| 1. |
- Singh, Sachin Kumar, et al.
(författare)
-
Soil erosion control from trash residues at varying land slopes under simulated rainfall conditions
- 2023
-
Ingår i: Mathematical Biosciences and Engineering. - : American Institute of Mathematical Sciences. - 1551-0018. ; 20:6, s. 11403-11428
-
Tidskriftsartikel (refereegranskat)abstract
- Trash mulches are remarkably effective in preventing soil erosion, reducing runoff-sediment transport-erosion, and increasing infiltration. The study was carried out to observe the sediment outflow from sugar cane leaf (trash) mulch treatments at selected land slopes under simulated rainfall conditions using a rainfall simulator of size 10 m × 1.2 m × 0.5 m with the locally available soil material collected from Pantnagar. In the present study, trash mulches with different quantities were selected to observe the effect of mulching on soil loss reduction. The number of mulches was taken as 6, 8 and 10 t/ha, three rainfall intensities viz. 11, 13 and 14.65 cm/h at 0, 2 and 4% land slopes were selected. The rainfall duration was fixed (10 minutes) for every mulch treatment. The total runoff volume varied with mulch rates for constant rainfall input and land slope. The average sediment concentration (SC) and sediment outflow rate (SOR) increased with the increasing land slope. However, SC and outflow decreased with the increasing mulch rate for a fixed land slope and rainfall intensity. The SOR for no mulch-treated land was higher than trash mulch-treated lands. Mathematical relationships were developed for relating SOR, SC, land slope, and rainfall intensity for a particular mulch treatment. It was observed that SOR and average SC values correlated with rainfall intensity and land slope for each mulch treatment. The developed models' correlation coefficients were more than 90%.
|
|
| 2. |
- Kumar, Ramesh, et al.
(författare)
-
Hydro-geochemical analysis of meltwater draining from Bilare Banga glacier, Western Himalaya
- 2019
-
Ingår i: Acta Geophysica. - : Springer. - 1895-6572 .- 1895-7455. ; 67:2, s. 651-660
-
Tidskriftsartikel (refereegranskat)abstract
- The changing climate is affecting the melting process of glacier ice and snow in Himalaya and may influence the hydro-geochemistry of the glacial meltwater. This paper represents the ionic composition of discharge from Bilare Banga glacier by carrying out hydro-geochemical analysis of water samples of melting season of 2017. The pH and EC were measured on-site in field, and others parameters were examined in the laboratory. The abundance of the ions observed in meltwater has been arranged in decreasing order for cations as Ca2+ > Mg2+ > Na+ > K+ and for anions as HCO3− > SO42− > Cl− > NO3−, respectively. Analysis suggests that the meltwater is mostly dominated by Ca2+ and HCO3−. It has been observed that the ionic concentration HCO3− is dominant and Cl− is the least in the catchment. Piper plot analysis suggests that the chemical composition of the glacier discharge not only has natural origin but also has some anthropogenic input. Hydro-geochemical heterogeneity reflected the carbonate-dominated features (Ca2+–HCO3−) in the catchment. The carbonate weathering was found as the regulatory factor to control the chemistry of the glacial meltwater due to the high enrichment ratio of (Ca2+ + Mg2+) against TZ+ and (Na+ + K+). In statistical approach, PCA analysis suggests that geogenic weathering dynamics in the catchment is associated with carbonate-dominant lithology.
|
|
| 3. |
- Kumar, Rajesh, et al.
(författare)
-
Development of a Glacio-hydrological Model for Discharge and Mass Balance Reconstruction
- 2016
-
Ingår i: Water resources management. - : Springer Science and Business Media LLC. - 0920-4741 .- 1573-1650. ; 30:10, s. 3475-3492
-
Tidskriftsartikel (refereegranskat)abstract
- The reconstruction of glacio-hydrological records for the data deficient Himalayan catchments is needed in order to study the past and future water availability. The study provides outcomes of a glacio-hydrological model based on the degree-day approach. The model simulates the discharge and mass balance for glacierised Shaune Garang catchment. The degree-day factors for different land covers, used in the model, were estimated using daily stake measurements on Shaune Garang glacier and they were found to be varying between 2.6 ± 0.4 and 9.3 ± 0.3 mm °C−1day−1. The model is validated using observed discharge during ablation season of 2014 with coefficient of determination (R2) 0.90 and root mean square error (RMSE) 1.05 m3 sec−1. The model is used to simulate discharge from 1985 to 2008 and mass balance from 2001 to 2008. The model results show significant contribution of seasonal snow and ice melt in total discharge of the catchment, especially during summer. We observe the maximum discharge in July having maximum contribution from snow and ice melt. The annual melt season discharge shows following a decreasing trend in the simulation period. The reconstructed mass balance shows mass loss of 0.89 m we per year between 2001 and 2008 with slight mass gain during 2000/01 and 2004/05 hydrological years.
