Target Based Design And Synthesis of Heterocycles in the Potential Treatment of Cancer and Opportunistic Infection

Dose limiting toxicity and development of multidrug resistance by the tumors are the major limitations of current cancer chemotherapy. Microtubule targeting agents (MTAs) are a structurally diverse set of compounds that disrupt microtubule dynamics and exert their anticancer effect. Among the various classes of such agents, the colchicine site binding agents are particularly important as they circumvent the Pgp and β-III tubulin mediated clinical resistance. These resistance mechanisms, when manifested, are a major reason for the failure of clinically used agents such as taxanes and vinca alkaloids. A series of monocyclic pyrimidine analogs were designed and synthesized as colchicine site binding agents to overcome Pgp and β-III tubulin meditaed drug resistance. Multitargeted single agents with dual mechanism of actions, containing both cytostatic and cyotoxic components are particularly relevant to cancer chemotherapy as they have the potential to overcome multidrug resistance and dose limiting toxicities. Antiangiogenic agents target tumor angiogenesis, an important phenomenon for tumor growth and metastasis. The angiogenic effect is mediated by receptor tyrosine kinases (RTKs) and therefore, RTK inhibitors are used widely in the treatment of various types of cancers. To overcome the limitations of current cancer chemotherapy namely, dose limiting toxicity and multidrug resistance, quinazolines were designed and synthesized as dual acting MTA and RTK inhibitors. Toll-like receptors (TLRs) are key mediators in regulating the inflammatory response. Currently, more than 50 clinical trails of TLR agonists in the treatment of cancer are being conducted, either alone or in combination. Multitargeted single agents with dual acting MTA and TLR agonist (2,5-diaminoquinolines) were designed and synthesized as potential anticancer agents. A major part of this project covers the Pd-catalyzed cross coupling reaction optimization on the 2,5-diaminoquinolines including mechanistic details of the coupling reaction. Opportunistic infection by Pneumocystis jirovecii in immunocompromised patients such as organ transplant, cancer and AIDS patients is associated with high mortality. The current treatment involving the use of a combination of trimethoprim and sulfamethoxazole is limited by drug resistance, treatment failures and adverse side effects. Dihydrofolate reductase (DHFR) is an essential enzyme that provides folate cofactor for DNA, RNA and methionine biosynthesis. Hence, selectively inhibiting pjDHFR is an important strategy for effective treatment of infection by the pathogen. Incorporating the key differences in the active site residues in pjDHFR and hDHFR, thieno[2,3-d]pyrimidines were designed and synthesized as selective pjDHFR inhibitors. In addition, molecular modeling studies were performed on a series of pyrimido[4,5-b]indoles and cyclopenta[d]pyrimidines to explain their observed in vitro biological activities. Molecular modeling studies were also performed on a series of furo[2,3-d]pyrimidines and pyrrolo[3,2-d]pyrimidines to explain their biological activities on multiple targets (colchicine site of tubulin and multiple RTKs)

Energy Efficient Cluster based Multipath Routing in Wireless Sensor Networks

Wireless sensor network can be defined as a network of densely deployed sensor nodes. These sensor nodes have limited energy and have low processing and storage capabilities. Due to this, we require energy efficient routing protocols so that much of the energy of the nodes is not wasted in routing of data packets. In this paper, we present and energy efficient routing scheme. This routing protocol is a combination of cluster-based routing and multipath routing. We arrange all the sensor nodes in the network in the form of small clusters. Each of these clusters has a cluster head. Nodes which lie within a cluster send its data to its respective cluster head. The transfer of data from nodes to cluster head is through direct communication. All the cluster heads transfer their data to the sink or base station. This transfer of data is through multipath routing

Feature Based Opinion Mining on Movie Review

Rapid flow in internet users along with increasing power of online review sites and social media has given Existence to Sentiment analysis or Opinion minning,which aims to determine what other people feel,think And Exprss.Sentiment or Opinions contain user generated comment about products,services,policies andPolitics.Opinion may be in the form of ‘positive’ or ‘negative’.Users can give various opinion about feature of the product or services.Therefore product feature or aspects have got significant role in sentimental Analysis.This review paper analyse existing techniques and approaches for feature extraction in opinion Minning and sentimental analysis.In this paper we proposed the technique to extract the feature from the Movie review dataset. There is a burst of movie domain opinion rich resources in the form of review siteslike IMDB,yahoo movies etc.In this paper we proposed the method to provide the review summarization based on the feature of the movie commented by the user

