Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual Ligand Insertion in gB and gD of Oncolytic Herpes Simplex Viruses for Retargeting to a Producer Vero Cell Line and to Cancer Cells

ABSTRACT Oncolytic viruses gain cancer specificity in several ways. Like the majority of viruses, they grow better in cancer cells that are defective in mounting the host response to viruses. Often, they are attenuated by deletion or mutation of virulence genes that counteract the host response or are naturally occurring oncolytic mutants. In contrast, retargeted viruses are not attenuated or deleted; their cancer specificity rests on a modified, specific tropism for cancer receptors. For herpes simplex virus (HSV)-based oncolytics, the detargeting-retargeting strategies employed so far were based on genetic modifications of gD. Recently, we showed that even gH or gB can serve as retargeting tools. To enable the growth of retargeted HSVs in cells that can be used for clinical-grade virus production, a double-retargeting strategy has been developed. Here we show that several sites in the N terminus of gB are suitable to harbor the 20-amino-acid (aa)-long GCN4 peptide, which readdresses HSV tropism to Vero cells expressing the artificial GCN4 receptor and thus enables virus cultivation in the producer noncancer Vero-GCN4R cell line. The gB modifications can be combined with a minimal detargeting modification in gD, consisting in the deletion of two residues, aa 30 and 38, and replacement of aa 38 with the scFv to human epidermal growth factor receptor 2 (HER2), for retargeting to the cancer receptor. The panel of recombinants was analyzed comparatively in terms of virus growth, cell-to-cell spread, cytotoxicity, and in vivo antitumor efficacy to define the best double-retargeting strategy. IMPORTANCE There is increasing interest in oncolytic viruses, following FDA and the European Medicines Agency (EMA) approval of HSV OncovexGM-CSF, and, mainly, because they greatly boost the immune response to the tumor and can be combined with immunotherapeutic agents, particularly checkpoint inhibitors. A strategy to gain cancer specificity and avoid virus attenuation is to retarget the virus tropism to cancer-specific receptors of choice. Cultivation of fully retargeted viruses is challenging, since they require cells that express the cancer receptor. We devised a strategy for their cultivation in producer noncancer Vero cell derivatives. Here, we developed a double-retargeting strategy, based on insertion of one ligand in gB for retargeting to a Vero cell derivative and of anti-HER2 ligand in gD for cancer retargeting. These modifications were combined with a minimally destructive detargeting strategy. This study and its companion paper explain the clinical-grade cultivation of retargeted oncolytic HSVs and promote their translation to the clinic.
Mechanical behaviour of asphalt binders at high temperatures and specification for rutting

This is a study of the temperature dependence of the mechanical behaviour of asphalt binders. Creep-recovery and steady-shear experiments were conducted on selected modified and unmodified binders at 60, 70 and 80 C, and the results were used to characterise the binders using a nonlinear viscoelastic model. Experimental and model parameters obtained in this manner were all found to follow Arrhenius relationship with temperature. Rutting parameters such as zero shear viscosity, non-recoverable creep compliance, Superpave criterion and apparent viscosity were predicted using the model, and were also found to follow an Arrhenius relationship with temperature. However, it was found that the temperature sensitivity of the binders can vary considerably. Issues with ‘failure temperature’-based grading systems, such as the Superpave high temperature specification, were analysed in the light of the Arrhenius-like temperature dependence and varying temperature sensitivities. Possible ways to consider varying temperature sensitivities in the high temperature specification are proposed.
NetMaster: Taming Energy Devourers on Smartphones

Smartphones nowadays are installed with diverse applications, each of which consumes energy and bandwidth. As more and more applications are crowded into a smart- phone, they cause serious problems with regard to battery life and bandwidth utilization. Existing proposals to tackle such challenges usually resort to two ways: avoiding energy- consuming network activities or improving communication efficiency in terms of power consumption. Those approaches either affect the smartphone users' experience, or offer little benefit in prolonging the battery life. Motivated by insightful understanding of users' habit, we in this paper propose a novel approach to orchestrate network activities of smartphone applications, based on user's habit. We implement our approach on smartphones as a middleware service called NetMaster. The performance evaluation with real traces shows that NetMaster reduces energy consumption of network activities by 77.8% in average and increases network bandwidth utilization by over 200%. The user experience is surprisingly well preserved. The chance of undesired interrupt during normal usage is less than 1%.
Through the Glance Mug: A Familiar Artefact to Support Opportunistic Search in Meetings

