Label-Free, Highly Sensitive Electrochemical Aptasensors Using Polymer-Modified Reduced Graphene Oxide for Cardiac Biomarker Detection

Acute myocardial infarction (AMI), also recognized as a ???heart attack,??? is one leading cause of death globally, and cardiac myoglobin (cMb), an important cardiac biomarker, is used for the early assessment of AMI. This paper presents an ultrasensitive, label-free electrochemical aptamer-based sensor (aptasensor) for cMb detection using polyethylenimine (PEI)-functionalized reduced graphene oxide (PEI???rGO) thin films. PEI, a cationic polymer, was used as a reducing agent for graphene oxide (GO), providing highly positive charges on the rGO surface and allowing direct immobilization of negatively charged single-strand DNA aptamers against cMb via electrostatic interaction without any linker or coupling chemistry. The presence of cMb was detected on Mb aptamer-modified electrodes using differential pulse voltammetry via measuring the current change due to the direct electron transfer between the electrodes and cMb proteins (Fe3+/Fe2+). The limits of detection were 0.97 pg mL???1 (phosphate-buffered saline) and 2.1 pg mL???1 (10-fold-diluted human serum), with a linear behavior with logarithmic cMb concentration. The specificity and reproducibility of the aptasensors were also examined. This electrochemical aptasensor using polymer-modified rGO shows potential for the early assessment of cMb in point-of-care testing applications

Computational and experimental investigation of elemental sulfur and polysulfide

Petroleum processing results in the generation of significant quantities of elemental sulfur (S8), leading to a surplus of sulfur worldwide. Despite its abundance and low cost, the use of sulfur in value-added organic compound synthesis is limited due to its unpredictable and misunderstood reactivity. This dissertation aims to address this issue by tackling it from two angles. Firstly, by utilizing Density Functional Theory (DFT) calculations, the reactivity of sulfur in the presence of nucleophiles is studied. This facilitates the identification of organic polysulfide intermediates that can be generated under different conditions, as well as the corresponding reactivity for each type of nucleophile. This computational study begins with a benchmarking of numerous DFT functionals against experimental data and high-accuracy ab initio computations to determine the best functional(s) for studying elemental sulfur and polysulfides in organic reactions. Using the best DFT method, the mechanism of monosulfide formation from cyanide and phosphines is explained. At the end of this computational study, the mechanism of 2-aminothiophene formation via the Gewald reaction is elucidated. Secondly, attempts are made to synthesize sulfur-based organic compounds using elemental sulfur or compounds with a sulfur source through the utilization of boron, imine, and aryne chemistry. In summary, this dissertation aims to expand the use of sulfur in organic chemistry by providing an understanding to predict its reactivity with nucleophiles, as well as demonstrating its potential for the low-cost synthesis of valuable sulfur-based organic compounds