Text Mining at Feature Level: A Review

Text Mining is the technique that helps users to find out useful information from a large amount of text documents on the web or database. Most popular text mining and classification methods have adopted term-based approaches. The term based approaches and the pattern-based method describing user preferences. This review paper analyse how the text mining work on the three level i.e sentence level, document level and feature level. In this paper we review the related work which is previously done. This paper also demonstrated that what are the problems arise while doing text mining done at the feature level. This paper presents the technique to text mining for the compound sentences

Evaluation of Biomedical Waste Management Practices in Multispeciality Tertiary Hospital

Background: Biomedical waste collection and proper disposal has become significant concern for medical and general community. The scientific hospital waste management is a vital importance as its improper management poses risk to healthcare workers, waste handlers, patients, community in general and largely the environment.Aims and Objectives: (i.)To assess current practices of biomedical waste management including generation, collection, transportation, storage, treatment and disposal technologies in tertiary health care center. (ii.)To assess health and safety practices for health care personal involved in biomedical waste management.Material and Method: Waste management practices in tertiary care center was study during in May 2016 to June 2016 the information/data regarding biomedical waste management practices and safety was collected by way of semi-structured interview, proforma being the one used for waste AUDITING QUESTIONNAIRE. The information collected was verified by personal observations of waste management practices in each ward of hospital.The information collected was verified by personal observation of waste management practices in each wards of hospital.Results: MMCH (Muzaffarnagar medical college and hospital) generates 1.25 kg wastes per bed per day and maximum waste is generated in wards. The hospital has got separate colour coded bins in each ward for collection of waste but segregation practices need to be more refined.The safety measure taken by health care workers was not satisfactory, it was not due to unavailability of personal protective measures but because un-awareness of health hazards which may occur due to improper waste management practices.Thus it concluded that there should be strict implementation of waste management policy set up in the hospital, training and motivation must be given paramount impotence to meet the current needs and standards of biomedical waste-management

Assessment of infectious diseases risks from dental aerosols in real-world settings

BACKGROUND: Infectious diseases physicians are leaders in assessing the health risks in a variety of community settings. An understudied area with substantial controversy is the safety of dental aerosols. Previous studies have used in vitro experimental designs and/or indirect measures to evaluate bacteria and viruses from dental surfaces. However, these findings may overestimate the occupational risks of dental aerosols. The purpose of this study was to directly measure dental aerosol composition to assess the health risks for dental healthcare personnel and patients. METHODS: We used a variety of aerosol instruments to capture and measure the bacterial, viral, and inorganic composition of aerosols during a variety of common dental procedures and in a variety of dental office layouts. Equipment was placed in close proximity to dentists during each procedure to best approximate the health risk hazards from the perspective of dental healthcare personnel. Devices used to capture aerosols were set at physiologic respiration rates. Oral suction devices were per the discretion of the dentist. RESULTS: We detected very few bacteria and no viruses in dental aerosols-regardless of office layout. The bacteria identified were most consistent with either environmental or oral microbiota, suggesting a low risk of transmission of viable pathogens from patients to dental healthcare personnel. When analyzing restorative procedures involving amalgam removal, we detected inorganic elements consistent with amalgam fillings. CONCLUSIONS: Aerosols generating from dental procedures pose a low health risk for bacterial and likely viral pathogens when common aerosol mitigation interventions, such as suction devices, are employed

14 Examples of How LLMs Can Transform Materials Science and Chemistry: A Reflection on a Large Language Model Hackathon

Chemistry and materials science are complex. Recently, there have been great successes in addressing this complexity using data-driven or computational techniques. Yet, the necessity of input structured in very specific forms and the fact that there is an ever-growing number of tools creates usability and accessibility challenges. Coupled with the reality that much data in these disciplines is unstructured, the effectiveness of these tools is limited. Motivated by recent works that indicated that large language models (LLMs) might help address some of these issues, we organized a hackathon event on the applications of LLMs in chemistry, materials science, and beyond. This article chronicles the projects built as part of this hackathon. Participants employed LLMs for various applications, including predicting properties of molecules and materials, designing novel interfaces for tools, extracting knowledge from unstructured data, and developing new educational applications. The diverse topics and the fact that working prototypes could be generated in less than two days highlight that LLMs will profoundly impact the future of our fields. The rich collection of ideas and projects also indicates that the applications of LLMs are not limited to materials science and chemistry but offer potential benefits to a wide range of scientific disciplines

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio