Miracle-dz/UniFAR-FTUs huggingface dataset:
Response of small intestinal epithelial cells to acute disruption of cell division through CDC25 deletion

The CDC25 protein phosphatases (CDC25A, B, and C) drive cell cycle transitions by activating key components of the cell cycle engine. CDC25A and CDC25B are frequently overproduced in human cancers. Disruption of Cdc25B or Cdc25C individually or in combination has no effect on mouse viability. Here we report that CDC25A is the only family member to provide an essential function during early embryonic development, and that other family members compensate for its loss in adult mice. In contrast, conditional disruption of the entire family is lethal in adults due to a loss of small intestinal epithelial cell proliferation in crypts of Lieberkühn. Cdc25 loss induced Wnt signaling, and overall crypt structures were preserved. In the face of continuous Wnt signaling, nearly all crypt epithelial progenitors differentiated into multiple cell lineages, including crypt base columnar cells, a proposed stem cell. A small population of Musashi/Dcamkl-1/nuclear β-catenin–positive epithelial cells was retained in these crypts. These findings have implications for the development of novel, less cytotoxic cancer chemotherapeutic drugs that specifically target the cell cycle.
Effect of dietary copper and fat on nutrient utilization, digestive enzyme activities, and tissue mineral levels in weanling pigs.

Two 15-d nutrient balance trials were conducted using a total of 32 weanling barrows (averaging 6.8 kg, 26 d). The effect of the addition of 15 or 250 ppm Cu (as CuSO4.5H2O) to diets containing 0 or 5% added animal fat on nutrient utilization, digestive enzyme activities, and tissue mineral levels in weanling pigs was investigated. In each trial, four groups of four littermate barrows were randomly assigned to one of four treatments in a 2 x 2 factorial arrangement. The addition of 250 ppm Cu improved apparent fat digestibility and apparent nitrogen retention (P < .02). The addition of 5% fat increased apparent fat digestibility (P < .01). There were no Cu x fat interactions (P > .10) for any of the digestibility indices measured. The addition of 250 ppm of Cu stimulated small intestinal lipase (P < .01) and phospholipase A (P < .05) activities but had no effect (P > .10) on pancreatic lipase or phospholipase activities and no effect on trypsin, chymotrypsin, or amylase activities in the small intestine or the pancreas. The addition of 250 ppm Cu to the diet increased Cu (P < .001) in plasma, liver, and kidney and decreased Fe in plasma (P < .05) and liver (P < .02). The addition of 5% fat increased Fe in kidney (P < .05) and heart (P < .08). Copper x fat interactions were observed for spleen Ca (P < .01), Mg (P < .08), Na (P < .05), and K (P < .08) and spleen weight (P < .05). In additional in vitro assays, increased Cu concentrations tended to consistently stimulate purified porcine pancreatic lipase activity (linear, P < .01) but not purified porcine pancreatic phospholipase A activity (P > .10). The results from this study indicate that 250 ppm Cu stimulated intestinal lipase and phospholipase A activities, leading to an improvement of dietary fat digestibility in weanling pigs.
Movement of Anopheles gambiae s.l. malaria vectors between villages in The Gambia

ovement of mosquitoes belonging to the Anopheles gambiae complex (mixed wild populations of An.arabiensis, An.gambiae and An.melas) between three neighbouring rural villages in The Gambia was investigated by mark‐release‐recapture. A total of 12,872 mosquitoes were collected in bednets, marked with a magenta fluorescent powder and released over a 15‐day period in one of the villages. A further 15,507 mosquitoes were collected in exit traps, marked with a yellow powder and released over the same period. Mosquitoes were captured daily in all three villages using pyrethrum spray catches, as well as bednet and exit trap catches. The catching period extended for 6 days after the last day of release.
The effect of light-emitting diode photobiomodulation on implant stability and biochemical markers in peri-implant crevicular fluid.

OBJECTIVE The purpose of this study was to determine the effect of light-emitting diode photomodulation (LED PBM) on implant osseointegration by measuring implant stability changes by resonance frequency analysis (RFA) and measuring interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), prostaglandin-E2 (PGE2), and nitric oxide (NO) levels in peri-implant crevicular fluid (PICF). BACKGROUND DATA Light therapy modulates various biological events and allows improved wound healing in ischemic and wounded tissues. METHODS Fifteen patients (8 control, 7 LED) participated in the study. In the LED group, LED device at a wavelength of 626 nm in the near-infrared (NIR) region (treatment array area: 4.80 cm2; average intensity: 38.5 mW/cm2; total power: 185 mW; total energy: 222 J; average density: 46.2 J/cm2) was applied for 20 min over the surgical area during 3 weeks, three times in a week, starting from the operation day. Implant stability quotient (ISQ) values were recorded at the time of operation, and 2, 4, 8, and 12 weeks postoperatively. PICF samples were collected in postoperative weeks 4 and 12 and IL-1β, TGF-β, PGE2, and NO levels were evaluated. Clinical indices were recorded around implants in postoperative weeks 4 and 12. RESULTS In the control group, significant reduction of ISQ values from week 2 to week 12 were demonstrated. In the LED group, baseline ISQ values were maintained during the study and no significant changes were observed. Changes in biochemical parameters were found to be similar between groups over time. However, in the LED group, a negative correlation was found between PGE2 and ISQ values. CONCLUSIONS LED application to surgical area has a positive effect on the osseointegration process, and implant stability can be maintained.
Genital Lichen Sclerosus in Male Patients: A New Treatment with Polydeoxyribonucleotide

Lichen sclerosus (LS) is an inflammatory and chronic disease that causes itching, pain, dysuria, urinary retention, dyspareunia and sexual dysfunction, in both men and women. The first line pharmacological treatment is based on the use of topical steroids, which have proved their efficacy in 60-70% of cases but with a high rate of relapses in time (50-80% of the patients of both sexes). The purpose of our non-randomised prospective pilot study was to evaluate the efficacy and tolerability of a new loco regional therapy with polydeoxyribonucleotides (PDRN) in the treatment of male genital LS. PDRN is an healing and anti-dystrophic drug with anti-inflammatory effects, through the reduction of cytokine. Twenty one male patients suffering from genital LS were recruited. All the patients were submitted to treatment using loco-regional intradermal injections with PDRN. Dermatology Life Quality Index (DLQI), International Index of Erectile Function (IIEF-5) and PGI-I questionnaires were administered at baseline and at the end of treatment in order to evaluate the results of this treatment. The statistical evaluation of the data obtained with the DLQI questionnaire showed a marked improvement of the overall conditions in terms of quality of life, with an average change of scores from 15 to 4 (p < 0.0001). PGI-I questionnaire showed that 80% of the patients treated considered their post-treatment conditions as ‘improved'. There was no significant change in terms of sexual function according to the IIEF questionnaire (p = 0.189). The results obtained show the excellent tolerability and the therapeutic efficacy of PDRN, with clear improvement of the local symptoms and of the quality of life.
Consensus in interpersonal perception: acquaintance and the big five.

Consensus refers to the extent to which judges agree in their ratings of a common target. Consensus has been an important area of research in social and personality psychology. In this article, generalizability theory is used to develop a percentage of total variance measure of consensus. This measure is used to review the level of consensus across 32 studies by considering the role of acquaintance level and trait dimension. The review indicates that consensus correlations ranged from zero to about . 3, with higher levels of consensus for ratings of Extraversion. The studies do not provide evidence that consensus increases with increasing acquaintance, a counterintuitive result that can be accounted for by a theoretical model (D.A. Kenny, 1991, in press). Problems in the interpretation of longitudinal research are reviewed.
Demethylation of IGFBP5 by Histone Demethylase KDM6B Promotes Mesenchymal Stem Cell‐Mediated Periodontal Tissue Regeneration by Enhancing Osteogenic Differentiation and Anti‐Inflammation Potentials