R-2-hydroxyglutarate modulates DNA Replication via Integrated Stress Response

Les gènes de l'isocitrate déshydrogénase (IDH) sont mutés dans 70 à 80 % des gliomes de bas grade. Les enzymes mutantes IDH qui en résultent présentent une activité de gain de fonction, produisant du R-2-hydroxyglutarate (R-2-HG), appelé oncométabolite en raison de son accumulation anormale dans les tumeurs et de ses activités oncogéniques potentielles. Parmi les caractéristiques du cancer telles que la reprogrammation métabolique et épigénétique, le stress réplicatif et la stabilité du génome ont été peu caractérisés dans les cancers IDH-mutants. Par conséquent, cette étude vise à étudier l'impact de l'accumulation de R-2-HG sur la réplication de l'ADN et sa contribution au stress réplicatif dans les cancers IDH-mutants. Nous avons étudié la dynamique de la fourche de réplication dans des astrocytes humains normaux et confirmé les résultats dans d'autres lignées cellulaires normales et cancéreuses. Nous avons constaté que le traitement exogène par l'octyl-R-2-HG entravait la progression de la fourche de réplication et retardait par conséquent l'achèvement de la phase S. L'évaluation des niveaux de phosphorylation des protéines RPA, CHK1 et H2AX a révélé que la réponse classique au stress réplicatif (RSR) n'était pas activée. Un état cellulaire dans lequel la réplication de l'ADN est altérée sans activation de la RSR a notamment été décrit dans la littérature comme résultant de l'activation de la réponse au stress intégré (ISR). Cependant, l'activation de la RSI dans les cancers mutants IDH n'est pas bien étudiée. En évaluant les marqueurs d'activation de la RSI, tels que la phosphorylation de l'eIF2α et les niveaux de protéines ATF4, nous avons montré que l'octyl-R-2-HG activait la RSI. De plus, le blocage de l'ISR a partiellement sauvé la fourche de réplication et la progression de la phase S. Nous avons répliqué cette étude oncométrique. Nous avons reproduit ce défaut de réplication de l'ADN lié à l'oncométabolite ainsi que l'effet de sauvetage partiel de l'ISRIB lors de l'induction de la surexpression du gène IDH mutant. Nos résultats indiquent que la production de R-2-HG associée à la mIDH peut inhiber la dynamique normale de réplication de l'ADN via la signalisation ISR.The isocitrate dehydrogenase (IDH) genes are mutated in 70-80% of low-grade gliomas. The resulting IDH mutant enzymes exhibit gain-of-function activity, producing R-2-hydroxyglutarate (R-2-HG), which is referred to as an oncometabolite due to its abnormal accumulation in tumours and potential oncogenic activities. Among the hallmarks of cancer such as metabolic and epigenetic reprogramming, replicative stress and genome stability have been poorly characterized in IDH-mutant cancer. Therefore, this study aims to investigate the impact of R-2-HG accumulation on DNA replication and its contribution to replicative stress in IDH-mutant cancers. We investigated replication fork dynamics in normal human astrocytes and confirmed the results in other normal and cancer cell lines. We found that exogenous treatment with octyl-R-2-HG impaired replication fork progression and consequently delayed S-phase completion. Assessment of RPA, CHK1 and H2AX protein phosphorylation levels revealed that the classical Replicative Stress Response (RSR) was not activated. Among others, a cell state in which DNA replication was impaired without activation of the RSR has been described in the literature as a result of activation of the Integrated Stress Response (ISR). However, ISR activation in IDH-mutant cancers is not well studied. Hence, by assessing ISR activation markers such as eIF2α phosphorylation and ATF4 protein levels, we showed that octyl-R-2-HG activated ISR. Moreover, blocking ISR partially rescued the replication fork and S-phase progression. We replicated this oncometabolite-related DNA replication defect as well as ISRIB’s partial rescue effect upon induction of mutant IDH gene overexpression. Our results indicate that mIDH-associated R-2-HG production possibly inhibits normal DNA replication dynamics via ISR signalling

Technical Efficiency of Dryland and Irrigated Wheat Based on Stochastic Model

The technical efficiency and factors affecting efficiency of wheat farmers under dryland and irrigated conditions in the Jammu district of J &K state have been reported for the year 2006. The stochastic frontier production function has been used to determine the technical efficiency of these farmers. Technical efficiency has been found different under both the conditions. The estimated mean technical efficiency of wheat farmers under dry condition has been found to be 0.84, indicating 84 per cent efficiency in their use of production inputs, and for irrigated condition it has been found to be 0.88, that means the average output of wheat could be increased by 12 per cent by adopting technology properly. The value of γ under dry and irrigated conditions has indicated that about 99 per cent and 88 per cent of the differences between the observed and the maximum production frontier outputs are due to the factors, which are under farmers’ control. The estimated value of λ under dry and irrigated conditions are significantly different from zero, indicating a good fit and the correctness of the distributional assumptions specified. The value of λ has been more than one, implying the dominance of one-sided component Ui in Ei and thus indicated high degree of technical inefficiency. In other words, the inefficiency component was not dominated by the random factors. The variance ratio γ has showed that the farm-specific variability contributed more to the variation in yield, which means that variation in output from frontier is attributed to technical inefficiency. Some of the factors found to influence the level of technical efficiency are higher level of education in irrigated condition and larger number of male workers under dry conditions.Agricultural and Food Policy,

