Miracle-dz/UniFAR-FTUs huggingface dataset:
The Problem of Calibrating an Agent-Based Model of High-Frequency Trading

Agent-based models, particularly those applied to financial markets, demonstrate the ability to produce realistic, simulated system dynamics, comparable to those observed in empirical investigations. Despite this, they remain fairly difficult to calibrate due to their tendency to be computationally expensive, even with recent advances in technology. For this reason, financial agent-based models are frequently validated by demonstrating an ability to reproduce well-known log return time series and central limit order book stylized facts, as opposed to being rigorously calibrated to transaction data. We thus apply an established financial agent-based model calibration framework to a simple model of high- and low-frequency trader interaction and demonstrate possible inadequacies of a stylized fact-centric approach to model validation. We further argue for the centrality of calibration to the validation of financial agent-based models and possible pitfalls of current approaches to financial agent-based modeling.
Pharmacological treatment for infectious corneal ulcers

Introduction: Cornea ulceration and infectious keratitis are leading causes of corneal morbidity and blindness. Infectious causes are among the most frequent and most severe. Management strategies for bacterial corneal ulcers have changed significantly over the last decades, however with a more limited progress in the treatment and management of nonbacterial, infectious ulcers. Areas covered: This paper provides an overview of the current principles, strategies and treatment choices for infectious corneal ulcers in adults. Expert opinion: Topical application with a broad-spectrum antimicrobial remains the preferred method for the pharmacological management of infectious corneal ulcers. Increasing reports of clinical failures and in vitro resistance to antibiotics to treat the most common infectious (bacterial) corneal ulcers are increasing concerns. New approaches for improvement in the pharmacological management of corneal ulcers should focus on strategies for a more rational and evidence-based use of current antimicrobials and development of products to modulate the host immune response and to neutralize microbial toxins and other immune modulators.
Characteristics associated with glycemic control among family medicine patients with type 2 diabetes.

BACKGROUND As new payment models are developed for chronic diseases such as diabetes, there is a need to understand which patient characteristics impact glycemic control. This study examines the relationship between patient variables and glycemic control, defined as a hemoglobin A1c (A1c) level of <7%, in a cohort of family medicine patients with type 2 diabetes. METHODS A total of 1,398 medical charts were selected using International Classification of Diseases, Ninth Revision, Clinical Modification codes for diabetes. To gather information not available through chart review, a survey was used to collect data on individual-level characteristics. Information included marital status, education level, income level, insurance status, activity level, receipt of diabetes education, living arrangement, employment status, and annual income. A cross-sectional design was used to obtain, via chart review, data about diabetes outcomes (ie, A1c level, blood pressure, and low-density lipoprotein cholesterol [LDL-C] level). RESULTS A mailed survey was completed by 669 patients (response rate, 47.9%). Almost half of patients in this sample achieved the goal A1c level, LDL-C level (ie, <100 mg/dL), and/or blood pressure (ie, <130/<80 mm Hg). Medicare insurance (odds ratio [OR], 2.16 [95% confidence interval {CI}, 1.18-3.96]) and female sex (OR, 1.61 [95% CI, 1.01-2.56]) were associated with glycemic control. Other variables, such as annual income, education level, and receipt of diabetes education, that were expected to impact glycemic control were not significantly associated with an A1c level of <7%. LIMITATIONS The survey response rate was <50%, the study was conducted at a single site, and the chart data were retrospective. CONCLUSIONS Our findings indicate that Medicare insurance and female sex were associated with glycemic control. Further evaluation is needed to identify determinants that lead to achievement of optimal glycemic control among individuals with type 2 diabetes.
Understanding jet noise

Jets are one of the most fascinating topics in fluid mechanics. For aeronautics, turbulent jet-noise modelling is particularly challenging, not only because of the poor understanding of high Reynolds number turbulence, but also because of the extremely low acoustic efficiency of high-speed jets. Turbulent jet-noise models starting from the classical Lighthill acoustic analogy to state-of-the art models were considered. No attempt was made to present any complete overview of jet-noise theories. Instead, the aim was to emphasize the importance of sound generation and mean-flow propagation effects, as well as their interference, for the understanding and prediction of jet noise.
Chronic angiotensin II infusion modulates angiotensin II type I receptor expression in the subfornical organ and the rostral ventrolateral medulla in hypertensive rats

Blood-borne angiotensin II (Ang II) has profound effects on the central nervous system, including regulation of vasopressin secretion and modulation of sympathetic outflow. However, the mechanism by which circulating Ang II affects the central nervous system remains largely unknown. We tested the hypothesis that increased circulating levels of Ang II activate angiotensin type I (AT1) receptors in the subfornical organ (SFO), increasing the Ang II signalling in the rostral ventrolateral medulla (RVLM). Male Wistar rats were subcutaneously implanted with two 14-day osmotic minipumps filled with Ang II (150ng/kg/minute), Losartan (10mg/kg/day), or saline. In addition, AT1 receptor mRNA levels in the SFO and RVLM were detected by reverse transcription polymerase chain reaction (RT-PCR). Infusion of Ang II-induced hypertension (134 ± 10 mmHg vs 98 ± 9 mmHg, n = 9, p < 0.05), which was blunted by concomitant infusion of Losartan (105 ± 8 vs 134 ± 10 mmHg, n = 9, p < 0.05). In addition, hexamethonium produced a greater decrease in blood pressure in Ang II-infused rats. Real time PCR revealed that chronic Ang II infusion induced an increase in AT1 receptor mRNA levels in the RVLM and a decrease in the SFO. Taken together, using combined in vivo and molecular biology approaches, our data suggest that Ang II-induced hypertension is mediated by an increase in sympathetic nerve activity, which seems to involve up-regulation of AT1 receptors in the RVLM and down-regulation of AT1 receptors in the SFO.
Highly Efficient Three-Way Saturated Doherty Amplifier With Digital Feedback Predistortion

A three-way saturated Doherty power amplifier (S-DPA) based on class-F topology is proposed to improve efficiency at large backed-off output power regions. The high efficiency is demonstrated by implementing the amplifier using Eudyna EGN010MK GaN HEMTs and testing it with a continuous wave (CW) signal and a forward-link wide-band code division multiple access (WCDMA) 1-FA signal at 2.14 GHz. The proposed S-DPA has a power-added efficiency (PAE) of 50% for the CW signal at 10 dB backed-off output power region, while a two-way S-DPA and class-F PA have PAEs of 39% and 25%, respectively. Also, the proposed S-DPA has a PAE of 46.7% for the WCDMA 1-FA signal with peak-to-average power ratio of 10 dB, while the two-way S-DPA and the class-F PA have PAEs of 42.7% and 28.7%, respectively. Moreover, the proposed S-DPA, when linearized by a digital feedback predistorter, delivers an adjacent channel leakage ratio of 49.2 dBc at a 2.5 MHz offset with a PAE of 45.9%.
Protein kinase C mediates lipopolysaccharide- and phorbol-induced nitric-oxide synthase activity and cellular injury in the rat colon.

The role of protein kinase C (PKC) in lipopolysaccharide (LPS)- and phorbol ester-induced changes in rat colonic cellular integrity and Ca(2+)-independent inducible nitric-oxide synthase (iNOS) activity was investigated. LPS treatment (3 mg kg(-1) i.p.) increased colonic cellular PKC activity within 1 h after administration. The percentage of nonviable cells and iNOS activity in response to LPS were reduced by pretreatment with the selective PKC antagonist GF 109203X (25 ng kg(-1) i.v. ). Pretreatment with the selective iNOS inhibitor 1400W (5 mg kg(-1) s.c. ) reduced the extent of cellular injury and iNOS activity but did not affect the increase in LPS-mediated PKC activation. Reduction of circulating neutrophils with anti-neutrophil serum reduced cell damage as well as the increases in PKC and iNOS activities in response to LPS. Intracolonic administration of the phorbol ester phorbol-12-myristate-13-acetate (PMA; 3 mg kg(-1)) increased colonic cellular PKC activity within 2 h after instillation. Cellular iNOS activity did not increase until 6 h after PMA administration. The colonic responses to PMA were eliminated by GF 109203X. The selective iNOS inhibitor 1400W reduced the increase in cell injury but did not affect the PKC activation in response to PMA. LPS treatment also increased in the proteins for PKC-alpha, PKC-delta, PKC-epsilon, and PKC-zeta. PMA treatment resulted in PKC-delta and PKC-epsilon translocation from cytosol to membrane. These data suggest that PKC mediates iNOS activation and subsequent colonic cell injury in response to LPS administration. The delta- and epsilon-isozymes appear to be most closely associated with these responses.
Dietary factors in pathogenesis of gallstone disease in southern India--a hospital-based case-control study.

