Добірка наукової літератури з теми "Vijayan Complex"

ABSTRACT The acute and chronic management of paroxysmal supraventricular tachycardia (PSVT) during pregnancy presents a challenging clinical situation as there are no evidence-based guidelines despite being the commonest arrhythmia found in pregnancy. We report a case of paroxysmal supraventricular tachycardia in a 25 years old antenatal woman with no organic heart disease, where she received verapamil followed by diltiazem as antiarrhythmics instead of adenosine for conversion into sinus rhythm. Since she had recurrent episodes in third trimester she received verapamil and metoprolol as prophylaxis with good fetal and maternal outcome. This case highlights the need to understand the complexities in diagnosis and management of paroxysmal supraventricular tachycardia during pregnancy. How to cite this article Kumare BD, Kawathalkar A, Vijay NR. Paroxysmal Supraventricular Tachycardia: A Complex Dilemma during Pregnancy. J South Asian Feder Obst Gynae 2015;7(1):44-47.

This study is an investigation of the theme of misogyny as represented by the female characters in the select plays of Vijay Tendulkar. The study argues that the Indian cultural context leaves space for man to be superior and woman to be inferior. The term misogyny denotes hatred, dislike, or mistrust of women, manifested in various forms such as physical intimidation and abuse, sexual harassment and rape, social shunning and ostracism, etc. In most of the plays of Vijay Tendulkar women stand to be the objects of subjugation in the hands of their male counterparts with whom they happen to connect with in the hope of leading their normal life. Tendulkar’s plays display a wide range of complex behaviours those constitute different forms of violence – physical attacks and verbal abuses. A thorough analysis of the situations and circumstances related to women in Vijay Tendulkar’s plays reveal that the domestic, personal, political and social ambience in which the characters live in contribute them much violence physically, sexually, psychologically and verbally. As Tendulkar’s plays stand for the middle class society, the man in his plays quite often is brutal towards his female counterpart with his deep rooted ideologies. The paper’s finding speaks on how the woman characters evolve to be strong individuals amidst their adverse ambience.

In the sphere of drama, the name of Vijay Tendulkar does not require any introduction. In the galaxy of Indo-Anglo playwrights, Tendulkar is one of the most shining stars. Marathi Theatre is incomplete without the contribution made by Vijay Tendulkar. This Marathi literary figure is a multifaceted personality. He is the one who brought revolution in Marathi Theatre. An avant-garde playwright, Tendulkar has shown versatility by writing several works including one-act plays, children’s plays, short stories, essay collections etc. Vijay Tendulkar is the mouthpiece of the oppressed women in male dominant society. He has deep insight into human nature. He has proved in his plays that it is the male dominant society that does not allow woman to rise from the status of man’s foot. They are exploited, tortured, taunted both physically and emotionally. They are considered inferior to male human beings as male human beings are victims of their superiority complex. Even in some of the societies they are treated as bane while the male child is hailed as boon. His plays depict that women are treated as mere commodities. He has shown how the voice of women is suppressed when they try to voice their concerns against the cruelties. He makes a psychological study of human characters in his plays. An analytical approach to his plays reveals that women are deprived of the life they wish to live. The present research paper focuses on his four plays, to bring to light the enslaved and exploited position of women in society. In ‘Sakharam Binder’ and ‘Kamala’ he brings to light how women are enslaved and exploited. In ‘Silence! The Court is in Session’ and ‘Kanaydaan’ he ascertains the fact that it is male human being who is responsible for the exploitation of women.

Abstract Bright Peak Therapeutics is developing a portfolio of differentiated biotherapeutics using chemistry for applications in immuno-oncology and autoimmune diseases. Our unique chemical protein synthesis and engineering platform allows us to fine-tune cytokines and other proteins to interrogate and modulate biological functions by incorporating new functional modifications. Standard recombinant bacterial or cellular expression systems used to produce proteins are largely restricted to using canonical amino acids, which limits access to diverse modifications that can bestow additional functional properties. With chemical protein synthesis technology, canonical and non-canonical modifications including conjugation handles can be easily introduced, ultimately enabling a medicinal chemistry approach for engineering cytokine structures. Enhanced cytokines with differentiated biology developed using this approach can be further elaborated by conjugating to a diverse array of molecules. We first applied our technology platform to identify BPT-143, a rationally designed enhanced IL-2 variant currently in IND-enabling studies. BPT-143 is engineered to have enhanced binding to IL2Rβ and no binding to IL2Rα for improved efficacy and safety independent of the conjugation to a half-life extending 30 kDa PEG. The chemical synthesis technology is robust, reproducible, and scalable. We are applying our platform to enhance a number of other cytokines for use in immuno-oncology and autoimmune diseases. Additionally, our synthetically engineered cytokines can be easily conjugated to monoclonal antibodies as ‘payloads’ using a distinct chemical conjugation technology. A rapid and simple chemical process allows site-selective conjugation of our engineered cytokines to existing antibodies ‘as-is’ to generate novel immunocytokines (IC). This ‘off-the-shelf’ approach is orthogonal to recombinant fusion methods to create ICs and does not require complex recombinant protein expression optimization and lengthy cell-line development. Moreover, it allows rapid screening of cytokine payloads in a structure-activity relationship (SAR) format to identify dual-targeting ICs with precisely tailored properties to generate the desired biological effect. We have prepared a number of ICs including anti-PD-1/IL-2 ICs with various drug-antibody ratio (DAR) and conjugation sites within the antibody. We will provide an overview of the platform technology and present highlights of its application for discovery and development of designer therapeutic cytokines and ICs. Citation Format: Vijaya R. Pattabiraman, Matilde Arévalo Ruiz, Régis Boehringer, Benoit Hornsperger, Roy Meoded, Robert C. Tam, Bertolt Kreft. Creating next-generation biologics using a novel chemistry platform technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2138.

Abstract Background: The BAF (SWI/SNF) chromatin remodeling complex comprises of two mutually exclusive ATPases, SMARCA2 (BRM) and SMARCA4 (BRG1), that affect the mobilization and positioning of nucleosomes on DNA and thereby regulates important cellular functions including transcription, DNA recombination, DNA repair and chromosome decatenation during mitosis. SMARCA4 is frequently overexpressed in several types of cancers. Overexpression has been linked to increased proliferation and survival, as well as aggressive tumors and poor prognosis. SMARCA4 knockdown in these tumors lead to inhibition of proliferation and increased sensitivity to known chemotherapeutic agents, supporting the validity of targeting SMARCA4. Genetic silencing studies have established that the oncogenic activity of tumors lacking SMARCA4 is primarily driven by SMARCA2-containing residual SWI/SNF complex, suggesting the importance of dual inhibition of SMARCA2 and SMARCA4. While SMARCA4 is known to play a vital role in maintaining the oncogenic transcription program and driving proliferation in leukemia, the impact of dual SMARCA2 and SMARCA4 inhibition/degradation in acute myeloid leukemia (AML) is largely unexplored. Methods and Results: As part of the initial design plan, selective SMARCA2/4 Bromodomain inhibitors and specific ligands of several E3 ligases were chosen to arrive at different degrader designs. A choice of linkers and different exit vectors were considered to construct a variety of hetero bifunctional molecules. Our proprietary ternary complex modeling algorithm, ALMOND (ALgorithm for MOdeling Neosubstrate Degraders) helped in prioritizing the designs. Short listed compounds were synthesized and profiled in multiple cellular assays to understand their degradation potential. Several compounds that degrade SMARCA2, SMARCA4 & PBRM1 with pico molar DC50 were identified. These compounds have shown very potent anti-proliferative activity in both SMARCA2/4 proficient (MV-4-11, VCaP etc) and SMARCA4 mutant cell lines (SK-MEL-5 & RERF-LC-A1 etc). Further, potent compounds were optimized for their pharmacokinetic properties. Multiple lead compounds with low IV clearance and good oral bioavailability in rodents were identified. Advanced lead compounds are currently being evaluated in rodent tolerability and PK-PD experiments to select doses for the efficacy study. Conclusions: Highly potent degraders of SMARCA2, SMARCA4 & PBRM1 were identified by conjugating selective SMARCA2/4 Bromodomain inhibitors and several E3 ligase specific ligands. Further optimization of the linkers resulted in compounds with improved pharmacokinetic profile and very good oral bioavailability in rodents. Highly potent and orally available degraders of SMARCA2, SMARCA4 are efficacious in AML xenograft models and advanced profiling of candidate molecule is in progress. Citation Format: Chandrasekhar Abbineni, Leena Khare, Bilash Kuila, Abdul Rawoof Khaji, Dhaytadak Bhagwan Mahadeo, Sandeep Vitthal Dukare, Bhagya M S Kumar, Suraj T Gore, Vijay Kamal Ahuja, Amit A Dhudashiya, Raghavendra N R, Nagesh Gowda, Charamanna K B, Kiran Aithal B, Samiulla D S, Subhendu Mukherjee, Thomas Antony, Sanjeev Giri, Shekar Chelur, Kavitha Nellore, Girish Daginakatte, Murali Ramachandra, Susanta Samajdar. Discovery of orally bioavailable SMARCA2/4 dual degraders for treatment of acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3729.

