Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy inhibitors regulate TRAIL sensitivity in human malignant cells by targeting the mitochondrial network and calcium dynamics

In a variety of cancer cell types, the pharmacological and genetic blockade of autophagy increases apoptosis induced by various anticancer drugs. These observations suggest that autophagy counteracts drug-induced apoptosis. We previously reported that in human melanoma and osteosarcoma cells, autophagy inhibitors, such as 3-methyladenine and chloroquine increased the sensitivity to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In the present study, we report that different autophagy inhibitors regulate the mitochondrial network and calcium (Ca2+) dynamics in these cells. We found that compared to tumor cells, normal fibroblasts were more resistant to the cytotoxicity of TRAIL and autophagy inhibitors used either alone or in combination. Notably, TRAIL increased the autophagic flux in the tumor cells, but not in the fibroblasts. Live-cell imaging revealed that in tumor cells, TRAIL evoked modest mitochondrial fragmentation, while subtoxic concentrations of the autophagy inhibitors led to mitochondrial fusion. Co-treatment with TRAIL and subtoxic concentrations of the autophagy inhibitors resulted in severe mitochondrial fragmentation, swelling and clustering, similar to what was observed with autophagy inhibitors at toxic concentrations. The enhanced aberration of the mitochondrial network was preceded by a reduction in mitochondrial Ca2+ loading and store-operated Ca2+ entry. On the whole, the findings of this study indicate that co-treatment with TRAIL and autophagy inhibitors leads to increased mitochondrial Ca2+ and network dysfunction in a tumor-selective manner. Therefore, the co-administration of TRAIL and autophagy inhibitors may prove to be a promising tumor-targeting approach for the treatment of TRAIL-resistant cancer cells.
2-Deoxyglucose-Modified Folate Derivative: Self-Assembling Nanoparticle Able to Load Cisplatin

Folic acid has been widely introduced into nano-drug delivery systems to give nanoparticle-targeted characteristics. However, the poor water solubility of folic acid may hinder the exploitation of its ability to load antineoplastic drugs. In the present study, we designed a new folate derivative (FA-2-DG) synthesized from folic acid and 2-Deoxyglucose (2-DG). The aim of this study was to evaluate the self-assembly characteristics of FA-2-DG, and its ability of loading cisplatin. The critical micelle concentration was 7.94 × 10−6 mol L−1. Fourier transform infrared spectroscopy indicated that hydrogen bonding interaction is a main driving force for the self–assembly of FA-2-DG. The particle was stable in pure water or 0.5% bovine serum albumin dispersions. By forming a coordination bond, the particles assembled from FA-2-DG can load cisplatin. The loading efficiency was maximal when the molar ratio of FA-2-DG to cisplatin was 2:1.
Individualized Multilayer Tensor Learning With an Application in Imaging Analysis

Abstract This work is motivated by multimodality breast cancer imaging data, which is quite challenging in that the signals of discrete tumor-associated microvesicles are randomly distributed with heterogeneous patterns. This imposes a significant challenge for conventional imaging regression and dimension reduction models assuming a homogeneous feature structure. We develop an innovative multilayer tensor learning method to incorporate heterogeneity to a higher-order tensor decomposition and predict disease status effectively through utilizing subject-wise imaging features and multimodality information. Specifically, we construct a multilayer decomposition which leverages an individualized imaging layer in addition to a modality-specific tensor structure. One major advantage of our approach is that we are able to efficiently capture the heterogeneous spatial features of signals that are not characterized by a population structure as well as integrating multimodality information simultaneously. To achieve scalable computing, we develop a new bi-level block improvement algorithm. In theory, we investigate both the algorithm convergence property, tensor signal recovery error bound and asymptotic consistency for prediction model estimation. We also apply the proposed method for simulated and human breast cancer imaging data. Numerical results demonstrate that the proposed method outperforms other existing competing methods. Supplementary materials for this article are available online.
Astro2020 Science White Paper Fundamental Physics with Radio Millisecond Pulsars

