Search results for: genetic modification
Commenced in January 2007
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Paper Count: 2609

Search results for: genetic modification

389 Security Issues in Long Term Evolution-Based Vehicle-To-Everything Communication Networks

Authors: Mujahid Muhammad, Paul Kearney, Adel Aneiba

Abstract:

The ability for vehicles to communicate with other vehicles (V2V), the physical (V2I) and network (V2N) infrastructures, pedestrians (V2P), etc. – collectively known as V2X (Vehicle to Everything) – will enable a broad and growing set of applications and services within the intelligent transport domain for improving road safety, alleviate traffic congestion and support autonomous driving. The telecommunication research and industry communities and standardization bodies (notably 3GPP) has finally approved in Release 14, cellular communications connectivity to support V2X communication (known as LTE – V2X). LTE – V2X system will combine simultaneous connectivity across existing LTE network infrastructures via LTE-Uu interface and direct device-to-device (D2D) communications. In order for V2X services to function effectively, a robust security mechanism is needed to ensure legal and safe interaction among authenticated V2X entities in the LTE-based V2X architecture. The characteristics of vehicular networks, and the nature of most V2X applications, which involve human safety makes it significant to protect V2X messages from attacks that can result in catastrophically wrong decisions/actions include ones affecting road safety. Attack vectors include impersonation attacks, modification, masquerading, replay, MiM attacks, and Sybil attacks. In this paper, we focus our attention on LTE-based V2X security and access control mechanisms. The current LTE-A security framework provides its own access authentication scheme, the AKA protocol for mutual authentication and other essential cryptographic operations between UEs and the network. V2N systems can leverage this protocol to achieve mutual authentication between vehicles and the mobile core network. However, this protocol experiences technical challenges, such as high signaling overhead, lack of synchronization, handover delay and potential control plane signaling overloads, as well as privacy preservation issues, which cannot satisfy the adequate security requirements for majority of LTE-based V2X services. This paper examines these challenges and points to possible ways by which they can be addressed. One possible solution, is the implementation of the distributed peer-to-peer LTE security mechanism based on the Bitcoin/Namecoin framework, to allow for security operations with minimal overhead cost, which is desirable for V2X services. The proposed architecture can ensure fast, secure and robust V2X services under LTE network while meeting V2X security requirements.

Keywords: authentication, long term evolution, security, vehicle-to-everything

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388 Esophageal Premalignant and Malignant Epithelial Lesions: Pathological Characteristics and Value of Cyclooxygenase-2 Expression.

Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani

Abstract:

Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.

Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.

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387 Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients

Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

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Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: diabetes, T2DM, SLC47A1, Pakistan, polymorphism

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386 Cryopreservation of Ring-Necked Pheasant (Phasianus colchicus) Semen for Establishing Cryobank

Authors: Rida Pervaiz, Bushra Allah Rakha, Muhammad Sajjad Ansari, Shamim Akhter, Kainat Waseem, Sumiyyah Zuha, Tooba Javed

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Ring-necked pheasant (Phasianus colchicus) belongs to order Galliformes and family Phasianidae. It has been recognized as the most hunted bird due to its attractive colorful appearance and meat. Loss of habitat and hunting pressure has caused population fluctuations in the native range. Under these circumstances, this species can be conserved by employing ex-situ in vitro conservation techniques. Captive breeding, in combination with semen cryobanking is the most appropriate option to conserve/propagate this species without deteriorating the genetic diversity. Cryopreservation protocols of adequate efficiency are necessary to establish semen cryobanking for a species. Therefore, present study was designed to devise an efficient extender for cryopreservation of ring-necked pheasant semen. For this purpose, a range of extenders (Beltsville Poultry, red fowl, Lake, EK, Tselutin Poultry and Chicken semen extenders) were evaluated for cryopreservation of ring-necked pheasant semen. Semen collected from 10 cocks, diluted in the Beltsville Poultry (BPSE), Red Fowl (RFE), Lake (LE), EK (EKE), Tselutin Poultry (TPE) and Chicken Semen (CSE) extenders and cryopreserved. Glycerol (10%) was added to semen at 4°C, equilibrated for 10 min, filled in 0.5 mL French straws, kept over liquid nitrogen vapors for 10 min, cryopreserved in LN2 and stored. Sperm motility (%), viability (%), live/dead ratio (%), plasma membrane (%) and DNA Integrity (%) were evaluated at post-dilution, post-cooling, post-equilibration and post-thawing stage of cryopreservation. Sperm motility (83.8 ± 3.1; 81.3 ± 3.8; 73.8 ± 2.4; 62.5 ± 1.4), viability (79.0 ± 1.7; 75.5 ± 1.6; 69.5 ± 2.3; 65.5 ± 2.4), live/dead ratio (80.5 ± 5.7; 77.3 ± 4.9; 76.0 ± 2.7; 68.3 ± 2.3), plasma membrane (74.5 ± 2.9; 73.8 ± 3.4; 71.3 ± 2.3; 75.0 ± 3.4) and DNA integrity (78.3 ± 1.7; 73.0 ± 1.2; 68.0 ± 2.0; 63.0 ± 2.5) at all four stages of cryopreservation were recorded higher (P < 0.05) in red fowl extender compared to all experimental extenders. It is concluded that red fowl extender is the best extender for cryopreservation of ring-necked pheasant semen and can be used in establishing cryobank for ex situ conservation.

