Conspiracy for good

"Tim Kring, Creator of the hit television show 'Heroes' tells how the big idea began, and where you can jump in. "A few years ago, I started thinking about an entirely new way to tell a story, far different from traditional TV. I didn't just want to talk about 'saving the world' in fiction, I wanted to create a narrative that spilled out into the streets. One that you could live inside of for a while. How cool would it be, I thought, to create a story that exists all around you all of the time? On your laptop, your mobile phone, on your sidewalks, as a secret message hidden in your favorite song or while standing at the bus stop on your way to work. And, taking it further, what if your participation over a few weeks or months actually impacts the story's development and creates positive change in the real world because a philanthropic mission is integrated into the narrative itself? The Conspiracy For Good is the culmination of this dream. This is the pilot project for a first-of-itskind interactive story that empowers its audience to take real-life action and create positive change in the world. Call it Social Benefit Storytelling. To achieve this, I need you to participate. Reality and fiction have to blur. Every story needs a villain and you will meet the villain in the STORY SO FAR section on this site. And every story needs a hero. That's where YOU come in. As part of The Conspiracy For Good you will join a collective of thinkers, artists, musicians, and causes, creating a unified voice to fight the forces of social and environmental injustice. This is our site, where together we can follow the story and build a community that focuses on changing the world for the better, one person and one action at a time. Welcome to the Conspiracy." Tim Kring"

Genotoxicity of inorganic mercury salts based on disturbed microtubule function

This study investigated the hypothesis that the chromosomal genotoxicity of inorganic mercury results from interaction(s) with cytoskeletal proteins. Effects of Hg2+ salts on functional activities of tubulin and kinesin were investigated by determining tubulin assembly and kinesin-driven motility in cell-free systems. Hg2+ inhibits microtubule assembly at concentrations above 1 μM, and inhibition is complete at about 10 μM. In this range, the tubulin assembly is fully (up to 6 μM) or partially (∼6-10 μM) reversible. The inhibition of tubulin assembly by mercury is independent of the anion, chloride or nitrate. The no-observed-effect- concentration for inhibition of microtubule assembly in vitro was 1 μM Hg2+, the IC50 5.8 μM. Mercury(II) salts at the IC 50 concentrations partly inhibiting tubulin assembly did not cause the formation of aberrant microtubule structures. Effects of mercury salts on the functionality of the microtubule motility apparatus were studied with the motor protein kinesin. By using a "gliding assay" mimicking intracellular movement and transport processes in vitro, HgCl2 affected the gliding velocity of paclitaxel-stabilised microtubules in a clear dose-dependent manner. An apparent effect is detected at a concentration of 0.1 μM and a complete inhibition is reached at 1 μM. Cytotoxicity of mercury chloride was studied in V79 cells using neutral red uptake, showing an influence above 17 μM HgCl2. Between 15 and 20 μM HgCl2 there was a steep increase in cell toxicity. Both mercury chloride and mercury nitrate induced micronuclei concentration-dependently, starting at concentrations above 0.01 μM. CREST analyses on micronuclei formation in V79 cells demonstrated both clastogenic (CREST-negative) and aneugenic effects of Hg2+, with some preponderance of aneugenicity. A morphological effect of high Hg2+ concentrations (100 μM HgCl2) on the microtubule cytoskeleton was verified in V79 cells by immuno-fluorescence staining. The overall data are consistent with the concept that the chromosomal genotoxicity could be due to interaction of Hg2+ with the motor protein kinesin mediating cellular transport processes. Interactions of Hg 2+ with the tubulin shown by in vitro investigations could also partly influence intracellular microtubule functions leading, together with the effects on the kinesin, to an impaired chromosome distribution as shown by the micronucleus test.

Thought balloon : Dr Christy Dena

In this interview, we discuss the basics of transmedia storytelling and lessons for creatives considering making the jump to a transmedia project.

