SOS rule formats for convex and abstract probabilistic bisimulations

Probabilistic transition system specifications (PTSSs) in the $nt \mu f\theta / nt\mu x\theta$ format provide structural operational semantics for Segala-type systems that exhibit both probabilistic and nondeterministic behavior and guarantee that bisimilarity is a congruence for all operator defined in such format. Starting from the $nt \mu f\theta / nt\mu x\theta$ format, we obtain restricted formats that guarantee that three coarser bisimulation equivalences are congruences. We focus on (i) Segala's variant of bisimulation that considers combined transitions, which we call here "convex bisimulation"; (ii) the bisimulation equivalence resulting from considering Park & Milner's bisimulation on the usual stripped probabilistic transition system (translated into a labelled transition system), which we call here "probability obliterated bisimulation"; and (iii) a "probability abstracted bisimulation", which, like bisimulation, preserves the structure of the distributions but instead, it ignores the probability values. In addition, we compare these bisimulation equivalences and provide a logic characterization for each of them.Comment: In Proceedings EXPRESS/SOS 2015, arXiv:1508.0634

Multimodal segmentation of lifelog data

A personal lifelog of visual and audio information can be very helpful as a human memory augmentation tool. The SenseCam, a passive wearable camera, used in conjunction with an iRiver MP3 audio recorder, will capture over 20,000 images and 100 hours of audio per week. If used constantly, very soon this would build up to a substantial collection of personal data. To gain real value from this collection it is important to automatically segment the data into meaningful units or activities. This paper investigates the optimal combination of data sources to segment personal data into such activities. 5 data sources were logged and processed to segment a collection of personal data, namely: image processing on captured SenseCam images; audio processing on captured iRiver audio data; and processing of the temperature, white light level, and accelerometer sensors onboard the SenseCam device. The results indicate that a combination of the image, light and accelerometer sensor data segments our collection of personal data better than a combination of all 5 data sources. The accelerometer sensor is good for detecting when the user moves to a new location, while the image and light sensors are good for detecting changes in wearer activity within the same location, as well as detecting when the wearer socially interacts with others

Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials

Allosteric Inhibition of Factor XIIIa. Non-Saccharide Glycosaminoglycan Mimetics, but Not Glycosaminoglycans, Exhibit Promising Inhibition Profile

Factor XIIIa (FXIIIa) is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors. Yet, allosteric inhibition of FXIIIa is a paradigm that may offer a key advantage of controlled inhibition over orthosteric inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We reasoned that targeting a collection of basic amino acid residues distant from FXIIIa’s active site by using sulfated glycosaminoglycans (GAGs) or non-saccharide GAG mimetics (NSGMs) would lead to the discovery of the first allosteric FXIIIa inhibitors. We tested a library of 22 variably sulfated GAGs and NSGMs against human FXIIIa to discover promising hits. Interestingly, although some GAGs bound to FXIIIa better than NSGMs, no GAG displayed any inhibition. An undecasulfated quercetin analog was found to inhibit FXIIIa with reasonable potency (efficacy of 98%). Michaelis-Menten kinetic studies revealed an allosteric mechanism of inhibition. Fluorescence studies confirmed close correspondence between binding affinity and inhibition potency, as expected for an allosteric process. The inhibitor was reversible and at least 9-fold- and 26-fold selective over two GAG-binding proteins factor Xa (efficacy of 71%) and thrombin, respectively, and at least 27-fold selective over a cysteine protease papain. The inhibitor also inhibited the FXIIIa-mediated polymerization of fibrin in vitro. Overall, our work presents the proof-of-principle that FXIIIa can be allosterically modulated by sulfated non-saccharide agents much smaller than GAGs, which should enable the design of selective and safe anticoagulants

The equilibrium model for the effect of temperature on enzymes: Insights and implications

A new, experimentally-validated “Equilibrium Model” describes the effect of temperature on enzymes, and provides a new mechanism for the reversible loss of enzyme activity with temperature. It incorporates two new, fundamental parameters that allow a complete description of the effect of temperature on enzyme activity: ΔHeq and Teq. ΔHeq emerges as an intrinsic and quantitative measure of enzyme eurythermal adaptation, while Teq, the equilibrium temperature, has fundamental and technological significance for our understanding of the effect of temperature on enzymatic reactions. For biotechnological purposes, these parameters need to be considered when enzymes are applied or engineered for activity at high temperatures

Computational Design and Characterization of a Temperature-Sensitive Plasmid Replicon for Gram Positive Thermophiles

Temperature-sensitive (Ts) plasmids are useful tools for genetic engineering, but there are currently none compatible with the gram positive, thermophilic, obligate anaerobe, Clostridium thermocellum. Traditional mutagenesis techniques yield Ts mutants at a low frequency, and therefore requires the development of high-throughput screening protocols, which are also not available for this organism. Recently there has been progress in the development of computer algorithms which can predict Ts mutations. Most plasmids currently used for genetic modification of C. thermocellum are based on the replicon of plasmid pNW33N, which replicates using the RepB replication protein. To address this problem, we set out to create a Ts plasmid by mutating the gene coding for the RepB replication protein using an algorithm designed by Varadarajan et al. (1996) for predicting Ts mutants based on the amino-acid sequence of the protein

Examining Strain in a School Context

General strain theory has accumulated a considerable amount of empirical support. Many of these assessments have tested the direct relationship that strain has on crime and delinquency. The research presented here examines the relationship between schools and delinquency within a general strain theory perspective. More specifically, this research examines how schools can not only act as a source of an individual\u27s strain and subsequent delinquency but also be a source for mediating or coping with strain and minimizing delinquency. To test the relationship between schools and delinquency, data from the National Educational Longitudinal Survey (NELS:88) are analyzed in a model of general strain that specifies sources of school-based strain and sources of school-based mechanisms for controlling strain