Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct‐acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local‐regional therapy or liver transplant waitlist dropout

Whether direct‐acting antivirals (DAAs) increase the risk of hepatocellular carcinoma (HCC) recurrence after tumor‐directed therapy is controversial. We sought to determine the impact of DAA therapy on HCC recurrence after local‐regional therapy (LRT) and waitlist dropout among liver transplant (LT) candidates with HCC. We performed a retrospective cohort study of 149 LT candidates with hepatitis C virus (HCV) and HCC at a single center from 2014 through 2016. Cumulative incidence of HCC recurrence post‐LRT and waitlist dropout was estimated by the DAA group. Factors associated with each outcome were evaluated using competing risks regression. A propensity score stabilized inverse probability weighting approach was used to account for differences in baseline characteristics between groups. The no DAA group (n = 87) had more severe cirrhosis and lower rates of complete radiologic tumor response after LRT than those treated with DAA (n = 62) but had similar alpha‐fetoprotein and tumor burden at listing. Cumulative incidence of HCC recurrence within 1 year of complete response after LRT was 47.0% in the DAA group and 49.8% in the no DAA group (P = 0.93). In adjusted competing risk analysis using weighted propensity score modeling, risk of HCC recurrence was similar in the DAA group compared to those without DAA (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.58‐1.42; P = 0.67). Patients treated with DAAs had lower risk of waitlist dropout due to tumor progression or death compared to the no DAA group in adjusted weighted analysis (HR, 0.30; 95% CI 0.13‐0.69; P = 0.005). Conclusion: In LT candidates with HCV and HCC with initial complete response to LRT, DAA use is not associated with increased risk of HCC recurrence but rather is associated with reduced risk of waitlist dropout due to tumor progression or death. (Hepatology 2018).
A Coupled Duration-Focused Architecture for Real-Time Music-to-Score Alignment

The capacity for real-time synchronization and coordination is a common ability among trained musicians performing a music score that presents an interesting challenge for machine intelligence. Compared to speech recognition, which has influenced many music information retrieval systems, music's temporal dynamics and complexity pose challenging problems to common approximations regarding time modeling of data streams. In this paper, we propose a design for a real-time music-to-score alignment system. Given a live recording of a musician playing a music score, the system is capable of following the musician in real time within the score and decoding the tempo (or pace) of its performance. The proposed design features two coupled audio and tempo agents within a unique probabilistic inference framework that adaptively updates its parameters based on the real-time context. Online decoding is achieved through the collaboration of the coupled agents in a Hidden Hybrid Markov/semi-Markov framework, where prediction feedback of one agent affects the behavior of the other. We perform evaluations for both real-time alignment and the proposed temporal model. An implementation of the presented system has been widely used in real concert situations worldwide and the readers are encouraged to access the actual system and experiment the results.
Apolipoprotein E4 Elicits Lysosomal Cathepsin D Release, Decreased Thioredoxin-1 Levels, and Apoptosis

The major genetic risk factor for Alzheimer’s disease (AD), apolipoprotein E4 (ApoE4), has been suggested to have detrimental effects on neurons, including direct toxicity via apoptosis. Thioredoxin-1 (Trx1) is an endogenous antioxidant protein important for redox regulation and participates in the regulation of apoptosis through the inhibition of apoptosis signal-regulating kinase-1 (Ask-1). In this study, we have investigated the effects of ApoE on Trx1 in the brain. Our results showed that the protein levels of Trx1 were reduced in the hippocampus of ApoE4 targeted replacement (TR) mice compared to ApoE3 TR mice. The reduction was also seen in vitro after treatment of both human primary cortical neurons and neuroblastoma cells with human recombinant ApoE4 (rApoE4). Furthermore, ApoE4 caused a disruption of lysosomal integrity and a shift in the localization of Cathepsin D, an enzyme known to degrade Trx1. ApoE4 treatment induced in addition apoptosis through translocation of Death-domain associated protein-6 (Daxx) from the nucleus to the cytosol, suggesting an activation of the Ask-1 pathway. This toxicity was prevented by overexpression of Trx1 and other endogenous Ask-1 inhibitors. Our data suggests that down-regulation of Trx1 is involved in the toxicity caused by ApoE4. An activated ASK-1 pathway might indeed make cells more vulnerable to other insults such as amyloid-β, which could partially explain the mechanism behind the strongest genetic risk factor for AD.
ACE-FTS measurements of trace species in the characterization of biomass burning plumes

