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    Publication
    Book Chapter
    Deep learning in drug discovery
    (Elsevier, 2023)
    Bhati, Meenu
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    Virmani, Tarun
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    Kumar, Girish
    ;
    Sharma, Ashwani
    ;

    Drug discovery is a process of recognizing the chemical moieties having the potential to serve as drugs. It involves the higher cost, low efficacy, and increased timelines for discovering a drug which have made it a complex process. Hence, there is an urge need of advancement in drug discovery process which can provide the revolutionary changes. In recent years, deep learning bears promise in the process of drug discovery. Deep learning plays a crucial role in various drug discovery processes namely drug monitoring, peptide synthesis, legend-based virtual screening, toxicity prediction, pharmacophore modeling, quantitative structural–activity relationship (QSAR), poly-pharmacology, drug repositioning, and physiochemical activities. This chapter presents an outline of these expanding topics related to drug discovery, the key concepts of prevalent deep learning algorithms, and motivation to investigate these techniques for their potential applications in computer-assisted drug discovery and design.

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    Journal Article
    Mitochondrial dysfunction in Alzheimer’s disease - a proteomics perspective
    (Taylor & Francis, 2021-04-03)
    Abyadeh, Morteza
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    Gupta, Vivek
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    Gupta, Veer
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    Wu, Yunqi
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    Saks, Danit
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    Wander Wall, Roshana
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    Fitzhenry, Matthew J
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    Basavarajappa, Devaraj
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    You, Yuyi
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    Salekdeh, Ghasem H
    ;
    Haynes, Paul a
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    Graham, Stuart L
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    Mirzaei, Mehdi

    Mitochondrial dysfunction is involved in Alzheimer’s disease (AD) pathogenesis. Mitochondria have their own genetic material; however, most of their proteins (∼99%) are synthesized as precursors on cytosolic ribosomes, and then imported into the mitochondria. Therefore, exploring proteome changes in these organelles can yield valuable information and shed light on the molecular mechanisms underlying mitochondrial dysfunction in AD. Here, we review AD-associated mitochondrial changes including the effects of amyloid beta and tau protein accumulation on the mitochondrial proteome. We also discuss the relationship of ApoE genetic polymorphism with mitochondrial changes, and present a meta-analysis of various differentially expressed proteins in the mitochondria in AD.

    Area covered: Proteomics studies and their contribution to our understanding of mitochondrial dysfunction in AD pathogenesis.

    Expert opinion: Proteomics has proven to be an efficient tool to uncover various aspects of this complex organelle, which will broaden our understanding of mitochondrial dysfunction in AD. Evidently, mitochondrial dysfunction is an early biochemical event that might play a central role in driving AD pathogenesis.

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    Publication
    Book Chapter
    Deep learning IoT in medical and healthcare
    (Elsevier Inc, 2023)
    Sharma, Ashwani
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    Sharma, Anjali
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    Virmani, Reshu
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    Kumar, Girish
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    Virmani, Tarun
    ;

    One of the most important aspects of human life is health. Every civilization is paying more attention to the early detection of a disease with its prevention along with implementing technology in the area of healthcare. The use of technology helps in identifying the most effective treatments for a variety of chronic illnesses. Deep learning (DL) and the Internet of Things (IoT) are rapidly expanding and playing an extremely important role in a wide range of applications such as healthcare and medical systems. Getting knowledge and useful insights from sophisticated, high-dimensional, and diverse biological data remain a major problem in healthcare transformation. The various kinds of data, such as electronic health records (EHRs) or electric medical records (EMRs), sensor data, text, and imaging, are all examples of variable, poorly documented, complex, and unstructured data that have emerged in modern biomedical research. As of now, COVID-19 has been wreaking havoc on the world since December 2019. Fortunately, the IoT is among the most significant paradigms in which artificial intelligence (AI) technology, such as big data analysis and cloud computing are playing a critical role in order to stop the spread of the COVID-19 virus. For instance, in the case of diagnosis and remote screening of COVID-19 patients, AI technology based on machine learning (ML) and DL has redefined the flow of work by having minimum contact with patients, moreover, allowing healthcare professionals to make clinical decisions in a more efficient manner, thus, helping in protecting not only patients but also healthcare professionals. Thus, in healthcare, the IoT plays a critical role in providing patients with better medical facilities as well as supporting hospitals and healthcare professionals. Because of IoT-enabled portable medical equipment, smart healthcare surveillance systems are on the rise. This chapter mainly focuses on the various approaches enabled by AI and DL and their significant applications in the field of medical and healthcare.

