Finite state machine based SDL

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Identifying individual differences of fluoxetine response in juvenile rhesus monkeys by metabolite profiling

Fluoxetine is the only psychopharmacological agent approved for depression by the US Food and Drug Administration for children and is commonly used therapeutically in a variety of neurodevelopmental disorders. Therapeutic response shows high individual variability, and severe side effects have been observed. In the current study we set out to identify biomarkers of response to fluoxetine as well as biomarkers that correlate with impulsivity, a measure of reward delay behavior and potential side effect of the drug, in juvenile male rhesus monkeys. The study group was also genotyped for polymorphisms of monoamine oxidase A (MAOA), a gene that has been associated with psychiatric disorders. We used peripheral metabolite profiling of blood and cerebrospinal fluid (CSF) from animals treated daily with fluoxetine or vehicle for one year. Fluoxetine response metabolite profiles and metabolite/reward delay behavior associations were evaluated using multivariate analysis. Our analyses identified a set of plasma and CSF metabolites that distinguish fluoxetine-from vehicle-treated animals and metabolites that correlate with impulsivity. Some metabolites displayed an interaction between fluoxetine and MAOA genotype. The identified metabolite biomarkers belong to pathways that have important functions in central nervous system physiology. Biomarkers of response to fluoxetine in the normally functioning brain of juvenile nonhuman primates may aid in finding predictors of response to treatment in young psychiatric populations and in progress toward the realization of a precision medicine approach in the area of neurodevelopmental disorders

Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function

To determine which of seven library design algorithms best introduces new protein function without destroying it altogether, seven combinatorial libraries of green fluorescent protein variants were designed and synthesized. Each was evaluated by distributions of emission intensity and color compiled from measurements made in vivo. Additional comparisons were made with a library constructed by error-prone PCR. Among the designed libraries, fluorescent function was preserved for the greatest fraction of samples in a library designed by using a structure-based computational method developed and described here. A trend was observed toward greater diversity of color in designed libraries that better preserved fluorescence. Contrary to trends observed among libraries constructed by error-prone PCR, preservation of function was observed to increase with a library's average mutation level among the four libraries designed with structure-based computational methods

Report on the Standardization Project ``Formal Methods in Conformance Testing''

This paper presents the latest developments in the “Formal Methods in Conformance Testing” (FMCT) project of ISO and ITU–T. The project has been initiated to study the role of formal description techniques in the conformance testing process. The goal is to develop a standard that defines the meaning of conformance in the context of formal description techniques. We give an account of the current status of FMCT in the standardization process as well as an overview of the technical status of the proposed standard. Moreover, we indicate some of its strong and weak points, and we give some directions for future work on FMCT

Manifestación atípica de enfermedad de Still

La enfermedad de Still del adulto (ESA) es un proceso inflamatorio sistémico, de etiología desconocida, que se caracteriza por fiebre, artritis y eritema evanescente, además de valores elevados de ferritina sérica. Sin embargo, hasta la fecha, no hay una prueba definitiva de laboratorio o de imagen disponible para su diagnóstico, por lo tanto, la ESA es un diagnóstico de exclusión. Presentamos el caso de una mujer de 44 años con manifestación cutánea atípica de ESA y cuadro clínico de 1 año de evolución caracterizado por fiebre de 40°C, linfadenopatía, hiperferritinemia, y que en la sistemática de estudio presentó positividad para anti-CCP (anticuerpo antipéptido cíclico citrulinado)

Access control and interlock system at the Advanced Photon Source

The Advanced Photon Source (APS) consists of a linac, position accumulator ring (PAR), booster synchrotron, storage ring, and up to 70 experimental beamlines. The Access Control and Interlock System (ACIS) utilizes redundant programmable logic controllers (PLCs) and a third hard-wired chain to protect personnel from prompt radiation generated by the linac, PAR, synchrotron, and storage ring. This paper describes the ACIS`s design philosophy, configuration, hardware, functionality, validation requirements, and operational experience

Engineered split in Pfu DNA polymerase fingers domain improves incorporation of nucleotide γ-phosphate derivative

Using compartmentalized self-replication (CSR), we evolved a version of Pyrococcus furiosus (Pfu) DNA polymerase that tolerates modification of the γ-phosphate of an incoming nucleotide. A Q484R mutation in α-helix P of the fingers domain, coupled with an unintended translational termination-reinitiation (split) near the finger tip, dramatically improve incorporation of a bulky γ-phosphate-O-linker-dabcyl substituent. Whether synthesized by coupled translation from a bicistronic (−1 frameshift) clone, or reconstituted from separately expressed and purified fragments, split Pfu mutant behaves identically to wild-type DNA polymerase with respect to chromatographic behavior, steady-state kinetic parameters (for dCTP), and PCR performance. Although naturally-occurring splits have been identified previously in the finger tip region of T4 gp43 variants, this is the first time a split (in combination with a point mutation) has been shown to broaden substrate utilization. Moreover, this latest example of a split hyperthermophilic archaeal DNA polymerase further illustrates the modular nature of the Family B DNA polymerase structure