Book review: ‘Anterior Eye Disease and Therapeutics A-Z' [2nd ed.] Edition, by A. Bruce and M. Loughnan. Churchill Livingstone (Elsevier), Edinburgh 2011

With the ever-increasing emphasis on ocular disease recognition in the practice of optometry and especially anterior eye disease management and therapeutics, any book addressing such issues is bound to have a captive audience. This second edition of Anterior Eye Disease and Therapeutics A–Z provides a succinct yet comprehensive coverage of this topic.

The role of the Eph and ephrin proteins in prostate cancer

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer related deaths in Australian men. Treatment in the early stages of the disease involves surgery, radiation and/or hormone therapy. However, in late stages of the disease these treatments are no longer effective and only palliative care is available. Therefore, there is a focus on exploration of novel therapies to increase survival and treatment efficacy. Advanced prostate cancer is characterised by bone or other distant metastasis. Spreading of the primary tumour to a secondary location is a complex process requiring an initial loss in cell-cell adhesion followed by increased cell migration and invasion. One gene family that has been known to affect cell-to-cell contact in other model systems are the Eph receptor tyrosine kinases. They are the largest family of receptor tyrosine kinases made up of 14 vertebrate Eph receptors that bind to nine cell membrane bound ephrin ligands. Eph-ephrin interaction is crucial in regulating cell behaviour in developmental processes and it is now thought that the underlying mechanisms involved in development may also be involved in cancer. Aberrant expression has been reported in many human malignancies including prostate cancer. Furthermore, expression has been linked with metastasis and poor prognosis in other tumour models. This study explores the potential role of the Eph receptor family in prostate cancer, in particular the roles of EphA2, EphA3 and ephrin-A5. Gene expression profiles were established for the Eph family in a series of prostate cancer cell lines using quantitative real time RT-PCR. A smaller subset of the most prominently expressed genes was chosen to screen a cohort of clinical samples. Elevated levels of EphA2, EphA3 and their ligands, ephrin-A1 and ephrin-A5 were observed in individual cell lines. Interestingly high EphA3 expression was observed in the androgen responsive cell lines while EphA2 was more prominent in the androgen independent cell lines. However, studies using 5-dihydrotestosterone suggest that EphA3 expression in not regulated by androgen. Cells expressing EphA2 showed a greater ability for migration and invasion while cells expressing EphA3 showed poor migration and invasion. Forced expression of EphA2 in the LNCaP cell line resulted in a more invasive phenotype while forced expression of EphA3 in the PC-3 cell line suggests a possible negative effect for EphA3 on cell migration and invasion. Cell signalling studies show activation of EphA2 decreases activity of proteins thought to be involved in pathways regulating cell movement including Akt, Src and FAK. Changes to the activation status of Rho family members, including RhoA and Rac1, associated with reorganisation of the actin cytoskeleton, an important part of cell migration was also observed. As a result, activation of EphA2 in PC-3 cells resulted in a less invasive phenotype. A novel finding in this study was the discovery of a combination of two EphA2 Mabs able to activate EphA2. Preliminary results show a potential for this antibody combination to reduce prostate cancer invasion in vitro. A unique aspect of Eph-ephrin interaction is the resulting bi-directional signalling that occurs through both the receptor and ligand. In this study a potential role for ephrin-A5 mediated signalling in prostate cancer was observed. LNCaP cells express high levels of EphA3 and its high affinity ligand ephrin-A5. In stripe assays, used to study guidance cues, LNCaP cells show strong attraction/migration to EphA3-Fc stripes but not ephrin-A5-Fc stripes suggesting ephrin-A5 mediated reverse cell signalling is involved. Knockdown of ephrin-A5 using shRNA resulted in a decrease in attraction/migration to EphA3-Fc stripes. Furthermore a reduction in proliferation was also observed in vitro. A subcutaneous xenograft model using ephrin-A5 shRNA cells versus controls showed a decrease in tumour formation. This study demonstrates a difference in EphA2 and EphA3 function in prostate cancer migration/invasion and a potential role for ephrin-A5 in prostate cancer cell adhesion and growth.

Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala

Glucocorticoids, released in high concentrations from the adrenal cortex during stressful experiences, bind to glucocorticoid receptors in nuclear and peri-nuclear sites in neuronal somata. Their classically known mode of action is to induce gene promoter receptors to alter gene transcription. Nuclear glucocorticoid receptors are particularly dense in brain regions crucial for memory, including memory of stressful experiences, such as the hippocampus and amygdala. While it has been proposed that glucocorticoids may also act via membrane bound receptors, the existence of the latter remains controversial. Using electron microscopy, we found glucocorticoid receptors localized to non-genomic sites in rat lateral amygdala, glia processes, presynaptic terminals, neuronal dendrites, and dendritic spines including spine organelles and postsynaptic membrane densities. The lateral nucleus of the amygdala is a region specifically implicated in the formation of memories for stressful experiences. These newly observed glucocorticoid receptor immunoreactive sites were in addition to glucocorticoid receptor immunoreactive signals observed using electron and confocal microscopy in lateral amygdala principal neuron and GABA neuron soma and nuclei, cellular domains traditionally associated with glucocorticoid immunoreactivity. In lateral amygdala, glucocorticoid receptors are thus also localized to non-nuclear-membrane translocation sites, particularly dendritic spines, where they show an affinity for postsynaptic membrane densities, and may have a specialized role in modulating synaptic transmission plasticity related to fear and emotional memory.

Breastfeeding self-efficacy of women using second-line strategies for healthy term infants in the first week postpartum : an Australian observational study

Background Breastfeeding self-efficacy (BFSE) supports breastfeeding initiation and duration. Challenges to breastfeeding may undermine BFSE, but second-line strategies including nipple shields, syringe, cup, supply line and bottle feeding may support breastfeeding until challenges are resolved. The primary aim of this study was to examine BFSE in a sample of women using second-line strategies for feeding healthy term infants in the first week postpartum. Methods A retrospective self-report study was conducted using the Breastfeeding Self-Efficacy Scale - Short Form (BSES-SF), demographic and infant feeding questionnaires. Breastfeeding women who gave birth to a singleton healthy term infant at one private metropolitan birthing facility in Australia from November 2008 to February 2009 returned anonymous questionnaires by mail. Results A total of 128 (73 multiparous, 55 primiparous) women participated in the study. The mean BSES-SF score was 51.18 (Standard deviation, SD: 12.48). The median BSES-SF score was 53. Of women using a second-line strategy, 16 exceeded the median, and 42 were below. Analyses using Kruskal-Wallis tests confirmed this difference was statistically significant (H = 21.569, p = 0.001). The rate of second-line strategy use was 48%. The four most commonly used second-line strategies were: bottles with regular teats (77%); syringe feeding (44%); bottles with wide teats (34%); and nipple shields (27%). Seven key challenges were identified that contributed to the decision to use second-line strategies, including: nipple pain (40%); unsettled infant (40%); insufficient milk supply (37%); fatigue (37%); night nursery care (25%); infant weight loss > 10% (24%); and maternal birth associated pain (20%). Skin-to-skin contact at birth was commonly reported (93%). At seven days postpartum 124 women (97%) were continuing to breastfeed. Conclusions The high rate of use of second-line strategies identified in this study and high rate of breastfeeding at day seven despite lower BFSE indicate that such practices should not be overlooked by health professionals. The design of this study does not enable determination of cause-effect relationships to identify factors which contribute to use of second-line strategies. Nevertheless, the significantly lower BSES-SF score of women using a second-line strategy highlights this group of women have particular needs that require attention.

