Miracle-dz/UniFAR-FTUs huggingface dataset:
Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis

Supplemental Digital Content is available in the text. Background: Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability. Methods: We conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis. Results: We provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target genes play an important role regulating SMC phenotypic changes. Single-cell RNA sequencing revealed remarkable similarity of transcriptomic clusters between mouse and human lesions and extensive plasticity of SMC- and endothelial cell-derived cells including 7 distinct clusters, most negative for traditional markers. In particular, SMC contributed to a Myh11-, Lgals3+ population with a chondrocyte-like gene signature that was markedly reduced with SMC-Klf4 knockout. We observed that SMCs that activate Lgals3 compose up to two thirds of all SMC in lesions. However, initial activation of Lgals3 in these cells does not represent conversion to a terminally differentiated state, but rather represents transition of these cells to a unique stem cell marker gene–positive, extracellular matrix-remodeling, “pioneer” cell phenotype that is the first to invest within lesions and subsequently gives rise to at least 3 other SMC phenotypes within advanced lesions, including Klf4-dependent osteogenic phenotypes likely to contribute to plaque calcification and plaque destabilization. Conclusions: Taken together, these results provide evidence that SMC-derived cells within advanced mouse and human atherosclerotic lesions exhibit far greater phenotypic plasticity than generally believed, with Klf4 regulating transition to multiple phenotypes including Lgals3+ osteogenic cells likely to be detrimental for late-stage atherosclerosis plaque pathogenesis.
Multi-level disourse relations between dialogue units

In order to analyse what happens in dialogue it is insufﬁcient to consider the content of its segments in isolation. In this paper we propose a meta-model for integrating discourse relations into a standard framework of dialogue act annotation (Bunt et al., 2010), considering in particular the various discourse units involved and the nature of their relations.
Feasibility of a Mobile Health App for Routine Outcome Monitoring and Feedback in Mutual Support Groups Coordinated by SMART Recovery Australia: Protocol for a Pilot Study

Background Despite the importance and popularity of mutual support groups, there have been no systematic attempts to implement and evaluate routine outcome monitoring (ROM) in these settings. Unlike other mutual support groups for addiction, trained facilitators lead all Self-Management and Recovery Training (SMART Recovery) groups, thereby providing an opportunity to implement ROM as a routine component of SMART Recovery groups. Objective This study protocol aims to describe a stage 1 pilot study designed to explore the feasibility and acceptability of a novel, purpose-built mobile health (mHealth) ROM and feedback app (Smart Track) in SMART Recovery groups coordinated by SMART Recovery Australia (SRAU) The secondary objectives are to describe Smart Track usage patterns, explore psychometric properties of the ROM items (ie, internal reliability and convergent and divergent validity), and provide preliminary evidence for participant reported outcomes (such as alcohol and other drug use, self-reported recovery, and mental health). Methods Participants (n=100) from the SMART Recovery groups across New South Wales, Australia, will be recruited to a nonrandomized, prospective, single-arm trial of the Smart Track app. There are 4 modes of data collection: (1) ROM data collected from group participants via the Smart Track app, (2) data analytics summarizing user interactions with Smart Track, (3) quantitative interview and survey data of group participants (baseline, 2-week follow-up, and 2-month follow-up), and (4) qualitative interviews with group participants (n=20) and facilitators (n=10). Feasibility and acceptability (primary objectives) will be analyzed using descriptive statistics, a cost analysis, and a qualitative evaluation. Results At the time of submission, 13 sites (25 groups per week) had agreed to be involved. Funding was awarded on August 14, 2017, and ethics approval was granted on April 26, 2018 (HREC/18/WGONG/34; 2018/099). Enrollment is due to commence in July 2019. Data collection is due to be finalized in October 2019. Conclusions To the best of our knowledge, this study is the first to use ROM and tailored feedback within a mutual support group setting for addictive behaviors. Our study design will provide an opportunity to identify the acceptability of a novel mHealth ROM and feedback app within this setting and provide detailed information on what factors promote or hinder ROM usage within this context. This project aims to offer a new tool, should Smart Track prove feasible and acceptable, that service providers, policy makers, and researchers could use in the future to understand the impact of SMART Recovery groups. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000686101; https://anzctr.org. au/Trial/Registration/TrialReview.aspx? id=377336. International Registered Report Identifier (IRRID) PRR1-10.2196/15113
Fixed-Time Synchronization of Coupled Neural Networks With Discontinuous Activation and Mismatched Parameters

This article is concerned with fixed-time synchronization of the nonlinearly coupled neural networks with discontinuous activation and mismatched parameters. First, a novel lemma is proposed to study fixed-time stability, which is less conservative than those in most existing results. Then, based on the new lemma, a discontinuous neural network with mismatched parameters will synchronize to the target state within a settling time via two kinds of unified and simple controllers. The settling time is theoretically estimated, which is independent of the initial values of the considered network. In particular, the estimated settling time is closer to the real synchronization time than those given in the existing literature. Finally, two numerical simulations are presented to illustrate the effectiveness and correctness of our results.
Automated analysis of natural speech in amyotrophic lateral sclerosis spectrum disorders

Objective We implemented automated methods to analyze speech and evaluate the hypothesis that cognitive and motor factors impair prosody in partially distinct ways in patients with amyotrophic lateral sclerosis (ALS). Methods We recruited 213 participants, including 67 with ALS (44 with motor ALS, 23 with ALS and frontotemporal degeneration [FTD]), 33 healthy controls, and neurodegenerative reference groups with behavioral variant FTD (n = 90) and nonfluent/agrammatic primary progressive aphasia (n = 23). Digitized, semistructured speech samples obtained from picture descriptions were automatically segmented with a Speech Activity Detector; continuous speech segments were pitch-tracked; and duration measures for speech and silent pause segments were extracted. Acoustic measures were calculated, including fundamental frequency (f0) range, mean speech and pause segment durations, total speech duration, and pause rate (pause count per minute of speech). Group comparisons related performance on acoustic measures to clinical scales of cognitive and motor impairments and explored MRI cortical thinning in ALS and ALS-FTD. Results The f0 range was significantly impaired in ALS spectrum disorders and was related to bulbar motor disease, and regression analyses related this to cortical thickness in primary motor cortex and perisylvian regions. Impaired speech and pause duration measures were related to the degree of cognitive impairment in ALS spectrum disorders, and regressions related duration measures to bilateral frontal opercula and left anterior insula. Conclusion Automated analyses of acoustic speech properties dissociate motor and cognitive components of speech deficits in ALS spectrum disorders.
Thermal Stability of Whey Proteins – A Calorimetric Study

Abstract Several factors affecting thermal stability of the proteins present in whey were studied over 2.5 to 6.5 pH range using differential scanning calorimetry and heat-induced precipitation. Heating whey at 95°C for 5min above pH 3.8 to 3.9 produced extensive protein coagulation. When the same heat treatment was applied below pH 3.7, protein precipitation was prevented; however, protein denaturation still occurred in various whey protein fractions. The highest denaturation temperature for an acid whey protein concentrate prepared by ultrafiltration was 88°C at pH 3.5, while for an isolated β-lactoglobulin preparation the highest denaturation temperature, obtained also at pH 3.5, was 81.9°C. Presence of milk sugars (lactose, glucose, and galactose) appeared to increase the resistance of β-lactoglobulin to thermal denaturation. Heat stability of α-lactalbumin was lower at pH 3.5 than in the pH 6.5 to 4.5 range; at all pH denaturation temperatures of α-lactalbumin (61.5 to 58.6°C) were lower than those for β-lactoglobulin or two serum albumin preparations. Sample of serum albumin containing 1.0 to 1.3mol of fatty acids/mol of albumin showed substantially higher denaturation temperatures than an essentially fatty acid free preparation. Thermal behavior of an ultrafiltration whey protein concentrate appears to be controlled by the dominating β-lactoglobulin fraction.
Studies on the Fatty Acid Composition of Edible Oil

Fatty acid analysis of the five types of locally consumed edible oils (n = 22) was carried out using a Gas Chromatograph (G.C) equipped with a Flame Ionization Detector (FID) and stainless steel packed column. The results showed that sunflower oil contained the highest percentage of long chain mono and polyunsaturated fatty acids (91.49 ± 1.91 %) compared to soybean oil (81.14 ± 1.49 %), mustard oil (86.80 ± 3.07 %), palm oil (53.30 ± 0.36 %) and coconut oil (7.12 ± 0.51 %). Two varieties of mustard oil, low erucic (= 5 %, n=3) and high erucic acid ( >14 %, n=2) and two varieties of sunflower oil, high linoleic-low oleic (61-66 % & 22-27 %, n=2) and low linoleic- high oleic (29-38 % and 53-63 %, n =3) were found. Sunflower oil with the highest percentage of mono and polyunsaturated fatty acids especially the high linoleic- low oleic variety appeared to be superior and most suitable edible oil for mass consumption. Key words: Fatty acid, Gas chomatograph, Sunflower oil, Soybean oil, Mustard oil, Palm oil, Coconut oil. Bangladesh J. Sci. Ind. Res. 42(3), 311-316, 2007
Short and Long Term Fluctuations of the Leaf Mass Per Area of Tomato Plants—Implications for Growth Models

