849 research outputs found
Redox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania
No full textLeishmaniasis, a vector-borne disease, is caused by intracellular parasite Leishmania donovani. Unlike most intracellular pathogens, Leishmania donovani are lodged in parasitophorous vacuoles and replicate within the phagolysosomes in macrophages. Effective vaccines against this disease are still under development, while the efficacy of the available drugs is being questioned owing to the toxicity for nonspecific distribution in human physiology and the reported drug-resistance developed by Leishmania donovani. Thus, a stimuli-responsive nanocarrier that allows specific localization and release of the drug in the lysosome has been highly sought after for addressing two crucial issues, lower drug toxicity and a higher drug efficacy. We report here a unique lysosome targeting polymeric nanocapsules, formed via inverse mini-emulsion technique, for stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line. A benign polymeric backbone, with a disulfide bonding susceptible to an oxidative cleavage, is utilized for the organelle-specific release of miltefosine. Oxidative rupture of the disulfide bond is induced by intracellular glutathione (GSH) as an endogenous stimulus. Such a stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line over a few hours helped in achieving an improved drug efficacy by 200 times as compared to pure miltefosine. Such a drug formulation could contribute to a new line of treatment for leishmaniasis.A. Das acknowledges SERB (India) Grants (CRG/2020/000492 and JCB/2017/000004) and DBT Grant (BT/PR22251/NNT/28/1274/2017) for supporting this research. N. Mukherjee acknowledges SERB (India) Grant PDF/2016/001437 and K. Das acknowledges the grant EMR/2015/001674 for supporting this research. Financial support from DST (DST/INSPIRE/03/2017/002477) is acknowledged by R.T. This manuscript bears CSMCRI registration no 7/2021.Pramanik, SK (corresponding author), CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India.
Mukherjee, N (corresponding author), CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, Kolkata 700032, India.
Chattopadhy, S (corresponding author), BITS Pilani, Pilani 403726, Goa, India.
Das, A (corresponding author), Indian Inst Sci Educ & Res Kolkata, Mohanpur 741246, W Bengal, India.
[email protected]; [email protected]; [email protected]
Chapter 22 Evidence for Early and Mid-Cryogenian glaciation in the Northern Arabian-Nubian Shield (Egypt, Sudan, and western Arabia) - Photograph supplement
No full textCompanion photographs to the book chapter Stern, Robert J., Johnson, Peter R., Ali, Kamal A., and Mukherjee, Sumit K. 2011. “Evidence for Early and Mid-Cryogenian glaciation in the Northern Arabian-Nubian Shield (Egypt, Sudan, and western Arabia).” In: Arnaud, E., Halverson, G. P. and Shields-Zhou, G. (eds) The Geological Record of Neoproterozoic Glaciations. Geological Society, London, Memoirs, 36, 277-284
Molecular dynamics simulation based analysis of celecoxib-polymer interactions
No full textThis dataset contains scripts and coordinate files for running and analysing molecular dynamics simulations to investigate celecoxib-polymer interactions in aqueous solution. Trajectory files (stripped of water and ions) are also included.
The associated study is described in:
" Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance", Sumit Mukesh, Goutam Mukherjee, Ridhima Singh, Nathan Steenbuck, Carolina Demidova, Prachi Joshi, Abhay T. Sangamwar, Rebecca C. Wade, submitted.This work was supported by the German Federal Ministry for Education and Research (BMBF) 01DQ19004, the
Klaus Tschira Foundation, and Baden-Württemberg bwHPC and German Research Foundation (DFG) grant INST 35/1134-1 FUGG for computing resources
Molecular dynamics simulation based analysis of celecoxib-polymer interactions
No full textThis dataset contains scripts and coordinate files for running and analysing molecular dynamics simulations to investigate celecoxib-polymer interactions in aqueous solution. Trajectory files (stripped of water and ions) are included.
The associated study is described in:
" Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance", Sumit Mukesh, Goutam Mukherjee, Ridhima Singh, Nathan Steenbuck, Carolina Demidova, Prachi Joshi, Abhay T. Sangamwar, Rebecca C. Wade, submitted.This work was supported by the German Federal Ministry for Education and Research (BMBF) FKZ 01DQ19004, the
Klaus Tschira Foundation, and Baden-Württemberg bwHPC and German Research Foundation (DFG) grant INST 35/1134-1 FUGG for computing resources
Performance analysis of the WiNC2R platform:
No full textA Cognitive Radio (CR) is an intelligent transceiver device, able to support multiple technologies, dynamic re-configurability, ease of programming and collaboration with other CR devices to improve the communication efficiency. The two key requirements for an efficient CR implementation are flexibility in operation/programming and speed.
