Miracle-dz/UniFAR-FTUs huggingface dataset:
Low dose of oleanolic acid protects against lithocholic acid-induced cholestasis in mice: potential involvement of Nrf2 mediated up-regulation of Mrps

: Oleanolic acid (OA) is a natural triterpenoid and has been demonstrated to protect against varieties of hepatotoxicants. However recently, OA at high doses was reported to produce apparent cholestasis in mice. In this study, we characterized the protective effect of OA at low doses against lithocholic acid (LCA)-induced cholestasis in mice and explored further mechanisms. OA co-treatment (5, 10, 20 mg/kg, i.p.) significantly improved mice survival rate, attenuated liver necrosis and decreased serum ALT, AST and ALP, more importantly, serum total bile acids and bilirubin, as well as hepatic total bile acids were also remarkably reduced. Gene and protein expression analysis showed that hepatic expression of Mrp2, Mrp3 and Mrp4 were significantly increased by OA co-treatment, whereas other bile acid metabolism and transport related genes including Ntcp, Oatp1b2, Bsep, Mdr3, Cyp3a11, Cyp2b10, Sult2a1 and Ugt1a1 were only slightly changed. OA also caused increased Nrf2 mRNA expression and nuclear protein accumulation, whereas nuclear receptors FXR, PXR and CAR were not significantly influenced by OA. Luciferase assays performed in HepG2 cells illustrated that OA was a strong Nrf2 agonist with moderate PXR and weak FXR agonism. Finally, in mice primary cultured hepatocytes, OA dose-and time-dependently induced expression of Mrp2, Mrp3 and Mrp4 , however, this up-regulation were abrogated when Nrf2 was silenced. In conclusion, OA produces protective effect against LCA-induced hepatotoxicity and cholestasis, possibly due to Nrf2-mediated up-regulation of Mrp2, Mrp3 and Mrp4.
Ad Hoc Networks

Wireless mesh networks are an attractive technology for providing broadband connectivity to mobile clients who are just on the edge of wired networks, and also for building selforganized networks in places where wired infrastructures are not available or not deemed to be worth deploying. This paper investigates the joint link scheduling and routing issues involved in the delivery of a given backlog from any node of a wireless mesh network towards a specific node (which acts as a gateway), within a given deadline. Scheduling and routing are assumed to be aware of the physical interference among nodes, which is modeled in the paper by means of a signal-to-interference ratio. Firstly, we present a theoretical model which allows us to formulate the task of deriving joint routing and scheduling as an integer linear programming problem. Secondly, since the problem cannot be dealt with using exact methods, we propose and use a technique based on genetic algorithms. To the best of our knowledge, these algorithms have never been used before for working out these kinds of optimization problems in a wireless mesh environment. We show that our technique is suitable for this purpose as it provides a good trade-off between fast computation and the overall goodness of the solution found. Our experience has in fact shown that genetic algorithms would seem to be quite promising for solving more complex models than the one dealt with in this paper, such as those including multiple flows and multi-radio multi-channels. 2008 Elsevier B.V. All rights reserved.
Moral Hazard Induced Unraveling∗

We identify and quantify a new form of welfare loss in insurance markets. We first show theoretically that moral hazard from subsidies for cost-sharing combined with community rating mimics adverse selection and can unravel insurance markets. To quantify the potential welfare loss, we use exogenous variation in the number of subsidized enrollees on the ACA exchanges. We find that subsidy-induced moral hazard led to higher premiums, which has lowered enrollment among the unsubsidized by 7.8 percentage points. We estimate the welfare costs of this “moral hazard induced unraveling” to be around 25% of the welfare loss from existing adverse selection. JEL Codes: D82, D60, G22, I13, I18
Behavioral and neuroimaging evidence for impaired executive function in “cognitively normal” older HIV-infected adults