Mesenchymal stem cell (MSC)‐mediated periodontal tissue regeneration is considered a promising method for periodontitis treatment. The molecular mechanism underlying directed differentiation and anti‐inflammatory actions remains unclear, thus limiting potential MSC application. We previously found that insulin‐like growth factor binding protein 5 (IGFBP5) is highly expressed in dental tissue‐derived MSCs compared with in non‐dental tissue‐derived MSCs. IGFBP5 is mainly involved in regulating biological activity of insulin‐like growth factors, and its functions in human MSCs and tissue regeneration are unclear. In this study, we performed gain‐ and loss‐of‐function assays to test whether IGFBP5 could regulate the osteogenic differentiation and anti‐inflammatory potential in MSCs. We found that IGFBP5 expression was upregulated upon osteogenic induction, and that IGFBP5 enhanced osteogenic differentiation in MSCs. We further showed that IGFBP5 prompted the anti‐inflammation effect of MSCs via negative regulation of NFκB signaling. Depletion of the histone demethylase lysine (K)‐specific demethylase 6B (KDM6B) downregulated IGFBP5 expression by increasing histone K27 methylation in the IGFBP5 promoter. Moreover, IGFBP5 expression in periodontal tissues was downregulated in individuals with periodontitis compared with in healthy people, and IGFBP5 enhanced MSC‐mediated periodontal tissue regeneration and alleviated local inflammation in a swine model of periodontitis. In conclusion, our present results reveal a new function for IGFBP5, provide insight into the mechanism underlying the directed differentiation and anti‐inflammation capacities of MSCs, and identify a potential target mediator for improving tissue regeneration. Stem Cells 2015;33:2523–2536
Smooth Muscle Hypoxia-Inducible Factor 1&agr; Links Intravascular Pressure and Atherosclerosis—Brief Report

Objective— We hypothesized that the hypoxia-inducible factor (HIF) 1&agr; in vascular smooth muscle contributes to the development of atherosclerosis, and links intravascular pressure to this process. Approach and Results— Transverse aortic constriction was used to create high-pressure vascular segments in control, apolipoprotein E (ApoE)−/−, smooth muscle-HIF1&agr;−/− , and ApoE−/− ×smooth muscle-HIF1&agr;−/− double-knockout mice. Transverse aortic constriction selectively induced atherosclerosis in high-pressure vascular segments in young ApoE−/− mice on normal chow, including coronary plaques within 1 month. Concomitant deletion of HIF1&agr; from smooth muscle significantly reduced vascular inflammation, and attenuated atherosclerosis. Conclusions— HIF1&agr; in vascular smooth muscle plays an important role in the pathogenesis of atherosclerosis, and may provide a mechanistic link between blood pressure, vascular inflammation, and lipid deposition.
A dynamic advertising model with reference price effect

This paper develops an advertising model in which goodwill affected by advertising effort has a positive effect on reference price and market demand. In a finite planning horizon, the optimal advertising strategy is provided by solving the optimization problem on the basis of Pontryagin’s maximum principle, then the optimal sales price is obtained through one time pricing strategy. Furthermore, we extend this problem to an infinite planning horizon and present the corresponding optimal strategies. In addition, the relationships between system parameters and optimal solutions are analyzed. Numerical examples are employed to illustrate the effectiveness of the theoretical results, and to assess the sensitivity analysis of system parameters on the optimal strategies.
Erythropoietin inhibits osteoblast function in myelodysplastic syndromes via the canonical Wnt pathway

The effects of erythropoietin on osteoblasts and bone formation are controversial. Since patients with myelodysplastic syndromes often display excessively high erythropoietin levels, we aimed to analyze the effect of erythropoietin on osteoblast function in myelodysplastic syndromes and define the role of Wnt signaling in this process. Expression of osteoblast-specific genes and subsequent osteoblast mineralization was increased in mesenchymal stromal cells from healthy young donors by in vitro erythropoietin treatment. However, erythropoietin failed to increase osteoblast mineralization in old healthy donors and in patients with myelodysplasia, whereas the basal differentiation potential of the latter was already significantly reduced compared to that of age-matched controls (P<0.01). This was accompanied by a significantly reduced expression of genes of the canonical Wnt pathway. Treatment of these cells with erythropoietin further inhibited the canonical Wnt pathway. Exposure of murine cells (C2C12) to erythropoietin also produced a dose-dependent inhibition of TCF/LEF promoter activity (maximum at 500 IU/mL, −2.8-fold; P<0.01). The decreased differentiation capacity of erythropoietin-pretreated mesenchymal stromal cells from patients with myelodysplasia could be restored by activating the Wnt pathway using lithium chloride or parathyroid hormone. Its hematopoiesis-supporting capacity was reduced, while reactivation of the canonical Wnt pathway in mesenchymal stromal cells could reverse this effect. Thus, these data demonstrate that erythropoietin modulates components of the osteo-hematopoietic niche in a context-dependent manner being anabolic in young, but catabolic in mature bone cells. Targeting the Wnt pathway in patients with myelodysplastic syndromes may be an appealing strategy to promote the functional capacity of the osteo-hematopoietic niche.
ExpressionTh17 Differentiation via Repression of IL-17 Transcriptional Regulator CTR9 Inhibits