Prescribing for nausea in palliative care : A cross-sectional national survey of Australian palliative medicine doctors

Background: Nausea can be a debilitating symptom for patients with a life-limiting illness. While addressing reversible components, nonpharmacological strategies and antiemetics are the main therapeutic option. The choice of medication, dose, and route of administration remain highly variable. Objective: The aim of this study was to codify the current clinical approaches and quantify any variation found nationally. Methods: A cross-sectional study utilizing a survey of palliative medicine clinicians examined prescribing preferences for nausea using a clinical vignette. Respondent characteristics, the use of nonpharmacological interventions, first- and second-line antiemetic choices, commencing and maximal dose, and time to review were collected. Results: Responding clinicians were predominantly working in palliative medicine across a range of settings with a 49% response rate (105/213). The main nonpharmacological recommendation was “small, frequent snacks.” Metoclopramide was the predominant first-line agent (69%), followed by haloperidol (26%), while second-line haloperidol was the predominant agent (47%), with wide variation in other nominated agents. Respondents favoring metoclopramide as first-line tended to use haloperidol second-line (65%), but not vice versa. Maximal doses for an individual antiemetic varied up to tenfold. Conclusion: For nausea, a commonly encountered symptom in palliative care, clinicians' favored metoclopramide and haloperidol; however, after these choices, there was large variation in antiemetic selection. While most clinicians recommended modifying meal size and frequency, use of other nonpharmacological therapies was limited.

Development of a polymer theranostic for prostate cancer

Theranostics offers an improved treatment strategy for prostate cancer by facilitating simultaneous targeting of tumour cells with subsequent drug delivery and imaging. In this report we describe the synthesis of hyperbranched polymers that are biocompatible, can specifically target and be internalised by prostate cancer cells (through targeting of prostate-specific membrane antigen – PSMA) and ultimately facilitate controlled delivery of a model drug. The theranostic also incorporates a far-red fluorescent dye that allows tracking of the polymer via optical imaging. Controlled synthesis of the polymer is achieved via reversible addition fragmentation chain transfer polymerisation of polyethylene glycol monomethyl methacrylate, with ethylene glycol dimethacrylate as the branching agent. Incorporation of 20 mol% of an hydrazide-methacrylate monomer allows post-ligation of a model drug, fluorene-2-carboxaldehyde, through a hydrolytically-degradable hydrazone linkage. The rate of degradation of this particular linker was enhanced at endosomal pH (pH = 5.5) where [similar]95% of the model drug was released in 4 hours compared to less than 5% released over the same period at physiological pH. The theranostic showed high uptake into prostate cancer cells expressing prostate-specific membrane antigen, while minimal uptake was observed in PC3 cells negative for PSMA, highlighting the enhanced efficacy of the targeting ligand.

Menstrual effluent induces epithelial-mesenchymal transitions in mesothelial cells

Background Menstrual effluent affects mesothelial cell (MC) morphology. We evaluated whether these changes were consistent with epithelial-mesenchymal transitions (EMT). Methods Monolayer cultures of MC were incubated overnight in conditioned media, prepared from cells isolated form menstrual effluent, with or without kinase and ATP inhibitors. Changes in cell morphology were monitored using time-lapse video microscopy and immunohistochemistry. Effects on the expression of EMT-associated molecules were evaluated using real-time RT-PCR and/or Western blot analysis. Results Incubation in conditioned media disrupted cell-cell contacts, and increased MC motility. The changes were reversible. During the changes the distribution of cytokeratins, fibrillar actin and α-tubulin changed. Sodium azide, an inhibitor of ATP production, and Genistein, a general tyrosine kinase inhibitor, antagonized these effects. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and SU6656, an Src tyrosine kinase inhibitor, only partially antagonized the effect. The expression of Snail and vimentin was markedly up-regulated, whereas the expression of E-cadherin was decreased and cytokeratins were altered. Conclusions In MC, menstrual effluent initiates a reversible, energy-dependent transition process from an epithelial to a mesenchymal phenotype. Involvement of the (Src) tyrosine kinase signalling pathway and the changes in the expression of cytokeratins, Snail, vimentin and E-cadherin demonstrate that the morphological changes are EMT.

Cold water immersion enhances recovery of submaximal muscle function after resistance exercise

We investigated the effect of cold water immersion (CWI) on the recovery of muscle function and physiological responses following high-intensity resistance exercise. Using a randomized, cross-over design, 10 physically active men performed high-intensity resistance exercise, followed by one of two recovery interventions: 10 min of cold water immersion at 10°C, or 10 min active recovery (low-intensity cycling). After the recovery interventions, maximal muscle function was assessed after 2 h and 4 h by measuring jump height and isometric squat strength. Submaximal muscle function was assessed after 6 h by measuring the average load lifted during six sets of 10 squats at 80% 1RM. Intramuscular temperature (1 cm) was also recorded, and venous blood samples were analyzed for markers of metabolism, vasoconstriction and muscle damage. CWI did not enhance recovery of maximal muscle function. However, during the final three sets of the submaximal muscle function test, the participants lifted a greater load (p<0.05; 38%; Cohen’s d 1.3) following CWI compared with active recovery. During CWI, muscle temperature decreased 6°C below post-exercise values, and remained below pre-exercise values for another 35 min. Venous blood O2 saturation decreased below pre-exercise values for 1.5 h after CWI. Serum endothelin-1 concentration did not change after CWI, whereas it decreased after active recovery. Plasma myoglobin concentration was lower, whereas plasma interleukin-6 concentration was higher after CWI compared with active recovery. These results suggest that cold water immersion after resistance exercise allow athletes to complete more work during subsequent training sessions, which could enhance long-term training adaptations.

Is there a potential relationship between prior h amstring strain injury and increased risk for future a nterior cruciate ligament injury?

Hamstring strain injuries (HSIs) are the most prevalent injury in a number of sports, and while anterior cruciate ligament (ACL) injuries are less common, they are far more severe and have long-term implications, such as an increased risk of developing osteoarthritis later in life. Given the high incidence and severity of these injuries, they are key targets of injury preventive programs in elite sport. Evidence has shown that a previous severe knee injury (including ACL injury) increases the risk of HSI; however, whether the functional deficits that occur after HSI result in an increased risk of ACL injury has yet to be considered. In this clinical commentary, we present evidence that suggests that the link between previous HSI and increased risk of ACL injury requires further investigation by drawing parallels between deficits in hamstring function after HSI and in women athletes, who are more prone to ACL injury than men athletes. Comparisons between the neuromuscular function of the male and female hamstring has shown that women display lower hamstring-to-quadriceps strength ratios during isokinetic knee flexion and extension, increased activation of the quadriceps compared with the hamstrings during a stop-jump landing task, a greater time required to reach maximal isokinetic hamstring torque, and lower integrated myoelectrical hamstring activity during a sidestep cutting maneuver. Somewhat similarly, in athletes with a history of HSI, the previously injured limb, compared with the uninjured limb, displays lower eccentric knee flexor strength, a lower hamstrings-to-quadriceps strength ratio, lower voluntary myoelectrical activity during maximal knee flexor eccentric contraction, a lower knee flexor eccentric rate of torque development, and lower voluntary myoelectrical activity during the initial portion of eccentric contraction. Given that the medial and lateral hamstrings have different actions at the knee joint in the coronal plane, which hamstring head is previously injured might also be expected to influence the likelihood of future ACL. Whether the deficits in function after HSI, as seen in laboratory-based studies, translate to deficits in hamstring function during typical injurious tasks for ACL injury has yet to be determined but should be a consideration for future work.

Synthesis of novel interlocked architectures in solution and solid phase

Mechanically interlocked molecules, such as catenanes and rotaxanes, are fascinating due to their unique sensing and catalytic properties and their potential to act as molecular motors or switches. Traditionally their synthesis has been laborious and expensive, however this research project endeavoured to overcome this challenge by exploring novel ways of preparing mechanically interlocked molecules both in solution and on surfaces. A series of disulfide-linked macrocycles, [2]catenanes and [2]rotaxanes were synthesised in solution using reversible dynamic covalent chemistry. Subsequently, the interlocked architectures were adapted into solid-tethered systems via attachment to swelling polystyrene resins.