Social networks in arid Australia : a review of concepts and evidence

Arid systems are markedly different from non-arid systems. This distinctiveness extends to arid-social networks, by which we mean social networks which are influenced by the suite of factors driving arid and semi-arid regions. Neither the process of how aridity interacts with social structure, nor what happens as a result of this interaction, is adequately understood. This paper postulates three relative characteristics which make arid-social networks distinct: that they are tightly bound, are hierarchical in structure and, hence, prone to power abuses, and contain a relatively higher proportion of weak links, making them reactive to crisis. These ideas were modified from workshop discussions during 2006. Although they are neither tested nor presented as strong beliefs, they are based on the anecdotal observations of arid-system scientists with many years of experience. This paper does not test the ideas, but rather examines them in the context of five arid-social network case studies with the aim of hypotheses building. Our cases are networks related to pastoralism, Aboriginal outstations, the ‘Far West Coast Aboriginal Enterprise Network’ and natural resources in both the Lake-Eyre basin and the Murray–Darling catchment. Our cases highlight that (1) social networks do not have clear boundaries, and that how participants perceive their network boundaries may differ from what network data imply, (2) although network structures are important determinants of system behaviour, the role of participants as individuals is still pivotal, (3) and while in certain arid cases weak links are engaged in crisis, the exact structure of all weak links in terms of how they place participants in relation to other communities is what matters.

Nedd4-2functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells

Constitutive albumin uptake by the proximal tubule is achieved by a receptor-mediated process in which the Cl– channel, ClC-5, plays an obligate role. Here we investigated the functional interaction between ClC-5 and ubiquitin ligases Nedd4 and Nedd4-2 and their role in albumin uptake in opossum kidney proximal tubule (OK) cells. In vivo immunoprecipitation using an anti-HECT antibody demonstrated that ClC-5 bound to ubiquitin ligases, whereas glutathione S-transferase pull-downs confirmed that the C terminus of ClC-5 bound both Nedd4 and Nedd4-2. Nedd4-2 alone was able to alter ClC-5 currents in Xenopus oocytes by decreasing cell surface expression of ClC-5. In OK cells, a physiological concentration of albumin (10 μg/ml) rapidly increased cell surface expression of ClC-5, which was also accompanied by the ubiquitination of ClC-5. Albumin uptake was reduced by inhibiting either the lysosome or proteasome. Total levels of Nedd4-2 and proteasome activity also increased rapidly in response to albumin. Overexpression of ligase defective Nedd4-2 or knockdown of endogenous Nedd4-2 with small interfering RNA resulted in significant decreases in albumin uptake. In contrast, pathophysiological concentrations of albumin (100 and 1000 μg/ml) reduced the levels of ClC-5 and Nedd4-2 and the activity of the proteasome to the levels seen in the absence of albumin. These data demonstrate that normal constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may act via ubiquitination to shunt ClC-5 into the endocytic pathway.

Arts practice and disconnected youth in Australia : impact and domains of change

Background: This paper describes research conducted with Big hART, Australia's most awarded participatory arts company. It considers three projects, LUCKY, GOLD and NGAPARTJI NGAPARTJI across separate sites in Tasmania, Western NSW and Northern Territory, respectively, in order to understand project impact from the perspective of project participants, Arts workers, community members and funders. Methods: Semi-structured interviews were conducted with 29 respondents. The data were coded thematically and analysed using the constant comparative method of qualitative data analysis. Results: Seven broad domains of change were identified: psychosocial health; community; agency and behavioural change; the Art; economic effect; learning and identity. Conclusions: Experiences of participatory arts are interrelated in an ecology of practice that is iterative, relational, developmental, temporal and contextually bound. This means that questions of impact are contingent, and there is no one path that participants travel or single measure that can adequately capture the richness and diversity of experience. Consequently, it is the productive tensions between the domains of change that are important and the way they are animated through Arts practice that provides sign posts towards the impact of Big hART projects.

