Miracle-dz/UniFAR-FTUs huggingface dataset:
Insight into resistance mechanism of anaplastic lymphoma kinase to alectinib and JH-VIII-157-02 caused by G1202R solvent front mutation

Background Mutated anaplastic lymphoma kinase (ALK) drives the development of advanced non-small cell lung cancer (NSCLC). Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02), which demonstrated potent effects against the G1202R mutation. Methods Molecular docking, conventional molecular dynamics (MD) simulations, free energy calculations, and umbrella sampling (US) simulations were carried out to make clear the principles of the binding preferences of alectinib and JH-VIII-157-02 toward ALKWT and the ALK G1202R (ALKG1202R) mutation. Results JH-VIII-157-02 has similar binding affinities to both ALKWT and ALKG1202R whereas it has has a much lower binding affinity for alectinib to ALKG1202R. Analysis of individual energy terms indicate the major variation involves the van der Waals and entropy terms. Structural analysis reveals that the conformational change of the ATP-binding glycine-rich loop was primarily responsible for the alectinib resistance, not JH-VIII-157-02. In addition, US simulations prove JH-VIII-157-02 has similar dissociative processes from both ALKWT and ALKG1202R, while alectinib is more easily dissociated from ALKG1202R than from ALKWT, thus indicating lesser residence time. Conclusion Both the binding affinity and the drug residence time should be emphasized in rational drug design to overcome the G1202R solvent front mutation in ALK resistance.
Developmental chromatin restriction of pro-growth gene networks acts as an epigenetic barrier to axon regeneration in cortical neurons

Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age-dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome-wide maps of chromatin accessibility. When applied to the developing cortex, this pipeline detected overall closure of chromatin in sub-networks of genes associated with axon growth. We next analyzed mature CNS neurons that were supplied with various pro-regenerative transcription factors. Unlike prior results with SOX11 and KLF7, here we found that neither JUN nor an activated form of STAT3 promoted substantial corticospinal tract regeneration. Correspondingly, chromatin accessibility in JUN or STAT3 target genes was substantially lower than in predicted targets of SOX11 and KLF7. Finally, we used the pipeline to predict pioneer factors that could potentially relieve chromatin constraints at growth-associated loci. Overall this integrated analysis substantiates the hypothesis that dynamic chromatin accessibility contributes to the developmental decline in axon growth ability and influences the efficacy of pro-regenerative interventions in the adult, while also pointing toward selected pioneer factors as high-priority candidates for future combinatorial experiments.
Reasoning about Cognitive Trust in Stochastic Multiagent Systems

We consider the setting of stochastic multiagent systems modelled as stochastic multiplayer games and formulate an automated verification framework for quantifying and reasoning about agents’ trust. To capture human trust, we work with a cognitive notion of trust defined as a subjective evaluation that agent A makes about agent B’s ability to complete a task, which in turn may lead to a decision by A to rely on B. We propose a probabilistic rational temporal logic PRTL*, which extends the probabilistic computation tree logic PCTL* with reasoning about mental attitudes (beliefs, goals, and intentions) and includes novel operators that can express concepts of social trust such as competence, disposition, and dependence. The logic can express, for example, that “agent A will eventually trust agent B with probability at least p that B will behave in a way that ensures the successful completion of a given task. ” We study the complexity of the automated verification problem and, while the general problem is undecidable, we identify restrictions on the logic and the system that result in decidable, or even tractable, subproblems.
Entity-Duet Neural Ranking: Understanding the Role of Knowledge Graph Semantics in Neural Information Retrieval

This paper presents the Entity-Duet Neural Ranking Model (EDRM), which introduces knowledge graphs to neural search systems. EDRM represents queries and documents by their words and entity annotations. The semantics from knowledge graphs are integrated in the distributed representations of their entities, while the ranking is conducted by interaction-based neural ranking networks. The two components are learned end-to-end, making EDRM a natural combination of entity-oriented search and neural information retrieval. Our experiments on a commercial search log demonstrate the effectiveness of EDRM. Our analyses reveal that knowledge graph semantics significantly improve the generalization ability of neural ranking models.
Caregiving burden and psychological distress in Chinese spousal caregivers: gender difference in the moderating role of positive aspects of caregiving