: We summarize the state of the art and future directions in using millisecond radio pulsars to test gravitation and measure intrinsic, fundamental parameters of the pulsar systems. As discussed below, such measurements continue to yield high-impact constraints on viable nuclear processes that govern the theoretically-elusive interior of neutron stars, and place the most stringent limits on the validity of general relativity in extreme environments. Ongoing and planned pulsar-timing measurements provide the greatest opportunities for measurements of compact-object masses and new general-relativistic variations in orbits.
Cognitive Wireless Power Transfer in the Presence of Reactive Primary Communication User

This paper studies a cognitive or secondary multi-antenna wireless power transfer (WPT) system over a multi-carrier channel, which shares the same spectrum with a primary wireless information transfer (WIT) system that employs adaptive water-filling power allocation. By controlling the transmit energy beamforming over sub-carriers (SCs), the secondary energy transmitter (S-ET) can directly charge the secondary energy receiver (S-ER), even purposely interfere with the primary WIT system, such that the primary information transmitter (P-IT) can reactively adjust its power allocation (based on water-filling) to facilitate the S-ER’s energy harvesting. We investigate how the secondary WPT system can exploit the primary WIT system’s reactive power allocation, for improving the wireless energy harvesting performance. In particular, our objective is to maximize the total energy received at the S-ER from both the S-ET and the P-IT, by optimizing the S-ET’s energy beamforming over SCs, subject to its maximum transmit power constraint, and the maximum interference power constraint imposed at the primary information receiver (P-IR) to protect the primary WIT. Although the formulated problem is non-convex and difficult to be optimally solved in general, we propose an efficient algorithm to obtain a high-quality solution by employing the Lagrange dual method together with an 1-D search. We also present two benchmark energy beamforming designs based on the zero-forcing (ZF) and maximum-ratio-transmission (MRT) principles, respectively, as well as the conventional design without considering the primary WIT system’s reaction. Numerical results show that our proposed design leads to significantly improved energy harvesting performance at the S-ER, as compared to these benchmark schemes.
Transcription Factors in the Development and Function of Group 2 Innate Lymphoid Cells

Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells and are a major source of innate TH2 cytokine secretion upon allergen exposure or parasitic-worm infection. Accumulating studies have revealed that transcription factors, including GATA-3, Bcl11b, Gfi1, RORα, and Ets-1, play a role in ILC2 differentiation. Recent reports have further revealed that the characteristics and functions of ILC2 are influenced by the physiological state of the tissues. Specifically, the type of inflammation strongly affects the ILC2 phenotype in tissues. Inhibitory ILC2s, memory-like ILC2s, and ex-ILC2s with ILC1 features acquire their characteristic properties following exposure to their specific inflammatory environment. We have recently reported a new ILC2 population, designated as exhausted-like ILC2s, which emerges after a severe allergic inflammation. Exhausted-like ILC2s are featured with low reactivity and high expression of inhibitory receptors. Therefore, for a more comprehensive understanding of ILC2 function and differentiation, we review the recent knowledge of transcriptional regulation of ILC2 differentiation and discuss the roles of the Runx transcription factor in controlling the emergence of exhausted-like ILC2s. The concept of exhausted-like ILC2s sheds a light on a new aspect of ILC2 biology in allergic diseases.
IntruDTree: A Machine Learning Based Cyber Security Intrusion Detection Model

Cyber security has recently received enormous attention in today’s security concerns, due to the popularity of the Internet-of-Things (IoT), the tremendous growth of computer networks, and the huge number of relevant applications. Thus, detecting various cyber-attacks or anomalies in a network and building an effective intrusion detection system that performs an essential role in today’s security is becoming more important. Artificial intelligence, particularly machine learning techniques, can be used for building such a data-driven intelligent intrusion detection system. In order to achieve this goal, in this paper, we present an Intrusion Detection Tree (“IntruDTree”) machine-learning-based security model that first takes into account the ranking of security features according to their importance and then build a tree-based generalized intrusion detection model based on the selected important features. This model is not only effective in terms of prediction accuracy for unseen test cases but also minimizes the computational complexity of the model by reducing the feature dimensions. Finally, the effectiveness of our IntruDTree model was examined by conducting experiments on cybersecurity datasets and computing the precision, recall, fscore, accuracy, and ROC values to evaluate. We also compare the outcome results of IntruDTree model with several traditional popular machine learning methods such as the naive Bayes classifier, logistic regression, support vector machines, and k-nearest neighbor, to analyze the effectiveness of the resulting security model.
The VHE Gamma-Ray View of the FSRQ PKS~1510-089

