Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

A pilot study assessing the feasibility of a home-based progressive resistance exercise program and trend toward healing rates for patients with venous leg ulcers

Venous leg ulceration is a serious condition affecting 1 – 3% of the population. Decline in the function of the calf muscle pump is correlated with venous ulceration. Many previous studies have reported an improvement in the function of the calf muscle pump, endurance of the calf muscle and increased range of ankle motion after structured exercise programs. However, there is a paucity of published research that assesses if these improvements result in an improvement in the healing rates of venous ulcers. The primary purpose of this pilot study was to establish the feasibility of a homebased progressive resistance exercise program and examine if there was any clinical significance or trend toward healing. The secondary aims were to examine the benefit of a home-based progressive resistance exercise program on calf muscle pump function and physical parameters. The methodology used was a randomised controlled trial where eleven participants were randomised into an intervention (n = 6) or control group (n = 5). Participants who were randomised to receive a 12-week home-based progressive resistance exercise program were instructed through weekly face-to-face consultations during their wound clinic appointment by the author. Control group participants received standard wound care and compression therapy. Changes in ulcer parameters were measured fortnightly at the clinic (number healed at 12 weeks, percentage change in area and pressure ulcer score healing score). An air plethysmography test was performed at baseline and following the 12 weeks of training to determine changes in calf muscle pump function. Functional measures included maximum number of heel raises (endurance), maximal isometric plantar flexion (strength) and range of ankle motion (ROAM); these tests were conducted at baseline, week 6 and week 12. The sample for the study was drawn from the Princess Alexandra Hospital in Brisbane, Australia. Participants with venous leg ulceration who met the inclusion criteria were recruited. The participants were screened via duplex scanning and ankle brachial pressure index (ABPI) to ensure they did not have any arterial complications. Participants were excluded if there was evidence of cellulitis. Demographic data were obtained from each participant and details regarding medical history, quality of life and geriatric depression scores were collected at baseline. Both the intervention and control group were required to complete a weekly exercise diary to monitor activity levels between groups. To test for the effect of the intervention over time, a repeated measures analysis of variance was conducted on the major outcome variables. Group (intervention versus control) was the between subject factor and time (baseline, week 6, week 12) was the within subject or repeated measures factor. Due to the small sample size, further tests were conducted to check the assumptions of the statistical test to be used. The results showed that Mauchly.s Test, the Sphericity assumptions of repeated measures for ANOVA were met. Further tests of homogeneity of variance assumptions also confirmed that this assumption was met. Data analysis was conducted using the software package SPSS for Windows Release 17.0. The pilot study proved feasible with all of the intervention (n=6) participants continuing with the resistance program for the 12 week duration and no deleterious effects noted. Clinical significance was observed in the intervention group with a 32% greater change in ulcer size (p= 0.26) than the control group, and a 10% (p = 0.74) greater difference between the numbers healed compared to the control group. Statistical significance was observed for the ejection fraction (p = 0.05), residual volume fraction (p = 0.04) and ROAM (p = 0.01), which all improved significantly in the intervention group over time. These results are encouraging, nevertheless, further investigations seem warranted to examine the effect exercise has on the healing rates of venous leg ulcers, with a multistudy site, larger sample size and longer follow up period.

Defending web services against denial of service attacks using client puzzles

The interoperable and loosely-coupled web services architecture, while beneficial, can be resource-intensive, and is thus susceptible to denial of service (DoS) attacks in which an attacker can use a relatively insignificant amount of resources to exhaust the computational resources of a web service. We investigate the effectiveness of defending web services from DoS attacks using client puzzles, a cryptographic countermeasure which provides a form of gradual authentication by requiring the client to solve some computationally difficult problems before access is granted. In particular, we describe a mechanism for integrating a hash-based puzzle into existing web services frameworks and analyze the effectiveness of the countermeasure using a variety of scenarios on a network testbed. Client puzzles are an effective defence against flooding attacks. They can also mitigate certain types of semantic-based attacks, although they may not be the optimal solution.

