICM showed poorer performance than conventional concrete, mainly because of the high porosity. Nonetheless, the ICM somewhate reduces the porosity and resists the penetration of chloride ions, thereby promoting concrete quality.

Conventional cementitious materials as tunnel supporting materials are utilised in the construction of the final repository for spent nuclear fuel. However, the use of cementitious material releases alkaline ions from pH12 to pH13 plumed into groundwater. Such a high pH is detrimental to the performance of the bentonite functioning, which may possibly enhance the dissolution and alteration of the fracture buffer and filling materials. Instead, low-pH cementitious materials are being developed for use in geological repositories. This study is aimed at evaluating the usability of low-pH cementitious materials containing 40% silica fume or composites blended with 20% silica fume and 40% fly ash. Engineering properties were analysed and verified through experimental research using the flow, compressive strength, pH measurement and hydraulic conductivity. Test results show that the replacement level with 40% of silica fume or 20% of silica fume and 40% of fly ash was suitable for the mixture of low-pH cementitious. Compared to the compressive strength and water permeability of ordinary cementitious, those of low-pH cementitious enhanced better engineered performances at the age of 91 days. The information is contributed us to establish the long-term durability and environmental requirements of disposal repositories in Taiwan.

The paper proposed a control scheme of three-level active power filter based on ip-iq harmonic current detection, fuzzy PI current control and space vector pulse width modulation. It established a mathematical model of the three-level active power filter, and introduced concrete realization of control method of DC-side voltage stabilization and neutral-point potential balancing of the three-level active power filter. The simulation and experimental results show that the three-level active power filter controlled by the scheme has good effect of harmonic compensation, and can stabilize DC-side voltage and capacitance neutral-point potential well.

This study investigates the effectiveness of concrete protection with two inorganic silicate sealer materials (ISSMs). The Taguchi method and grey relational analysis (GRA) have been used to identify the key factors influencing concrete protection provided by the surface treatment. Seven control factors with two levels were selected. By using the orthogonal array L12 (27), 12 experiments are chosen and four tests—the compressive strength test, resistivity test, absorption test and permeability test—were performed. Results have shown that the major factors affecting the protection effectiveness of ISSM are the water-binder ratio of mortar substrate, age of substrate for sealer application, addition of pozzolanic material and sealer type.

For the sake of environmental protection and circular economy, cement reduction and cement substitutes have become popular research topics, and the application of green materials has become an important issue in the development of building materials. This study developed green pervious concrete using water-quenched blast-furnace slag (BFS) and co-fired fly ash (CFFA) to replace cement. The objectives of this study were to gauge the feasibility of using a non-cement binder in pervious concrete and identify the optimal binder mix design in terms of compressive strength, permeability, and durability. For filled percentage of voids by cement paste (FPVs) of 70%, 80%, and 90%, which mixed with CFFA and BFS as the binder (40 + 60%, 50 + 50%, and 60 + 40%) to create pervious concrete with no cement. The results indicate that the complete (100%) replacement of cement with CFFA and BFS with no alkaline activator could induce hydration, setting, and hardening. After a curing period of 28 days, the compressive strength with different FPVs could reach approximately 90% that of the control cement specimens. The cementless pervious concrete specimens with BFS:CFFA = 7:3 and FPV = 90% presented better engineering properties and permeability.

This study aims to investigate the effect of adding circulating fluidized bed combustion (CFBC) ash, desulfurization slag, air-cooled blast-furnace slag and coal bottom ash to the controlled low-strength material (CLSM). Test methods include slump flow test, ball drop test, water soluble chloride ion content measurement, compressive strength and length change measurement. The results show that (1) the use of CFBC hydration ash with desulfurization slag of slump flow is the best, and the use of CFBC hydration ash with coal bottom ash and slump flow is the worst; (2) CFBC hydration ash with desulfurization slag and chloride ion content is the highest; (3) 24 h ball drop test (diameter ≤ 76 mm), and test results are 70 mm to 76 mm; (4) CFBC hydration ash with desulfurization slag and compression strength is the highest, with the coal bottom ash being the lowest; increase of CFBC hydration ash can reduce compressive strength; and (5) the water-quenched blast furnace slag and CFBC hydration ash would expand, which results in length changes of CLSM specimens.