Background:Interstitial lung disease is a well described extra-articular manifestation in a range of rheumatic diseases. It carries significant morbidity and mortality. Management of rheumatic diseases associated ILD (r-ILD) requires expertise as the needs of such patients are complex and treatment options limited. Historically, such complex ILD has been managed in tertiary referral centres.Objectives:We set up a combined service incorporating both rheumatology and respiratory domains in a district general hospital (DGH) to help patients avoid long journeys and improve their experience whilst focusing on an integrated care pathway. We evaluated the outcomes of the first set of patients managed in this proof-of-concept service model.Methods:Referrals were accepted from any hospital specialist involved in the management r-ILD. They were triaged by lead ILD pulmonologist to monthly ILD MDT comprising a rheumatologist, respiratory physician, a radiologist and ILD specialist nurse. Appropriate patients were booked into combined clinic, run by the respective rheumatology and chest specialists with ILD interest, attracting a multi-speciality tariff. All the data was recorded electronically with full access to demographics, disease parameters, investigations and drug management.Results:89 patients were included in this proof-of-concept. Mean age was 66.1 yrs (19-90 yrs) and 44% (n=39) were male. 35 (40%) had RA, 34 (39%) had CTD, eight (10%) had sarcoidosis, five had IPAF and seven others. Most predominant HRCT pattern was NSIP (n=53,60%) followed by UIP (n=23, 21%), sarcoid (n=10, 12%) and miscellaneous (LIP and mixed). Mean FVC was 2.64 L/min (1.93-4.13) with DLCOc of 52.7% (28.9-90.1%) predicted. Only two patients had all antibodies negative whilst 87 had at least one antibody positive with ANA being the most common (n=28).Most (83%) patients were treated with immunomodulators including nine with rituximab. 39 (44.3%) patients had significant improvement in clinical, imaging and pulmonary parameters with DLCOc improving to 56.57% and FVC to 2.70 L/min. There were similar improvements in six minute walk test. 17 patients died and 20 patients required long term oxygen therapy.Conclusion:This proof-of-concept real world study confirms the utility of a combined specialist service in a district general hospital. Nearly half of this complex and resource intensive patient cohort had good clinical outcomes and derived benefit from the expertise in one room. Feedback from both patients and referrers was unanimously positive. No patient required tertiary centre referral and all could be managed adequately in the clinical setting.Our report confirms that r-ILD can be managed in a DGH setting with a stream-lined service offering clear benefits to patients. We would argue that r-ILD service, congruent to satellite pulmonary hypertension clinics in secondary care with hub-and-spoke model liaison with tertiary centre, can be established on similar principles and could help over-stretched tertiary care with repatriation of services whilst helping develop local expertise in the management of chronic ILD.Disclosure of Interests:Karim Salama: None declared, Natasha Ramsundar: None declared, Vijay Joshi: None declared, Muhammad Khurram Nisar Grant/research support from: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB, Consultant of: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB, Speakers bureau: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Celgene, Novartis and UCB

