Assessing differential gene expression with small sample sizes in oligonucleotide arrays using a mean-variance model

The identification of the genes that are differentially expressed in two-sample microarray experiments remains a difficult problem when the number of arrays is very small. We discuss the implications of using ordinary t-statistics and examine other commonly used variants. For oligonucleotide arrays with multiple probes per gene, we introduce a simple model relating the mean and variance of expression, possibly with gene-specific random effects. Parameter estimates from the model have natural shrinkage properties that guard against inappropriately small variance estimates, and the model is used to obtain a differential expression statistic. A limiting value to the positive false discovery rate (pFDR) for ordinary t-tests provides motivation for our use of the data structure to improve variance estimates. Our approach performs well compared to other proposed approaches in terms of the false discovery rate.     

First record of Cricetops rodent in the Oligocene of southwestern China

The muroid Cricetops Matthew and Granger, 1923 commonly occurred in the Oligocene terrestrial deposits in central and northern Asia. Here we report the first record of Cricetops in the southern part of Asia. Isolated rodent molars named as a new species, Cricetops auster sp. nov., were discovered from the early Oligocene sediments at the Lijiawa locality in Yunnan Province in southwestern China. Compared to previously known Cricetops, C. auster is smaller than Cricetops dormitor Matthew and Granger, 1923 and Cricetops aeneus Shevyreva, 1965, but larger than Cricetops minor Wang, 1987. The cusps of C. auster are less conical. The ridges and crests are longer, higher and thicker. Relatively long and high crests, ridges and arms extending from the main cusps in the new species make those cusps more crescent in appearance than in C. dormitor, C. aeneus and C. minor. C. auster is a rare species in the Lijiawa mammalian fauna. Well-developed shearing tooth crests and ridges of C. auster probably suggest a different diet from the Cricetops from the northern part of Asia.     

Time-dependent cross ratio estimation for bivariate failure times

In the analysis of bivariate correlated failure time data, it is important to measure the strength of association among the correlated failure times. One commonly used measure is the cross ratio. Motivated by Cox's partial likelihood idea, we propose a novel parametric cross ratio estimator that is a flexible continuous function of both components of the bivariate survival times. We show that the proposed estimator is consistent and asymptotically normal. Its finite sample performance is examined using simulation studies, and it is applied to the Australian twin data.     

Spectrin folding versus unfolding reactions and RBC membrane stiffness

Spectrin (Sp), a key component of the erythrocyte membrane, is routinely stretched to near its fully folded contour length during cell deformations. Such dynamic loading may induce domain unfolding as suggested by recent experiments. Herein we develop a model to describe the folding/unfolding of spectrin during equilibrium or nonequilibrium extensions. In both cases, our model indicates that there exists a critical extension beyond which unfolding occurs. We further deploy this model, together with a three-dimensional model of the junctional complex in the erythrocyte membrane, to explore the effect of Sp unfolding on the membrane's mechanical properties, and on the thermal fluctuation of membrane-attached beads. At large deformations our results show a distinctive strain-induced unstiffening behavior, manifested in the slow decrease of the shear modulus, and accompanied by an increase in bead fluctuation. Bead fluctuation is also found to be influenced by mode switching, a phenomenon predicted by our three-dimensional model. The amount of stiffness reduction, however, is modest compared with that reported in experiments. A possible explanation for the discrepancy is the occurrence of spectrin head-to-head disassociation which is also included within our modeling framework and used to analyze bead motion as observed via experiment.     

Roles of phospholipase D in phorbol myristate acetate‐stimulated neutrophil respiratory burst

The phorbol myristate acetate (PMA) stimulated nutrophil respiratory burst has been considered to simply involve the activation of protein kinase C (PKC). However, the PLD activity was also increased by 10‐fold in human neutrophils stimulated with 100 nM PMA. Unexpectedly, U73122, an inhibitor of phospholipase C, was found to significantly inhibit PMA‐stimulated respiratory burst in human neutrophils. U73122 at the concentrations, which were sufficient to inhibit the respiratory burst completely, caused partial inhibition of the PLD activity but no inhibition on PKC translocation and activation, suggesting that PLD activity is also required in PMA‐stimulated respiratory burst. Using 1‐butanol, a PLD substrate, to block phosphatidic acid (PA) generation, the PMA‐stimulated neutrophil respiratory burst was also partially inhibited, further indicating that PLD activation, possibly its hydrolytic product PA and diacylglycerol (DAG), is involved in PMA‐stimulated respiratory burst. Since GF109203X, an inhibitor of PKC that could completely inhibit the respiratory burst in PMA‐stimulated neutrophils, also caused certain suppression of PLD activation, it may suggest that PLD activation in PMA‐stimulated neutrophils might be, to some extent, PKC dependent. To further study whether PLD contributes to the PMA stimulated respiratory burst through itself or its hydrolytic product, 1,2‐dioctanoyl‐sn‐glycerol, an analogue of DAG , was used to prime cells at low concentration, and it reversed the inhibition of PMA‐stimulated respiratory burst by U73122. The results indicate that U73122 may act as an inhibitor of PLD, and PLD activation is required in PMA‐stimulated respiratory burst.     

Efficiency Boost in All-Small-Molecule Organic Solar Cells: Insights from the Re-Ordering Kinetics

Achieving high-performance in all-small-molecule organic solar cells (ASM-OSCs) significantly relies on precise nanoscale phase separation through domain size manipulation in the active layer. Nonetheless, for ASM-OSC systems, forging a clear connection between the tuning of domain size and the intricacies of phase separation proves to be a formidable challenge. This study investigates the intricate interplay between domain size adjustment and the creation of optimal phase separation morphology, crucial for ASM-OSCs’ performance. It is demonstrated that exceptional phase separation in ASM-OSCs’ active layer is achieved by meticulously controlling the continuity and uniformity of domains via re-packing process. A series of halogen-substituted solvents (Fluorobenzene, Chlorobenzene, Bromobenzene, and Iodobenzene) is adopted to tune the re-packing kinetics, the ASM-OSCs treated with CB exhibited an impressive 16.2% power conversion efficiency (PCE). The PCE enhancement can be attributed to the gradual crystallization process, promoting a smoothly interconnected and uniformly distributed domain size. This, in turn, leads to a favorable phase separation morphology, enhanced charge transfer, extended carrier lifetime, and consequently, reduced recombination of free charges. The findings emphasize the pivotal role of re-packing kinetics in achieving optimal phase separation in ASM-OSCs, offering valuable insights for designing high-performance ASM-OSCs fabrication strategies.