Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of extracellular vesicles derived from cardiac cells in an in vitro model of preconditioning

ABSTRACT Preconditioning is a promising technique to protect the heart from ischaemia-reperfusion injury. In this context, the crosstalk between different cardiac cell types and especially the exchange of cardioprotective mediators has come into the focus of current research. Recently, extracellular vesicles (EVs), nano-sized structures, emerged as possible communication mediators. They are taken up by recipient cells and can alter gene expression or activate intracellular signal cascades. It has been shown that all cardiac cell types are able to secrete EVs, but so far the influence of an in vitro preconditioning stimulus on EV concentration and composition has not been investigated. Therefore, we stimulated primary cardiac myocytes and fibroblasts from neonatal rats, as well as H9c2 cells, with two known in vitro preconditioning stimuli: hypoxia or isoflurane. EVs were isolated from cell culture supernatants 48 h after stimulation by differential centrifugation and size exclusion chromatography. They were characterized by transmission electron microscopy, tunable resistive pulse sensing, miRNA array and Western blot analysis. The detected EVs had the typical cup-shaped morphology and a size of about 150 nm. No significant differences in EV concentration were observed between the different groups. The protein and miRNA load was affected by in vitro preconditioning with isoflurane or hypoxia. EV markers like Alix, CD63, flotillin-1 and especially heat shock protein 70 were significantly up-regulated by the treatments. Several miRNAs like miR-92b-3p, miR-761 and miR-101a-5p were also significantly affected. A migration assay confirmed the physiological benefit of these EVs. Taken together, our findings show that a model of in vitro preconditioning of cardiac cells does not influence EV concentration but strongly regulates the EV cargo and affects migration. This might indicate a role for EV-mediated communication in isoflurane- and hypoxia-induced in vitro preconditioning.
Exploring the influence of encoding format on subsequent memory

ABSTRACT Distinctive encoding is greatly influenced by gist-based processes and has been shown to suffer when highly similar items are presented in close succession. Thus, elucidating the mechanisms underlying how presentation format affects gist processing is essential in determining the factors that influence these encoding processes. The current study utilised multivariate partial least squares (PLS) analysis to identify encoding networks directly associated with retrieval performance in a blocked and intermixed presentation condition. Subsequent memory analysis for successfully encoded items indicated no significant differences between reaction time and retrieval performance and presentation format. Despite no significant behavioural differences, behaviour PLS revealed differences in brain–behaviour correlations and mean condition activity in brain regions associated with gist-based vs. distinctive encoding. Specifically, the intermixed format encouraged more distinctive encoding, showing increased activation of regions associated with strategy use and visual processing (e.g., frontal and visual cortices, respectively). Alternatively, the blocked format exhibited increased gist-based processes, accompanied by increased activity in the right inferior frontal gyrus. Together, results suggest that the sequence that information is presented during encoding affects the degree to which distinctive encoding is engaged. These findings extend our understanding of the Fuzzy Trace Theory and the role of presentation format on encoding processes.
Melatonin promotes goat spermatogonia stem cells (SSCs) proliferation by stimulating glial cell line-derived neurotrophic factor (GDNF) production in Sertoli cells

Melatonin has been reported to be an important endogenous hormone for regulating neurogenesis, immunityand the biological clock. Recently, the effects of melatonin on neural stem cells (NSCs), mesenchymal stem cells(MSCs), and induced pluripotent stem cells(iPSCs) have been reported; however, the effects of melatonin on spermatogonia stem cells (SSCs) are not clear. Here, 1μM and 1nM melatonin was added to medium when goat SSCs were cultured in vitro, the results showed that melatonin could increase the formation and size of SSC colonies. Real-time quantitative PCR (QRT-PCR) and western blot analysis showed that the expression levels of SSC proliferation and self-renewal markers were up-regulated. Meanwhile, QRT-PCR results showed that melatonin inhibit the mRNA expression level of SSC differentiation markers. ELISA analysis showed an obvious increase in the concentration of GDNF (a niche factor secreted by Sertoli cells) in the medium when treated with melatonin. Meanwhile, the phosphorylation level of AKT, a downstream of GDNF-GFRa1-RET pathway was activated. In conclusion, melatonin promotes goat SSC proliferation by stimulating GDNF production in Sertoli cells.
A High-Coverage Genome Sequence from an Archaic Denisovan Individual

