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  1. AU="Velhal, S"
  2. AU="Lutz, Richard A"
  3. AU="Raveesh Kumar"
  4. AU="Andreas von Deimling"
  5. AU="Erik MeersauthorLaboratory of Analytical and Applied Ecochemistry, Faculty of Bioscience Engineering, University of Ghent, Coupure Links 653, 9000 Ghent, Belgium"
  6. AU="Thakkar, Nitya"
  7. AU="Hongtao Tie"
  8. AU="Bhati, Saurabh Kumar"
  9. AU="Choi, Hyunho"
  10. AU="Jayaprakash, Balamuralikrishna"
  11. AU="Lee, Brian H"
  12. AU="May, Susann"
  13. AU="Remondes-Costa, Sónia"
  14. AU="Lauren Sauer"
  15. AU="G Saiz, Paula"
  16. AU="Stoica, George"
  17. AU=Odorizzi Pamela M.
  18. AU=Pollaers Katherine
  19. AU="Stefanova, Veselina"
  20. AU="Geraldine M. O’Connor"
  21. AU="Jim E. Banta"
  22. AU="Marti-Bonmati, Luis"
  23. AU="Doris Kampner"
  24. AU="Luca Soraci"

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  1. Artikel ; Online: Bioactive phytocompound mulberroside C and endophytes of Morus alba as potential inhibitors of HIV-1 replication: a mechanistic evaluation.

    Vora, J / Velhal, S / Sinha, S / Patel, V / Shrivastava, N

    HIV medicine

    2021  Band 22, Heft 8, Seite(n) 690–704

    Abstract: Objectives: Despite considerable advancement in antiretroviral therapy, development of safe, effective, and multi-targeted drugs for HIV still remains a big challenge. Endophytes are untouched and, hence, an important and novel sources in drug discovery ...

    Abstract Objectives: Despite considerable advancement in antiretroviral therapy, development of safe, effective, and multi-targeted drugs for HIV still remains a big challenge. Endophytes are untouched and, hence, an important and novel sources in drug discovery endeavours. The present study was conducted to identify the anti-HIV compounds from Morus alba and endophytes isolated from it.
    Methods: The extracts of isolated endophytes were screened using high-performance liquid chromatography (HPLC). Further, all samples were analysed for their cytotoxicity using a thiazolyl blue tetrazolium bromide assay. Subsequently, anti-HIV activity was performed using cell-based and cell-free assay. At the end, potential endophytes were identified using gene sequencing.
    Results: A total of 27 endophytes were isolated from the eight stem bark samples of M. alba. Of the 27 endophytes, extracts of total of four endophytes showed a profile similar to the M. alba plant when analysed by HPLC. Further experimentation with extracts of these four endophytes, along with an extract of M. alba stem bark and its bioactive molecule, mulberroside C, revealed that all these six samples have good inhibitory potential for HIV. Among them, mulberroside C and two endophytic fungal extracts showed very potent anti-HIV activity. Subsequently, mechanistic studies at the molecular level showed that out of six test samples, three acted as protease inhibitors. Further, all four potential endophytes were identified using gene sequencing.
    Conclusions: The overall findings of these studies can help in the development of a novel anti-HIV candidate from mulberroside C, an extract of stem bark of M. alba and extracts of these endophytes. However, further validation and clinical studies are required to develop an anti-HIV drug.
    Mesh-Begriff(e) Endophytes/chemistry ; HIV Infections/drug therapy ; HIV-1/drug effects ; HIV-1/physiology ; Humans ; Morus/chemistry ; Morus/microbiology ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Virus Replication/drug effects
    Chemische Substanzen Plant Extracts
    Sprache Englisch
    Erscheinungsdatum 2021-05-14
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2001932-4
    ISSN 1468-1293 ; 1464-2662
    ISSN (online) 1468-1293
    ISSN 1464-2662
    DOI 10.1111/hiv.13116
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  2. Buch ; Online: A Decentralized Spike-based Learning Framework for Sequential Capture in Discrete Perimeter Defense Problem

    Thousif, Mohammed / Velhal, Shridhar / Sundaram, Suresh / Dora, Shirin

    2023  

    Abstract: This paper proposes a novel Decentralized Spike-based Learning (DSL) framework for the discrete Perimeter Defense Problem (d-PDP). A team of defenders is operating on the perimeter to protect the circular territory from radially incoming intruders. At ... ...

