Search results for: 177Lu labeled somatostatin analogues

Authors: Ting-Ying Su, Meng-Shiou Lee, Shyang-Chwen Sheu

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Garlic is used commonly as a seasoning around the world. But some people suffer from allergy to garlic. Garlic may also cause burning of mouth, stomach, and throat. In some Buddhist traditions, consuming garlic is not allowed. The objective of this study is to develop a LAMP based method for detection of garlic in food. We designed specific primers targeted on ITS1-5.8S rRNA-ITS2 sequence of garlic DNA. The LAMP assay was performed using a set of four different primers F3, B3, FIP and BIP at 60˚C in less than 60 mins. Results showed that the primer was not cross-reactive to other commonly used spice including Chinese leek, Chinese onion, green onion, onion, pepper, basil, parsley, pepper and ginger. As low as 2% of garlic DNA could be detected. Garlic still could be detected by developed LAMP after boiled at 100˚C for 80 minutes and autoclaved at 121˚C for 60 minutes. Commercial products labeled with garlic ingredient could be identified by the developed method.

Keywords: garlic, loop-mediated isothermal amplification, processing, DNA

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Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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Authors: M. Salvador, J. C. Martinez-Garcia, A. Moyano, M. C. Blanco-Lopez, M. Rivas

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Biosensors play a crucial role in the detection of molecules nowadays due to their advantages of user-friendliness, high selectivity, the analysis in real time and in-situ applications. Among them, Lateral Flow Immunoassays (LFIAs) are presented among technologies for point-of-care bioassays with outstanding characteristics such as affordability, portability and low-cost. They have been widely used for the detection of a vast range of biomarkers, which do not only include proteins but also nucleic acids and even whole cells. Although the LFIA has traditionally been a positive/negative test, tremendous efforts are being done to add to the method the quantifying capability based on the combination of suitable labels and a proper sensor. One of the most successful approaches involves the use of magnetic sensors for detection of magnetic labels. Bringing together the required characteristics mentioned before, our research group has developed a biosensor to detect biomolecules. Superparamagnetic nanoparticles (SPNPs) together with LFIAs play the fundamental roles. SPMNPs are detected by their interaction with a high-frequency current flowing on a printed micro track. By means of the instant and proportional variation of the impedance of this track provoked by the presence of the SPNPs, quantitative and rapid measurement of the number of particles can be obtained. This way of detection requires no external magnetic field application, which reduces the device complexity. On the other hand, the major limitations of LFIAs are that they are only qualitative or semiquantitative when traditional gold or latex nanoparticles are used as color labels. Moreover, the necessity of always-constant ambient conditions to get reproducible results, the exclusive detection of the nanoparticles on the surface of the membrane, and the short durability of the signal are drawbacks that can be advantageously overcome with the design of magnetically labeled LFIAs. The approach followed was to coat the SPIONs with a specific monoclonal antibody which targets the protein under consideration by chemical bonds. Then, a sandwich-type immunoassay was prepared by printing onto the nitrocellulose membrane strip a second antibody against a different epitope of the protein (test line) and an IgG antibody (control line). When the sample flows along the strip, the SPION-labeled proteins are immobilized at the test line, which provides magnetic signal as described before. Preliminary results using this practical combination for the detection and quantification of the Prostatic-Specific Antigen (PSA) shows the validity and consistency of the technique in the clinical range, where a PSA level of 4.0 ng/mL is the established upper normal limit. Moreover, a LOD of 0.25 ng/mL was calculated with a confident level of 3 according to the IUPAC Gold Book definition. Its versatility has also been proved with the detection of other biomolecules such as troponin I (cardiac injury biomarker) or histamine.