|
|
| 4. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Adjuvant properties of a biocompatible thermo-responsive polymer of N-isopropylacrylamide in autoimmunity and arthritis
- 2011
-
Ingår i: Journal of the Royal Society Interface. - London : The Royal Society Publishing. - 1742-5689 .- 1742-5662. ; 8:65, s. 1748-1759
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate the thermo-responsive poly(N-isopropylacrylamide) (PNiPAAm) polymer as an adjuvant, we synthesized PNiPAAm through free radical polymerization and characterized it both in vitro and in vivo. The polymer when mixed with collagen type II (CII) induced antigen-specific autoimmunity and arthritis. Mice immunized with PNiPAAm-CII developed significant levels of CII-specific IgG response comprising major IgG subclasses. Antigen-specific cellular recall response was also enhanced in these mice, while negligible level of IFN-gamma was detected in splenocyte cultures, in vitro. PNiPAAm-CII-immunized arthritic mouse paws showed massive infiltration of immune cells and extensive damage to cartilage and bone. As determined by immunostaining, most of the CII protein retained its native configuration after injecting it with PNiPAAm in naive mice. Physical adsorption of CII and the high-molecular-weight form of moderately hydrophobic PNiPAAm induced a significant anti-CII antibody response. Similar to CII, mice immunized with PNiPAAm and ovalbumin (PNiPAAm-Ova) induced significant anti-ovalbumin antibody response. Comparable levels of serum IFN-gamma, IL-1beta and IL-17 were observed in ovalbumin-immunized mice with complete Freund, incomplete Freund (CFA and IFA) or PNiPAAm adjuvants. However, serum IL-4 levels were significantly higher in PNiPAAm-Ova and CFA-Ova groups compared with the IFA-Ova group. Thus, we show for the first time, biocompatible and biodegradable thermo-responsive PNiPAAm can be used as an adjuvant in several immunological applications as well as in better understanding of the autoimmune responses against self-proteins. © 2011 The Royal Society
|
|
| 5. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Collagen type II and a thermo-responsive polymer of N-isopropylacrylamide induce arthritis independent of Toll-like receptors : a strong influence by major histocompatibility complex class II and Ncf1 genes
- 2011
-
Ingår i: American Journal of Pathology. - New York : Elsevier. - 0002-9440 .- 1525-2191. ; 179:5, s. 2490-2500
-
Tidskriftsartikel (refereegranskat)abstract
- We established and characterized an arthritis mouse model using collagen type II (CII) and a thermo-responsive polymer, poly(N-isopropylacrylamide) (PNiPAAm). The new PNiPAAm adjuvant is TLR-independent, as all immunized TLR including MyD88-deficient mice developed an anti-CII response. Unlike other adjuvants, PNiPPAm did not skew the cytokine response (IL-1beta, IFN-gamma, IL-4, and IL-17), as there was no immune deviation towards any one type of immune spectrum after immunization with CII/PNiPPAm. Hence, using PNiPAAm, we studied the actual immune response to the self-protein, CII. We observed arthritis and autoimmunity development in several murine strains having different major histocompatibility complex (MHC) haplotypes after CII/PNiPAAm immunization but with a clear MHC association pattern. Interestingly, C57Bl/6 mice did not develop CII-induced arthritis, with PNiPAAm demonstrating absolute requirement for a classical adjuvant. Presence of a gene (Ncf1) mutation in the NADPH oxidation complex has a profound influence in arthritis and using PNiPAAm we could show that the high CIA severity in Ncf1 mutated mice is independent of any classical adjuvant. Macrophages, neutrophils, eosinophils, and osteoclasts but not mast cells dominated the inflamed joints. Furthermore, arthritis induction in the adjuvant-free, eosinophil-dependent Vbeta12 DBA/1 mice could be shown to develop arthritis independent of eosinophils using CII/PNiPAAm. Thus, biocompatible and biodegradable PNiPAAm offers unique opportunities to study actual autoimmunity independent of TLR and a particular cytokine phenotype profile.