    Abstract This paper proposes a novel Decentralized Spike-based Learning (DSL) framework for the discrete Perimeter Defense Problem (d-PDP). A team of defenders is operating on the perimeter to protect the circular territory from radially incoming intruders. At first, the d-PDP is formulated as a spatio-temporal multi-task assignment problem (STMTA). The problem of STMTA is then converted into a multi-label learning problem to obtain labels of segments that defenders have to visit in order to protect the perimeter. The DSL framework uses a Multi-Label Classifier using Synaptic Efficacy Function spiking neuRON (MLC-SEFRON) network for deterministic multi-label learning. Each defender contains a single MLC-SEFRON network. Each MLC-SEFRON network is trained independently using input from its own perspective for decentralized operations. The input spikes to the MLC-SEFRON network can be directly obtained from the spatio-temporal information of defenders and intruders without any extra pre-processing step. The output of MLC-SEFRON contains the labels of segments that a defender has to visit in order to protect the perimeter. Based on the multi-label output from the MLC-SEFRON a trajectory is generated for a defender using a Consensus-Based Bundle Algorithm (CBBA) in order to capture the intruders. The target multi-label output for training MLC-SEFRON is obtained from an expert policy. Also, the MLC-SEFRON trained for a defender can be directly used for obtaining labels of segments assigned to another defender without any retraining. The performance of MLC-SEFRON has been evaluated for full observation and partial observation scenarios of the defender. The overall performance of the DSL framework is then compared with expert policy along with other existing learning algorithms. The scalability of the DSL has been evaluated using an increasing number of defenders.

    Comment: Mohammed Thousif and Shridhar Velhal has equal contribution to this manuscript
    Schlagwörter Computer Science - Robotics ; Computer Science - Artificial Intelligence ; Computer Science - Machine Learning ; Computer Science - Multiagent Systems ; Computer Science - Neural and Evolutionary Computing ; Electrical Engineering and Systems Science - Systems and Control
    Thema/Rubrik (Code) 006
    Erscheinungsdatum 2023-05-26
    Erscheinungsland us
    Dokumenttyp Buch ; Online
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  3. Buch ; Online: Priority-based DREAM Approach for Highly Manoeuvring Intruders in A Perimeter Defense Problem

    Velhal, Shridhar / Sundaram, Suresh / Sundararajan, Narasimhan

    2023  

    Abstract: In this paper, a Priority-based Dynamic REsource Allocation with decentralized Multi-task assignment (P-DREAM) approach is presented to protect a territory from highly manoeuvring intruders. In the first part, static optimization problems are formulated ... ...

    Abstract In this paper, a Priority-based Dynamic REsource Allocation with decentralized Multi-task assignment (P-DREAM) approach is presented to protect a territory from highly manoeuvring intruders. In the first part, static optimization problems are formulated to compute the following parameters of the perimeter defense problem; the number of reserve stations, their locations, the priority region, the monitoring region, and the minimum number of defenders required for the monitoring purpose. The concept of a prioritized intruder is proposed here to identify and handle those critical intruders (computed based on the velocity ratio and location) to be tackled on a priority basis. The computed priority region helps to assign reserve defenders sufficiently earlier such that they can neutralize the prioritized intruders. The monitoring region defines the minimum region to be monitored and is sufficient enough to handle the intruders. In the second part, the earlier developed DREAM approach is modified to incorporate the priority of an intruder. The proposed P-DREAM approach assigns the defenders to the prioritized intruders as the first task. A convex territory protection problem is simulated to illustrate the P-DREAM approach. It involves the computation of static parameters and solving the prioritized task assignments with dynamic resource allocation. Monte-Carlo results were conducted to verify the performance of P-DREAM, and the results clearly show that the P-DREAM approach can protect the territory with consistent performance against highly manoeuvring intruders.
    Schlagwörter Electrical Engineering and Systems Science - Systems and Control ; Computer Science - Multiagent Systems ; Computer Science - Robotics
    Thema/Rubrik (Code) 006
    Erscheinungsdatum 2023-07-19
    Erscheinungsland us
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  4. Artikel ; Online: pH-triggered polymeric nanoparticles in gel for preventing vaginal transmission of HIV and unintended pregnancy.