ABSTRACT The increased prevalence of HIV among adults >50 years underscores the importance of improving our understanding of mechanisms causing HIV-associated neurocognitive disorders (HAND). Identifying novel and noninvasive diagnostic predictors of HAND prior to clinical manifestation is critical to ultimately identifying means of preventing progression to symptomatic HAND. Here, using a task-switching paradigm, in which subjects were cued (unpredictably) to perform a face-gender or a word-semantic task on superimposed face and word images, we examined the behavioral and neural profile of impaired cognitive control in older HIV + adults (N = 14, 9 HIV+). Functional magnetic resonance imaging (fMRI) and behavioral data were acquired while subjects were performing the face-gender or word-semantic task. We found that, despite comparable performance in standard neuropsychology tests that are designed to probe executive deficits, HIV-infected participants were significantly slower than uninfected controls in adapting to change in task demand, and the behavioral impairments can be quantitatively related to difference in fMRI signal at the dorsal anterior cingulate cortex (ACC). Due to the limited sample size of this hypothesis-generating study, we should take caution with these findings and future studies with a large and better matched sample size are needed. However, these rather novel findings in this study have a few important implications: first, the prevalence of cognitive impairments in HIV+ older adults might be even higher than previously proposed; second, ACC (in particularly its dorsal region) might be one of the key regions underlying cognitive impairments (in particularly executive functions) in HIV; and third, it might be beneficial to adopt paradigms developed and validated in cognitive neuroscience to study HAND, as these techniques might be more sensitive to some aspects of HIV-associated neurocognitive impairments than standard neuropsychology tests.
Hopf Bifurcation and Time Periodic Orbits with pde2path – Algorithms and Applications

We describe the algorithms used in the Matlab continuation and bifurcation package pde2path for Hopf bifurcation and continuation of branches of periodic orbits in systems of PDEs in 1, 2, and 3 spatial dimensions, including the computation of Floquet multipliers. We first test the methods on three reaction diffusion examples, namely a complex Ginzburg-Landau equation as a toy problem, a reaction diffusion system on a disk with rotational waves including stable (anti) spirals bifurcating out of the trivial solution, and a Brusselator system with interaction of Turing and Turing-Hopf bifurcations. Then we consider a system from distributed optimal control, which is ill-posed as an initial value problem and thus needs a particularly stable method for computing Floquet multipliers, for which we use a periodic Schur decomposition. The implementation details how to use pde2path on these problems are given in an accompanying tutorial, which, together with all other downloads (function libraries, demos and further documentation) can be found at http://www.staff. uni-oldenburg.de/hannes.uecker/pde2path.
Assessment of the ECCO2 Coupled Ocean and Sea Ice Solution in the Arctic

3) Kwok, R. , “Exchange of sea ice between the Arctic Ocean and the Canadian Arctic Archipelago”, Geophys. Res. Lett. , 33, L1651, doi: 10.1029/2006GL027094, 2006. 4) Marks and Smith, “An evaluation of publicly available global altimetry grids”, Marine Geophys. Res., 27(1) 19-34, March 2006 5) Schauer and Fahrbach, “Arctic warming through the Fram Strait: Oceanic heat transport from 3 years of measurements”, J. Geophys. Res., 109, C06026, doi: 10.1029/2003JC001823, 2004 6) Woodgate et al., “Interannual changes in the Bering Strait fluxes of volume, heat and freshwater between 1991 and 2004”, Geophys. Res. Lett. , 33, L15609, doi: 10.1029/2006GL026931, 2006 7) ASOF-N data: 8) ECCO2 project: 9) PANGAEA: the Publishing Network for Geoscientific & Environmental Data 10) SSM/I data, ULS data: 11) SCICEX data: 12) WHOI: Contact: An T. Nguyen (818-354-4122) 7. Summary and Ongoing Work:
Development and Evaluation of Methods for Producing a Radioimmunotherapy Pretargeting Agent