Keywords: ring-necked pheasant; extenders; cryopreservation; semen quality; DNA integrity

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385 Detection of Glyphosate Using Disposable Sensors for Fast, Inexpensive and Reliable Measurements by Electrochemical Technique

Authors: Jafar S. Noori, Jan Romano-deGea, Maria Dimaki, John Mortensen, Winnie E. Svendsen

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Pesticides have been intensively used in agriculture to control weeds, insects, fungi, and pest. One of the most commonly used pesticides is glyphosate. Glyphosate has the ability to attach to the soil colloids and degraded by the soil microorganisms. As glyphosate led to the appearance of resistant species, the pesticide was used more intensively. As a consequence of the heavy use of glyphosate, residues of this compound are increasingly observed in food and water. Recent studies reported a direct link between glyphosate and chronic effects such as teratogenic, tumorigenic and hepatorenal effects although the exposure was below the lowest regulatory limit. Today, pesticides are detected in water by complicated and costly manual procedures conducted by highly skilled personnel. It can take up to several days to get an answer regarding the pesticide content in water. An alternative to this demanding procedure is offered by electrochemical measuring techniques. Electrochemistry is an emerging technology that has the potential of identifying and quantifying several compounds in few minutes. It is currently not possible to detect glyphosate directly in water samples, and intensive research is underway to enable direct selective and quantitative detection of glyphosate in water. This study focuses on developing and modifying a sensor chip that has the ability to selectively measure glyphosate and minimize the signal interference from other compounds. The sensor is a silicon-based chip that is fabricated in a cleanroom facility with dimensions of 10×20 mm. The chip is comprised of a three-electrode configuration. The deposited electrodes consist of a 20 nm layer chromium and 200 nm gold. The working electrode is 4 mm in diameter. The working electrodes are modified by creating molecularly imprinted polymers (MIP) using electrodeposition technique that allows the chip to selectively measure glyphosate at low concentrations. The modification included using gold nanoparticles with a diameter of 10 nm functionalized with 4-aminothiophenol. This configuration allows the nanoparticles to bind to the working electrode surface and create the template for the glyphosate. The chip was modified using electrodeposition technique. An initial potential for the identification of glyphosate was estimated to be around -0.2 V. The developed sensor was used on 6 different concentrations and it was able to detect glyphosate down to 0.5 mgL⁻¹. This value is below the accepted pesticide limit of 0.7 mgL⁻¹ set by the US regulation. The current focus is to optimize the functionalizing procedure in order to achieve glyphosate detection at the EU regulatory limit of 0.1 µgL⁻¹. To the best of our knowledge, this is the first attempt to modify miniaturized sensor electrodes with functionalized nanoparticles for glyphosate detection.

Keywords: pesticides, glyphosate, rapid, detection, modified, sensor

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384 Developing a Model to Objectively Assess the Culture of Individuals and Teams in Order to Effectively and Efficiently Achieve Sustainability in the Manpower

Authors: Ahmed Mohamed Elnady Mohamed Elsafty

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This paper explains a developed applied objective model to measure the culture qualitatively and quantitatively, whether in individuals or in teams, in order to be able to use culture correctly or modify it efficiently. This model provides precise measurements and consistent interpretations by being comprehensive, updateable, and protected from being misled by imitations. Methodically, the provided model divides the culture into seven dimensions (total 43 cultural factors): First dimension is outcome-orientation which consists of five factors and should be highest in leaders. Second dimension is details-orientation which consists of eight factors and should be in highest intelligence members. Third dimension is team-orientation which consists of five factors and should be highest in instructors or coaches. Fourth dimension is change-orientation which consists of five factors and should be highest in soldiers. Fifth dimension is people-orientation which consists of eight factors and should be highest in media members. Sixth dimension is masculinity which consists of seven factors and should be highest in hard workers. Last dimension is stability which consists of seven factors and should be highest in soft workers. In this paper, the details of all cultural factors are explained. Practically, information collection about each cultural factor in the targeted person or team is essential in order to calculate the degrees of all cultural factors using the suggested equation of multiplying 'the score of factor presence' by 'the score of factor strength'. In this paper, the details of how to build each score are explained. Based on the highest degrees - to identify which cultural dimension is the prominent - choosing the tested individual or team in the supposedly right position at the right time will provide a chance to use minimal efforts to make everyone aligned to the organization’s objectives. In other words, making everyone self-motivated by setting him/her at the right source of motivation is the most effective and efficient method to achieve high levels of competency, commitment, and sustainability. Modifying a team culture can be achieved by excluding or including new members with relatively high or low degrees in specific cultural factors. For conclusion, culture is considered as the software of the human beings and it is one of the major compression factors on the managerial discretion. It represents the behaviors, attitudes, and motivations of the human resources which are vital to enhance quality and safety, expanding the market share, and defending against attacks from external environments. Thus, it is tremendously essential and useful to use such a comprehensive model to measure, use, and modify culture.

Keywords: culture dimensions, culture factors, culture measurement, cultural analysis, cultural modification, self-motivation, alignment to objectives, competency, sustainability

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383 Ecological Evaluation and Conservation Strategies of Economically Important Plants in Indian Arid Zone

Authors: Sher Mohammed, Purushottam Lal, Pawan K. Kasera

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The Thar Desert of Rajasthan covers a wide geographical area spreading between 23.3° to 30.12°, North latitude and 69.3◦ to 76◦ Eastern latitudes; having a unique spectrum of arid zone vegetation. This desert is spreading over 12 districts having a rich source of economically important/threatened plant diversity interacting and growing with adverse climatic conditions of the area. Due to variable geological, physiographic, climatic, edaphic and biotic factors, the arid zone medicinal flora exhibit a wide collection of angiosperm families. The herbal diversity of this arid region is medicinally important in household remedies among tribal communities as well as in traditional systems. The on-going increasing disturbances in natural ecosystems are due to climatic and biological, including anthropogenic factors. The unique flora and subsequently dependent faunal diversity of the desert ecosystem is losing its biotic potential. A large number of plants have no future unless immediate steps are taken to arrest the causes, leading to their biological improvement. At present the potential loss in ecological amplitude of various genera and species is making several plant species as red listed plants of arid zone vegetation such as Commmiphora wightii, Tribulus rajasthanensis, Calligonum polygonoides, Ephedra foliata, Leptadenia reticulata, Tecomella undulata, Blepharis sindica, Peganum harmala, Sarcostoma vinimale, etc. Mostly arid zone species are under serious pressure against prevailing ecosystem factors to continuation their life cycles. Genetic, molecular, cytological, biochemical, metabolic, reproductive, germination etc. are the several points where the floral diversity of the arid zone area is facing severe ecological influences. So, there is an urgent need to conserve them. There are several opportunities in the field to carry out remarkable work at particular levels to protect the native plants in their natural habitat instead of only their in vitro multiplication.

