Nutrient element-based bioceramic coatings on titanium alloy stimulating osteogenesis by inducing beneficial osteoimmmunomodulation

A paradigm shift has taken place in which bone implant materials has gone from being relatively inert to having immunomodulatory properties, indicating the importance of immune response when these materials interact with the host tissues. It has therefore become important to endow the implant materials with immunomodulatory properties favouring osteogenesis and osseointegration. Strontium, zinc and silicon are bioactive elements that have important roles in bone metabolism and that also elicit significant immune responses. In this study, Sr-, Zn- and Si-containing bioactive Sr2ZnSi2O7 (SZS) ceramic coatings on Ti–6Al–4V were successfully prepared by a plasma-spray coating method. The SZS coatings exhibited slow release of the bioactive ions with significantly higher bonding strength than hydroxyapatite (HA) coatings. SZS-coated Ti–6Al–4V elicited significant effects on the immune cells, inhibiting the release of pro-inflammatory cytokines and fibrosis-enhancing factors, while upregulating the expression of osteogenic factors of macrophages; moreover, it could also inhibit the osteoclastic activities. The RANKL/RANK pathway, which enhances osteoclastogenesis, was inhibited by the SZS coatings, whereas the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) was significantly enhanced by the SZS coatings/macrophages conditioned medium, probably via the activation of BMP2 pathway. SZS coatings are, therefore, a promising material for orthopaedic applications, and the strategy of manipulating the immune response by a combination of bioactive elements with controlled release has the potential to endow biomaterials with beneficial immunomodulatory properties.

On the provable security of an efficient RSA-based pseudorandom generator

Pseudorandom Generators (PRGs) based on the RSA inversion (one-wayness) problem have been extensively studied in the literature over the last 25 years. These generators have the attractive feature of provable pseudorandomness security assuming the hardness of the RSA inversion problem. However, despite extensive study, the most efficient provably secure RSA-based generators output asymptotically only at most O(logn) bits per multiply modulo an RSA modulus of bitlength n, and hence are too slow to be used in many practical applications. To bring theory closer to practice, we present a simple modification to the proof of security by Fischlin and Schnorr of an RSA-based PRG, which shows that one can obtain an RSA-based PRG which outputs Ω(n) bits per multiply and has provable pseudorandomness security assuming the hardness of a well-studied variant of the RSA inversion problem, where a constant fraction of the plaintext bits are given. Our result gives a positive answer to an open question posed by Gennaro (J. of Cryptology, 2005) regarding finding a PRG beating the rate O(logn) bits per multiply at the cost of a reasonable assumption on RSA inversion.

Gentrification and the artistic dividend : the role of the arts in neighborhood change

Problem, research strategy, and findings: There is a conflict between recent creative placemaking policies intended to promote positive neighborhood development through the arts and the fact that the arts have long been cited as contributing to gentrification and the displacement of lower-income residents. Unfortunately, we do not have data to demonstrate widespread evidence of either outcome. We address the dearth of comprehensive research and inform neighborhood planning efforts by statistically testing how two different groups of arts activities—the fine arts and commercial arts industries—are associated with conditions indicative of revitalization and gentrification in 100 large U.S. metropolitan areas. We find that different arts activities are associated with different types and levels of neighborhood change. Commercial arts industries show the strongest association with gentrification in rapidly changing areas, while the fine arts are associated with stable, slow-growth neighborhoods. Takeaway for practice: This research can help planners to more effectively incorporate the arts into neighborhood planning efforts and to anticipate the potential for different outcomes in their arts development strategies, including gentrification-related displacement.

