Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance

ABSTRACT Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6-dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13Rα1 and IL-4Rα chains. We used mice deficient in IL-13Rα1 (IL-13Rα1−/−) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasite Heligmosomoides bakeri. There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13Rα2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13Rα1−/− mice. Goblet cell numbers and resistin-like molecule beta (RELM-β) expression were attenuated significantly in IL-13Rα1−/− mice following Hb2 infections. IL-13Rα1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13Rα1−/− mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13Rα1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion.
Height growth determinants and adaptation to temperature in pines : a case study of Pinus contorta and Pinus monticola

In this study we aimed to compare and explain the height growth performance of two contrasting pine spe- cies: lodgepole pine (Pinus contorta Dougl. ex. Loud) and western white pine (Pinus monticola Dougl. ex D. Don.). We compiled measurements of total height growth at different ages and shoot elongation phenology realized in several provenance test trials for 109 provenances of lodgepole pine and 54 provenances of western white pine. The response of shoot elongation to temperature was assessed using a phenological model fitted on provenance mean growth curves. Although total height growth followed the same geographic trends in both species, the response of shoot elongation to temperature was different between the two, with few (lodgepole pine) or no differences among provenances (western white pine) from diverse geographic regions. The temperature for which potential cell growth rate is 50% was 10.8 ± 0.13 °C (mean ± standard error) for western white pine compared to 5.26 ± 0.075 °C for lodgepole pine. Phenology did not explain growth performance differences among geographical regions in both species, which instead were ex- plained by differences in the number of internodes set the preceding summer; provenances originating from stressful environments produced the fewest internodes, possibly due to reallocation of carbohydrates to stress resistance. Resume : Cette etude avait pour but de comparer et d'expliquer les performances de croissance en hauteur de deux es- peces de pins tres differentes: pin lodgepole (Pinus contorta Dougl. ex. Loud) et pin blanc de l'Ouest (Pinus monticola Dougl. ex D. Don.). Nous avons compile des mesures de croissance en hauteur totale a differents âges ainsi que des mesures de phenologie d'elongation des pousses de l'annee, realisees dans plusieurs tests de provenances pour 109 pro- venances de lodgepole pine et 54 provenances de pin blanc de l'Ouest. La reponse de l'elongation des pousses a la temperature a ete determinee a l'aide d'un modele phenologique ajuste sur les courbes de croissance moyenne des pro- venances. Alors que la croissance totale en hauteur suivit les memes patrons de variations geographiques chez les deux especes, la reponse de l'elongation des pousses a la temperature etait tres differente entre les deux especes, avec peu (pin lodgepole) ou pas de differences entre les provenances (pin blanc de l'Ouest) des diverses regions geographiques. La temperature pour laquelle le taux de croissance potentielle des cellules est 50 % etait de 10.8 ± 0.13 °C (moyen ± erreur-type) pour pin blanc de l'Ouest et de 5.26 ± 0.075 °C pour pin lodgepole. La phenologie n'expliqua pas les dif- ferences de performance de croissance entre les differentes regions geographiques chez les deux especes, qui etaient davantage expliquees par les differences de nombre d'entre-nœuds produit pendant l'ete precedent, les provenances ori- ginaires d'environnements stressant produisant moins d'entre-noeuds, possiblement du fait de la reallocation des hydra- tes de carbone a la resistance aux stresses.
Genome and epigenome engineering CRISPR toolkit for in vivo modulation of cis-regulatory interactions and gene expression in the chicken embryo