A comparison of the gas phase acidities of phospholipid headgroups: Experimental and computational studies

Proton-bound dimers consisting of two glycerophospholipids with different headgroups were prepared using negative ion electrospray ionization and dissociated in a triple quadrupole mass spectrometer. Analysis of the tandem mass spectra of the dimers using the kinetic method provides, for the first time, an order of acidity for the phospholipid classes in the gas phase of PE < PA << PG < PS < PI. Hybrid density functional calculations on model phospholipids were used to predict the absolute deprotonation enthalpies of the phospholipid classes from isodesmic proton transfer reactions with phosphoric acid. The computational data largely support the experimental acidity trend, with the exception of the relative acidity ranking of the two most acidic phospholipid species. Possible causes of the discrepancy between experiment and theory are discussed and the experimental trend is recommended. The sequence of gas phase acidities for the phospholipid headgroups is found to (1) have little correlation with the relative ionization efficiencies of the phospholipid classes observed in the negative ion electrospray process, and (2) correlate well with fragmentation trends observed upon collisional activation of phospholipid \[M - H](-) anions. (c) 2005 American Society for Mass Spectrometry.

Digital Literacy and the Spaces of Academic Discourse

Digital literacy poses a particular challenge to the research-led university. Although these universities are often at the forefront of introducing digital literacy initiatives—such as e-learning platforms, technological infrastructure, and digital repositories—these applications of digital literacy tend to be more instrumental or functional than critical or creative. Certainly, this clash of cultures between the instrumental/functional and the critical/analytical is at the heart of debates over the uses of digital literacy in higher education. However, this simple equation of political forces with instrumentality and the corresponding equation of the university with a tradition of reflective thought that brings criticism to bear on instrumentality elide the fact that this conflict is more deeply rooted within the academy. This essay argues that, in fact, much of the resistance to critical uses of digital literacy comes from within the institution of the university itself. That is, the university is bound up in a scriptural economy that prioritises the printed word and that reinforces its power by way of a normative, political, and spatialised academic discourse. It is this print-based scriptural economy—in which this essay must acknowledge its own complicity—that a critical approach to digital literacy threatens to disrupt or lay bare.

Geographies/aerographies of contagion

In this paper I argue that geography, contagion, and the element of air have historically overlapped in interesting ways and that they continue to do so. By tracing metaphors of air, wind, miasma, and contagion through literary works that span nearly three centuries, I argue that the element of air tends to signify, in cultural expression, a more ambiguous, affective form of contagion that is also bound up with the spread of ideas and information.

Unconditionally secure disjointness tests for private datasets

We present two unconditional secure protocols for private set disjointness tests. In order to provide intuition of our protocols, we give a naive example that applies Sylvester matrices. Unfortunately, this simple construction is insecure as it reveals information about the intersection cardinality. More specifically, it discloses its lower bound. By using the Lagrange interpolation, we provide a protocol for the honest-but-curious case without revealing any additional information. Finally, we describe a protocol that is secure against malicious adversaries. In this protocol, a verification test is applied to detect misbehaving participants. Both protocols require O(1) rounds of communication. Our protocols are more efficient than the previous protocols in terms of communication and computation overhead. Unlike previous protocols whose security relies on computational assumptions, our protocols provide information theoretic security. To our knowledge, our protocols are the first ones that have been designed without a generic secure function evaluation. More important, they are the most efficient protocols for private disjointness tests in the malicious adversary case.

Does counting still count? Revisiting the security of counting based user authentication protocols against statistical attacks

At NDSS 2012, Yan et al. analyzed the security of several challenge-response type user authentication protocols against passive observers, and proposed a generic counting based statistical attack to recover the secret of some counting based protocols given a number of observed authentication sessions. Roughly speaking, the attack is based on the fact that secret (pass) objects appear in challenges with a different probability from non-secret (decoy) objects when the responses are taken into account. Although they mentioned that a protocol susceptible to this attack should minimize this difference, they did not give details as to how this can be achieved barring a few suggestions. In this paper, we attempt to fill this gap by generalizing the attack with a much more comprehensive theoretical analysis. Our treatment is more quantitative which enables us to describe a method to theoretically estimate a lower bound on the number of sessions a protocol can be safely used against the attack. Our results include 1) two proposed fixes to make counting protocols practically safe against the attack at the cost of usability, 2) the observation that the attack can be used on non-counting based protocols too as long as challenge generation is contrived, 3) and two main design principles for user authentication protocols which can be considered as extensions of the principles from Yan et al. This detailed theoretical treatment can be used as a guideline during the design of counting based protocols to determine their susceptibility to this attack. The Foxtail protocol, one of the protocols analyzed by Yan et al., is used as a representative to illustrate our theoretical and experimental results.