Ancient Genomics The Denisovans were archaic humans closely related to Neandertals, whose populations overlapped with the ancestors of modern-day humans. Using a single-stranded library preparation method, Meyer et al. (p. 222, published online 30 August) provide a detailed analysis of a high-quality Denisovan genome. The genomic sequence provides evidence for very low rates of heterozygosity in the Denisova, probably not because of recent inbreeding, but instead because of a small population size. The genome sequence also illuminates the relationships between humans and archaics, including Neandertals, and establishes a catalog of genetic changes within the human lineage. A close-up look provides clues to the relationships between modern humans, Denisovans, and Neandertals. We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of “missing evolution” in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.
System-Aware Optimization for Machine Learning at Scale

Author(s): Smith, Virginia | Advisor(s): Jordan, Michael I; Culler, David | Abstract: New computing systems have emerged in response to the increasing size and complexity of modern datasets. For best performance, machine learning methods must be designed to closely align with the underlying properties of these systems.In this thesis, we illustrate the impact of system-aware machine learning through the lens of optimization, a crucial component in formulating and solving most machine learning problems. Classically, the performance of an optimization method is measured in terms of accuracy (i.e., does it realize the correct machine learning model? ) and convergence rate (after how many iterations? ). In modern computing regimes, however, it becomes critical to additionally consider a number of systems-related aspects for best overall performance. These aspects can range from low-level details, such as data structures or machine specifications, to higher-level concepts, such as the tradeoff between communication and computation.We propose a general optimization framework for machine learning, CoCoA, that gives careful consideration to systems parameters, often incorporating them directly into the method and theory. We illustrate the impact of CoCoA in two popular distributed regimes: the traditional cluster-computing environment, and the increasingly common setting of on-device (federated) learning. Our results indicate that by marrying systems-level parameters and optimization techniques, we can achieve orders-of-magnitude speedups for solving modern machine learning problems at scale. We corroborate these empirical results by providing theoretical guarantees that expose systems parameters to give further insight into empirical performance.
Introgression of exotic Cervus (nippon and canadensis) into red deer (Cervus elaphus) populations in Scotland and the English Lake District

Abstract Since the mid‐19th century, multiple introductions of Japanese sika deer (Cervus nippon nippon) and North American wapiti (C. canadensis) have taken place in the British Isles. While wapiti have generally been unsuccessful, sika have been very successful, especially in Scotland where they now overlap at least 40% of the range of native red deer (C. elaphus). Hybridization between these two species and red deer has been demonstrated in captivity and in the wild. Using a panel of 22 microsatellite loci that are highly diagnostic between red deer and sika, and moderately diagnostic between red deer and wapiti, we investigated the extent of introgression between these species in 2,943 deer sampled from around Scotland and from the English Lake District using the Bayesian clustering software STRUCTURE. We also used a diagnostic mitochondrial marker for red deer and sika. Our survey extends previous studies indicating little introgression of wapiti nuclear alleles into red deer, in particular in Northern Scotland, Kintyre, and the Lake District. We found a new area of extensive sika introgression in South Kintyre. In the North Highlands, we show for the first time geographically scattered evidence of past hybridization followed by extensive backcrossing, including one red‐like individual with sika introgression, two sika‐like individuals with red deer introgression, and six individuals that were apparently pure sika at the nuclear markers assessed but which carried red deer mitochondria. However, there has not been a collapse of assortative mating in this region. Similarly, in the English Lake District red deer, we found only traces of past sika introgression. No sika alleles were detected in the Central Highlands or the Hebridean red deer refugia. We make suggestions for management to prevent further spread of sika alleles into red deer and vice versa.
Nonlinear optical and multi-photon absorption properties in graphene–ZnO nanocomposites