ABSTRACT CRISPR/Cas9 genome engineering has revolutionised all aspects of biological research, with epigenome engineering transforming gene regulation studies. Here, we present an optimised, adaptable toolkit enabling genome and epigenome engineering in the chicken embryo, and demonstrate its utility by probing gene regulatory interactions mediated by neural crest enhancers. First, we optimise novel efficient guide-RNA mini expression vectors utilising chick U6 promoters, provide a strategy for rapid somatic gene knockout and establish a protocol for evaluation of mutational penetrance by targeted next-generation sequencing. We show that CRISPR/Cas9-mediated disruption of transcription factors causes a reduction in their cognate enhancer-driven reporter activity. Next, we assess endogenous enhancer function using both enhancer deletion and nuclease-deficient Cas9 (dCas9) effector fusions to modulate enhancer chromatin landscape, thus providing the first report of epigenome engineering in a developing embryo. Finally, we use the synergistic activation mediator (SAM) system to activate an endogenous target promoter. The novel genome and epigenome engineering toolkit developed here enables manipulation of endogenous gene expression and enhancer activity in chicken embryos, facilitating high-resolution analysis of gene regulatory interactions in vivo. Summary: The use of an optimised toolkit for efficient genome and epigenome engineering using CRISPR in chicken embryos is demonstrated, focussing on probing gene regulatory interactions during neural crest development.
Comparison of electrophysiological properties of two types of pre-sympathetic neurons intermingled in the hypothalamic paraventricular nucleus

The hypothalamic paraventricular nucleus (PVN) contains two types of neurons projecting to either the rostral ventrolateral medulla (PVNRVLM) or the intermediolateral horn (IML) of the spinal cord (PVNIML). These two neuron groups are intermingled in the same subdivisions of the PVN and differentially regulate sympathetic outflow. However, electrophysiological evidence supporting such functional differences is largely lacking. Herein, we compared the electrophysiological properties of these neurons by using patch-clamp and retrograde-tracing techniques. Most neurons (>70%) in both groups spontaneously fired in the cell-attached mode. When compared to the PVNIML neurons, the PVNRVLM neurons had a lower firing rate and a more irregular firing pattern (p < 0.05). The PVNRVLM neurons showed smaller resting membrane potential, slower rise and decay times, and greater duration of spontaneous action potentials (p < 0.05). The PVNRVLM neurons received greater inhibitory synaptic inputs (frequency, p < 0.05) with a shorter rise time (p < 0.05). Taken together, the results indicate that the two pre-sympathetic neurons differ in their intrinsic and extrinsic electrophysiological properties, which may explain the lower firing activity of the PVNRVLM neurons. The greater inhibitory synaptic inputs to the PVNRVLM neurons also imply that these neurons have more integrative roles in regulation of sympathetic activity.
Motor reattachment kinetics play a dominant role in multimotor-driven cargo transport

Kinesin-based cargo transport in cells frequently involves the coordinated activity of multiple motors, including kinesins from different families that move at different speeds. However, compared to the progress at the single-molecule level, mechanisms by which multiple kinesins coordinate their activity during cargo transport are poorly understood. To understand these multi-motor coordination mechanisms, defined pairs of kinesin-1 and kinesin-2 motors were assembled on DNA scaffolds and their motility examined in vitro. Although less processive than kinesin-1 at the single-molecule level, addition of kinesin-2 motors more effectively amplified cargo run lengths. By applying the law of total expectation to cargo binding durations in ADP, the kinesin-2 microtubule reattachment rate was shown to be 4-fold faster than that of kinesin-1. This difference in microtubule binding rates was also observed in solution by stopped-flow. High-resolution tracking of gold-nanoparticle-labeled cargo with 1 ms and 2 nm precision revealed that kinesin-2 motors detach and rebind to the microtubule much more frequently than do kinesin-1. Finally, cargo transported by kinesin-2 motors more effectively navigated roadblocks on the microtubule track. These results highlight the importance of motor reattachment kinetics during multi-motor transport and suggest a coordinated transport model in which kinesin-1 motors step effectively against loads while kinesin-2 motors rapidly unbind and rebind to the microtubule. This dynamic tethering by kinesin-2 maintains the cargo near the microtubule and enables effective navigation along crowded microtubules.
Impact of Code Obfuscation on Android Malware Detection based on Static and Dynamic Analysis

The huge diffusion of malware in mobile platform is plaguing users. New malware proliferates at a very fast pace: as a matter of fact, to evade the signature-based mechanism implemented in current antimalware, the application of trivial obfuscation techniques to existing malware is sufficient. In this paper, we show how the application of several morphing techniques affects the effectiveness of two widespread malware detection approaches based on Machine Learning coupled respectively with static and dynamic analysis. We demonstrate experimentally that dynamic analysis-based detection performs equally well in evaluating obfuscated and non-obfuscated malware. On the other hand, static analysis-based detection is more accurate on nonobfuscated samples but is greatly negatively affected by obfuscation: however, we also show that this effect can be mitigated by using obfuscated samples also in the learning phase.
Association between Urinary Phytoestrogens and C-reactive Protein in the Continuous National Health and Nutrition Examination Survey

ABSTRACT Objective: A reduced risk of some cancers and cardiovascular disease associated with phytoestrogen intake may be mediated through its effect on serum C-reactive protein (CRP; an inflammation biomarker). Therefore, this study examined the associations between urinary phytoestrogens and serum CRP. Methods: Urinary phytoestrogen and serum CRP data obtained from 6009 participants aged ≥ 40 years in the continuous National Health and Nutrition Examination Survey during 1999–2010 were analyzed. Results: After adjustment for confounders, urinary concentrations of total and all individual phytoestrogens were inversely associated with serum concentrations of CRP (all p < 0.004). The largest reductions in serum CRP (mg/L) per interquartile range increase in urinary phytoestrogens (ng/mL) were observed for total phytoestrogens (β = −0.18; 95% confidence interval [CI], −0.22, −0.15), total lignan (β = −0.15; 95% CI, −0.18, −0.12), and enterolactone (β = −0.15; 95% CI, −0.19, −0.12). A decreased risk of having high CRP concentrations (≥3.0 mg/L) for quartile 4 vs quartile 1 was also found for total phytoestrogens (OR = 0.63; 95% CI, 0.53, 0.73), total lignan (OR = 0.64; 95% CI, 0.54, 0.75), and enterolactone (OR = 0.59; 95% CI, 0.51, 0.69). Conclusion: Urinary total and individual phytoestrogens were significantly inversely associated with serum CRP in a nationally representative sample of the U.S. population.
Changes in structural network are associated with cortical demyelination in early multiple sclerosis

The aim of this study was to investigate the interplay between structural connectivity and cortical demyelination in early multiple sclerosis. About 27 multiple sclerosis patients and 18 age‐matched controls underwent two MRI scanning sessions. The first was done at 7T and involved acquiring quantitative T1 and T2* high‐resolution maps to estimate cortical myelination. The second was done on a Connectom scanner and consisted of acquiring high angular resolution diffusion‐weighted images to compute white matter structural connectivity metrics: strength, clustering and local efficiency. To further investigate the interplay between structural connectivity and cortical demyelination, patients were divided into four groups according to disease‐duration: 0–1 year, 1–2 years, 2–3 years, and >3 years. ANOVA and Spearman's correlations were used to highlight relations between metrics. ANOVA detected a significant effect between disease duration and both cortical myelin (p = 2 × 10−8) and connectivity metrics (p < 10−4). We observed significant cortical myelin loss in the shorter disease‐duration cohorts (0–1 year, p = .0015), and an increase in connectivity in the longer disease‐duration cohort (2–3 years, strength: p = .01, local efficiency: p = .002, clustering: p = .001). Moreover, significant covariations between myelin estimation and white matter connectivity metrics were observed: Spearman's Rho correlation coefficients of 0.52 (p = .0003), 0.55 (p = .0001), and 0.53 (p = .0001) for strength, local efficiency, and clustering, respectively. An association between cortical myelin loss and changes in white matter connectivity in early multiple sclerosis was detected. These changes in network organization might be the result of compensatory mechanisms in response to the ongoing cortical diffuse damage in the early stages of multiple sclerosis.
Evidence-based review and appraisal of the use of droperidol in the emergency department

Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood–brain barrier. A black box warning was issued for droperidol by the United States Food and Drug Administration in 2001 because of a risk of development of torsades de pointes induced by QT prolongation. Many experts feel that the incidence of arrhythmia is overestimated, and low-dose droperidol is almost always used by anesthesiologists for postoperative nausea and vomiting. In this review, we used evidence-based analysis to appraise high-quality studies with a low risk of bias published after 2001 on the use of droperidol in the emergency department (ED). Droperidol appears not only efficacious but also safe to treat patients with nausea/vomiting, acute psychosis, and migraine in the ED. For these conditions, droperidol may be an option for shared decision-making.
Blood brain barrier: A review of its anatomy and physiology in health and disease

The blood–brain barrier (BBB) is the principal regulator of transport of molecules and cells into and out of the central nervous system (CNS). It comprises endothelial cells, pericytes, immune cells, astrocytes, and basement membrane, collectively known as the neurovascular unit. The development of the barrier involves many complex pathways from all the progenitors of the neurovascular unit, but the timing of its formation is not entirely known. The coordinated activities of all the components of the neurovascular unit and other tissues ensure that materials required for growth and maintenance are allowed into the CNS while extraneous ones are excluded. This review summarizes current knowledge of the anatomy, development, and physiology of the BBB, and alterations that occur in disease conditions. Clin. Anat. 31:812–823, 2018. © 2018 Wiley Periodicals, Inc.
A Practical O(Rlog log n+n) time Algorithm for Computing the Longest Common Subsequence

In this paper, we revisit the much studied LCS problem for two given sequences. Based on the algorithm of Iliopoulos and Rahman for solving the LCS problem, we have suggested 3 new improved algorithms. We first reformulate the problem in a very succinct form. The problem LCS is abstracted to an abstract data type DS on an ordered positive integer set with a special operation Update(S,x). For the two input sequences X and Y of equal length n, the first improved algorithm uses a van Emde Boas tree for DS and its time and space complexities are O(R\log\log n+n) and O(R), where R is the number of matched pairs of the two input sequences. The second algorithm uses a balanced binary search tree for DS and its time and space complexities are O(R\log L+n) and O(R), where L is the length of the longest common subsequence of X and Y. The third algorithm uses an ordered vector for DS and its time and space complexities are O(nL) and O(R).
The interplay between lnRNAs, SNPs, and protein complexes - what does it mean for cancer metabolism?

ABSTRACT Long non-coding RNAs (lncRNAs) exert most of their functions through protein interactions. A better understanding of these interactions will facilitate the development of novel therapeutics. Recently, we described how the lncRNA CCAT2 located at the 8q24 cancer amplicon reprograms cancer metabolism by directly interacting in an allele-specific manner with a protein complex.
Offline Object Extraction from Dynamic Occupancy Grid Map Sequences

A dynamic occupancy grid map (DOGMa) allows a fast, robust, and complete environment representation for automated vehicles. Dynamic objects in a DOGMa, however, are commonly represented as independent cells while modeled objects with shape and pose are favorable. The evaluation of algorithms for object extraction or the training and validation of learning algorithms rely on labeled ground truth data. Manually annotating objects in a DOGMa to obtain ground truth data is a time consuming and expensive process. Additionally the quality of labeled data depend strongly on the variation of filtered input data. The presented work introduces an automatic labeling process, where a full sequence is used to extract the best possible object pose and shape in terms of temporal consistency. A two direction temporal search is executed to trace single objects over a sequence, where the best estimate of its extent and pose is refined in every time step. Furthermore, the presented algorithm only uses statistical constraints of the cell clusters for the object extraction instead of fixed heuristic parameters. Experimental results show a well-performing automatic labeling algorithm with real sensor data even at challenging scenarios.
Superconductivity in Lu3Os4Ge13

