Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment and characterization of a canine keratinocyte organoid culture system

BACKGROUND Perturbations of epidermal and follicular homeostasis have been attributed to a variety of skin diseases affecting dogs. The availability of an in vitro system to investigate these diseases is important to understand underlying pathomechanisms. OBJECTIVES To establish an accurate and reliable in vitro 3D system of canine keratinocyte organoids to lay the basis for studying functional defects in interfollicular epidermis (IFE) and hair follicle (HF) morphogenesis, reconstitution and differentiation that lead to alopecic and epidermal diseases. ANIMALS Skin biopsies were obtained from freshly euthanized dogs of different breeds with no skin abnormalities. METHODS Cells derived from microdissected IFE and HFs were seeded in Matrigel and keratinocyte organoids were grown and characterized using immunohistochemistry, RT-qPCR and RNA sequencing. RESULTS Both organoid lines develop into a basal IFE-like cell type. Gene and protein expression analysis revealed high mRNA and protein levels of keratins 5 and 14, IFE differentiation markers and intercellular molecules. Key markers of HF stem cells were lacking. Withdrawal of growth factors resulted in upregulation of markers such as KRT16, Involucrin, KRT17 and SOX9, showing the potential of the organoids to develop towards more differentiated tissue. CONCLUSION AND CLINICAL IMPORTANCE Our 3D in vitro culture system provides the basis to explore epidermal function, to investigate the culture conditions necessary for the development of organoids with a HF signature and to address cutaneous disorders in dogs. However, for induction of HF signatures or hair growth, addition of different growth factors or co-culture with dermal papilla will be required.
Two sugar beet chitinase genes, BvSP2 and BvSE2, analysed with SNP Amplifluor-like markers, are highly expressed after Fusarium root rot inoculations and field susceptibility trial

Background The pathogens from Fusarium species can cause Fusarium root rot (RR) and other diseases in plant species including sugar beet (Beta vulgaris L.), and they have a strong negative impact on sugar beet yield and quality. Methods A total of 22 sugar beet breeding lines were evaluated for the symptoms of RR after inoculation with Fusarium oxysporum Sch. , isolate No. 5, and growth in a field trial. Two candidate genes for RR resistance, BvSP2 and BvSE2, encoding chitinases Class IV and III, respectively, were previously identified in sugar beet, and used for genotyping using modern Amplifluor-like single nucleotide polymorphism (SNP) genotyping approach. The qPCR expression analysis was used to verify responses of the candidate genes for RR infections. Results A strong association of two SNP markers for BvSP2 and BvSE2 with resistance to RR in sugar beet was found in our study. Very high BvSP2 expression (100-fold compared to Controls) was observed in three RR resistant accessions (2182, 2236 and KWS2320) 14 days after inoculation which returned to the control level on Day 18. RR sensitive breeding line 2210 showed a delay in mRNA level, reaching maximal expression of BvSP2 18 days after inoculation. The gene BvSE2, showed a strong expression level in leaf samples from the infected field trial only in the breeding line 2236, which showed symptoms of RR, and this may be a response to other strains of F. oxysporum.
Impact of the Acid Treatment on Lignocellulosic Biomass Hard Carbon for Sodium-Ion Battery Anodes.

The investigation of phosphoric acid treatment on the performance of hard carbon from a typical lignocellulosic biomass waste (peanut shell) is herein reported. A strong correlation is discovered between the treatment time and the structural properties and electrochemical performance in sodium-ion batteries. Indeed, a prolonged acid treatment enables the use of lower temperatures, that is, lower energy consumption, for the carbonization step as well as improved high-rate performance (122 mAh g-1 at 10 C).
Role of the ocean's AMOC in setting the uptake efficiency of transient tracers