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    Journal Article
    Chitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: A new dimension to an anticancer drug
    (Elsevier BV, 2023-01-01)
    Sharma, Deep Shikha
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    Wadhwa, Sheetu
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    Gulati, Monica
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    Kumar, Bimlesh
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    Gupta, Vivek Kumar
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    Alrouji, Mohammed
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    Alhajlah, Sharif
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    AlOmeir, Othman
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    Vishwas, Sukriti
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    Khursheed, Rubiya
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    Saini, Sumant
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    Kumar, Ankit
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    Parveen, Shaik Rahana
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    Gupta, Gaurav
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    Zacconi, Flavia
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    Chellappan, Dinesh Kumar
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    Morris, Andrew
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    Loebenberg, Raimar
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    Dua, Kamal
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    Singh, Sachin Kumar

    Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.

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    Open Access
    Journal Article
    Neuroserpin gene therapy inhibits retinal ganglion cell apoptosis and promotes functional preservation in glaucoma
    (Cell Press, 2023-07-05) ;
    Rajput, Rashi
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    Godinez, Angela
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    Pushpitha, Kanishka
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    Mirzaei, Mehdi
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    Basavarajappa, Devaraj
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    Gupta, Veer
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    Sharma, Samridhi
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    You, Yuyi
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    Galliciotti, Giovanna
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    Salekdeh, Ghasem H
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    Baker, Mark S
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    Graham, Stuart L
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    Gupta, Vivek K

    Our research has proven that the inhibitory activity of the serine protease inhibitor neuroserpin (NS) is impaired because of its oxidation deactivation in glaucoma. Using genetic NS knockout (NS−/−) and NS overexpression (NS+/+ Tg) animal models and antibody-based neutralization approaches, we demonstrate that NS loss is detrimental to retinal structure and function. NS ablation was associated with perturbations in autophagy and microglial and synaptic markers, leading to significantly enhanced IBA1, PSD95, beclin-1, and LC3-II/LC3-I ratio and reduced phosphorylated neurofilament heavy chain (pNFH) levels. On the other hand, NS upregulation promoted retinal ganglion cell (RGC) survival in wild-type and NS−/− glaucomatous mice and increased pNFH expression. NS+/+Tg mice demonstrated decreased PSD95, beclin-1, LC3-II/LC3-I ratio, and IBA1 following glaucoma induction, highlighting its protective role. We generated a novel reactive site NS variant (M363R-NS) resistant to oxidative deactivation. Intravitreal administration of M363R-NS was observed to rescue the RGC degenerative phenotype in NS−/− mice. These findings demonstrate that NS dysfunction plays a key role in the glaucoma inner retinal degenerative phenotype and that modulating NS imparts significant protection to the retina. NS upregulation protected RGC function and restored biochemical networks associated with autophagy and microglial and synaptic function in glaucoma.