Abstract The leaf mass per unit leaf area (LMA) is a key variable in many growth models, since it is often used to predict leaf area expansion from leaf dry weight increase, orvice versa. Influences of source-sink balance on leaf area, leaf dry weight, LMA, and leaf content in non-structural carbohydrates were investigated in glasshouse tomato crops. The source-sink balance was manipulated by artificial shading, CO2enrichment or fruit removal using different tomato cultivars. Leaf area was hardly affected by competition for assimilates except under extreme conditions. In contrast, leaf dry weight, and consequently LMA, underwent large and rapid fluctuations in response to any factor that changed source and sink activities. A 60% reduction of photosynthetically active radiation involved a 24% decrease in LMA after 10 d. Carbon dioxide enrichment and fruit removal induced about a 45% and 15% increase in LMA, respectively, on plants with two fruiting trusses, but hardly affected LMA of producing plants. No significant cultivar effect could be identified. Changes in starch and soluble sugar content in leaves accounted for only 29% of diurnal variations in LMA, suggesting regular fluctuations of other components. We propose that structural LMA varies between a maximum and a minimum value according to the ratio of assimilate supply and demand during leaf development. Leaf area is independent of the supply of assimilates when the minimum structural LMA is realised. When the maximum structural LMA is attained, a storage pool of assimilates may accumulate in leaves during periods of high supply and low demand. We present a model including these hypotheses, which predicts structural and non-structural LMA variations of plants with different source-sink ratios.
Comparative study of photoinitiators for the synthesis and 3D printing of a light-curable, degradable polymer for custom-fit hard tissue implants

Three-dimensional (3D) printing enhances the production of on-demand fabrication of patient-specific devices, as well as anatomically fitting implants with high complexity in a cost-effective manner. Additive systems that employ vat photopolymerisation such as stereolithography (SLA) and digital light projection are used widely in the field of biomedical science and engineering. However, additive manufacturing methods can be limited by the types of materials that can be used. In this study, we present an isosorbide-based formulation for a polymer resin yielding a range of elastic moduli between 1.7 and 3 GN mm−2 dependent on the photoinitiator system used as well as the amount of calcium phosphate filler added. The monomer was prepared and enhanced for 3D-printing using an SLA technique that delivered stable and optimized 3D-printed models. The resin discussed could potentially be used following major surgery for the correction of congenital defects, the removal of oral tumours and the reconstruction of the head and neck region. The surgeon is usually limited with devices available to restore both function and appearance and with the ever-increasing demand for low-priced and efficient facial implants, there is an urgent need to advance new manufacturing approaches and implants with a higher osseointegration performance.
Economic Perspectives of Biogas Production via Anaerobic Digestion

As the demand for utilizing environment-friendly and sustainable energy sources is increasing, the adoption of waste-to-energy technologies has started gaining attention. Producing biogas via anaerobic digestion (AD) is promising and well-established; however, this process in many circumstances is unable to be cost competitive with natural gas. In this research, we provide a technical assessment of current process challenges and compare the cost of biogas production via the AD process from the literature, Aspen Plus process modeling, and CapdetWorks software. We also provide insights on critical factors affecting the AD process and recommendations on optimizing the process. We utilize four types of wet wastes, including wastewater sludge, food waste, swine manure, and fat, oil, and grease, to provide a quantitative assessment of theoretical energy yields of biogas production and its economic potential at different plant scales. Our results show that the cost of biogas production from process and economic models are in line with the literature with a potential to go even lower for small-scale plants with technological advancements. This research illuminates potential cost savings for biogas production using different wastes and guide investors to make informed decisions, while achieving waste management goals.
Expression and synthesis of fibroblast growth factor‐9 in human γδ T‐lymphocytes. Response to isopentenyl pyrophosphate and TGF‐β1/IL‐15