Graphene–ZnO (GZO) nanocomposites were synthesized by a modified solvothermal method, and characterized by transmission electron microscopy, x-ray diffraction, Raman spectra, and UV–vis absorption spectra. The controllable nonlinear optical (NLO) properties of as-prepared GZO nanocomposites were tested by an open-aperture Z-scan method with 1030 nm fs laser pulses; the tested results showed that there were five-photon absorption (5PA) at 46.8 GW cm−2, 3PA at 28.1 GW cm−2, 2PA at 18.7 GW cm−2, and a vital change from saturable absorption (SA) to reverse SA (RSA) with the increase of incident intensity. This was the first time that 5PA was found in GZO nanocomposites at such a low intensity, 46.8 GW cm−2. The tunable NLO property from SA to RSA and controllable multi-photon absorption provided a facile approach for their applications in optical, optoelectronic devices, and information storage.
MicroRNA Profile in Patients with Alzheimer's Disease: Analysis of miR-9-5p and miR-598 in Raw and Exosome Enriched Cerebrospinal Fluid Samples.

BACKGROUND MicroRNAs have been postulated as potential biomarkers for Alzheimer's disease (AD). Exosomes are nanovesicles which transport microRNAs, proteins, and other cargos. It has been hypothesized that the exosome traffic might be increased in neurodegenerative disorders. OBJECTIVE i) To assess the cerebrospinal fluid (CSF) microRNA profile in a group of AD patients and control subjects and to validate a group of microRNAs previously reported by other authors. ii) To compare microRNA levels in whole CSF and in the exosome-enriched fraction in AD patients. METHODS A panel of 760 microRNAs was analyzed in the CSF of 10 AD patients and 10 healthy subjects. Among microRNAs differently expressed, we selected those that had been previously reported by other authors. Candidates were validated in a larger group by individual qPCR assays. MicroRNA expression was also evaluated in exosome-enriched CSF samples of patients with AD and controls. RESULTS Fifteen microRNAs were differently expressed in AD. MiR-9-5p, miR-134, and miR-598 were selected as candidates for further analysis. MiR-9-5p and miR-598 were detected in 50 and 75% of control CSF samples, respectively, while they were not detected in any AD CSF samples. We observed an opposite pattern when we evaluated the microRNA expression in the exosome-enriched CSF AD samples. No pattern variations were noted among healthy subjects. CONCLUSION These data propose miR-9-5p and miR-598 as potential biomarkers for AD. Further studies in plasma and other body fluids will confirm their potential role as easily accessible biomarkers. In addition, our data suggest that exosome trafficking is different between AD and control subjects raising the need to take this phenomenon into consideration in future studies of AD biomarkers.
Leukocyte telomere length and mortality among U.S. adults: Effect modification by physical activity behaviour

ABSTRACT The purpose of this study was to examine the association between leukocyte telomere length (LTL) and mortality (outcome variable), with consideration by physical activity behaviour. Data from the 1999–2002 National Health and Nutrition Examination Survey were employed (N = 6,611; 20–85 yrs), with follow-up mortality assessment through 31 December 2006. DNA was extracted from whole blood to assess LTL via quantitative polymerase chain reaction. Compared to those in the first LTL tertile, the adjusted hazard ratio for all-cause mortality for those in the 2nd and 3rd LTL tertiles, respectively, was 0.82 (95% CI: 0.60–1.12; P = .22) and 0.76 (95% CI: 0.50–1.14; P = .18). However, after adjustments, LTL tertile 3 (vs. 1) was associated with all-cause mortality (HR = 0.37; 95% CI: 0.14–0.93; P = .03) for those who engaged in moderate-intensity exercise. Similarly, LTL was associated with CVD-specific mortality for those who engaged in moderate-intensity exercise (HR = 0.17; 95% CI: 0.04–0.73; P = .02). Longer telomeres are associated with increased survival, particularly among men and those who are active, underscoring the importance of promotion of physical activity behaviour.
Relations of Dispositions toward Ridicule and Histrionic Self-Presentation with Quantitative and Qualitative Humor Creation Abilities