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    Conference Publication
    Orgasmic Gushing: where does the fluid come from and how is it produced?
    (Women in Research (WiR), 2005)
    O'Brien, GM
    There are three sexual fluids from women: lubrication (e.g. transudation of fluid across the mucosa of the vagina, and mucus from the greater vestibular glands); female ejaculation (from paraurethral glands); and gushing. Orthodox western medicine and physiology does not yet have a standardized description or explanation for the third, gushing. The present paper proposes that the gushing fluid is a filtrate of plasma, produced by the mechanism known as transudation. This is an additional application for the transudation mechanism, after the well accepted roles in lubrication of the vagina, and in generating serous fluids. The present model proposes that the fluid released in a gush arises from the ventral wall of the vagina due to the presence there of increased surface area of mucosa, dilated arterioles, pressurized venous and lymphatic plexuses, and compression provided by muscle contraction during orgasm.
      65017
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    Dataset
    Mapping Long Term Changes in Mangrove Cover and Predictions of Future Change under Different Climate Change Scenarios in the Sundarbans, Bangladesh
    (2018-05-22)
    Ghosh, Manoj Kumer
    ;
    Ground-based readings of temperature and rainfall, satellite imagery, aerial photographs, ground verification data and Digital Elevation Model (DEM) were used in this study. Ground-based meteorological information was obtained from Bangladesh Meteorological Department (BMD) for the period 1977 to 2015 and was used to determine the trends of rainfall and temperature in this thesis. Satellite images obtained from the US Geological Survey (USGS) Center for Earth Resources Observation and Science (EROS) website (www.glovis.usgs.gov) in four time periods were analysed to assess the dynamics of mangrove population at species level. Remote sensing techniques, as a solution to lack of spatial data at a relevant scale and difficulty in accessing the mangroves for field survey and also as an alternative to the traditional methods were used in monitoring of the changes in mangrove species composition, . To identify mangrove forests, a number of satellite sensors have been used, including Landsat TM/ETM/OLI, SPOT, CBERS, SIR, ASTER, and IKONOS and Quick Bird. The use of conventional medium-resolution remote sensor data (e.g., Landsat TM, ASTER, SPOT) in the identification of different mangrove species remains a challenging task. In many developing countries, the high cost of acquiring high- resolution satellite imagery excludes its routine use. The free availability of archived images enables the development of useful techniques in its use and therefor Landsat imagery were used in this study for mangrove species classification. Satellite imagery used in this study includes: Landsat Multispectral Scanner (MSS) of 57 m resolution acquired on 1st February 1977, Landsat Thematic Mapper (TM) of 28.5 m resolution acquired on 5th February 1989, Landsat Enhanced Thematic Mapper (ETM+) of 28.5 m resolution acquired on 28th February 2000 and Landsat Operational Land Imager (OLI) of 30 m resolution acquired on 4th February 2015. To study tidal channel dynamics of the study area, aerial photographs from 1974 and 2011, and a satellite image from 2017 were used. Satellite images from 1974 with good spatial resolution of the area were not available, and therefore aerial photographs of comparatively high and fine resolution were considered adequate to obtain information on tidal channel dynamics. Although high-resolution satellite imagery was available for 2011, aerial photographs were used for this study due to their effectiveness in terms of cost and also ease of comparison with the 1974 photographs. The aerial photographs were sourced from the Survey of Bangladesh (SOB). The Sentinel-2 satellite image from 2017 was downloaded from the European Space Agency (ESA) website (https://scihub.copernicus.eu/). In this research, elevation data acts as the main parameter in the determination of the sea level rise (SLR) impacts on the spatial distribution of the future mangrove species of the Bangladesh Sundarbans. High resolution elevation data is essential for this kind of research where every centimeter counts due to the low-lying characteristics of the study area. The high resolution (less than 1m vertical error) DEM data used in this study was obtained from Water Resources Planning Organization (WRPO), Bangladesh. The elevation information used to construct the DEM was originally collected by a Finnish consulting firm known as FINNMAP in 1991 for the Bangladesh government.
      48195  50
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    Conference Publication
    Reinforced Behavioral Variability and Sequence Learning Across Species
    (Association for Behavior Analysis International (ABAI), 2012)
    Doolan, Kathleen
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    McEwan, James
    Previous research shows that reinforcement of variable responding will facilitate sequence learning in rats (Neuringer, Deiss & Olson, 2000) but may interfere with sequence learning in humans (Maes & van der Goot, 2006). The present study aimed to replicate and extend previous research by assessing the role of behavioral variability in the learning of difficult target sequences across 3 species: humans (n = 60), hens (n = 18) and possums (n = 6). Participants were randomly allocated to one of three experimental conditions (Control, Variable, Any). In the Control conditions sequences were only reinforced if they were the target sequence, in the Variability conditions sequences were concurrently reinforced on a Variable Interval 60-s schedule if the just entered sequence met a variability criterion, and in the Any condition sequences were concurrently reinforced on a Variable Interval 60-s schedule for any sequence entered. The results support previous findings with animals and humans; hens and possums were more likely to learn the target sequence in the Variability condition, and human participants were more likely to learn the target sequence in the Control condition. Possible explanations for differences between the performance of humans and animals on this task will be discussed.
      39891  1
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    Open Access
    Dataset
    The drivers and consequences of change to the physical character of waterholes on an Australian dryland river
    This dataset provides all the raw and analysed data for the thesis titled 'The drivers and consequences of change to the physical character of waterholes on an Australian dryland river'.
    The data has been divided into four folders that are aligned with the data chapters for the thesis. These being: (Ch 2) waterhole mapping, (Ch 3) floodplain gullies, (Ch 4) sediment transport and (Ch 5) fish.
    A README file is provided for each chapter which contains a description of the individual datasets and a list of files that make up each dataset.
    The data in this archive is a combination of data obtained from desktop studies as well as field work on the Darling River (i.e., the fish data).
    Further, fish data were collected on the Darling River between Bourke and Wilcannia. Waterhole mapping was undertaken on the Barwon-Darling between Walgett and Wilcannia. Gully mapping was undertaken on the Barwon-Darling River between Mungindi and Wilcannia. Sediment transport capacity was assessed at five sites between Collarenebri and Tilpa.
      37773  2895
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    Open Access
    Journal Article
    A Review into Effective Classroom Management and Strategies for Student Engagement: Teacher and Student Roles in Today’s Classrooms
    (Redfame Publishing Inc, 2019-12)
    Franklin, Hayley
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    A teacher's role encompasses far more than just imparting curricula outcomes to their students: they need to equip students with the necessary tools to experience social and academic success both inside the classroom and beyond it. Teachers need to empower students with the means to critically analyse the world around them in order to develop into critical independent thinkers. Students need to be proficient in utilising skills associated with higher levels of thinking, that will empower them with the ability to identify, analyse and evaluate the infinite volume of information available through our rapidly changing digital world. Just as teachers need to take responsibility for the various methods of teaching and instruction in the classroom, it is essential for students to take ownership of the learning process, to ensure future success in university environments, where sustained personal effort and metacognitive skills are fundamental to academic success. The object of the review of the literature surrounding the roles of teacher and student, effective classroom management strategies, and successful evidence-based teaching and learning pedagogies, is to assist new and experienced teachers in the promotion of a positive classroom experience for all.
      29905  47858