Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition and stimulation of intestinal and hepatic CYP3A activity: studies in humanized CYP3A4 transgenic mice using triazolam

CYP3A4 is an important determinant of drug-drug interactions. Here, we evaluated whether Cyp3a -/- and CYP3A4 transgenic (CYP3A4-Tg) mice can be utilized to study drug-drug interactions in the liver and intestine. Triazolam was used as a probe drug because it is a highly specific CYP3A substrate and not a P-glycoprotein substrate. Triazolam metabolism was profoundly reduced in Cyp3a -/- mice, both in vitro and in vivo . In vitro studies revealed clear species differences in human and mouse, but triazolam metabolism in microsomes derived from CYP3A4-Tg “humanized” mice closely resembled that in human microsomes. Interestingly, studies with tissue-specific CYP3A4-Tg mice revealed that intestinal CYP3A4 has a major impact on oral triazolam exposure, whereas the effect of hepatic CYP3A4 was limited. To mimic a drug-drug interaction, we co-administered triazolam with the prototypical CYP3A inhibitor ketoconazole, which increased triazolam exposure in all CYP3A-proficient mouse strains but not in Cyp3a -/- mice. We further found that the anti-cancer drug gefitinib is a potent stimulator of 1’-OH triazolam formation, in vitro . Importantly, also in vivo we could demonstrate stimulation of triazolam metabolism by gefitinib, resulting in a lower oral triazolam exposure. To our knowledge this is the first in vivo example of direct stimulation of CYP3A4 activity after oral drug administration. Overall, this study illustrates how Cyp3a -/- and CYP3A4-Tg mice can be utilized to study drug-drug interactions. The data clarify that also for drugs that are not P-glycoprotein substrates, intestinal metabolism can be more important than hepatic metabolism after oral administration. gefitinib primarily takes place in the liver. These results illustrate how Cyp3a -/- and CYP3A4-Tg mice can be utilized to study CYP3A4-dependent drug-drug interactions in vivo .
Terahertz Linear to Circular Polarization Converter Based on Reflective Metasurface

Metasurfaces are two-dimensional artificial structures which have extraordinary electromagnetic properties. They have been used in myriad of devices such as nano-antennas, cloaking coatings, imaging devices, flat lenses, and polarization converters over a wide range of frequency. Due to high dependency of many devices on incident wave polarization, manipulating the polarization of electromagnetic waves would be useful, especially in the THz regime. In this study, we propose a linear to circular polarization converter (LTC-PC) based on a THz reflective metasurface. For a TE linear polarization incident wave, this structure has two distinct bands; the first one lays in a wideband frequency range of 0.5-1.41 THz, in which the reflected wave would be a left-handed circular polarization (LHCP) with minimum efficiency of 89% and maximum efficiency of more than 95% in 80% of the bandwidth. The second band lays in the narrowband frequency range of 1.45-1.55 THz, resulting a right-handed circular polarization (RHCP) wave with a minimum efficiency of 82%. The proposed polarization converter can be used in optical communication and electronic devices.
EVALUATION OF GREEN MANUFACTURING IMPLEMENTATION ON REGULATION, COSTS, AND KNOWLEDGE

Introduction: This study aims to analyze whether there is motivation of knowledge, regulations, and costs on the effect of the application of Green Manufacturing. Part of green manufacturing has been implemented. However, its implementation is not easy for various reasons and it has not a significant effect on the industrial world from several sectors. Methods: Data collection methods include questionnaires and interviews. This study uses primary data obtained through direct respondents. The statistical analysis tool in this study uses SPSS. Results: Based on the results of data analysis and discussion, it shows that the knowledge variable has a positive effect on the motivation to implement green manufacturing. In addition, the second variable, namely regulation, also shows a positive effect on the motivation to implement green manufacturing. However, the third variable shows that costs have a negative effect on the motivation to implement green manufacturing.
Pricing Determinants of selected Bookbuilt IPOs issued in India

This study attempts to decode the puzzle surrounding the pricing of equity IPOs issued through bookbuilding pricing method in India in the period from 2000 to 2014. Using a sample of 100 bookbuilt IPO issues in the study period the study reveals the significant value drivers for IPO price by applying multivariate regression analysis to a select set of explanatory variables for IPO value. The study results establish post issue promoter and promoter groups retained ownership levels, Net worth per equity share, industry composite price to earnings ratio, earnings per share and rate of subscription of IPOs by institutional investors as significant pricing determinants of sample bookbuilt IPOs.
Generalizable Identity Classifiers from Self-Reporting Statements on Reddit