BACKGROUND Pigment or mixed gallstones are common in southern India. The etiology is not established. Known risk factors include an obese, diabetic female and a nonsmoker male. AIM To determine the association of dietary factors with mixed/pigment gallstones amongst southern Indian patients. METHODS Diet details were obtained from 346 patients (178 women) with gallstones and an equal number of healthy controls who were age- and sex-matched attendants of the patients, sharing similar socioeconomic and demographic characteristics, with normal abdominal ultrasonogram. Data recorded included the number of daily meals, nature of cereal used, vegetarianism, oil consumed per month, sugar consumption per day, tamarind (Garcinia camborginia ) usage per week, and per-day beverage consumption. RESULTS There was no difference between cases and controls in consumption of non-vegetarian food, type of cereal, average oil and sugar consumption, and type of beverage consumed (tea/coffee/milk/combination). Individuals with BMI> 22 were at higher risk to develop gallstones (OR 1.49; 95% CI 1.09, 2.04; p=0.01). There was significant risk of gallstone formation with the use of tamarind when consumed > 3 times a week (OR 1.76; 95% CI 1.05, 2.96; p=0.03). Higher BMI and tamarind use were significant risk factors even on multivariate logistic regression analysis (p=0.02). CONCLUSION Higher BMI and use of tamarind, a common ingredient of diet in southern India, are risk factors in the formation of gallstones in southern India.
Spontaneous bacterial peritonitis is associated with high levels of interleukin‐6 and its secondary mediators in ascitic fluid

Abstract. We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin‐6, as well as acute phase reactants a‐l‐antitrypsin and C‐reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF‐α), neopterin, interleukin 2–receptor and granu‐locyte‐macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin‐2 and interleukin‐1 levels. In addition, interleukin‐6, TNF‐α and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.
Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules

MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.
High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

ABSTRACT hnRNPs are polyvalent RNA binding proteins that have been implicated in a range of regulatory roles including splicing, mRNA decay, translation, and miRNA metabolism. A variety of genome wide studies have taken advantage of methods like CLIP and RIP to identify the targets and binding sites of RNA binding proteins. However, due to the complex nature of RNA-binding proteins, these studies are incomplete without assays that characterize the impact of RBP binding on mRNA target expression. Here we used a suite of high-throughput approaches (RIP-Seq, iCLIP, RNA-Seq and shotgun proteomics) to provide a comprehensive view of hnRNP H1s ensemble of targets and its role in splicing, mRNA decay, and translation. The combination of RIP-Seq and iCLIP allowed us to identify a set of 1,086 high confidence target transcripts. Binding site motif analysis of these targets suggests the TGGG tetramer as a prevalent component of hnRNP H1 binding motif, with particular enrichment around intronic hnRNP H1 sites. Our analysis of the target transcripts and binding sites indicates that hnRNP H1s involvement in splicing is 2-fold: it directly affects a substantial number of splicing events, but also regulates the expression of major components of the splicing machinery and other RBPs with known roles in splicing regulation. The identified mRNA targets displayed function enrichment in MAPK signaling and ubiquitin mediated proteolysis, which might be main routes by which hnRNP H1 promotes tumorigenesis.
Glycaemic index, glycaemic load and risk of endometrial cancer: a prospective cohort study

