Exploring Fitness and Edit Distance of Mutated Python Programs

Genetic Improvement (GI) is the process of using computational search techniques to improve existing software e.g. in terms of execution time, power consumption or correctness. As in most heuristic search algorithms, the search is guided by fitness with GI searching the space of program variants of the original software. The relationship between the program space and fitness is seldom simple and often quite difficult to analyse. This paper makes a preliminary analysis of GI’s fitness distance measure on program repair with three small Python programs. Each program undergoes incremental mutations while the change in fitness as measured by proportion of tests passed is monitored. We conclude that the fitnesses of these programs often does not change with single mutations and we also confirm the inherent discreteness of bug fixing fitness functions. Although our findings cannot be assumed to be general for other software they provide us with interesting directions for further investigation

Radiation dose reduction at a price: the effectiveness of a male gonadal shield during helical CT scans

BACKGROUND: It is estimated that 60 million computed tomography (CT) scans were performed during 2006, with approximately 11% of those performed on children age 0–15 years. Various types of gonadal shielding have been evaluated for reducing exposure to the gonads. The purpose of this study was to quantify the radiation dose reduction to the gonads and its effect on image quality when a wrap-around male pediatric gonad shield was used during CT scanning. This information is obtained to assist the attending radiologist in the decision to utilize such male gonadal shields in pediatric imaging practice. METHODS: The dose reduction to the gonads was measured for both direct radiation and for indirect scattered radiation from the abdomen. A 6 cm(3 )ion chamber (Model 10X5-6, Radcal Corporation, Monrovia, CA) was placed on a Humanoid real bone pelvic phantom at a position of the male gonads. When exposure measurements with shielding were made, a 1 mm lead wrap-around gonadal shield was placed around the ion chamber sensitive volume. RESULTS: The use of the shields reduced scatter dose to the gonads by a factor of about 2 with no appreciable loss of image quality. The shields reduced the direct beam dose by a factor of about 35 at the expense of extremely poor CT image quality due to severe streak artifacts. CONCLUSION: Images in the direct exposure case are not useful due to these severe artifacts and the difficulties in positioning these shields on patients in the scatter exposure case may not be warranted by the small absolute reduction in scatter dose unless it is expected that the patient will be subjected to numerous future CT scans

The EHEC Type III Effector NleL Is an E3 Ubiquitin Ligase That Modulates Pedestal Formation

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote the formation of actin-rich pedestals via translocated type III effectors. Two EHEC type III secreted effectors, Tir and EspFu/TccP, are key players for pedestal formation. We discovered that an EHEC effector protein called Non-LEE-encoded Ligase (NleL) is an E3 ubiquitin ligase. In vitro, we showed that the NleL C753 residue is critical for its E3 ligase activity. Functionally, we demonstrated that NleL E3 ubiquitin ligase activity is involved in modulating Tir-mediated pedestal formation. Surprisingly, EHEC mutant strain deficient in the E3 ligase activity induced more pedestals than the wild-type strain. The canonical EPEC strain E2348/69 normally lacks the nleL gene, and the ectopic expression of the wild-type EHEC nleL, but not the catalytically-deficient nleL(C753A) mutant, in this strain resulted in fewer actin-rich pedestals. Furthermore, we showed that the C. rodentium NleL homolog is a E3 ubiquitin ligase and is required for efficient infection of murine colonic epithelial cells in vivo. In summary, our study demonstrated that EHEC utilizes NleL E3 ubiquitin ligase activity to modulate Tir-mediated pedestal formation.National Institutes of Health (U.S.) (grant AI078092)National Institutes of Health (U.S.) (grant AI068655

Older adults experiences of learning to use tablet computers: a mixed methods study

YesBackground: We wanted to understand older adults’ experiences of learning how to use a tablet computer in the context of an intervention trial, including what they found helpful or unhelpful about the tablet training, to guide future intervention studies. Methods: Mixed methods study using questionnaire and focus group approaches. Forty-three participants aged between 65 and 76 years old from the “Tablet for Healthy Ageing” study (comprising 22 in the intervention group and 21 controls) completed a post-intervention tablet experience questionnaire. Those who completed the tablet training intervention were invited to share their experiences of engaging with new technology in post-intervention focus groups. We conducted three separate focus groups with 14 healthy older adults (10 females). Results: Questionnaire data suggested that the overall experience of the 22 participants who participated in the tablet training intervention was positive. The majority of participants said that it was likely or very likely they would use a tablet in the future. The focus group themes that emerged were related to the perception of tablet training, the experience of using tablets, and suggestions for future studies. Participants mentioned that their confidence was increased, that they enjoyed being part of a social group and downloading applications, but they also felt challenged at times. Advantages of using tablets included the ability to keep in touch with family and friends, a motivation to contribute to the community, and the potential for tablets to improve mental abilities and overall health and wellbeing. Participants made suggestions that would enable tablet usage, including improvement of features, and suggestions that would improve future tablet training studies, including smaller classes. Conclusion: Our findings have implications for the development of interventions utilizing new technologies that might promote the health and wellbeing of older adults.This work was supported by The Dunhill Medical Trust (R359/0514)

Conditionally Replicating Adenovirus Expressing TIMP2 Increases Survival in a Mouse Model of Disseminated Ovarian Cancer

Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds) are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2) containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs) in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer

Overcoming leakage in scalable quantum error correction

Leakage of quantum information out of computational states into higher energy states represents a major challenge in the pursuit of quantum error correction (QEC). In a QEC circuit, leakage builds over time and spreads through multi-qubit interactions. This leads to correlated errors that degrade the exponential suppression of logical error with scale, challenging the feasibility of QEC as a path towards fault-tolerant quantum computation. Here, we demonstrate the execution of a distance-3 surface code and distance-21 bit-flip code on a Sycamore quantum processor where leakage is removed from all qubits in each cycle. This shortens the lifetime of leakage and curtails its ability to spread and induce correlated errors. We report a ten-fold reduction in steady-state leakage population on the data qubits encoding the logical state and an average leakage population of less than $1 \times 10^{-3}$ throughout the entire device. The leakage removal process itself efficiently returns leakage population back to the computational basis, and adding it to a code circuit prevents leakage from inducing correlated error across cycles, restoring a fundamental assumption of QEC. With this demonstration that leakage can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure