38 research outputs found
ROBUST MODEL DEVELOPMENT FOR EVALUATION OF EXISTING STRUCTURES
In the context of scientific computing, validation aims to determine the worthiness of a model in supporting critical decision making. This determination must occur given the imperfections in the mathematical representation resulting from the unavoidable idealizations of physics phenomena. Uncertainty in parameter values furthers the validation problems due to the inevitable lack of information about material properties, boundary conditions, loads, etc. which must be taken into account in making predictions about structural response. The determination of worthiness then becomes assessing whether an unavoidably imperfect mathematical model, subjected to poorly known input parameters, can predict sufficiently well in its intended purpose. The maximum degree of uncertainty in the model\u27s input parameters which the model can tolerate and still produce predictions within a predefined error tolerance is termed as robustness of the model. A trade-off exists between a model’s robustness to unavoidable uncertainty and its agreement with experiments, i.e. fidelity. This dissertation introduces the concept of satisfying boundary to evaluate such a trade-off. This boundary encompasses the model predictions that meet prescribed error tolerances. Decisions regarding allocation of resources for additional experiments to reduce uncertainty, relaxation of error tolerances, or the required confidence in the model predictions can be arrived at with the knowledge of this trade-off. This new approach for quantifying robustness based on satisfying boundaries is demonstrated on an application to a nonlinear finite element model of a historic masonry monument Fort Sumter
Determining the in vitro anti-cancer effects of various novel indoles and an anti-microbial peptide towards a potential treatment of glioma.
Substituted indoles (2-arylindoles) and related structures are known to exhibit potent anti-cancer activity against human breast cancer cell lines, and a range of other therapeutic targets. This activity, and other factors such as their biological activity, the fact that they are privileged structures, and the presence of the indole nucleus in various commercial anti-cancer drugs led to the choosing of indoles for the current study as a starting point for the development of new treatments against glioma. Investigation began on determining the anti-cancer activity of a variety of indoles against glioma cell lines (1321N1 and U87MG) using a number of different cell-based assays and also to compare them with conventional anti-cancer drugs. The aim was to find potent anti-cancer compound(s), amongst the compounds tested, and by studying its preliminary structure-activity-relationships (SAR), try to determine how the active compound(s) may be exerting their effects.
The SAR screening was divided into two main groups: indoles without a 2-aryl group and indoles with a 2-aryl group. The most potent compound identified, and its analogues, were further tested on the non-cancerous SVGp12 cell line to check for specificity of these indoles towards cancer cells, wherein it was found that these compounds were not specific to any particular cell type. Furthermore, activity was also observed for the best lead compound in the glioblastoma short-term culture, IN859, in which it gave a relatively low micromolar IC50 value (400 μM).
The results indicated that the anti-cancer activity of these compounds started within 2 h and therefore it was speculated that the mechanism of action of these compounds might work through the generation of reactive oxygen species (ROS). A ROS-detection kit was used to demonstrate this hypothesis, a result which was later corroborated using flow cytometry, and also provided quantitative analysis of the amount of ROS generated. It was further hypothesised that in the cells studied, autophagy was mediated due to excessive ROS generation. This was also confirmed over a similar time course by quantifying the amount of fluorescence generated in the 1321N1 and U87MG cell lines when labelled with acridine orange (a dye used to detect the formation of autophagosomes during autophagy) using flow cytometry. Moreover, the use of an autophagy inhibitor, 3-methyladenine, was shown to inhibit autophagy in these cell lines, again validating this hypothesis.
In conclusion, it has been demonstrated that the ability of certain substituted privileged indoles possessing a 2-aryl group and having an attached –OH group to it may have a rapid, deleterious effect on the viability of a primary short term culture (IN859) and glioma cell lines (1321N1 and U87MG). The mechanism of action of these indoles to cause cell death may be via the generation of ROS, leading to cell death initiated by autophagy.
