1,059 research outputs found
Abstract 5856: Molecular mechanism underlying breast cancer cell radioresistance: role of radiation-induced NF-KB self-sustenance
No full textAbstract
Understanding the mechanism of breast cancer cell radioresistance and the associated selection pressure, tumor recurrence, would help us to develop molecular interventions and achieve disease/progression-free survival in patients with cancer. In the present study, we investigated the molecular mechanisms prompted in breast cancer cells in response to clinical radiation and the associated coordination of intra- and inter-cellular signaling that orchestrate radioresistance and tumor relapse/recurrence. Our findings showed that clinical doses of radiation increase NF-κB transcription and DNA-binding activity. Further, radiation exposure resulted in de novo TNF-α synthesis and secretion. An NF-κB gene manipulation approach revealed that NF-κB triggered NF-κB-mediated TNF-α transcriptional activity. NF-κB DNA binding kinetic analysis demonstrated both sustained and dual phase NF-κB activation with radiation. Radiation prompted NF-κB-dependent synthesis/secretion of TNF-α, a requisite for the second phase of NF-κB activation and maintenance. Radiation-associated NF-κB-dependent secretion of TNF-α from irradiated cells also activated NF-κB in the non-irradiated, non-targeted bystander cells. Together, these findings demonstrated that radiation-triggered NF-κB-dependent TNFα secretion is critical for self-sustenance of NF-κB (through autocrine positive feedback signaling) and for coordinating bystander response (through intercellular signaling: de novo activation of NF-κB in bystander cells) after radiation exposure. Further, the data suggest that this NF-κB→TNF-α→NF-κB feedback-dependent self-sustenance of NF-κB could drive the selection pressure (proliferation, clonal expansion) of surviving breast cancer cells and subsequent tumor relapse/recurrence.
Note: This abstract was not presented at the meeting.
Citation Format: Hui Yu, Natarajan Aravindan, Ji Xu, Mohan Natarajan. Molecular mechanism underlying breast cancer cell radioresistance: role of radiation-induced NF-KB self-sustenance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5856. doi:10.1158/1538-7445.AM2017-5856</jats:p
Factorization of isometries of hyperbolic 4-space and a discreteness condition:
No full textGilman's NSDC condition is a sufficient condition for the discreteness of a two generator subgroup of PSL(2,C). We address the question of the extension of this condition to subgroups of isometries of hyperbolic 4-space. While making this new construction, namely the NSDS condition, we are led to ask whether every orientation preserving isometry of hyperbolic 4-space can be factored into the product of two half-turns. We use some techniques developed by Wilker to first, define a half-turn suitably in dimension 4 and then answer the former question. It turns out that defining a half-turn in this way in any dimension n enables us to generalize some of Gilman's theorems to dimension greater than or equal to 4. We also give an exposition on part of Wilker's work and give new proofs for some of his results.Ph.D.Includes bibliographical references (p. 52-53)by Karan Mohan Pur
Posterior urethral valve in neonates - overview in a tertiary care center
No full textBackground: Posterior urethral valves are a unique obstructive pathology occurring in male children. Although known to present during various age groups when diagnosed in the neonatal period itself the outcome is better.
Aims and Objectives: To study the incidence, clinical presentation, investigations, and management of neonates with posterior urethral valves and compare with literature.
Materials and Methods: Retrospective study of neonates admitted to Government Mohan Kumaramangalam Medical College Hospital in South India for 1 year from August 2022 to July 2023.
Results: Of a total of 16 cases studied the age of incidence of posterior urethral valve is 1–28 days with antenatally detected in nine cases. Fulguration was done in all 14 cases with vesicostomy in one case, bilateral ureterostomy in one case, and death in one case.
Conclusion: Posterior urethral valve is a rare neonatal disease which is most often diagnosed antenatally. The investigations and modalities of management in our institution are inline with other studies in literature
Bibliographics for the 983 eprints in the live archives of E-LIS : trends and status report up to 7th July 2004, based on author-self-archiving metadata
No full textThe priority for ideas and philosophy related to "Network Theory" have been traced back and documented by Braun(2004),and credit goes to Karinthy(1929).The IT has empowered to realise it, as the most practical phenomena and it is no more a humour. The OAI (Open Archives Initiatives)and ACIS (Academic Contributor Information System)are progressive in the direction ,which may lead to realise the "Collective Genius" at global level. Focus of present study is on Author-Self-Archiving (A-S-A)Metadata of the 983 Eprints in the Live Archives of the E-LIS (EPrints of Library and Information Science),which were approved till 7th July 2004.The A-S-A Metadata was used for librametric analysis. Self-explanatory bibliographics are illustrated.The highlights include: Conference papers (34%); highest approval, June 2004 (28%); published archives (76%);not refereed (52%); not in public domain (60%); highest self-archiving-author (De Robbio, Antonella).The Nos. of EPrints having single JITA domain specifications were: Theoretical and general aspects of libraries and information(27); Information use and sociology of information(80);Users,literacy and reading(13);Libraries as physical collections(30);Publishing and legal issues(57);Management(13);Industry, profession and education(36);Information sources, supports, channels(113) ; Information treatment for information services, Information functions and techniques (101); Technical services libraries, archives and museums(25); Housing technologies(1); Information technology and library technology(92); and Inter-domainery (395) i.e. having specifications of two or more than two JITA classes
Designing a successful library school field experience
No full textTo share the library school field experience paradigm that the authors developed after their successful participation as a supervisor and student.
