Miracle-dz/UniFAR-FTUs huggingface dataset:
A  $16\times256$  SPAD Line Detector With a 50-ps, 3-bit, 256-Channel Time-to-Digital Converter for Raman Spectroscopy

A <inline-formula> <tex-math notation="LaTeX">$16\times256$ </tex-math></inline-formula> element single-photon avalanche diode array with a 256-channel, 3-bit on-chip time-to-digital converter (TDC) has been developed for fluorescence-suppressed Raman spectroscopy. The circuit is fabricated in <inline-formula> <tex-math notation="LaTeX">$0.35~\mu \text{m}$ </tex-math></inline-formula> high-voltage CMOS technology and it allows a measurement rate of 400 kframe/s. In order to be able to separate the Raman and fluorescence photons even in the presence of the unavoidable timing skew of the timing signals of the TDC, the time-of-arrival of every detected photon is recorded with high time resolution at each spectral point with respect to the emitted short and intensive laser pulse (~150 ps). The dynamic range of the TDC is set so that no Raman photon is lost due to the timing skew, and thus the complete time history of the detected photons is available at each spectral point. The resolution of the TDC was designed to be adjustable from 50 ps to 100 ps. The error caused by the timing skew and the residual variation in the resolution of the TDC along the spectral points is mitigated utilizing a calibration measurement from reference sample with known smooth fluorescence spectrum. As a proof of concept, the Raman spectrum of sesame seed oil, having a high fluorescence-to-Raman ratio and a short fluorescence lifetime of 1.9 ns, was successfully recorded.
Wearable Handwriting Recognition with an Inertial Sensor on a Finger Nail

In this paper, a new handwriting recognition system is proposed with an inertial sensor attached on the fingertip to automatically digitalize the cursive handwriting characters. Specifically, it focus on the issues and methods about the sensor node design, automatic spotting, reconstruction of writing trajectory, and feature selection. The performance of the system was evaluated on a set of 36 vocabularies (10 digits and 26 English lower-case characters). The recognition rate is 88.0% on SVM with user-independent 5 fold cross evaluation protocol.
Epstein-Barr Virus LMP1-Mediated Oncogenicity

ABSTRACT Epstein-Barr virus latent membrane protein 1 (LMP1) is expressed in multiple human malignancies, including nasopharyngeal carcinoma and Hodgkin and immunosuppression-associated lymphomas. LMP1 mimics CD40 signaling to activate multiple growth and survival pathways, in particular, NF-κB. LMP1 has critical roles in Epstein-Barr virus (EBV)-driven B-cell transformation, and its expression causes fatal lymphoproliferative disease in immunosuppressed mice. Here, we review recent developments in studies of LMP1 signaling, LMP1-induced host dependency factors, mouse models of LMP1 lymphomagenesis, and anti-LMP1 immunotherapy approaches.
Nursing students' attitudes toward research and development within nursing: Does writing a bachelor thesis make a difference?*†

The aim of this study was to investigate the effect of writing a bachelor's thesis on nursing students' attitudes towards research and development in nursing. The study sample consisted of 91 nursing students who were required to complete a bachelor's thesis and 89 nursing students who were not required to complete a bachelor's thesis. Data were collected via self-report questionnaire that was distributed in May and June 2012. The questionnaire comprised 3 parts: (1) demographic items; (2) questions about "scientific activities," and (3) the nursing students' attitudes towards and awareness of research and development within nursing scale (version 2). The mean age of the students was 23 (1.3) years. The students who wrote a bachelor's thesis achieved a median score of 110.0, whereas the students in the other group had a median score of 105.0 on the scale. All the items were assigned a 3 or higher. A statistically significant difference was found between the 2 groups in their attitudes towards and awareness of research (U = 3265.5; P = .025). The results of this study suggest that writing a thesis in nursing education has a positive influence on nursing students' attitudes towards and awareness of research and development in nursing.
Navigating Transporter Sciences in Pharmacokinetics Characterization Using the Extended Clearance Classification System