Antibodies can be used to target receptors that are over-expressed on certain types of cancer. By using radiolabeled antibodies cytotoxic radiation can be delivered to cancerous cells while minimizing the dose absorbed by healthy tissue. When administering a pretargeting agent and radionuclide separately, radionuclides with shorter half life can be used. In this thesis work the production of the pretargeting agent is investigated. By using the pH dependent interaction between iminobiotin and avidin a possible new production route is examined. The project did not generate a novel working production process but several of the necessary production steps were investigated and can act as a basis for future work. The iminobiotin-agarose column performed very well outside the manufacturers stated pH interval. This enables some of the pH dependent reaction steps to be performed in the iminobiotin column. The iminobiotin column could advantageously be used to separate avidin conjugated molecules from molecules not containing avidin. Fast protein liquid chromatography (FPLC) system together with a size exclusion column can be used for identifying and to certain extent isolating the product. This however require that the presence of avidin containing complexes are well separated from the conjugate in terms of molecular weight. The formation of unwanted products can be minimized by optimizing the reaction parameters. When coupling succinimidyl-4-(N-maleimidomethyl)cyclohexane-1carboxylate (SMCC) to form a precursor for protein-protein binding the reaction time should be kept to approximately 30 minutes when using an avidin concentration of 20mg/ml. The molar ratio of SMCC should also be kept under five times the amount of avidin. If an antibody, e.g. trastuzumab, is treated with a reducing agent some of the disulfide bridges are split allowing modification on the sulfhydryl groups. Sulfhydryl groups located on different antibodies can react causing the formation of dimers. Low concentration, short reaction times and quenching prevent this formation. The reaction between the reduced sulfhydryl group and a maleimide is dominant at pH below 8.5. At pH above 8.5 the reaction between the maleimide and primary amines are dominant. This reaction will create unwanted complexes and will also interfere with the intended site specificity of the maleimide-sulfhydryl reaction.
On the Size of the Active Management Industry by *

We argue that the popularity of active management is not puzzling despite the industry’s poor track record. Our model features decreasing returns to scale: as the industry’s size increases, every manager’s ability to outperform passive benchmarks declines. We find that the active management industry can remain large even after significantly negative underperformance. Given the observed performance of active mutual funds, investors’ proportional allocation to active management should have shrunk only modestly since 1962. We also find investors face endogeneity that limits their learning about returns to scale and allows prolonged departures of the industry’s size from its optimal level. *The University of Chicago Booth School of Business, NBER, and CEPR (Pástor) and the Wharton School, University of Pennsylvania, and NBER (Stambaugh). We are grateful for comments from Andrew Ang, Lord John Eatwell, Gene Fama, Vincent Glode, Rick Green, Ralph Koijen, Kim Min, Dimitris Papanikolaou, Luke Taylor, Rob Vishny, Guofu Zhou, workshop participants at Michigan State University, Ohio State University, University of Chicago, and University of Pennsylvania, as well as participants in the meetings of the NBER Asset Pricing Program, Western Finance Association, European Finance Association, Cambridge/Penn conference, and Q-Group. Support as an Initiative for Global Markets Visiting Fellow (Stambaugh) at the University of Chicago is gratefully acknowledged.
SLO-MSNet: Discrimination of Multiple Sclerosis using Scanning Laser Ophthalmoscopy Images with Autoencoder-Based Feature Extraction

Background: Optical coherence tomography (OCT) studies have revealed that compared to healthy control (HC) individuals, retinal nerve fiber, ganglionic cell, and inner plexiform layers become thinner in multiple sclerosis (MS) patients. To date, a number of machine learning (ML) studies have utilized Optical coherence tomography (OCT) data for classifying MS, leading to encouraging results. Scanning laser ophthalmoscopy (SLO) uses laser light to capture high-resolution fundus images, often performed in conjunction with OCT to lock B-scans at a fixed position, removing the effects of eye motion on image quality and allowing for evaluating the disease progression at follow-up examinations. To our knowledge, no ML work has taken advantage of SLO images for automated diagnosis of MS. Methods: In this study, SLO images were utilized for the first time with the purpose of fully automated classification of MS and healthy control (HC) cases. First, a subject-wise k-fold cross-validation data splitting approach was followed to minimize the risk of model overestimation due to data leakage between train and validation datasets. Subsequently, we used several state-of-the-art convolutional neural networks (CNNs), including VGG-16, VGG-19, ResNet-50, and InceptionV3, as well as a custom CNN architecture trained from scratch. In the next step, we designed a convolutional autoencoder (CAE) to extract semantic features from the images which are then given as the input to four conventional ML classifiers, including support vector machine (SVM), k-nearest neighbor (K-NN), random forest (RF), and multi-layer perceptron (MLP). Results: The custom CNN model outperformed state-of-the-art models with an accuracy (ACC) of 85%, sensitivity (SE) of 85%, specificity (SP) of 87%, and AUROC of 93%; however, utilizing a combination of the CAE and MPL yields even superior results achieving an ACC of 88%, SE of 86%, SP of 91%, and AUROC of 94%, while maintaining high per-class accuracies. The best performing model was also found to be generalizable to an external dataset from an independent source, achieving an ACC of 83%, SE of 87%, and SP of 79%. Conclusion: For the first time, we utilized SLO images to differentiate between MS and HC eyes, with promising results achieved using combination of designed CAE and MLP which we named SLO-MSNet. Should the results of the SLO-MSNet be validated in future works with larger and more diverse datasets, SLO-based diagnosis of MS can be reliably integrated into routine clinical practice. Keywords: Multiple Sclerosis; Optical Coherence Tomography; Scanning Laser Ophthalmoscopy; Feature Extraction; Machine Learning; Deep Learning
Structure et connectivité de la mégafaune marine à l'échelle d’une région océanique : enjeux pour la gestion durable des tortues vertes dans l'océan Indien occidental

