Optimal sampling for positive only electronic health record data.

Identifying a patient's disease/health status from electronic medical records is a frequently encountered task in electronic health records (EHR) related research, and estimation of a classification model often requires a benchmark training data with patients' known phenotype statuses. However, assessing a patient's phenotype is costly and labor intensive, hence a proper selection of EHR records as a training set is desired. We propose a procedure to tailor the best training subsample with limited sample size for a classification model, minimizing its mean-squared phenotyping/classification error (MSE). Our approach incorporates "positive only" information, an approximation of the true disease status without false alarm, when it is available. In addition, our sampling procedure is applicable for training a chosen classification model which can be misspecified. We provide theoretical justification on its optimality in terms of MSE. The performance gain from our method is illustrated through simulation and a real-data example, and is found often satisfactory under criteria beyond MSE.

Plant water transport and aquaporins in oxygen-deprived environments.

Oxygen deprivation commonly affects plants exposed to flooding and soil compaction. The resulting root hypoxia has an immediate effect on plant water relations and upsets water balance. Hypoxia inhibits root water transport and triggers stomatal closure. The processes contributing to the inhibition of root hydraulic conductivity and conductance (hydraulic conductivity of the whole root system) are complex and involve changes in root morphology and the functions of aquaporins. Aquaporins (AQPs) comprise a group of membrane intrinsic proteins that are responsible for the transport of water, as well as some small neutral solutes and ions. They respond to a wide range of environmental stresses including O2 deprivation, but the underlying functional mechanisms are still elusive. The aquaporin-mediated water transport is affected by the acidification of the cytoplasm and depletion of ATP that is required for aquaporin phosphorylation and membrane functions. Cytoplasmic pH, phosphorylation, and intracellular Ca2+ concentration directly control AQP gating, all of which are related to O2 deprivation. This review addresses the structural determinants that are essential for pore conformational changes in AQPs, to highlight the underlying mechanisms triggered by O2 deprivation stress. Gene expression of AQPs is modified in hypoxic plants, which may constitute an important, yet little explored, mechanism of hypoxia tolerance. In addition to water transport, AQPs may contribute to hypoxia tolerance by transporting O2, H2O2, and lactic acid. Responses of plants to O2 deprivation, and especially those that contribute to maintenance of water transport, are highly complex and entail the signals originating in roots and shoots that lead to and follow the stomatal closure. These complex responses may involve ethylene, abscisic acid, and possibly other hormonal factors and signaling molecules in ways that remain to be elucidated.

Regulation of aquaporin-mediated water transport in Arabidopsis roots exposed to NaCl.

The effects of Ca(NO3)2, KF and okadaic acid (OA) on cell hydraulic responses to NaCl were examined in roots of Arabidopsis thaliana wild-type plants and compared with plants overexpressing plasma membrane intrinsic protein PIP2;5. Root treatment with 10 mM NaCl rapidly and sharply reduced cell hydraulic conductivity (L(p)) in the wild-type Arabidopsis plants, but had no effect on L(p) in Arabidopsis plants overexpressing PIP2;5, suggesting that changes in protein and aquaporin gene expression were among the initial targets responsible for the inhibition of L(p) by NaCl. The down-regulation of PIP transcripts after 1 h exposure to 10 mM NaCl was likely a significant factor in the reduction of L(p). The effect of NaCl on L(p) in the wild-type plants was abolished when the NaCl-treated roots were subsequently exposed to 5 mM KF, 5 mM Ca(NO3)2 and 5 µM OA. The reduction of L(p) by 5 mM KF could not be prevented by treatment with 5 mM Ca(NO3)2 in both wild-type and PIP2;5-overexpressing plants. However, 5 µM OA, which was added following NaCl or KF treatment, completely reversed L(p) within several minutes. The results provide evidence for high sensitivity of aquaporin-mediated water transport to relatively low NaCl concentrations and point to the phosphorylation and/or dephosphorylation processes as those that are likely responsible for the protection of L(p) by fluoride and calcium treatments against the effects of NaCl.

Hydraulic adjustments in aspen (Populus tremuloides) seedlings following defoliation involve root and leaf aquaporins.

MAIN CONCLUSION: Changes in root and leaf hydraulic properties and stimulation of transpiration rates that were initially triggered by defoliation were accompanied by corresponding changes in leaf and root aquaporin expression. Aspen (Populus tremuloides) seedlings were subjected to defoliation treatments by removing 50, 75 % or all of the leaves. Root hydraulic conductivity (Lpr) was sharply reduced in plants defoliated for 1 day and 1 week. The decrease in L pr could not be prevented by stem girdling and it was accompanied in one-day-defoliated plants by a large decrease in the root expression of PIP1,2 aquaporin and an over twofold decrease in hydraulic conductivity of root cortical cells (L pc). Contrary to L pr and L pc, 50 and 75 % defoliation treatments profoundly increased leaf lamina conductance (K lam) after 1 day and this increase was similar in magnitude for both defoliation treatments. Transpiration rates (E) rapidly declined after the removal of 75 % of leaves. However, E increased by over twofold in defoliated plants after 1 day and the increases in E and K lam were accompanied by five- and tenfold increases in the leaf expression of PIP2;4 in 50 and 75 % defoliation treatments, respectively. Defoliation treatments also stimulated net photosynthesis after 1 day and 3 weeks, although the increase was not as high as E. Leaf water potentials remained relatively stable following defoliation with the exception of a small decrease 1 day after defoliation which suggests that root water transport did not initially keep pace with the increased transpirational water loss. The results demonstrate the importance of root and leaf hydraulic properties in plant responses to defoliation and point to the involvement of PIP aquaporins in the early events following the loss of leaves.

Relative quantification in imaging of a peptide on a mouse brain tissue by matrix-assisted laser desorption ionization.

It is well-known that the number of analyte ions generated by matrix-assisted laser desorption ionization (MALDI) is not directly proportional to the analyte concentration at the irradiated spot. This is an obstacle to acquiring quantitatively meaningful maps for materials in a tissue by MALDI imaging. The problem worsens as the matrix suppression due to contaminants in the sample increases. In this work, we use a peptide as an example and show that we can overcome this problem by utilizing three guidelines derived from our recent studies on the generation of reproducible MALDI spectra. First is to acquire MALDI spectra under a temperature-controlled condition. Second is to keep the matrix suppression below an experimentally determined limit, and the third is to construct the image map using the peptide-to-matrix ion abundance ratio rather than the peptide ion abundance. The strategy works well for contaminated tissue samples and generates quantitatively meaningful maps. Also, it is demonstrated that a preposterous map can be generated when the peptide ion abundance is used in the construction of the map.