Membrane transporters play an important role in the absorption, distribution, clearance, and elimination of drugs. Supported by the pharmacokinetics data in human, several transporters including organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2, multidrug and toxin extrusion (MATE) proteins, P-glycoprotein and breast cancer resistance protein are suggested to be of clinical relevance. An early understanding of the transporter role in drug disposition and clearance allows reliable prediction/evaluation of pharmacokinetics and changes due to drug-drug interactions (DDIs) or genetic polymorphisms. We recently proposed an extended clearance classification system (ECCS) based on simple drug properties (i.e., ionization, permeability, and molecular weight) to predict the predominant clearance mechanism. According to this framework, systemic clearance of class 1B and 3B drugs is likely determined by the OATP-mediated hepatic uptake. Class 3A and 4 drugs, and certain class 3B drugs, are predominantly cleared by renal, wherein, OAT1, OAT3, OCT2, and MATE proteins could contribute to their active renal secretion. Intestinal efflux and uptake transporters largely influence the oral pharmacokinetics of class 3A, 3B, and 4 drugs. We discuss the paradigm of applying the ECCS framework in mapping the role of clinically relevant drug transporters in early discovery and development; thereby implementing the right strategy to allow optimization of drug exposure and evaluation of clinical risk due to DDIs and pharmacogenomics.
MONITOR-IC study, a mixed methods prospective multicentre controlled cohort study assessing 5-year outcomes of ICU survivors and related healthcare costs: a study protocol

Introduction Due to advances in critical care medicine, more patients survive their critical illness. However, intensive care unit (ICU) survivors often experience long-term physical, cognitive and mental problems, summarised as post-intensive care syndrome (PICS), impacting their health-related quality of life (HRQoL). In what frequency PICS occurs, and to what extent this influences ICU survivors’ HRQoL, is mostly unknown. The aims of this study are therefore to study the: (1) 5-year patient outcomes, (2) predictors for PICS, (3) ratio between HRQoL of ICU survivors and healthcare-related costs, and (4) care and support needs. Methods The MONITOR-IC study is a multicentre prospective controlled cohort study, carried out in ICUs in four Dutch hospitals. Patients will be included between July 2016 and July 2021 and followed for 5 years. We estimated to include 12000 ICU patients. Outcomes are the HRQoL, physical, cognitive and mental symptoms, ICU survivors’ care and support needs, healthcare use and related costs. A control cohort of otherwise seriously ill patients will be assembled to compare long-term patient-reported outcomes. We will use a mixed methods design, including questionnaires, medical data from patient records, cost data from health insurance companies and interviews with patients and family members. Ethics and dissemination Insights from this study will be used to inform ICU patients and their family members about long-term consequences of ICU care, and to develop prediction and screening instruments to detect patients at risk for PICS. Subsequently, tailored interventions can be developed and implemented to prevent and mitigate long-term consequences. Additionally, insights into the ratio between HRQoL of ICU patients and related healthcare costs during 5 years after ICU admission can be used to discuss the added value of ICU care from a community perspective. The study has been approved by the research ethics committee of the Radboud University Medical Center (2016-2724). Clinical trial registration NCT03246334
Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes

ABSTRACT African horse sickness virus (AHSV), an orbivirus in the Reoviridae family with nine different serotypes, causes devastating disease in equids. The virion particle is composed of seven proteins organized in three concentric layers, an outer layer made of VP2 and VP5, a middle layer made of VP7, and inner layer made of VP3 that encloses a replicase complex of VP1, VP4, and VP6 and a genome of 10 double-stranded RNA segments. In this study, we sought to develop highly efficacious candidate vaccines against all AHSV serotypes, taking into account not only immunogenic and safety properties but also virus productivity and stability parameters, which are essential criteria for vaccine candidates. To achieve this goal, we first established a highly efficient reverse genetics (RG) system for AHSV serotype 1 (AHSV1) and, subsequently, a VP6-defective AHSV1 strain in combination with in trans complementation of VP6. This was then used to generate defective particles of all nine serotypes, which required the exchange of two to five RNA segments to achieve equivalent titers of particles. All reassortant-defective viruses could be amplified and propagated to high titers in cells complemented with VP6 but were totally incompetent in any other cells. Furthermore, these replication-incompetent AHSV particles were demonstrated to be highly protective against homologous virulent virus challenges in type I interferon receptor (IFNAR)-knockout mice. Thus, these defective viruses have the potential to be used for the development of safe and stable vaccine candidates. The RG system also provides a powerful tool for the study of the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis. IMPORTANCE African horse sickness virus is transmitted by biting midges and causes African horse sickness in equids, with mortality reaching up to 95% in naive horses. Therefore, the development of efficient vaccines is extremely important due to major economic losses in the equine industry. Through the establishment of a highly efficient RG system, replication-deficient viruses of all nine AHSV serotypes were generated. These defective viruses achieved high titers in a cell line complemented with VP6 but failed to propagate in wild-type mammalian or insect cells. Importantly, these candidate vaccine strains showed strong protective efficacy against AHSV infection in an IFNAR−/− mouse model.
Conference Paper Recommendation for Academic Conferences

With the rapid growth of scientific publications, research paper recommendation which suggests relevant research papers to users can bring great benefits to researchers. In this paper, we focus on the problem of recommending conference papers to the conference attendees. While most of the related existing methods depend on the content-based filtering, we propose a unified conference paper recommendation method named $CPRec$ , which exploits both the contents and the authorship information of the papers. In particular, besides the contents, we exploit the relationships between a user and the authors of a paper for recommendation. In our method, we extract several features for a user-paper pair from the citation network, the coauthor network, and the contents, respectively. In addition, we derive a user’s pairwise preference towards the conference papers from the user’s bookmarked papers in each conference. Furthermore, we employ a pairwise learning to rank model which exploits the pairwise user preference to learn a function that predicts a user’s preference towards a paper based on the extracted features. We conduct a recommendation performance evaluation using real-world data and the experimental results demonstrate the effectiveness of our proposed method.
Retrovirus-Based Virus-Like Particle Immunogenicity and Its Modulation by Toll-Like Receptor Activation

ABSTRACT Retrovirus-derived virus-like particles (VLPs) are particularly interesting vaccine platforms, as they trigger efficient humoral and cellular immune responses and can be used to display heterologous antigens. In this study, we characterized the intrinsic immunogenicity of VLPs and investigated their possible adjuvantization by incorporation of Toll-like receptor (TLR) ligands. We designed a noncoding single-stranded RNA (ncRNA) that could be encapsidated by VLPs and induce TLR7/8 signaling. We found that VLPs efficiently induce in vitro dendritic cell activation, which can be improved by ncRNA encapsidation (ncRNAVLPs). Transcriptome studies of dendritic cells harvested from the spleens of immunized mice identified antigen presentation and immune activation as the main gene expression signatures induced by VLPs, while TLR signaling and Th1 signatures characterize ncRNAVLPs. In vivo and compared with standard VLPs, ncRNAVLPs promoted Th1 responses and improved CD8+ T cell proliferation in a MyD88-dependent manner. In an HIV vaccine mouse model, HIV-pseudotyped ncRNAVLPs elicited stronger antigen-specific cellular and humoral responses than VLPs. Altogether, our findings provide molecular evidence for a strong vaccine potential of retrovirus-derived VLPs that can be further improved by harnessing TLR-mediated immune activation. IMPORTANCE We previously reported that DNA vaccines encoding antigens displayed in/on retroviral VLPs are more efficient than standard DNA vaccines at inducing cellular and humoral immune responses. We aimed to decipher the mechanisms and investigated the VLPs' immunogenicity independently of DNA vaccination. We show that VLPs have the ability to activate antigen-presenting cells directly, thus confirming their intrinsic immunostimulatory properties and their potential to be used as an antigenic platform. Notably, this immunogenicity can be further improved and/or oriented by the incorporation into VLPs of ncRNA, which provides further TLR-mediated activation and Th1-type CD4+ and CD8+ T cell response orientation. Our results highlight the versatility of retrovirus-derived VLP design and the value of using ncRNA as an intrinsic vaccine adjuvant.
Analysis of vertical marginal discrepancy in feldspathic porcelain crowns manufactured with different CAD/CAM systems: Closed and open