ABSTRACT Objectives: This study endeavors to advance the current literature by examining the gender differences in the caregiving experiences and the stress-buffering role of positive aspects of caregiving (PAC) among Chinese spousal caregivers of frail elders in Hong Kong. Method: Forty-nine husband caregivers and 121 wife caregivers of frail elders in Hong Kong (N = 170) responded to the Positive Aspects of Caregiving (PAC) scale, the Zarit Burden Interview (ZBI), the 21-item Depression, Anxiety, and Stress Scales (DASS-21), and demographic questions. These spousal caregivers were diverse in age, and their care receivers were diverse in terms of age and health condition. Results: As predicted, there were significant gender differences in the moderating effects of PAC on the relationships of caregiving burden to depression, anxiety, and overall psychological distress. While PAC significantly buffered the effects of caregiving burden on depression, anxiety, and overall psychological distress for wife caregivers, the moderating effects of PAC were not significant for husband caregivers. Unexpectedly, wife caregivers reported lower PAC, higher caregiving burden, and higher psychological distress. Conclusion: As these findings suggest that PAC is lower but more beneficial for Chinese wife caregivers than Chinese husband caregivers, helping professionals are recommended to use strengths-based interventions that target PAC when working with Chinese wife caregivers.
S I ] 1 1 A pr 2 01 8 Dynamic Competition Networks : detecting alliances and leaders ⋆

We consider social networks of competing agents that evolve dynamically over time. Such dynamic competition networks are directed, where a directed edge from nodes u to v corresponds a negative social interaction. We present a novel hypothesis that serves as a predictive tool to uncover alliances and leaders within dynamic competition networks. Our focus is in the present study is to validate it on competitive networks arising from social game shows such as Survivor and Big Brother.
Over-Sampling Codebook-Based Hybrid Minimum Sum-Mean-Square-Error Precoding for Millimeter-Wave 3D-MIMO

Hybrid precoding design is challenging for millimeter-wave massive MIMO. Most prior hybrid precoding schemes are designed to maximize the sum spectral efficiency, while seldom investigating the bit-error-rate (BER). Therefore, this letter designs an over-sampling codebook (OSC)-based hybrid minimum sum-mean-square-error (min-SMSE) precoding to optimize the BER. Specifically, given the effective baseband channel consisting of the real channel and analog precoding, we first design the digital precoder/combiner based on min-SMSE criterion to optimize the BER. To further reduce the SMSE between the transmit and receive signals, we propose an OSC-based joint analog precoder/combiner design. Simulation results show that the proposed scheme can achieve the better performance than its conventional counterparts.
Treatment of dental biofilm with a tincture of Bauhinia forficata leaves: an ex-vivo study

Abstract The inhibitory activity of a Bauhinia forficata tincture (TBF) was investigated against oral microorganism’s strains and against a mature oral biofilm. The viability of planktonic cells was analyzed by Minimal Inhibitory and Microbicidal concentrations of TBF. Salivary samples from health volunteers were collected and mixed to form a saliva pool. An aliquot from this pool were seeded on membranes, which were incubated to form biofilm (48 h). The biofilm was treated according to the groups: G1-Chlorhexidine 0.12%; G2-TBF at the highest MMC; G3-Ethanol at the TBF highest MMC. G4 was the growth control. Streptococcus spp. (S) and total microorganisms (TM) from biofilm were counted. TBF was microbicidal against all oral pathogens. G2 was able to reduce the counts of S and TM from biofilm compared to G3 and G4, but less than G1 (p < 0.05). TBF is able to reduce the microbial levels from a mature oral biofilm.
Building Scalable and Consistent Distributed Databases Under Conflicts

Distributed databases, which rely on redundant and distributed storage across multiple servers, are able to provide mission-critical data management services at large scale. Parallelism is the key to the scalability of distributed databases, but concurrent queries having conflicts may block or abort each other when strong consistency is enforced using rigorous concurrency control protocols. This thesis studies the techniques of building scalable distributed databases under strong consistency guarantees even in the face of high contention workloads. The techniques proposed in this thesis share a common idea, conflict mitigation, meaning mitigating conflicts by rescheduling operations in the concurrency control in the first place instead of resolving contending conflicts. Using this idea, concurrent queries under conflicts can be executed with high parallelism. This thesis explores this idea on both databases that support serializable ACID (atomic, consistency, isolation, durability) transactions, and eventually consistent NoSQL systems. First, the epoch-based concurrency control (ECC) technique is proposed in ALOHA-KV, a new distributed key-value store that supports high performance read-only and writeonly distributed transactions. ECC demonstrates that concurrent serializable distributed transactions can be processed in parallel with low overhead even under high contention. With ECC, a new atomic commitment protocol is developed that only requires amortized one round trip for a distributed write-only transaction to commit in the absence of failures. Second, a novel paradigm of serializable distributed transaction processing is developed to extend ECC with read-write transaction processing support. This paradigm uses a newly proposed database operator, functors, which is a placeholder for the value of a key, which can be computed asynchronously in parallel with other functor computations of the same or other transactions. Functor-enabled ECC achieves more fine-grained concurrency control than transaction level concurrency control, and it never aborts transactions due to read-write or write-write conflicts but allows transactions to fail due to logic errors or constraint violations while guaranteeing serializability. Lastly, this thesis explores consistency in the eventually consistent system, Apache Cassandra, for an investigation of the consistency violation, referred to as “consistency spikes”. This investigation shows that the consistency spikes exhibited by Cassandra are strongly correlated with garbage collection, particularly the “stop-the-world” phase in the Java virtual machine. Thus, delaying read operations artificially at servers immediately after a garbage collection pause can virtually eliminate these spikes. All together, these techniques allow distributed databases to provide scalable and consistent storage service.
Backtracking adaptive matching pursuit reconstruction algorithm based on improved matching criterion