The flat spectrum radio quasar PKS 1510-089 is a monitored target in many wavelength bands due to its high variability. It was detected as a very-high-energy (VHE) $\gamma$-ray emitter with H.E. S.S. in 2009, and has since been a regular target of VHE observations by the imaging Cherenkov observatories H.E. S.S. and MAGIC. In this paper, we summarize the current state of results focusing on the monitoring effort with H.E. S.S. and the discovery of a particularly strong VHE flare in 2016 with H.E. S.S. and MAGIC. While the source has now been established as a weak, but regular emitter at VHE, no correlation with other energy bands has been established. This is underlined by the 2016 VHE flare, where the detected optical and high-energy $\gamma$-ray counterparts evolve differently than the VHE flux.
A specialized condensin complex participates in somatic nuclear maturation in Tetrahymena thermophila

Condensins are highly conserved proteins that are important for chromosome maintenance in nearly all forms of life. Although many organisms employ two forms of the condensin complex, the condensin genes in Tetrahymena have expanded even further. Here we report a form of condensin that is specifically active during sexual reproduction. This complex, condensin D, is composed of the core condensin proteins, Smc2 and Smc4, and two unique subunits, the kleisin Cph5 and Cpd2. Cpd2 is also found in somatic nuclei in vegetative cells, but is dispensable for growth and nuclear division. Immunoprecipitation experiments show that condensin D interacts with a putative member of a chromatin-remodeling complex during development. Condensin D is required for sexual reproduction and for endoreplication and genome reduction of the progeny’s somatic nuclei. Altogether, Tetrahymena possesses at least four forms of condensin to fulfill the needs of maintaining chromosomes in two different nuclei containing the somatic and germline genomes.
Improving oral healthcare using academic detailing – design of the ADVOCATE Field Studies

Abstract Background: Academic detailing (AD) is a defined form of educational outreach that can be deployed to intrinsically motivate practitioners towards improving quality of care. This paper describes the design of the ADVOCATE Field Studies. This proof of concept study aims to evaluate the feasibility, acceptability and usefulness of AD, reinforced with feedback information to promote prevention-oriented, patient-centred and evidence-based oral healthcare delivery by general dental practitioners (GDPs). Methods: Six groups of GDPs will be recruited; two groups of six to eight GDPs in each of three countries – the Netherlands, Germany and Denmark. GDPs will meet for four Academic Detailing Group (ADG) meetings for open discussions using comparative feedback data to stimulate debate about their dental practice performance and care delivery. Group meetings will be moderated using the AD methodology. Qualitative data will be collected through focus group interviews, an online discussion forum, field notes and debriefs of ADG meetings and analysed by conventional content analysis using MaxQDA software. Discussion: The results of the study will provide novel information on the feasibility, perceived acceptability and usefulness of AD and feedback data for GDPs to improve oral healthcare delivery.
A Systematic Review of Patient-Reported Outcomes for Cosmetic Indications of Botulinum Toxin Treatment