We report the normal and superconducting state properties of high quality single crystal of Lu3Os4Ge13 grown by Czochralski method. Lu3Os4Ge13 crystallises in the cubic crystal structure (space group Pm3n) . Lu3Os4Ge13 is a type-II superconductor (Tc = 3.1 K) as determined by the electrical transport, magnetisation and heat capacity measurements. The thermopower measurement shows a large phonon drag effect at low temperatures. The electronic band structure calculations show a multi-valley type band structure and a complex Fermi surface in Lu3Os4Ge13, making it a possible candidate to observe a magnetic field induced triplet superconductivity at ultra-low temperatures.
Targeting DNA Methyltranferases in Urological Tumors

Urological cancers are a heterogeneous group of malignancies accounting for a considerable proportion of cancer-related morbidity and mortality worldwide. Aberrant epigenetic traits, especially altered DNA methylation patterns constitute a hallmark of these tumors. Nonetheless, these alterations are reversible, and several efforts have been carried out to design and test several epigenetic compounds that might reprogram tumor cell phenotype back to a normal state. Indeed, several DNMT inhibitors are currently under evaluation for therapeutic efficacy in clinical trials. This review highlights the critical role of DNA methylation in urological cancers and summarizes the available data on pre-clinical assays and clinical trials with DNMT inhibitors in bladder, kidney, prostate, and testicular germ cell cancers.
Foreign-Particle Reinforcement of a Zr-Cu-X BMG

The yield strength of a Zr-based bulk metallic glass was improved by up to 20% in comparison to the as-received alloy via dispersion of graphite nanoparticles into the matrix. The resulting material also had high plasticity and good elasticity and the use of reinforcement particles was found to suppress heterogeneous nucleation. The graphite nanoparticles additionally improved the alloy’s thermal stability as compared to that of the monolithic alloy.
The impact of contrast-enhanced spectral mammogram (CESM) and three-dimensional breast ultrasound (3DUS) on the characterization of the disease extend in cancer patients.

OBJECTIVE The main importance of imaging breast cancer is to guide conservative surgeries. In this study, we evaluated the role of contrast-enhanced spectral mammogram (CESM) in correlation with three-dimensional (3D) breast ultrasound in characterizing the extension of the intramammary cancer in view of the: (i) the size of the main tumor, (ii) the multiplicity of the breast cancer, and (iii) the peri-tumoral stromal involvement (i.e. free or intraductal extension of the cancer). METHODS The study is a prospective analysis that included 300 breast masses proved to be malignant. The masses were evaluated for their size, multiplicity and surrounding stromal involvement. Contrast-based mammography performed with low (22-33 kVp) and high (44-49 kVp) energy exposures that were taken after i.v. injection of contrast agent and followed by bilateral 3D breast ultrasound. Operative data were the gold standard reference. RESULTS There was no significant difference between the sizes of the included cancers as measured by CESM and 3D ultrasound and that measured at the pathological analysis. CESM showed higher accuracy (32.7%, n = 98) than 3D ultrasound (24.7%, n = 74) in the size agreement within 5% range. CESM was the most accurate modality (94%, n = 282) in detecting tumor multiplicity, followed by traditional sonomammogram (88%, n = 264), then 3D breast ultrasound (84%, n = 252). Intraductal extension of the breast cancer was best evaluated by the 3D ultrasound with an accuracy value of 98% (n = 294) compared to only 60% (n = 180) by CESM. CONCLUSION CESM is a recommended investigation in breast cancer to increase the accuracy of size measurement and the detection of multiple tumors. The addition of 3D ultrasound can enhance the detection of intraductal extension. Advances in knowledge: Choice of conservative breast surgery vs mastectomy is still a debate. We used an advanced, contrast-based, application of the mammogram: CESM and a non-invasive 3D breast ultrasound in the assessment of the local extension of the breast cancer regarding size, perifocal stromal infiltration and multiplicity to guide the selection of proper management in proved cases of breast cancer.