Miracle-dz/UniFAR-FTUs huggingface dataset:
P450 inhibition profile of mibefradil’s hydrolyzed metabolite, Ro 40-5966 in comparison to

The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil Abstract A novel mibefradil derivative, NNC55-0396, designed to be hydrolysis resistant was shown to be a selective T-type Ca 2+ channel inhibitor without L-type Ca 2+ channel efficacy. However, its effects on cytochrome P450s have not previously been examined. We investigated the inhibitory effects of NNC55-0396 toward 7 major recombinant human cytochrome P450s: CYP3A4, 2D6, 1A2, 2C9, 2C8, C19, and 2E1, and compared its effects with those of mibefradil and its hydrolyzed metabolite, Ro40-5966. Our results show that CYP3A4 and 2D6 are the two P450s most affected by mibefradil, Ro40-5966, and NNC55-0396. Mibefradil (IC 50 =33±3 nM, K i =23±0.5 nM) and Ro40-5966 (IC 50 =30±7.8 nM, K i =21±2.8 nM) have a nine to ten-fold greater inhibitory activity towards recombinant CYP3A4 benzyloxy-4-trifluoromethylcoumarin O-debenzylation activity than NNC55-0396 (IC 50 =300±30 nM, K i =210±6 nM). More dramatically, mibefradil (IC 50 =566±71 nM, K i =202±39 nM) shows 19-fold higher inhibition of CYP3A-associated testosterone 6 β -hydroxylase activity in human liver microsomes compared to NNC55-0396 (IC 50 =11±1.1 µM, K i =3.9±0.4 µM). Loss of testosterone 6 β hydroxylase activity by recombinant CYP3A4 was shown to be time- and concentration-dependent with both compounds. However, NNC55-0396 (K I =3.87µM, K inact =0.061 min -1 ) is a much less potent mechanism-based inhibitor than mibefradil (K I =83 In have a three to four-fold greater activity towards recombinant CYP2D6 than mibefradil Our results suggest that NNC55-0396 could microsomes. These in vitro studies suggest that NNC55-0396 may be a more beneficial therapeutic agent for T-type Ca 2+ channels antagonist.
Choriomeningitis Virus-Infected Mice Precursors in the Brains of Lymphocytic Accumulation of Immunoproteasomal Reduced Immunoproteasome Formation and

Tissue inﬂammation is accompanied by the cytokine-mediated replacement of constitutive proteasomes by immunoproteasomes that ﬁnally leads to an optimized generation of MHC class I restricted epitopes for Ag presentation. The brain is considered an immunoprivileged organ, where both the special anatomy as well as active tolerance mechanisms repress the development of inﬂammatory responses and help to prevent immunopathological damage. We analyzed the immunoproteasome expression in the brain after an infection with lymphocytic choriomeningitis virus (LCMV) and could show that LCMV-infection of mice leads to the transcriptional induction of inducible proteasome subunits in the brain. However, compared with other organs, i.p. and even intracranial infection with LCMVonly led to a faint expression of mature immunoproteasome in the brain and resulted in the accumulation of immunoproteasomal precursors. By immunohistology, we could identify microglia-like cells as the main producers of immunoproteasome, whereas in astrocytes immunoproteasome expression was almost exclusively restricted to nuclei. Neither the immunoproteasome subunits low molecular mass polypeptide 2 nor multicatalytic endopeptidase complex-like–1 were detected in neurons or oligodendrocytes. In vitro studies of IFN- g –stimulated primary astrocytes suggested that the observed accumulation of immunoproteasomal precursor complexes takes place in this cell population. Functionally, the lack of immunoproteasomes protracted and lowered the severity of LCMV-induced meningitis in LMP7 2 / 2 mice suggesting a contribution of immunoproteasomes in microglia to exacerbate immunopathological damage. We postulate a posttranslationally regulated mechanism that prevents abundant and inappropriate immunoproteasome assembly in the brain and may contribute to the protection of poorly regenerating cells of the CNS from immunopathological destruction.
Precise-Orientation-Beamforming Scheme for Wireless Communications between Buoys

Utilizing wireless sensor network (WSN) to monitor the marine environment is one of the major techniques in oceanographic monitoring, and how to increase the limited communication distance between the buoys in WSN has become a hot research issue. In this paper, a new technique called precise-orientation-beamforming (POB) which uses the beamforming algorithm to increase the communication distance between buoys is presented. As was widely applied in the radar and sonar, the beamforming method was not used to extend the communication distance between buoys so far. The POB method overcomes the unstable position of buoys caused by waves by implementing the orientation filter. The whole process includes two steps: First, the real-time attitude of the antenna array is calculated by the orientation filter. With the known relative direction of the destination node to the antenna array, the second step is to control phased array antenna beamforming parameters, directing the beam at the destination node. The POB scheme has been simulated under the condition of regular waves. The results reveal that POB provides significant power gains and improves the distance between two communicating nodes effectively.
Building bridges for future sustainability? Breaching the research-teaching nexus in engineering education

