Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of Novel HIV Entry Inhibitors for the CXCR4 Receptor by Prospective Virtual Screening

The process of HIV entry begins with the binding of the viral envelope glycoprotein gp120 to both the CD4 receptor and one of CXCR4 or CCR5 chemokine coreceptors. There is currently considerable interest in developing novel ligands which can attach to these coreceptors and hence block virus-cell fusion. This article compares the application of structure-based (docking) and ligand-based (QSAR analyses, pharmacophore modeling, and shape matching) virtual screening tools to find new potential HIV entry inhibitors for the CXCR4 receptor. The comparison is based on retrospective virtual screening of a library containing different known CXCR4 inhibitors from the literature, a smaller set of active CXCR4 inhibitors selected from a large combinatorial virtual library and synthesized by us, and some druglike presumed inactive molecules as the reference set. The enrichment factors and diversity of the retrieved molecular scaffolds in the virtual hit lists was determined. Once the different virtual screening approaches had been validated and the best parameters had been selected, prospective virtual screening of our virtual library was applied to identify new anti-HIV compounds using the same protocol as in the retrospective virtual screening analysis. The compounds selected using these computational tools were subsequently synthesized and assayed and showed activity values ranging from 4 to 0.022 microg/mL.
Genome-Wide Analysis of Simple Sequence Repeats in Cabbage (Brassica oleracea L.)

Cabbage (Brassica oleracea L. var. capitata) accounts for a critical vegetable crop belonging to Brassicaceae family, and it has been extensively planted worldwide. Simple sequence repeats (SSRs), the markers with high polymorphism and co-dominance degrees, offer a crucial genetic research resource. The current work identified totally 64,546 perfect and 93,724 imperfect SSR motifs in the genome of the cabbage ‘TO1000. ’ Then, we divided SSRs based on the respective overall length and repeat number into different linkage groups. Later, we characterized cabbage genomes from the perspectives of motif length, motif-type classified and SSR level, and compared them across cruciferous genomes. Furthermore, a large set of 64,546 primer pairs were successfully identified, which generated altogether 1,113 SSR primers, including 916 (82.3%) exhibiting repeated and stable amplification. In addition, there were 32 informative SSR markers screened, which might decide 32 cabbage genotypes for their genetic diversity, with level of polymorphism information of 0.14–0.88. Cultivars were efficiently identified by the new strategy designating manual diagram for identifying cultivars. Lastly, 32 cabbage accessions were clearly separately by five Bol-SSR markers. Besides, we verified whether such SSRs were available and transferable in 10 Brassicaceae relatives. Based on the above findings, those genomic SSR markers identified in the present work may facilitate cabbage research, which lay a certain foundation for further gene tagging and genetic linkage analyses, like marker-assisted selection, genetic mapping, as well as comparative genomic analysis.
Tumor‐associated macrophages induce lymphangiogenesis in cervical cancer via interaction with tumor cells

Our studies were conducted to investigate the clinical and functional significance of tumor‐associated macrophages (TAMs) in cervical tumor lymphatic metastasis. We found that the increase in macrophages in tumor stroma is significantly associated with lymphatic metastasis (p = 0.017), through performing immunohistochemical staining in 111 cervical samples (55 invasive squamous carcinomas of uterine cervix, 27 cervical intraepithelial neoplasms III, and 29 normal cervix). The human lymphatic endothelial cells (HLEC), which were cultured in conditioned medium of cervical cancer cell‐macrophage coculture, formed more tube‐like structures in vitro, when compared with those in conditioned mediums of LEC, normal cervical epithelium, single macrophage, and single cervical cancer cell (all p < 0.001). The mRNA expressions of IL‐1β and IL‐8 in cervical cancer cells cocultured with macrophages were increased, compared with those in cervical cancer cell cultured alone (pIL‐1β < 0.05 and pIL‐8 < 0.01). Meanwhile, the mRNA expression of VEGF‐C and VEGF‐A was increased in macrophages cocultured with cervical cancer cells, compared with the expression in those macrophages cultured alone (both p < 0.05). Taken together, the results suggest that TAMs promote lymphangiogenesis mainly through interaction with surrounding cervical cancer cells.
Total dietary antioxidant capacity, individual antioxidant intake and breast cancer risk: The Rotterdam study

