القيم الحكيمة لدى الشخصيات الرئيسية في رواية "وكانت صديقة" لكمال السيد: دراسة سيكولوجية أدبية على أساس نظرية مارتن سليجمان

مستخلص البحث تمكّن قيم الحكيمة البشر من تحقيق السعادة الحقيقية ولا يمكن إنكار أن السعادة عامل مهم في حياة الإنسان. تظهر هذه الدراسة أن البشر الذين لديهم المزيد من الفضائل سيشعرون بالسعادة والرضا في حياتهم ، وبالتالي زيادة الرفاهية النفسية وتحسين نوعية الحياة. لمعرفة قيمة الحكيمة ، يستخدم الباحث نظرية السيكولوجية الإيجابية لمارتن سيليجمان كأحد مؤسسي علم النفس الإيجابي. يؤكد سيليجمان على أهمية التغلب على المشكلات ويؤكد على تطوير السمات الإيجابية ويقسم الفضائل إلى ستة أنواع ، وهي الحكمة والمعرفة والشجاعة والإنسانية والحب والعدل والتواضع والتعالي. الهدف من هذا البحث هو لبيان القيم الحكيمة للشخصية فاطمة وعلي في رواية "وكانت صدّيقة" لكمال السيد من وجهة نظرية مارتن سليجمان. المنهج في هذا البحث وصفي نوعي. تُستخدم طرق البحث الوصفي النوعي لوصف وشرح ظاهرة أو حدث بالتفصيل والعمق والتفاصيل وفقًا لنظرية مارتن سيليجمان. في هذه الدراسة ، كانت تقنيات جمع البيانات من خلال قراءة الروايات وتسجيل الأشياء التي تصف سلوك الشخصية للحصول على البيانات ذات الصلة. ثم تم تحليل البيانات التي تم جمعها لإنتاج وصف معمق ومفصل لفضائل الشخصية فاطمة وعلي في رواية "وكانت صدّيقة" لكمال السيد. بناء على نتائج هذه الدراسة تبين أن شخصية خمس لها أربع فضائل هي: الحكمة والمعرفة والشجاعة والإنسانية والمحبة والبساطة والتعالي. شخصية علي لها خمس فضائل في شكل ؛ الحكمة والمعرفة ، والشجاعة ، والإنسانية والمحبة ، والعدل ، والتواضع ، والتعالي. يمكن أن توفر قيم الحكيمة في كلا الحرفين فهماً أفضل وفهماً أفضل لكيفية تأثير السمات الإيجابية على تطور وجودة حياة الشخصيات. ABSTRACT Virtues enable people to achieve true happiness and it is undeniable that happiness is an important factor in human life. This study shows that humans who have more virtues will feel happier and more satisfied in their lives, thus increasing psychological well-being and improving quality of life. To see the value of virtue, the researcher uses the theory of positive psychology by Martin Seligman, one of Positive Psychology’s founders. Seligman emphasizes the importance of overcoming problems and emphasizes the development of positive traits and divides virtues into six kinds, namely Wisdom and Knowledge, Courage, Humanity and Love, Justice, Temperance, and Transcendence. This study aims to determine the value of virtue in the characters Fatimah and Ali in the novel "Wa Kanat Shiddiqoh" by Kamal Sayyid. The method in this research is descriptive qualitative. The descriptive qualitative research method is used to describe and explain a phenomenon or event in detail, in-depth, and detail according with Martin Seligman's theory. In this study, the data collection technique is through reading the novel and recording things that describe the character's behavior to get related data. The data collected is then analyzed to produce an in-depth and detailed description of the value of virtue in the characters Fatimah and Ali in the novel "Wa Kanat Shiddiqoh" by Kamal Sayyid. Based on the results of this study, shows that Fatimah has five virtues in the form of; Wisdom and Knowledge, Courage, Humanity and Love, Temperance, and Transcendence. Ali's character has five virtues in the form of; Wisdom and Knowledge, Courage, Humanity and Love, Justice Temperance, and Transcendence. Virtue values in both characters can provide a better understanding and understand how positive traits affect the development and quality of life of the characters. ABSTRAK Nilai-nilai kebajikan menjadikan manusia dapat mencapai kebahagiaan yang sesungguhnya dan tidak bisa dipungkiri bahwa kebahagiaan adalah salah faktor penting dalam kehidupan manusia. Studi ini menunjukkan bahwa manusia yang memiliki lebih banyak kebajikan akan merasa lebih bahagia dan puas dalam hidup mereka, sehingga dapat meningkatkan kesejahteraan psikologis dan peningkatan kualitas hidup. Untuk melihat nilai kebajikan peneliti menggunakan teori psikologi posititf martin Seligman sebagai salah satu pendiri dari Psikologi Positif. Seligman menekankan pentingnya mengatasi masalah dan menekankan pada pengembangan sifat-sifat positif dan membagi nilai-nilai kebajikan menjadi enam macam, yaitu Kearifan dan Pengetahuan, Keteguhan hati, Perikemanusiaan dan Cinta Kasih, Keadilan, Kesederhanaan, dan Transendensi. Penelitian ini bertujuan untuk mengetahui nilai kebajikan pada tokoh Fatimah dan Ali dalam novel “Wa Kanat Shiddiqoh” karya Kamal Sayyid. Metode dalam penelitian ini adalah deskriptif kualitatif. Metode penelitian deskriptif kualitatif digunakan untuk menggambarkan dan menjelaskan suatu fenomena atau peristiwa secara rinci, mendalam, dan terperinci sesuai dengan teori martin Seligman. Dalam penelitian ini, teknik pengumpulan data melalui membaca novel dan mencatat hal-hal yang menggambarkan perilaku tokoh untuk mendapatkan data yang berkaitan. Data yang dikumpulkan selanjutnya dianalisis untuk menghasilkan deskripsi yang mendalam dan detail mengenai nilai kebajikan pada tokoh Fatimah dan Ali dalam novel “Wa Kanat Shiddiqoh” karya Kamal Sayyid. Berdasarkan hasil dari penelitian ini menunjukkan bahwa tokoh Fatimah memiliki lima nilai kebajikan berupa; Kearifan dan Pengetahuan, Keteguhan hati, Perikemanusiaan dan Cinta Kasih, Kesederhanaan, dan Transendensi. Tokoh Ali memiliki lima nilai kebajikan berupa; Kearifan dan Pengetahuan, Keteguhan hati, Perikemanusiaan dan Cinta Kasih, Keadilan, Kesederhanaan, dan Transendensi. Nilai-nilai kebajikan pada kedua tokoh dapat memberikan pemahaman yang lebih baik dan memahami bagaimana sifat-sifat positif mempengaruhi perkembangan dan kualitas hidup tokoh