    Fernandes, Trinette / Patel, Vainav / Aranha, Clara / Velhal, Shilpa / Momin, Munira / Mulkutkar, Madhura / Sawarkar, Sujata

    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

    2023  Band 191, Seite(n) 219–234

    Abstract: Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/ AIDS) and unplanned pregnancy affect female reproductive health globally. A single product providing a dual purpose of HIV prophylaxis and contraception may improve adherence to the ... ...

    Abstract Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/ AIDS) and unplanned pregnancy affect female reproductive health globally. A single product providing a dual purpose of HIV prophylaxis and contraception may improve adherence to the therapy. Thus, we formulated a female-centric multipurpose prevention technology (MPT) comprising of nanoparticle loaded vaginal gel formulation acting as a contraceptive and microbicide. Eudragit® S100 nanoparticles of Atazanavir sulphate (ATZ; antiviral) and Fluoxetine hydrochloride (FLX; repurposed spermicide) were prepared for pH dependent drug release and loaded in carrageenan and HPMC K200M gel. The particle size of ATZ and FLX nanoparticles was 396.7 ± 20.64 nm and 226.5 ± 2.08 nm respectively. The in vitro release of the gel formulation in simulated seminal fluid (pH 7.6) showed 96.16% and 95.98% release of ATZ and FLX respectively at the end of 8 h. The in vitro anti-HIV and spermicidal activity of the formulation was above 80% for low drug concentrations. In vivo studies on murine model showed no signs of inflammation or vaginal epithelial injury. Curcumin based imaging confirmed the retention of the formulation in the reproductive tract of mice with minimal leakage. Nanoparticles in gel enabled non-invasive and localised delivery with minimal side effects and can be an effective prophylactic therapy.
    Mesh-Begriff(e) Pregnancy ; Female ; Humans ; Animals ; Mice ; HIV ; Pregnancy, Unplanned ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; Spermatocidal Agents ; Nanoparticles ; Hydrogen-Ion Concentration
    Chemische Substanzen Spermatocidal Agents
    Sprache Englisch
    Erscheinungsdatum 2023-09-03
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 1065368-5
    ISSN 1873-3441 ; 0939-6411
    ISSN (online) 1873-3441
    ISSN 0939-6411
    DOI 10.1016/j.ejpb.2023.09.001
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  5. Buch ; Online: A Dynamic Heterogeneous Team-based Non-iterative Approach for Online Pick-up and Just-In-Time Delivery Problems

    Velhal, Shridhar / R, Srikrishna B / Bharatheesha, Mukunda / Sundaram, Suresh

    2023  

    Abstract: This paper presents a non-iterative approach for finding the assignment of heterogeneous robots to efficiently execute online Pickup and Just-In-Time Delivery (PJITD) tasks with optimal resource utilization. The PJITD assignments problem is formulated as ...