Keywords: biosensor, lateral flow immunoassays, point-of-care devices, superparamagnetic nanoparticles

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Authors: Shao-Di Feng, Von-Wun Soo

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To generate symbolic music with specific emotions is a challenging task due to symbolic music datasets that have emotion labels are scarce and incomplete. This research aims to generate more refined emotions based on the training datasets that are only labeled with four quadrants in Russel’s 2D emotion model. We focus on the theory of Music Fadernet and map arousal and valence to the low-level attributes, and build a symbolic music generation model by combining transformer and GM-VAE. We adopt an in-attention mechanism for the model and improve it by allowing modulation by conditional information. And we show the music generation model could control the generation of music according to the emotions specified by users in terms of high-level linguistic expression and by manipulating their corresponding low-level musical attributes. Finally, we evaluate the model performance using a pre-trained emotion classifier against a pop piano midi dataset called EMOPIA, and by subjective listening evaluation, we demonstrate that the model could generate music with more refined emotions correctly.

Keywords: music generation, music emotion controlling, deep learning, semi-supervised learning

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Authors: Rui Yin, Haojie Wang, Xun Li

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Recently, mainstream dense retrieval methods have obtained state-of-the-art results on some datasets and tasks. However, they require large amounts of training data, which is not available in most domains. The severe performance degradation of dense retrievers on new data domains has limited the use of dense retrieval methods to only a few domains with large training datasets. In this paper, we propose an unsupervised domain-adaptive approach based on query generation. First, a generative model is used to generate relevant queries for each passage in the target corpus, and then the generated queries are used for mining negative passages. Finally, the query-passage pairs are labeled with a cross-encoder and used to train a domain-adapted dense retriever. Experiments show that our approach is more robust than previous methods in target domains that require less unlabeled data.

Keywords: dense retrieval, query generation, unsupervised training, text retrieval

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Authors: Shelby Simpson, William Stanley, Namir Naba, Xiaodi Wang

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Both t-SNE and UMAP are brand new state of art tools to predominantly preserve the local structure that is to group neighboring data points together, which indeed provides a very informative visualization of heterogeneity in our data. In this research, we develop a t-SNE and UMAP base neural network image classification algorithm to embed the original dataset to a corresponding low dimensional dataset as a preprocessing step, then use this embedded database as input to our specially designed neural network classifier for image classification. We use the fashion MNIST data set, which is a labeled data set of images of clothing objects in our experiments. t-SNE and UMAP are used for dimensionality reduction of the data set and thus produce low dimensional embeddings. Furthermore, we use the embeddings from t-SNE and UMAP to feed into two neural networks. The accuracy of the models from the two neural networks is then compared to a dense neural network that does not use embedding as an input to show which model can classify the images of clothing objects more accurately.

Keywords: t-SNE, UMAP, fashion MNIST, neural networks

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Authors: Lilia M. Fernando, Matthew K. Vasher, Evangelyn C. Alocilja

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This paper describes the development of a DNA-based nanobiosensor to detect the dengue virus in mosquito using electrically active magnetic (EAM) nanoparticles as the concentrator and electrochemical transducer. The biosensor detection encompasses two sets of oligonucleotide probes that are specific to the dengue virus: the detector probe labeled with the EAM nanoparticles and the biotinylated capture probe. The DNA targets are double hybridized to the detector and the capture probes and concentrated from nonspecific DNA fragments by applying a magnetic field. Subsequently, the DNA sandwiched targets (EAM-detector probe–DNA target–capture probe-biotin) are captured on streptavidin modified screen printed carbon electrodes through the biotinylated capture probes. Detection is achieved electrochemically by measuring the oxidation–reduction signal of the EAM nanoparticles. Results indicate that the biosensor is able to detect the redox signal of the EAM nanoparticles at dengue DNA concentrations as low as 10 ng/ul.

Keywords: dengue, magnetic nanoparticles, mosquito, nanobiosensor

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Authors: Ali Ulvi Uzer

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Data reduction is an important topic in the field of pattern recognition applications. The basic concept is the reduction of multitudinous amounts of data down to the meaningful parts. The Principal Component Analysis (PCA) method is frequently used for data reduction. The Support Vector Machine (SVM) method is a discriminative classifier formally defined by a separating hyperplane. In other words, given labeled training data, the algorithm outputs an optimal hyperplane which categorizes new examples. This study offers a hybrid approach that uses the PCA for data reduction and Support Vector Machines (SVM) for classification. In order to detect the accuracy of the suggested system, two boreholes taken from the soil sample was used. The classification accuracies for this dataset were obtained through using ten-fold cross-validation method. As the results suggest, this system, which is performed through size reduction, is a feasible system for faster recognition of dataset so our study result appears to be very promising.