Abstract Objective High-glycaemic-load diets may increase endometrial cancer risk by increasing circulating insulin levels and, as a consequence, circulating oestrogen levels. Given the paucity of epidemiological data regarding the relationship between dietary glycaemic index and glycaemic load and endometrial cancer risk, we sought to examine these associations using data from a prospective cohort study. Design, setting and subjects We examined the association between dietary glycaemic load and endometrial cancer risk in a cohort of 49 613 Canadian women aged between 40 and 59 years at baseline who completed self-administered food-frequency questionnaires between 1982 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. Results During a mean of 16.4 years of follow-up, we observed 426 incident cases of endometrial cancer. Hazard ratios for the highest versus the lowest quartile level of overall glycaemic index and glycaemic load were 1.47 (95% confidence interval (CI) = 0.90–2.41; P for trend = 0.14) and 1.36 (95% CI = 1.01–1.84; P for trend = 0.21), respectively. No association was observed between total carbohydrate or total sugar consumption and endometrial cancer risk. Among obese women (body mass index > 30 kg m−2) the hazard ratio for the highest versus the lowest quartile level of glycaemic load was 1.88 (95% CI = 1.08–3.29; P for trend = 0.54) and there was a 55% increased risk for the highest versus the lowest quartile level of glycaemic load among premenopausal women. There was also evidence to support a positive association between glycaemic load and endometrial cancer risk among postmenopausal women who had used hormone replacement therapy. Conclusions Our data suggest that diets with high glycaemic index or high glycaemic load may be associated with endometrial cancer risk overall, and particularly among obese women, premenopausal women and postmenopausal women who use hormone replacement therapy.
Environmental DNA metabarcoding of lake fish communities reflects long‐term data from established survey methods

Organisms continuously release DNA into their environments via shed cells, excreta, gametes and decaying material. Analysis of this ‘environmental DNA’ (eDNA) is revolutionizing biodiversity monitoring. eDNA outperforms many established survey methods for targeted detection of single species, but few studies have investigated how well eDNA reflects whole communities of organisms in natural environments. We investigated whether eDNA can recover accurate qualitative and quantitative information about fish communities in large lakes, by comparison to the most comprehensive long‐term gill‐net data set available in the UK. Seventy‐eight 2L water samples were collected along depth profile transects, gill‐net sites and from the shoreline in three large, deep lakes (Windermere, Bassenthwaite Lake and Derwent Water) in the English Lake District. Water samples were assayed by eDNA metabarcoding of the mitochondrial 12S and cytochrome b regions. Fourteen of the 16 species historically recorded in Windermere were detected using eDNA, compared to four species in the most recent gill‐net survey, demonstrating eDNA is extremely sensitive for detecting species. A key question for biodiversity monitoring is whether eDNA can accurately estimate abundance. To test this, we used the number of sequence reads per species and the proportion of sampling sites in which a species was detected with eDNA (i.e. site occupancy) as proxies for abundance. eDNA abundance data consistently correlated with rank abundance estimates from established surveys. These results demonstrate that eDNA metabarcoding can describe fish communities in large lakes, both qualitatively and quantitatively, and has great potential as a complementary tool to established monitoring methods.
Pharmacological Manipulation of Serotonin Levels in the Nervous System of the Opisthobranch Mollusc Tritonia diomedea

Serotonin-related disorders can be treated by manipulating serotonin synthesis with the serotonin precursor 5-hydroxytryptophan (5-HTP) or other pharmacological agents. The mollusc Tritonia diomedea is a model for investigating the effects of altering serotonin content on the functions of identified neurons. We used high-performance liquid chromatography and immunohistochemistry to examine the amount and localization of 5-HTP, serotonin, and the serotonin breakdown product 5-hydroxyindolacetic acid (5-HIAA) in the Tritonia brain after various pharmacological treatments. Exposure to 5-HTP (2 mM for 30 min–1 h) caused an immediate and massive increase in total 5-HTP content, which lasted more than 20 h, and the widespread appearance of 5-HTP immunoreactivity in neurons. Serotonin levels rose gradually, but only a restricted number of additional neurons displayed serotonin immunoreactivity. 5-HTP treatment also caused an increase in the total amount of 5-HIAA and the appearance of 5-HIAA immunoreactivity throughout the brain. Treatment with the synthesis cofactor tetrahydrobiopterin, the initial precursor tryptophan, or serotonin itself had no persistent effect on total serotonin content. The amino acid decarboxylase inhibitor hydroxybenzylhydrazine (NSD-1015) also had no effect on the total serotonin content, although it caused an accumulation of 5-HTP. Thus, serotonin levels in the brain of T. diomedea appear to be maintained by a homeostatic mechanism that can be disrupted by 5-HTP.
Herbivore-Induced Resistance against Microbial Pathogens in Arabidopsis1