|
|
| 6. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Macrophage-derived reactive oxygen species protects against autoimmune priming with a defined polymeric adjuvant
- 2016
-
Ingår i: Immunology. - Chichester : Wiley-Blackwell. - 0019-2805 .- 1365-2567. ; 147:1, s. 125-132
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the nature of adjuvants and the immune priming events in autoimmune diseases, such as rheumatoid arthritis, is a key challenge to identify their aetiology. Adjuvants are, however, complex structures with inflammatory and immune priming properties. Synthetic polymers provide a possibility to separate these functions and allow studies of the priming mechanisms in vivo. A well-balanced polymer, poly-N-isopropyl acrylamide (PNiPAAm) mixed with collagen type II (CII) induced relatively stronger autoimmunity and arthritis compared with more hydrophilic (polyacrylamide) or hydrophobic (poly-N-isopropylacrylamide-co-poly-N-tertbutylacrylamide and poly-N-tertbutylacrylamide) polymers. Clearly, all the synthesized polymers except the more hydrophobic poly-N-tertbutylacrylamide induced arthritis, especially in Ncf1-deficient mice, which are deficient in reactive oxygen species (ROS) production. We identified macrophages as the major infiltrating cells present at PNiPAAm-CII injection sites and demonstrate that ROS produced by the macrophages attenuated the immune response and the development of arthritis. Our results reveal that thermo-responsive polymers with high immune priming capacity could trigger an autoimmune response to CII and the subsequent arthritis development, in particular in the absence of NOX2 derived ROS. Importantly, ROS from macrophages protected against the autoimmune priming, demonstrating a critical regulatory role of macrophages in immune priming events. © 2016 John Wiley & Sons Ltd.
|
|
| 7. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Polymeric cryogels are biocompatible, and their biodegradation is independent of oxidative radicals
- 2014
-
Ingår i: Journal of Biomedical Materials Research. Part A. - Hoboken, NJ : John Wiley & Sons. - 1549-3296 .- 1552-4965. ; 102:10, s. 3409-3418
-
Tidskriftsartikel (refereegranskat)abstract
- Biocompatibility and in vivo degradation are two important characteristics of cell scaffolds. We evaluated these properties for four different polymeric macroporous cryogels, polyvinylcaprolactam, polyvinyl alcohol-alginate-bioactive glass composite, polyhydroxyethylmethacrylate-gelatin (pHEMA-gelatin), and chitosan-agarose-gelatin in mice. All the cryogels were synthesized at subzero temperature and were implanted subcutaneously in C57Bl/10.Q inbred mice. Both local and systemic toxicities were negligible as determined by serum tumor necrosis factor α analysis and histology of surrounding tissues nearby the implants. Complete integration of cryogels into the surrounding tissues with neovascular formation was evident in all the mice. At the implantation site, massive infiltration of macrophages and few dendritic cells were observed but neutrophils and mast cells were clearly absent. Macrophage infiltrations were observed even inside the pores of cryogel implants. To ascertain whether oxidative radicals are involved in the cryogel degradation, we implanted these gels in mice deficient for reactive oxygen species (ROS) production. Rapid gel degradation was observed in the absence of ROS, and there was no significant difference in the biodegradation of these cryogels between ROS sufficient and deficient mice thereby excluding any major role for ROS in this process. Thus, we demonstrate the biocompatibility and ROS-independent biodegradable properties of cryogels that could be useful for tissue-specific tissue engineering applications. © 2013 Wiley Periodicals, Inc.
|
|
| 8. |
- Singh, Shaktiman, et al.
(författare)
-
Changing climate and glacio-hydrology in Indian Himalayan Region : a review
- 2016
-
Ingår i: Wiley Interdisciplinary Reviews. - : Wiley. - 1757-7780 .- 1757-7799. ; 7:3, s. 393-410
-
Tidskriftsartikel (refereegranskat)abstract
- This study presents a comprehensive review of the published literature on the evidences of a changing climate in the Indian Himalayan Region (IHR) and its impacts on the glacio-hydrology of the region. The IHR serves as an important source of fresh water for the densely populated areas downstream. It is evident from the available studies that temperature is significantly increasing in all parts of the IHR, whereas precipitation is not indicative of any particular spatiotemporal trend. Glacio-hydrological proxies for changing climate, such as, terminus and areal changes of the glaciers, glacier mass balance, and streamflow in downstream areas, highlight changes more evidently in recent decades. On an average, studies have predicted an increase in temperature and precipitation in the region, along with increase in streamflow of major rivers. Such trends are already apparent in some sub-basins of the western IHR. The region is particularly vulnerable to changing climate as it is highly dependent on snow and glacier melt run-off to meet its freshwater demands. We present a systematic review of key papers dealing with changing temperature, precipitation, glaciers, and streamflow in the IHR. We discuss these interdisciplinary themes in relation to each other, in order to establish the present and future impacts of climatic, glaciological, and hydrological changes in the region.
|
|
| 9. |
- Aich, Pijush Kanti, et al.
(författare)
-
Enhancement of Photosensitivity in a Low-Operating-Voltage Organic-Inorganic Bilayer Thin-Film Transistor by Using an Asymmetric Source-Drain Electrode
- 2024
-
Ingår i: ACS Photonics. - 2330-4022. ; In Press
-
Tidskriftsartikel (refereegranskat)abstract
- A solution-processed inorganic-organic bilayer semiconductor channel-based red-light-sensitive thin-film transistor (TFT) has been fabricated by using an ion-conducting Li-Al2O3 gate dielectric that limits the operating voltage of this TFT within 2 V. In this device, a high-electron-mobility inorganic metal-oxide semiconductor (SnO2) was used as the primary charge transport layer, whereas the polymer (PIDT-2TPD) was used as the photoactive layer. To improve its red photosensitivity, an asymmetric work function source-drain (S-D) electrode was fabricated, which allows a selective carrier (electron or hole) injection and collection from the channel. Besides, the work function difference of this asymmetric S-D electrode generates a potential difference between electrodes that allows faster charge collection from the channel. As a consequence, the photosensitivity of this asymmetric S-D electrode TFT enhanced by ∼103 times under red illumination with respect to the symmetric S-D electrode TFT and the detectivity of this device increased ∼20 times. In addition, the on/off ratio of asymmetric TFT is 4 times greater than that of the symmetric TFT, whereas the subthreshold swing (SS) of this TFT is reduced from 200 to 144 mV/decade.
|
|
| 10. |
- Chavez, Juan D, et al.
(författare)
-
A General Method for Targeted Quantitative Cross-Linking Mass Spectrometry.
- 2016
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
-
Tidskriftsartikel (refereegranskat)abstract
- Chemical cross-linking mass spectrometry (XL-MS) provides protein structural information by identifying covalently linked proximal amino acid residues on protein surfaces. The information gained by this technique is complementary to other structural biology methods such as x-ray crystallography, NMR and cryo-electron microscopy[1]. The extension of traditional quantitative proteomics methods with chemical cross-linking can provide information on the structural dynamics of protein structures and protein complexes. The identification and quantitation of cross-linked peptides remains challenging for the general community, requiring specialized expertise ultimately limiting more widespread adoption of the technique. We describe a general method for targeted quantitative mass spectrometric analysis of cross-linked peptide pairs. We report the adaptation of the widely used, open source software package Skyline, for the analysis of quantitative XL-MS data as a means for data analysis and sharing of methods. We demonstrate the utility and robustness of the method with a cross-laboratory study and present data that is supported by and validates previously published data on quantified cross-linked peptide pairs. This advance provides an easy to use resource so that any lab with access to a LC-MS system capable of performing targeted quantitative analysis can quickly and accurately measure dynamic changes in protein structure and protein interactions.
|
|
| 11. |
|
|
| 12. |
- Mata Las Heras, Erika, 1980, et al.
(författare)
-
Regionalization of buildings-stock description as basis for evaluating energy conservation measures - South East Norway and South West Sweden
- 2014
-
Ingår i: World Sustainable Building 2014 Conference. - 9788469718155
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a description of regional building stocks in the South West of Sweden and the South East of Norway and provides a first validation by means of modelled Final Energy Demand, which is compared with available statistics. The aim of the work is to provide a basis for modelling the assessment of effects and costs of various energy conservation measures applied to the existing building stocks of regions within a country. The aggregated descriptions of the national building stocks of Sweden and Norway through representative buildings are downscaled to the regions. We conclude that the uncertainty in the methodology applied is higher for the regions than for the national level, due primarily to less data available for validation than on the national level. This uncertainty raises concern about how targets on increased energy efficiency and emissions reductions and are going to be monitored, if such targets are to be fulfilled.
|
|
| 13. |
- Sanjiv, Kumar, et al.
(författare)
-
MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia
- 2021
-
Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:22, s. 5733-5744
-
Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin−CD34+CD38−), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial.
|
|
| 14. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
A Perspective on Oral Immunotherapeutic Tools and Strategies for Autoimmune Disorders
- 2023
-
Ingår i: Vaccines. - Basel : MDPI. - 2076-393X. ; 11:6
-
Forskningsöversikt (refereegranskat)abstract
- Oral immune tolerance is a physiological process to achieve tolerance against autoimmunity by oral ingestion of self-antigen(s) or other therapeutics. At the cellular level, oral tolerance suppresses autoimmune diseases by activating FoxP-positive and -negative regulatory T cells (Tregs) and/or causing clonal anergy or deletion of autoreactive T cells, affecting B cell tolerance. However, oral delivery of antigens/biologics is challenging due to their instability in the harsh environment of the gastrointestinal (GI) tract. Several antigen/drug delivery tools and approaches, including micro/nanoparticles and transgenic plant-based delivery systems, have been explored to demonstrate oral immune tolerance for different autoimmune diseases successfully. However, despite the effectiveness, variation in results, dose optimization, and undesirable immune system activation are the limitations of the oral approach to further advancement. From this perspective, the current review discusses the oral tolerance phenomenon, cellular mechanisms, antigen delivery tools and strategies, and its challenges. © 2023 by the authors.
|
|
| 15. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
An update on smart biocatalysts for industrial and biomedical applications
- 2018
-
Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 15:139
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, smart biocatalysts, where enzymes are conjugated to stimuli-responsive (smart) polymers, have gained significant attention. Based on the presence or absence of external stimuli, the polymer attached to the enzyme changes its conformation to protect the enzyme from the external environment and regulate the enzyme activity, thus acting as a molecular switch. Owing to this behaviour, smart biocatalysts can be separated easily from a reaction mixture and re-used several times. Several such smart polymer-based biocatalysts have been developed for industrial and biomedical applications. In addition, they have been used in biosensors, biometrics and nano-electronic devices. This review article covers recent advances in developing different kinds of stimuli-responsive enzyme bioconjugates, including conjugation strategies, and their applications.
|
|
| 16. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Antigen-Specific Tolerization and Targeted Delivery as Therapeutic Strategies for Autoimmune Diseases
- 2018
-
Ingår i: Trends in Biotechnology. - Cambridge, MA : Elsevier. - 0167-7799 .- 1879-3096. ; 36:7, s. 686-699
-
Forskningsöversikt (refereegranskat)abstract
- The prevalence of autoimmune disorders is increasing steadily and there is no permanent cure available. Immunomodulation through repeated exposure of antigens, known as antigen-specific immune tolerance or antigen-specific immunotherapy (ASI), is a promising approach to treat or prevent autoimmune disorders. Different optimization protocols (immunization routes, delivery systems, and approaches) are being developed to implement ASI against self-proteins. Including appropriate adjuvants, altered peptide ligand, and using multipeptides are approaches that can be used to specifically target autoimmunity. This review explores various ASI application methods, including different routes of antigen-specific sensitization, delivery systems, immunomodulators containing specific antigens, and other targeted approaches that have been successfully demonstrated to have therapeutic effects on autoimmune diseases. © 2018 Elsevier Ltd.
|
|
| 17. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Applications of nanomaterials for activation and suppression of immune responses
- 2014
-
Ingår i: Handbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering. - Pennsylvania, USA : IGI Global. - 9781466663633 - 1466663634 ; , s. 205-220
-
Bokkapitel (refereegranskat)abstract
- Evaluation of immuno-modulating properties of nanomaterials is important to develop new potential therapeutics for inflammatory diseases and cancer. Activation and suppressive effects of nanomaterials on immune responses occur through various interactions with different host proteins. They can also be engineered as carriers and/or adjuvants for different proteins or antigens. Particles, emulsions, and tubes/rods are the major formats of nanomaterials currently used in biomedical applications. Sometimes, nanomaterials induce side effects like undesired immunosuppression and toxicities, which are major concerns at present in designing optimal nanotherapeutics. This chapter summarizes different types of nanomaterials and their effect on immune responses. © 2015 by IGI Global. All rights reserved.
