The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

Differential expression of VEGF ligands and receptors in prostate cancer

BACKGROUND Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer. METHODS The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer. RESULTS Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue. CONCLUSIONS These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism.

The influence of school science teachers : the differential importance attributed by males and females to encouragement from science teachers

Research on the achievement and retention of female students in science and mathematics is located within a context of falling levels of participation in physical science and mathematics courses in Australian schools, and underrepresentation of females in some science, technology, engineering and mathematics (STEM) courses. The Interests and Recruitment in Science (IRIS) project is an international project that aims to contribute to understanding and improving recruitment, retention and gender equity in STEM higher education. Nearly 3500 first year students in 30 Australian universities responded to the IRIS survey of 5-point Likert items and open responses. This paper explores gender differences in first year university students’ responses to three questions about important influences on their course choice. The IRIS study found good teachers were rated highly by both males and females as influential in choosing STEM courses, and significantly higher numbers of females rated personal encouragement from senior high school science teacher as very important. In suggestions for addressing sex disparities in male-dominated STEM courses, more females indicated the importance of good teaching/encouragement and more females said (unspecified) encouragement. This study relates to the influence of school science teachers and results are discussed in relation to implications for science education.

Acoustic emission condition monitoring : an application for wind turbine fault detection

Low speed rotating machines which are the most critical components in drive train of wind turbines are often menaced by several technical and environmental defects. These factors contribute to mount the economic requirement for Health Monitoring and Condition Monitoring of the systems. When a defect is happened in such system result in reduced energy loss rates from related process and due to it Condition Monitoring techniques that detecting energy loss are very difficult if not possible to use. However, in the case of Acoustic Emission (AE) technique this issue is partly overcome and is well suited for detecting very small energy release rates. Acoustic Emission (AE) as a technique is more than 50 years old and in this new technology the sounds associated with the failure of materials were detected. Acoustic wave is a non-stationary signal which can discover elastic stress waves in a failure component, capable of online monitoring, and is very sensitive to the fault diagnosis. In this paper the history and background of discovering and developing AE is discussed, different ages of developing AE which include Age of Enlightenment (1950-1967), Golden Age of AE (1967-1980), Period of Transition (1980-Present). In the next section the application of AE condition monitoring in machinery process and various systems that applied AE technique in their health monitoring is discussed. In the end an experimental result is proposed by QUT test rig which an outer race bearing fault was simulated to depict the sensitivity of AE for detecting incipient faults in low speed high frequency machine.

The resistance of PRESENT-80 against related-key differential attacks

We examine the security of the 64-bit lightweight block cipher PRESENT-80 against related-key differential attacks. With a computer search we are able to prove that for any related-key differential characteristic on full-round PRESENT-80, the probability of the characteristic only in the 64-bit state is not higher than 2−64. To overcome the exponential (in the state and key sizes) computational complexity of the search we use truncated differences, however as the key schedule is not nibble oriented, we switch to actual differences and apply early abort techniques to prune the tree-based search. With a new method called extended split approach we are able to make the whole search feasible and we implement and run it in real time. Our approach targets the PRESENT-80 cipher however,with small modifications can be reused for other lightweight ciphers as well.

Bucket attack on numeric set watermarking model and safeguards

Numeric set watermarking is a way to provide ownership proof for numerical data. Numerical data can be considered to be primitives for multimedia types such as images and videos since they are organized forms of numeric information. Thereby, the capability to watermark numerical data directly implies the capability to watermark multimedia objects and discourage information theft on social networking sites and the Internet in general. Unfortunately, there has been very limited research done in the field of numeric set watermarking due to underlying limitations in terms of number of items in the set and LSBs in each item available for watermarking. In 2009, Gupta et al. proposed a numeric set watermarking model that embeds watermark bits in the items of the set based on a hash value of the items’ most significant bits (MSBs). If an item is chosen for watermarking, a watermark bit is embedded in the least significant bits, and the replaced bit is inserted in the fractional value to provide reversibility. The authors show their scheme to be resilient against the traditional subset addition, deletion, and modification attacks as well as secondary watermarking attacks. In this paper, we present a bucket attack on this watermarking model. The attack consists of creating buckets of items with the same MSBs and determine if the items of the bucket carry watermark bits. Experimental results show that the bucket attack is very strong and destroys the entire watermark with close to 100% success rate. We examine the inherent weaknesses in the watermarking model of Gupta et al. that leave it vulnerable to the bucket attack and propose potential safeguards that can provide resilience against this attack.

Extensions of the cube attack based on low degree annihilators

At Crypto 2008, Shamir introduced a new algebraic attack called the cube attack, which allows us to solve black-box polynomials if we are able to tweak the inputs by varying an initialization vector. In a stream cipher setting where the filter function is known, we can extend it to the cube attack with annihilators: By applying the cube attack to Boolean functions for which we can find low-degree multiples (equivalently annihilators), the attack complexity can be improved. When the size of the filter function is smaller than the LFSR, we can improve the attack complexity further by considering a sliding window version of the cube attack with annihilators. Finally, we extend the cube attack to vectorial Boolean functions by finding implicit relations with low-degree polynomials.

Application of machine learning technique in wind turbine fault diagnosis

In this study, a machine learning technique called anomaly detection is employed for wind turbine bearing fault detection. Basically, the anomaly detection algorithm is used to recognize the presence of unusual and potentially faulty data in a dataset, which contains two phases: a training phase and a testing phase. Two bearing datasets were used to validate the proposed technique, fault-seeded bearing from a test rig located at Case Western Reserve University to validate the accuracy of the anomaly detection method, and a test to failure data of bearings from the NSF I/UCR Center for Intelligent Maintenance Systems (IMS). The latter data set was used to compare anomaly detection with SVM, a previously well-known applied method, in rapidly finding the incipient faults.

Fault diagnosis of low speed bearing based on acoustic emission signal and multi-class relevance vector machine

This study presents an acoustic emission (AE) based fault diagnosis for low speed bearing using multi-class relevance vector machine (RVM). A low speed test rig was developed to simulate the various defects with shaft speeds as low as 10 rpm under several loading conditions. The data was acquired using anAEsensor with the test bearing operating at a constant loading (5 kN) andwith a speed range from20 to 80 rpm. This study is aimed at finding a reliable method/tool for low speed machines fault diagnosis based on AE signal. In the present study, component analysis was performed to extract the bearing feature and to reduce the dimensionality of original data feature. The result shows that multi-class RVM offers a promising approach for fault diagnosis of low speed machines.

Fault detection of slow speed rolling element bearing with noise removal techniques

Rolling Element Bearings (REBs) are vital components in rotating machineries for providing rotating motion. In slow speed rotating machines, bearings are normally subjected to heavy static loads and a catastrophic failure can cause enormous disruption to production and human safety. Due to its low operating speed the impact energy generated by the rotating elements on the defective components is not sufficient to produce a detectable vibration response. This is further aggravated by the inability of general measuring instruments to detect and process the weak signals at the initiation of the defect accurately. Furthermore, the weak signals are often corrupted by background noise. This is a serious problem faced by maintenance engineers today and the inability to detect an incipient failure of the machine can significantly increases the risk of functional failure and costly downtime. This paper presents the application of noise removal techniques for enhancing the detection capability for slow speed REB condition monitoring. Blind deconvolution (BD) and adaptive line enhancer (ALE) are compared to evaluate their performance in enhancing the source signal with consequential removal of background noise. In the experimental study, incipient defects were seeded on a number of roller bearings and the signals were acquired using acoustic emission (AE) sensor. Kurtosis and modified peak ratio (mPR) were used to determine the detectability of signal corrupted by noise.

Apple skin patterning is associated with differential expression of MYb10

Background Some apple (Malus × domestica Borkh.) varieties have attractive striping patterns, a quality attribute that is important for determining apple fruit market acceptance. Most apple cultivars (e.g. 'Royal Gala') produce fruit with a defined fruit pigment pattern, but in the case of 'Honeycrisp' apple, trees can produce fruits of two different kinds: striped and blushed. The causes of this phenomenon are unknown. Results Here we show that striped areas of 'Honeycrisp' and 'Royal Gala' are due to sectorial increases in anthocyanin concentration. Transcript levels of the major biosynthetic genes and MYB10, a transcription factor that upregulates apple anthocyanin production, correlated with increased anthocyanin concentration in stripes. However, nucleotide changes in the promoter and coding sequence of MYB10 do not correlate with skin pattern in 'Honeycrisp' and other cultivars differing in peel pigmentation patterns. A survey of methylation levels throughout the coding region of MYB10 and a 2.5 Kb region 5' of the ATG translation start site indicated that an area 900 bp long, starting 1400 bp upstream of the translation start site, is highly methylated. Cytosine methylation was present in all three contexts, with higher methylation levels observed for CHH and CHG (where H is A, C or T) than for CG. Comparisons of methylation levels of the MYB10 promoter in 'Honeycrisp' red and green stripes indicated that they correlate with peel phenotypes, with an enrichment of methylation observed in green stripes. Conclusions Differences in anthocyanin levels between red and green stripes can be explained by differential transcript accumulation of MYB10. Different levels of MYB10 transcript in red versus green stripes are inversely associated with methylation levels in the promoter region. Although observed methylation differences are modest, trends are consistent across years and differences are statistically significant. Methylation may be associated with the presence of a TRIM retrotransposon within the promoter region, but the presence of the TRIM element alone cannot explain the phenotypic variability observed in 'Honeycrisp'. We suggest that methylation in the MYB10 promoter is more variable in 'Honeycrisp' than in 'Royal Gala', leading to more variable color patterns in the peel of this cultivar.

Characterising transiting exoplanets by way of differential photometry

This paper describes a simple activity for plotting and characterising the light curve from an exoplanet transit event by way of differential photometry analysis. Using free digital imaging software, participants analyse a series of telescope images with the goal of calculating various exoplanet parameters, including its size, orbital radius and habitability. The activity has been designed for a high-school or undergraduate university level and introduces fundamental concepts in astrophysics and an understanding of the basis for exoplanetary science, the transit method and digital photometry.

High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

Differential regulation of growth and invasiveness of MCF-7 breast cancer cells by antiestrogens

Estrogen increases the ability of the estrogen-dependent MCF-7 human breast cancer cell line to both proliferate and invade through an artificial basement membrane. In studying the response of MCF-7 cells to various antiestrogens, we found that 4-hydroxytamoxifen and tamoxifen inhibited cell proliferation but increased their invasiveness. In contrast, the structurally unrelated benzothiophene antiestrogens, LY117018 and LY156758, were potent antiproliferative agents which did not stimulate invasiveness. The differential effects of these antiestrogenic agents on invasion correlated with changes in production of collagenase IV, while no significant change was seen in the chemotactic activity of the cells. Invasiveness was increased by 17β-estradiol or 4-hydroxytamoxifen after a few hours of treatment and was rapidly lost when 17β-estradiol was withdrawn. Stimulation of invasiveness with 17β-estradiol was blocked by the antiestrogen, LY117018. Cells from the MDA-MB-231 line which lacks estrogen receptors were not affected by estrogen or antiestrogen in terms of proliferation or invasion. These studies indicate that the invasiveness of MCF-7 cells is regulated by antiestrogens through the estrogen receptor and may be mediated by collagenase IV activity. Antiestrogens which reduce both the proliferation and invasiveness of these cells may be interesting new candidates for clinical application.