PAF complex is an evolutionarily conserved transcriptional complex that associates with RNA polymerase II in the coding region of actively transcribing genes. Although its transcriptional activity is closely related to diverse cellular processes, such as cell-cycle progression or development in mammals, its role in immune responses has not been addressed yet. In this study, we show that CTR9, a component of PAF complex, functions as a repressor of Th17 differentiation. Both mRNA and protein levels of CTR9 were signiﬁcantly decreased during the differentiation processes of naive T into Th17 effector cells. When CTR9 was depleted, IL-17 expression was induced and differentiation into Th17 cells enhanced. In naive T cells, CTR9 occupied the coding region of Il17a , but dissociated under Th17 in vitro-polarizing conditions. In contrast, both CDC73 and PAF1 were recruited to the Il17a locus under Th17-differentiation conditions. In the IL-6–stimulated splenocytes, expression of CTR9 was decreased, and chromatin-bound CTR9 disappeared in the coding region of Il17a . IL-6 also directly repressed expression of CTR9 gene, as promoter activity of CTR9 was similarly repressed by IL-6 treatment. Moreover, in mice with collagen-induced arthritis, lentivirus-mediated CTR9 overexpression in the joints ameliorated arthritis severity, decreasing the frequency of CD4 + IL-17 + T cells in lymph nodes. In conclusion, our data propose a novel feed-forward loop of IL-17 transcriptional regulatory circuit, via IL-6–mediated repression of CTR9 which is a transcriptional repressor of IL-17. The Journal of Immunology , 2014, 192: 000–000. interplay
Integrating engineering, economic, and social modeling in risks of cascading failures across interdependent complex networks

Planning for electric power reliability and recovery from catastrophic failures requires knowledge of the interdependencies between electrical systems and the economic and social systems mat they serve. To date, however, such planning has been conducted in an atomistic fashion, with little recognition that system interdependencies have major effects on benefits and costs of catastrophic failures. This paper stresses the need to integrate social, economic and engineering modeling in the risk assessment and management of cascading failures leading to blackouts. Evaluation of cascading economic and social impacts of major power losses will be based on contingent and subjective valuation methods built into a computable general equilibrium model. This model is being validated using surveys in the Washington DC Metropolitan region. The assessed risks and costs are integrated in the power system planning phase.
Symptoms, airway responsiveness, and exposure to dust in beech and oak wood workers

OBJECTIVES To investigate the relation between levels of cumulative exposure to wood dust and respiratory symptoms and the occurrence of bronchial hyperresponsiveness among beech and oak workers. METHODS 114 Male woodworkers from five furniture factories and 13 male unexposed controls were examined. The unexposed control group was supplemented by 200 male historical controls. Statistical analyses were performed excluding and including the historical controls. Dust concentration was measured by personal sampling methods. Cumulative exposure to dust was calculated for each woodworker by multiplying the duration of the work by the intensity of exposure (years.mg/m3). Bronchial hyperresponsiveness was assessed by the methacholine bronchial challenge test. Subjects were labelled methacholine bronchial challenge positive if forced expiratory volume in 1 second (FEV1) fell by ⩾20%. The linear dose-response slope was calculated as the last dose divided by the total dose given. RESULTS 443 Dust samples were collected. The median cumulative exposure to dust was 110 years.mg/m3 with lower and upper quartiles at 70 and 160 years.mg/m3 Overall, no declines in FEV1 and forced vital capacity (FVC) were found with increasing exposures. A dose-response relation was found between intensity of exposure on the one hand, and sore throat, increased prevalence of positive methacholine bronchial challenge tests, and steeper dose-response slope, on the other. CONCLUSION Exposure to oak and beech dust may lead to the development of sore throat and bronchial hyperresponsiveness.
Creativity and Financial Incentives September 12 , 2014

Creativity is a complex and multi-dimensional phenomenon with tremendous economics importance. Yet, despite this importance, there is very little work on the topic in the economics literature. In this paper, we consider the effect of incentives on creativity. We present a first series of experiments on individual creativity where subjects face creativity tasks where, in one case, ex-ante goals and constraints are imposed on their answers, and in the other case no restrictions apply. The effects of financial incentives in stimulating creativity in both types of tasks is then tested, together with the impact of personal features like risk and ambiguity aversion. Our findings show that, in general, financial incentives affect “closed” (constrained) creativity, but do not facilitate “open” (unconstrained) creativity. However, in the latter case incentives do play a role for ambiguity-averse agents, who tend to be significantly less creative and seem to need extrinsic motivation to exert effort in a task whose odds of success they don’t know. The second set of experiments aims at exploring group creativity in contexts where the “corporate culture” is either cooperative or individualistic. Our results show that, in the case of closed tasks, financial incentives and collectivist attitudes foster creativity, but only with cooperative corporate culture.
SAR Algorithm for Sea Ice Concentration—Evaluation for the Baltic Sea

A new sea ice concentration algorithm has been developed for C-band synthetic aperture radar data. Detailed autocorrelation statistics are derived and adopted by the algorithm, and a neural network is utilized for training against 41 sea ice charts. The charts are produced by ice analysts at the Swedish Ice Service and cover the Baltic Sea. The classification of open water pixels is accurate to 94% on average, and the classification of sea ice pixels has an accuracy of 87%. This results in a root-mean-square error of 6.7 percentage points in estimating the sea ice concentration.
Giant hair matrix tumor

Twelve cases of a peculiar, relatively uncommon, benign but locally invasive tumor occurring in the skin of the scalp and mocha are reported. The neoplasm occurs primarily in elderly women and only exceptionally in men. Its growth is very slow and usually many years elapse before the patient comes under treatment; thus, the tumor may attain a huge size. These deeply invasive neoplasms do not metastasize but may recur if not completely excised. Morphologically, it is an epithelial keratinizing growth clearly showing differentiation into the pilosebaceous structures, especially into the outer sheath of the hair follicle. It does not correspond to the “pilomatrixoma” of Forbes and Helwig (calcifying epithelioma of Malherbe) and constitutes a distinct clinicopathologic entity.
Morphoregulation by acetylcholinesterase in fibroblasts and astrocytes

Acetylcholinesterase (AChE) terminates neurotransmission at cholinergic synapses by hydrolysing acetylcholine, but also has non‐enzymatic morphoregulatory effects on neurons such as stimulation of neurite outgrowth. It is widely expressed outside the nervous system, but its function in non‐neuronal cells is unclear. Here we have investigated the distribution and function of AChE in fibroblasts and astrocytes. We show that these cells express high levels of AChE protein that co‐migrates with recombinant AChE but contains little catalytic activity. Fibroblasts express transcripts encoding the synaptic AChE‐T isoform and its membrane anchoring peptide PRiMA‐I. AChE is strikingly distributed in arcs, rings and patches at the leading edge of spreading and migrating fibroblasts and astrocytes, close to the cell–substratum interface, and in neuronal growth cones. During in vivo healing of mouse skin, AChE becomes highly expressed in re‐epithelialising epidermal keratinocytes 1 day after wounding. AChE appears to be functionally important for polarised cell migration, since an AChE antibody reduces substratum adhesion of fibroblasts, and slows wound healing in vitro as effectively as a β1‐integrin antibody. Moreover, elevation of AChE expression increases fibroblast wound healing independently of catalytic activity. Interestingly, AChE surface patches precisely co‐localise with amyloid precursor protein and the extracellular matrix protein perlecan, but not focal adhesions or α‐dystroglycan, and contain a high concentration of tyrosine phosphorylated proteins in spreading cells. These findings suggest that cell surface AChE, possibly in a novel signalling complex containing APP and perlecan, contributes to a generalised mechanism for polarised membrane protrusion and migration in all adherent cells. J. Cell. Physiol. 215: 82–100, 2008. © 2007 Wiley‐Liss, Inc.