Probes that allow accurate delineation of chromosome-specific DNA sequences in interphase or metaphase cell nuclei have become important clinical tools that deliver life-saving information about the gender or chromosomal make-up of a product of conception or the probability of an embryo to implant, as well as the definition of tumor-specific genetic signatures. Often such highly specific DNA probes are proprietary in nature and have been the result of extensive probe selection and optimization procedures. We describe a novel approach that eliminates costly and time consuming probe selection and testing by applying data mining and common bioinformatics tools. Similar to a rational drug design process in which drug-protein interactions are modeled in the computer, the rational probe design described here uses a set of criteria and publicly available bioinformatics software to select the desired probe molecules from libraries comprised of hundreds of thousands of probe molecules. Examples describe the selection of DNA probes for the human X and Y chromosomes, both with unprecedented performance, but in a similar fashion, this approach can be applied to other chromosomes or species.

In the usual treatment of electronic structure, all matter has cusps in the electronic density at nuclei. Cusps can produce nonanalytic behavior in time, even in response to perturbations that are time analytic. We analyze these nonanalyticities in a simple case from many perspectives. We describe a method, the s expansion, that can be used in several such cases and illustrate it with a variety of examples. These include both the sudden appearance of electric fields and disappearance of nuclei in both one and three dimensions. When successful, the s expansion yields the dominant short-time behavior, no matter how strong the external electric field, but agrees with linear-response theory in the weak limit. We discuss the relevance of these results to time-dependent density functional theory. © 2013 American Physical Society.

Kernel-based nonparametric hazard rate estimation is considered with a special class of infinite-order kernels that achieves favorable bias and mean square error properties. A fully automatic and adaptive implementation of a density and hazard rate estimator is proposed for randomly right censored data. Careful selection of the bandwidth in the proposed estimators yields estimates that are more efficient in terms of overall mean squared error performance, and in some cases achieves a nearly parametric convergence rate. Additionally, rapidly converging bandwidth estimates are presented for use in second-order kernels to supplement such kernel-based methods in hazard rate estimation. Simulations illustrate the improved accuracy of the proposed estimator against other nonparametric estimators of the density and hazard function. A real data application is also presented on survival data from 13,166 breast carcinoma patients.

A new method for extracting ensemble Kohn-Sham potentials from accurate excited state densities is applied to a variety of two-electron systems, exploring the behavior of exact ensemble density functional theory. The issue of separating the Hartree energy and the choice of degenerate eigenstates is explored. A new approximation, spin eigenstate Hartree-exchange, is derived. Exact conditions that are proven include the signs of the correlation energy components and the asymptotic behavior of the potential for small weights of the excited states. Many energy components are given as a function of the weights for two electrons in a one-dimensional flat box, in a box with a large barrier to create charge transfer excitations, in a three-dimensional harmonic well (Hooke's atom), and for the He atom singlet-triplet ensemble, singlet-triplet-singlet ensemble, and triplet bi-ensemble.

Chromosome enumeration in interphase and metaphase cells using fluorescence in situ hybridization (FISH) is an established procedure for the rapid and accurate cytogenetic analysis of cell nuclei and polar bodies, the unambiguous gender determination, as well as the definition of tumor-specific signatures. Present bottlenecks in the procedure are a limited number of commercial, non-isotopically labeled probes that can be combined in multiplex FISH assays and the relatively high price and effort to develop additional probes. We describe a streamlined approach for rapid probe definition, synthesis and validation, which is based on the analysis of publicly available DNA sequence information, also known as “database mining”. Examples of probe preparation for the human gonosomes and chromosome 16 as a selected autosome outline the probe selection strategy, define a timeline for expedited probe production and compare this novel selection strategy to more conventional probe cloning protocols.

Background

There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs) contribute to neovascularization and play an important role in the development of COPD. The gene for p16^Ink4a is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16^Ink4a in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE), and further to search for a potential candidate agent protecting against emphysema induced by CSE.