Abstract. To further our understanding of the effects of biomass burning emissions on atmospheric composition, we report measurements of trace species in biomass burning plumes made by the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) instrument on the SCISAT-1 satellite. An extensive set of 15 molecules, C 2 H 2 , C 2 H 6 , CH 3 OH, CH 4 , CO, H 2 CO, HCN, HCOOH, HNO 3 , NO, NO 2 , N 2 O 5 , O 3 , OCS and SF 6 are used in our analysis. Even though most biomass burning smoke is typically confined to the boundary layer, some of these emissions are injected directly into the free troposphere via fire-related convective processes and transported away from the emission source. Further knowledge of the aging of biomass burning emissions in the free troposphere is needed. Tracer-tracer correlations are made between known pyrogenic species in these plumes in an effort to characterize them and follow their chemical evolution. Criteria such as age and type of biomass material burned are considered.
LncRNAs in pancreatic cancer

Pancreatic cancer (PC) is one of the most common causes of cancer-related death. The underlying mechanism of PC is not completely understood at present. Studies in recent years have demonstrated that long non-coding RNAs (lncRNAs) have multiple biological functions in cell growth, differentiation and proliferation. Notably, expressions of some lncRNAs undergo significant changes in the initiation and progression of cancers. In addition, lncRNAs are reported to be involved in various steps of PC development and have a potential value in the diagnosis, treatment and prognostic prediction of PC. In this review, we highlight recent evidence related to the molecular mechanism of lncRNAs in growth, survival, invasion, metastasis, angiogenesis and apoptosis of PC cells, and discuss the potential clinical application of lncRNAs to the diagnosis, treatment and prognostic prediction of PC.
Decentralized Power Control for Random Access with Successive Interference Cancellation

This paper is concerned with the decentralized power allocation problem in random access systems. We propose a scheme that is especially suitable for systems requiring high throughput but with difficulty in establishing centralized control, such as cognitive radio environments. Specifically, we assume successive interference cancellation (SIC) at the receiver for multi-packet reception (MPR). We consider a decentralized random power transmission strategy where each user selects its transmitted power level randomly according to a power distribution conditioned on its own channel state. Our focus is on the design of this distribution such that the system packet throughput is maximized under rate and power constraints. We start from a two-user system. A main finding of this paper is that the supports of the optimal power distributions are of discrete nature. This finding greatly simplifies the distribution optimization problem. We also discuss a sub-optimal solution to systems with more than two users. Numerical results demonstrate that the proposed scheme can achieve noticeable performance improvement compared with conventional single-user detection (SUD) based ones and offer a flexible tradeoff between the system throughput and power consumption.
Inhibition of Transient Receptor Potential Channel Mucolipin-1 (TRPML1) by Lysosomal Adenosine Involved in Severe Combined Immunodeficiency Diseases*