The central role played by the ocean's Atlantic Meridional Overturning Circulation (AMOC) in the uptake and sequestration of transient tracers is studied in a series of experiments with the Goddard Institute for Space Studies and Massachusetts Institute of Technology ocean circulation models. Forced by observed atmospheric time series of CFC‐11, both models exhibit realistic distributions in the ocean, with similar surface biases but different response over time. To better understand what controls uptake, we ran idealized forcing experiments in which the AMOC strength varied over a wide range, bracketing the observations. We found that differences in the strength and vertical scale of the AMOC largely accounted for the different rates of CFC‐11 uptake and vertical distribution thereof. A two‐box model enables us to quantify and relate uptake efficiency of passive tracers to AMOC strength and how uptake efficiency decreases in time. We also discuss the relationship between passive tracer and heat uptake efficiency, of which the latter controls the transient climate response to anthropogenic forcing in the North Atlantic. We find that heat uptake efficiency is substantially less (by about a factor of 5) than that for a passive tracer.
Are the American Heart Association/American College of Cardiology High Blood Pressure Guidelines Fit for Global Purpose?: Thoughts From the International Society of Hypertension.

In 2017, the American College of Cardiology (ACC), the American Heart Association (AHA), and 9 other American societies released guidelines for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults.1 These guidelines are perhaps the most controversial set of US guidelines—even more so than those attributed to some of the committee set up to produce the guidelines of the Eighth Joint National Committee in 2014.2 Before discussing the various controversial aspects of the ACC/AHA guidelines, the International Society of Hypertension would like to congratulate the authors on 3 counts. First, emphasis was placed on the appropriate technique of BP measurements and the increased need for out-of-office BP measurement. Second, the value of risk assessment was recognized and introduced for the first time in US guidelines and finally, perhaps in part because of the controversial nature of the document, awareness of the importance of BP as a global cause of morbidity and mortality has been raised. The central controversy around which several others arise is the redefining of hypertension—as a systolic BP ≥130 mm Hg or a diastolic BP ≥80 mm Hg. Although there is a clear dose-response relationship between increasing BP levels and adverse cardiovascular outcomes,3 this preempts the ability, based on predicting cardiovascular events, of precisely defining hypertension. However, the pragmatic definition proposed by Geoffrey Rose decades ago should perhaps be considered—viz: “that level of BP above which investigation and management does more good than harm. ”4 Does the new BP level proposed in the ACC/AHA guidelines fully satisfy that criterion? Perhaps not. To date, the relevant data are inconsistent and hence controversial. The problem arises because the definition of hypertension, treatment thresholds, and BP targets should …
Enhancing the Business Value of Business Intelligence: The Role of Shared Knowledge and Assimilation

ABSTRACT: Business intelligence (BI) systems have attracted significant interest from senior executives and consultants for their ability to exploit organizational data and provide operational and strategic benefits through improved management control systems. A large body of literature indicates that organizations have largely failed to use their business intelligence investments effectively to exploit the wealth of data they capture in their ERP systems. As a result, BI has too often failed to support organizations' managerial decision making at both the strategic and operational levels and, thus, failed to enhance business value. Whether and how organizations achieve business benefits from their BI investments remains unclear. This study draws on the strategic alignment and IT assimilation literature to develop a research model that theorizes the importance of BI systems assimilation, and the need for shared knowledge among the strategic and operational levels as the drivers of BI business value. Resul.
Effect of platelet-rich plasma (PRP) on ovarian structures in cyclophosphamide-induced ovarian failure in female rats: a stereological study