Keywords: ecology, evaluation, xerophytes, economically, threatened plants, conservation

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382 Generalized Synchronization in Systems with a Complex Topology of Attractor

Authors: Olga I. Moskalenko, Vladislav A. Khanadeev, Anastasya D. Koloskova, Alexey A. Koronovskii, Anatoly A. Pivovarov

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Generalized synchronization is one of the most intricate phenomena in nonlinear science. It can be observed both in systems with a unidirectional and mutual type of coupling including the complex networks. Such a phenomenon has a number of practical applications, for example, for the secure information transmission through the communication channel with a high level of noise. Known methods for the secure information transmission needs in the increase of the privacy of data transmission that arises a question about the observation of such phenomenon in systems with a complex topology of chaotic attractor possessing two or more positive Lyapunov exponents. The present report is devoted to the study of such phenomenon in two unidirectionally and mutually coupled dynamical systems being in chaotic (with one positive Lyapunov exponent) and hyperchaotic (with two or more positive Lyapunov exponents) regimes, respectively. As the systems under study, we have used two mutually coupled modified Lorenz oscillators and two unidirectionally coupled time-delayed generators. We have shown that in both cases the generalized synchronization regime can be detected by means of the calculation of Lyapunov exponents and phase tube approach whereas due to the complex topology of attractor the nearest neighbor method is misleading. Moreover, the auxiliary system approaches being the standard method for the synchronous regime observation, for the mutual type of coupling results in incorrect results. To calculate the Lyapunov exponents in time-delayed systems we have proposed an approach based on the modification of Gram-Schmidt orthogonalization procedure in the context of the time-delayed system. We have studied in detail the mechanisms resulting in the generalized synchronization regime onset paying a great attention to the field where one positive Lyapunov exponent has already been become negative whereas the second one is a positive yet. We have found the intermittency here and studied its characteristics. To detect the laminar phase lengths the method based on a calculation of local Lyapunov exponents has been proposed. The efficiency of the method has been verified using the example of two unidirectionally coupled Rössler systems being in the band chaos regime. We have revealed the main characteristics of intermittency, i.e. the distribution of the laminar phase lengths and dependence of the mean length of the laminar phases on the criticality parameter, for all systems studied in the report. This work has been supported by the Russian President's Council grant for the state support of young Russian scientists (project MK-531.2018.2).

Keywords: complex topology of attractor, generalized synchronization, hyperchaos, Lyapunov exponents

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381 Ultrasensitive Detection and Discrimination of Cancer-Related Single Nucleotide Polymorphisms Using Poly-Enzyme Polymer Bead Amplification

Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou

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The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.

Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms

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380 Recurrent Wheezing and Associated Factors among 6-Year-Old Children in Adama Comprehensive Specialized Hospital Medical College

Authors: Samrawit Tamrat Gebretsadik

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Recurrent wheezing is a common respiratory symptom among children, often indicative of underlying airway inflammation and hyperreactivity. Understanding the prevalence and associated factors of recurrent wheezing in specific age groups is crucial for targeted interventions and improved respiratory health outcomes. This study aimed to investigate the prevalence and associated factors of recurrent wheezing among 6-year-old children attending Adama Comprehensive Specialized Hospital Medical College in Ethiopia. A cross-sectional study design was employed, involving structured interviews with parents/guardians, medical records review, and clinical examination of children. Data on demographic characteristics, environmental exposures, family history of respiratory diseases, and socioeconomic status were collected. Logistic regression analysis was used to identify factors associated with recurrent wheezing. The study included X 6-year-old children, with a prevalence of recurrent wheezing found to be Y%. Environmental exposures, including tobacco smoke exposure (OR = Z, 95% CI: X-Y), indoor air pollution (OR = Z, 95% CI: X-Y), and presence of pets at home (OR = Z, 95% CI: X-Y), were identified as significant risk factors for recurrent wheezing. Additionally, a family history of asthma or allergies (OR = Z, 95% CI: X-Y) and low socioeconomic status (OR = Z, 95% CI: X-Y) were associated with an increased likelihood of recurrent wheezing. The impact of recurrent wheezing on the quality of life of affected children and their families was also assessed. Children with recurrent wheezing experienced a higher frequency of respiratory symptoms, increased healthcare utilization, and decreased physical activity compared to their non-wheezing counterparts. In conclusion, recurrent wheezing among 6-year-old children attending Adama Comprehensive Specialized Hospital Medical College is associated with various environmental, genetic, and socioeconomic factors. These findings underscore the importance of targeted interventions aimed at reducing exposure to known triggers and improving respiratory health outcomes in this population. Future research should focus on longitudinal studies to further elucidate the causal relationships between risk factors and recurrent wheezing and evaluate the effectiveness of preventive strategies.

Keywords: wheezing, inflammation, respiratory, crucial

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379 The Effect of a Probiotic Diet on htauE14 in a Rodent Model of Alzheimer’s Disease

Authors: C. Flynn, Q. Yuan, C. Reinhardt

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.

Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration

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378 Molecular Diversity of Forensically Relevant Insects from the Cadavers of Lahore

Authors: Sundus Mona, Atif Adnan, Babar Ali, Fareeha Arshad, Allah Rakha

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Molecular diversity is the variation in the abundance of species. Forensic entomology is a neglected field in Pakistan. Insects collected from the crime scene should be handled by forensic entomologists who are currently virtually non-existent in Pakistan. Correct identification of insect specimen along with knowledge of their biodiversity can aid in solving many problems related to complicated forensic cases. Inadequate morphological identification and insufficient thermal biological studies limit the entomological utility in Forensic Medicine. Recently molecular identification of entomological evidence has gained attention globally. DNA barcoding is the latest and established method for species identification. Only proper identification can provide a precise estimation of postmortem intervals. Arthropods are known to be the first tourists scavenging on decomposing dead matter. The objective of the proposed study was to identify species by molecular techniques and analyze their phylogenetic importance with barcoded necrophagous insect species of early succession on human cadavers. Based upon this identification, the study outcomes will be the utilization of established DNA bar codes to identify carrion feeding insect species for concordant estimation of post mortem interval. A molecular identification method involving sequencing of a 658bp ‘barcode’ fragment of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene from collected specimens of unknown dipteral species from cadavers of Lahore was evaluated. Nucleotide sequence divergences were calculated using MEGA 7 and Arlequin, and a neighbor-joining phylogenetic tree was generated. Three species were identified, Chrysomya megacephala, Chrysomya saffranea, and Chrysomya rufifacies with low genetic diversity. The fixation index was 0.83992 that suggests a need for further studies to identify and classify forensically relevant insects in Pakistan. There is an exigency demand for further research especially when immature forms of arthropods are recovered from the crime scene.

Keywords: molecular diversity, DNA barcoding, species identification, forensically relevant

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377 Interventions to Improve the Performance of Community Based Health Insurance in Low- and Lower Middle-Income-Countries: a Systematic Review

Authors: Scarlet Tabot Enanga Longsti

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Community-Based Health Insurance (CBHI) schemes have been proposed as a possible means to achieve affordable health care in low-and lower-middle-income countries. The existing evidence provides mixed results on the impact of CBHI schemes on healthcare utilisation and out -of-pocket payments (OOPP) for healthcare. Over 900 CBHI schemes have been implemented in underdeveloped countries, and these schemes have undergone different modifications over the years. Prior reviews have suggested that different designs of CBHI schemes may result in different outcomes. Objectives: This review sought to determine the interventions that affect the impact of CBHI schemes on OOPP and health service utilisation. Interventions in this study referred to any action or modification in the design of a CBHI scheme that affected the impact of the scheme on OOPP and/or healthcare utilization. Methods: Any CBHI study that was done in a lower middle-income country, that used an experimental design, that included OOPP or health care utilisation as outcome variables, and that was published in either English or French was included in this study. Studies were searched for in MEDLINE, Embase, CINAHL, EconLit, IBSS, Web of Science, Cochrane Library, and Global Index Medicus from July to August 2023. Bias was assessed using Joanna Brigs Institute tools for quality assessment for randomized control trials and quasi experimental studies. A narrative synthesis was done. Results: 12 studies were included in the review, with a total of 69 villages, 13,653 households, and 62,786 participants. Average premium collection was 4.8 USD/year. Most CBHI schemes had flat rates. The study revealed that a range of interventions impact OOPP and health care utilisation. Five categories of interventions were identified. The intervention with the highest impact on OOPP and utilisation was “Audit visits”. Next in line came external funds, training scheme workers, and engaging community leaders and village heads to advertise the scheme. Free healthcare led to a significant increase in utilisation of health services, a significant reduction in Catastrophic health expenditure, but an insignificant effect on OOPP among insured compared with uninsured. Conclusions: Community-Based Health Insurance could pave the way for Universal Health Care in low and middle-income countries. However, this can only be possible if careful thought is given to how schemes are designed. Due to the heterogeneity of studies and results on CBHI schemes, there is need for further research for more effective designs to be developed.

Keywords: community based health insurance, developing countries, health service utilisation, out of pocket payment

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376 Identification of Rare Mutations in Genes Involved in Monogenic Forms of Obesity and Diabetes in Obese Guadeloupean Children through Next-Generation Sequencing

Authors: Lydia Foucan, Laurent Larifla, Emmanuelle Durand, Christine Rambhojan, Veronique Dhennin, Jean-Marc Lacorte, Philippe Froguel, Amelie Bonnefond

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In the population of Guadeloupe Island (472,124 inhabitants and 80% of subjects of African descent), overweight and obesity were estimated at 23% and 9% respectively among children. High prevalence of diabetes has been reported (~10%) in the adult population. Nevertheless, no study has investigated the contribution of gene mutations to childhood obesity in this population. We aimed to investigate rare genetic mutations in genes involved in monogenic obesity or diabetes in obese Afro-Caribbean children from Guadeloupe Island using next-generation sequencing. The present investigation included unrelated obese children, from a previous study on overweight conducted in Guadeloupe Island in 2013. We sequenced coding regions of 59 genes involved in monogenic obesity or diabetes. A total of 25 obese schoolchildren (with Z-score of body mass index [BMI]: 2.0 to 2.8) were screened for rare mutations (non-synonymous, splice-site, or insertion/deletion) in 59 genes. Mean age of the study population was 12.4 ± 1.1 years. Seventeen children (68%) had insulin-resistance (HOMA-IR > 3.16). A family history of obesity (mother or father) was observed in eight children and three of the accompanying parent presented with type 2 diabetes. None of the children had gonadotrophic abnormality or mental retardation. We detected five rare heterozygous mutations, in four genes involved in monogenic obesity, in five different obese children: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations which were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations which were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutation in ABCC8 or KCNJ11 (involved in monogenic diabetes), which were of uncertain significance (KCNJ11 p.Val13Met, KCNJ11 p.Val151Met, ABCC8 p.Lys1521Asn and ABCC8 p.Ala625Val). Rare pathogenic or likely pathogenic mutations, linked to severe obesity were detected in more than 15% of this Afro-Caribbean population at high risk of obesity and type 2 diabetes.

