958 research outputs found
A comprehensive computational analysis of NR2F2/6 receptors for drug repurposing
No full textNuclear Receptors (ORFs) are a small family of transcription factors (15 members)
playing a crucial role in regulating various physiological and developmental processes.
Within this superfamily, NR2Fs, also known as Chicken Ovalbumin Upstream Promoter
Transcription Factor (COUP-TF), is a family of nuclear orphan receptors, due to the lack of
endogenous ligands. The NR2Fs are composed of three members: NR2F1 (COUP-TFI, EAR-
3), NR2F2 (COUP-TFII, ARP-1) and NR2F6 (COUP-TFIII, EAR-2). Due to the pivotal functions
of NR2Fs in cell growth, they are regarded as promising candidates for the development
of novel therapeutic targets in cancer treatment [1]. In the context of the PNRR project,
"HEAL ITALIA", a comprehensive computational analysis was conducted on the X-ray
crystal structures of the human ligand binding domain of NR2F2 (PDB ID: 3CJW) and the
NR2F6 (PDB ID: 8C5L). To date, only compound CIA1 has been identified as an inhibitor of
NR2F2 in prostate cancer cell lines (IC50 1.2-7.6 μM). To this aim, the ligand binding
domain was mapped identifying potential binding sites, designated as site 1 and site 2.
Followed by classic docking with CIA1, molecular dynamics (MD), Binding Pose
Metadynamics (BPMD), and Molecular Mechanics-Generalized Born Surface Area
continuum solvation (MM-GBSA) were conducted to assess the stability of the complexes
NR2F2-CIA in the two sites. For NR2F6 no inhibitor has been identified in the literature.
Potential hotspot binding sites were identified and their potential for drug use was
predicted. Subsequently, the identified binding sites for NR2F2 and NR2F6 were then
used to perform a virtual screening protocol involving pharmacophore models and
docking studies on extensive libraries, such as Drugbank, FDA and commercial libraries
for drug repurposing
Part of speech (POS) tagging in Roman Urdu: datasets and models
No full textRoman Urdu is a prevalent medium of expression on social media, news websites, and text messages in the subcontinent, making it a valuable data source for social media and text analytics, particularly in the Indo-Pak perspective. However, despite the immense potential, limited efforts have been made in the area of Roman Urdu text analytics due to various complexities, such as a lack of a standard lexicon, the informal nature of the text, and the lack of text processing tools. The development of the Roman Urdu Part-of-Speech (POS) dataset and the implementation of a robust tagger hold immense importance for text analytics in Roman Urdu. In this work, we created a comprehensive, large-scale Roman Urdu POS dataset and developed a Roman Urdu POS tagger, laying the foundation for future advancements in advanced text analysis. Our approach involved the utilization of Hidden Markov Models, Neural Networks, state-of-the-art transformer models, and Large Language Models as baselines. In our work, we curated two distinct test datasets: one with lexical variation and the other without such variation. This approach allowed us to test the model’s robustness in handling different linguistic challenges posed by lexical variations. Our tagger yields high-quality output with an accuracy score of 96% without lexical variation and 86% on test data with lexical variations. We also evaluated state-of-the-art Large Language Models (GPT-4o and Llama-3-8B) in zero-shot and few-shot settings, with GPT-4o achieving up to 53.78% accuracy in the few-shot configuration, demonstrating a substantial performance gap compared to specialized models. This work establishes a comprehensive framework for Roman Urdu POS tagging that effectively addresses lexical variation challenges, providing essential resources and benchmarks for advancing Roman Urdu natural language processing research
sj-pdf-1-dos-10.1177_15593258221108280 – Supplemental Material for In-silico Studies Calculated a New Chitin Oligomer Binding Site Inside Vicilin: A Potent Antifungal and Insecticidal Agent
No full textSupplemental Material, sj-pdf-1-dos-10.1177_15593258221108280 for In-silico Studies Calculated a New Chitin Oligomer Binding Site Inside Vicilin: A Potent Antifungal and Insecticidal Agent by Ahsan Saeed, Zahra Rafiq, Muhammad Imran, Qamar Saeed, Muhammad Q. Saeed, Zahid Ali, Rana K. Iqbal, Saber Hussain, Binish Khaliq, Sohaib Mehmood and Ahmed Akrem in Dose-Response</p
Social Transformation of Pakistan under the Speech of Muhammad Ali Jinnah on 11th August 1947
No full textMuhammad Ali Jinnah is the founder of Pakistan, delivered his first speech as Governor General of Pakistan in first session of the first Constituent Assembly of Pakistan on 11th August 1947. The speech has divided Pakistani society into 2 groups (i) first group advocates secularism in Pakistan, as (ii) second group emphasis that Pakistan is an Islamic State outcome of the struggle of Muslims of British India therefore there is no space of secularism in Pakistan. Muhammad Ali Jinnah stated that every individual living in Pakistan is the citizen of Pakistan without discrimination as to cast, color, creed, and community. If we look back to first Islamic State founded by Prophet Muhammad ﷺ it is clearly held that Muslims and Jews of the first Islamic State were declared as equal citizens and one community without discrimination under clause 30 of the Constitution of Madinah (Misaq e Madinah), therefore Islamic State does not mean discrimination based on religion as all citizens have equal rights before law without discrimination as to cast, color, creed and community
A CNN based coronavirus disease prediction system for chest X-rays
No full textCoronavirus disease (COVID-19) proliferated globally in early 2020, causing existential dread in the whole world. Radiography is crucial in the clinical staging and diagnosis of COVID-19 and offers high potential to improve healthcare plans for tackling the pandemic. However high variations in infection characteristics and low contrast between normal and infected regions pose great challenges in preparing radiological reports. To address these challenges, this study presents CODISC-CNN (CNN based Coronavirus DIsease Prediction System for Chest X-rays) that can automatically extract the features from chest X-ray images for the disease prediction. However, to get the infected region of X-ray, edges of the images are detected by applying image preprocessing. Furthermore, to attenuate the shortage of labeled datasets data augmentation has been adapted. Extensive experiments have been performed to classify X-ray images into two classes (Normal and COVID), three classes (Normal, COVID, and Virus Bacteria), and four classes (Normal, COVID, and Virus Bacteria, and Virus Pneumonia) with the accuracy of 97%, 89%, and 84% respectively. The proposed CNN-based model outperforms many cutting-edge classification models and boosts state-of-the-art performance
