Caspase-generated fragment of the Met receptor favors apoptosis via the intrinsic pathway independently of its tyrosine kinase activity

The receptor tyrosine kinase Met and its ligand, the hepatocyte growth factor, are essential to embryonic development, whereas the deregulation of Met signaling is associated with tumorigenesis. While ligand-activated Met promotes survival, caspase-dependent generation of the p40 Met fragment leads to apoptosis induction – hallmark of the dependence receptor. Although the survival signaling pathways induced by Met are well described, the pro-apoptotic signaling pathways are unknown. We show that, although p40 Met contains the entire kinase domain, it accelerates apoptosis independently of kinase activity. In cell cultures undergoing apoptosis, the fragment shows a mitochondrial localization, required for p40 Met-induced cell death. Fulminant hepatic failure induced in mice leads to the generation of p40 Met localized also in the mitochondria, demonstrating caspase cleavage of Met in vivo. According to its localization, the fragment induces mitochondrial permeabilization, which is inhibited by Bak silencing and Bcl-xL overexpression. Moreover, Met silencing delays mitochondrial permeabilization induced by an apoptotic treatment. Thus, the Met-dependence receptor in addition to its well-known role in survival signaling mediated by its kinase activity, also participates in the intrinsic apoptosis pathway through the generation of p40 Met – a caspase-dependent fragment of Met implicated in the mitochondrial permeabilization process

A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children

Background: Atopic dermatitis (AD) aetiology is not exactly identified, but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Despite the fact that Corticosteroids are the mainstay therapy in the management of AD, they have many local and systemic adverse effects.Objective: The aim of this study is to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in the management of the AD of children diagnosed with AD.Patients and Methods: This study was conducted on 200 children with AD. They were simply randomized into two groups, the tacrolimus group treated with 0.03% topical tacrolimus ointment and the hydrocortisone group treated with 1% hydrocortisone cream twice daily during the 3 weeks study period.Results: At the end of the study, both the tacrolimus and hydrocortisone groups showed a significant decline in the mean serum level of IL-10, IL-17, and IL-23 (p < 0.05) when compared to their baseline levels. However, the tacrolimus group showed a more significant decrease (p < 0.05) in the mean serum level of IL-10, IL-17, and IL-23 as compared to the hydrocortisone group [Mean differences = 1.600, 95% CI: 0.9858–2.214; 1.300, 95% CI: 1.086–1.514 and 4.200, 95% CI: 3.321–5.079]. Moreover, the median mEASI decreased similarly from 32 to 21 in the tacrolimus group and from 30 to 22 in the hydrocortisone group (p > 0.05) [Median difference = −2.000, 95% CI: −2.651 to −1.349; Median difference = 1.000, 95% CI: 0.3489–1.651]. Mild to moderate transient stinging and erythema were the main adverse effects that showed higher incidence in the tacrolimus group than in the hydrocortisone group (p < 0.05). In most cases, they resolved within 3–4 days. Besides, tacrolimus ointment did not cause skin atrophy as compared to the hydrocortisone group (p < 0.05).Conclusion: Tacrolimus ointment is more beneficial than hydrocortisone cream in managing AD in children in terms of lowering the inflammatory markers, however, there is no difference on the dermatitis severity scale. Moreover, tacrolimus is safer with a better side effect profile compared to hydrocortisone.Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05324618

The Effect of Evolved Attributes on Classification Algorithms

We carry out a systematic study of the effect on the performance of a range of classification algorithms with the inclusion of attributes constructed using genetic programming. The genetic program uses information gain as the basis of its fitness. The classification algorithms used are C5, CART, CHAID and a MLP. The results show that, for the majority of the data sets used, all algorithms benefit by the inclusion of the evolved attributes. However, for one data set, whilst the performance of C5 improves, the performance of the other techniques deteriorates. Whilst this is not statistically significant, it does indicate that care must be taken when a pre-processing technique (attribute construction using GP) and the classification technique (in this case, C5) use the same fundamental technology, in this case Information Gain

Perancangan Video Mobil Antik Presiden Ir. Soekarno Sebagai Media Untuk Mengenalkan Kepada Masyarakat Surabaya

President Ir. Soekarno is a hero who inspired many people in Indonesia. But many people is unknowning about a precious objects relics of President Ir. Soekarno, for example found 23 units of antique presidential car ever used by President Ir. Soekarno to lead him to carry out his duties as a leader of the Indonesian state. In fact, not all of people, especially of Surabaya know what antique car ever used by President Ir. Soekarno in his tenure. This is based on the results of interviews conducted by several collectors who became resource persons. Lack of knowledge on President Ir. Sukarno led to low public awareness, especially in Surabaya about Presidential antique presidential car. Sukarno. From that case, this research is aimed to make a video of antique car of President Ir. Soekarno as a media to introduce to the people in Surabaya

Improvement of E-learning Based via Learning Management Systems (LMS) Using Artificial Neural Networks

E-Learning nowadays is one of the learning system which uses the latest technologies in the field of innovative learning, it has been an extension of traditional education. The effectiveness of E-Learning lies in achievement of education and improving the student's performance and its reflection on the demands of students by discovering the weaknesses and strengths of the factors affecting distance learning. In this research we have used the multilayered neural networks (feedforward neural network) with an input of five neurons which represent the five criteria (virtual class presence, Discussion during semester, Solving Quiz, Mid-term examination, Assignment), hidden layer has two neurons and the output layers have one neuron. to estimate the performance of the students attending an E-Learning course, feedforward neural network was  applied to real data )400 student records (80%) are used for training data and the remaining 100 records (20%) are used as test data, performance = 0.0699), to  predict the performance of  the students   that reflect their real grades

The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial

Background and Aim: Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes. Hence, the present study aimed to assess the efficacy and safety of oral cholecalciferol on Non-alcoholic fatty liver patients.Subjects and Methods: This study was conducted on 140 patients that were randomized either to group 1 that received the standard conventional therapy in addition to placebo or group 2 that received the standard conventional therapy in addition to cholecalciferol during the 4 months study period.Results: At the end of the study group 2 revealed significant decrease (p < 0.05) in the mean serum level of TG, LDL-C, TC, hsCRP as compared to their baseline results and group 1 results. Additionally, a significant improvement in the serum levels of ALT (p = 0.001) was seen in group 2 at the end of the study when compared to group 1. Whereas group 1 did not show any change in these parameters when compared to group 2 and their baseline results.Conclusion: Cholecalciferol was shown to have beneficial effects on serum ALT levels, hsCRP levels and lipid profile of NAFLD patients.Clinical Trial Registration:https://prsinfo.clinicaltrials.gov/prs-users-guide.html, identifier NCT0561319