WiNC2R (Winlab Network Centric Cognitive Radio) achieves high speed of operation using its hardware platform and flexibility using its software-configurable architecture. The current WiNC2R architecture implements an 802.11a-like OFDM flow. We evaluate the WiNC2R hardware architecture to see the modularity in the architecture, separation of data and control flow and the performance in terms of latency and throughput. To test the system, the Xilinx Bus Functional Model environment, which is designed to test the IBM standard bus-architecture-based hardware systems, is used. We use a simple ALOHA protocol in the MAC layer to communicate between two WiNC2R nodes and evaluate the performance under the best-case scenario, where the performance is only hindered by the architecture itself rather than external conditions like channel state.
The results of our basic experiments showed that for a single OFDM 802.11a-like flow, the Unit Control Modules (UCM) were idle for almost 80% of the total processing time.
We then tested the WiNC2R system to study the effects of changing the frame size. It was seen that the latencies in the WiNC2R transmitter are frame-size dependent while those in the receiver mainly depend on the size of the data in the last chunk rather than the size of the whole frame. We suggest that chunk size should be 2 OFDM symbols, and chunking be moved to MAC layer for better performance. We give analytical estimates of resulting performance improvement. In the next experiment, we describe virtualization in the WiNC2R by adding more flows. We describe the steps to implement the additional flows and estimate maximum number of concurrent flows possible.
In the last analysis, we show the effect of operating clock frequency on the performance. We prove that at 250 MHz operating frequency and 2 OFDM symbols per chunk, the current WiNC2R implementation will be able to satisfy the SIFS criterion.M.S.Includes bibliographical references (p. 72-73)by Sumit Satarka
Development of biodegradable polymer based tamoxifen citrate loaded nanoparticles and effect of some manufacturing process parameters on them: a physicochemical and in-vitro evaluation
No full textBasudev Sahana, Kousik Santra, Sumit Basu, Biswajit MukherjeeDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata, IndiaAbstract: The aim of the present study was to develop nanoparticles of tamoxifen citrate, a non-steroidal antiestrogenic drug used for the treatment of breast cancer. Biodegradable poly (D, L- lactide-co-glycolide)-85:15 (PLGA) was used to develop nanoparticles of tamoxifen citrate by multiple emulsification (w/o/w) and solvent evaporation technique. Drug-polymer ratio, polyvinyl alcohol concentrations, and homogenizing speeds were varied at different stages of preparation to optimize the desired size and release profile of drug. The characterization of particle morphology and shape was performed by field emission scanning electron microscope (FE-SEM) and particle size distribution patterns were studied by direct light scattering method using zeta sizer. In vitro drug release study showed that release profile of tamoxifen from biodegradable nanoparticles varied due to the change in speed of centrifugation for separation. Drug loading efficiency varied from 18.60% to 71.98%. The FE-SEM study showed that biodegradable nanoparticles were smooth and spherical in shape. The stability studies of tamoxifen citrate in the experimental nanoparticles showed the structural integrity of tamoxifen citrate in PLGA nanoparticles up to 60°C in the tested temperatures. Nanoparticles containing tamoxifen citrate could be useful for the controlled delivery of the drug for a prolonged period.Keywords: biodegradable, nanoparticles, PLGA, stability, tamoxifen citrat
Abstract 4577: Appropriately delivered curcumin causes recruitment of natural killer cells into glioblastoma brain, stabilizing M1 polarization of tumor-associated microglia
No full textAbstract
Glioblastoma (GBM) is the most insidious form of primary adult brain tumor with a mean life expectancy of 12-24 months. Previously, we have used the non-invasive strategies of (1) intranasal delivery of a glioblastoma-directed curcumin (CC) adduct (CC-CD68Ab) and (2) the intraperitoneal (i.p.) infusion of a lipid-encapsulated formulation of CC-phytosome to rescue orthotopically GL261-implanted GBM mice and study the effect of CC on the phenotype of the tumor-associated microglial cells (TAMs). Both treatment regimens not only caused tumor remission in 50-60% of GL261-implanted GBM mice, but also induced a dramatic change in the tumor-associated Iba1+ TAMs, suppressing the tumor-promoting Arginase1high, IL10high, iNOSlow, IL12low M2-type TAMs, while simultaneously inducing the Arginase1low, IL10low, iNOShigh, IL12high M1-type TAMs. Concurrently, we observed a marked induction and phosphorylation-mediated activation of microglial p65 NF-kB and STAT1, with concomitant suppression and inactivation of STAT3. p-STAT1high, p-STAT3low M1 microglia are known to cause IL12-dependent recruitment/activation of tumoricidal NKp46high natural killer (NK) cells. In determining the kinetics of CC-induced M1 repolarization of M2-TAMs, we observed that five days of CCP treatment (i.p.) was sufficient to induce a dramatic change in the tumor-associated Iba1+ TAMs, inhibiting the tumor-promoting M2-type TAM population, while activating M1-type microglia. As expected, we observed a concomitant recruitment of NKp46high NK cells into the GBM tumor. Cognizant of the fact that NK cells activate and stabilize the M1-microglia, we eliminated the NK cells in these GBM mice using the NK cell-targeted antibody NK1.1 Ab to observe a significant reduction in CC-evoked repolarization of TAMs. Our results demonstrate a unique oncoimmunotherapeutic function of CC, which when appropriately delivered, not only eliminates GBM directly, but also indirectly elicits recruitment and activation of tumoricidal NK cells and M1-TAMs. Furthermore, maintenance of this CC-evoked M1 phenotype is contingent upon CC-induced recruitment and activation of NK cells. Thus, when delivered appropriately, CC functions on GBM both directly as well as by stimulating and recruiting an army of immune cells that eliminate both GBM and GBM-initiating cells.
Citation Format: Sumit Mukherjee, Angela Fried, Rahman Hussaini, Richard White, Aheli Chatterjee, Probal Banerjee. Appropriately delivered curcumin causes recruitment of natural killer cells into glioblastoma brain, stabilizing M1 polarization of tumor-associated microglia [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 4577. doi:10.1158/1538-7445.AM2017-4577</jats:p
PREVALENCE OF BOVINE HERPES VIRUS - 1 IN ORGANIZED FARMS OF WEST BENGAL, INDIA
No full textInfectious Bovine Rhinotracheitis, caused by Bovine Herpesvirus-1 (BoHV-1) maintains
latency in trigeminal nerve ganglia of bovine. The sero-positive bull infected with BoHV-1 secretes
the virus through semen intermittently, when the immune system is compromised. Sera from bulls
housed at different bull stations were analyzed using gE protein specific IDEXX Kit, which showed
78.69% positivity. Each batch of semen from sero-positive bull was investigated further for presence
of virus in semen by Real Time-PCR technique for validation of presence of virus in the frozen semen
doses using gB specific primers and probe, which showed 0.968 % semen batches positive. This study
showed that despite high sero prevalence in bull, the semen excretes very negligible amount of the
virus indicating the subtypes circulating in farms of West Bengal, India is assumed to be respiratory
type
Query optimization in mobile environments
No full textWe consider the issue of optimizing queries for distributed processing in mobile environment. An interesting characteristic of mobile machines is that they depend on battery as a source of energy which may not be substantial enough. Hence, the appropriate optimization criterion in a mobile environment considers both resource utilization and energy consum- ption at the mobile client.
In this scenario, the optimal plan for a query depends on the residual battery level of the mobile client and the load at the server. We approach this problem by compiling a query into a sequence of candidate plans, such that for any state of the client-server system, the optimal plan is one of the candidate plans.
A general solution is proposed by adapting the partial order dynamic programming search algorithm (p.o dp) such that the coverset of the query is the set of candidate plans. We propose two novel algorithms, namely, the linear combinations algorithm and the linearset algorithm (referred to as the linear algorithms) that compute the linearset of a query. The linear- set of a query is an approximation to the coverset returned by p.o. dp.
We show, by means of simulation, that (1) the linearset is an excellent approximation of the coverset, (2) query compilation using the linear algorithms outperform query compilation using p.o. dp by factors ranging from 2 to 9, (3) the time taken to compile queries using the linear algorithms for the general optimization criterion is at most twice the time taken by a System R* like standard query optimizer search algorithm, and (4) the run time overhead incurred by the linear algorithms technique is minimal.
The techniques presented in the paper are of general applicability to multi-criterion optimization problems in distributed databases, where each criterion is an additive metric.Technical report lcsr-tr-21
Interactive machine learning for complex graphics selection
No full textThesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 89-91).Modern vector graphics editors support the creation of a wonderful variety of complex designs and artwork. Users produce highly realistic illustrations, stylized representational art, even nuanced data visualizations. In light of these complex graphics, selections, representations of sets of objects that users want to manipulate, become more complex as well. Direct manipulation tools that artists and designers find accessible and useful for editing graphics such as logos and icons do not have the same applicability in these more complex cases. Given that selection is the first step for nearly all editing in graphics, it is important to enable artists and designers to express these complex selections. This thesis explores the use of interactive machine learning techniques to improve direct selection interfaces. To investigate this approach, I created Insight, an interactive machine learning selection tool for making a relevant class of complex selections: visually similar objects. To make a selection, users iteratively provide examples of selection objects by clicking on them in the graphic. Insight infers a selection from the examples at each step, allowing users to quickly understand results of actions and reactively shape the complex selection. The interaction resembles the direct manipulation interactions artists and designers have found accessible, while helping express complex selections by inferring many parameter changes from simple actions. I evaluated Insight in a user study of digital designers and artists, finding that Insight enabled users to effectively and easily make complex selections not supported by state-of-the-art vector graphics editors. My results contribute to existing work by both indicating a useful approach for providing complex representation access to artists and designers, and showing a new application for interactive machine learning.by Sumit Gogia.M. Eng
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