Abstract Background: Ovarian failure is diagnosed by ovarian destruction and reducing sex hormonal levels. Platelet-rich plasma (PRP) contains several growth factors that induce tissue repair and may induce folliculogenesis. Objective: This study evaluates the effect of PRP on ovarian structures and function in cyclophosphamide (Cy)-induced ovarian failure in female rats by a stereological method. Methods: Thirty-two adult female rats were divided into four groups (Control, Cy, Cy + PRP, and PRP). Female infertility was induced by Cy (75 mg/kg, single dose, intraperitoneally). Animals were treated by PRP which was obtained from age-matched male rats (200 μL, single dose, intraperitoneally). Blood samples were collected for measurement of hormones. The animals were dissected and the right ovaries were removed, fixed, sectioned, and stained by H&E. Stereological methods were used to estimate cortex and medulla volume, and the number and diameter of follicles, follicular cell, and oocyte using light microscopy. Results: Cyclophosphamide had the maximum effect in decreasing on cortex volume, the pre-antral follicles number, a diameter of follicular cells and oocyte diameter in the antral follicle and the reduction of estradiol and progesterone levels compared with the control group. PRP had a dominant positive effect on the ovarian cortex volume, pre-antral follicles number and antral follicle diameter relative to the control group. PRP also decreased oocyte diameter in pre-antral follicle in infertile animals (p < 0.001). Conclusion: It seems that PRP has a protective effect on ovarian failure in the infertile female rat model.
Continuous Auditing and Continuous Monitoring in ERP Environments: Case Studies of Application Implementations

ABSTRACT: The need for continuous auditing and continuous monitoring (CA/CM) has increased in the global digital economy. Modern computer-based systems make it possible to measure and monitor business processes at an unprecedented level of detail in a real- or near real-time basis. This empowers auditors to become increasingly dependent on computer technology and software tools. While there is a growing body of literature related to this domain, there is a need for empirical evidence from actual implementations that document these systems in detail. In this research, we perform such an investigation on three CA/CM systems, namely SAPSECURE, CAMAP, and Bagheera-S™.
Immersive 360° VR tiled streaming system for esports service

This paper shows how a system was designed and implemented for the live tiled streaming of 360° Virtual Reality(VR) eSports based on HEVC. A virtual camera technique was designed and implemented based on the Unity and Unreal engines as a means of capturing 360° videos in a virtual space, and a MPEG-DASH SRD(Spatial Relation Description)[1-2] Based dashing and streaming server was configured to build a live HEVC encoding system and for real-time internet streaming. Finally, an integrated 360° VR client was configured for use as a multi-platform. Each technological element was designed to service the client through a 360° VR 3D stereo method, and the MPEG-DASH SRD was expanded such that high-quality game videos can be played at lower bandwidths.
Statistical harmonization corrects site effects in functional connectivity measurements from multi‐site fMRI data

Acquiring resting‐state functional magnetic resonance imaging (fMRI) datasets at multiple MRI scanners and clinical sites can improve statistical power and generalizability of results. However, multi‐site neuroimaging studies have reported considerable nonbiological variability in fMRI measurements due to different scanner manufacturers and acquisition protocols. These undesirable sources of variability may limit power to detect effects of interest and may even result in erroneous findings. Until now, there has not been an approach that removes unwanted site effects. In this study, using a relatively large multi‐site (4 sites) fMRI dataset, we investigated the impact of site effects on functional connectivity and network measures estimated by widely used connectivity metrics and brain parcellations. The protocols and image acquisition of the dataset used in this study had been homogenized using identical MRI phantom acquisitions from each of the neuroimaging sites; however, intersite acquisition effects were not completely eliminated. Indeed, in this study, we found that the magnitude of site effects depended on the choice of connectivity metric and brain atlas. Therefore, to further remove site effects, we applied ComBat, a harmonization technique previously shown to eliminate site effects in multi‐site diffusion tensor imaging (DTI) and cortical thickness studies. In the current work, ComBat successfully removed site effects identified in connectivity and network measures and increased the power to detect age associations when using optimal combinations of connectivity metrics and brain atlases. Our proposed ComBat harmonization approach for fMRI‐derived connectivity measures facilitates reliable and efficient analysis of retrospective and prospective multi‐site fMRI neuroimaging studies.
Pathogen invasion and non-epizootic dynamics in Pacific newts in California over the last century