This thesis presents a descriptive analysis of self-identity on Reddit. Following previous work on mental health disorders that use patterns like “I was just diagnosed with depression”, we analyze self-identification on Reddit more broadly. We show which group memberships people tend to assert, and analyze which forums people disproportionately self-identify or self-distance in. To show the type of socio-linguistic studies that can be performed, we analyze linguistic traits of different groups. In addition, we define a heuristic that should be followed while building binary identity classification models on using Reddit.
ROLE OF MICRO RNA-21 IN EGYPTIAN PATIENTS WITH ISCHEMIC HEART DISEASE

Background: Ischemic heart diseases are major sources of morbidity and mortality worldwide. Several biomarkers have been suggested to aid in the diagnosis of myocardial infarction and unstable angina. Multiple micro-RNAs, a class of regulatory ribonucleic acids, have been studied in ischemic heart disease patients for a potential role in diagnosis. Objective: To study the role of micro RNA-21(miRNA21 or miR21) in Egyptian patients with ischemic heart diseases(IHD), myocardial infarction (MI) and unstable angina (UA) to evaluate its diagnostic value in IHDs. Patients and Methods: This prospective case-control study included 50 subjects, divided into two groups: Patient group including 30 subjects, and control group including 20 subjects. Subjects were subjected to full history taking and clinical assessment, routine lab investigations, cardiac markers assay, and determination of serum expression of Micro RNA-21 using real-time polymerase chain reaction (PCR). This study was conducted on patients attending at cardiology department, Al-Hussein University Hospital. Study started in March 2018, and ended in October 2018. Results: Micro-RNA expression profile showed that miR-21 was up-regulated in MI and UA patients in general, with a statistically extremely highly significant difference (p=<0.001). Its diagnostic performance was marvelous, but couldn’t distinguish between UA and MI. Conclusions: In conclusion, we found that Micro RNA-21 showed a statistically extremely high significant up regulation in MI and UA patients, with strong diagnostic performance, but couldn't distinguish between UA and MI. Micro RNA-21 might be biomarker for ischemic heart disease.
Minimizing the Casting Defects in High Pressure Die Casting Using Taguchi Analysis

High-Pressure Die Casting (HPDC) is one of the major production processes of automotive industry, widely used to manufacture geometrically complex nonferrous castings. The mechanical strength and microstructure of HPDC-manufactured products changes with variation in several process control parameters such as injection pressure, molten temperature, 1st and 2nd stage plunger velocity, cooling temperature, etc. Since these process parameters directly affect casting quality, their optimum combination is needed to maximize the productivity of process and minimize casting defects such as porosity, pinholes, blowholes, inclusions, etc. Hence, to tackle this problem, an approach is presented in this paper that minimizes the major casting defect, i.e., porosity, in the HPDC process by optimizing controlling parameters through Design of Experiments (DOE) in combination with a Taguchi Analysis. The results obtained showed that cooling time, injection pressure, and 2nd stage plunger velocity have a major influence on the response factor (density of the cast part). It was also concluded that, by using a 178 bar injection pressure, 665 °C molten temperature, 5 second cooling time, 210 °C mold temperature, 0.20 m·s−1 1st stage plunger velocity, and 6.0 m·s−1 2nd stage plunger velocity, the rejection rate of the selected part due to porosity was reduced by 61%.
ROLE OF MIDDLE CEREBRAL ARTERY DOPPLER AND AMNIOTIC FLUID INDEX IN PREDICTING PERINATAL OUTCOME IN POSTDATED PREGNANCIES

Background: Post-date pregnancy carries many fold problems for both pregnancy and fetal outcome. Abnormal middle cerebral artery Dopplers are strongly associated with preterm delivery and antenatal steroid administration. Objective: To identify the relationship between middle cerebral artery Doppler, Amniotic fluid index and perinatal outcomes in postdated pregnancies. Patients and Methods: This study was performed on 50 pregnant women whose gestational age was 40–42 weeks’ gestation attending the antenatal clinic of Zefta General Hospital. The study was done during the period between December 2017 and August 2019.Inclusion criteria included singleton living fetuses with vertex presentation in postdated pregnancies (40 – 42) week gestation. Exclusion criteria included cases with premature rupture of membranes, antepartum hemorrhage and maternal medical disorders as hypertension, diabetes mellitus, hepatic, cardiac, renal or anemia with pregnancy, patients with uterine scar. All patients were subjected to detailed history taking, physical examination and routine investigations including complete blood picture, Rh typing, fasting blood sugar, liver functions, kidney functions and urine analysis. Ultrasound and Doppler study were done twice weekly till the onset of labor or termination of pregnancy in order to assess GA, estimated fetal weight (EFW), placental site and grading, amniotic fluid volume (AFV) (oligohydramnios was diagnosed if the largest vertical pocket less than 2 cm), Doppler study of the MCA. The study population was divided into two groups based on the presence or absence of adverse perinatal outcome. Results: Expected fetal weight (EFW), resistive Index of middle cerebral artery (MCA) and resistive Index of umbilical artery (UA) were not significantly predicting perinatal outcome of postdated pregnancies among the studied pregnant women. Amniotic fluid index (AFI) and biophysical profile (BPP) were significant predictors for perinatal outcome of postdated pregnancies. Conclusion: Resistive Index of (MCA) was not significant predictor for perinatal outcome of postdated pregnancies. Amniotic fluid index was significant predictor for perinatal outcome of postdated pregnancies.
Nurses Perception of Incentives System in Assiut University Hospital