    Abstract This paper presents a non-iterative approach for finding the assignment of heterogeneous robots to efficiently execute online Pickup and Just-In-Time Delivery (PJITD) tasks with optimal resource utilization. The PJITD assignments problem is formulated as a spatio-temporal multi-task assignment (STMTA) problem. The physical constraints on the map and vehicle dynamics are incorporated in the cost formulation. The linear sum assignment problem is formulated for the heterogeneous STMTA problem. The recently proposed Dynamic Resource Allocation with Multi-task assignments (DREAM) approach has been modified to solve the heterogeneous PJITD problem. At the start, it computes the minimum number of robots required (with their types) to execute given heterogeneous PJITD tasks. These required robots are added to the team to guarantee the feasibility of all PJITD tasks. Then robots in an updated team are assigned to execute the PJITD tasks while minimizing the total cost for the team to execute all PJITD tasks. The performance of the proposed non-iterative approach has been validated using high-fidelity software-in-loop simulations and hardware experiments. The simulations and experimental results clearly indicate that the proposed approach is scalable and provides optimal resource utilization.
    Schlagwörter Computer Science - Multiagent Systems ; Computer Science - Robotics ; Electrical Engineering and Systems Science - Systems and Control
    Erscheinungsdatum 2023-04-14
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  6. Buch ; Online: A Non-iterative Spatio-temporal Multi-task Assignments based Collision-free Trajectories for Music Playing Robots

    Velhal, Shridhar / VS, Krishna Kishore / Sundaram, Suresh

    2022  

    Abstract: In this paper, a non-iterative spatio-temporal multi-task assignment approach is used for playing piano music by a team of robots. This paper considers the piano playing problem, in which an algorithm needs to compute the trajectories for a dynamically ... ...

    Abstract In this paper, a non-iterative spatio-temporal multi-task assignment approach is used for playing piano music by a team of robots. This paper considers the piano playing problem, in which an algorithm needs to compute the trajectories for a dynamically sized team of robots who will play the musical notes by traveling through the specific locations associated with musical notes at their respective specific times. A two-step dynamic resource allocation based on a spatio-temporal multi-task assignment problem (DREAM), has been implemented to assign robots for playing the musical tune. The algorithm computes the required number of robots to play the music in the first step. In the second step, optimal assignments are computed for the updated team of robots, which minimizes the total distance traveled by the team. Even for the individual feasible trajectories, the multi-robot execution may fail if robots encounter a collision. As some time will be utilized for this conflict resolution, robots may not be able to reach the desired location on time. This paper analyses and proves that, if robots are operating in a convex region, the solution of the DREAM approach provides collision-free trajectories. The working of the DREAM approach has been illustrated with the help of the high fidelity simulations in Gazebo operated using ROS2. The result clearly shows that the DREAM approach computes the required number of robots and assigns multiple tasks to robots in at most two steps. The simulation of the robots playing music, using computed assignments, is demonstrated in the attached video. video link: \url{https://youtu.be/XToicNm-CO8}
    Schlagwörter Computer Science - Robotics ; Computer Science - Multiagent Systems ; Electrical Engineering and Systems Science - Systems and Control
    Thema/Rubrik (Code) 629 ; 780
    Erscheinungsdatum 2022-10-14
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  7. Artikel ; Online: Highly dampened HIV-specific cytolytic effector T cell responses define viremic non-progression.

    Kumar Singh, Amit / Padwal, Varsha / Palav, Harsha / Velhal, Shilpa / Nagar, Vidya / Patil, Priya / Patel, Vainav

    Immunobiology

    2022  Band 227, Heft 4, Seite(n) 152234

    Abstract: This study reports on HIV-specific T cell responses in HIV-1 infected Viremic Non-Progressors (VNPs), a rare group of people living with HIV that exhibit asymptomatic infection over several years accompanied by stable CD4+ T cell counts in spite of ... ...