The relationship between research and learning and teaching represents what has been described as amongst the most intellectually tangled, managerially complex and politically contentious issues in mass higher education (Scott, 2005, p 53). Despite this, arguments that in order to achieve high quality scholarly outcomes, university teachers need to adopt an approach to teaching similar to that of research (founded upon academic rigour and evidence), has long been discussed in the literature. However, the practicalities of promoting an empirical and evidence-based approach to teaching in engineering education make dealing with the research / teaching nexus a somewhat challenging proposition. Using a phenomenographic approach, bringing together and applying the findings of a mixed methodological study, the workshop will adopt an activity based, interactive approach to encourage staff to consider the challenges and benefits of adopting an evidence-based approach to learning and teaching through the utilisation of research to inform their own practice.
Microstrip antennas with frequency agility and polarization diversity

AbsWacf-A technique is investigated for controlling the operating frequency and polarization of microstrip antennas. The control is achieved by placing shorting posts at appropriate locations within the antenna’s bonndaries. By changing the number and locations of the posts, the operating frequency can be tuned over a 1.540-1 range, and the polarization can be changed from horizontal to vertical, right- hand circular, or left-hand circular. All of these changes are obtained without significantly altering the inpnt impedance or radiation patterns of the antena and without increasing the complexity of the external microwave feed network. The frequency and polarization can be electronically controlled by nsing microwave switching diodes for the shorting posts. Antennas that have two feeds and operate si- multaneously in two orthogonal polarizations have been constructed with the capability to switch between linear and circular polarization. Also, a thin frequency-scanned array has been built with the fre- quency-agile microstrip elements.
BMP-signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13-driven tuft cell hyperplasia

The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes of immune defense. The intestinal epithelium has a pivotal role in both immune initiation and effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, and IL-22. Here, we studied intestinal epithelial immune responses using organoid image analysis based on a convolutional neural network, transcriptomic analysis, and in vivo infection models. We found that IL-13 and IL-22 both induce genes associated with goblet cells, but the resulting goblet cell phenotypes are dichotomous. Moreover, only IL-13–driven goblet cells are associated with classical NOTCH signaling. We further showed that IL-13 induces the bone morphogenetic protein (BMP) pathway, which acts in a negative feedback loop on immune type 2–driven tuft cell hyperplasia. This is associated with inhibiting Sox4 expression to putatively limit the tuft cell progenitor population. Blocking ALK2, a BMP receptor, with the inhibitor dorsomorphin homolog 1 (DMH1) interrupted the feedback loop, resulting in greater tuft cell numbers both in vitro and in vivo after infection with Nippostrongylus brasiliensis. Together, this investigation of cytokine effector responses revealed an unexpected and critical role for the BMP pathway in regulating type 2 immunity, which can be exploited to tailor epithelial immune responses. Description Developmental pathways, such as BMP and NOTCH, tailor intestinal epithelial responses to cytokines during immunity to infection. BMP puts the brakes on tuft cells Intestinal parasite infections or allergic reactions promote IL-13–induced differentiation of tuft cells as one manifestation of type 2 immunity in the gut. Using organoid cultures of intestinal epithelial cells, Lindholm et al. investigated how the lymphocyte cytokines IL-13, IL-22, and IFNγ regulate the signaling pathways that influence epithelial differentiation. While tuft cell IL-25 promoted expansion of IL-13–producing ILC2s in a feed-forward loop, the resulting IL-13 also induced ligands of the bone morphogenetic protein (BMP) signaling pathway. BMP agonists acted on stem cells to prevent runaway tuft cell expansion by limiting expression of Sox4, a transcription factor required for tuft cell differentiation. These findings provide new molecular insights into how intestinal epithelial differentiation is carefully choreographed in response to a diverse array of cytokine signals.
A collaboration between physicians and journalists to create unbiased health information

In an era where “fake news” and biased information are shared in the traditional press and on social media, collaboration between physicians and journalists is increasingly important to help disseminate accurate and trustworthy health information to the general public.1 Our experience from Japan shows how independent investigative journalists and physicians can collaborate together topublishunbiasedandobjectivehealth information.
Less Sugar and More Whole Grains in Infant Cereals: A Sensory Acceptability Experiment With Infants and Their Parents