BACKGROUND Botulinum toxin (BTX) injection is the most popular cosmetic procedure in the United States. Although facial rejuvenation is considered cosmetic, physical appearance has meaningful impact on quality of life (QOL), best measured by patient-reported outcomes (PROs). Patient-reported outcomes are now often required for Food and Drug Administration approval of new pharmaceuticals. OBJECTIVE This review summarizes the PRO instruments and outcomes in evaluating patient QOL after aesthetic BTX administration. METHODS PubMed, MEDLINE, Embase, Cochrane Library, CINAHL Plus, and PsycINFO databases were searched for prospective studies using PRO instruments to directly evaluate the success of cosmetic BTX intervention. RESULTS Five psychometrically validated, facial rhytid-specific PRO tools are currently used in clinical research. Most studies addressing PROs after cosmetic BTX treatment use 1-item Likert scales evaluating overall satisfaction. BTX treatment generally resulted in improved satisfaction and QOL metrics, such as perception of youthfulness, attractiveness, restedness, affect, mood, and self-confidence. Combination treatments, whether of multiple facial areas or with multiple treatment modalities, may improve PROs even further. CONCLUSION Validated, specific PRO instruments can be used to better understand patient expectations in regards to cosmetic treatment, thus helping aesthetic dermatologists maximize patient satisfaction and retention.
Effect of ellagic acid on body fat and triglyceride reduction in healthy overweight volunteers: a randomized, double-blind, placebo-controlled parallel group study

Background: Worldwide, those categorized as overweight or obese are increasing at an alarming rate, posing a serious public health problem. Current management methods vary, ranging from surgery, dieting and exercise, to the use of synthetic and natural compounds. Previous studies reported the use of an Irvingia gabonensis extract containing ellagic acid in reducing weight and other related parameters in overweight participants. The present study investigated the efficacy of ellagic acid on anthropometric parameters as well as body fat ratio and blood triglyceride levels in otherwise healthy overweight Japanese adults.Participants and Methods: Overall, 32 participants (23 males and 9 females) aged between 20 and 64 years with a BMI of 25 or more but less than 30 kg/m2 and a visceral fat area of 80 cm2 or more were included in this randomized double-blind clinical trial. The 20-week intervention involved two groups of participants -placebo group and ellagic acid (3.0 mg per day) group. The placebo or ellagic acid was taken daily with water 30 minutes before the main meal. At baseline (T0) and at 6 and 12 weeks, anthropometric measurements (body weight, BMI, body fat ratio, waist circumference, hip circumference), CT scans and blood triglyceride levels were measured. Results: Compared to the placebo, ellagic acid brought about statistically significant reductions in body fat ratio, triglycerides, body weight, BMI, waist circumference, hip circumference and visceral fat over the twelve-week trial period.Conclusion: The use of 3.0 mg ellagic acid daily for a 12-week period was effective in reducing body fat ratio and blood triglycerides as well as other anthropometric parameters, confirming the potential use of ellagic acid in the management of overweight patients. Keywords: Ellagic acid, Irvingia gabonensis, overweight, obesity, body fat, triglyceride, body weight, metabolic syndrome.
Regulatory T Cells in an Endogenous Mouse Lymphoma Recognize Specific Antigen Peptides and Contribute to Immune Escape

In a mouse model of B-cell lymphoma, regulatory T cells suppressed antitumor responses. Treg cells recognized nonmutated self epitopes, which were characteristic of lymphoma and which were related to malignancy. Foxp3+ regulatory T cells (Tregs) sustain immune homeostasis and may contribute to immune escape in malignant disease. As a prerequisite for developing immunologic approaches in cancer therapy, it is necessary to understand the ontogeny and the antigenic specificities of tumor-infiltrating Tregs. We addressed this question by using a λ-MYC transgenic mouse model of endogenously arising B-cell lymphoma, which mirrors key features of human Burkitt lymphoma. We show that Foxp3+ Tregs suppress antitumor responses in endogenous lymphoma. Ablation of Foxp3+ Tregs significantly delayed tumor development. The ratio of Treg to effector T cells was elevated in growing tumors, which could be ascribed to differential proliferation. The Tregs detected were mainly natural Tregs that apparently recognized self-antigens. We identified MHC class II–restricted nonmutated self-epitopes, which were more prevalent in lymphoma than in normal B cells and could be recognized by Tregs. These epitopes were derived from proteins that are associated with cellular processes related to malignancy and may be overexpressed in the tumor.
Effect of interprofessional (IP) faculty development on perceptions of IP collaboration and on IP behaviors