Some studies suggest a favorable role of antioxidants on breast cancer risk but this is still inconclusive. The aim of this study was to assess whether overall dietary antioxidant capacity, as assessed by dietary ferric reducing antioxidant potential (FRAP), and individual dietary antioxidant intake were associated with breast cancer risk. Data was used from women participating in the Rotterdam Study, a prospective cohort study among subjects aged 55 years and older (N = 3,209). FRAP scores and antioxidant intake (i.e., vitamin A, C, E, selenium, flavonoids and carotenoids) was assessed at baseline by a food frequency questionnaire. Incident cases of breast cancer were confirmed through medical reports. During a median follow‐up of 17 years, 199 cases with breast cancer were identified. High dietary FRAP score was associated with a lower risk of breast cancer [hazard ratio (HR): 0.68; 95% confidence intervals (CI): 0.49, 0.96]. No overall association between individual antioxidant intake and breast cancer risk was found. However, low intake of alpha carotene and beta carotene was associated with a higher risk of breast cancer among smokers (HR: 2.48; 95% CI: 1.21, 5.12 and HR: 2.31; 95% CI: 1.12, 4.76 for alpha and beta carotene, respectively) and low intake of flavonoids was associated with breast cancer risk in women over the age of 70 (HR: 1.80; 95% CI: 1.09, 2.99). These results suggest that high overall dietary antioxidant capacity is associated with a lower risk of breast cancer. Individual effects of dietary carotenoids and dietary flavonoids may be restricted to subgroups such as smokers and elderly.
Robust Low-Complexity MMSE Precoding Algorithm for Cloud Radio Access Networks

In this paper, the robust transceiver design for multi-cell distributed antenna systems is investigated, which is of great importance for the future mobile communication network architecture namely cloud radio access networks (C-RAN). In order to make the algorithm suitable for the multi-cell network with a large number of remote radio heads (RRHs), a low complexity robust design is proposed based on alternating direction method of multipliers (ADMM) algorithm. Exploiting the elegant properties of ADMM algorithm, the complicated relationship between the optimization objective and the per-antenna power constraint is decoupled by introducing an auxiliary variable. Meanwhile the complexity of the proposed algorithm is also significantly reduced. Finally, it is demonstrated by the simulation that the proposed robust algorithm has better performance than the existing non-robust design.
Patient-reported visual function outcomes improve after ranibizumab treatment in patients with vision impairment due to diabetic macular edema: randomized clinical trial.

IMPORTANCE Few data are available on relative changes in vision-related function after treatment for diabetic macular edema (DME). OBJECTIVE To determine the impact of intravitreal ranibizumab, 0.5 mg, compared with laser on patient-reported visual function. DESIGN Phase 3, randomized, double-masked, 12-month study (RESTORE). SETTING Outpatient retina practices in Australia, Canada, and Europe. PARTICIPANTS Patients 18 years or older with type 1 or 2 diabetes mellitus and visual impairment due to DME. INTERVENTIONS Patients were randomized to ranibizumab plus sham laser (n = 116), ranibizumab plus laser (n = 118), or sham injections plus laser (n = 111). Ranibizumab and sham injections were given for 3 consecutive months then as needed; laser or sham laser treatment was given at baseline then as needed. MAIN OUTCOMES AND MEASURES National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) scores at 0, 3, and 12 months for patients receiving 1 or more study treatments with 1 or more postbaseline NEI VFQ-25 assessments and last observation carried forward for missing data. RESULTS Mean baseline NEI VFQ-25 composite scores were 72.8, 73.5, and 74.1 in the ranibizumab, laser, and ranibizumab plus laser groups, respectively. At 12 months, the mean composite scores (95% CIs) improved by 5.0 (ranibizumab vs laser, 2.6 to 7.4; P = .01 vs laser) and 5.4 (ranibizumab plus laser vs laser alone, 3.3 to 7.4; P = .004 vs laser) from baseline in the ranibizumab and ranibizumab plus laser groups, respectively, compared with 0.6 (-1.8 to 3.0) for the laser group. Near activities scores improved by 9.0 (ranibizumab vs laser, 5.0 to 13.0; P = .01) and 9.1 (ranibizumab plus laser vs laser, 5.6 to 12.6; P = .006) compared with 1.1 (-3.0 to 5.2) for the laser group, whereas distance activities scores improved by 5.3 (ranibizumab vs laser, 1.8 to 8.9; P = .04) and 5.6 (ranibizumab plus laser vs laser, 2.3 to 9.0; P = .03) compared with 0.4 (-3.1 to 3.8) for the laser group. Patients with better baseline visual acuity or lower central retinal thickness had greater improvements with ranibizumab treatment compared with laser in composite and some subscale scores compared with patients with worse visual acuity or higher central retinal thickness. CONCLUSIONS AND RELEVANCE These data provide vision-related, patient-reported outcome evidence that mirrors visual acuity outcomes and supports benefits from ranibizumab or ranibizumab plus laser treatment for patients with DME and characteristics similar to those enrolled in this randomized clinical trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00687804.
Introduction to Spark 2.0 for Database Researchers