|
|
| 18. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases
- 2013
-
Ingår i: Journal of the Royal Society Interface. - London : Royal Society Publishing. - 1742-5689 .- 1742-5662. ; 10:79
-
Tidskriftsartikel (refereegranskat)abstract
- Polymers as an adjuvant are capable of enhancing the vaccine potential against various infectious diseases and also are being used to study the actual autoimmune responses using self-antigen(s) without involving any major immune deviation. Several natural polysaccharides and their derivatives originating from microbes and plants have been tested for their adjuvant potential. Similarly, numerous synthetic polymers including polyelectrolytes, polyesters, polyanhydrides, non-ionic block copolymers and external stimuli responsive polymers have demonstrated adjuvant capacity using different antigens. Adjuvant potential of these polymers mainly depends on their solubility, molecular weight, degree of branching and the conformation of polymeric backbone. These polymers have the ability not only to activate humoral but also cellular immune responses in the host. The depot effect, which involves slow release of antigen over a long duration of time, using different forms (particulate, solution and gel) of polymers, and enhances the co-stimulatory signals for optimal immune activation, is the underlying principle of their adjuvant properties. Possibly, polymers may also interact and activate various toll-like receptors and inflammasomes, thus involving several innate immune system players in the ensuing immune response. Biocompatibility, biodegradability, easy production and purification, and non-toxic properties of most of the polymers make them attractive candidates for substituting conventional adjuvants that have undesirable effects in the host. © 2012 The Author(s) Published by the Royal Society. All rights reserved.
|
|
| 19. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Biomaterials for induction and treatment of autoimmunity
- 2017
-
Ingår i: Advances in Biomaterials for Biomedical Applications. - Singapore : Springer. - 9789811033278 - 9789811033285 ; , s. 167-184
-
Bokkapitel (refereegranskat)abstract
- Use of biomaterials in autoimmunity research is widely explored, as an adjuvant to induce antigen specific immune responses, for facilitating induction of experimental models to study disease pathogenesis and for designing novel therapeutic targets. Similarly, polymeric biomaterials are explored as a delivery vehicle for sustained and specific release of auto-antigens/drugs to treat autoimmune disorders. Although considered as biocompatible, implantation/injection of polymers like silica and metallic implants are associated with development of chronic inflammation and autoimmunity. Despite these compatibility concerns, biomaterials are still considered as favorable materials for several applications in the autoimmunity field.
|
|
| 20. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Nano-size based drug delivery systems for autoimmune diseases
- 2019. - 1
-
Ingår i: Autoimmune diseases. - USA : Nova Science Publishers, Inc.. - 1536160466 - 9781536160468 ; , s. 245-270
-
Bokkapitel (refereegranskat)abstract
- Autoimmune diseases are polygenic and multifactorial, which target different organs either specifically or systematically. The prevalence of these autoimmune diseases is steadily increasing worldwide. Recently, many new drugs are successfully marketed to treat these diseases. However, currently available drugs are rapidly metabolized in their free form after administered into the body, thus cleared off before reaching to the target organ(s) in optimal concentrations. During last few decades, several carrier systems in nano-sized form have been developed to maintain sustained release of these drugs for longer period of time and also to moderate the toxicity profile of these drugs. These drug carrier systems include nano-sized liposomes, metallic nanoparticles (NPs), micelles, stimuli-responsive NPs, nano-emulsions and the nano-gels. These carriers are successfully demonstrated for the delivery of different drugs and their therapeutic or preventive potential has been assessed in different experimental conditions. In this chapter we have updated our current knowledge on these nano-sized carriers, and their in vitro and in vivo therapeutic efficacy using, rheumatoid arthritis (RA), as main example autoimmune disorder. © 2004 - 2023 Nova Science Publishers
|
|
| 21. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Nanobiocatalysts for Industrial Applications
- 2019
-
Ingår i: Characterization and Biology of Nanomaterials for Drug Delivery. - Amsterdam : Elsevier. - 9780128140314 ; , s. 553-562
-
Bokkapitel (refereegranskat)abstract
- During the past several decades, various types of nanocarriers have been explored for the development of stable and reusable biocatalysts to improve traditional enzyme immobilization approaches. These include polymeric nanoparticles (NPs), magnetic NPs, nanofibers, and nanotubes, which offer high enzyme-loading efficacy due to large surface area, excellent diffusivity of solutes, and easy separation procedures from the reaction medium. These nanobiocatalysts show functional and structural stabilities at different temperatures and pH conditions compared to the free enzyme. They also retain significant catalytic activities after several days under different storage conditions. Thus, these nanobiocatalysts represent an attractive format of biocatalyst preparations for different industrial applications.
|
|
| 22. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
New generation vaccines : need for safe and improved adjuvants
- 2014
-
Ingår i: Vaccines and Vaccine Technologies. - Foster City,CA : OMICS Group International.