Known and chosen key differential distinguishers for block ciphers

In this paper we investigate the differential properties of block ciphers in hash function modes of operation. First we show the impact of differential trails for block ciphers on collision attacks for various hash function constructions based on block ciphers. Further, we prove the lower bound for finding a pair that follows some truncated differential in case of a random permutation. Then we present open-key differential distinguishers for some well known round-reduced block ciphers.

Multi-party computation with omnipresent adversary

Secure multi-party computation (MPC) protocols enable a set of n mutually distrusting participants P 1, ..., P n , each with their own private input x i , to compute a function Y = F(x 1, ..., x n ), such that at the end of the protocol, all participants learn the correct value of Y, while secrecy of the private inputs is maintained. Classical results in the unconditionally secure MPC indicate that in the presence of an active adversary, every function can be computed if and only if the number of corrupted participants, t a , is smaller than n/3. Relaxing the requirement of perfect secrecy and utilizing broadcast channels, one can improve this bound to t a  < n/2. All existing MPC protocols assume that uncorrupted participants are truly honest, i.e., they are not even curious in learning other participant secret inputs. Based on this assumption, some MPC protocols are designed in such a way that after elimination of all misbehaving participants, the remaining ones learn all information in the system. This is not consistent with maintaining privacy of the participant inputs. Furthermore, an improvement of the classical results given by Fitzi, Hirt, and Maurer indicates that in addition to t a actively corrupted participants, the adversary may simultaneously corrupt some participants passively. This is in contrast to the assumption that participants who are not corrupted by an active adversary are truly honest. This paper examines the privacy of MPC protocols, and introduces the notion of an omnipresent adversary, which cannot be eliminated from the protocol. The omnipresent adversary can be either a passive, an active or a mixed one. We assume that up to a minority of participants who are not corrupted by an active adversary can be corrupted passively, with the restriction that at any time, the number of corrupted participants does not exceed a predetermined threshold. We will also show that the existence of a t-resilient protocol for a group of n participants, implies the existence of a t’-private protocol for a group of n′ participants. That is, the elimination of misbehaving participants from a t-resilient protocol leads to the decomposition of the protocol. Our adversary model stipulates that a MPC protocol never operates with a set of truly honest participants (which is a more realistic scenario). Therefore, privacy of all participants who properly follow the protocol will be maintained. We present a novel disqualification protocol to avoid a loss of privacy of participants who properly follow the protocol.

Built to last or meant to end : intertemporal choice in strategic alliance portfolios

A salient but rarely explicitly studied characteristic of interfirm relationships is that they can intentionally be formed for finite periods of time. What determines firms' intertemporal choices between different alliance time horizons? Shadow of the future theorists suggest that when an alliance has an explicitly set short-term time frame, there is an increased risk that partners may behave opportunistically. This does not readily explain the high incidence of time-bound alliances being formed. Reconciling insights from the shadow of the future perspective with nascent research on the flexibility of temporary organizations, and shifting the focus from the level of individual transactions to that of strategic alliance portfolios, we argue that firms may be willing to accept a higher risk of opportunism when there are offsetting gains in strategic flexibility in managing their strategic alliance portfolio. Consequently, we hypothesize that environmental factors that increase the need for strategic flexibility—namely, dynamism and complexity in the environment—are likely to increase the relative share of time-bound alliances in strategic alliance portfolios. Our analysis of longitudinal data on the intertemporal alliance choices of a large sample of small and medium-sized enterprises provides support for this argument. Our findings fill an important gap in theory about time horizons in interfirm relationships and temporary organizations and show the importance of separating planned terminations from duration-based performance measures.