Does labour epidural slow the progress of labour and lead to complications? Obstetricians′ perception working in private and public sector teaching hospitals in a developing country
No full textBackground and Aims: Obstetricians play a major role in the decision making for provision of analgesia for the woman in labour. As epidural analgesia (EA) is the most preferred technique, it is important to know obstetricians′ perception regarding its effect on progress of labour and associated complications. Methods: The 6 months cross-sectional study included 114 obstetricians from teaching hospitals. After informed consent, obstetricians were asked to fill a predesigned questionnaire containing 13 close ended questions regarding their perception on the effect of EA on progress of labour, EA complications and whether they would recommend EA to their patients or not. Other variables included age, gender, training in EA, practice type and hospital settings (private or public sector). Results: Majority of the obstetricians had the perception of EA prolonging the first stage (89.5%) and second stage (98.2%) of labour, increasing the rate of caesarean section (87.7%), instrumental delivery (58.8%) and increasing the incidence of backache (85.5%). None of the obstetricians received any formal training in EA. Majority (84.2%) were not sure if they would recommend EA to their patients. When these responses were compared between public and private sector, a statistically higher percentage (P < 0.001) of public sector obstetricians had negative perception of EA. Conclusion: Perception of obstetrician regarding EA is contrary to the current evidence. There is a need to introduce formal curriculum on EA in obstetric training program and conduct regular refresher courses
In defense of the codification of the Islamic Law of Hudud into the law of Pakistan
No full textIslamic Law has three types of punishments for criminal offences: fixed punishment, which is called Hudud; retaliation, which is called Qisas; and discretionary punishment, which is called Tazir. Hudud, fixed, punishments, are predetermined by Al-Mighty Allah and his last Prophet Muhammad صلى الله عليه وسلم in the Holy Quran and in the Sunnah of Prophet Muhammad صلى الله عليه وسلم . Hudud punishments are used mainly for five crimes: adultery, false accusation of adultery, theft, drinking liquor, and apostasy. The fifth President of Pakistan, General Muhammad Zia-ul-haq, introduced Hudud codified laws in Pakistan in 1979 for four of the criminal offences: adultery, false accusation of adultery, drinking Khamr, and theft. No law was promulgated for the offence of apostasy; rather, one ordinance was introduced on the regulation of whipping, which was later repealed by the Pakistani parliament in 1996.
Secular groups advocate for the complete abrogation of Hudud law from the judicial system of Pakistan in the name of the protection of women, but the basic purpose of these groups is to spread licentious behavior in a Muslim society. Hudud law actually protects men and women from false accusations of adultery; it also protects them from unlawful fornication and from drinking Khamr, which leads to adultery and other harmful offences. During the rule of the tenth President Pervez Musharaf, in 2006, the Pakistani government repealed many provisions of the Zina and Qazf ordinances through the Protection of Women Act. But the Government of Pakistan did not change anything in the theft and drinking Khamr Ordinances, which is a clearcut indication that the amendments to the Zina and Qazf Ordinances were made to portray a liberal image of Pakistan while making the Zina and correlated acts easier in Pakistan.
It is true that the Law of Hudud needs procedural changes. But that does not mean that we should abrogate the whole Law of Hudud and its punishments, fixed by Al-Mighty Allah and his last Prophet Muhammad صلى الله عليه وسلم, from the judicial system of Pakistan. The author recommends that rather than making different ordinances of Hudud, a Hudud chapter should be added to the existing Pakistan Penal Code of 1860 to get rid of the procedural difficulties. If a survey were to be conducted today in Pakistan, the majority would vote in favor of implementing Hudud Law in the Islamic Republic of Pakistan. Law is made to control the behavior of a society. If the majority of the population is happy with a law, one group of people cannot be given the right to snatch the voice of the general public and impose their verdict on the majority of the people
Design of small molecules and identification of putative anticancer therapeutic targets via in silico tools
No full textComputational approaches are a key component in drug design and discovery workflows. Several computational tools have been implemented in the last years to help researchers save time and reduce costs. They can be used to identify a therapeutic target, understand ligand-protein and protein-protein interactions, and identify putative binding sites, even though their principal use remains the identification of hit compounds through ligand-based and structure-based virtual screening and optimizing lead compounds [1]. Here, in the context of the PNRR project "HEAL ITALIA", we present the computational workflows to identify new potential anticancer compounds. Ligand-based approaches will be discussed guiding our research for new active compounds together with advanced docking approaches, biased and unbiased molecular dynamics simulations. In vitro test confirmed the results of the computational approaches and paved the way for the hits optimizatio
A reliable alternative of fiberoptic bronchoscope in unanticipated difficult airway: Flexible fiberoptic cystoscope
No full textMass transfer efficiency of a tall and low plate free area liquid pulsed sieve-plate extraction column
No full textAcknowledgements The authors would like to acknowledge Chakwal group of industries for funding the project. Ms. Madiha, Ms. Zona, Mr. Sohaib, Mr. Abdullah, Mr. Mudassar, and Mr. Salahuddin also deserve our acknowledgements for their assistance in different ways.Peer reviewe
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