Eigenvalues of matrices with tree graphs

AbstractWhen the undirected graph of a real square matrix is a tree of forest, we establish finitely computable tests yielding information about the magnitudes and multiplicities to the eigenvalues of the matrix. Applying these tests to system designs expressed as signed directed graphs can be sufficient to guarantee controllability of the associated linear dynamical systems

Bipartite and tripartite systems and matrices from genetic control research

Discovering the organizational principles of genetic expression has recently become an arena of substantial investigative effort and modeling challenges. Laboratory findings of geneticists can be couched in terms of classes of stoichiometric networks that through stability analysis lead to classes of matrix patterns. In particular, targets, blocks, and decoys are variables in genetic systems with relationships that can be described by bipartite and tripartite graphs. Related dynamical systems will exhibit stability if a mixture of qualitative and quantitative criteria is applied. Analyses of the models suggest limits of total induction rates of blocks and decoys relative to other rates

The stellar association around Gamma Velorum and its relationship with Vela OB2

We present the results of a photometric BVI survey of 0.9 square degrees around the Wolf-Rayet binary gamma^2 Vel and its early-type companion gamma^1 Vel. Several hundred PMS stars are identified and the youth of a subset of these is confirmed by the presence of lithium, H-alpha emission and X-ray activity. We show that the PMS stars are kinematically coherent and spatially concentrated around gamma Vel. The PMS stars have similar proper motions to gamma Vel, to main-sequence stars around gammaVel and to early-type stars of the wider Vela OB2 association of which gamma^2 Vel is the brightest member. The ratio of main-sequence stars to low-mass (0.1-0.6 Msun) PMS stars is consistent with a Kroupa mass function. Main-sequence fitting to stars around gamma Vel gives a distance modulus of 7.76+/-0.07 mag, consistent with a similarly-determined distance for Vela OB2 and with interferometric distances to gamma^2 Vel. High-mass stellar models indicate an age of 3-4 Myr for gamma^2 Vel, but the low-mass PMS stars have ages of ~10 Myr according to low-mass evolutionary models and 5-10 Myr by empirically placing them in an age sequence with other clusters based on colour-magnitude diagrams and lithium depletion. We conclude that the low-mass PMS stars form a genuine association with gamma Vel and that this is a subcluster within the larger Vela OB2 association. We speculate that gamma^2 Vel formed after the low-mass stars, expelling gas, terminating star formation and unbinding the association. The velocity dispersion of the PMS stars is too low for this star forming event to have produced all the stars in Vela OB2. Instead, star formation must have started at several sites within a molecular cloud, either sequentially or, simultaneously after some triggering event [abridged].Comment: Accepted for publication in MNRA

A Flexible and Qualitatively Stable Model for Cell Cycle Dynamics Including DNA Damage Effects

This paper includes a conceptual framework for cell cycle modeling into which the experimenter can map observed data and evaluate mechanisms of cell cycle control. The basic model exhibits qualitative stability, meaning that regardless of magnitudes of system parameters its instances are guaranteed to be stable in the sense that all feasible trajectories converge to a certain trajectory. Qualitative stability can also be described by the signs of real parts of eigenvalues of the system matrix. On the biological side, the resulting model can be tuned to approximate experimental data pertaining to human fibroblast cell lines treated with ionizing radiation, with or without disabled DNA damage checkpoints. Together these properties validate a fundamental, first order systems view of cell dynamics. Classification Codes: 15A6

Additional layers of gene regulatory complexity from recently discovered microRNA mechanisms

In recent years microRNAs have become recognized as pervasive, versatile agents of gene regulation. Some widely embraced rules involving Watson-Crick hybridization of microRNAs with mRNAs have generated great interest as scientists envision potential RNA cargoes for gene therapy and other experimental systems. However, while researchers ardently seek simplifying principles, nature seems very uncooperative. This article reviews some small RNA mechanisms that potentially regulate genes and which are not covered by previous microRNAs characterizations. In addition, we report here results of fluorescence microscopy experiments to directly demonstrate nuclear importation of small RNAs equal in length to typical mature microRNAs, implying that gene regulation at the locus of transcription might be possible

Association of Reduced Long-Lasting Insecticidal Net Efficacy and Pyrethroid Insecticide Resistance With Overexpression of CYP6P4, CYP6P3, and CYP6Z1 in Populations of Anopheles coluzzii From Southeast Côte d'Ivoire.

BACKGROUND: Resistance to major public health insecticides in Côte d'Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions. METHODS: This study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from Southeast Côte d'Ivoire in 2019. RESULTS: Phenotypic resistance was intense: >25% of mosquitoes survived exposure to 10 times the doses of pyrethroids required to kill susceptible populations. Similarly, the 24-hour mortality rate with deltamethrin-only LLINs was very low and not significantly different from that with an untreated net. Sublethal pyrethroid exposure did not induce significant delayed vector mortality effects 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide, or new insecticides clothianidin and chlorfenapyr, were highly toxic to A. coluzzii. Pyrethroid-susceptible A. coluzzii were significantly more likely to be infected with malaria, compared with those that survived insecticidal exposure. Pyrethroid resistance was associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1. CONCLUSIONS: Study findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating piperonyl butoxide, chlorfenapyr, or clothianidin in areas of high resistance intensity in Côte d'Ivoire

Reduced long-lasting insecticidal net efficacy and pyrethroid insecticide resistance are associated with over-expression of <i>CYP6P4, CYP6P3</i> and <i>CYP6Z1</i> in populations of <i>Anopheles coluzzii</i> from South-East Côte d’Ivoire

AbstractBackgroundResistance to major public health insecticides in Côte d’Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions.MethodsThis study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from South-East Côte d’Ivoire in 2019.ResultsPhenotypic resistance was intense: more than 25% of mosquitoes survived exposure to ten times the doses of pyrethroids required to kill susceptible populations. Similarly, 24-hour mortality to deltamethrin-only LLINs was very low and not significantly different to an untreated net. Sub-lethal pyrethroid exposure did not induce significant delayed vector mortality 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide (PBO), or new insecticides, clothianidin and chlorfenapyr, were highly toxic to An. coluzzii. Pyrethroid-susceptible An. coluzzii were significantly more likely to be infected with malaria, compared to those that survived insecticidal exposure. Pyrethroid resistance was associated with significant over-expression of CYP6P4, CPY6Z1 and CYP6P3.ConclusionsStudy findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating PBO, chlorfenapyr or clothianidin in areas of high resistance intensity in Côte d’Ivoire.</jats:sec

microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder

BACKGROUND: microRNAs (miRNAs) are small, noncoding RNA molecules that are now thought to regulate the expression of many mRNAs. They have been implicated in the etiology of a variety of complex diseases, including Tourette's syndrome, Fragile × syndrome, and several types of cancer. RESULTS: We hypothesized that schizophrenia might be associated with altered miRNA profiles. To investigate this possibility we compared the expression of 264 human miRNAs from postmortem prefrontal cortex tissue of individuals with schizophrenia (n = 13) or schizoaffective disorder (n = 2) to tissue of 21 psychiatrically unaffected individuals using a custom miRNA microarray. Allowing a 5% false discovery rate, we found that 16 miRNAs were differentially expressed in prefrontal cortex of patient subjects, with 15 expressed at lower levels (fold change 0.63 to 0.89) and 1 at a higher level (fold change 1.77) than in the psychiatrically unaffected comparison subjects. The expression levels of 12 selected miRNAs were also determined by quantitative RT-PCR in our lab. For the eight miRNAs distinguished by being expressed at lower microarray levels in schizophrenia samples versus comparison samples, seven were also expressed at lower levels with quantitative RT-PCR. CONCLUSION: This study is the first to find altered miRNA profiles in postmortem prefrontal cortex from schizophrenia patients

Expressions 2010

https://openspace.dmacc.edu/expressions/1026/thumbnail.jp

Severity of thought disorder predicts psychosis in persons at clinical high-risk

BACKGROUND: Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction. METHODS: Subjects were from two cohorts of the North American Prodrome Longitudinal Study. All subjects met Criteria of Psychosis-Risk States. In Cohort-1 (n=296) we developed a classifier that included those items of the Scale of Psychosis-Risk Symptoms that best distinguished subjects who converted to psychosis from nonconverters, with performance initially validated by randomization tests in Cohort-1. Cohort-2 (n=592) served as an independent test set. RESULTS: We derived 2-Item and 4-Item subscales. Both included unusual thought content and suspiciousness; the latter added reduced ideational richness and difficulties with focus/concentration. The Concordance Index (C-Index), a measure of discrimination, was similar for each subscale across cohorts (4-Item subscale Cohort-2: 0.71, 95% CI=[0.64, 0.77], Cohort-1: 0.74, 95% CI=[0.69, 0.80]; 2-Item subscale Cohort-2: 0.68, 95% CI=[0.3, 0.76], Cohort-1: 0.72, 95% CI=[0.66-0.79]). The 4-Item performed better than the 2-Item subscale in 742/1000 random selections of 80% subsets of Cohort-2 subjects (p-value=1.3E-55). Subscale calibration between cohorts was proportional (higher scores/lower survival), but absolute conversion risk predicted from Cohort-1 was higher than that observed in Cohort-2, reflecting the cohorts\u27 differences in 2-year conversion rates (Cohort-2: 0.16, 95% CI=[0.13, 0.19]; Cohort-1: 0.30, 95% CI=[0.24, 0.36]). CONCLUSION: Severity of unusual thought content, suspiciousness, reduced ideational richness, and difficulty with focus/concentration informed psychosis risk prediction. Scales based on these symptoms may have utility in research and, assuming further validation, eventual clinical applications