Impaired adenosine homeostasis has been associated with numerous human diseases. Lysosomes are referred to as the cellular recycling centers that generate adenosine by breaking down nucleic acids or ATP. Recent studies have suggested that lysosomal adenosine overload causes lysosome defects that phenocopy patients with mutations in transient receptor potential channel mucolipin-1 (TRPML1), a lysosomal Ca2+ channel, suggesting that lysosomal adenosine overload may impair TRPML1 and then lead to subsequent lysosomal dysfunction. In this study, we demonstrate that lysosomal adenosine is elevated by deleting adenosine deaminase (ADA), an enzyme responsible for adenosine degradation. We also show that lysosomal adenosine accumulation inhibits TRPML1, which is rescued by overexpressing ENT3, the adenosine transporter situated in the lysosome membrane. Moreover, ADA deficiency results in lysosome enlargement, alkalinization, and dysfunction. These are rescued by activating TRPML1. Importantly, ADA-deficient B-lymphocytes are more vulnerable to oxidative stress, and this was rescued by TRPML1 activation. Our data suggest that lysosomal adenosine accumulation impairs lysosome function by inhibiting TRPML1 and subsequently leads to cell death in B-lymphocytes. Activating TRPML1 could be a new therapeutic strategy for those diseases.
Exception handling in agent systems

A critical challenge to creating effective agent-based systems is allowing them to operate effectively when the operating environment is complex, dynamic, and error-prone. In this paper we will review the limitations of current "agent-local" approaches to exception handling in agent systems, and propose an alternative approach based on a shared exception handling service that is "plugged", with little or no customization, into existing agent systems. This service can be viewed as a kind of "coordination doctor"; it knows about the different ways multi-agent systems can get "sick", actively looks system-wide for symptoms of such "illnesses", and prescribes specific interventions instantiated for this particular context from a body of general treatment procedures. Agents need only implement their normative behavior plus a minimal set of interfaces. We claim that this approach offers simplified agent development as well as more effective and easier to modify exception handling behavior.
HIPdb: A Database of Experimentally Validated HIV Inhibiting Peptides

Background Besides antiretroviral drugs, peptides have also demonstrated potential to inhibit the Human immunodeficiency virus (HIV). For example, T20 has been discovered to effectively block the HIV entry and was approved by the FDA as a novel anti-HIV peptide (AHP). We have collated all experimental information on AHPs at a single platform. Descriptions HIPdb is a manually curated database of experimentally verified HIV inhibiting peptides targeting various steps or proteins involved in the life cycle of HIV e.g. fusion, integration, reverse transcription etc. This database provides experimental information of 981 peptides. These are of varying length obtained from natural as well as synthetic sources and tested on different cell lines. Important fields included are peptide sequence, length, source, target, cell line, inhibition/IC50, assay and reference. The database provides user friendly browse, search, sort and filter options. It also contains useful services like BLAST and ‘Map’ for alignment with user provided sequences. In addition, predicted structure and physicochemical properties of the peptides are also included. Conclusion HIPdb database is freely available at http://crdd.osdd. net/servers/hipdb. Comprehensive information of this database will be helpful in selecting/designing effective anti-HIV peptides. Thus it may prove a useful resource to researchers for peptide based therapeutics development.
Toward a Self-Updating Platform for Estimating Rates of Speciation and Migration, Ages, and Relationships of Taxa

&NA; Rapidly growing biological data—including molecular sequences and fossils—hold an unprecedented potential to reveal how evolutionary processes generate and maintain biodiversity. However, researchers often have to develop their own idiosyncratic workflows to integrate and analyze these data for reconstructing time‐calibrated phylogenies. In addition, divergence times estimated under different methods and assumptions, and based on data of various quality and reliability, should not be combined without proper correction. Here we introduce a modular framework termed SUPERSMART (Self‐Updating Platform for Estimating Rates of Speciation and Migration, Ages, and Relationships of Taxa), and provide a proof of concept for dealing with the moving targets of evolutionary and biogeographical research. This framework assembles comprehensive data sets of molecular and fossil data for any taxa and infers dated phylogenies using robust species tree methods, also allowing for the inclusion of genomic data produced through next‐generation sequencing techniques. We exemplify the application of our method by presenting phylogenetic and dating analyses for the mammal order Primates and for the plant family Arecaceae (palms). We believe that this framework will provide a valuable tool for a wide range of hypothesis‐driven research questions in systematics, biogeography, and evolution. SUPERSMART will also accelerate the inference of a “Dated Tree of Life” where all node ages are directly comparable.
Effects of Smoking and Cessation on Subclinical Arterial Disease: A Substudy of a Randomized Controlled Trial