Accurate matching the best atom is the key factor for compressed sensing reconstruction process to precisely recovery of the goal signal. The inner product matching criterion applied by Backtracking adaptive matching pursuit algorithm (BAOMP) is the lack of consideration of information, leading to the imprecise matching of the best atoms. The matching criterion of Dice coefficient considered the signal reduces the reconstruction error. So this paper proposed a new algorithm named Dice-BAOMP, which get the better performance. Simulation results verified the performance of proposed algorithms that success rates of reconstruction are 8%-10% higher than original algorithm.
Randomized Strategies for Robust Combinatorial Optimization

In this paper, we study the following robust optimization problem. Given an independence system and candidate objective functions, we choose an independent set, and then an adversary chooses one objective function, knowing our choice. The goal is to find a randomized strategy (i.e., a probability distribution over the independent sets) that maximizes the expected objective value in the worst case. This problem is fundamental in wide areas such as artificial intelligence, machine learning, game theory and optimization. To solve the problem, we propose two types of schemes for designing approximation algorithms. One scheme is for the case when objective functions are linear. It first finds an approximately optimal aggregated strategy and then retrieves a desired solution with little loss of the objective value. The approximation ratio depends on a relaxation of an independence system polytope. As applications, we provide approximation algorithms for a knapsack constraint or a matroid intersection by developing appropriate relaxations and retrievals. The other scheme is based on the multiplicative weights update (MWU) method. The direct application of the MWU method does not yield a strict multiplicative approximation algorithm but yield one with an additional additive error term. A key technique to overcome the issue is to introduce a new concept called (η,γ)-reductions for objective functions with parameters η and γ. We show that our scheme outputs a nearly α-approximate solution if there exists an α-approximation algorithm for a subproblem defined by (η,γ)-reductions. This improves approximation ratios in previous results. Using our result, we provide approximation algorithms when the objective functions are submodular or correspond to the cardinality robustness for the knapsack problem.
Blockage of store-operated Ca2+ entry antagonizes Epstein–Barr virus-promoted angiogenesis by inhibiting Ca2+ signaling-regulated VEGF production in nasopharyngeal carcinoma

Background Epstein–Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store-operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF-mediated angiogenesis remains to be further clarified. Materials and methods Two EBV-infected NPC cell lines, CNE2-EBV and HK1-EBV, along with their parental cell lines were employed in the present study. Dynamic cytosolic Ca2+ changes were measured in individual fluorescent Ca2+ indicator-loaded cells. Amounts of VEGF production were determined by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs)-formed tube networks were quantitatively evaluated as an in vitro angiogenesis assay. A mouse model concurrently bearing EBV-positive/negative xenografts was utilized to evaluate the tumor growth and angiogenesis in vivo. Results EBV infection reliably promoted transplanted tumor growth while enhancing angiogenesis. Introduction of EBV into EBV-negative NPC cells increased the EGF-stimulated VEGF production while amplifying the EGF-evoked Ca2+ responses. Inhibition of the EBV-boosted Ca2+ signaling using 2-aminoethyl diphenylborinate (2-APB), a specific SOCE inhibitor, effectively antagonized the EBV-promoted VEGF production and endothelial tube formation in vitro. Pharmacological blockage of SOCE exhibited anti-angiogenic effect in the EBV-positive xenografts. Conclusion SOCE can serve as a candidate pharmacological target for treating NPC, as blockage of the Ca2+ signaling via SOCE is a feasible strategy to suppress the EBV-driven malignant profiles in NPC cells.
Sequential adaptive elastic net approach for single-snapshot source localization