There is an urgent need to reduce sugar intake in early childhood. Commercial infant cereals are among the first solid foods introduced to infants at the beginning of the complementary feeding period in most countries. The aim of this study was to examine infants’ overall acceptability of low-sugar complementary cereals. To do so, a between-subjects experimental study with 165 parents and their infants aged 6–24 months was conducted where one group tested a high-sugar refined cereal (21 g/100 g), and the other a low-sugar cereal (<1 g/100 g) with 50% of whole grain, which represented a 95.2% decrease in sugar content. We found no significant differences between the two groups in terms of infants’ overall acceptability (infant’s reaction, estimated intake and relative intake). Importantly, infants’ reactions to high- and low-sugar cereals were not influenced by the time that infants had been consuming sweet cereals (15–25% sugar) before the experiment took place. In addition, parent’s overall liking and sensory evaluation (sweetness, color, taste, texture, and aroma) was positive and very similar in both groups. Overall, our findings show that it is feasible to reduce sugar content in infant cereals without sacrificing its sensory acceptability by infants and their parents. This represents a good opportunity for the infant food industry to adhere to current healthy and sustainable demands of lowering the sugar intake leading to important benefits in infants’ health, without compromising competitiveness in the market.
Does Environmental, Social, and Governance Drive the Sustainability of Multinational Corporation’s Subsidiaries? Evidence From Korea

We examined the relations between environmental, social, and governance (ESG) activities and the performance of subsidiaries of multinational corporations (MNCs). We further investigated the moderating effect of market-oriented organizational culture on the relationship between ESG and performance. Employing generalized least square regression analysis using survey data, we show that ESG activities of MNC subsidiaries are positively associated with financial and non-financial performance. These results suggest that ESG improves the financial and non-financial performance of subsidiaries. The test for the moderating effect of the market-oriented organizational culture shows that it weakens the positive relationship between ESG activities and financial performance. This could be due to the incongruous nature of the short-term focus of a market-oriented organizational culture versus the long-term orientation of the sustainability of ESG activities.
Will the “Prosperity of the Population and Son” Affect the Hiring of the “Shopkeeper”?—Research on Succession Decisions of Actual Controllers in Chinese Family Firms

“The prosperity of the population and son, the prosperity of the country” means that the more family members and male offspring, the more stable and prosperous the family foundation of future generations. This concept is deeply engraved in China’s traditional culture, and affects the behavior and decision-making of the actual controller as a parent. Chinese family enterprises are facing urgent problems such as power transfer and leader replacement. Although some studies have paid attention to the relationship between children’s characteristics and enterprise inheritance, they have not connected this relationship with the internal mechanism of successor selection. The existing theoretical research lacks in-depth analysis of the influence mechanism of children’s characteristics on professional manager appointment. Therefore, we attempt to make up for this deficiency. Based on this, we take Chinese family listed companies from 2009 to 2019 as a sample to test the impact of the number and the gender structure of actual controllers’ children on family enterprises’ professional management. The study found that the number of children, especially the number of sons, will inhibit the professional operation of enterprises. This conclusion is still true after the robustness test. Further research found that compared with daughters, sons have a more significant impact on professional management. At the same time, the greater the ownership proportion of the actual controller, the stronger the correlation between children’s characteristics and professional management. We not only studied the influencing factors of enterprise succession from the perspective of children’s characteristics, but also enriched the organization theory in the context of family business, which is helpful to promote the benign evolution and healthy and sustainable development of enterprises.
Comparative labour productivity in British and Russian manufacturing, circa 1908

ABSTRACT Using data from official manufacturing censuses, we compare labour productivity in the UK and the Russian Empire around 1908 in the industries in which medium- and large-size enterprises predominated. We find that Russia’s labour productivity was 75.3 or 57.4% of the British level, depending on whether we include or exclude Russia’s large and highly productive spirits industry. Russia’s productivity was between France’s and the Netherlands’, if we include the spirits industry; and between the Netherlands’ and Italy’s, if we exclude it. We find that the majority of Russian industries underperformed the British ones. However, some of the industries that had been established or modernized during the state-induced industrialization policies of the 1890s, including the metallurgy in the Southern industrial region, iron and steel tubes, railway carriages, and butter and cheese, performed on a par with or close to their British counterparts. The remaining modernized industries, including spirits, tobacco, and petrochemical sectors, outperformed their British equivalents. Our findings suggest that although Russia’s aggregate labour productivity lagged behind the UK’s, Russia’s modernized industries achieved, and in some cases surpassed, the productivity level of their British counterparts.
Change in Defensive Functioning Following Group Psychodynamic-Interpersonal Psychotherapy in Women With Binge-Eating Disorder

ABSTRACT We examined change in defensive functioning following group psychodynamic-interpersonal psychotherapy (GPIP) for binge-eating disorder (BED) compared to a waitlist control. We hypothesized that defensive functioning will improve to a greater extent at posttreatment for those in GPIP compared with those in a waitlist control condition. Participants were women with BED assigned to GPIP (n = 131) or a waitlist control (n = 44) condition in a quasi-experimental design. Those who received GPIP had significantly greater improvements in defensive functioning from pretreatment to six months posttreatment compared to the control group. GPIP may be effective for improving defensive functioning in individuals with BED. A randomized controlled trial is needed to confirm that GPIP is efficacious for addressing defensive functioning among women with BED.
Augmented Security System for Commercial buildings by Manipulating Object Detection and Admin Panel