Keywords: childhood obesity, MC4R, monogenic obesity, SIM1

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375 Phytochemistry and Alpha-Amylase Inhibitory Activities of Rauvolfia vomitoria (Afzel) Leaves and Picralima nitida (Stapf) Seeds

Authors: Oseyemi Omowunmi Olubomehin, Olufemi Michael Denton

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Diabetes mellitus is a disease that is related to the digestion of carbohydrates, proteins and fats and how this affects the blood glucose levels. Various synthetic drugs employed in the management of the disease work through different mechanisms. Keeping postprandial blood glucose levels within acceptable range is a major factor in the management of type 2 diabetes and its complications. Thus, the inhibition of carbohydrate-hydrolyzing enzymes such as α-amylase is an important strategy in lowering postprandial blood glucose levels, but synthetic inhibitors have undesirable side effects like flatulence, diarrhea, gastrointestinal disorders to mention a few. Therefore, it is necessary to identify and explore the α-amylase inhibitors from plants due to their availability, safety, and low costs. In the present study, extracts from the leaves of Rauvolfia vomitoria and seeds of Picralima nitida which are used in the Nigeria traditional system of medicine to treat diabetes were tested for their α-amylase inhibitory effect. The powdered plant samples were subjected to phytochemical screening using standard procedures. The leaves and seeds macerated successively using n-hexane, ethyl acetate and methanol resulted in the crude extracts which at different concentrations (0.1, 0.5 and 1 mg/mL) alongside the standard drug acarbose, were subjected to α-amylase inhibitory assay using the Benfield and Miller methods, with slight modification. Statistical analysis was done using ANOVA, SPSS version 2.0. The phytochemical screening results of the leaves of Rauvolfia vomitoria and the seeds of Picralima nitida showed the presence of alkaloids, tannins, saponins and cardiac glycosides while in addition Rauvolfia vomitoria had phenols and Picralima nitida had terpenoids. The α-amylase assay results revealed that at 1 mg/mL the methanol, hexane, and ethyl acetate extracts of the leaves of Rauvolfia vomitoria gave (15.74, 23.13 and 26.36 %) α-amylase inhibitions respectively, the seeds of Picralima nitida gave (15.50, 30.68, 36.72 %) inhibitions which were not significantly different from the control at p < 0.05, while acarbose gave a significant 56 % inhibition at p < 0.05. The presence of alkaloids, phenols, tannins, steroids, saponins, cardiac glycosides and terpenoids in these plants are responsible for the observed anti-diabetic activity. However, the low percentages of α-amylase inhibition by these plant samples shows that α-amylase inhibition is not the major way by which both plants exhibit their anti-diabetic effect.

Keywords: alpha-amylase, Picralima nitida, postprandial hyperglycemia, Rauvolfia vomitoria

Procedia PDF Downloads 187
374 Identification of New Familial Breast Cancer Susceptibility Genes: Are We There Yet?

Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

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The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

Procedia PDF Downloads 489
373 Unequal Contributions of Parental Isolates in Somatic Recombination of the Stripe Rust Fungus

Authors: Xianming Chen, Yu Lei, Meinan Wang

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The dikaryotic basidiomycete fungus, Puccinia striiformis, causes stripe rust, one of the most important diseases of wheat and barley worldwide. The pathogen is largely reproduced asexually, and asexual recombination has been hypothesized to be one of the mechanisms for the pathogen variations. To test the hypothesis and understand the genetic process of asexual recombination, somatic recombinant isolates were obtained under controlled conditions by inoculating susceptible host plants with a mixture of equal quantity of urediniospores of isolates with different virulence patterns and selecting through a series of inoculation on host plants with different genes for resistance to one of the parental isolates. The potential recombinant isolates were phenotypically characterized by virulence testing on the set of 18 wheat lines used to differentiate races of the wheat stripe rust pathogen, P. striiformis f. sp. tritici (Pst), for the combinations of Pst isolates; or on both sets of the wheat differentials and 12 barley differentials for identifying races of the barley stripe rust pathogen, P. striiformis f. sp. hordei (Psh) for combinations of a Pst isolate and a Psh isolate. The progeny and parental isolates were also genotypically characterized with 51 simple sequence repeat and 90 single-nucleotide polymorphism markers. From nine combinations of parental isolates, 68 potential recombinant isolates were obtained, of which 33 (48.5%) had similar virulence patterns to one of the parental isolates, and 35 (51.5%) had virulence patterns distinct from either of the parental isolates. Of the 35 isolates of distinct virulence patterns, 11 were identified as races that had been previously detected from natural collections and 24 were identified as new races. The molecular marker data confirmed 66 of the 68 isolates as recombinants. The percentages of parental marker alleles ranged from 0.9% to 98.9% and were significantly different from equal proportions in the recombinant isolates. Except for a couple of combinations, the greater or less contribution was not specific to any particular parental isolates as the same parental isolates contributed more to some of the progeny isolates but less to the other progeny isolates in the same combination. The unequal contributions by parental isolates appear to be a general role in somatic recombination for the stripe rust fungus, which may be used to distinguish asexual recombination from sexual recombination in studying the evolutionary mechanisms of the highly variable fungal pathogen.