Originally started as an academic research project at UC Berkeley, Apache Spark is one of the most popular open source projects for big data analytics. Over 1000 volunteers have contributed code to the project; it is supported by virtually every commercial vendor; many universities are now offering courses on Spark. Spark has evolved significantly since the 2010 research paper: its foundational APIs are becoming more relational and structural with the introduction of the Catalyst relational optimizer, and its execution engine is developing quickly to adopt the latest research advances in database systems such as whole-stage code generation. This tutorial is designed for database researchers (graduate students, faculty members, and industrial researchers) interested in a brief hands-on overview of Spark. This tutorial covers the core APIs for using Spark 2.0, including DataFrames, Datasets, SQL, streaming and machine learning pipelines. Each topic includes slide and lecture content along with hands-on use of a Spark cluster through a web-based notebook environment. In addition, we will dive into the engine internals to discuss architectural design choices and their implications in practice. We will guide the audience to "hack" Spark by extending its query optimizer to speed up distributed join execution.
CK1ε targets Cdc25A for ubiquitin-mediated proteolysis under normal conditions and in response to checkpoint activation

Cdc25A phosphatase, which is essential in cell cycle progression, is degraded by the proteasome throughout interphase and in response to genotoxic stress. Phosphorylation of Cdc25A on Ser82 in the DSG motif is important in the recognition by β-TrCP, resulting in targeting of Cdc25A for ubiquitination. Chk1 is known to phosphorylate Cdc25A on Ser76, and NEK11 or CK1α relays phosphorylation of Cdc25A to Ser82 in a hierarchical manner. In this study, we found that CK1ε has unique enzymatic activity on the serine residue in the DSG motif using a β-catenin N-terminal region as a substrate. We then examined whether CK1ε has activity on the DSG motif of Cdc25A. We found CK1ε directly phosphorylated Ser82 without any prior phosphorylation of Cdc25A, and depletion of CK1ε stabilized the cellular Cdc25A in 293 cells. Moreover, we found that CK1ε also has activity as a relaying kinase like NEK11 or CK1α when the cell is exposed to DNA damage. Taken together, our results indicate that CK1ε regulates the cellular levels of Cdc25A in parallel with Chk1-dependent Cdc25A degradation, contributing to the precise control of cell division.
Wavelet electromagnetic field processing: Multidimensional fast wavelet transform decomposition of time and frequency domain electromagnetic fields

The research in the computational electromagnetics (CEM) community over the past several decades has lead to the parallelization of time and frequency domain CEM codes that harness the computational power of large scale, parallel and distributed computing platforms [1, 2]. Whether differential equation [2] or integral equation [1] based methods are employed for radiation and scattering analyses, parallel electromagnetic solvers often lead to overwhelming amounts of data [3] that may be difficult (if not impossible) to process on personal computers for timely interpretation, preparation and exposition of the numerical results that demonstrate the versatility of a given CEM method. Moreover, information regarding the spatial and/or temporal locations of highly varying oscillatory electromagnetic fields may not be known a priori. Scientists and engineers may need to localize specific regions in the solution space where the fields are highly varying [4]. It is thus imperative that algorithms be developed that can rigorously and efficiently inspect field solutions such that the underlying electromagnetic wave physics for a given problem is clearly understood.
Does Insurance Promote Economic Growth

Damian Ward and Ralf Zurbruegg, 'Does insurance promote economic growth? Evidence fro OECD countries', The Journal of Risk and Insurance, Vol. 67 (4): 489-506, 2000, doi: 10.2307/253847. © The Journal of Risk and Insurance, 2000.
Methotrexate-conjugated quantum dots: synthesis, characterisation and cytotoxicity in drug resistant cancer cells

Abstract Methotrexate (MTX), a folic acid derivative, is a potent anticancer used for treatment of different malignancies, but possible initiation of drug resistance to MTX by cancer cells has limited its applications. Nanoconjugates (NCs) of MTX to quantum dots (QDs) may favour the cellular uptake via folate receptors (FRs)-mediated endocytosis that circumvents the efflux functions of cancer cells. We synthesised MTX-conjugated l-cysteine capped CdSe QDs (MTX-QD nanoconjugates) and evaluated their internalisation and cytotoxicity in the KB cells with/without resistancy to MTX. The NCs were fully characterised by high resolution transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and optical spectroscopy. Upon conjugation with MTX, the photoluminescence (PL) properties of QDs altered, while an obvious quenching in PL of QDs was observed after physical mixing. The MTX-QD nanoconjugates efficiently internalised into the cancer cells, and induced markedly high cytotoxicity (IC50, 12.0 µg/mL) in the MTX-resistant KB cells as compared to the free MTX molecules (IC50,105.0 µg/mL), whereas, these values were respectively about 7.0 and 0.6 µg/mL in the MTX-sensitive KB cells. Based on these findings, the MTX-QD nanoconjugates are proposed for the targeted therapy of MTX-resistant cancers, which may provide an improved outcome in the relapsed FR-overexpressing cancers.
Features of Influenza HA Required for Apical Sorting Differ from Those Required for Association with DRMs or MAL

The influenza virus hemagglutinin (HA) is sorted to the apical membrane in polarized epithelial cells and associates with detergent‐resistant membranes (DRMs). By systematic mutagenesis of the transmembrane residues, we show that hemagglutinin requires 10 contiguous transmembrane amino acids to enter detergent‐resistant membranes and that the surface of the trimeric hemagglutinin transmembrane domain facing the lipid environment as well as that facing the interior of the trimer is important for stable association with detergent‐resistant membranes. However, association with detergent‐resistant membranes was not required for apical sorting. MAL/VIP17 is a protein that is required for apical transport and a small fraction of hemagglutinin co‐precipitates with MAL. Mutations that prevented HA from being isolated in detergent‐resistant membranes decreased co‐precipitation with MAL. The hemagglutinin and MAL that co‐precipitated were contained in a detergent‐resistant vesicle. However, most of the co‐precipitation of newly synthesized hemagglutinin with MAL occurred only after the majority of hemagglutinin reached the cell surface. Both the timing and the limited extent of co‐precipitation suggest that the majority of vesicles containing hemagglutinin and MAL are not the detergent‐resistant membrane transport intermediates carrying hemagglutinin from the TGN to the apical surface.
Exploiting the Trade Potential from Integration: Analysing the Impact of Free Trade Agreements between ASEAN and India and China

In this article, we use the technique of stochastic frontier estimation for the structural gravity model to analyse Vietnam’s bilateral trade and evaluate its exploitation of trade efficiency before and after its free trade agreements (FTAs) with China and India entered into force. The results from Vietnam’s bilateral trade data between 2000 and 2015 show that the ASEAN–India Free Trade Agreement (AIFTA) has had a positive impact on Vietnam’s bilateral trade flows while we found a remarkably negative effect on Vietnam’s exports but not imports after the entry into force of the ASEAN-China Free Trade Agreement (ACFTA). In addition, Vietnam’s participation in the regional trade agreements (RTAs) and FTAs has significantly reduced the costs of trade over time, and these impacts on Vietnam’s imports are much higher than those on Vietnam's exports.
An organizational approach for the assessment of DNA adduct data in risk assessment: case studies for aflatoxin B1, tamoxifen and vinyl chloride