Emerging infectious disease is a growing threat to global biodiversity. The infectious disease chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd) has led to the decline and extinction of hundreds of amphibian species. Severe Bd-caused epizootics have been documented in North, Central and South America—with many of the research focused on anurans. California, where Bd-related epizootics and amphibian declines have been reported, has some of the highest diversity of salamanders. After more than a decade since the first known epizootic in California, little is known about Bd disease dynamics in salamanders. Pacific newts (Genus: Taricha) are ideal study species because of their abundance, wide geographic range, occurrence in both aquatic and terrestrial habitats, and how little is known about Bd infection dynamics for this group. We conducted a retrospective study to determine the relationship between Pacific newts and the fungal pathogen. We tested 1895 specimens collected between 1889–2009 and found no evidence of Bd-infected Pacific newts until the late 1940’s. Although we estimate that Bd emerged in this genus and rapidly spread geographically throughout California, we did not find evidence for epizootic dynamics. Bd infection prevalence and intensity, two measures commonly used to estimate dynamics, remained consistently low over time; suggesting Pacific newts may not be highly susceptible. Also, we found the timing of first Bd emergence in Pacific newts predate Bd emergence in other California salamander species. In addition, we found several environmental and anthropogenic factors correlated with Bd prevalence which may help explain Bd disease dynamics in the genus Taricha. Pacific newts may be a reservoir species that signal pathogen invasion into California salamanders, though further studies are needed.
Impact of TCAD model parameters on optical and electrical characteristics of radiation-hard photodiode in 0.35bm CMOS technology

In this paper, a variability Design of Experiment (DoE) is performed on a radiation-hard photodiode structure in order to understand how the physical parameters of the device impact its spectral responsivity and dark current. The varied physical parameters describe the carrier mobility, lifetime, energy bandgap and recombination models. The electrical and optical performance of the device are simulated using TCAD software, as a function of varied physical parameters. The simulations are calibrated to the device measurements. The analysis of the design showed that the carrier lifetime is the most influencing parameter that impacts both the spectral responsivity and the dark current. Mobility parameters and Auger recombination parameters impact the spectral responsivity, while the energy bandgap at 340 K impacts the dark current. Finally, the model parameters that fit the measured dark current are obtained by the thorough variation simulations.
Targeting the PI3K/Akt/mTOR signaling pathway by pterostilbene attenuates mantle cell lymphoma progression

Mantle cell lymphoma (MCL) is an aggressive and mostly incurable B-cell malignancy with frequent relapses after an initial response to standard chemotherapy. Therefore, novel therapies are urgently required to improve MCL clinical outcomes. In this study, MCL cell lines were treated with pterostilbene (PTE), a non-toxic natural phenolic compound primarily found in blueberries. The antitumor activity of PTE was examined by using the Cell Counting Kit-8, apoptosis assays, cell cycle analysis, JC-1 mitochondrial membrane potential assay, western blot analysis, and tumor xenograft models. PTE treatment induced a dose-dependent inhibition of cell proliferation, including the induction of cell apoptosis and cell cycle arrest at the G0/G1 phase. Moreover, the PI3K/Akt/mTOR pathway was downregulated after PTE treatment, which might account for the anti-MCL effects of PTE. Synergistic cytotoxicity was also observed, both in MCL cells and in xenograft mouse models, when PTE was administered in combination with bortezomib (BTZ). The antitumor effects of PTE shown in our study provide an innovative option for MCL patients with poor responses to standardized therapy. It is noteworthy that the treatment combining PTE with BTZ warrants clinical investigation, which may offer an alternative and effective MCL treatment in the future.
Hydroxypyridonecarboxylic Acids as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease

Human cytomegalovirus (HCMV) infection poses a major health threat to immunocompromised individuals. Until recently, treatment of HCMV infection has relied solely on polymerase inhibitors that have safety and resistance issues. pUL89 provides the enzymatic functions for the HCMV terminase complex in viral DNA packaging and is an attractive target for developing a new class of HCMV drugs. However, inhibitors of the endonuclease activity of the C terminus of pUL89 (pUL89‐C) were unknown before our recently characterized hydroxypyridonecarboxylic acid (HPCA) hit 7 r (1‐(3‐chloro‐4‐fluorobenzyl)‐5‐hydroxy‐4‐oxo‐1,4‐dihydropyridine‐3‐carboxylic acid; numbered as 10 k in our previous publication: Y. Wang, L. Mao, J. Kankanala, Z. Wang, R. J. Geraghty, J. Virol. 2017, 91, e02152‐16). Herein, we explored the structure–activity relationship (SAR) of the HPCA chemotype mainly with regard to the N1 site through the synthesis of 35 analogues. The SAR studies, along with molecular modeling, identified a possible pharmacophore model minimally consisting of a chelating triad and a hydrophobic phenyl or biphenyl methyl substituent at N1. Lastly, our best compounds consistently inhibited pUL89‐C in the low micromolar range in biochemical assays and exhibited strong antiviral activity without cytotoxicity, laying a solid medicinal chemistry foundation for further HCMV drug discovery efforts targeting pUL89‐C.
SUPPLEMENTARY INFORMATION (SI) APPENDIX FOR Costs and benefits of provocation in bacterial warfare

To whom correspondence should be addressed. D.A.I. Mavridou, MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, Kensington, London, SW7 2DD, UK, Tel: +44(0)2075949936 E-mail: d.mavridou@imperial.ac. uk; D. Gonzalez, Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland, Email: diego.gonzalez@unil.ch.
Origins of STIL‐TAL1 fusion genes in children who later developed paediatric T‐cell acute lymphoblastic leukaemia: An investigation of neonatal blood spots

SCL/TAL1 interrupting locus (STIL)‐T‐cell acute leukaemia (TAL1) fusion genes are present in approximately 11‐27% of children with paediatric T‐cell acute lymphoblastic leukaemia (T‐ALL), but the developmental timing of the rearrangement is still unknown. To investigate whether the fusion gene can be detected in neonatal blood spots (NBSs) from paediatric patients diagnosed with T‐cell ALL, we analysed DNA from 38 paediatric patients with T‐ALL by nested polymerase chain reaction and electrophoresis. The STIL‐TAL1 fusion gene was not detected in NBSs from any of the 38 patients with T‐ALL, suggesting that STIL‐TAL1 fusion genes are most probably postnatal events in paediatric T‐ALL.
PD-L1, TIM-3, and CTLA-4 Blockade Fails To Promote Resistance to Secondary Infection with Virulent Strains of Toxoplasma gondii

T cell exhaustion is a state of hyporesponsiveness that develops during many chronic infections and cancer. Neutralization of inhibitory receptors, or “checkpoint blockade,” can reverse T cell exhaustion and lead to beneficial prognoses in experimental and clinical settings. ABSTRACT T cell exhaustion is a state of hyporesponsiveness that develops during many chronic infections and cancer. Neutralization of inhibitory receptors, or “checkpoint blockade,” can reverse T cell exhaustion and lead to beneficial prognoses in experimental and clinical settings. Whether checkpoint blockade can resolve lethal acute infections is less understood but may be beneficial in vaccination protocols that fail to elicit sterilizing immunity. Since a fully protective vaccine for any human parasite has yet to be developed, we explored the efficacy of checkpoint inhibitors in a mouse model of Toxoplasma gondii reinfection. Mice chronically infected with an avirulent type III strain survive reinfection with the type I RH strain but not the MAS, GUY-DOS, and GT1 parasite strains. We report here that mouse susceptibility to secondary infection correlates with the initial parasite burden and that protection against the RH strain is dependent on CD8 but not CD4 T cells in this model. When given a lethal secondary infection, CD8 and CD4 T cells upregulate several coinhibitory receptors, including PD-1, TIM-3, 4-1bb, and CTLA-4. Moreover, the gamma interferon (IFN-γ) response of CD8 but not CD4 T cells is significantly reduced during secondary infection with virulent strains, suggesting that checkpoint blockade may reduce disease severity. However, single and combination therapies targeting TIM-3, CTLA-4, and/or PD-L1 failed to reverse susceptibility to secondary infection. These results suggest that additional host responses, which are refractory to checkpoint blockade, are likely required for immunity to this pathogen.