-
Bokkapitel (refereegranskat)abstract
- Vaccines are formulated to generate strong immune responses against administered antigens thereby providing long-term immunity,especially against microbial infections. To achieve this goal, safe and optimal vaccines are designed by developing new generationvaccines with efficacious adjuvants. These vaccines are mainly based on recombinant forms of protein subunits that are purified frommolecular constructs of microbial agents with known chemical structures. However, these vaccines are poorly immunogenic and thuscannot induce an appropriate protective immune response. Therefore, to increase in vivo efficacy and stability of these vaccines, a safeand improved adjuvant is essential. Adjuvants in human vaccine formulations should be non-toxic, biologically inert, biocompatible,biodegradable as well as capable of facilitating the induction of antigen-specific immune responses. Currently, alum compounds are theonly adjuvants approved in human vaccines. Though many clinically tested adjuvants more potent than alum are available, safety andregulatory concerns preclude their use for human applications. To address life-threatening pandemic diseases and ever evolving drug-resistant microbial infections worldwide, designing vaccines with safe and efficacious adjuvant is a major challenge for the scientificcommunity that needs to be addressed systematically. © 2014 OMICS Group
|
|
| 23. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Polymer Chemistry Defines Adjuvant Properties and Determines the Immune Response against the Antigen or Vaccine
- 2023
-
Ingår i: Vaccines. - Basel : MDPI. - 2076-393X. ; 11:9
-
Forskningsöversikt (refereegranskat)abstract
- Activation of the immune system is a needed for designing new antigen/drug delivery systems to develop new therapeutics and for developing animal disease models to study the disease pathogenesis. A weak antigen alone is insufficient to activate the immune system. Sometimes, assistance in the form of polymers is needed to control the release of antigens under in vivo conditions or in the form of an adjuvant to activate the immune system efficiently. Many kinds of polymers from different functional groups are suitable as microbial antigens for inducing therapeutic immune responses against infectious diseases at the preclinical level. The choice of the functionality of polymer varies as per the application type. Polymers from the acid and ester groups are the most common types investigated for protein-based antigens. However, electrostatic interaction-displaying polymers like cationic polymers are the most common type for nucleic acid-based antigens. Metal coordination chemistry is commonly used in polymers designed for cancer immunotherapeutic applications to suppress inflammation and induce a protective immune response. Amide chemistry is widely deployed in polymers used to develop antigen-specific disease models like the experimental autoimmune arthritis murine model. © 2023 by the authors.
|
|
| 24. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Stimuli responsive polymers as adjuvants and carriers for antigen delivery
- 2013. - 1
-
Ingår i: Responsive Materials and Methods. - Hoboken, NJ, USA : Wiley-Scrivener Publishing LLC. - 9781118686225 - 9781118842843 ; , s. 123-139
-
Bokkapitel (refereegranskat)abstract
- Stimuli responsive polymers are gaining importance in immunology not only as carriers for delivering antigens to target tissues but also as immunologically inert adjuvants. Delivery of antigens in the presence or absence of a specific stimulus like pH, temperature, ionic strength offers wide range of application possibilities to these smart polymers including vaccine formulations, implantation studies, targeted therapies and induction of autoimmunity. Other properties of polymers such as biocompatibility, biodegradability with different kinetics, non-toxicity, easy and defined chemical synthesis and, the ability to incorporate different types of antigens/immuno-stimulators make them promising candidates over other conventional materials for biomedical applications. Activation or suppression of antigen-specific immune responses and protection of antigens from in vivo degradation are some of the other advantages with these polymers. Changes in physical conformation of the polymers due to an environment stimulus provide an optimal release of an antigen. Varying the ratio of monomers and cross linkers in their synthesis controlled the release of antigens and degradation of polymers. In particulate form (as nano-sized) polymers can efficiently encapsulate desired amount of antigens, which can easily cross across several biological barriers. However, adjuvant and carrier properties of these smart polymers depend not only on their intrinsic properties such as chain length, molecular weight, charge and a balance between hydrophobic and hydrophilic functional moieties but also on extrinsic properties like format, shape and distribution of polymeric chains. In conclusion, further characterization of smart polymers could facilitate their direct application in humans.
|
|
| 25. |
- Shakya, Akhilesh Kumar, et al.