This paper proposes efficient algorithms for accurate recovery of direction-of-arrivals (DoAs) of sources from single-snapshot measurements using compressed beamforming (CBF). In CBF, the conventional sensor array signal model is cast as an underdetermined complex-valued linear regression model and sparse signal recovery methods are used for solving the DoA finding problem. A complex-valued pathwise weighted elastic net (c-PW-WEN) algorithm is developed that finds solutions at the knots of penalty parameter values over a path (or grid) of elastic net (EN) tuning parameter values. c-PW-WEN also computes least absolute shrinkage and selection operator (LASSO) or weighted LASSO in its path. A sequential adaptive EN (SAEN) method is then proposed that is based on c-PW-WEN algorithm with adaptive weights that depend on previous solution. Extensive simulation studies illustrate that SAEN improves the probability of exact recovery of true support compared to conventional sparse signal recovery approaches such as LASSO, EN, or orthogonal matching pursuit in several challenging multiple target scenarios. The effectiveness of SAEN is more pronounced in the presence of high mutual coherence.
[18F]FDG-PET/CT in Hodgkin Lymphoma: Current Usefulness and Perspectives

Functional imaging using 18-fluorodeoxyglycose ([18F]FDG) positron emission tomography combined with computed tomography (PET/CT) has become a major imaging modality in Hodgkin lymphoma. This imaging modality allows for a significant improvement in staging, increased sensitivity, which involves differentiating residual tumors from fibrosis during assessment, and highly impacts treatment decisions into new PET-driven strategies. This review presents the main scientific data concerning the current applications of [18F]FDG-PET/CT in Hodgkin lymphoma at baseline, interim, and the end of treatment evaluation along with the main PET-driven trials for therapeutic decisions. The emergence of total metabolic tumor volume as a new functional prognostic factor will also be discussed.
Custom-made tangible interfaces with touchtokens

TouchTokens were introduced recently as a means to design low-cost tangible interfaces. The technique consists in recognizing multi-touch patterns associated with specific tokens, and works on any touch-sensitive surface, with passive tokens that can be made out of any material. TouchTokens have so far been limited to a few basic geometrical shapes only, which puts a significant practical limit to how tailored token sets can be. In this article, we introduce TouchTokenBuilder and TouchTokenTracker that, taken together, aim at facilitating the development of tailor-made tangible interfaces. TouchTokenBuilder is an application that assists interface designers in creating token sets using a simple direct-manipulation interface. TouchTokenTracker is a library that enables tracking the tokens' full geometry. We report on experiments with those tools, showing the strengths and limitations of tangible interfaces with passive tokens.
In Vitro Estrogenic and Breast Cancer Inhibitory Activities of Chemical Constituents Isolated from Rheum undulatum L.

We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized E-screen assay in estrogen receptor (ER)-positive MCF-7 cells. The mechanism underlying the breast cancer inhibitory activity of the compounds was studied using human ER-negative MDA-MB-231 and ER-positive MCF-7 cells. The activation of apoptosis pathway-related proteins was investigated by western blotting, using extracts of R. undulatum prepared in three solvent conditions (EX1, EX2, and EX3). The R. undulatum chemical constituents (compounds 1–3) showed estrogen-like activity in the concentration range of 10 to 50 μM, by increasing the proliferation of human ER-positive MCF-7 cells. These effects were attenuated by co-treatment with 100 nM fulvestrant, an ER antagonist. Compounds 1–3 decreased the viability of MCF-7 cells in a concentration-dependent manner. Compounds 1 (aloe emodin) and 2 (rhapontigenin) induced mitochondria-independent apoptosis by activating the caspase-8 pathway, whereas the cytotoxic effect of compound 3 (chrysophanol 1-O-β-d-glucopyranoside) was mediated through the mitochondria-dependent apoptotic pathway.
CIAO: Cache Interference-Aware Throughput-Oriented Architecture and Scheduling for GPUs

A modern GPU aims to simultaneously execute more warps for higher Thread-Level Parallelism (TLP) and performance. When generating many memory requests, however, warps contend for limited cache space and thrash cache, which in turn severely degrades performance. To reduce such cache thrashing, we may adopt cache locality-aware warp scheduling which gives higher execution priority to warps with higher potential of data locality. However, we observe that warps with high potential of data locality often incurs far more cache thrashing or interference than warps with low potential of data locality. Consequently, cache locality-aware warp scheduling may undesirably increase cache interference and/or unnecessarily decrease TLP. In this paper, we propose Cache Interference-Aware throughput-Oriented (CIAO) on-chip memory architecture and warp scheduling which exploit unused shared memory space and take insight opposite to cache locality-aware warp scheduling. Specifically, CIAO on-chip memory architecture can adaptively redirect memory requests of severely interfering warps to unused shared memory space to isolate memory requests of these interfering warps from those of interfered warps. If these interfering warps still incur severe cache interference, CIAO warp scheduling then begins to selectively throttle execution of these interfering warps. Our experiment shows that CIAO can offer 54% higher performance than prior cache locality-aware scheduling at a small chip cost.