Keywords: feature selection, sequential forward selection, support vector machines, soil sample

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Authors: Saba Rahimi, Ozan Oktay, Javier Alvarez-Valle, Sujeeth Bharadwaj

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Successful application of deep learning in medical image analysis necessitates unprecedented amounts of labeled training data. Unlike conventional 2D applications, radiological images can be three-dimensional (e.g., CT, MRI), consisting of many instances within each image. The problem is exacerbated when expert annotations are required for effective pixel-wise labeling, which incurs exorbitant labeling effort and cost. Active learning is an established research domain that aims to reduce labeling workload by prioritizing a subset of informative unlabeled examples to annotate. Our contribution is a cost-effective approach for U-Net 3D models that uses Monte Carlo sampling to analyze pixel-wise uncertainty. Experiments on the AAPM 2017 lung CT segmentation challenge dataset show that our proposed framework can achieve promising segmentation results by using only 42% of the training data.

Keywords: image segmentation, active learning, convolutional neural network, 3D U-Net

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Authors: Lauren E. Church

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Background: Extravehicular activities (EVAs) are a critical aspect of missions aboard the International Space Station (ISS). It has long been noted that the spaceflight environment and the physical demands of EVA cause physiological and metabolic changes in humans; this review aims to combine these findings with nutritional studies in analogues of the spaceflight and EVA environments to make nutritional recommendations for astronauts scheduled for and immediately returning from EVAs. Results: Energy demands increase during orbital spaceflight and see further increases during EVA. Another critical element of EVA nutrition is adequate hydration. Orbital EVA appears to provide adequate hydration under current protocol, but during lunar surface EVA (LEVA) and in a 10km lunar walk-back test astronauts have stated that up to 20% more water was needed. Previous attempts for in-suit edible sustenance have not been adequately taken up by astronauts to be economically viable. In elite endurance athletes, a mixture of glucose and fructose is used in gels, improving performance. Discussion: A combination of non-caffeinated energy drink and simple water should be available for astronauts during EVA, allowing more autonomy. There should also be provision of gels or a similar product containing appropriate sodium levels to maintain hydration, but not so much as to hyperhydrate through renal water reabsorption. It is also suggested that short breaks be built into the schedule of EVAs for these gels to be consumed, as it is speculated that reason for low uptake of in-suit sustenance is the lack of time available in which to consume it.

Keywords: astronaut, nutrition, space, sport

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Authors: Maha Wiss, Wael Khreich

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Animals, objects, foods, plants, and other non-human terms are commonly used as a source of metaphors to describe females in formal and slang language. Comparing women to non-human items not only reflects cultural views that might conceptualize women as subordinates or in a lower position than humans, yet it conveys this degradation to the listeners. Moreover, the dehumanizing representation of females in the language normalizes the derogation and even encourages sexism and aggressiveness against women. Although dehumanization has been a popular research topic for decades, according to our knowledge, no studies have linked women's dehumanizing language to the machine learning field. Therefore, we introduce our research work as one of the first attempts to create a tool for the automated detection of the dehumanizing depiction of females in English texts. We also present the first labeled dataset on the charted topic, which is used for training supervised machine learning algorithms to build an accurate classification model. The importance of this work is that it accomplishes the first step toward mitigating dehumanizing language against females.

Keywords: gender bias, machine learning, NLP, women dehumanization

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Authors: Tomasz Sapiński, Dorota Kamińska, Adam Pelikant, Egils Avots, Cagri Ozcinar, Gholamreza Anbarjafari

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People express emotions through different modalities. Integration of verbal and non-verbal communication channels creates a system in which the message is easier to understand. Expanding the focus to several expression forms can facilitate research on emotion recognition as well as human-machine interaction. In this article, the authors present a Polish emotional database composed of three modalities: facial expressions, body movement and gestures, and speech. The corpora contains recordings registered in studio conditions, acted out by 16 professional actors (8 male and 8 female). The data is labeled with six basic emotions categories, according to Ekman’s emotion categories. To check the quality of performance, all recordings are evaluated by experts and volunteers. The database is available to academic community and might be useful in the study on audio-visual emotion recognition.

Keywords: body movement, emotion recognition, emotional corpus, facial expressions, gestures, multimodal database, speech

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Authors: Steven Woods

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The use of Corporate Social Responsibility Statements has become ubiquitous in society. The appeal to consumers by being a well-behaved social entity has become a strategy not just to ensure brand loyalty but also to further larger scale projects of corporate interests. Specifically, the use of CSR to position corporations as good planetary citizens involves not just self-promotion but also a way of transferring responsibility from systems to individuals. By using techniques labeled as “greenwashing” and emphasizing ethical consumption choices as the solution, corporations present themselves as good members of the community and pursuing sustainability. Ultimately, the primary function of Corporate Social Responsibility statements is to maintain the economic status quo of ongoing growth and consumption while presenting and environmentally progressive image to the public, as well as reassuring them corporate behavior is superior to government intervention. By analyzing the communication techniques utilized through content analysis of specific examples, along with an analysis of the frames of meaning constructed in the CSR statements, the practices of Corporate Responsibility and Sustainability will be addressed from an ethical perspective.

Keywords: corporate social responsibility, ethics, greenwashing, sustainability

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Authors: Sefa Aksu, Ünal Kızıl

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For this study, a town based soil database created in Gümüşçay District of Biga Town, Çanakkale, Turkey. Crop and livestock production are major activities in the district. Nutrient management is mainly based on commercial fertilizer application ignoring the livestock manure. Within the boundaries of district, 122 soil sampling points determined over the satellite image. Soil samples collected from the determined points with the help of handheld Global Positioning System. Labeled samples were sent to a commercial laboratory to determine 11 soil parameters including salinity, pH, lime, organic matter, nitrogen, phosphorus, potassium, iron, manganese, copper and zinc. Based on the test results soil maps for mentioned parameters were developed using remote sensing, GIS, and geostatistical analysis. In this study we developed a GIS database that will be used for soil nutrient management. Methods were explained and soil maps and their interpretations were summarized in the study.

Keywords: geostatistics, GIS, nutrient management, soil mapping

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Authors: Takanori Tanaka, Daisuke Kitao, Daisuke Ikeda

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The aurora is an attractive phenomenon but it is difficult to understand the whole mechanism of it. An approach of data-intensive science might be an effective approach to elucidate such a difficult phenomenon. To do that we need labeled data, which shows when and what types of auroras, have appeared. In this paper, we propose an image retrieval system for auroral all-sky images, some of which include discrete and diffuse aurora, and the other do not any aurora. The proposed system retrieves images which are similar to the query image by using a popular image recognition method. Using 300 all-sky images obtained at Tromso Norway, we evaluate two methods of image recognition methods with or without our original color filtering method. The best performance is achieved when SIFT with the color filtering is used and its accuracy is 81.7% for discrete auroras and 86.7% for diffuse auroras.

Keywords: data-intensive science, image classification, content-based image retrieval, aurora

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Authors: Deepika Saini, Sandeep Jain, Ajay Kumar

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The quinoline scaffold is one of the most widely studied in the discovery of derivatives with various heterocyclic moieties due to its potential antimalarial activities. In the present study, a chalcone series of quinoline derivatives clubbed with pyrazole were synthesized to evaluate their antimalarial property by in vitro schizont maturation inhibition assay against both chloroquine sensitive, 3D7 and chloroquine resistant, RKL9 strain of Plasmodium falciparum. Further, top five compounds were studied for in vivo preclinical study for antimalarial potential against P. berghei in Swiss albino mice. To understand the mechanism of synthesized analogues, they were screened computationally by molecular docking techniques. Compounds were docked into the active site of a protein receptor, Plasmodium falciparum Cysteine Protease Falcipain-2. The compounds were successfully synthesized, and structural confirmation was performed by FTIR, 1H-NMR, mass spectrometry and elemental analysis. In vitro study suggested that the compounds 5b, 5g, 5l, 5s and 5u possessed best antimalarial activity and further tested for in vivo screening. Compound 5u (CH₃ on both rings) with EC₅₀ 0.313 & 0.801 µg/ml against CQ-S & CQ-R strains of P. falciparum respectively and 78.01% suppression of parasitemia. The molecular docking studies of the compounds helped in understanding the mechanism of action against falcipain-2. The present study reveals the binding signatures of the synthesized ligands within the active site of the protein, and it explains the results from in vitro study in their EC₅₀ values and percentage parasitemia.

Keywords: antimalarial activity, chalcone, docking, quinoline

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Authors: Mostafa ‘Neo’ Mohsenvand, Mohammad Rasool Izadi, Pattie Maes

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EEG-based biometrics (user identification) has been explored on small datasets of no more than 157 subjects. Here we show that the accuracy of modern supervised methods falls rapidly as the number of users increases to a few thousand. Moreover, supervised methods require a large amount of labeled data for training which limits their applications in real-world scenarios where acquiring data for training should not take more than a few minutes. We show that using contrastive learning for pre-training, it is possible to maintain high accuracy on a dataset of 2130 subjects while only using a fraction of labels. We compare 5 different self-supervised tasks for pre-training of the encoder where our proposed method achieves the accuracy of 96.4%, improving the baseline supervised models by 22.75% and the competing self-supervised model by 3.93%. We also study the effects of the length of the signal and the number of channels on the accuracy of the user-identification models. Our results reveal that signals from temporal and frontal channels contain more identifying features compared to other channels.

Keywords: brainprint, contrastive learning, electroencephalo-gram, self-supervised learning, user identification

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Authors: Khalak Bin Khair, Saqib Jahir, Mohammed Ibrahim, Fahad Bin, Debajyoti Karmaker

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Object detection is a computer technology that deals with searching through digital images and videos for occurrences of semantic elements of a particular class. It is associated with image processing and computer vision. On top of object detection, we detect camouflage objects within an image using Deep Learning techniques. Deep learning may be a subset of machine learning that's essentially a three-layer neural network Over 6500 images that possess camouflage properties are gathered from various internet sources and divided into 4 categories to compare the result. Those images are labeled and then trained and tested using vgg16 architecture on the jupyter notebook using the TensorFlow platform. The architecture is further customized using Transfer Learning. Methods for transferring information from one or more of these source tasks to increase learning in a related target task are created through transfer learning. The purpose of this transfer of learning methodologies is to aid in the evolution of machine learning to the point where it is as efficient as human learning.

Keywords: deep learning, transfer learning, TensorFlow, camouflage, object detection, architecture, accuracy, model, VGG16

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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Authors: Go Woon Kwak, Siyoung Jun, Soyun Maeng, Haeyoung Lee

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Entry is an education platform used in South Korea, created to help students learn to program, in which they can learn to code while playing. Using the online version of the entry, teachers can easily assign programming homework to the student and the students can make programs simply by linking programming blocks. However, the programs may be made by others, so that the authors of the programs should be identified. In this paper, as the first step toward author identification of entry programs, we present an artificial neural network based classification approach to identify genders of authors of a program written in an entry. A neural network has been trained from labeled training data that we have collected. Our result in progress, although preliminary, shows that the proposed approach could be feasible to be applied to the online version of entry for gender identification of authors. As future work, we will first use a machine learning technique for age identification of entry programs, which would be the second step toward the author identification.