ABSTRACT Objective: The objective of this study is to compare the marginal adaptation of feldspathic porcelain crowns using two computer-aided design/computer-aided manufacturing systems, one of them is open and the other is closed. Materials and Methods: Twenty identical titanium abutments were divided into two groups: open system (OS), where ceramic crowns were created using varied equipment and software, and closed system (CS), where ceramic crowns were created using the CEREC system. Through optical microscopy analysis, we assess the marginal adaptation of the prosthetic interfaces. The data were subjected to the distribution of normality and variance. The i-test was used for the analysis of the comparison factor between the groups, and the one-way ANOVA was used to compare the variance of crown analysis regions within the group. A significance level of 5% was considered for the analyses. Results: There was a significant difference between the systems (P = 0.007), with the CS group having the higher mean (23.75 pm ± 3.05) of marginal discrepancy when compared to the open group (17.94 pm ± 4.77). Furthermore, there were no differences in marginal discrepancy between the different points between the groups (P > 0.05). Conclusions: The studied groups presented results within the requirements set out in the literature. However, the OS used presented better results in marginal adaptation.
Lipid transfer from plants to arbuscular mycorrhiza fungi

Arbuscular mycorrhiza (AM) symbioses contribute to global carbon cycles as plant hosts divert up to 20% of photosynthate to the obligate biotrophic fungi. Previous studies suggested carbohydrates as the only form of carbon transferred to the fungi. However, de novo fatty acid (FA) synthesis has not been observed in AM fungi in absence of the plant. In a forward genetic approach, we identified two Lotus japonicus mutants defective in AM-specific paralogs of lipid biosynthesis genes (KASI and GPAT6). These mutants perturb fungal development and accumulation of emblematic fungal 16:1ω5 FAs. Using isotopolog profiling we demonstrate that 13C patterns of fungal FAs recapitulate those of wild-type hosts, indicating cross-kingdom lipid transfer from plants to fungi. This transfer of labelled FAs was not observed for the AM-specific lipid biosynthesis mutants. Thus, growth and development of beneficial AM fungi is not only fueled by sugars but depends on lipid transfer from plant hosts.
Characterization of Influenza Vaccine Hemagglutinin Complexes by Cryo-Electron Microscopy and Image Analyses Reveals Structural Polymorphisms

ABSTRACT Influenza virus afflicts millions of people worldwide on an annual basis. There is an ever-present risk that animal viruses will cross the species barrier to cause epidemics and pandemics resulting in great morbidity and mortality. Zoonosis outbreaks, such as the H7N9 outbreak, underscore the need to better understand the molecular organization of viral immunogens, such as recombinant influenza virus hemagglutinin (HA) proteins, used in influenza virus subunit vaccines in order to optimize vaccine efficacy. Here, using cryo-electron microscopy and image analysis, we show that recombinant H7 HA in vaccines formed macromolecular complexes consisting of variable numbers of HA subunits (range, 6 to 8). In addition, HA complexes were distributed across at least four distinct structural classes (polymorphisms). Three-dimensional (3D) reconstruction and molecular modeling indicated that HA was in the prefusion state and suggested that the oligomerization and the structural polymorphisms observed were due to hydrophobic interactions involving the transmembrane regions. These experiments suggest that characterization of the molecular structures of influenza virus HA complexes used in subunit vaccines will lead to better understanding of the differences in vaccine efficacy and to the optimization of subunit vaccines to prevent influenza virus infection.
BAX 855, a PEGylated rFVIII product with prolonged half-life