Another short separate study was also performed in order to investigate the anti-cancer activity of an anionic host defence peptide, Cn-AMP2, on the above mentioned cell lines. This peptide was found to exhibit a modest cytostatic effect on both the cell lines but at higher concentrations (> 1 mM) and only when the serum concentrations were weaned down from 10 % to 2.5 %
Article ID 020115, 4
Abstract The concept of pain has evolved from that of a one-dimensional sensation to that of a multi-dimensional experience encompassing sensory, discriminate, cognitive, motivational and aff ective qualities. Pain is the presenting symptom of a broad spectrum of diseases that needs to be diagnosed and treated. Establishing a precise diagnosis and providing eff ective treatment have become major challenges in medical and dental profession. Oro-facial pain is the fi eld of dentistry devoted to the diagnosis and management of chronic, complex, facial pain and oro-motor disorders. Since diff erent diseases produce characteristic patterns of tissue damage, the quality, time course, location of a patient's pain complaint and the location of tenderness provide important diagnostic clues and are used to evaluate the response to treatment. The general characteristics, etiologic characteristics, pathophysiology, diff erential diagnostic criteria, and therapeutic options of atypical facial pain and atypical odontalgia are described
Atypical facial pain and atypical odontalgia: A concise review
The concept of pain has evolved from that of a one-dimensional sensation to that of a multi-dimensional experience encompassing sensory, discriminate, cognitive, motivational and aff ective qualities. Pain is the presenting symptom of a broad spectrum of diseases that needs to be diagnosed and treated. Establishing a precise diagnosis and providing effective treatment have become major challenges in medical and dental profession. Oro-facial pain is the fi eld of dentistry devoted to the diagnosis and management of chronic, complex, facial pain and oro-motor disorders. Since different diseases produce characteristic patterns of tissue damage, the quality, time course, location of a patient’s pain complaint and the location of tenderness provide important diagnostic clues and are used to evaluate the response to treatment. The general characteristics, etiologic characteristics, pathophysiology, diff erential diagnostic criteria, and therapeutic options of atypical facial pain and atypical odontalgia are described
Wi-Fi Signal Strength and Analysis
This work includes wifi signal strength survey of 'VIT Campus' wifi network. After analysing the AP's throughout the college, the wifi signal strength on each floor of each building was recorded using "wifi analyser" app. The recorded readings were mapped and discrepancies and redundancies in the placements of AP's was studied considering the facts such as student densities, obstacles, laboratories, classrooms. Dead zones were identified and the AP's were optimised and additional AP's are suggested to have a more effective coverage
Seismic Vulnerability Assessment of Anchored Block Type Contents Due to Sliding and Overturning
Damage to contents and nonstructural components is often the main driver of property losses against smaller earthquakes as evidenced by empirical evidence from past events. In the 2014 South Napa earthquake in California, for example, 56% of the affected buildings reported content damage. The primary modes of content damage include sliding, rocking, and overturning. The FEMA P-58 document provides seismic fragility functions for sliding and overturning of unanchored block content types, but no data is provided for anchored components. The ASCE/SEI 7-16 provides stability guidelines for different types of nonstructural components, but falls short of providing recommendations for the contents and furniture. This study investigates the behavior of anchored contents in commercial buildings and explores the impact of anchorage on the economic losses caused by content damage due to earthquake shaking. Anchored contents are generally represented here by rigid blocks with post-tensioned cables. The presented methodology adopts two engineering demand parameters (EDPs), the sliding displacement and the rotation angle of the rigid block, which are estimated by analytically modeling sliding and overturning responses due to ground motions. Their respective fragility functions are subsequently used to quantify the content seismic vulnerability by taking the maximum losses from sliding and overturning failure modes. The vulnerability functions of anchored versus unanchored contents are compared for commercial buildings of two different structural systems: steel and reinforced concrete moment resisting frames. Comparing the anchored and unanchored vulnerability functions reveals that the unanchored contents are more susceptible to damage and losses than the anchored ones. Moreover, numerical simulations show the extent of reduction in vulnerability, in terms of financial losses, for each level of spectral acceleration as the result of anchorage
Probabilistic Methodology for Terrorism Blast Risk Assessment
In this study, a probabilistic methodology has been developed to quantify terrorism blast risk for buildings. Concept of protection zones, which are zones in building with varying level of security, has been introduced based on the principle - as security increases the probable size of bomb should decrease. Probable bombs are uniformly placed at each protection zone to create many possible scenarios of terrorism event. Blast parameters (pressure and impulse) are estimated at many locations in 3D model of building for each scenario using a modified Kingery and Bulmash (KB) blast model called KB beta model. The United States Department of Defenses Pressure - Impulse damage curves are used to convert blast parameters to damage. The average damage to the building is estimated based on aggregation of damages to the building components. The methodology is applied to investigate the recent Brussels airport attack incident and the results are compared with actual Brussels Airport Attack. The terrorism-blast risk assessment shows that the attack could have been worse
Nanoparticulate RNA delivery systems in cancer
Background: Drug delivery system is a common practice in cancer treatment. RNA interference-mediated post-transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy). Recent findings: In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/shRNA, will assist in developing improved drug delivery strategies in basic and clinical research. Conclusion: These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades
Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens
This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility
STRUCTURAL HEALTH MONITORING OF HISTORIC MASONRY MONUMENTS
Structural Health Monitoring (SHM) is a well-accepted diagnostic technique being used to evaluate modern structures. This method involves monitoring the vibration response of a structure to detect changes in its structural state. The primary intention of this thesis is to address two practical and technical difficulties encountered in deploying SHM on historic masonry monuments: (i) the selection of suitable low dimensional vibration response features that are highly sensitive to the presence and extent of damage, while having low sensitivity to extraneous noise and (ii) the selection of optimal sensor locations for efficient system identification applied to Gothic Cathedrals. Both of the features of this thesis achieve reduction in the size of the raw data to be analyzed leading to reduced computational as well as monetary effort. Compression of the raw vibration response data acquired from the vibration tests on structures is vital from the standpoint of faster real time monitoring of historic structures. This thesis is composed of two manuscripts. The first manuscript illustrates the concepts of feature assimilation and noise sensitivity on an arch-like structure using both numerical and experimental analysis. The second study is focused on finding optimal sensor locations for vibration testing of Gothic Cathedrals. A modified version of the Effective Independence Method is used for this purpose. This thesis aims to develop a best-practices guide for effective application of SHM for the use of professionals involved in assessing, preserving and maintaining cultural monuments