Background The mechanisms by which smoking cessation reduces cardiovascular disease risk are unclear. We evaluated longitudinal changes in carotid intima-media thickness among current smokers enrolled in a prospective, randomized smoking cessation clinical trial. Methodology/Principal Findings Subjects were enrolled in a randomized, double-blind, placebo-controlled trial of 5 smoking cessation pharmacotherapies and underwent carotid ultrasonography with carotid intima-media thickness measurement. Subjects were classified as continuously abstinent (biochemically confirmed abstinence at 6 months, 1 year, and 3 years post-quit attempt), intermittently abstinent (reported smoking at one of the three time points), or smoked continuously (reported smoking at all three time points). The primary endpoint was the absolute change (mm) in carotid intima-media thickness (ΔCIMTmax) before randomization and 3 years after the target quit date. Pearson correlations were calculated and multivariable regression models (controlling for baseline CIMTmax and research site) were analyzed. Among 795 subjects (45.2±10.6 years old, 58.5% female), 189 (23.8%) were continuously abstinent, 373 (46.9%) smoked continuously, and 233 (29.3%) were abstinent intermittently. There was a greater increase in carotid intima-media thickness among subjects who were continuously abstinent than among those who smoked continuously (p = 0.020), but not intermittently (p = 0.310). Antihypertensive medication use (p = 0.001) and research site (p<0.001) independently predicted ΔCIMTmax – not smoking status. The greatest increase in carotid intima-media thickness among continuous abstainers was related to increases in body-mass index (p = 0.043). Conclusions/Significance Smoking status did not independently predict ΔCIMTmax; increasing body-mass index and antihypertensive medication use were the most important independent predictors. The rapid reduction in cardiovascular disease events observed with smoking cessation is unlikely to be mediated by changes in subclinical atherosclerosis burden. Trial Registration ClinicalTrials.gov NCT00332644
Multivariable sliding-mode extremum seeking control with application to alternator maximum power point tracking

A common problem with conventional alternator-based energy converters in vehicular applications is that they do not work at optimal operating points in their speed-power curves. This paper addresses the above problem by utilizing a Switched- Mode Rectifier (SMR) load-matching technique using real-time extremum seeking control. To this end, a multivariable control strategy is presented to track the maximum power in an alternator-based system. In particular, we propose a novel multivariable sliding-mode technique for maximum power point tracking (MPPT) in a Lundell alternator system. The proposed controller, combines the merits of multivariable extremum seeking and sliding-mode control. Utilizing the multivariable extremum seeking control makes the control model-free and increases the controller efficiency. Besides, the sliding-mode controller is robust in the face of parametric and dynamic uncertainties. The proposed controller is compared with two recent multivariable and decentralized methods. The simulation results demonstrate the advantages of the proposed controller in terms of fast and precise convergence and robust performance in face of disturbances and uncertainties.
Sample size effects on the behavior of EPS geofoam

Expanded polystyrene (EPS) geofoam has now been used around the world as a remarkable lightweight soil substitute for a variety of geotechnical applications in soft ground construction. Property characterizations of EPS for determination of design parameters have relied on laboratory testing of small samples. For the most part much of what is commonly known is based on data derived from unconfined compression testing of standard 50 mm cube samples. Performance observations suggest that Young's modulus values derived from laboratory tests when used in analysis tend to overestimate deformations. Available information on Poisson's ratio values widely varies. Little is known about the influence of sample size on desired elastic parameters. Studies of EPS behavior under unconfined compression were conducted on both cubic and cylindrical samples of different material densities. Both axial and lateral deformations were monitored to enable simultaneous evaluation of Young's modulus and Poisson's ratio. The results indicate significant sample size influence on elastic parameters. Young's modulus and Poisson's ratio values tend to ,. be underestimated. The cause for the under estimation is attributed to be due to non uniformity and end effects in the proximity of the rigid loading platens. Introduction The use of Expanded Polystyrene (EPS) as a lightweight material is growing rapidly in the United States and elsewhere. Various geotechnical applications use geofoam. Among these are embankments, retaining walls, slope stabilization and bridge abutments. lResearch Assistant, Geofoam Research Center and ESF, Syracuse, NY 13244 2Director, Geofoam Research Center, Syracuse University, Syracuse, NY 13244 3prof. Chairman, CMWPE Dept. SUNY-ESF, 403 Baker Lab, Syracuse, NY 13210
Identification of potential ibrutinib combinations in hematological malignancies using a combination high-throughput screen

Abstract Matrix high-throughput screening (HTS) methods are increasingly employed to rapidly define potential therapeutic drug combinations. We used combination HTS to identify compounds showing synergistic anti-proliferative activity with ibrutinib, an irreversible, small-molecule inhibitor of Bruton’s tyrosine kinase. The goal was to identify ibrutinib combinations with maximum synergistic effects in heme malignancy lines, particularly in non-Hodgkin lymphoma including diffuse large B-cell lymphoma (DLBCL). Growth inhibition (GI) was used to measure cell viability; synergy scores characterized strength of synergistic interaction. Single-agent ibrutinib demonstrated varying degrees of activity across 30 cell lines evaluated. In DLBCL lines, TMD8 was the most sensitive to ibrutinib (GI50 = 0.001); combinations with BCL-2 inhibitor ABT-199, and PI3K inhibitors IPI-145 and GDC-0941 showed the strongest synergistic activity. Anti-proliferative synergies were also observed with BET bromodomain inhibitor (+)-JQ1, XPO1 inhibitor selinexor, and IRAK4 inhibitor, and confirmed using apoptosis assay. These findings are intended to inform and advance treatment of B-cell malignancies.
On water-filling precoding for coded single-carrier systems

We study the spectrum shaping gain in single carrier systems through water-filling precoding. We show that water-filling precoding outperforms other existing alternatives when iterative linear minimum mean square error (LMMSE) detection is involved, which is confirmed by both evolution analysis and simulation results. This technique does not incur any extra receiver cost when it is used together with frequency domain equalization (FDE).
Professional and practice characteristics associated with self-efficacy in assessment and intervention among social workers in aging

ABSTRACT This study examined professional and practice characteristics associated with assessment and intervention self-efficacy among gerontological social workers in Ontario, Canada who participated in online surveys. Results from multivariate analyses indicated that higher client acuity, longer duration of practice experience, smaller caseloads, and a greater proportion of clients 85 and over were significantly associated with greater assessment self-efficacy. Greater client acuity and smaller caseloads were also significantly associated with greater intervention self-efficacy. Implications for education include the importance of providing practical experience with the oldest old and with clients with greater biopsychosocial complexity. Also recommended is the need for manageable caseloads, especially when older adults with complex needs are part of the practice milieu.
The Full Spectrum of Hepatic Steatosis in Children

Objective: We aim to identify the spectrum of etiologies of steatosis in pediatric liver biopsies. Methods: Information was collected from 155 children with steatosis on liver biopsy, including anthropometrics, laboratory, and radiologic data. Biopsies were reviewed by a liver pathologist. Results: The 4 major diagnoses associated with hepatic steatosis were nonalcoholic fatty liver disease (37%), metabolic disease (9%), oncologic disease (8%) and viral hepatitis (7%). Patients with nonalcoholic fatty liver disease were older (P = .0001) and more likely to have a body mass index z score >2 (P < .0001). Patients with a metabolic diagnosis were younger (P = .0002). Radiologic imaging of the liver yielded normal results in 44 of 108 of children (30%); 7 of these had >66% macrovesicular fatty change on biopsy, and 3 had severe fibrosis/cirrhosis. Conclusions: The range of causes of steatosis in pediatric liver biopsies is broad. Not all patients, even with advanced liver disease, had abnormalities with liver imaging, emphasizing the role for liver biopsy in certain cases.