Summary A longer acting recombinant FVIII is expected to serve patients’ demand for a more convenient prophylactic therapy. We have developed BAX 855, a PEGylated form of Baxter’s rFVIII product ADVATE™ based on the ADVATE™ manufacturing process. The conjugation process for preparing BAX 855 uses a novel PEG reagent. The production process was adjusted to yield a rFVIII conjugate with a low PEGylation degree of about 2 moles PEG per FVIII molecule. This optimised modification degree resulted in an improved PK profile for rFVIII without compromising its specific activity. PEGylation sites were identified by employing various HPLC- and MS-based methods. These studies not only indicated that about 60% of the PEG chains are localised to the B-domain, which is cleaved off upon physiological activation during the coagulation process, but also demonstrated an excellent lot to lot consistency with regard to PEGylation site distribution. Detailed biochemical characterization further showed that PEGylated FVIII retained all the physiological functions of the FVIII molecule with the exception of binding to the LRP clearance receptor which was reduced for BAX 855 compared to ADVATE™. This might provide an explanation for the prolonged circulation time of BAX 855 as reduced receptor binding might slow-down clearance. Preclinical studies showed improved pharmacokinetic behaviour and clinically relevant prolonged efficacy compared to ADVATE™ without any signs of toxicity or elevated immunogenicity. The comprehensive preclinical data package formed the basis for approval of the phase 1 clinical study by European authorities which started in 2011.
Learning to Extract a Video Sequence from a Single Motion-Blurred Image

We present a method to extract a video sequence from a single motion-blurred image. Motion-blurred images are the result of an averaging process, where instant frames are accumulated over time during the exposure of the sensor. Unfortunately, reversing this process is nontrivial. Firstly, averaging destroys the temporal ordering of the frames. Secondly, the recovery of a single frame is a blind deconvolution task, which is highly ill-posed. We present a deep learning scheme that gradually reconstructs a temporal ordering by sequentially extracting pairs of frames. Our main contribution is to introduce loss functions invariant to the temporal order. This lets a neural network choose during training what frame to output among the possible combinations. We also address the ill-posedness of deblurring by designing a network with a large receptive field and implemented via resampling to achieve a higher computational efficiency. Our proposed method can successfully retrieve sharp image sequences from a single motion blurred image and can generalize well on synthetic and real datasets captured with different cameras.
Diversity of Arbuscular Mycorrhizal Fungi and Their Roles in Ecosystems

Abstract Arbuscular mycorrhizal fungi (AMF) have mutualistic relationships with more than 80% of terrestrial plant species. This symbiotic relationship is ancient and would have had important roles in establishment of plants on land. Despite their abundance and wide range of relationship with plant species, AMF have shown low species diversity. However, molecular studies have suggested that diversity of these fungi may be much higher, and genetic variation of AMF is very high within a species and even within a single spore. Despite low diversity and lack of host specificity, various functions have been associated with plant growth responses to arbuscular mycorrhizal fungal colonization. In addition, different community composition of AMF affects plants differently, and plays a potential role in ecosystem variability and productivity. AMF have high functional diversity because different combinations of host plants and AMF have different effects on the various aspects of symbiosis. Consequently, recent studies have focused on the different functions of AMF according to their genetic resource and their roles in ecosystem functioning. This review summarizes taxonomic, genetic, and functional diversities of AMF and their roles in natural ecosystems.
Towards Distributed Model Analytics with Apache Spark

The growing number of models and other related artefacts in model-driven engineering has recently led to the emergence of approaches and tools for analyzing and managing them on a large scale. The framework SAMOS applies techniques inspired by information retrieval and data mining to analyze large sets of models. As the data size and analysis complexity goes up, however, further scalability is needed. In this paper we extend SAMOS to operate on Apache Spark, a popular engine for distributed Big Data processing, by partitioning the data and parallelizing the comparison and analysis phase. We present preliminary studies using a cluster infrastructure and report the results for two datasets: one with 250 Ecore metamodels where we detail the performance gain with various settings, and a larger one of 7.3k metamodels with nearly one million model elements for further demonstrating scalability.