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Although the quantity and quality of single‐cell data have progressed rapidly, making quantitative predictions with single‐cell stochastic models remains challenging. The stochastic nature of cellular processes leads to at least three challenges in building models with single‐cell data: (a) because variability in single‐cell data can be attributed to multiple different sources, it is difficult to rule out conflicting mechanistic models that explain the same data equally well; (b) the distinction between interesting biological variability and experimental variability is sometimes ambiguous; (c) the nonstandard distributions of single‐cell data can lead to violations of the assumption of symmetric errors in least‐squares fitting. In this review, we first discuss recent studies that overcome some of the challenges or set up a promising direction and then introduce some powerful statistical approaches utilized in these studies. We conclude that applying and developing statistical approaches could lead to further progress in building stochastic models for single‐cell data. [ABSTRACT FROM AUTHOR]

Abstract Background Over the past decade, gene expression microarray studies have greatly expanded our knowledge of genetic mechanisms of human diseases. Meta-analysis of substantial amounts of accumulated data, by integrating valuable information from multiple studies, is becoming more important in microarray research. However, collecting data of special interest from public microarray repositories often present major practical problems. Moreover, including low-quality data may significantly reduce meta-analysis efficiency. Results M2DB is a human curated microarray database designed for easy querying, based on clinical information and for interactive retrieval of either raw or uniformly pre-processed data, along with a set of quality-control metrics. The database contains more than 10,000 previously published Affymetrix GeneChip arrays, performed using human clinical specimens. M2DB allows online querying according to a flexible combination of five clinical annotations describing disease state and sampling location. These annotations were manually curated by controlled vocabularies, based on information obtained from GEO, ArrayExpress, and published papers. For array-based assessment control, the online query provides sets of QC metrics, generated using three available QC algorithms. Arrays with poor data quality can easily be excluded from the query interface. The query provides values from two algorithms for gene-based filtering, and raw data and three kinds of pre-processed data for downloading. Conclusion M2DB utilizes a user-friendly interface for QC parameters, sample clinical annotations, and data formats to help users obtain clinical metadata. This database provides a lower entry threshold and an integrated process of meta-analysis. We hope that this research will promote further evolution of microarray meta-analysis.

Fragment coupling reactions that form carbon–carbon bonds are valuable transformations in synthetic design. Advances in metal‐catalyzed cross‐coupling reactions in the early 2000s brought a high level of predictability and reliability to carbon–carbon bond constructions involving the union of unsaturated fragments. By comparison, recent years have witnessed an increase in fragment couplings proceeding via carbanionic and open‐shell (free radical) intermediates. The latter has been driven by advances in methods to generate and utilize carbon‐centered radicals under mild conditions. In this Review, we survey a selection of recent syntheses that have implemented carbanion‐ or radical‐based fragment couplings to form carbon–carbon bonds. We aim to highlight the strategic value of these disconnections in their respective settings and to identify extensible lessons from each example that might be instructive to students. [ABSTRACT FROM AUTHOR]

Fragmentverknüpfungen unter Bildung von C‐C‐Bindungen sind nützlich für die Syntheseplanung. Die Fortschritte auf dem Gebiet der metallkatalysierten Kreuzkupplungen Anfang der 2000er Jahre sorgten für eine hohe Planbarkeit und Zuverlässigkeit bei C‐C‐Verknüpfungen zwischen ungesättigten Synthesebausteinen. In den vergangenen Jahren stieg hingegen das Interesse an Fragmentverknüpfungen, die über carbanionische oder offenschalige (radikalische) Zwischenstufen verlaufen. Radikalische Fragmentverknüpfungen wurden vor allem durch die Weiterentwickelung von Methoden zur Herstellung und Verwendung von Kohlenstoffradikalen unter milden Bedingungen vorangebracht. In diesem Aufsatz geben wir einen Überblick über ausgewählte neue Synthesen, in denen auf Carbanionen oder Radikalen basierende Fragmentverknüpfungen zur Bildung von C‐C‐Bindungen genutzt wurden. Unser Ziel ist, den strategischen Nutzen dieser Bindungsbrüche in ihren jeweiligen Anordnungen hervorzuheben und aus jedem Beispiel breiter anwendbare Lehren zu ziehen, die für Studierende aufschlussreich sein könnten. [ABSTRACT FROM AUTHOR]

Seeds, the reproductive organs of plants, are common as trace evidence from crime scenes. Seed evidence could be grouped into several categories based on the types of crimes they are associated with, including child abuse, homicides and drugs. Most commonly, seeds are examined microscopically and identified to the plant species level to show a linkage between persons and places. More recently, forensic researchers have evaluated the potential for extracting and typing DNA from seeds to further individualize the samples. As a model system, tomato seeds were examined microscopically after different cooking treatments and assessed for the potential to DNA type seeds for variety identification. A sufficient quantity and quality of DNA were recovered from uncooked, digested and undigested tomato seeds for amplified fragment length polymorphism (AFLP) analysis; however, any form of cooking destroyed the seed DNA. A simple microscopic analysis was able to distinguish between a cooked tomato seed versus an uncooked seed. This article is intended to provide an overview of case examples and current techniques for the forensic examination of seeds as plant-derived evidence. [ABSTRACT FROM AUTHOR]

Radiation therapy for cancer patients works by ionizing damage to nuclear DNA, primarily by creating double-strand breaks (DSB). A major shortcoming of traditional radiation therapy is the set of side effect associated with its long-range interaction with nearby tissues. Low-energy Auger electrons have the advantage of an extremely short effective range, minimizing damage to healthy tissue. Consequently, the isotope 99mTc, an Auger electron source, is currently being studied for its beneficial potential in cancer treatment. We examined the dose effect of a pyrene derivative 99mTc complex on plasmid DNA by using gel electrophoresis in both aqueous and methanol solutions. In aqueous solutions, the average yield per decay for double-strand breaks is 0.011±0.005 at low dose range, decreasing to 0.0005±0.0003 in the presence of 1 M dimethyl sulfoxide (DMSO). The apparent yield per decay for single-strand breaks (SSB) is 0.04±0.02, decreasing to approximately a fifth with 1 M DMSO. In methanol, the average yield per decay of DSB is 0.54±0.06 and drops to undetectable levels in 2 M DMSO. The SSB yield per decay is 7.2±0.2, changing to 0.4±0.2 in the presence of 2 M DMSO. The 95% decrease in the yield of DSB in DMSO indicates that the main mechanism for DSB formation is through indirect effect, possibly by cooperative binding or clustering of intercalators. In the presence of non-radioactive ligands at a near saturation concentration, where radioactive Tc compounds do not form large clusters, the yield of SSB stays the same while the yield of DSB decreases to the value in DMSO. DSBs generated by 99mTc conjugated to intercalators are primarily caused by indirect effects through clustering. [ABSTRACT FROM AUTHOR]