Ce travail de these s'insere dans une demarche globale d'acquisition des connaissances sur la tortue verte (Chelonia mydas) dans l'ocean Indien occidental et ce afin de disposer d'elements scientifiques essentiels a la mise en place d'une gestion coherente et efficace de cette espece menacee. Dans un premier temps, appliquant differentes modeles statistiques, ce travail a vise a etablir des donnees de reference sur l'abondance des tortues vertes femelles en reproduction et les tendances sur le long terme des principales populations. Dans un second temps, il a consiste a determiner la structure genetique et les relations qui existent entre les differentes populations de cette espece. Enfin, la conservation des tortues marines etant etroitement liee aux pressions exterieures, ce travail a tente dans un troisieme temps de caracteriser les pressions anthropiques qu'elles subissent, et notamment celles liees a la peche. L'ensemble de ces resultats a permis de realiser des avancees majeures dans la connaissance de la biologie et de l'ecologie de la tortue verte et de disposer d'une vision regionale fiable de l'etat de conservation de cette espece dans l'ocean Indien occidental. Leur compilation a ainsi permis d'identifier des zones regionales prioritaires de protection mais aussi des sites de vigilance plus specifiques comme celui d'Europa. Enfin cette synthese met en lumiere les priorites de recherche et les approches scientifiques a favoriser a l'avenir pour ameliorer les connaissances et affiner les priorites de conservation non seulement des tortues marines, mais aussi de la megafaune marine en general.
Testing Trade-Off and Pecking Order Predictions About Dividends and Debt

Confirming predictions shared by the trade-off and pecking order models, more profitable firms and firms with fewer investments have higher dividend payouts. Confirming the pecking order model but contradicting the trade-off model, more profitable firms are less levered. Firms with more investments have less market leverage, which is consistent with the trade-off model and a complex pecking order model. Firms with more investments have lower long-term dividend payouts, but dividends do not vary to accommodate shortterm variation in investment. As the pecking order model predicts, short-term variation in investment and earnings is mostly absorbed by debt.
Total cloud cover climatology over the United Arab Emirates

Cloud climatologies are of great importance in the study of cloud dynamics and interactions with land, oceans and atmosphere. This study analyzes the climatology of Total Cloud Cover (TCC) over the United Arab Emirates (UAE). Monthly mean TCC data between 1984 and 2009 from ground observations at six UAE airport stations and the satellite‐based (CLARA A2) product are utilized.
FOXA2 suppresses gallbladder carcinoma cell migration, invasion, and epithelial‐mesenchymal transition by targeting SERPINB5

Gallbladder cancer (GBC), a highly malignant gastrointestinal tumor, lacks effective therapies. Foxhead box A2 (FOXA2) is a tumor suppressor that is poorly expressed in various human malignancies. This study aimed to ascertain FOXA2 expression in GBC and its relevance to tumor metastasis, and to elucidate its regulatory mechanism with epithelial‐mesenchymal transition (EMT) as an entry point, in the hope of providing a potential therapeutic target for GBC.
Spexin role in human granulosa cells physiology and PCOS: expression and negative impact on steroidogenesis and proliferation