Background: Incentives play an important role in organizations as it influences a variety of work-related behavior, as well as the motivation of employees. Aim of the study: The present study was conducted in the main Assiut University Hospital to assess nurse’s perception about the incentives system. Subject sand Methods: This study included 271 nurses who randomly selected from all units at the main Assiut University Hospital. The study included both quantitative and qualitative methods for data collection. Results: High percent of the participants reported that the most important incentives are fair remuneration, bounces, appropriate working hours, and different services (health/ education). The promotion, appreciation of work efforts, a good relations with colleagues and superior encouragement were the most important morale incentives. This is confirmed by the results of Focus group discussions as about half of the participants especially female nurses considered the morale incentives are more important than the financial one especially the good dealing and the respect from the physicians. Conclusion and Recommendations: In conclusion, this study indicates that nurses know what they want from incentives. Attention to priorities and flexible incentives system may help to create the cohesive work environment that nurses seek. Determine the objectives are the most important factors to increase the effectiveness of the incentive system.
TITLE: Prevalence and impact of oprD mutations in Pseudomonas aeruginosa strains in 1 cystic fibrosis 2

49 Defective OprD porins contribute to carbapenem resistance and may be important in 50 Pseudomonas aeruginosa adaptation to cystic fibrosis airways. It is unclear whether oprD 51 mutations are fixed in populations of shared strains that are transmitted between patients or 52 whether novel variants arise during infection. We investigated oprD sequences and 53 antimicrobial resistance of two common Australian shared strains, constructed P. aeruginosa 54 mutants with the most common oprD allelic variants and compared characteristics between 55 patients with or without evidence of infection with strains harbouring these variants. Our data 56 show that three independently acquired nonsense mutations arising from a 1-base pair 57 substitution are fixed in strain sub-lineages. These nonsense mutations are likely to contribute 58 to reduced carbapenem susceptibility in the sub-lineages without compromising in vitro 59 fitness. Not only was lung function worse among patients infected with strains harbouring the 60 nonsense mutations than those without, but they also had an increased hazard rate of lung 61 transplantation/death. Our findings further highlight that understanding adaptive changes may 62 help to distinguish patients with greater adverse outcomes despite infection with the same 63 strain. 64
Copper ecotoxicology of marine algae: a methodological appraisal

ABSTRACT The production of accurate and reliable data on copper ecotoxicology of marine algae depends on the use of trace metal clean techniques during experimentation. We reviewed the methodologies used in the literature on copper ecotoxicology of marine macro- and microalgae, specifically the use of trace metal clean procedures such as the labware used (glassware vs. plasticware), methods of cleaning the labware (acid soaking and ultrapure water rinsing), stock solution preparation (copper source and acidification), and measurement and reporting of dissolved copper concentrations. In terms of taxonomic classification, the most studied algal groups were the Phyla Ochrophyta, Bacillariophyta, Rhodophyta, and Chlorophyta. In terms of methodology, ∼50% of the articles did not specify the labware, ∼25% used glassware, and ∼25% plasticware; ∼30% of the studies specified cleaning protocols for labware to remove trace metal impurities; the copper form used to prepare the stock solutions was specified in ∼80% of studies but acidification to stabilise the dissolved copper was performed in only ∼20%; and the dissolved copper concentration was measured in only ∼40% of studies. We discuss the importance of following trace metal clean techniques for the comparison and interpretation of data obtained on copper ecotoxicology in algae.
Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic

Abstract Introduction: This observational study looked at 255 COVID19 patients who required invasive mechanical ventilation (IMV) during the first two months of the US pandemic. Through comprehensive, longitudinal evaluation and new consideration of all the data, we were able to better describe and understand factors affecting outcome after intubation. Methods: All vital signs, laboratory values, and medication administrations (time, date, dose, and route) were collected and organized. Further, each patient's prior medical records, including PBM data and available ECG, were reviewed by a physician. These data were incorporated into time-series database for statistical analysis. Results: By discharge or Day 90, 78.2% of the cohort expired. The most common pre-existing conditions were hypertension, (63.5%), diabetes (59.2%) and obesity (50.4%). Age correlated with death. Comorbidities and clinical status on presentation were not predictive of outcome. Admission markers of inflammation were universally elevated (>96%). The cohort's weight range was nearly 7-fold. Causal modeling establishes that weight-adjusted HCQ and AZM therapy improves survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum levels. Discussion: This detailed approach gives us better understanding of risk factors, prognostic indicators, and outcomes of Covid patients needing IMV. Few variables were related to outcome. By considering more factors and using new methods, we found that when increased doses of co-administered HCQ and AZM were associated with >100% increase in survival. Comparison of absolute with weight-adjusted cumulative doses proves administration [≥]80 mg/kg of HCQ with > 1 gm AZM increases survival in IMV-requiring Covid patients by over 100%. According to our data, HCQ is not associated with prolongation. Studies, which reported QTc prolongation secondary to HCQ, need to be re-evaluated more stringently and with controls. The weight ranges of Covid patient cohorts are substantially greater than those of most antibiotic RCTs. Future clinical trials need to consider the weight variance of hospitalized Covid patients and need to study therapeutics more thoughtfully.
Environmental and Geological Study of the Suggested Marine Port Site at Sahl Hasheesh area, Hurghada, Red Sea coast, Egypt (A case study).

The Red Sea constitutes a unique ecosystem with high biological diversity (EEAA, 2016). Its natural resources provide a substantial economic in addition to the fishery industry, which has ensured food security to many people of the region and created jobs for others (EEAA, 2016). The Red Sea tourism is an ever growing and increasingly important industry for commerce and other economic activities. With increasing the urban occupations along the Red Sea coast due to the progressive development in the tourism and related industries throughout the last three decades, the rapid and uncontrolled human activities along the Red Sea coast increased intensively in ARTICLE INFO ABSTRACT Article History: Received: March 1, 2021 Accepted: March 30, 2021 Online: April 22, 2021 _______________
Cash Holdings and Relationship Lending

We examine the effect of relationship lending on a firm's cash-holding levels. Relationship lending allows lenders to generate private information about borrowers which mitigates their financial constraints. We find that cash-holding levels for firms with a relationship lender are significantly lower compared to non-relationship borrowers. Within the group of firms with established lending relationships, it is the firms with high precautionary cash needs that benefit from these relationships. Such firms hold significantly less cash compared to relationship borrowers with low precautionary cash needs. We report that relationship lending is not associated with the market value of firms' cash holdings.
Foreign Direct Investment in the Context of Global Value Chains and Superstar Firms

The emergence of GVCs and recently superstar firms has been well documented, but less attention has been paid to what these joint developments mean for how we think about and need to examine FDI. Against this setting, I explore four dimensions of FDI: its conceptual aspects, measurement, determinants and implications. I show that including relevant aspects of GVCs and superstar firms emphasizes better both the highly productive and “monopolistic” nature of superstar firms as well as the equity and non-equity investments that such firms make to organize production at the global level. Following this definition, there are multiple measures and recently novel datasets that allow to examine new and decisive mechanisms that dictate determinants and implications of FDI. From the analysis emerges that relational costs of production, firm-level characteristics and changes in global economic environment are important FDI determinants (additional to country-level issues). I find that the new data (and advances in underlying firm-level theories) allow to study more clearly the various (coinciding) mechanisms affecting firm productivity after foreign entry, which shows positive effects, although evidence on competition effects is limited and distributional effects exist. It too highlights an important implication previous unobserved: that the most productive firms tend to self-select into FDI, which plausibly increases market concentration in global markets, which may change how the various mechanisms affect domestic firms and workers upon foreign entry.
Relative Performance Evaluation and the Peer Group Opportunity Set

We develop an algorithm that mimics the relative performance evaluation (“RPE”) peer selection process used for CEOs’ incentive plans. Our algorithm constructs the portfolio of peer firms that exhibits the highest in-sample stock performance correlation with the focal firm, which we then use as a counterfactual to better understand firms’ actual RPE choices. We find that most firms use RPE in a manner consistent with optimal risk-sharing; firms are more likely to use RPE when a viable peer group is available, and they construct peer groups that are about as effective as possible at shielding CEOs from outcome risk. However, some firms choose not to use RPE even when an effective peer group is available; non-reliance on RPE in these cases appears to be related to competitive sabotage concerns. Other firms choose to use RPE, but benchmark against a peer group that is not effective from a risk-sharing perspective; reliance on RPE in these cases appears to be related to rent-extraction. Collectively, our study improves the understanding of firms’ ex ante ability to construct an effective peer group, and thereby sheds new light on why firms do—and perhaps more importantly, why some firms do not—use relative performance evaluation in their CEOs’ incentive plans.