Materials and methods

An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR) was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16^Ink4a protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively.

Results

CSE induced emphysema with increased p16^Ink4a expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16^Ink4a in EPCs and lung tissue induced by CSE.

Conclusion

5-Aza-CdR partly protected against emphysema in mice via suppressing p16^Ink4a expression in EPCs and lung tissue.

Wang et al. (Research Articles, 11 December 2020, p. 1295) reported a large decrease in CO₂ fertilization effect (CFE) across the globe during the period 1982–2015 and suggested that ecosystem models underestimate the rate of CFE decline. We find that their claims are artifacts of incorrect processing of satellite data and problematic methods for deriving and comparing CFE between satellite data and model simulations.

Wildfire-altered soil may be an important source of polycyclic aromatic hydrocarbons (PAHs) in the environment. With projected increase of wildfire frequency and intensity due to changing global climate, understanding the quantity and speciation of PAHs, including halogenated PAHs (XPAHs), resulting from different burn intensities has important ramifications for environmental quality concerns and global soil carbon dynamics. Here, we quantified levels of 16 U.S. Environmental Protection Agency regulated PAHs, 3 chlorinated PAHs, and 6 brominated PAHs in nonburned forest soils and burned ash/soil samples covered with black ash (B-Ash; moderate burn intensity) or white ash (W-Ash; severe burn intensity) from the 2013 Rim Fire (1,041 km 2 ) in California. The - 16 PAH concentrations follow (mean ± standard deviation; μg/kg) B-Ash (893 ± 285) > W-Ash (515 ± 333) ≈ nonburned soils (247 ± 58). Moreover, the - 16 PAH profiles were altered by both moderate and severe burn conditions with the size of aromatic structures following B-Ash > W-Ash > nonburned soils. Neither chlorinated nor brominated PAH concentration was significantly elevated by moderate or severe wildfire. Overall, fire intensity is critical in regulating soil PAH concentrations and profiles. Given the high erodibility of wildfire ash, these PAHs can be easily transported to rivers and reservoirs where they could impact the aquatic food web and drinking source water.

Background

There has recently been considerable interest in better understanding how blood pressure should be managed after an episode of hospitalized AKI, but there are scant data regarding the associations between blood pressure measured after AKI and subsequent adverse outcomes. We hypothesized that among AKI survivors, higher blood pressure measured three months after hospital discharge would be associated with worse outcomes. We also hypothesized these associations between blood pressure and outcomes would be similar among those who survived non-AKI hospitalizations.

Methods

We quantified how systolic blood pressure (SBP) observed three months after hospital discharge was associated with risks of subsequent hospitalized AKI, loss of kidney function, mortality, and heart failure events among 769 patients in the prospective ASSESS-AKI cohort study who had hospitalized AKI. We repeated this analysis among the 769 matched non-AKI ASSESS-AKI enrollees. We then formally tested for AKI interaction in the full cohort of 1538 patients to determine if these associations differed among those who did and did not experience AKI during the index hospitalization.

Results

Among 769 patients with AKI, 42 % had subsequent AKI, 13 % had loss of kidney function, 27 % died, and 18 % had heart failure events. SBP 3 months post-hospitalization did not have a stepwise association with the risk of subsequent AKI, loss of kidney function, mortality, or heart failure events. Among the 769 without AKI, there was also no stepwise association with these risks. In formal interaction testing using the full cohort of 1538 patients, hospitalized AKI did not modify the association between post-discharge SBP and subsequent risks of adverse clinical outcomes.

Conclusions

Contrary to our first hypothesis, we did not observe that higher stepwise blood pressure measured three months after hospital discharge with AKI was associated with worse outcomes. Our data were consistent with our second hypothesis that the association between blood pressure measured three months after hospital discharge and outcomes among AKI survivors is similar to that observed among those who survived non-AKI hospitalizations.