• A new cementless binder is developed from CFA, ggbs and DG. • Innovative cementless mixtures can be used as a binder for pervious concrete. • Reasonable amount of DG content can effectively improve the strength. • Main hydration reactants of cementless binders are C-S-H and AFt crystals. • Cementless pervious concrete has a compressive strength of 12 MPa. In this study, alkali-free activator-type ternary cementless binders were developed using ground granulated blast-furnace slag (GGBS), co-fired fly ash (CFA), and desulfurization gypsum (DG). The properties of cementless binders were verified and used to investigate the feasibility of application to pervious concrete. The results indicated that including CFA in cementless binders increased the initial and final setting times. The addition of DG shortened the setting time and the addition exceeded 7 wt% resulting in a rapid setting, which did not meet the ASTM C150 specification. A binary cementless binder with a CFA-GGBS mix achieved a maximum compressive strength up to 54% of the cement group, and the optimum mixture was 70% GGBS with 30% CFA. DG increased the SO 3 content of the binder and promoted the production of ettringite (AFt), resulting in an effective increase in compressive strength up to 92% of the cement group. The optimum proportion of cementless binders to meet the setting times was 70% GGBS, 25% CFFA, and 5% FGDG, resulting in maximum compressive strength up to 79% of the cement group. During the hardening period of the cementless pastes, the generation of AFt affected the internal pore structures of the C-S-H colloids, resulting in higher capillary pores. DG also accelerated the production of AFt, causing an increase in capillary pores. In addition, the maximum compressive strength of cementless pervious concrete developed in this study reached 12 MPa, and the permeability coefficient was up to 0.156 cm/s. It can meet the requirements of the general pervious pavement specification in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer and colorectal cancer, the two most frequent cancers within the gastrointestinal tract, account for a large proportion of human malignancies worldwide. The initiation and progression of gastrointestinal cancer (GIC) is controlled by both genetic and epigenetic events. Epigenetic alterations, including changes in DNA methylation, specific histone modifications, chromatin remodeling and noncoding RNA-mediated gene silencing, are potentially reversible and heritable., Summary: In this article, we summarize the current advances in epigenetic biomarkers as potential substrates for GIC detection. The combined screening of a panel of methylated genes, hyperacetylated histones, microRNAs or other noncoding RNAs is currently under evaluation to improve sensitivity., Key Message: Current studies concentrated on the development of cost-effective epigenetic diagnostic biomarkers for GIC based on noninvasive blood or stool samples. The combined blood or stool test with a relatively high sensitivity could be a cost-effective screening tool for the detection of patients with asymptomatic cancers who could therefore choose whether or not to go for further examinations, such as endoscopy or colonoscopy., Practical Implications: A better understanding of epigenetic mechanisms has not only offered new insights into a deeper understanding of the underlying mechanisms of carcinogenesis, but has also allowed identification of clinically relevant putative biomarkers for the early detection, disease monitoring, prognosis and risk assessment of GIC. In particular, noninvasive biomarkers in serum or fecal samples for the detection of GIC could have potential for better compliance and can be incorporated into routine clinical practice in the foreseeable future, pending their validation in large-scale prospective trials.

Background: Imatinib mesylate (IM) induces clinical remission of chronic myeloid leukemia (CML). The Abelson helper integration site 1 (AHI-1) oncoprotein interacts with BCR-ABL and Janus kinase 2 (JAK2) to mediate IM response of primitive CML cells, but the effect of the interaction complex on the response to ABL and JAK2 inhibitors is unknown., Methods: The AHI-1-BCR-ABL-JAK2 interaction complex was analyzed by mutational analysis and coimmunoprecipitation. Roles of the complex in regulation of response or resistance to ABL and JAK2 inhibitors were investigated in BCR-ABL (+) cells and primary CML stem/progenitor cells and in immunodeficient NSG mice. All statistical tests were two-sided., Results: The WD40-repeat domain of AHI-1 interacts with BCR-ABL, whereas the N-terminal region interacts with JAK2; loss of these interactions statistically significantly increased the IM sensitivity of CML cells. Disrupting this complex with a combination of IM and an orally bioavailable selective JAK2 inhibitor (TG101209 [TG]) statistically significantly induced death of AHI-1-overexpressing and IM-resistant cells in vitro and enhanced survival of leukemic mice, compared with single agents (combination vs TG alone: 63 vs 53 days, ratio = 0.84, 95% confidence interval [CI] = 0.6 to 1.1, P = .004; vs IM: 57 days, ratio = 0.9, 95% CI = 0.61 to 1.2, P = .003). Combination treatment also statistically significantly enhanced apoptosis of CD34(+) leukemic stem/progenitor cells and eliminated their long-term leukemia-initiating activity in NSG mice. Importantly, this approach was effective against treatment-naive CML stem cells from patients who subsequently proved to be resistant to IM therapy., Conclusions: Simultaneously targeting BCR-ABL and JAK2 activities in CML stem/progenitor cells may improve outcomes in patients destined to develop IM resistance.

Objective: To compare the effect of botulinum neurotoxin A (BTA) and denervation in inducing masseter muscle atrophy in rabbits to provide experimental evidence for the safe clinical application of BTA., Methods: Seventy-five healthy adult New Zealand white rabbits were randomized equally into denervation group, BTA group and normal control group. In the former two groups, the rabbits were subjected to right masseter muscle denervation and botulinum (3 µg/kg) injection at the muscle, respectively, with the left side as the control. The thickness of the denervated masseter was determined using B type ultrasound and its weight measured after the treatment., Results: The thickness of the masseter muscle on the experimental side was significantly decreased to 50.80% and 54.07%, and its weight to 66.80% and 56.16% of the normal level after denervation and BTA injection, respectively., Conclusion: BTA-induced denervation produces less potent atrophy-inducing effect on skeletal muscle than surgical denervation. BTA causes atrophy mainly at the injection site of the target muscle without significant diffusion or toxicity to the muscular cells.