An improved Bayesian pick-the-winner (IBPW) design for randomized phase II clinical trials

Phase II clinical trials play a pivotal role in drug development by screening a large number of drug candidates to identify those with promising preliminary efficacy for phase III testing. Trial designs that enable efficient decision-making with small sample sizes and early futility stopping while controlling for type I and II errors in hypothesis testing, such as Simon’s two-stage design, are preferred. Randomized multi-arm trials are increasingly used in phase II settings to overcome the limitations associated with using historical controls as the reference. However, how to effectively balance efficiency and accurate decision-making continues to be an important research topic. A notable development in phase II randomized design methodology is the Bayesian pick-the-winner (BPW) design that extends a Simon’s two-stage based multi-arm design with a Bayesian winner-selection strategy. Despite multiple appealing features, this method cannot easily control for overall type I and II errors for winner selection. Here, we introduce an improved randomized two-stage Bayesian pick-the-winner (IBPW) design that formalizes the winner-selection based hypothesis testing, optimizes sample sizes and decision cut-offs by strictly controlling the type I and type II errors under a set of flexible hypotheses for winner-selection across two treatment arms. Simulation studies demonstrate that our new design offers improved operating characteristics for winner selection while retaining the desirable features of the BPW design

Scheme for demonstrating Bell theorem in tripartite entanglement between atomic ensembles

We propose an experimentally feasible scheme to demonstrate quantum nonlocality, using Greenberger-Horne-Zeilinger (GHZ) and $W$ entanglement between atomic ensembles generated by a new developed method based on laser manipulation and{} single-photon detection.Comment: 10 pages, 4 figure

Efficient quantum cryptography network without entanglement and quantum memory

An efficient quantum cryptography network protocol is proposed with d-dimension polarized photons, without resorting to entanglement and quantum memory. A server on the network, say Alice, provides the service for preparing and measuring single photons whose initial state are |0>. The users code the information on the single photons with some unitary operations. For preventing the untrustworthy server Alice from eavesdropping the quantum lines, a nonorthogonal-coding technique (decoy-photon technique) is used in the process that the quantum signal is transmitted between the users. This protocol does not require the servers and the users to store the quantum state and almost all of the single photons can be used for carrying the information, which makes it more convenient for application than others with present technology. We also discuss the case with a faint laser pulse.Comment: 4 pages, 1 figures. It also presented a way for preparing decoy photons without a sinigle-photon sourc

Asymptotic quasinormal modes of scalar field in a gravity's rainbow

In the context of a gravity's rainbow, the asymptotic quasinormal modes of the scalar perturbation in the quantum modified Schwarzschild black holes are investigated. By using the monodromy method, we calculated and obtained the asymptotic quasinormal frequencies, which are dominated not only by the mass parameter of the spacetime, but also by the energy functions from the modified dispersion relations. However, the real parts of the asymptotic quasinormal modes is still $T_H\ln 3$, which is consistent with Hod's conjecture. In addition, for the quantum corrected black hole, the area spacing is calculated and the result is independent of the energy functions, in spite of the area itself is energy dependence. And that, by relating the area spectrum to loop quantum gravity, the Barbero-Immirzi parameter is given and it remains the same as from the usual black hole

Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis.

Obesity and extracellular matrix (ECM) density are considered independent risk and prognostic factors for breast cancer. Whether they are functionally linked is uncertain. We investigated the hypothesis that obesity enhances local myofibroblast content in mammary adipose tissue and that these stromal changes increase malignant potential by enhancing interstitial ECM stiffness. Indeed, mammary fat of both diet- and genetically induced mouse models of obesity were enriched for myofibroblasts and stiffness-promoting ECM components. These differences were related to varied adipose stromal cell (ASC) characteristics because ASCs isolated from obese mice contained more myofibroblasts and deposited denser and stiffer ECMs relative to ASCs from lean control mice. Accordingly, decellularized matrices from obese ASCs stimulated mechanosignaling and thereby the malignant potential of breast cancer cells. Finally, the clinical relevance and translational potential of our findings were supported by analysis of patient specimens and the observation that caloric restriction in a mouse model reduces myofibroblast content in mammary fat. Collectively, these findings suggest that obesity-induced interstitial fibrosis promotes breast tumorigenesis by altering mammary ECM mechanics with important potential implications for anticancer therapies

Anomalies of upper critical field in the spinel superconductor LiTi2_2O4−δ_{4-\delta}