Previous research has shown that humor and self-presentation are linked in several ways. With regard to individual differences, it turned out that gelotophilia (the joy of being laughed at) and katagelasticism (the joy of laughing at others) are substantially associated with the histrionic self-presentation style that is characterized by performing explicit As-If-behaviors (e.g., irony, parodying others) in everyday interactions. By contrast, gelotophobia (the fear of being laughed at) shows a negative correlation with histrionic self-presentation. In order to further contribute to the nomological network, we have explored whether the three dispositions toward ridicule and laughter as well as histrionic self-presentation are related to humor creation abilities. In doing so, we have assessed the four constructs in a study with 337 participants that also completed the Cartoon Punch line Production Test (CPPT, Köhler and Ruch, 1993, unpublished). In the CPPT, subjects were asked to generate as many funny punch lines as possible for six caption-removed cartoons. The created punch lines were then analyzed with regard to quantitative (e.g., number of punch lines) and qualitative (e.g., wittiness of the punch lines and overall wittiness of the person as evaluated by three independent raters) humor creation abilities. Results show that both gelotophilia and histrionic self-presentation were positively correlated with quantitative and qualitative humor creation abilities. By contrast, gelotophobia showed slightly negative and katagelasticism no associations with the assessed humor creation abilities. These findings especially apply to the subgroup of participants that created punch lines for each of the six cartoons and partly replicate and extend the results of a previous study by Ruch et al. (2009). Altogether, the results of our study show that individual differences in humor-related traits are associated with the quantity and quality of humorous punch lines. It is argued that behavior-related or performative humor creation tasks should be considered in addition to the CPPT in order to open up new avenues that can cross-fertilize research on individual differences in humor and self-presentation.
Electrical and Self-Sensing Properties of Ultra-High-Performance Fiber-Reinforced Concrete with Carbon Nanotubes

This study examined the electrical and self-sensing capacities of ultra-high-performance fiber-reinforced concrete (UHPFRC) with and without carbon nanotubes (CNTs). For this, the effects of steel fiber content, orientation, and pore water content on the electrical and piezoresistive properties of UHPFRC without CNTs were first evaluated. Then, the effect of CNT content on the self-sensing capacities of UHPFRC under compression and flexure was investigated. Test results indicated that higher steel fiber content, better fiber orientation, and higher amount of pore water led to higher electrical conductivity of UHPFRC. The effects of fiber orientation and drying condition on the electrical conductivity became minor as sufficiently high amount of steel fibers, 3% by volume, was added. Including only steel fibers did not impart UHPFRC with piezoresistive properties. Addition of CNTs substantially improved the electrical conductivity of UHPFRC. Under compression, UHPFRC with a CNT content of 0.3% or greater had a self-sensing ability that was activated by the formation of cracks, and better sensing capacity was achieved by including greater amount of CNTs. Furthermore, the pre-peak flexural behavior of UHPFRC was precisely simulated with a fractional change in resistivity when 0.3% CNTs were incorporated. The pre-cracking self-sensing capacity of UHPFRC with CNTs was more effective under tensile stress state than under compressive stress state.
Non-deterministic Predator-Prey Model with Accelerating Prey

This paper presents a data-driven, non-deterministic model of the dynamics of predator-prey interactions where the prey accelerates to a speed faster than the predator speed. The method proposed in this work predicts the probability of prey survival after a given number of approaches. The work presented here makes no assumptions about the form of the probability density function (PDF) of model parameters such as escape time, sensing range, strike distance, and strike success rate. It may therefore use empirical PDFs, i.e., those collected in biological experiments, for calculating the probability of capture. This allows for an investigation of parameters that are the most important to prey survival. A case study of the predation of larval zebrafish by adult zebrafish demonstrates the proposed technique.
Genomic regulation of invasion by STAT3 in triple negative breast cancer