Abstract Spexin (SPX) is a novel neuropeptide and adipokine negatively correlated with obesity and insulin resistance. A recent study investigated expression and regulatory function of SPX in the hypothalamus and pituitary; however, the effect on ovarian function is still unknown. The aim of this study was to characterize the expression of SPX and its receptors, galanin receptors 2 and 3 (GALR2/3), in the human ovary and to study its in vitro effect on granulosa cells (GC) function. Follicular fluid (FF) and GC were obtained from normal weight and obese healthy and diagnosed with polycystic ovarian syndrome (PCOS) women. Expression of SPX and GALR2/3 in the ovary was studied by qPCR, western blot, and immunohistochemistry. The level of SPX in FF was assessed by enzyme-linked immunosorbent assay. The in vitro effect of recombinant human SPX on GC proliferation, steroidogenesis, and signaling pathways (MAP3/1, STAT3, AKT, PKA) was analyzed. Moreover, GC proliferation and estradiol (E2) secretion were measured with and without an siRNA against GALR2/3 and pharmacological inhibition of the above kinases. The results showed that both the SPX concentration in FF and its gene expression were decreased in GC of obese and PCOS women, while the protein expression of GALR2/3 was increased. We noted that SPX reduced GC proliferation and steroidogenesis; these effects were mediated by GALR2/3 and kinases MAP3/1, AKT, and STAT3 for proliferation or kinases MAP3/1 and PKA for E2 secretion. The obtained data clearly documented that SPX is a novel regulator of human ovarian physiology and possibly plays a role in PCOS pathogenesis. Summary Sentence We observed decreased spexin (SPX) levels in granulosa cells (GC) and follicular fluid collected from obese and polycystic ovarian syndrome women, and we noted an inhibitory effect of SPX on GC proliferation and steroidogenesis. Graphical Abstract
The effects of purslane (Portulaca oleracea) on glycemic indices: A GRADE‐assessed systematic review and meta‐analysis of randomized controlled trials

Although several studies have revealed the benefits of purslane on glycemic indices, the results of some studies reject such effect. Therefore, aim of this meta‐analysis of randomized controlled trials (RCTs) was to assess the effects of purslane supplementation on glycemic indices. Scientific international databases as Scopus, Web of Sciences, PubMed, Embase, and the Cochrane library were searched up to December 2022. For net changes in glycemic indices, weighted mean differences (WMDs) were calculated using random‐effects models. Purslane supplementation had a statistically significant reduction in fasting blood glucose [FBG, WMD: −6.37; 95% CI: −9.34, −3.40, p < 0.001]. In addition, purslane did not significant effect on serum levels of insulin [WMD: −0.74; 95% CI: −2.58, 1.10; p = 0.430], homeostasis model assessment for insulin resistance [HOMA‐IR, WMD: −0.25; 95% CI: −0.88, 0.37, p = 0.429], and QUICKI [WMD: −0.01; 95% CI: −0.01, 0.03, p = 0.317] compared with the control group. The results of our meta‐analysis revealed a beneficial effect of purslane supplementation as a tool to decrease FBG levels, but not to HOMA‐IR, insulin, and QUICKI levels. However, future high‐quality, long‐term clinical trials are needed to confirm our results.
Effect of laparoscopic mini-gastric bypass versus laparoscopic sleeve gastrectomy on hypertension and dyslipidemia in obese type 2 diabetes mellitus patients

Objective: The aim of the research was to compare the effect of the laparoscopic mini-gastric bypass (LMGB) technique with the laparoscopic sleeve gastrectomy (LSG) technique in bariatric surgery on type 2 diabetes mellitus (T2DM), hypertension (HTN), and dyslipidemia in obese T2DM patients. Materials and methods: A prospective, cross-sectional study, conducted in Surgery Department at Al-Mouwasat and Al-Assad University Hospitals in Damascus, and included T2DM obese patients who would undergo bariatric surgery using the LMGB or LSG technique. Results: The research included two groups: the LSG group (92 patients, 60.9% female, age 44.6 year, BMI 41.85 kg/m2) and the LMGB group (137 patients, 59.1% female, age 47.1 year, BMI 43 kg/m2). Before surgery, the prevalence of HTN and dyslipidemia were similar in the two groups. After one year: T2DM improvement and remission rate in the LMGB group (13.9, 80.3%) were greater than in the LSG group (13, 62%), the difference was statistically significant. The HTN improvement and remission rate in the LMGB group (52.9, 41.4%) were greater than in the LSG group (47.5, 39%), the difference was not statistically significant. The dyslipidemia improvement rate was greater in LSG group (47.2 vs. 32.7%), while the dyslipidemia remission rate was greater in LMGB group (67.3 vs. 52.8%), the difference was statistically significant. Conclusions: The authors found that the LMGB technique was more effective than the LSG technique in controlling cardiovascular risk factors of obesity, T2DM, HTN, and dyslipidemia.