Quick Calculation for Sample Size while Controlling False Discovery Rate with Application to Microarray Analysis

Sample size estimation is important in microarray or proteomic experiments since biologists can typically afford only a few repetitions. In the multiple testing problems involving these experiments, it is more powerful and more reasonable to control false discovery rate (FDR) or positive FDR (pFDR) instead of type I error, e.g., family-wise error rate (FWER) (Storey and Tibshirani, 2003). However, the traditional approach of estimating sample size is no longer applicable to controlling FDR, which has left most practitioners to rely on haphazard guessing. We propose a procedure to calculate sample size while controlling false discovery rate. Two major definitions of the false discovery rate (FDR in Benjamini and Hochberg, 1995, and pFDR in Storey, 2002) vary slightly. Our procedure applies to both definitions. The proposed method is straightforward to apply and requires minimal computation, as illustrated with two sample t-tests and F-tests. We have also demonstrated by simulation that, with the calculated sample size, the desired level of power is achievable by the q-value procedure (Storey, Taylor and Siegmund, 2004) when gene expressions are either independent or dependent

Superior pre-osteoblast cell response of etched ultrafine-grained titanium with a controlled crystallographic orientation

Ultrafine-grained (UFG) Ti for improved mechanical performance as well as its surface modification enhancing biofunctions has attracted much attention in medical industries. Most of the studies on the surface etching of metallic biomaterials have focused on surface topography and wettability but not crystallographic orientation, i.e., texture, which influences the chemical as well as the physical properties. In this paper, the influences of texture and grain size on roughness, wettability, and pre-osteoblast cell response were investigated in vitro after HF etching treatment. The surface characteristics and cell behaviors of ultrafine, fine, and coarse-grained Ti were examined after the HF etching. The surface roughness during the etching treatment was significantly increased as the orientation angle from the basal pole was increased. The cell adhesion tendency of the rough surface was promoted. The UFG Ti substrate exhibited a higher texture energy state, rougher surface, enhanced hydrophilic wettability, and better cell adhesion and proliferation behaviors after etching than those of the coarse- and fine-grained Ti substrates. These results provide a new route for enhancing both mechanical and biological performances using etching after grain refinement of Ti. ? The Author(s) 2017.115Ysciescopu

Human muscle-derived cell populations isolated by differential adhesion rates: Phenotype and contribution to skeletal muscle regeneration in Mdx/SCID mice

Muscle-derived stem cells (MDSCs) isolated from murine skeletal tissue by the preplate method have displayed the capability to commit to the myogenic lineage and regenerate more efficiently than myoblasts in skeletal and cardiac muscle in murine Duchenne Muscular Dystrophy mice (mdx). However, until now, these studies have not been translated to human muscle cells. Here, we describe the isolation, by a preplate technique, of candidate human MDSCs, which exhibit myogenic and regenerative characteristics similar to their murine counterparts. Using the preplate isolation method, we compared cells that adhere faster to the flasks, preplate 2 (PP2), and cells that adhere slower, preplate 6 (PP6). The human PP6 cells express several markers of mesenchymal stem cells and are distinct from human PP2 (a myoblast-like population) based on their expression of CD146 and myogenic markers desmin and CD56. After transplantation to the gastrocnemius muscle of mdx/SCID mice, we observe significantly higher levels of PP6 cells participating in muscle regeneration as compared with the transplantation of PP2 cells. This study supports some previous findings related to mouse preplate cells, and also identifies some differences between mouse and human muscle preplate cells

Estimating the number of true null hypotheses from a histogram of p values

In an earlier article, an intuitively appealing method for estimating the number of true null hypotheses in a multiple test situation was proposed. That article presented an iterative algorithm that relies on a histogram of observed p values to obtain the estimator. We characterize the limit of that iterative algorithm and show that the estimator can be computed directly without iteration. We compare the performance of the histogram-based estimator with other procedures for estimating the number of true null hypotheses from a collection of observed p values and find that the histogram-based estimator performs well in settings similar to those encountered in microarray data analysis. We demonstrate the approach using p values from a large microarray experiment aimed at uncovering molecular mechanisms of barley resistance to a fungal pathogen

61MO Biomarker analysis of men with enzalutamide (enza)-resistant metastatic castration-resistant prostate cancer (mCRPC) treated with pembrolizumab (pembro) + enza in KEYNOTE-199