Caterpillars of the herbivore Pieris rapae stimulate the production of jasmonic acid (JA) and ethylene (ET) in Arabidopsis (Arabidopsis thaliana) and trigger a defense response that affects insect performance on systemic tissues. To investigate the spectrum of effectiveness of P. rapae-induced resistance, we examined the level of resistance against different pathogens. Although the necrotrophic fungus Alternaria brassicicola is sensitive to JA-dependent defenses, herbivore-induced resistance was not effective against this pathogen. By contrast, caterpillar feeding significantly reduced disease caused by the bacterial pathogens Pseudomonas syringae pv tomato and Xanthomonas campestris pv armoraciae. However, this effect was apparent only locally in caterpillar-damaged tissue. Arabidopsis mutants jar1, coi1, ein2, sid2, eds5, and npr1 showed wild-type levels of P. rapae-induced protection against P. syringae pv tomato, suggesting that this local, herbivore-induced defense response does not depend exclusively on either JA, ET, or salicylic acid (SA). Resistance against the biotroph Turnip crinkle virus (TCV) requires SA, but not JA and ET. Nevertheless, herbivore feeding strongly affected TCV multiplication and TCV lesion formation, also in systemic tissues. Wounding alone was not effective, but application of P. rapae regurgitate onto the wounds induced a similar level of protection. Analysis of SA-induced PATHOGENESIS RELATED-1 (PR-1) expression revealed that P. rapae grazing primed Arabidopsis leaves for augmented expression of SA-dependent defenses. Pharmacological experiments showed that ET acts synergistically on SA-induced PR-1, suggesting that the increased production of ET upon herbivore feeding sensitizes the tissue to respond faster to SA, thereby contributing to an enhanced defensive capacity toward pathogens, such as TCV, that trigger SA-dependent defenses upon infection.
Celastrol-Induced Suppression of the MiR-21/ERK Signalling Pathway Attenuates Cardiac Fibrosis and Dysfunction

Backgroud: Myocardial fibrosis results in myocardial remodelling and dysfunction. Celastrol, a traditional oriental medicine, has been suggested to have cardioprotective effects. However, its underlying mechanism is unknown. This study investigated the ability of celastrol to prevent cardiac fibrosis and dysfunction and explored the underlying mechanisms. Methods: Animal and cell models of cardiac fibrosis were used in this study. Myocardial fibrosis was induced by transverse aortic constriction (TAC) in mice. Cardiac hypertrophy and fibrosis were evaluated based on histological and biochemical measurements. Cardiac function was evaluated by echocardiography. The levels of transforming growth factor beta 1 (TGF-β1), extracellular signal regulated kinases 1/2 (ERK1/2) signalling were measured using Western blotting, while the expression of miR-21was analyzed by real-time qRT-PCR in vitro and in vivo. In vitro studies, cultured cardiac fibroblasts (CFs) were treated with TGF-β1 and transfected with microRNA-21(miR21). Results: Celastrol treatment reduced the increased collagen deposition and down-regulated α-smooth muscle actin (α-SMA), atrial natriuretic peptide (ANP), brain natriuretic peptides (BNP), beta-myosin heavy chain (β-MHC), miR-21 and p-ERK/ERK. Cardiac dysfunction was significantly attenuated by celastrol treatment in the TAC mice model. Celastrol treatment reduced myocardial fibroblast viability and collagen content and down-regulated α-SMA in cultured CFs in vitro. Celastrol also inhibited the miR-21/ERK signalling pathway. Celastrol attenuated miR-21 up-regulation by TGF-β1 and decreased elevated p-ERK/ERK levels in CFs transfected with miR-21. Conclusion: MiR-21/ERK signalling could be a potential therapeutic pathway for the prevention of myocardial fibrosis. Celastrol ameliorates myocardial fibrosis and cardiac dysfunction, these probably related to miR-21/ERK signaling pathways in vitro and in vivo.