A Tobit model for analyzing speed limit compliance in work zones

Poor compliance with speed limits is a serious safety concern in work zones. Most studies of work zone speeds have focused on descriptive analyses and statistical testing without systematically capturing the effects of vehicle and traffic characteristics. Consequently, little is known about how the characteristics of surrounding traffic and platoons influence speeds. This paper develops a Tobit regression technique for innovatively modeling the probability and the magnitude of non-compliance with speed limits at various locations in work zones. Speed data is transformed into two groups—continuous for non-compliant and left-censored for compliant drivers—to model in a Tobit model framework. The modeling technique is illustrated using speed data from three long-term highway work zones in Queensland, Australia. Consistent and plausible model estimates across the three work zones support the appropriateness and validity of the technique. The results show that the probability and magnitude of speeding was higher for leaders of platoons with larger front gaps, during late afternoon and early morning, when traffic volumes were higher, and when higher proportions of surrounding vehicles were non-compliant. Light vehicles and their followers were also more likely to speed than others. Speeding was more common and greater in magnitude upstream than in the activity area, with higher compliance rates close to the end of the activity area and close to stop/slow traffic controllers. The modeling technique and results have great potential to assist in deployment of appropriate countermeasures by better identifying the traffic characteristics associated with speeding and the locations of lower compliance.

The Saccharomyces cerevisiae RNA-binding protein Rbp29 functions in cytoplasmic mRNA metabolism

Here we report that the Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encodes a 29-kDa cytoplasmic protein that binds to mRNA in vivo. Rbp29p can be co-immunoprecipitated with the poly(A) tail-binding protein Pab1p from crude yeast extracts in a dosageand RNA-dependent manner. In addition, recombinant Rbp29p binds preferentially to poly(A) with nanomolar binding affinity in vitro. Although RBP29 is not essential for cell viability, its deletion exacerbates the slow growth phenotype of yeast strains harboring mutations in the eIF4G genes TIF4631 and TIF4632. Furthermore, overexpression of RBP29 suppresses the temperaturesensitive growth phenotype of specific tif4631, tif4632, and pab1 alleles. These data suggest that Rbp29p is an mRNA-binding protein that plays a role in modulating the expression of cytoplasmic mRNA.

Solution-processed dual-gate polymer field-effect transistors for display applications

We describe the advantages of dual-gate thin-film transistors (TFTs) for display applications. We show that in TFTs with active semiconductor layers composed of diketopyrrolopyrrole-naphthalene copolymer, the on-current is increased, the off-current is reduced, and the sub-threshold swing is improved compared to single-gate devices. Charge transport measurements in steady-state and under non-quasi-static conditions reveal the reasons for this improved performance. We show that in dual-gate devices, a much smaller fraction of charge carriers move in slow trap states. We also compare the activation energies for charge transport in the top-gate and bottom-gate configurations.

Role of the N-terminal region in G protein-coupled receptor functions : negative modulation revealed by 5-HT2B receptor polymorphisms

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family

Seasonal factors influencing the failure of buried water reticulation pipes

While the use of environmental factors in the analysis and prediction of failures of buried reticulation pipes in cold environments has been the focus of extensive work, the same cannot be said for failures occurring on pipes in other (non-freezing) environments. A novel analysis of pipe failures in such an environment is the subject of this paper. An exploratory statistical analysis was undertaken, identifying a peak in failure rates during mid to late summer. This peak was found to correspond to a peak in the rate of circumferential failures, whilst the rate of longitudinal failures remained constant. Investigation into the effect of climate on failure rates revealed that the peak in failure rates occurs due to differential soil movement as the result of shrinkage in expansive soils.

Automated diagnosis of Age-related Macular Degeneration using greyscale features from digital fundus images

Age-related Macular Degeneration (AMD) is one of the major causes of vision loss and blindness in ageing population. Currently, there is no cure for AMD, however early detection and subsequent treatment may prevent the severe vision loss or slow the progression of the disease. AMD can be classified into two types: dry and wet AMDs. The people with macular degeneration are mostly affected by dry AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These lesions are identified by manual inspection of fundus images by the ophthalmologists. It is a time consuming, tiresome process, and hence an automated diagnosis of AMD screening tool can aid clinicians in their diagnosis significantly. This study proposes an automated dry AMD detection system using various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS) bispectra features, Fractional Dimension (FD), and Gabor wavelet features extracted from greyscale fundus images. The features are ranked using t-test, Kullback–Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance (CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking methods in order to select optimum features and classified into normal and AMD classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers. The performance of the proposed system is evaluated using private (Kasturba Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) datasets. The proposed system yielded the highest average classification accuracies of 90.19%, 95.07% and 95% with 42, 54 and 38 optimal ranked features using SVM classifier for private, ARIA and STARE datasets respectively. This automated AMD detection system can be used for mass fundus image screening and aid clinicians by making better use of their expertise on selected images that require further examination.