Breast cancer is a heterogeneous disease comprised of four molecular subtypes defined by whether the tumor-originating cells are luminal or basal epithelial cells. Breast cancers arising from the luminal mammary duct often express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2). Tumors expressing ER and/or PR are treated with anti-hormonal therapies, while tumors overexpressing HER2 are targeted with monoclonal antibodies. Immunohistochemical detection of ER, PR, and HER2 receptors/proteins is a critical step in breast cancer diagnosis and guided treatment. Breast tumors that do not express these proteins are known as “triple negative breast cancer” (TNBC) and are typically basal-like. TNBCs are the most aggressive subtype, with the highest mortality rates and no targeted therapy, so there is a pressing need to identify important TNBC tumor regulators. The signal transducer and activator of transcription 3 (STAT3) transcription factor has been previously implicated as a constitutively active oncogene in TNBC. However, its direct regulatory gene targets and tumorigenic properties have not been well characterized. By integrating RNA-seq and ChIP-seq data from 2 TNBC tumors and 5 cell lines, we discovered novel gene signatures directly regulated by STAT3 that were enriched for processes involving inflammation, immunity, and invasion in TNBC. Functional analysis revealed that STAT3 has a key role regulating invasion and metastasis, a characteristic often associated with TNBC. Our findings suggest therapies targeting STAT3 may be important for preventing TNBC metastasis.
Correlation between the visibility of submandibular fossa and mandibular canal cortication on panoramic radiographs and submandibular fossa depth on CBCT

Background To identify a correlation between the submandibular fossa (SF) visibility and mandibular canal (MC) cortication on panoramic image and the depth of SF measured on CBCT and also correlation between the depth of SF and vertical and horizontal location of MC on CBCT. Material and Methods 500 CBCT scans and panoramic radiographs were evaluated. SF depth types were classified as type I (< 2mm); type II (2-3mm) and type III (> 3mm) on CBCT. Visibility of SF and the cortication of MC on panoramic radiographs were compared with the depth of SF on CBCT. Distances between MC and mandibular inferior, buccal and lingual cortices were measured. Results No statistically significant correlation was found between radiolucent appearances of SF, cortication of MC, and depth of SF. The deepest part of the fossa was in the second molar area followed by third and first molars. Negative weak correlations were found between B-MC, L-MC distances and depth of SF. Conclusions Visibility of SF and cortication of MC on panoramic radiographs did not correlate with the depth of SF. A marked radiolucent submandibular fossa on panoramic image does not undoubtedly indicate a deep fossa, which emphasizes the importance of 3-D imaging in implant planning. Key words:Cone beam computed tomography, panoramic radiography, dental implants, submandibular fossa, intraoperative complications, mandible, mandibular nerve.
A Synchronous Look at the Simulink Standard Library

Hybrid systems modelers like Simulink come with a rich collection of discrete-time and continuous-time blocks. Most blocks are not defined in terms of more elementary ones—and some cannot be—but are instead written in imperative code and explained informally in a reference manual. This raises the question of defining a minimal set of orthogonal programming constructs such that most blocks can be programmed directly and thereby given a specification that is mathematically precise, and whose compiled version performs comparably to handwritten code. In this paper, we show that a fairly large set of blocks of a standard library like the one provided by Simulink can be programmed in a precise, purely functional language using stream equations, hierarchical automata, Ordinary Differential Equations (ODEs), and deterministic synchronous parallel composition. Some blocks cannot be expressed in our setting as they mix discrete-time and continuous-time signals in unprincipled ways that are statically forbidden by the type checker. The experiment is conducted in Zélus, a synchronous language that conservatively extends Lustre with ODEs to program systems that mix discrete-time and continuous-time signals.