Community-based protest against construction projects : a case study of movement continuity

Community-based activism against proposed construction projects is growing. Many protests are poorly managed and escalate into long-term and sometimes acrimonious disputes which damage communities, firms and the construction industry as a whole. Using a thematic storytelling approach which draws on ethnographic method, within a single case study framework, new insights into the social forces that shape and sustain community-based protest against construction projects are provided. A conceptual model of protest movement continuity is presented which highlights the factors that sustain protest continuity over time. The model illustrates how social contagion leads to common community perceptions of development risk and opportunity, to a positive internalization of collective values and identity, to a strategic utilization of social capital and an awareness of the need to manage the emotional dynamics of protest through mechanisms such as symbolic artefacts.

Partial protection against chlamydial reproductive tract infection by a recombinant major outer membrane protein/CpG/cholera toxin intranasal vaccine in the guinea pig Chlamydia cavaie model

Chlamydia trachomatis is a major cause of sexually transmitted diseases worldwide. There currently is no vaccine to protect against chlamydial infection of the female reproductive tract. Vaccine development has predominantly involved using the murine model, however infection of female guinea pigs with Chlamydia caviae more closely resembles chlamydial infection of the human female reproductive tract, and presents a better model to assess potential human chlamydial vaccines. We immunised female guinea pigs intranasally with recombinant major outer membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants. Both systemic and mucosal immune responses were elicited in immunised animals. MOMP-specific IgG and IgA were present in the vaginal mucosae, and high levels of MOMP-specific IgG were detected in the serum of immunised animals. Antibodies from the vaginal mucosae were also shown to be capable of neutralising C. caviae in vitro. Following immunisation, animals were challenged intravaginally with a live C. caviae infection of 102 inclusion forming units. We observed a decrease in duration of infection and a significant (p<0.025) reduction in infection load in r-MOMP immunised animals, compared to animals immunised with adjuvant only. Importantly, we also observed a marked reduction in upper reproductive tract (URT) pathology in r-MOMP immunised animals. Intranasal immunisation of female guinea pigs with r-MOMP was able to provide partial protection against C. caviae infection, not only by reducing chlamydial burden but also URT pathology. This data demonstrates the value of using the guinea pig model to evaluate potential chlamydial vaccines for protection against infection and disease pathology caused by C. trachomatis in the female reproductive tract.

Open problems in the security of learning

Machine learning has become a valuable tool for detecting and preventing malicious activity. However, as more applications employ machine learning techniques in adversarial decision-making situations, increasingly powerful attacks become possible against machine learning systems. In this paper, we present three broad research directions towards the end of developing truly secure learning. First, we suggest that finding bounds on adversarial influence is important to understand the limits of what an attacker can and cannot do to a learning system. Second, we investigate the value of adversarial capabilities-the success of an attack depends largely on what types of information and influence the attacker has. Finally, we propose directions in technologies for secure learning and suggest lines of investigation into secure techniques for learning in adversarial environments. We intend this paper to foster discussion about the security of machine learning, and we believe that the research directions we propose represent the most important directions to pursue in the quest for secure learning.

Alone against the crowd: Individual differences in referees' ability to cope under pressure

This paper contributes to the recent debate about the role of referees in the home advantage phenomenon. Specifically, it aims to provide a convincing answer to the newly posed question of the existence of individual differences among referees in terms of the home advantage (Boyko, Boyko, & Boyko, 2007; Johnston, 2008). Using multilevel modelling on a large and representative dataset we find that (1) the home advantage effect differs significantly among referees, and (2) this relationship is moderated by the size of the crowd. These new results suggest that a part of the home advantage is due to the effect of the crowd on the referees, and that some referees are more prone to be influenced by the crowd than others. This provides strong evidence to indicate that referees are a significant contributing factor to the home advantage. The implications of these findings are discussed both in terms of the relevant social psychological research, and with respect to the selection, assessment, and training of referees.