Keywords: artificial intelligence, author identification, deep neural network, gender identification, machine learning

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Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

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To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

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Authors: Mohamad Sharif bin Mustaffa, Maizatul Akmam binti Abu Bakar, Mohd Harriszamani bin Abu Bakar

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Most teens who gave birth to an illegitimate child will suffer from depression. This depression issues arising from the incident itself which contains the teen will feel ashamed because labeled as immoral, apart from that most teenagers go through this episode without support from their spouse or family. Teens also face the possibility of a large part with the will be born babies because the issue of too young and needs to go back to school. Teens also can not make a decision on the future of the baby later because they are too immature and no baby care skills other than financial issues, where young people themselves are still dependent on their family. This paper will look at how to apply neurofeedback can be used to see the level of depression experienced by teenagers who get pregnant out of wedlock. Play therapy that will help improve adolescent focus will be used for this purpose. Each level experienced by teenagers going through the phase of easy-to-high difficulty level. Apart from that a recovery module will also be developed as a whole to reduce the level of depression to enable the youth to perform routine healthy activities and can go back to school with cheerful feeling, motivated and active.

Keywords: neurofeedback, depression, pregnant, adolescent, illegitimate

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Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Muhamad Afiq Faisal, Yahaya, Mohd Faizal, Hamzah

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Genetic modification technology allows scientists to alter the genetic information of a particular organism. The technology allows the production of genetically modified organism (GMO) that has the enhanced property compared to the unmodified organism. The application of such technology is not only in agriculture industry, it is now has been applied extensively in biopharmaceutical industry such as transgenic vaccines. In Malaysia, Biosafety Act 2007 has been enacted in which all GMO-based products must be labeled with adequate information before being marketed. This paper aims to determine the awareness level amongst Malaysian consumers on the GM products available in the market and the efficiency of information supplied in the GM product labeling. The result of the survey will serve as a guideline for Malaysia government agency bodies to provide comprehensive yet efficient information to consumers for the purpose of GM product labeling in the near future. In conclusion, the efficiency of information delivery plays a vital role in ensuring that the information is being conveyed clearly to Malaysian consumers during the selection process of GM products available in the market.

Keywords: genetic modification technology, genetically modified organisms, genetically modified organism products labeling, Biosafety Act 2007

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Authors: Isabelle Snyder, Travis Smith

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Microgrid protection presents challenges to conventional protection techniques due to the low-induced fault current. Protection relays present in microgrid applications require a combination of settings groups to adjust based on the architecture of the microgrid in islanded and grid-connected modes. In a radial system where the microgrid is at the other end of the feeder, directional elements can be used to identify the direction of the fault current and switch settings groups accordingly (grid-connected or microgrid-connected). However, with multiple microgrid connections, this concept becomes more challenging, and the direction of the current alone is not sufficient to identify the source of the fault current contribution. ORNL has previously developed adaptive relaying schemes through other DOE-funded research projects that will be evaluated and used as a baseline for this research. The four protection techniques in this study are labeled as follows: (1) Adaptive Current only Protection System (ACPS), Intentional (2) Unbalanced Control for Protection Control (IUCPC), (3) Adaptive Protection System with Communication Controller (APSCC) (4) Adaptive Model-Driven Protective Relay (AMDPR).

Keywords: adaptive relaying, microgrid protection, sequence components, islanding detection

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Authors: Umair Rashid

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Normally softmax loss is used as the supervision signal in face recognition (FR) system, and it boosts the separability of features. In the last two years, a number of techniques have been proposed by reformulating the original softmax loss to enhance the discriminating power of Deep Convolutional Neural Networks (DCNNs) for FR system. To learn angularly discriminative features Cosine-Margin based softmax has been adjusted as monotonically decreasing angular function, that is the main challenge for angular based softmax. On that issue, we propose monotonically decreasing element for Cosine-Margin based softmax and also, we discussed the effect of different monotonically decreasing parameters on angular Margin softmax for FR system. We train the model on publicly available dataset CASIA- WebFace via our proposed monotonically decreasing parameters for cosine function and the tests on YouTube Faces (YTF, Labeled Face in the Wild (LFW), VGGFace1 and VGGFace2 attain the state-of-the-art performance.

Keywords: deep convolutional neural networks, cosine margin face recognition, softmax loss, monotonically decreasing parameter

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Authors: Bernard L. Middleton, Susan P. Cosgrove

Abstract:

There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Alternatives currently approved for the purposes of clinical administration includes antivirals and a reduced set of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. The tested 5CC were noted as being functional in the application of eliminating the DNA synthesis of herpes viral interferon (IFN) - induced cellular antiviral response. They were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. The activity of the 5CC was tested on RC-37 in vitro using an assay plaque reduction and in vivo against HSV-1 and HSV-2. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests were performed to evaluate the susceptibility of HSV-1 and HSV-2 to anti-herpetic drugs in Vero cells after virus entry. There were high-level markers of the 5CC virucidal activity in the viral suspension of HSV-1 and HSV-2. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. The results concluded the 5CC as being an effective treatment option for the herpes simplex virus.

Keywords: synergy pharmaceuticals, herpes treatment, herpes cure, synergy pharmaceuticals treatment

Procedia PDF Downloads 238

Authors: Rui Yin, Haojie Wang, Xun Li

Abstract:

Recently, mainstream dense retrieval methods have obtained state-of-the-art results on some datasets and tasks. However, they require large amounts of training data, which is not available in most domains. The severe performance degradation of dense retrievers on new data domains has limited the use of dense retrieval methods to only a few domains with large training datasets. In this paper, we propose an unsupervised domain-adaptive approach based on query generation. First, a generative model is used to generate relevant queries for each passage in the target corpus, and then, the generated queries are used for mining negative passages. Finally, the query-passage pairs are labeled with a cross-encoder and used to train a domain-adapted dense retriever. We also explore contrastive learning as a method for training domain-adapted dense retrievers and show that it leads to strong performance in various retrieval settings. Experiments show that our approach is more robust than previous methods in target domains that require less unlabeled data.

Keywords: dense retrieval, query generation, contrastive learning, unsupervised training

Procedia PDF Downloads 94

Authors: Jiangbo Shi, Zeyu Gao, Chen Li

Abstract:

Nuclei segmentation is a fundamental task in digital pathology analysis and can be automated by deep learning-based methods. However, the development of such an automated method requires a large amount of data with precisely annotated masks which is hard to obtain. Training with weakly labeled data is a popular solution for reducing the workload of annotation. In this paper, we propose a novel meta-learning-based nuclei segmentation method which follows the label correction paradigm to leverage data with noisy masks. Specifically, we design a fully conventional meta-model that can correct noisy masks by using a small amount of clean meta-data. Then the corrected masks are used to supervise the training of the segmentation model. Meanwhile, a bi-level optimization method is adopted to alternately update the parameters of the main segmentation model and the meta-model. Extensive experimental results on two nuclear segmentation datasets show that our method achieves the state-of-the-art result. In particular, in some noise scenarios, it even exceeds the performance of training on supervised data.

Keywords: deep learning, histopathological image, meta-learning, nuclei segmentation, weak annotations

Procedia PDF Downloads 136

Authors: Li Qingjian, Li Ke, He Chun, Huang Yong

Abstract:

In this paper, the method of combining the Pohl Seidman's deep belief network with the self-organizing neural network is proposed to classify the target. This method is mainly aimed at the high nonlinearity of the hyperspectral image, the high sample dimension and the difficulty in designing the classifier. The main feature of original data is extracted by deep belief network. In the process of extracting features, adding known labels samples to fine tune the network, enriching the main characteristics. Then, the extracted feature vectors are classified into the self-organizing neural network. This method can effectively reduce the dimensions of data in the spectrum dimension in the preservation of large amounts of raw data information, to solve the traditional clustering and the long training time when labeled samples less deep learning algorithm for training problems, improve the classification accuracy and robustness. Through the data simulation, the results show that the proposed network structure can get a higher classification precision in the case of a small number of known label samples.

Keywords: DBN, SOM, pattern classification, hyperspectral, data compression

Procedia PDF Downloads 338