During collocated meetings, the spontaneous need for information, called opportunistic search, might arise while conversing. However, using smartphones to look up information might be disruptive, disrespectful or even embarrassing in social contexts. We propose an alternative instrument for this practice: Glance Mug, a touch-sensitive mug prototype that listens to the conversation and displays browsable content-driven results on its inner screen. We organized 15 pairs of one-to-one meetings between students to gather user reflections. The user study revealed that the mug has the potential for supporting instant search and affords sufficient subtlety to conceal user actions. Yet, it provoked some anxiety for the users in maintaining eye contact with their partners. Our main contributions are the context-aware mug concept tested in a real-life setting and the analysis through Hornecker and Buur's Tangible Interaction Framework that discusses its design space, and its impact on the users and social interaction.
ESFR core optimization and uncertainty studies

In the European Sodium Fast Reactor (ESFR) project supported by EURATOM in 2008-2012, a concept for a large 3600 MWth sodium-cooled fast reactor design was investigated. In particular, reference core designs with oxide and carbide fuel were optimized to improve their safety parameters. Uncertainties in these parameters were evaluated for the oxide option. Core modifications were performed first to reduce the sodium void reactivity effect. Introduction of a large sodium plenum with an absorber layer above the core and a lower axial fertile blanket improve the total sodium void effect appreciably, bringing it close to zero for a core with fresh fuel, in line with results obtained worldwide, while not influencing substantially other core physics parameters. Therefore an optimized configuration, CONF2, with a sodium plenum and a lower blanket was established first and used as a basis for further studies in view of deterioration of safety parameters during reactor operation. Further options to study were an inner fertile blanket, introduction of moderator pins, a smaller core height, special designs for pins, such as 'empty' pins, and subassemblies. These special designs were proposed to facilitate melted fuel relocation in order to avoid core re-criticality under severe accident conditions. In the paper further CONF2 modifications are compared in terms of safety and fuel balance. They may bring further improvements in safety, but their accurate assessment requires additional studies, including transient analyses. Uncertainty studies were performed by employing a so-called Total Monte-Carlo method, for which a large number of nuclear data files is produced for single isotopes and then used in Monte-Carlo calculations. The uncertainties for the criticality, sodium void and Doppler effects, effective delayed neutron fraction due to uncertainties in basic nuclear data were assessed for an ESFR core. They prove applicability of the available nuclear data for ESFR optimization studies.
β-mannanase and mannan oligosaccharides in broiler chicken feed

The study aimed to evaluate the use of β-mannanase and mannan oligosaccharides (MOS) to replace growth promoters in broiler diets. Four hundred male Cobb broiler chicks were used, with initial weight of 45±1g, distributed in a completely randomized design with five treatments and eight repetitions of ten birds. The treatments were: basal feed; basal feed without growth promoter; basal feed without growth promoter + β-mannanase; basal feed without growth promoter + MOS; and basal feed without growth promoter + β-mannanase + MOS. The feed intake of the birds increased in response to dietary treatments compared to basal diet during the period 1-21 days of age. A higher weight gain and improved feed conversion was found at 42 days of age among birds that had received the basal diet without growth promoter + MOS. The absolute weight at slaughter, relative carcass and prime cuts except breast weights improved in response to dietary treatments compared to the basal diet at 42 days of age. No difference was observed in relative weight of the liver, while significant differences were found in the weight of heart, gizzard, and abdominal fat. It was concluded that β-mannanase and MOS can replace the growth promoters in broiler diets without compromising production and economic performance. However, the association of these products into the feed may cause negative interaction that reduces the broiler chickens' performance
Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus–hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed. DOI: http://dx.doi. org/10.7554/eLife.06576. 001
Beyond sixfold coordinated Si in SiO2 glass at ultrahigh pressures

Significance The combination of multichannel collimator and diamond anvil cells enabled the investigation of the real-space structure of an amorphous material >100 GPa. We have measured the structure of SiO2 glass by angle-dispersive X-ray diffraction up to 172 GPa. Our results are in agreement with existing data up to 50 GPa showing a sharp change from fourfold to sixfold Si–O coordination number (CN). However, at higher pressures, CN continuously increases to values beyond 6 without sharp structural changes. The behavior of SiO2 glass at high pressure serves as a model for more complex silicate glasses and melts. Thus, our results provide experimental insight into the structural evolution of silicate glasses and melts at ultrahigh pressures. We investigated the structure of SiO2 glass up to 172 GPa using high-energy X-ray diffraction. The combination of a multichannel collimator with diamond anvil cells enabled the measurement of structural changes in silica glass with total X-ray diffraction to previously unachievable pressures. We show that SiO2 first undergoes a change in Si–O coordination number from fourfold to sixfold between 15 and 50 GPa, in agreement with previous investigations. Above 50 GPa, the estimated coordination number continuously increases from 6 to 6.8 at 172 GPa. Si–O bond length shows first an increase due to the fourfold to sixfold coordination change and then a smaller linear decrease up to 172 GPa. We reconcile the changes in relation to the oxygen-packing fraction, showing that oxygen packing decreases at ultrahigh pressures to accommodate the higher than sixfold Si–O coordination. These results give experimental insight into the structural changes of silicate glasses as analogue materials for silicate melts at ultrahigh pressures.
Image Classification of Human Carcinoma Cells Using Complex Wavelet-Based Covariance Descriptors

Cancer cell lines are widely used for research purposes in laboratories all over the world. Computer-assisted classification of cancer cells can alleviate the burden of manual labeling and help cancer research. In this paper, we present a novel computerized method for cancer cell line image classification. The aim is to automatically classify 14 different classes of cell lines including 7 classes of breast and 7 classes of liver cancer cells. Microscopic images containing irregular carcinoma cell patterns are represented by subwindows which correspond to foreground pixels. For each subwindow, a covariance descriptor utilizing the dual-tree complex wavelet transform (DT-WT) coefficients and several morphological attributes are computed. Directionally selective DT-WT feature parameters are preferred primarily because of their ability to characterize edges at multiple orientations which is the characteristic feature of carcinoma cell line images. A Support Vector Machine (SVM) classifier with radial basis function (RBF) kernel is employed for final classification. Over a dataset of 840 images, we achieve an accuracy above 98%, which outperforms the classical covariance-based methods. The proposed system can be used as a reliable decision maker for laboratory studies. Our tool provides an automated, time- and cost-efficient analysis of cancer cell morphology to classify different cancer cell lines using image-processing techniques, which can be used as an alternative to the costly short tandem repeat (STR) analysis. The data set used in this manuscript is available as supplementary material through http://signal.ee. bilkent.edu. tr/cancerCellLineClassificationSampleImages.html.
Learning a No-Reference Quality Assessment Model of Enhanced Images With Big Data

In this paper, we investigate into the problem of image quality assessment (IQA) and enhancement via machine learning. This issue has long attracted a wide range of attention in computational intelligence and image processing communities, since, for many practical applications, e.g., object detection and recognition, raw images are usually needed to be appropriately enhanced to raise the visual quality (e.g., visibility and contrast). In fact, proper enhancement can noticeably improve the quality of input images, even better than originally captured images, which are generally thought to be of the best quality. In this paper, we present two most important contributions. The first contribution is to develop a new no-reference (NR) IQA model. Given an image, our quality measure first extracts 17 features through analysis of contrast, sharpness, brightness and more, and then yields a measure of visual quality using a regression module, which is learned with big-data training samples that are much bigger than the size of relevant image data sets. The results of experiments on nine data sets validate the superiority and efficiency of our blind metric compared with typical state-of-the-art full-reference, reduced-reference and NA IQA methods. The second contribution is that a robust image enhancement framework is established based on quality optimization. For an input image, by the guidance of the proposed NR-IQA measure, we conduct histogram modification to successively rectify image brightness and contrast to a proper level. Thorough tests demonstrate that our framework can well enhance natural images, low-contrast images, low-light images, and dehazed images. The source code will be released at https://sites.google. com/site/guke198701/publications.
Dual-Function Hybrid Beamforming and Transmit Diversity Aided Millimeter Wave Architecture

In this correspondence, we propose a dual-function hybrid beamforming architecture, where the antenna array is split into sub-arrays that are separated by a sufficiently large distance so that each sub-array experiences independent fading. The proposed architecture attains the dual-functions of beamforming and diversity. We then demonstrate that splitting the array into two sub-arrays provides the best performance in terms of the achievable rate as a benefit of the diversity gain obtained in addition to the beamforming gain. However, the performance starts depleting if the array is partitioned into more than two sub-arrays because of diminishing additional diversity gains, which fails to compensate for the beamforming gain erosion due to splitting the antenna arrays. Additionally, we analyze the so-called discrete Fourier transform-mutually unbiased bases (DFT-MUB) aided codebook invoked for the conceived design, which imposes an appealingly low complexity. Explicitly, we show that for the proposed dual-function sub-array-connected design, the DFT-MUB assisted codebook outperforms the state-of-the-art precoding benchmarks and performs close to the optimal precoding matrix.
Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

Significance Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Despite extensive cancer genome-sequencing efforts, there is still an incomplete understanding of the genetic networks driving TNBC. Here, we used Sleeping Beauty transposon mutagenesis to identify genes that cooperate with mutant Pten in the induction of TNBC. We identified 12 candidate TNBC trunk drivers and a larger number of progression genes. Subsequent functional validation studies identified eight human TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1, which was shown to inhibit lung metastasis by deregulating the expression of multiple serpin and epithelial-to-mesenchymal transition (EMT) pathway genes. Our study provides a better understanding of the genetic forces driving TNBC and discovered genes with clinical importance in TNBC. Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1. Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC.
Generalizing data to provide anonymity when disclosing information (abstract)

The proliferation of information on the Internet and access to fast computers with large storage capacities has increased tho volume of information collected and disseminated about individuals, The existence of these other data sources makes it much easier to re-identify individuals whose private information is released in data believed to be anonymous. At the same time, increasing demands are made on organizations to release individualized data rather than aggregate statistical information. Even when explicit identifiers, such as name and phone number, are removed or encrypted when releasing individualized data, other characteristic data may still uniquely combine into a quasi-identifier, which can allow data recipients to re-identify individuals to whom the data refer. In this paper, we provide a technique for releasing information such that the ability to link the released data to other information is limited in an attempt to protect the idcntitics of individuals. We use generalization, by which stored values can be replaced with semantically consistent but less precise alternatives, and k-anonymity. A table provides k-anonymity when each combination of values that is associated with a quasi-identifier occurs k or more times, making it difficult to link the quasi-identifier to other data with confidence. We introduce the notions of generalized table and of minimal generalization of a table with respect to a k-anonymity requirement. As an optimization problcm, the objective is to minimally distort the data while providing adequate protection. We describe an algorithm that, given a table, efficiently computes a preferred minimal gcnoralization to provide anonymity.
Bayesian semiparametric modeling for HIV longitudinal data with censoring and skewness

In biomedical studies, the analysis of longitudinal data based on Gaussian assumptions is common practice. Nevertheless, more often than not, the observed responses are naturally skewed, rendering the use of symmetric mixed effects models inadequate. In addition, it is also common in clinical assays that the patient’s responses are subject to some upper and/or lower quantification limit, depending on the diagnostic assays used for their detection. Furthermore, responses may also often present a nonlinear relation with some covariates, such as time. To address the aforementioned three issues, we consider a Bayesian semiparametric longitudinal censored model based on a combination of splines, wavelets, and the skew-normal distribution. Specifically, we focus on the use of splines to approximate the general mean, wavelets for modeling the individual subject trajectories, and on the skew-normal distribution for modeling the random effects. The newly developed method is illustrated through simulated data and real data concerning AIDS/HIV viral loads.