The Gammaherpesvirus m2 Protein Manipulates the Fyn/Vav Pathway through a Multidocking Mechanism of Assembly

To establish latent infections in B-cells, gammaherpesviruses express proteins in the infected B-cells of the host that spuriously activate signalling pathways located downstream of the B-cell receptor. One such protein is M2, a murine gammaherpesvirus 68-encoded molecule that activates the Vav1/Rac1 pathway via the formation of trimolecular complexes with Scr family members. Previous reports have shown that the formation of this heteromolecular complex involves interactions between a proline rich region of M2 and the Vav1 and Fyn SH3 domains. Here, we show that the optimal association of these proteins requires a second structural motif encompassing two tyrosine residues (Tyr120 and 129). These residues are inducibly phosphorylated by Fyn in non-hematopoietic cells and constitutively phosphorylated in B-cells. We also demonstrate that the phosphorylation of Tyr120 creates specific docking sites for the SH2 domains of both Vav1 and Fyn, a condition sine qua non for the optimal association of these two signalling proteins in vivo. Interestingly, signaling experiments indicate that the expression of M2 in B-cells promotes the tyrosine phosphorylation of Vav1 and additional signaling proteins, a biological process that requires the integrity of both the M2 phosphotyrosine and proline rich region motifs. By infecting mice with viruses mutated in the m2 locus, we show that the integrity of each of these two M2 docking motifs is essential for the early steps of murine gammaherpesvirus-68 latency. Taken together, these results indicate that the M2 phosphotyrosine motif and the previously described M2 proline rich region work in a concerted manner to manipulate the signaling machinery of the host B-cell

A Single CD8+ T Cell Epitope Sets the Long-Term Latent Load of a Murid Herpesvirus

The pathogenesis of persistent viral infections depends critically on long-term viral loads. Yet what determines these loads is largely unknown. Here, we show that a single CD8+ T cell epitope sets the long-term latent load of a lymphotropic gamma-herpesvirus, Murid herpesvirus-4 (MuHV-4). The MuHV-4 M2 latency gene contains an H2-Kd -restricted T cell epitope, and wild-type but not M2− MuHV-4 was limited to very low level persistence in H2d mice. Mutating the epitope anchor residues increased viral loads and re-introducing the epitope reduced them again. Like the Kaposi's sarcoma–associated herpesvirus K1, M2 shows a high frequency of non-synonymous mutations, suggesting that it has been selected for epitope loss. In vivo competition experiments demonstrated directly that epitope presentation has a major impact on viral fitness. Thus, host MHC class I and viral epitope expression interact to set the long-term virus load

Defects in tRNA Modification Associated with Neurological and Developmental Dysfunctions in Caenorhabditis elegans Elongator Mutants

Elongator is a six subunit protein complex, conserved from yeast to humans. Mutations in the human Elongator homologue, hELP1, are associated with the neurological disease familial dysautonomia. However, how Elongator functions in metazoans, and how the human mutations affect neural functions is incompletely understood. Here we show that in Caenorhabditis elegans, ELPC-1 and ELPC-3, components of the Elongator complex, are required for the formation of the 5-carbamoylmethyl and 5-methylcarboxymethyl side chains of wobble uridines in tRNA. The lack of these modifications leads to defects in translation in C. elegans. ELPC-1::GFP and ELPC-3::GFP reporters are strongly expressed in a subset of chemosensory neurons required for salt chemotaxis learning. elpc-1 or elpc-3 gene inactivation causes a defect in this process, associated with a posttranscriptional reduction of neuropeptide and a decreased accumulation of acetylcholine in the synaptic cleft. elpc-1 and elpc-3 mutations are synthetic lethal together with those in tuc-1, which is required for thiolation of tRNAs having the 5′methylcarboxymethyl side chain. elpc-1; tuc-1 and elpc-3; tuc-1 double mutants display developmental defects. Our results suggest that, by its effect on tRNA modification, Elongator promotes both neural function and development

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

The relationship between mood and sleep in different female reproductive states

Peer reviewe

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting