Viral quantitative capillary electrophoresis for counting intact viruses

The quantification of a virus plays an important role in vaccine development, clinical diagnostics, and environmental contamination assays. In all these cases, it is essential to calculate the concentration or number of intact virus particles (ivp) and estimate the degree of degradation and contamination of virus samples. In this work, we propose a cost-efficient, robust method for the quantification and characterization of intact viruses based on capillary zone electrophoresis. This separation method is demonstrated on vaccinia virus (VV) with oncolytic properties. After virus sample preparation, the solution contains intact VV as well as broken viruses and residual DNA from the host cell used for preparation. Regulatory requirements limit the amount of the host cell DNA that can be present in vaccines or human therapeutics. We apply capillary electrophoresis to separate intact virus particles and the residual DNA and to measure the level of virus contamination with DNA impurities. Intercalating YOYO-1 dye is used to detect the encapsulated and free DNA by laser-induced fluorescence. After soft lysis of VV with proteinase K, all encapsulated DNA is dissolved to the free DNA. The change in peak areas and a DNA calibration curve help determine the initial concentration of intact viruses. This viral quantitative capillary electrophoresis (Viral qCE) is able to quantify the oncolytic vaccinia virus in the range of 10(6) to 10(12) ivp/mL.     

Dendrimer-encapsulated metal nanoparticles: synthesis, characterization, and applications to catalysis

This Account reports the synthesis and characterization of dendrimer-encapsulated metal nanoparticles and their applications to catalysis. These materials are prepared by sequestering metal ions within dendrimers followed by chemical reduction to yield the corresponding zerovalent metal nanoparticle. The size of such particles depends on the number of metal ions initially loaded into the dendrimer. Intradendrimer hydrogenation and carbon-carbon coupling reactions in water, organic solvents, biphasic fluorous/organic solvents, and supercritical CO2 are also described.     

Neuronal regulation: A mechanism for synaptic pruning during brain maturation

Human and animal studies show that mammalian brains undergo massive synaptic pruning during childhood, losing about half of the synapses by puberty. We have previously shown that maintaining the network performance while synapses are deleted requires that synapses be properly modified and pruned, with the weaker synapses removed. We now show that neuronal regulation, a mechanism recently observed to maintain the average neuronal input field of a postsynaptic neuron, results in a weight-dependent synaptic modification. Under the correct range of the degradation dimension and synaptic upper bound, neuronal regulation removes the weaker synapses and judiciously modifies the remaining synapses. By deriving optimal synaptic modification functions in an excitatory-inhibitory network, we prove that neuronal regulation implements near-optimal synaptic modification and maintains the performance of a network undergoing massive synaptic pruning. These findings support the possibility that neural regulation complements the action of Hebbian synaptic changes in the self-organization of the developing brain.     

Formal reasoning for analyzing goal models that evolve over time

Requirements Engineering - In early-phase requirements engineering, modeling stakeholder goals and intentions helps stakeholders understand the problem context and evaluate tradeoffs, by exploring...     

Temporal logic query checking: a tool for model exploration

Temporal logic query checking was first introduced by W. Chan in order to speed up design understanding by discovering properties not known a priori. A query is a temporal logic formula containing a special symbol ?/sub 1/, known as a placeholder. Given a Kripke structure and a propositional formula /spl phi/, we say that /spl phi/ satisfies the query if replacing the placeholder by /spl phi/ results in a temporal logic formula satisfied by the Kripke structure. A solution to a temporal logic query on a Kripke structure is the set of all propositional formulas that satisfy the query. Query checking helps discover temporal properties of a system and, as such, is a useful tool for model exploration. In this paper, we show that query checking is applicable to a variety of model exploration tasks, ranging from invariant computation to test case generation. We illustrate these using a Cruise Control System. Additionally, we show that query checking is an instance of a multi-valued model checking of Chechik et al. This approach enables us to build an implementation of a temporal logic query checker, TLQSolver, on top of our existing multi-valued model checker /sub /spl chi//Chek. It also allows us to decide a large class of queries and introduce witnesses for temporal logic queries-an essential notion for effective model exploration.     

Selected Extended Papers of VSTTE 2016

This special issue collects current efforts to advance the state of the art in the science and technology of software verification, through the interaction of theory development, tool evolution, and experimental validation.     

Data structures for symbolic multi-valued model-checking

Multi-valued logics provide an interesting alternative to classical boolean logic for modeling and reasoning about systems. Such logics can be used for reasoning about partially-specified systems, effectively encode vacuity detection and query-checking problems, help in detecting inconsistencies, and many others.In our earlier work, we identified a useful family of multi-valued logics: those specified over finite distributive lattices where negation preserves involution, i.e., for every element a of the logic. Such structures are called quasi-boolean algebras, and model-checking over these not only extends the domain of applicability of automated reasoning to new problems, but can also speed up solutions to some classical verification problems.Symbolic model-checking over quasi-boolean algebras can be cast in terms of operations over multi-valued sets: sets whose membership functions are multi-valued. In this paper, we propose and empirically evaluate several choices for implementing multi-valued sets with decision diagrams. In particular, we describe two major approaches: (1) representing the multi-valued membership function canonically, using MDDs or ADDs; (2) representing multi-valued sets as a collection of classical sets, using a vector of either MBTDDs or BDDs. The naive implementation of (2) includes having a classical set for each value of the algebra. We exploit a result of lattice theory to reduce the number of such sets that need to be represented.The major contribution of this paper is the evaluation of the different implementations of multi-valued sets, done via a series of experiments and using several case studies.