(författare)
-
Synthetic polymer as an adjuvant in collagen-induced arthritis
- 2014
-
Ingår i: Current protocols in mouse biology. - Hoboken, NJ : John Wiley & Sons. - 2161-2617. ; 4:1, s. 11-24
-
Tidskriftsartikel (refereegranskat)abstract
- Collagen-induced arthritis (CIA), the classical animal model for experimental arthritis, resembles human rheumatoid arthritis in several aspects. However, the most widely used method of inducing CIA utilizes Freund's adjuvants, which can skew the elicited immune responses and also pose toxicity problems. This unit describes a new method of inducing CIA using a well defined stimuli-responsive synthetic polymer, poly-N-isopropylacrylamide-based adjuvant, mixed with the joint cartilage protein collagen type II (CII). PNiPAAm as an adjuvant is biodegradable and biocompatible, and does not skew immune responses. Thus, it is helpful in the development of arthritis models for studying antigen and tissue -specific autoimmune responses in an unbiased manner. This model is valuable for analyzing disease pathways, positional identification of genes regulating arthritis, validation of existing therapies, and exploring new therapeutic targets. Furthermore, this newly developed PNiPAAm adjuvant allows investigation of disease induction using specific autoantigens in several autoimmune diseases independently of toll-like receptors, as well as optimization of vaccine delivery systems for infectious diseases. © 2014 John Wiley & Sons, Inc.
|
|
| 26. |
- Shukla, Sanjay, et al.
(författare)
-
Inertial particles in superfluid turbulence : Coflow and counterflow
- 2023
-
Ingår i: Physics of fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 35:1, s. 015153-
-
Tidskriftsartikel (refereegranskat)abstract
- We use pseudospectral direct numerical simulations to solve the three-dimensional (3D) Hall-Vinen-Bekharevich-Khalatnikov (HVBK) model of superfluid helium. We then explore the statistical properties of inertial particles, in both coflow and counterflow superfluid turbulence (ST) in the 3D HVBK system; particle motion is governed by a generalization of the Maxey-Riley-Gatignol equations. We first characterize the anisotropy of counterflow ST by showing that there exist large vortical columns. The light particles show confined motion as they are attracted toward these columns, and they form large clusters; by contrast, heavy particles are expelled from these vortical regions. We characterize the statistics of such inertial particles in 3D HVBK ST: (1) The mean angle (SIC)(tau) between particle positions, separated by the time lag r, exhibits two different scaling regions in (a) dissipation and (b) inertial ranges, for different values of the parameters in our model; in particular, the value of (SIC)(tau), at large r, depends on the magnitude of U-ns. (2) The irreversibility of 3D HVBK turbulence is quantified by computing the statistics of energy increments for inertial particles. (3) The probability distribution function (PDF) of energy increments is of direct relevance to recent experimental studies of irreversibility in superfluid turbulence; we find, in agreement with these experiments, that, for counterflow ST, the skewness of this PDF is less pronounced than its counterparts for coflow ST or for classical fluid turbulence.
|
|
| 27. |
- Verma, Akhilesh Kumar, et al.
(författare)
-
First-passage-time problem for tracers in turbulent flows applied to virus spreading
- 2020
-
Ingår i: Physical Review Research. - : American Physical Society (APS). - 2643-1564. ; 2:3
-
Tidskriftsartikel (refereegranskat)abstract
- We study the spreading of viruses, such as SARS-CoV-2, by airborne aerosols, via a first-passage-time problem for Lagrangian tracers that are advected by a turbulent flow: By direct numerical simulations of the three-dimensional (3D) incompressible Navier-Stokes equation, we obtain the time t(R) at which a tracer, initially at the origin of a sphere of radius R, crosses the surface of the sphere for the first time. We obtain the probability distribution function P(R, t(R)) and show that it displays two qualitatively different behaviors: (a) for R << L-I, P(R, t(R)) has a power-law tail similar to t(R)(-alpha), with the exponent alpha = 4 and L-I the integral scale of the turbulent flow; (b) for L-I less than or similar to R, the tail of P(R, t(R)) decays exponentially. We develop models that allow us to obtain these asymptotic behaviors analytically. We show how to use P(R, t(R)) to develop social-distancing guidelines for the mitigation of the spreading of airborne aerosols with viruses such as SARS-CoV-2.
|
|