Abstract The framework analysis previously presented for using DNA adduct information in the risk assessment of chemical carcinogens was applied in a series of case studies which place the adduct information into context with the key events in carcinogenesis to determine whether they could be used to support a mutagenic mode of action (MOA) for the examined chemicals. Three data-rich chemicals, aflatoxin B1 (AFB1), tamoxifen (Tam) and vinyl chloride (VCl) were selected for this exercise. These chemicals were selected because they are known human carcinogens and have different characteristics: AFB1 forms a unique adduct and human exposure is through contaminated foods; Tam is a pharmaceutical given to women so that the dose and duration of exposure are known, forms unique adducts in rodents, and has both estrogenic and genotoxic properties; and VCl, to which there is industrial exposure, forms a number of adducts that are identical to endogenous adducts found in unexposed people. All three chemicals produce liver tumors in rats. AFB1 and VCl also produce liver tumors in humans, but Tam induces human uterine tumors, only. To support a mutagenic MOA, the chemical-induced adducts must be characterized, shown to be pro-mutagenic, be present in the tumor target tissue, and produce mutations of the class found in the tumor. The adducts formed by AFB1 and VCl support a mutagenic MOA for their carcinogenicity. However, the data available for Tam shows a mutagenic MOA for liver tumors in rats, but its carcinogenicity in humans is most likely via a different MOA.
Performance Optimization of Left Ventricular Assistance A Computer Model Study

Performance of temporary parallel left ventricular assistance was investigated and the theoretic conditions leading to optimal behavior of the mechanical system were explored. Computer models of nonpulsatile and pulsatile left ventricular assist devices (LVADs) were incorporated into a previously reported closed-loop simulation of the canine cardiovascular system. Assuming the assisted heart was capable of recovery, LVAD performance was assessed based on both myocardial oxygen balance and cardiac output. With a synchronous LVAD, and operating in a counterpulsation mode, these variables were sensitive to the phasing of pump ejection. Maximum reduction in cardiac oxygen consumption, maximum increase in oxygen availability, and maximum increase in cardiac output with the atrio-aortic device were obtained when pump ejection immediately followed aortic valve closure. These variables were directly proportional to the magnitude of bypass volume. The pulsatile asynchronous and nonpulsatile LVAD models affected oxygen balance in a similar manner, but neither performed so well as the synchronous model when equal bypass volumes were used. Ventricular uptake of blood provided a further 27% decrease in oxygen consumption and further 78% increase in oxygen availability than atrial uptake. In summary, the model predicted that the pulsatile synchronous LVAD, filling from the ventricle during heart systole and ejecting into either the ascending or descending aorta just after ventricular systole, would be most beneficial to both myocardial oxygen balance and cardiac output.
Multiple event detection for multistatic radar in the presence of non-ideal channels: Modulation and power control

We study the distributed detection of multiple hypotheses via a multistatic radar system where N geographically separated radar receivers communicate their local decisions to a fusion center over an orthogonal multiple access channel. Due to the availability of only limited bandwidth to the fusion center, each receiver forwards a locally processed information compressed to a few bits. Each receiver observes multiple signals, each of which is associated with K different binary hypothesis testing problems, and then makes K binary decisions, 0 or 1, for each test. The resulting bit sequence is transferred to a fusion center over an additive white Gaussian channel using an uncoded digital modulation technique. The fusion center uses the signals received from radar receivers and makes the final decision for each event. We analyze the impact of modulation and power control on the detection performance of multiple events, and determine the power-detection rate performance for various uncoded modulation schemes. We also investigate the use of hierarchical modulation to achieve some desired power-detection rate region for the proposed scheme. It is shown via simulations that one can achieve desired detection performance trade-off among different hypothesis testing problems by varying local decision rules, modulation and power control setting and constellation selection.
A First Baseline for the Magnets in the High Luminosity LHC Insertion Regions

The High Luminosity LHC (HL-LHC) project aims at accumulating 3000 fb-1 in the years 2023-2035, i.e., ten times more w.r. t. the nominal LHC performance expected for 2010-2021. One key element to reach this challenging performance is a new insertion region to reduce the beam size in the interaction point by approximately a factor two. This requires larger aperture magnets in the region spanning from the interaction point to the matching section quadrupoles. This aperture has been fixed to 150 mm for the inner triplet quadrupoles in 2012. In this paper, we give a first baseline of the interaction region. We discuss the main motivations that lead us to choose the technology, the combination of fields/gradients and lengths, the apertures, the quantity of superconductor, and the operational margin. Key elements are also the constraints given by the energy deposition in terms of heat load and radiation damage; we present the main features related to shielding and heat removal.