Sacralizing the City: The Begums of Bhopal and their Mosques

Princely building ventures in post 1857 colonial India included, among others, construction of religious buildings, even as their patrons enthusiastically pursued the colonial modernist agenda. This paper examines the architectural patronage of the Bhopal Begums, the women rulers of Bhopal State, who raised three grand mosques in their capital, Bhopal, in the 19th and early 20th century. As Bhopal marched on the road to progress under the Begums’ patronage, the mosques heralded the presence of Islam in the city in the post uprising scenario where both Muslims and mosques were subjected to retribution for fomenting the 1857 insurrection. Bhopal’s mosques were not only sacred sites for the devout but also impacted the public realm of the city. Their construction drew significantly on the Mughal architectural archetype, thus affording the Begums an opportunity to assert themselves, via their mosques, as legitimate inheritors of the Mughal legacy, including taking charge of the latter’s legacy of stewardship of Iam. Today, the Bhopal mosques constitute an integral part of the city’s built heritage corpus. It is worth underscoring that they are not only important symbols of the Muslim faith but also markers of their patrons’ endeavour to position themselves at the forefront in the complex political and cultural scenario of post uprising colonial India. Search Keywords for This Page Taj ul masjid, Moti masjid Bhopal, Jama masjid Bhopal, Bhopal masjid, Taj ul masjid Bhopal, Tajul masjid Bhopal, Bhopal mosque, Who built moti masjid, Taj-ul-masjid, Bhopal ki jama masjid, Bhopal architecture style, Bhopal jama masjid, Sikandar badshah image, Moti masjid in Bhopal, Moti masjid in Bhopal, Taj ul masjid in Bhopal, Who built moti masjid in delhi, Begum of Bhopal, Shahjehan begu

Colonial intervention and urban transformation : a case study of Shahjahanabad / Old Delhi

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Building for Modernity in Post Uprising Colonial India: Sanderson’s Survey and other Tales of Modern Indian Architecture

The post uprising colonial modern state zealously ushered modernity in the Indian Subcontinent. In the domain of architecture it produced a building frenzy from implementation of urban improvement schemes to raising infrastructure including buildings patronised by the government, Indian rulers and the masses. In a departure from the state’s view to impose the Eurocentric, universal idea of modernity as the only legitimate form of architectural expression, the corpus of buildings built at the turn of the century was a hybrid product of entanglement of tradition and modernity. Indeed, the various actors engaged in the production of buildings, from patrons to designers including architects and Mistris (craftsmen) negotiated modernity on their own individual terms in the absence of any established framework. Types of buildings ranged from state buildings for governance to opulent princely palaces to innumerable every day buildings. This Paper examines the many trajectories of architectural expression that prevailed in the Indian Subcontinent at the turn of the century and argues that the notion of modernity was not homogenous and was characterised by hybridity. It further asserts that this extant building corpus should get its due as modern heritage and be conserved today. Search Keywords for This Page Indian building, Modern indian architecture, Indian building design, Allen sanderson plagiarism, Colonial buildings in india, Colonial buildings in delh

Myoepithelioma of parotid: an unusual clinical entity with immunohistochemistry

Myoepithelioma was recognized as a histological distinct entity by World Health organization (WHO) in 1991. Only 1% of all salivary gland neoplasms are myoepithelioma. Most commonly affect parotid in approximately 40%. Myoepithelioma is usually a benign tumour arising from neoplastic myoepithelial cells which lack ductal differentiation. The salivary gland tumors in which the ducts comprise less than 5% of the section are classified as myoepitheliomas and in contrast to pleomorphic adenoma myoepithelioma does not show chondroid or osteoid formation. Immunohistochemical analysis can aid in the diagnosis with immunoreactivity to S-100, P63, Calponin, GFAP and myogenic markers. In this report we present a case of myoepithelioma in retroauricular region