In this study, cobalt-zinc ferrite (Co0.5Zn0.5Fe2O4) was obtained by the glycine-nitrate method followed by annealing in a high-temperature furnace at a temperature of 1300 °С. The qualitative composition and its microstructural characteristics were determined using energy-dispersive X-ray spectroscopy, X-ray diffraction analysis, and scanning electron microscopy.The analysis of the micrographs demonstrated that the cobalt-zinc ferrite micropowder obtained after thermal annealing has an average particle size of 1.7±1 μm. The analysis of XRD data showed that the annealed cobalt-zinc ferrite micropowder has a cubic crystal structure with a lattice parameter of a = 8.415 Å. Using the Scherrer and Williamson-Hall equations we calculated the average sizes of the coherent scattering regions, which were commensurate with the size of crystallites: according to the Scherrer equation D = 28.26 nm and according to the Williamson-Hall equation D = 33.59 nm and the microstress value e = 5.62×10–4 in the ferrite structure.Using a vector network analyser, the electromagnetic properties of a composite material based on synthesized cobalt-zinc ferrite were determined. The frequency dependences of the magnetic and dielectric permeability values from the measured S-parameters of the composite material (50% ferrite filler by weight and 50% paraffin) were determined using the Nicolson-Ross-Weir method and were in the range of 0.015–7 GHz. The analysis of the graphs of the dependence of the magnetic permeability on the frequency of electromagnetic radiation revealed a resonance frequency of fr ≈ 2.3 GHz. 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The island of Sri Lanka is the focus of Neoproterozoic super continent Gondwana. But the geological origin and paleotectonic position of Sri Lanka are least understood without knowing age and provenance of the four main crustal units, the Wanni Complex (WC), Highland Complex (HC), Vijayan Complex (VC) and the Kadugannawa Complex (KC). The study of age and provenance of metaquartzites of the WC and HC, leucosomes and paleosomes of migmatites of the WC, and charnockites of the HC and VC of Sri Lanka and sedimentary rocks of neighboring Proterozoic rift basins like Pranhita-Godavari basin of central India is significant in research on origin of Sri Lanka and also continental evolution to unravel the paleotectonic position of Sri Lanka before Gondwana being amalgamated in the Neoproterozoic. This study examined age of detrital zircon cores and metamorphic rims of metaquartzite, migmatite and charnockite samples along two west to east transects across the island of Sri Lanka as well as sedimentary rock samples from the Pranhita-Godavari rift basin of India using the LA-ICPMS method. The U-Pb zircon isotopic data from metaquartzites of WC ( near WC-HC boundary) and HC demonstrate dominant Mesoarchaean to Paleoproterozoic (2.0-2.8 Ga) detrital input into the metasedimentary make up and near boundary WC and HC metaquartzites were deposited between 2000 Ma and ~550 Ma with a maximum age of deposition ~ 2000 Ma, however a sample from the western WC was deposited in early Neoproterozpoic and mixed with Paleoproterozoic to Neoarchaean detritus indicating WC and HC terranes existed adjacent to each other since early Neoproterozoic and current WC-HC boundary is inaccurate and to be shifted westwards. This study reveals that parent materials of leucosomes of WC migmatitic gneisses are metasedimentary and showing late Mesoproterozoic to Neoproterozoic provenance (0.70-1.15 Ga) with maximum age of deposition at ~700 Ma. But paleosomes of WC migmatites show metaigneous origin with older Mesoarchaean ages (2.85-3.0 Ga) and have been identified in this study as the Mesoarchaean reworked continental basement material of WC. The HC charnockites clearly show metaigneous origin and primary intrusion ages of ~1.82 to 1.85 Ga. whilst a sample from the VC shows metasedimentary origin. A weighted mean of all rim data of WC and HC yields an age of 545.1 ± 9.7 Ma, supporting the age of Ediacaran-Cambrian metamorphism. Metaquartzite rocks of the HC of Sri Lanka are correlated with the Trivandrum Block and Northern Madurai Block of South India and the Itremo Group of Madagascar whilst metaquartzites of the western WC of Sri Lanka are correlated with the Southern Madurai Block of South India and the Molo Group of Madagascar and Sri Lankan metaquartzites were most probably sourced from east African igneous protolith sources. These differences in sedimentary provenance and maximum age of deposition prove and confirm that WC was a different crustal domain from the HC terrane. All this strongly supports a double subduction and collisional geological origin for the island of Sri Lanka with ‘HC orogeny’ occurred when the Southern Madurai Block of India (SMB)-WC and VC Mesoarchaean continental blocks collided with the HC orogenic belt and the oceanic crust of deeper basin of HC had subducted underneath the SMB-WC and VC continental blocks when ancient south Mozambique ocean closed along WC-HC boundary and HC-VC boundary sutures. This study reveals that Sri Lanka’s paleotectonic position could be south east of south India connecting Trivandrum Block to the HC and WC to the Southern Madurai Block. The study also reveals that the Pranhita-Godavari Basin was sourced from Eastern Ghats and Antarctica unlike Sri Lankan terranes were sourced from East Africa indicating Southern Granulite Terrane of India and Sri Lanka were not parts of mainland cratonic India until Ediacaran-Cambrian times.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Physical Sciences, 2017.