Prototype of Fault Adaptive Embedded Software for Large-Scale Real-Time Systems

This paper describes a comprehensive prototype of large-scale fault adaptive embedded software developed for the proposed Fermilab BTeV high energy physics experiment. Lightweight self-optimizing agents embedded within Level 1 of the prototype are responsible for proactive and reactive monitoring and mitigation based on specified layers of competence. The agents are self-protecting, detecting cascading failures using a distributed approach. Adaptive, reconfigurable, and mobile objects for reliablility are designed to be self-configuring to adapt automatically to dynamically changing environments. These objects provide a self-healing layer with the ability to discover, diagnose, and react to discontinuities in real-time processing. A generic modeling environment was developed to facilitate design and implementation of hardware resource specifications, application data flow, and failure mitigation strategies. Level 1 of the planned BTeV trigger system alone will consist of 2500 DSPs, so the number of components and intractable fault scenarios involved make it impossible to design an `expert system' that applies traditional centralized mitigative strategies based on rules capturing every possible system state. Instead, a distributed reactive approach is implemented using the tools and methodologies developed by the Real-Time Embedded Systems group.Comment: 2nd Workshop on Engineering of Autonomic Systems (EASe), in the 12th Annual IEEE International Conference and Workshop on the Engineering of Computer Based Systems (ECBS), Washington, DC, April, 200

Fire and Climate Change in the North American Great Lakes Pine Transition Forest

This chapter explores potential changes in fire regimes and biodiversity given projected changes in climate in the Great Lakes Pine Transition Forest (GLPF), a portion of the southern boreal forest. We have studied how forest structure, composition, and biodiversity changed over nearly 500 years by comparing communities on comparable edaphic locations of various ages since stand-replacing disturbance. Our interpretation of probable future changes is based on how these ecosystems have reassembled after wildfire, blowdown, and insect disturbances in the past and projections of climate change in the next 75 years. Rapid climate change is now introducing different conditions from those to which this ecosystem was historically adapted, and therefore, projections of future change are more subjective

Prototype of Fault Adaptive Embedded Software for Large-Scale Real-Time Systems

This paper describes a comprehensive prototype of large-scale fault adaptive embedded software developed for the proposed Fermilab BTeV high energy physics experiment. Lightweight self-optimizing agents embedded within Level 1 of the prototype are responsible for proactive and reactive monitoring and mitigation based on specified layers of competence. The agents are self-protecting, detecting cascading failures using a distributed approach. Adaptive, reconfigurable, and mobile objects for reliability are designed to be self-configuring to adapt automatically to dynamically changing environments. These objects provide a self-healing layer with the ability to discover, diagnose, and react to discontinuities in real-time processing. A generic modeling environment was developed to facilitate design and implementation of hardware resource specifications, application data flow, and failure mitigation strategies. Level 1 of the planned BTeV trigger system alone will consist of 2500 DSPs, so the number of components and intractable fault scenarios involved make it impossible to design an “expert system” that applies traditional centralized mitigative strategies based on rules capturing every possible system state. Instead, a distributed reactive approach is implemented using the tools and methodologies developed by the RealTime Embedded Systems group

Oral Cannabidiol Does Not Produce a Signal for Abuse Liability in Frequent Marijuana Smokers

Background—Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability. Methods—Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800 mg) alone and in combination with smoked marijuana (0.01%, 5.3-5.8% THC). Participants received one dose combination across 8 once-weekly outpatient sessions (7.5 hrs). The primary findings on the drug interaction effects were previously reported (Haney et al., 2016). The present study is a secondary analysis of the data to examine the abuse liability profile of oral cannabidiol (200, 400, 800 mg) in comparison to oral placebo and active smoked marijuana (5.3-5.8% THC). Results—Active marijuana reliably produced abuse-related subjective effects (e.g., high) (p \u3c .05). However, CBD was placebo-like on all measures collected (p \u3e .05). Conclusions—Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA

Monocoque structure for the SKITTER three-legged walker

The SKITTER 2 design is a monocoque version of the proposed lunar three-legged walker. By the definition of monocoque, the body and legs are a shell with no internal ribbing or supports added for absorbing stresses. The purpose of the monocoque is to encase the elements used for power transmission, power supply, and control of the motion. The material for the structure is a vinyl ester resin, Derakane 8084. This material is easily formable and locally obtainable. The body consists of a hexagonally shaped cylinder with truncated hexagonal pyramids on the top and botton. The legs are eight inch diameter cylinders. The legs are comprised of a tibia section and a femur section. The SKITTER 2 is powered by six actuators which provide linear forces that are transformed into rotary torques by a series of chains and sprockets. The joints connect the femur to the body and the tibia to the femur. Surrounding the joints are flexible rubber hoses that fully encase the chains and sprockets. The SKITTER 2 is capable of walking upside down, righting itself after being overturned, and has the ability to perform in many environments. Applications for this walker include lunar transport or drilling, undersea exploration, and operation in severe surroundings such as arctic temperatures or high radiation

Impact of wound edge protection devices on surgical site infection after laparotomy: multicentre randomised controlled trial (ROSSINI Trial).

OBJECTIVE: To determine the clinical effectiveness of wound edge protection devices in reducing surgical site infection after abdominal surgery. DESIGN: Multicentre observer blinded randomised controlled trial. PARTICIPANTS: Patients undergoing laparotomy at 21 UK hospitals. INTERVENTIONS: Standard care or the use of a wound edge protection device during surgery. MAIN OUTCOME MEASURES: Surgical site infection within 30 days of surgery, assessed by blinded clinicians at seven and 30 days and by patient's self report for the intervening period. Secondary outcomes included quality of life, duration of stay in hospital, and the effect of characteristics of the patient and operation on the efficacy of the device. RESULTS: 760 patients were enrolled with 382 patients assigned to the device group and 378 to the control group. Six patients in the device group and five in the control group did not undergo laparotomy. Fourteen patients, seven in each group, were lost to follow-up. A total of 184 patients experienced surgical site infection within 30 days of surgery, 91/369 (24.7%) in the device group and 93/366 (25.4%) in the control group (odds ratio 0.97, 95% confidence interval 0.69 to 1.36; P=0.85). This lack of benefit was consistent across wound assessments performed by clinicians and those reported by patients and across all secondary outcomes. In the secondary analyses no subgroup could be identified in which there was evidence of clinical benefit associated with use of the device. CONCLUSIONS: Wound edge protection devices do not reduce the rate of surgical site infection in patients undergoing laparotomy, and therefore their routine use for this role cannot be recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 40402832

Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1-3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain

Image-Based Assessment of Growth and Signaling Changes in Cancer Cells Mediated by Direct Cell-Cell Contact

Many important biological processes are controlled through cell-cell interactions, including the colonization of metastatic tumor cells and the control of differentiation of stem cells within their niche. Despite the crucial importance of the cellular environment in regulating cellular signaling, in vitro methods for the study of such interactions are difficult and/or indirect.We report on the development of an image-based method for distinguishing two cell types grown in coculture. Furthermore, cells of one type that are in direct contact with cells of a second type (adjacent cells) can be analyzed separately from cells that are not within a single well. Changes are evaluated using population statistics, which are useful in detecting subtle changes across two populations. We have used this system to characterize changes in the LNCaP prostate carcinoma cell line when grown in contact with human vascular endothelial cells (HUVECs). We find that the expression and phosphorylation of WWOX is reduced in LNCaP cells when grown in direct contact with HUVECs. Reduced WWOX signaling has been associated with reduced activation or expression of JNK and p73. We find that p73 levels are also reduced in LNCaP cells grown in contact with HUVECs, but we did not observe such a change in JNK levels.We find that the method described is statistically robust and can be adapted to a wide variety of studies where cell function or signaling are affected by heterotypic cell-cell contact. Ironically, a potential challenge to the method is its high level of sensitivity is capable of classifying events as statistically significant (due to the high number cells evaluated individually), when the biological effect may be less clear. The methodology would be best used in conjunction with additional methods to evaluate the biological role of potentially subtle differences between populations. However, many important events, such as the establishment of a metastatic tumor, occur through rare but important changes, and methods such as we describe here can be used to identify and characterize the contribution of the environment to these changes

siRNA Off-Target Effects Can Be Reduced at Concentrations That Match Their Individual Potency

Small interfering RNAs (siRNAs) are routinely used to reduce mRNA levels for a specific gene with the goal of studying its function. Several studies have demonstrated that siRNAs are not always specific and can have many off-target effects. The 3′ UTRs of off-target mRNAs are often enriched in sequences that are complementary to the seed-region of the siRNA. We demonstrate that siRNA off-targets can be significantly reduced when cells are treated with a dose of siRNA that is relatively low (e.g. 1 nM), but sufficient to effectively silence the intended target. The reduction in off-targets was demonstrated for both modified and unmodified siRNAs that targeted either STAT3 or hexokinase II. Low concentrations reduced silencing of transcripts with complementarity to the seed region of the siRNA. Similarly, off-targets that were not complementary to the siRNA were reduced at lower doses, including up-regulated genes that are involved in immune response. Importantly, the unintended induction of caspase activity following treatment with a siRNA that targeted hexokinase II was also shown to be a concentration-dependent off-target effect. We conclude that off-targets and their related phenotypic effects can be reduced for certain siRNA that potently silence their intended target at low concentrations