ABSTRACT Positive interprofessional (IP) collaboration is an expectation in healthcare to ensure positive patient care outcomes, and IP faculty development is one way to promote self-efficacy gains. Our pilot study assessed interprofessional behaviors and positive interprofessional perceptions with faculty/staff using two interventions. We hypothesized that increased interprofessional faculty development in simulation would have a positive effect on faculty/staff behavior and would result in increased positivity regarding interprofessional behaviors. We collected data on positive IP perceptions. The interventions included standard and intensive faculty development in simulation as compared to a control. Our mixed-method study design consisted of qualitative and quantitative assessments, including focus group interviews and demographics and Interdisciplinary Education Perception Scale (IEPS) questionnaires. Assessments occurred at baseline, 1–3 months and 3–6 months. Data suggested better retention of positive interprofessional perceptions in the intensive training group; however, all groups had a gradual decline in positive interprofessional perceptions. Our outcomes contribute to the literature focused on improved collaborative patient care.
The moving groups as the origin of the vertical phase space spiral

Using the Gaia data release 2 (DR2), we analyzed the distribution of stars in the close vicinity of the Sun in the full 3D position-velocity space. We have found no evidence of incomplete phase mixing in the vertical direction of the disk, which could be originated by some external events. We show that the vertical phase space spiral $Z$-$V_z$ is produced by the well-known moving groups (MGs), mainly by Coma-Berenices, Pleiades-Hyades and Sirius, when the statistical characteristics (mean, median, or mode) of the azimuthal velocity $V_\varphi$ are used to analyze the distribution in the vertical position-velocity plane. This result does not invoke external perturbations and is independent on the internal dynamical mechanisms that originate the MGs. Our conclusions counterbalance current arguments in favor of short-lived (between 300 and 900 Myr) structures in the solar neighborhood. Contrarily, they support the hypothesis of a longer formation time scale (around a few Gyr) for the MGs.
A characterization of the U(Omega,m) sets of a hyperelliptic curve as Omega and m vary

In this article we consider a certain distinguished set $U(\Omega,m) \subseteq \{1,2,\ldots,2g+1,\infty\}$ that can be attached to a marked hyperelliptic curve of genus $g$ equipped with a small period matrix $\Omega$ for its polarized Jacobian. We show that as $\Omega$ and the marking $m$ vary, this set ranges over all possibilities prescribed by an argument of Poor.
The Risk of Making False Confessions: The Role of Developmental Disorders, Conduct Disorder, Psychiatric Symptoms, and Compliance

Objective: To investigate salient predictors of self-reported false confessions. The conditions included mild intellectual disability (ID), autism spectrum disorder (ASD), ADHD, conduct disorder (CD), psychiatric symptoms, and compliance. Method: The sample consisted of 386 male Scottish prisoners, who completed a diagnostic ADHD interview, psychometric tests, and a questionnaire about false confessions they had given to police over their lifetime. Results: There was a high rate of reported false confessions (33.4%); the reason for the majority (62.2%) being to “cover up for somebody else. ” CD, ADHD, psychological distress and psychiatric symptoms, and compliance were all significant predictors of false confession. When examining the influence of underlying domains of ADHD, it was found that hyperactivity/impulsivity drove the association with false confession after adjusting for coexisting CD. Conclusion: CD and ADHD were the two most powerful predictors of false confessions, with CD mediating some of the effects of ADHD.
Notes on flat pseudo-Riemannian manifolds

In these notes we survey basic concepts of affine geometry and their interaction with Riemannian geometry. We give a characterization of affine manifolds which has as counterpart those pseudo-Riemannian manifolds whose Levi-Civita connection is flat. We show that no connected semisimple Lie group admits a left invariant flat affine connection. We characterize flat pseudo-Riemannian Lie groups. For a flat left-invariant pseudo-metric on a Lie group, we show the equivalence between the completeness of the Levi-Civita connection and unimodularity of the group. We emphasize the case of flat left invariant hyperbolic metrics on the cotangent bundle of a simply connected flat affine Lie group. We also discuss Lie groups with bi-invariant pseudo-metrics and the construction of orthogonal Lie algebras.