    Abstract This study reports on HIV-specific T cell responses in HIV-1 infected Viremic Non-Progressors (VNPs), a rare group of people living with HIV that exhibit asymptomatic infection over several years accompanied by stable CD4+ T cell counts in spite of ongoing viral replication. We attempted to identify key virus-specific functional attributes that could underlie the apparently paradoxical virus-host equilibrium observed in VNPs. Our results revealed modulation of HIV-specific CD4+ and CD8+ effector T cell responses in VNPs towards a dominant non-cytolytic profile with concomitantly diminished degranulation (CD107a+) ability. Further, the HIV specific CD8+ effector T cell response was primarily enriched for MIP-1β producing cells. As expected, concordant with better viral suppression, VCs exhibit a robust cytolytic T cell response. Interestingly, PuPs shared features common to both these responses but did not exhibit a CD4+ central memory IFN-γ producing Gag-specific response that was shared by both non-progressor (VC and VNP) groups, suggesting CD4 helper response is critical for non-progression. Our study also revealed that cytolytic response in VNPs is primarily limited to polyfunctional cells while both monofunctional and polyfunctional cells significantly contribute to cytolytic responses in VCs. To further understand mechanisms underlying the unique HIV-specific effector T cell response described here in VNPs we also evaluated and demonstrated a possible role for altered gut homing in these individuals. Our findings inform immunotherapeutic interventions to achieve functional cures in the context of ART resistance and serious non AIDS events.
    Mesh-Begriff(e) CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; HIV Infections ; HIV-1/physiology ; Humans ; T-Lymphocytes, Cytotoxic ; Viral Load ; Viremia
    Sprache Englisch
    Erscheinungsdatum 2022-06-02
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 563292-4
    ISSN 1878-3279 ; 0171-2985
    ISSN (online) 1878-3279
    ISSN 0171-2985
    DOI 10.1016/j.imbio.2022.152234
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  8. Artikel ; Online: Integrated immune monitoring of HCMV infection in pregnant women with complications and its association with adverse pregnancy outcomes.

    Palav, Harsha Chandrashekhar / Bhonde, Gauri / Padwal, Varsha / Velhal, Shilpa / Pereira, Jacintha / Singh, Amit Kumar / Ghosh, Sayantani / Karandikar, Kalyani / Satoskar, Purnima / Bhor, Vikrant / Patel, Vainav

    Microbial pathogenesis

    2023  Band 179, Seite(n) 106109

    Abstract: Human Cytomegalovirus (HCMV) infection is associated with bad obstetric history (BOH) and adverse pregnancy outcomes (APO). Here, we characterized antiviral humoral profiles, systemic and virus specific cellular immune responses concurrently in pregnant ... ...

    Abstract Human Cytomegalovirus (HCMV) infection is associated with bad obstetric history (BOH) and adverse pregnancy outcomes (APO). Here, we characterized antiviral humoral profiles, systemic and virus specific cellular immune responses concurrently in pregnant women (n = 67) with complications including BOH and associated these signatures with pregnancy outcomes. Infection status was determined using nested blood PCR, seropositivity and IgG avidity by ELISA. Systemic and HCMV specific (pp65) cellular immune responses were evaluated by flow cytometry. Seropositivity was determined for other TORCH pathogens (n = 33) on samples with recorded pregnancy outcomes. This approach was more sensitive in detecting HCMV infection. Blood PCR positive participants, irrespective of their IgG avidity status, had higher cytotoxic potential in circulating CD8
    Mesh-Begriff(e) Pregnancy ; Humans ; Female ; Pregnancy Outcome ; Pregnant Women ; Cytomegalovirus Infections/diagnosis ; Pregnancy Complications, Infectious ; CD8-Positive T-Lymphocytes ; Monitoring, Immunologic ; Cytomegalovirus ; Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
    Chemische Substanzen Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
    Sprache Englisch
    Erscheinungsdatum 2023-04-09
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 632772-2
    ISSN 1096-1208 ; 0882-4010
    ISSN (online) 1096-1208
    ISSN 0882-4010
    DOI 10.1016/j.micpath.2023.106109
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  9. Artikel ; Online: A novel gut microbiome-immune axis influencing pathology in HCMV infected infants with neonatal cholestasis.

    Karandikar, Kalyani / Bhonde, Gauri / Palav, Harsha / Padwal, Varsha / Velhal, Shilpa / Pereira, Jacintha / Meshram, Himali / Goel, Akshat / Shah, Ira / Patel, Vainav / Bhor, Vikrant M

    Microbes and infection

    2023  Band 25, Heft 7, Seite(n) 105165

    Abstract: The interplay of active HCMV infection with gut dysbiosis in the immunopathology of cholestasis in neonates and infants remains unexplored. In this study, we evaluated gut microbiome profiles and immune dysfunction in a cohort of HCMV infected ... ...

    Abstract The interplay of active HCMV infection with gut dysbiosis in the immunopathology of cholestasis in neonates and infants remains unexplored. In this study, we evaluated gut microbiome profiles and immune dysfunction in a cohort of HCMV infected cholestatic infants (IgM positive, N = 21; IgM negative, N = 25) compared to healthy infants, N = 10. HCMV infected IgM positive individuals exhibited increased clinical severity in terms of liver dysfunction, altered CD4
    Mesh-Begriff(e) Infant, Newborn ; Humans ; Infant ; Granzymes ; Gastrointestinal Microbiome ; Cholestasis/microbiology ; Liver Diseases ; Cytomegalovirus Infections ; Immunoglobulin M
    Chemische Substanzen Granzymes (EC 3.4.21.-) ; Immunoglobulin M
    Sprache Englisch
    Erscheinungsdatum 2023-05-27
    Erscheinungsland France
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1465093-9
    ISSN 1769-714X ; 1286-4579
    ISSN (online) 1769-714X
    ISSN 1286-4579
    DOI 10.1016/j.micinf.2023.105165
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  10. Artikel ; Online: Small double-stranded RNA with anti-HIV activity abundantly produced by Bacillus subtilis MTCC5480 isolated from fermented soybean.

    Imrat / Labala, Rajendra Kumar / Velhal, Shilpa / Bhagat, Sharad / Patel, Vainav / Jeyaram, Kumaraswamy

    International journal of biological macromolecules

    2020  Band 161, Seite(n) 828–835

    Abstract: Anti-viral RNA therapy is on high demand nowadays due to the emergence of several new viral infections. The small non-coding regulatory RNAs (dsRNA) from the microbial sources are not yet explored for anti-viral activity. In this study, we assessed the ... ...

    Abstract Anti-viral RNA therapy is on high demand nowadays due to the emergence of several new viral infections. The small non-coding regulatory RNAs (dsRNA) from the microbial sources are not yet explored for anti-viral activity. In this study, we assessed the anti-HIV activity of the small dsRNA produced by 12 different microbial species isolated from naturally fermented foods of North-East India. For this, we selectively extracted the dsRNA from the microbial culture, confirmed its double-stranded nature by immunoblotting, and deep sequenced the cDNA library using Illumina platform. Further, we used conventional algorithms to predict the potential targets of the dsRNA sequences within the 3'-UTR region of HIV-1. A small dsRNA fragment with 34 bases in size with a sequence of 3'-UUGGUACACGAGAUGGUUCGACUCGAUGAAGGGC-5' produced abundantly (9.17% of the total dsRNA fraction) by Bacillus subtilis MTCC5480 showed a much higher base complementarity values than previously reported miRNAs analysed against HIV-1. We separated the dsRNA fraction and validated the anti-HIV activity against human peripheral blood mononuclear cells (PBMC) infected with JRCSF strain of HIV-1 virus and the EC
    Mesh-Begriff(e) 3' Untranslated Regions/genetics ; Anti-HIV Agents/pharmacology ; Antiviral Agents/pharmacology ; Bacillus subtilis/genetics ; Cell Line ; Cells, Cultured ; Fermentation/genetics ; Fermented Foods/microbiology ; HIV-1/drug effects ; Humans ; Leukocytes, Mononuclear/microbiology ; Leukocytes, Mononuclear/virology ; RNA, Double-Stranded/genetics ; Glycine max/microbiology
    Chemische Substanzen 3' Untranslated Regions ; Anti-HIV Agents ; Antiviral Agents ; RNA, Double-Stranded
    Sprache Englisch
    Erscheinungsdatum 2020-06-15
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 282732-3
    ISSN 1879-0003 ; 0141-8130
    ISSN (online) 1879-0003
    ISSN 0141-8130
    DOI 10.1016/j.ijbiomac.2020.06.112
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