The Augmented security system is an ultra-modern security system with the latest hybrid technology of artificial intelligence. This system overcomes all the major problems that are faced by other security systems. This idea is created to prevent heists in highly protected places. This is an eccentric idea, which uses two-step security protection. Object detection software and A.I. cameras are created to detect intruders. After which it sends a picture to the authorities through a telegram application with an alert message. Laser security protection is installed at all the possible entry points and tear gas guns inside the highly protected places. As the GSM module plays an important role it is placed in a safe place. Once the beam gets interrupted tear gas guns, siren, and GSM module gets activated. The module makes a call to the authorities about the heist and Tear gas gives out eye irritation gas which produces a burning sensation to the eyes which distracts them. Ultimately this results in detaining the intruders and does not allow the intruders to go in further and helps the authorities to arrive at the location on time. This system has an admin control panel access to switch off and on the whole system, Admin panel is controlled using RFID. MasterCard can activate and deactivate the whole system and in addition, it has a key fob that can only activate the system. This security system must be implemented in highly protected areas. So that we can avoid theft and robbery
Perceived Stress Prediction among Employees using Machine Learning techniques

Stress is an overworked emotion that can arise from a multitude of factors in our daily lives. It has produced a potentially dangerous scenario for employee mental health throughout the world. To treat and minimize the consequences of stress, there must first be a reliable and reproducible technique for determining the degree of stress being experienced. To date, there have been limited studies to quantify individual stress levels beyond self-reporting by EEG, ECG, questionnaires, and other methods. All of these approaches have an issue with estimating stress accurately. As a result, this inspired me to concentrate on a better understanding of employee stress. In this research, we used the Perceived Stress Scale (PSS) technique for stress prediction. The motivation for using the PSS technique is, an easy-to-use questionnaire with well-established psychometric traits, in which the questions are prioritized using a weighted average approach, and PSS scores are computed by inverting responses, which improves the accuracy even further. In this process, we have collected the data from 251 employees via a questionnaire and used Exploratory Data Analysis (EDA) to visualize the data. According to the results of this study that used the Random Forest, Logistic Regression, and SVM techniques, only about 9.6% of employees are stress-free. From the experimental findings, the logistic regression method gives the highest prediction accuracy of 99 percent.
An Optimized Mobility Management Framework for Routing Protocol Lossy Networks using Optimization Algorithm

As a large number of sensor nodes as well as limited resources such as energy, memory, computing power, as well as bandwidth. Lossy linkages connect these nodes together. In early 2008,IETF working group looked into using current routing protocols for LLNs. Routing Over minimum power and Lossy networksROLL standardizes an IPv6 routing solution for LLNs because of the importance of LLNs in IoT.IPv6 Routing Protocol is based on the 6LoWPAN standard. RPL has matured significantly. The research community is becoming increasingly interested in it. The topology of RPL can be built in a variety of ways. It creates a topology in advance. Due to the lack of a complete review of RPL, in this paper a mobility management framework has been proposed along with experimental evaluation by applying parameters likePacket Delivery Ratio, throughput, end to end delay, consumed energy on the basis of the various parameters and its analysis done accurately. Finally, this paper can help academics better understand the RPL and engage in future research projects to improve it.
A Comprehensive Study on Threat Intelligence Platform

Cyber security has become one of the most significant industries in the digital world as securing information has become one of the most difficult tasks in today's world. Because numerous types of cyberattacks are posing a threat to global enterprises, it is critical to safeguard all types of data against theft. Cyberthreat intelligence data can be used as an assistant tool for companies in focusing and prioritizing the huge amount of complex databases they encounter today. Although there is still an organized and standardized representation of this data to make it computable. The concept of Threat Intelligence Platforms (TIPs) was created to combat cybercrime. TIPs examine historical data and correlate it with real-time data, allowing for better prioritization and faster event identification. TIPs collect indications of compromise (IoCs) from a variety of open-source feeds, like AlienVault OTX and others, to make up the majority of threat intelligence. TIPs then use complicated processes and data gathered from other sources to collect the threat score. Security analysts and incident responders can benefit from this processed information. TIPs generate graphs and visualizations based on the threat data which is used by an organization to analyze them and prevent the incident. This paper deals with the numerous aspects of cybersecurity, from the basics of collection of threat intelligence data to the information produced by Threat Intelligence Platforms (TIPs). This paper also sheds light on the current approaches and the evaluation criteria used by current Threat Intelligence Platforms (TIPs).