Keywords: molecular markers, Puccinia striiformis, somatic recombination, stripe rust

Procedia PDF Downloads 237
372 Management Practices and Economic Performance of Smallholder Dairy Cattle Farms in Southern Vietnam

Authors: Ngoc-Hieu Vu

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Although dairy production in Vietnam is a relatively new agricultural activity, milk production increased remarkably in recent years. Smallholders are still the main drivers for this development, especially in the southern part of the country. However, information on the farming practices is very limited. Therefore, this study aimed to characterize husbandry practices, educational experiences, decision-making practices, constraints, income and expenses of smallholder dairy farms in Southern Vietnam. A total of 200 farms, located in the regions Ho Chi Minh (HCM, N=80 farms), Lam Dong (N=40 farms), Binh Duong (N=40 farms) and Long An (N=40 farms) were included. Between October 2013 and December 2014 farmers were interviewed twice. On average, farms owned 3.200m2, 2.000m2, and 193m2 of pasture, cropping and housing area, respectively. The number of total, milking and dry cows, heifers, and calves were 20.4, 11.6, 4.7, 3.3, and 2.9 head. The number of lactating dairy cows was higher (p<0.001) in HCM (15.5) and Lam Dong (14.7) than in Binh Duong (6.7) and Long An (10.7). Animals were mainly crossbred Holstein-Friesian (HF) cows with at least 75% HF origin (84%), whereas a higher (P<0.001) percentage of purebred HF was found in HCM and Lam Dong and crossbreds in Binh Duong and Long An. Animals were mainly raised in tie-stalls (94%) and machine-milked (80%). Farmers used their own replacement animals (76%), and both genetic and phenotypic information (67%) for selecting sires. Farmers were predominantly educated at primary school level (53%). Major constraints for dairy farming were the lack of capital (43%), diseases (17%), marketing (22%), lack of knowledge (8%) and feed (7%). Monthly profit per lactating cow was superior in Lam Dong (2,817 thousand VND) and HCM (2,798 thousand VND) compared to other regions in Long An (2,597 thousand VND), and Binh Duong (1,775 thousand VND). Regional differences may be mainly attributed to environmental factors, urbanization, and particularly governmental support and the availability of extension and financial institutions. Results from this study provide important information on farming practices of smallholders in Southern Vietnam that are useful in determining regions that need to be addressed by authorities in order to improve dairy production.

Keywords: dairy farms, milk yield, Southern Vietnam, socio-economics

Procedia PDF Downloads 457
371 Preparation of Allyl BODIPY for the Click Reaction with Thioglycolic Acid

Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

Procedia PDF Downloads 131
370 Spatial Ecology of an Endangered Amphibian Litoria Raniformis within Modified Tasmanian Landscapes

Authors: Timothy Garvey, Don Driscoll

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Within Tasmania, the growling grass frog (Litoria raniformis) has experienced a rapid contraction in distribution. This decline is primarily attributed to habitat loss through landscape modification and improved land drainage. Reductions in seasonal water-sources have placed increasing importance on permanent water bodies for reproduction and foraging. Tasmanian agricultural and commercial forestry landscapes often feature small artificial ponds, utilized for watering livestock and fighting wildfires. Improved knowledge of how L. raniformis may be exploiting anthropogenic ponds is required for improved conservation management. We implemented telemetric tracking in order to evaluate the spatial ecology of L. raniformis (n = 20) within agricultural and managed forestry sites, with tracking conducted periodically over the breeding season (November/December, January/February, March/April). We investigated (1) potential differences in habitat utilization between agricultural and plantation sites, and (2) the post-breeding dispersal of individual frogs. Frogs were found to remain in close proximity to ponds throughout November/December, with individuals occupying vegetative depauperate water bodies beginning to disperse by January/February. Dispersing individuals traversed exposed plantation understory and agricultural pasture land in order to enter patches of native scrubland. By March/April all individuals captured at minimally vegetated ponds had retreated to adjacent scrub corridors. Animals found in ponds featuring dense riparian vegetation were not recorded to disperse. No difference in behavior was recorded between sexes. Rising temperatures coincided with increased movement by individuals towards native scrub refugia. The patterns of movement reported in this investigation emphasize the significant contribution of manmade water-bodies towards the conservation of L. raniformis within modified landscapes. The use of natural scrubland as cyclical retreats between breeding seasons also highlights the importance of the continued preservation of remnant vegetation corridors. Loss of artificial dams or buffering scrubland in heavily altered landscapes could see the breakdown of the greater L. raniformis meta-population further threatening their regional persistence.

Keywords: habitat loss, modified landscapes, spatial ecology, telemetry

Procedia PDF Downloads 111
369 Literature Review of Rare Synchronous Tumours

Authors: Diwei Lin, Amanda Tan, Rajinder Singh-Rai

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We present the first reported case of a concomitant Leydig cell tumor (LCT) and paratesticular leiomyoma in an adult male with a known history of bilateral cryptorchidism. An 80-year-old male presented with a 2-month history of a left testicular lump associated with mild discomfort and a gradual increase in size on a background of bilateral cryptorchidism requiring multiple orchidopexy procedures as a child. Ultrasound confirmed a lesion suspicious for malignancy and he proceeded to a left radical orchidectomy. Histopathological assessment of the left testis revealed a concomitant testicular LCT with malignant features and paratesticular leiomyoma. Leydig cell tumors (LCTs) are the most common pure testicular sex cord-stromal tumors, accounting for up to 3% of all testicular tumors. They can occur at almost any age, but are noted to have a bi-modal distribution, with a peak incidence at 6 to 10 and at 20 to 50 years of age. LCT’s are often hormonally active and can lead to feminizing or virilizing syndromes. LCT’s are usually regarded as benign but can rarely exhibit malignant traits. Paratesticular tumours are uncommon and their reported prevalence varies between 3% and 16%. They occur in a complex anatomical area which includes the contents of the spermatic cord, testicular tunics, epididymis and vestigial remnants. Up to 90% of paratesticular tumours are believed to originate from the spermatic cord, though it is often difficult to definitively ascertain the exact site of origin. Although any type of soft-tissue neoplasm can be found in the paratesticular region, the most common benign tumors reported are lipomas of the spermatic cord, adenomatoid tumours of the epididymis and leiomyomas of the testis. Genetic studies have identified potential mutations that could potentially cause LCTs, but there are no known associations between concomitant LCTs and paratesticular tumors. The presence of cryptorchidism in adults with both LCTs and paratesticular neoplasms individually has been previously reported and it appears intuitive that cryptorchidism is likely to be associated with the concomitant presentation in this case report. This report represents the first documented case in the literature of a unilateral concomitant LCT and paratesticular leiomyoma on a background of bilateral cryptorchidism.

