2,139 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]
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
Emergence of Photomodulated Protometabolism by Short Peptide-Based Assemblies
No full textIn the early Earth, rudimentary enzymes must have utilized the available light energy source to modulate protometabolic processes. Herein, we report the light-responsive C-C bond manipulation via short peptide-based assemblies bound to the photosensitive molecular cofactor (azo-based photoswitch) where the energy of the light source regulated the binding sites which subsequently modulated the retro-aldolase activity. In the presence of a continual source of high-energy photons, temporal realization of a catalytically more proficient state could be achieved under nonequilibrium conditions. Further, the hydrophobic surface of peptide assemblies facilitated the binding of an orthogonal molecular catalyst that showed augmented activity (promiscuous hydrolytic activity) upon binding. This latent activity was utilized for the in situ generation of light-sensitive cofactor that subsequently modulated the retro-aldolase activity, thus creating a reaction network
Dual-Enzyme Encapsulated Porous Nanocapsules for Lysosome-Targeted, Hypoxia-Amplified Cancer Therapy
No full textGlucose oxidase (GOx) catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide (H2O2), while horseradish peroxidase (HRP) converts H2O2 into cytotoxic hydroxyl radicals (center dot OH) under acidic conditions, such as those in lysosomes. Harnessing this tandem enzymatic activity offers a promising strategy to exacerbate tumor hypoxia and induce cancer cell death. Herein, we report the synthesis of hollow, porous organic nanocapsules (HPOCs; average diameter similar to 145 nm, wall thickness similar to 11 nm) via an inverse mini-emulsion technique using functionalized diamine and tetracarbaldehyde precursors. These nanocapsules coencapsulate GOx and HRP while acting as size-exclusion membranes, allowing selective diffusion of small molecules while retaining the enzymes. Confocal studies with BODIPY-labeled GOx and Cy5-labeled HRP ensure the encapsulation of both enzymes within the HPOCs and are found to be localized in the lysosome. The HPOCs exhibit excellent biocompatibility and, under hypoxic conditions, trigger substantial cancer cell apoptosis (similar to 75% cell death) and G2/M cell cycle arrest. Control nanocapsules lacking either or both enzymes show negligible therapeutic effect, underscoring the synergistic mechanism. This work presents a proof-of-concept for two-enzyme-loaded HPOCs as an effective platform for synergistic, hypoxia-amplified cancer therapy.A.D. acknowledges SERB (India) for financial support through JBR/2023/000005 grants. A.D. also acknowledges the MoESTARS research grant (STARS2/2023-47). S.K.P. acknowledges a mobility grant funded by the BOF Special Research Fund of Hasselt University. We acknowledge Biorender for the use of their software to generate the graphics. CSIR-CSMCRI PRIS no 133/2025
sj-docx-1-pij-10.1177_13506501211039736 - Supplemental material for Tribological Characteristics of Thermomechanically Processed 7075 Al Alloy Through Nano-scratch Characterization
No full textSupplemental material, sj-docx-1-pij-10.1177_13506501211039736 for Tribological Characteristics of Thermomechanically Processed 7075 Al Alloy Through Nano-scratch Characterization by Souriddha Sanyal, Ashoktaru Chakraborty, Angshuman Sarkar, Susanta K Pradhan, Utpal Madhu, Sumit Chabri, Apurba Das and Arijit Sinha in Proceedings of the Institution of Mechanical Engineers, Part J: Journal of Engineering Tribology</p
TIME-DEPENDENT SYSTEMS AND CHAOS IN STRING THEORY
No full textOne of the phenomenal results emerging from string theory is the AdS/CFT correspondence or gauge-gravity duality: In certain cases a theory of gravity is equivalent to a dual gauge theory, very similar to the one describing non-gravitational interactions of fundamental subatomic particles. A difficult problem on one side can be mapped to a simpler and solvable problem on the other side using this correspondence. Thus one of the theories can be understood better using the other.
The mapping between theories of gravity and gauge theories has led to new approaches to building models of particle physics from string theory. One of the important features to model is the phenomenon of confinement present in strong interaction of particle physics. This feature is not present in the gauge theory arising in the simplest of the examples of the duality. However this N = 4 supersymmetric Yang-Mills gauge theory enjoys the property of being integrable, i.e. it can be exactly solved in terms of conserved charges. It is expected that if a more realistic theory turns out to be integrable, solvability of the theory would lead to simple analytical expressions for quantities like masses of the hadrons in the theory. In this thesis we show that the existing models of confinement are all nonintegrable--such simple analytic expressions cannot be obtained.
We moreover show that these nonintegrable systems also exhibit features of chaotic dynamical systems, namely, sensitivity to initial conditions and a typical route of transition to chaos. We proceed to study the quantum mechanics of these systems and check whether their properties match those of chaotic quantum systems. Interestingly, the distribution of the spacing of meson excitations measured in the laboratory have been found to match with level-spacing distribution of typical quantum chaotic systems. We find agreement of this distribution with models of confining strong interactions, conforming these as viable models of particle physics arising from string theory
The Kashmir conflict of 1947 : testimonies of a contested history
No full text[Abstract not included]
Pokhar ke dunu paar: Things falling apart
No full textWhen a friend comes to visit Priyanka (Tanaya Jha Khan), the female protagonist of Pokhar Ke Dunu Paar, their reunion is bittersweet. Priyanka is living in a room of a boys’ hostel in Darbhanga, a small town about 140 kilometres northeast of Bihar’s capital Patna, with Sumit (Abhinav Jha). Sumit and Priyanka eloped earlier and migrated to New Delhi, but have been forced to return to their hometown in the wake of the Covid 19-induced lockdown and loss of income. Unable to return to their families, the couple struggles to find economic and emotional stabilit
EVALUATION OF FROZEN SEMEN BY A CROSOMAL INTEGRITY AND SPERM CONCENTRATION - TWO VITAL QUALITY PARAMETERS OF MALE FERTILITY IN BOVINES
No full textAcrosomal integrity and sperm concentration are two important parameters to assess
the quality of frozen semen doses which in terms validates the fertilizing capacity and conception
rate. The present study was undertaken to evaluate acrosomal integrity by Giemsa’s stain and sperm
concentration of FSS using improved neubauer chamber in Exotic pure Jersey, Crossbred Jersey,
Indigenous Gir cattle and Indigenous Murrah buffalo prior to the field use. The overall values of
Giemsa’s stain were observed as 73.74±0.31, 18.65±0.33 and 7.79±0.25 percent for Intact Acrosome,
Partially Damaged Acrosome and Fully Damaged Acrosome, respectively. Overall values of sperm
concentration were 21.98±0.28 million per straw. The study indicated that there was no significant
difference (P<0.05) among the breeds and the values mostly correlates with the guideline of Minimum
Standard Protocol for Production of bovine semen, 2012 of Govt. of India
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