High-field electrical transport and point-contact tunneling spectroscopy were used to investigate superconducting properties of the unique spinel oxide, LiTi$_2$O$_{4-\delta}$ films with various oxygen content. We find that the upper critical field $B_\mathrm{c2}$ gradually increases as more oxygen impurities are brought into the samples by carefully tuning the deposition atmosphere. It is striking that although the superconducting transition temperature and energy gap are almost unchanged, an astonishing isotropic $B_\mathrm{c2}$ up to $\sim$ 26 Tesla is observed in oxygen-rich sample, which is doubled compared to the anoxic sample and breaks the Pauli limit. Such anomalies of $B_\mathrm{c2}$ were rarely reported in other three dimensional superconductors. Combined with all the anomalies, three dimensional spin-orbit interaction induced by tiny oxygen impurities is naturally proposed to account for the remarkable enhancement of $B_\mathrm{c2}$ in oxygen-rich LiTi$_2$O$_{4-\delta}$ films. Such mechanism could be general and therefore provides ideas for optimizing practical superconductors with higher $B_\mathrm{c2}$

SmartMal: A Service-Oriented Behavioral Malware Detection Framework for Mobile Devices

This paper presents SmartMal—a novel service-oriented behavioral malware detection framework for vehicular and mobile devices. The highlight of SmartMal is to introduce service-oriented architecture (SOA) concepts and behavior analysis into the malware detection paradigms. The proposed framework relies on client-server architecture, the client continuously extracts various features and transfers them to the server, and the server’s main task is to detect anomalies using state-of-art detection algorithms. Multiple distributed servers simultaneously analyze the feature vector using various detectors and information fusion is used to concatenate the results of detectors. We also propose a cycle-based statistical approach for mobile device anomaly detection. We accomplish this by analyzing the users’ regular usage patterns. Empirical results suggest that the proposed framework and novel anomaly detection algorithm are highly effective in detecting malware on Android devices

Biology, invasion and management of the agricultural invader: Fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae)

The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith), is native to the Americas. It has rapidly invaded 47 African countries and 18 Asian countries since the first detection of invasion into Nigeria and Ghana in 2016. It is regarded as a super pest based on its host range (at least 353 host plants), its inherent ability to survive in a wide range of habitats, its strong migration ability, high fecundity, rapid development of resistance to insecticides/viruses and its gluttonous characteristics. The inherently superior biological characteristics of FAW contribute to its invasiveness. Integrated pest management (IPM) of FAW has relied on multiple applications of monitoring and scouting, agricultural control, chemical pesticides, viral insecticides, sex attractants, bio-control agents (parasitoids, predators and entomopathogens) and botanicals. Knowledge gaps remain to be filled to: (1) understand the invasive mechanisms of S. frugiperda; (2) understand how to prevent its further spread and (3) provide better management strategies. This review summarizes the biological characters of FAW, their association with its invasiveness and IPM strategies, which may provide further insights for future management

Clinical and genetic spectrum of a Chinese cohort with SCN4A gene mutations

Skeletal muscle sodium channelopathies due to SCN4A gene mutations have a broad clinical spectrum. However, each phenotype has been reported in few cases of Chinese origin. We present detailed phenotype and genotype data from a cohort of 40 cases with SCN4A gene mutations seen in neuromuscular diagnostic service in Huashan hospital, Fudan University. Cases were referred from 6 independent provinces from 2010 to 2018. A questionnaire covering demographics, precipitating factors, episodes of paralysis and myotonia was designed to collect the clinical information. Electrodiagnostic studies and muscle MRI were retrospectively analyzed. The clinical spectrum of patients included: 6 Hyperkalemic periodic paralysis (15%), 18 Hypokalemic periodic paralysis (45%), 7 sodium channel myotonia (17.5%), 4 paramyotonia congenita (10%) and 5 heterozygous asymptomatic mutation carriers (12.5%). Review of clinical information highlights a significant delay to diagnosis (median 15 years), reports of pain and myalgia in the majority of patients, male predominance, circadian rhythm and common precipitating factors. Electrodiagnostic studies revealed subclinical myotonic discharges and a positive long exercise test in asymptomatic carriers. Muscle MRI identified edema and fatty infiltration in gastrocnemius and soleus. A total of 13 reported and 2 novel SCN4A mutations were identified with most variants distributed in the transmembrane helix S4 to S6, with a hotspot mutation p.Arg675Gln accounting for 32.5% (13/40) of the cohort. Our study revealed a higher proportion of periodic paralysis in SCN4A-mutated patients compared with cohorts from England and the Netherlands. It also highlights the importance of electrodiagnostic studies in diagnosis and segregation studies