Keywords: testicular cancer, leydig cell tumour, leiomyoma, paratesticular neoplasms

Procedia PDF Downloads 358
368 Radiation Induced DNA Damage and Its Modification by Herbal Preparation of Hippophae rhamnoides L. (SBL-1): An in vitro and in vivo Study in Mice

Authors: Anuranjani Kumar, Madhu Bala

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Ionising radiation exposure induces generation of free radicals and the oxidative DNA damage. SBL-1, a radioprotective leaf extract prepared from leaves Hippophae rhamnoides L. (Common name; Seabuckthorn), showed > 90% survival in mice population that was treated with lethal dose (10 Gy) of ⁶⁰Co gamma irradiation. In this study, early effects of pre-treatment with or without SBL-1 in blood peripheral blood lymphocytes (PBMCs) were investigated by cell viability assays (trypan blue and MTT). The quantitative in vitro study of Hoescht/PI staining was performed to check the apoptosis/necrosis in PBMCs irradiated at 2 Gy with or without pretreatment of SBL-1 (at different concentrations) up to 24 and 48h. Comet assay was performed in vivo, to detect the DNA strands breaks and its repair mechanism on peripheral blood lymphocytes at lethal dose (10 Gy). For this study, male mice (wt. 28 ± 2g) were administered radioprotective dose (30mg/kg body weight) of SBL-1, 30 min prior to irradiation. Animals were sacrificed at 24h and 48h. Blood was drawn through cardiac puncture, and blood lymphocytes were separated using histopaque column. Both neutral and alkaline comet assay were performed using standardized technique. In irradiated animals, alkaline comet assay revealed single strand breaks (SSBs) that showed significant (p < 0.05) increase in percent DNA in tail and Olive tail moment (OTM) at 24 h while at 48h the percent DNA in tail further increased significantly (p < 0.02). The double strands breaks (DSBs) increased significantly (p < 0.01) at 48 h in neutral assay, in comparison to untreated control. The animals pre-treated with SBL-1 before irradiation showed significantly (p < 0.05) less DSBs at 48 h treatment in comparison to irradiated group of animals. The SBL-1 alone treated group itself showed no toxicity. The antioxidant potential of SBL-1 were also investigated by in vitro biochemical assays such as DPPH (p < 0.05), ABTS, reducing ability (p < 0.09), hydroxyl radical scavenging (p < 0.05), ferric reducing antioxidant power (FRAP), superoxide radical scavenging activity (p < 0.05), hydrogen peroxide scavenging activity (p < 0.05) etc. SBL-1 showed strong free radical scavenging power that plays important role in the studies of radiation-induced injuries. The SBL-1 treated PBMCs showed significant (p < 0.02) viability in trypan blue assay at 24-hour incubation.

Keywords: radiation, SBL-1, SSBs, DSBs, FRAP, PBMCs

Procedia PDF Downloads 151
367 An Investigation of Peptide Functionalized Gold Nanoparticles On Colon Cancer Cells For Biomedical Application

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

Procedia PDF Downloads 86
366 Towards Learning Query Expansion

Authors: Ahlem Bouziri, Chiraz Latiri, Eric Gaussier

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The steady growth in the size of textual document collections is a key progress-driver for modern information retrieval techniques whose effectiveness and efficiency are constantly challenged. Given a user query, the number of retrieved documents can be overwhelmingly large, hampering their efficient exploitation by the user. In addition, retaining only relevant documents in a query answer is of paramount importance for an effective meeting of the user needs. In this situation, the query expansion technique offers an interesting solution for obtaining a complete answer while preserving the quality of retained documents. This mainly relies on an accurate choice of the added terms to an initial query. Interestingly enough, query expansion takes advantage of large text volumes by extracting statistical information about index terms co-occurrences and using it to make user queries better fit the real information needs. In this respect, a promising track consists in the application of data mining methods to extract dependencies between terms, namely a generic basis of association rules between terms. The key feature of our approach is a better trade off between the size of the mining result and the conveyed knowledge. Thus, face to the huge number of derived association rules and in order to select the optimal combination of query terms from the generic basis, we propose to model the problem as a classification problem and solve it using a supervised learning algorithm such as SVM or k-means. For this purpose, we first generate a training set using a genetic algorithm based approach that explores the association rules space in order to find an optimal set of expansion terms, improving the MAP of the search results. The experiments were performed on SDA 95 collection, a data collection for information retrieval. It was found that the results were better in both terms of MAP and NDCG. The main observation is that the hybridization of text mining techniques and query expansion in an intelligent way allows us to incorporate the good features of all of them. As this is a preliminary attempt in this direction, there is a large scope for enhancing the proposed method.