Hydrotherapy as a recovery strategy after exercise: A pragmatic controlled trial

Background Our aim was to evaluate the recovery effects of hydrotherapy after aerobic exercise in cardiovascular, performance and perceived fatigue. Methods A pragmatic controlled repeated measures; single-blind trial was conducted. Thirty-four recreational sportspeople visited a Sport-Centre and were assigned to a Hydrotherapy group (experimental) or rest in a bed (control) after completing a spinning session. Main outcomes measures including blood pressure, heart rate, handgrip strength, vertical jump, self-perceived fatigue, and body temperature were assessed at baseline, immediately post-exercise and post-recovery. The hypothesis of interest was the session*time interaction. Results The analysis revealed significant session*time interactions for diastolic blood pressure (P=0.031), heart rate (P=0.041), self perceived fatigue (P=0.046), and body temperature (P=0.001); but not for vertical jump (P=0.437), handgrip (P=0.845) or systolic blood pressure (P=0.266). Post-hoc analysis revealed that hydrotherapy resulted in recovered heart rate and diastolic blood pressure similar to baseline values after the spinning session. Further, hydrotherapy resulted in decreased self-perceived fatigue after the spinning session. Conclusions Our results support that hydrotherapy is an adequate strategy to facilitate cardiovascular recovers and perceived fatigue, but not strength, after spinning exercise. Trial registration ClinicalTrials.gov Identifier: NCT01765387 Keywords: Hydrotherapy; Heart rate; Fatigue; Strength; Blood pressure; Body temperature

Content-independent embedding scheme for multi-modal medical image watermarking

Background As the increasing adoption of information technology continues to offer better distant medical services, the distribution of, and remote access to digital medical images over public networks continues to grow significantly. Such use of medical images raises serious concerns for their continuous security protection, which digital watermarking has shown great potential to address. Methods We present a content-independent embedding scheme for medical image watermarking. We observe that the perceptual content of medical images varies widely with their modalities. Recent medical image watermarking schemes are image-content dependent and thus they may suffer from inconsistent embedding capacity and visual artefacts. To attain the image content-independent embedding property, we generalise RONI (region of non-interest, to the medical professionals) selection process and use it for embedding by utilising RONI’s least significant bit-planes. The proposed scheme thus avoids the need for RONI segmentation that incurs capacity and computational overheads. Results Our experimental results demonstrate that the proposed embedding scheme performs consistently over a dataset of 370 medical images including their 7 different modalities. Experimental results also verify how the state-of-the-art reversible schemes can have an inconsistent performance for different modalities of medical images. Our scheme has MSSIM (Mean Structural SIMilarity) larger than 0.999 with a deterministically adaptable embedding capacity. Conclusions Our proposed image-content independent embedding scheme is modality-wise consistent, and maintains a good image quality of RONI while keeping all other pixels in the image untouched. Thus, with an appropriate watermarking framework (i.e., with the considerations of watermark generation, embedding and detection functions), our proposed scheme can be viable for the multi-modality medical image applications and distant medical services such as teleradiology and eHealth.

The impact of simulated astigmatism on functional measures of visual performance

Uncorrected refractive error, including astigmatism, is a leading cause of reversible visual impairment. While the ability to perform vision-related daily activities is reduced when people are not optimally corrected, only limited research has investigated the impact of uncorrected astigmatism. Given the capacity to perform vision-related daily activities involves integration of a range of visual and cognitive cues, this research examined the impact of simulated astigmatism on visual tasks that also involved cognitive input. The research also examined whether the higher levels of complexity inherent in Chinese characters makes them more susceptible to the effects of astigmatism. The effects of different powers of astigmatism, as well as astigmatism at different axes were investigated in order to determine the minimum level of astigmatism that resulted in a decrement in visual performance.

A low-cost attack on branch-based software watermarking schemes

In 2005, Ginger Myles and Hongxia Jin proposed a software watermarking scheme based on converting jump instructions or unconditional branch statements (UBSs) by calls to a fingerprint branch function (FBF) that computes the correct target address of the UBS as a function of the generated fingerprint and integrity check. If the program is tampered with, the fingerprint and integrity checks change and the target address will not be computed correctly. In this paper, we present an attack based on tracking stack pointer modifications to break the scheme and provide implementation details. The key element of the attack is to remove the fingerprint and integrity check generating code from the program after disassociating the target address from the fingerprint and integrity value. Using the debugging tools that give vast control to the attacker to track stack pointer operations, we perform both subtractive and watermark replacement attacks. The major steps in the attack are automated resulting in a fast and low-cost attack.