A computational model for BMP movement in sea urchin embryos

Bone morphogen proteins (BMPs) are distributed along a dorsal-ventral (DV) gradient in many developing embryos. The spatial distribution of this signaling ligand is critical for correct DV axis specification. In various species, BMP expression is spatially localized, and BMP gradient formation relies on BMP transport, which in turn requires interactions with the extracellular proteins Short gastrulation/Chordin (Chd) and Twisted gastrulation (Tsg). These binding interactions promote BMP movement and concomitantly inhibit BMP signaling. The protease Tolloid (Tld) cleaves Chd, which releases BMP from the complex and permits it to bind the BMP receptor and signal. In sea urchin embryos, BMP is produced in the ventral ectoderm, but signals in the dorsal ectoderm. The transport of BMP from the ventral ectoderm to the dorsal ectoderm in sea urchin embryos is not understood. Therefore, using information from a series of experiments, we adapt the mathematical model of Mizutani et al. (2005) and embed it as the reaction part of a one-dimensional reaction–diffusion model. We use it to study aspects of this transport process in sea urchin embryos. We demonstrate that the receptor-bound BMP concentration exhibits dorsally centered peaks of the same type as those observed experimentally when the ternary transport complex (Chd-Tsg-BMP) forms relatively quickly and BMP receptor binding is relatively slow. Similarly, dorsally centered peaks are created when the diffusivities of BMP, Chd, and Chd-Tsg are relatively low and that of Chd-Tsg-BMP is relatively high, and the model dynamics also suggest that Tld is a principal regulator of the system. At the end of this paper, we briefly compare the observed dynamics in the sea urchin model to a version that applies to the fly embryo, and we find that the same conditions can account for BMP transport in the two types of embryos only if Tld levels are reduced in sea urchin compared to fly.

Going through the obstruction, the Torrens System Assurance Fund and contemporary solutions : a tale weaved from a story of a nun, a romantic triangle and sibling corruption

Private title insurance has been the subject of much debate by law reform bodies and academics. This article adds a new dimension to the discussion by analysing its role against a recent scenario where a nun was betrayed by the actions of her brother, and compensation payable from the assurance fund, after much challenge by the registrar, amounted to in excess of $4 million.We ask whether the slow burning of title insurance into the psyche of Australian home purchasers will see state-based assurance fundings looking to minismise their role in the Torrens system. We also query how the rather more immediate electronic establishment of electronic conveyancing will alter the balance between the assurance fund, private title insurance and the increasing responsibilities on stakeholdes involved in conveyancing.

Occurrence of urinary tract tumors in miners highly exposed to dinitrotoluene

Between 1984 and 1997, six cases of urothelial cancer and 14 cases of renal cell cancer occurred in a group of 500 underground mining workers in the copper-mining industry of the former German Democratic Republic, with high exposures to explosives containing technical dinitrotoluene. Exposure durations ranged from 7 to 37 years, and latency periods ranged from 21 to 46 years. The incidences of both urothelial and renal cell tumors in this group were much higher than anticipated on the basis of the cancer registers of the German Democratic Republic by factors of 4.5 and 14.3, respectively. The cancer cases and a representative group of 183 formerly dinitrotoluene- exposed miners of this local industry were interviewed for their working history and grouped into four exposure categories. This categorization of the 14 renal cell tumor cases revealed no dose-dependency concerning explosives in any of the four exposure categories and was similar to that of the representative group of employees, whereas the urothelial tumor cases were predominantly confined to the high-exposure categories. Furthermore, all identified tumor patients were genotyped by polymerase chain reaction, using lymphocyte DNA, regarding their genetic status of the polymorphic xenobiotic metabolizing enzymes, including the N-acetyltransferase 2 and the glutathione-S-transferases M1 and T1. This genotyping revealed remarkable distributions only for the urothelial tumor cases, who were exclusively identified as 'slow acetylators.' This points to the possibility of human carcinogenicity of dinitrotoluene, with regard to the urothelium as the target tissue.

Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered

Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Markers of genetic susceptibility in human environmental hygiene and toxicology : the role of selected CYP, NAT and GST genes

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1 *0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.