γδ T‐lymphocytes are believed to play a role in maintaining the normal configuration of epithelial tissue. As little is known about the factors mediating this function, we addressed the question of whether γδ T‐lymphocytes produce fibroblast growth factor (FGF)‐9 as well as two other growth factors associated with epithelial tissue reconstitution. Blood γδ T cells isolated from healthy donors were grown in the presence of isopentenyl pyrophosphate (IPP) or transforming growth factor‐β1 (TGF‐β1)/interleukin‐15 (IL‐15) for 24 h and were assessed for the expression and synthesis of FGF‐9, keratinocyte growth factor (KGF), and epidermal growth factor (EGF). Resting human γδ T cells constitutively expressed KGF and FGF‐9 mRNA but no EGF mRNA. In the presence of IPP, FGF‐9 mRNA expression significantly increased in a dose‐dependent manner, expression of KGF remained unaltered, and EGF mRNA could not be detected. In contrast to IPP, stimulation of the cells with TGF‐β1/IL‐15 did not alter FGF‐9 expression. Moreover, stimulation with anti‐CD3 does not induce FGF‐9 expression but triggers a high signal of interferon‐γ mRNA. Western blot analysis of γδ T cell lysates, prepared 4 days following stimulation with IPP, showed an increase of FGF‐9 protein as compared with control cells. In conclusion, the results demonstrate for the first time that human blood and bronchoalveolar lavage γδ T‐lymphocytes are capable of expressing FGF‐9. The data also provide novel evidence that immunoregulatory cells can synthesize FGF‐9.
Improvements in anchorage provided by the acclimation of forest trees to wind stress

Summary Trees are known to modify their growth in windy climates, but these responses have not previously been linked to alterations in anchorage strength. The effects of stem mass, soil group, rooting depth and wind exposure (Detailed Aspect Method of Scoring (DAMS)) on anchorage were modelled using data from experiments where Sitka spruce ( Picea sitchensis (Bong.) Carr. ) trees had been mechanically overturned. Regressions of critical turning moment against stem mass were performed on combinations of soil group (mineral, gleyed mineral, peaty mineral and deep peat) and rooting depth ( 80 cm), with DAMS as an additional factor. Correlations of DAMS with critical turning moment were positive for all combinations, and DAMS had a positive effect on the slope of all critical turning moment against stem mass regressions. When DAMS was added to the model, it increased the variance accounted for, from 66.5 to 71.2 per cent. When revised anchorage coeffi cients were applied to the ForestGALES wind risk model, critical wind speeds and associated return times for a 55-year-old stand were reduced on a relatively sheltered DAMS 14 site and increased on a wind-exposed DAMS 18 site. The implications of trees developing stronger anchorage in locations with greater wind exposure are discussed in relation to management of wind risk.
T-box transcription factor 3 governs a transcriptional program for the function of the mouse atrioventricular conduction system

Significance Genome-wide association studies have identified common noncoding variants associated with ECG parameters in the TBX3 locus, suggesting that a modest change in TBX3/Tbx3 expression level affects heart function. We characterized the morphology, physiology, and gene expression profile of the atrioventricular conduction system in a Tbx3 haploinsufficient mouse model. We identified Tbx3-dependent regulatory DNA elements active in the atrioventricular conduction system and validated the functionality of these elements in vivo. Using genome editing, we deleted a regulatory DNA element from the mouse genome and show it drives expression of Cacna1g in the cardiac conduction system. Our study unveils a Tbx3-dependent gene regulatory network in the AV conduction system that contributes to heart electrophysiology. Genome-wide association studies have identified noncoding variants near TBX3 that are associated with PR interval and QRS duration, suggesting that subtle changes in TBX3 expression affect atrioventricular conduction system function. To explore whether and to what extent the atrioventricular conduction system is affected by Tbx3 dose reduction, we first characterized electrophysiological properties and morphology of heterozygous Tbx3 mutant (Tbx3+/−) mouse hearts. We found PR interval shortening and prolonged QRS duration, as well as atrioventricular bundle hypoplasia after birth in heterozygous mice. The atrioventricular node size was unaffected. Transcriptomic analysis of atrioventricular nodes isolated by laser capture microdissection revealed hundreds of deregulated genes in Tbx3+/− mutants. Notably, Tbx3+/− atrioventricular nodes showed increased expression of working myocardial gene programs (mitochondrial and metabolic processes, muscle contractility) and reduced expression of pacemaker gene programs (neuronal, Wnt signaling, calcium/ion channel activity). By integrating chromatin accessibility profiles (ATAC sequencing) of atrioventricular tissue and other epigenetic data, we identified Tbx3-dependent atrioventricular regulatory DNA elements (REs) on a genome-wide scale. We used transgenic reporter assays to determine the functionality of candidate REs near Ryr2, an up-regulated chamber-enriched gene, and in Cacna1g, a down-regulated conduction system-specific gene. Using genome editing to delete candidate REs, we showed that a strong intronic bipartite RE selectively governs Cacna1g expression in the conduction system in vivo. Our data provide insights into the multifactorial Tbx3-dependent transcriptional network that regulates the structure and function of the cardiac conduction system, which may underlie the differences in PR duration and QRS interval between individuals carrying variants in the TBX3 locus.