Keywords: supervised leaning, classification, query expansion, association rules

Procedia PDF Downloads 319
365 TP53 Mutations in Molecular Subtypes of Breast Cancer in Young Pakistani Patients

Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

Procedia PDF Downloads 152
364 Krill-Herd Step-Up Approach Based Energy Efficiency Enhancement Opportunities in the Offshore Mixed Refrigerant Natural Gas Liquefaction Process

Authors: Kinza Qadeer, Muhammad Abdul Qyyum, Moonyong Lee

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Natural gas has become an attractive energy source in comparison with other fossil fuels because of its lower CO₂ and other air pollutant emissions. Therefore, compared to the demand for coal and oil, that for natural gas is increasing rapidly world-wide. The transportation of natural gas over long distances as a liquid (LNG) preferable for several reasons, including economic, technical, political, and safety factors. However, LNG production is an energy-intensive process due to the tremendous amount of power requirements for compression of refrigerants, which provide sufficient cold energy to liquefy natural gas. Therefore, one of the major issues in the LNG industry is to improve the energy efficiency of existing LNG processes through a cost-effective approach that is 'optimization'. In this context, a bio-inspired Krill-herd (KH) step-up approach was examined to enhance the energy efficiency of a single mixed refrigerant (SMR) natural gas liquefaction (LNG) process, which is considered as a most promising candidate for offshore LNG production (FPSO). The optimal design of a natural gas liquefaction processes involves multivariable non-linear thermodynamic interactions, which lead to exergy destruction and contribute to process irreversibility. As key decision variables, the optimal values of mixed refrigerant flow rates and process operating pressures were determined based on the herding behavior of krill individuals corresponding to the minimum energy consumption for LNG production. To perform the rigorous process analysis, the SMR process was simulated in Aspen Hysys® software and the resulting model was connected with the Krill-herd approach coded in MATLAB. The optimal operating conditions found by the proposed approach significantly reduced the overall energy consumption of the SMR process by ≤ 22.5% and also improved the coefficient of performance in comparison with the base case. The proposed approach was also compared with other well-proven optimization algorithms, such as genetic and particle swarm optimization algorithms, and was found to exhibit a superior performance over these existing approaches.

Keywords: energy efficiency, Krill-herd, LNG, optimization, single mixed refrigerant

Procedia PDF Downloads 153
363 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach

Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 164
362 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach

Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 153
361 Isolation, Identification and Screening of Marine Fungi for Potential Tyrosinase Inhibitor, Antibacterial and Antioxidant for Future Cosmeceuticals

Authors: Shivankar Agrawal, Sunil Kumar Deshmukh, Colin Barrow, Alok Adholeya

Abstract:

A variety of genetic and environmental factors cause various cosmetics and dermatological problems. There are already claimed drugs available in market for treating these problems. However, the challenge remains in finding more potent, environmental friendly, causing minimal side effects and economical cosmeceuticals. This leads to an increased demand for natural cosmeceutical products in the last few decades. Plant derived ingredients are limited because plants either contain toxic metabolites, grow too slow or seasonal harvesting is a problem. To identify new bioactive cosmetics ingredients of marine microbial bioresource, we screened 35 marine fungi isolated from marine samples collected from Andaman Island and west coast of India. Fungal crude extracts were investigated for their antityrosinase, antioxidant and antibacterial activities for the purpose of identifying anti-aging, skin-whitening and anti-acne biomolecule with the potential in cosmetics. In the tyrosinase inhibition and 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays, two fungal extracts, including “P2”, Talaromyces stipitatus and “D4”, Aspergillus terreus showed high inhibitory activity at 1mg/mL for tyrosinase inhibition and 0.5mg/mL for DPPH scavenging. The in vitro antimicrobial activity was investigated by the agar well diffusion method. In the tyrosinase inhibition assay, 8 extracts showed significant antibacterial activity against bacteria causing skin and wound infection in humans. In the course of systematic screening program for bioactive marine fungi, strain “D5” was found to be most potent strain with MIC value of 1mg/mL, which was morphologically identified as Simplicillium lamellicola. The effects of the most active crude extracts against their susceptible test microorganisms were also investigated by SEM analysis. Further investigations will focus on purification and characterization major active components responsible for these activities.

Keywords: antioxidant, antimicrobial activity, tyrosinase, cosmeceuticals, marine fungi

Procedia PDF Downloads 277
360 The Revival of Cultural Heritage through Social Space Upliftment: Case Study of the Walled City of Ajmer, India

Authors: Vaishali Sharma

Abstract:

The research is an attempt to hunt a scientific and objective method to transform Ajmer's traditional walled city into a living cultural heritage space, exploring urban management methods to elevate local economy and social space in relation to specific cultural-based initiatives. Ajmer is among the oldest and religiously diverse settlements in Rajasthan, that has seen superimposed developments through the eras. With numerous agencies operating towards the development of the town core of Ajmer, it becomes essential to structure development changes in tune with the transformations and the existing heritage. The study was radio-controlled by the subsequent analysis question: What is the way to overcome the genetic social and economic stress inside the communities and revive public life? In order to create necessary interventions at the neighbourhood level, fifteen neighbourhoods were identified. Each of those was analyzed relatively on three major dimensions: Heritage, Social and Local Economy. Each dimension was further broken down into multiple sub-aspects for an overall and exhaustive understanding. The average median values of the responses were used to develop a color-coded matrix to represent the scores in an exceedingly structured quantified manner, moreover, linking it to the spatial structure. Respondent perceptions on numerous dimensions were additionally recorded, so that the proposals are inclusive in nature. The goals are targeted at Ajmer's traditional walled towns, which will make it easier for the community to regulate the rapid transformations and commercialization occurring within the space. The study recommends the necessity for accrued support in methods and policies from the non-public sector, businesses as well as local stakeholders. An expansion, revitalization and maintenance of the major business and heritage corridors, for an increased local and visitor experience, can produce an impetus for promotion of the intangible heritage, to spur the local economic processes, conservation of heritage precincts and upward development.

Keywords: cultural heritage, economic revitalization, neighbourhoods in walled cities, social space, tangible and intangible heritage

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