Background: In KEYNOTE-199 (NCT02787005), pembro + enza had durable antitumor activity in enza-refractory mCRPC. We evaluated the association between prespecified biomarkers and clinical outcomes. Methods: Cohorts 4 (C4; RECIST-measurable disease) and 5 (C5; nonmeasurable, bone-predominant disease) enrolled men with chemotherapy-naive mCRPC, irrespective of PD-L1 status, that progressed after initial response to enza. We evaluated TMB by whole exome sequencing (n = 64), PD-L1 combined positive score (CPS) by IHC (n = 124), and 18-gene T-cell–inflamed gene expression profile (TcellinfGEP) by NanoString (n = 51). Outcomes were DCR, PFS, PSA response, PSA progression, OS, and ORR per blinded independent review (C4 only). Significance of continuous biomarkers (CPS, TMB, GEP) was prespecified at 0.05 for 1-sided P values from logistic (ORR, DCR, PSA response) and Cox proportional hazard (PFS, OS, PSA progression) regression adjusted for ECOG PS. Results: In C4, ORR was 10% (5/48) in pts with evaluable TMB data and 12% (10/81) in pts with CPS data. In C4 and C5, 16% (10/64) and 14% (17/124) of pts with TMB and CPS data, respectively, achieved a PSA response. TMB was significantly associated with DCR (P = 0.03) and trended toward an association with PSA response (P = 0.08). TMB (AUROC [95% CI]: 0.68 [0.51-0.86]), but not CPS (0.54 [0.41-0.67]) or TcellinfGEP (0.55 [0.37-0.74]), enriched for PSA response. TMB (P = 0.04), but not CPS (P = 0.57) or TcellinfGEP (P = 0.32), was significantly associated with PSA progression. There was 1 MSI-H pt (per Promega PCR assay); this pt achieved an objective and PSA response and had PFS \u3e6 months. TMB, CPS, and TcellinfGEP were not associated with PFS or OS. There was a low prevalence of TMB ≥175 mut/exome (11%) and TcellinfGEP-high (≥−0.318; 16%). Conclusions: In this biomarker analysis of KEYNOTE-199 C4-C5, PD-L1 CPS and TcellinfGEP were not significantly associated with clinical outcome. Despite the low prevalence of TMB ≥175 mut/exome, TMB was positively associated with outcomes of pembro + enza in pts with mCRPC. The sample sizes for the exploratory analyses were small, and results should be interpreted with caution

Seller’s optimal credit period and replenishment time in a supply chain with up-stream and down-stream trade credits

[[abstract]]In practice, a supplier often offers its retailers a permissible delay period M to settle their unpaid accounts. Likewise, a retailer in turn offers another trade credit period N to its customers. The benefits of trade credit are not only to attract new buyers who consider it a type of price reduction, but also to provide a competitive strategy other than introduce permanent price reductions. On the other hand, the policy of granting credit terms adds an additional cost to the seller as well as an additional dimension of default risk. In this paper, we first incorporate the fact that trade credit has a positive impact on demand but negative impacts on costs and default risks to establish an economic order quantity model for the seller in a supply chain with up-stream and down-stream trade credits. Then we derive the necessary and sufficient conditions to obtain the optimal replenishment time and credit period for the seller. Finally, we use some numerical examples to illustrate the theoretical results.[[incitationindex]]SCI[[booktype]]電子

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed

The Scientific Foundations of Forecasting Magnetospheric Space Weather

The magnetosphere is the lens through which solar space weather phenomena are focused and directed towards the Earth. In particular, the non-linear interaction of the solar wind with the Earth's magnetic field leads to the formation of highly inhomogenous electrical currents in the ionosphere which can ultimately result in damage to and problems with the operation of power distribution networks. Since electric power is the fundamental cornerstone of modern life, the interruption of power is the primary pathway by which space weather has impact on human activity and technology. Consequently, in the context of space weather, it is the ability to predict geomagnetic activity that is of key importance. This is usually stated in terms of geomagnetic storms, but we argue that in fact it is the substorm phenomenon which contains the crucial physics, and therefore prediction of substorm occurrence, severity and duration, either within the context of a longer-lasting geomagnetic storm, but potentially also as an isolated event, is of critical importance. Here we review the physics of the magnetosphere in the frame of space weather forecasting, focusing on recent results, current understanding, and an assessment of probable future developments.Peer reviewe