Design/methodology/approach – A review of field experience literature is provided. The field experience paradigms and perspectives pertaining to the supervisor and the student are explained. The paradigm is suggested as a model for field experience participants and their supervisors.
Findings – The field experience paradigm for the supervisors elucidates the stages – planning, training, mentoring and evaluation. The paradigm for students explains the phases – awareness, interests, planning and participation.
Research limitations/implications – The focus of the field experience, from which the paradigm emanated, was to train and prepare the student for agricultural librarianship in an academic library. The application of the paradigm may vary for different situations.
Practical implications – The paradigm is expected to be useful for supervisors and students of field experience programs.
Originality/value – This paradigm stems from the participation of the authors as a field experience supervisor and student. The steps and methods the authors followed will help advance future field experience programs
Decision-making in Herpes Simplex viral keratitis grafts
No full textBackground: Keratoplasty after healed herpes simplex viral keratitis is a challenge due to problems arising preoperatively, intraoperatively, and postoperatively. Purpose: In this video, we describe the necessary challenges and the steps, which can be taken to prevent and manage those cases of healed herpes simplex virus (HSV) keratitis that would require a keratoplasty.Synopsis: The video talks about both the typical and atypical features of HSV keratitis, clinical examination, the scenarios which would require a keratoplasty, problems arising intraoperatively and how to manage them, and finally how to approach these high-risk grafts postoperatively. Highlights: Our video highlights the diagnosis of HSV keratitis, which cases are ready for surgery, and preoperative, intraoperative, and postoperative considerations before corneal transplantation in healed HSV keratitis. Decision-making before corneal transplant in HSV grafts can become more structured if these points are followed. Video Link: https://youtu.be/xMT7Ki8vuc
Rethinking web platform extensibility
No full textThe modern Web platform provides an extensible architecture that lets third party extensions, often untrusted, enhance and customize the Web browser and the Web applications. While the prevalence of extensions for both browsers and applications has been instrumental in making the Web browser hugely successful, there are two critical issues that the designers of the modern Web platform have not yet tackled in a principled manner. First, both the third party extensions and the extensible components of the Web platform include numerous vulnerabilities, which can compromise the security and privacy of end users. Second, the black-box and opaque nature of the Web platform limits the extent of extensibility achievable for Web developers, thereby hampering the development of novel browser-based user applications. This dissertation develops new tools and techniques to address the problem of insecure extensibility in the Web platform, proposes novel language and system level solutions to make extensibility a first class primitive for developing Web software, and demonstrates that these methods are applicable to real-world Web applications and Web browser extensions. Specifically, this dissertation makes the following three contributions. First, it studies and characterizes the problem of insecure JavaScript-based Web browser extensions using a specialized program analysis system, Sabre, which leverages JavaScript-level information flow mechanism to detect violations in client’s confidentiality and integrity arising from execution of untrusted extensions. Second, it formalizes the concept of transactions for JavaScript and implements Transcript, a language runtime system that allows hosting principals, i.e., Web browser and Web applications, to isolate untrusted JavaScript-based extensions using speculative execution. Lastly, this dissertation presents the design and implementation of Atlantis, a novel, extensible browser architecture that allows Web applications to define their own runtime environment and become more secure and robust. Atlantis enables developers with primitives to manage the Web application’s security and privacy, and removes their dependence on opaque, legacy Web interfaces.Ph. D.Includes bibliographical referencesby Mohan Dhawa
INSPEC database analysis for Knowledge Management records
No full textThe study deals with the Knowledge Management papers covered in the INSPEC, an international database on Information Science, Physical Sciences, Engineering and Computer Sciences. The papers have been analysed in terms of their content and other scientometric parameters
Physically interpretable machine learning methods for transcription factor binding site identification using principled energy thresholds and occupancy:
No full textRegulation of gene expression is pivotal to cell behavior. It is achieved predominantly by transcription factor proteins binding to specific DNA sequences (sites) in gene promoters. Identification of these short, degenerate sites is therefore an important problem in biology. The major drawbacks of the probabilistic machine learning methods in vogue are the use of arbitrary thresholds and the lack of biophysical interpretations of statistical quantities. We have developed two machine learning methods and linked them to the biophysics of transcription factor binding by incorporating simple physical interactions. These methods estimate site binding energy, recognizing that it determines a site's function and evolutionary fitness. They use the occupancy probability of a transcription factor on a DNA sequence as the discriminant function because it has a straightforward physical interpretation, forms a bridge between binding energy and evolutionary fitness, and has a natural threshold for classifying sequences into sites that allows establishing the threshold in a principled manner. Our methods incorporate additional characteristics of sites to enhance their identification. The first method, based on a hidden Markov model (HMM), identifies self-overlapping sites by combining the effects of their alternative binding modes. It learns the threshold by training emission probabilities using unaligned sequences containing known sites and estimating transition probabilities to reflect site density in all promoters in a genome. While identifying sites, it adjusts parameters to model site density changing with the distance from the transcription start site. Moreover, it provides guidance for designing padding sequences in experiments involving self-overlapping sites. Our second method, the Phylogeny-based Quadratic Programming Method of Energy Matrix Estimation (PhyloQPMEME), integrates evolutionary conservation to reduce false positives while identifying sites. It learns the threshold by solving an iterative quadratic programming problem to optimize the distribution of correlated binding energies of neutrally evolving orthologous sequences while restricting the values of binding energies of known sites and their orthologs. We have used the NF-κB transcription factor family as a case study for both methods and gained new insights into its biology.Ph.D.Includes bibliographical references (p. 210-226)by Amar Mohan Drawi
Breaking-Down Barriers: Proposal of Using Cellulose Biosynthesis Inhibitors and Cellulase Enzyme as a Novel Treatment Modality for Vision Threatening Pythium Insidiosum Keratitis
No full textBharat Gurnani,1 Radhika Natarajan,2 Madhuvanthi Mohan,2 Kirandeep Kaur3 1Department of Cataract, Cornea and Refractive Surgery, ASG Eye Hospital, Jodhpur, Rajasthan, 342008, India; 2Department of Cornea and Refractive Surgery, Sankara Nethralaya Medical Research Foundation, Chennai, Tamil Nadu, 600006, India; 3Department of Pediatric Ophthalmology and Strabismus, ASG Eye Hospital, Jodhpur, Rajasthan, 342008, IndiaCorrespondence: Bharat Gurnani, Department of Cornea and Refractive Surgery, ASG Eye Hospital, Jodhpur, Rajasthan, 342008, India, Tel +919080523059, Email [email protected]: Pythium insidiosum, an Oomycete, causes severe keratitis that endangers vision. Its clinical, morphological, and microbiological characteristics are often indistinguishable from those of fungal keratitis, earning it the moniker “parafungus”. Distinctive clinical hallmarks that set it apart from other forms of keratitis include radial keratoneuritis, tentacles, marginal infiltration, and a propensity for rapid limbal spread. The therapeutic approach to Pythium keratitis (PK) has long been a subject of debate, and topical and systemic antifungals and antibacterials have been tried with limited success. Approximately 80% of these eyes undergo therapeutic keratoplasty to salvage the eye. Hence, there is a need to innovate for alternative and better medical therapy to safeguard these eyes. The resistance of Pythium to standard antifungal treatments can be attributed to the absence of ergosterol in its cell wall. Cell walls of plants and algae have cellulose as an essential constituent. Cellulose imparts strength and structure and acts as the “skeleton” of the plant. Fungal and animal cell walls typically lack cellulose. The cellular architecture of Pythium shares a similarity with plant and algal cells through the incorporation of cellulose within its cell wall structure. Inhibitors targeting cellulose biosynthesis (CBI), such as Indaziflam, Isoxaben, and Quinoxyphen, serve as critical tools for elucidating the pathways of cellulose synthesis. Furthermore, the enzymatic action of cellulase is instrumental for the extraction of proteins and DNA. To circumvent this issue, we hypothesize that CBI’s and cellulase enzymes can act on the Pythium cell wall and may effectively treat PK. The available literature supporting the hypothesis and proof of concept has also been discussed. We have also discussed these drugs’ molecular mechanism of action on the Pythium cell wall. We also aim to propose how these drugs can be procured and used as a potential medical management option for this devastating entity.Keywords: Pythium insidiosum, keratitis, cellulose biosynthesis inhibitors, cellulase enzyme, antifungal
- …
