RESEARCH PUBLICATIONS

Research Articles

The Good, The Bad and The Ugly: A Mathematical Model Investigates the Differing Outcomes Among CoVID-19 Patients

Sarthak Sahoo, Siddharth Jhunjhunwala & Mohit Kumar Jolly. J Indian Inst Sci (2020). DOI:10.1007/s41745-020-00205-1

The disease caused by SARS-CoV-2—CoVID-19—is a global pandemic that has brought severe changes worldwide. Approximately 80% of the infected patients are largely asymptomatic or have mild symptoms such as fever or cough, while rest of the patients display varying degrees of severity of symptoms, with an average mortality rate of 3–4%. Severe symptoms such as pneumonia and acute respiratory distress syndrome may be caused by tissue damage, which is mostly due to aggravated and unresolved innate and adaptive immune response, often resulting from a cytokine storm. Here, we discuss how an intricate interplay among infected cells and cells of innate and adaptive immune system can lead to such diverse clinicopathological outcomes. Particularly, we discuss how the emergent nonlinear dynamics of interaction among the components of adaptive and immune system components and virally infected cells can drive different disease severity. Such minimalistic yet rigorous mathematical modeling approaches are helpful in explaining how various co-morbidity risk factors, such as age and obesity, can aggravate the severity of CoVID-19 in patients. Furthermore, such approaches can elucidate how a fine-tuned balance of infected cell killing and resolution of inflammation can lead to infection clearance, while disruptions can drive different severe phenotypes. These results can help further in a rational selection of drug combinations that can effectively balance viral clearance and minimize tissue damage.

Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors Driving Pathogenesis of SARS-CoV-2

Ashary N, Bhide A, Chakraborty P, Colaco S, Mishra A, Chhabria K, Jolly MK, and Modi D. Frontiers in Cell and Developmental Biology (2020). DOI:10.3389/fcell.2020.00783

Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease COVID-19, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications such as preterm labor and premature rupture of membranes, and a proportion of neonates born to infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. To predict if the placenta is permissive to SARS-CoV-2, we utilized publicly available single-cell RNA-seq data to identify if the placental cells express the necessary factors required for infection. SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extravillous trophoblasts (EVT) in the second trimester human placenta. In addition, the non-canonical receptor BSG/CD147 and other proteases (CTSL, CTSB, and FURIN) are detected in most of the placental cells. Other coronavirus family receptors (ANPEP and DPP4) were also expressed in the first and second trimester placental cells. Additionally, the term placenta of multiple species including humans expressed ACE2, DPP4, and ANPEP along with the viral S protein proteases. The ACE2- and TMPRSS2-positive (ACE2 + TMPRSS2 +) placental subsets expressed mRNA for proteins involved in viral budding and replication. These cells also had the mRNA for proteins that physically interact with SARS-CoV-2 in host cells. Further, we discovered unique signatures of genes in ACE2 + TMPRSS2 + STBs and EVTs. The ACE2 + TMPRSS2 + STBs are highly differentiated cells and express genes involving mitochondrial metabolism and glucose transport. The second trimester ACE2 + TMPRSS2 + EVTs are enriched for markers of endovascular trophoblasts. Both these subtypes abundantly expressed genes in the Toll-like receptor pathway. The second trimester EVTs are also enriched for components of the JAK-STAT pathway that drives inflammation. We carried out a systematic review and identified that in 12% of pregnant women with COVID-19, the placenta was infected with SARS-CoV-2, and the virus was detected in STBs. To conclude, herein we have uncovered the cellular targets for SARS-CoV-2 entry and have shown that these cells can potentially drive viremia in the developing human placenta. Our results provide a basic framework toward understanding the paraphernalia involved in SARS-CoV-2 infections in pregnancy.

Mechanistic modeling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinicopathological outcomes.

Sarthak Sahoo, Kishore Hari, Siddharth Jhunjhunwala, and Mohit Kumar Jolly. Frontiers in Cell and Developmental Biology (2020). DOI:10.1101/2020.05.16.097238v1

The disease caused by SARS-CoV-2 is a global pandemic that threatens to bring long-term changes worldwide. Approximately 80% of infected patients are asymptomatic or have mild symptoms such as fever or cough, while rest of the patients have varying degrees of severity of symptoms, with 3-4% mortality rate. Severe symptoms such as pneumonia and Acute Respiratory Distress Syndrome can be caused by tissue damage mostly due to aggravated and unresolved innate and adaptive immune response, often resulting from a cytokine storm. However, the mechanistic underpinnings of such responses remain elusive, with an incomplete understanding of how an intricate interplay among infected cells and cells of innate and adaptive immune system can lead to such diverse clinicopathological outcomes. Here, we use a dynamical systems approach to dissect the emergent nonlinear intra-host dynamics among virally infected cells, the immune response to it and the consequent immunopathology. By mechanistic analysis of cell-cell interactions, we have identified key parameters affecting the diverse clinical phenotypes associated with COVID-19. This minimalistic yet rigorous model can explain the various phenotypes observed across the clinical spectrum of COVID-19, various co-morbidity risk factors such as age and obesity, and the effect of antiviral drugs on different phenotypes. It also reveals how a fine-tuned balance of infected cell killing and resolution of inflammation can lead to infection clearance, while disruptions can drive different severe phenotypes. These results will help further the case of rational selection of drug combinations that can effectively balance viral clearance and minimize tissue damage simultaneously.

Significance Statement The SARS-CoV-2 pandemic has already infected millions of people, and thousands of lives have been lost to it. The pandemic has already tested the limits of our public healthcare systems with a wide spectrum of clinicopathological symptoms and outcomes. The mechanistic underpinnings of the resultant immunopathology caused by the viral infection still remains to be elucidated. Here we propose a minimalistic but rigorous description of the interactions of the virus infected cells and the core components of the immune system that can potentially explain such diversity in the observed clinical outcomes. Our proposed framework could enable a platform to determine the efficacy of various treatment combinations and can contributes a conceptual understanding of dynamics of disease pathogenesis in SARS-CoV-2 infections.

Competing Interest Statement
The authors have declared no competing interest.

.

A Report on Impact of Nutrition through Mid Day Meals: Building a Comprehensive Assessment Model

Deepika Swami, Anjula Gurtoo, and Bita Afsharia. (2020) 01B/04/2020, pp. 01-28

The Report proposes a framework to build a comprehensive mid-day meal (MDM) assessment model. The framework provides the foundation to evaluate the multi-level impacts of the MDM scheme on a child’s nutritional health. The inter-sectoral convergence in the framework ensures a balanced and holistic view of the MDM scheme. The framework also gives us the potential to identify effective, high potential, policy interventions for improved nutritional health of a child in India.

Sustainability Transition in Established Corporations: Role of Technological Innovation

Rahul Patil, Akriti Jain, and Anjula Gurtoo. (2020) Sixth Biennial Conference of the Indian Academy of Management (INDAM) – 2020, IIM Trichy – India on 1-4 January 2020. SSRN ID 3635658, pp. 01-12

Sustainability transition theories analyze a systematic shift towards sustainability at micro (niche), meso (regime) and macro (landscape) level. The assessment of technological systems and structures at the firm level in sustainability transition literature is scant. The present study, taking the technological assessment perspective at the firm level, finds answers to questions like (a) how do established corporations move towards sustainable practices? (b) what role does technological innovation play in the firm’s transition towards sustainability? (c) what technological modes get adopted for sustainability transition? We find answers to these questions through an in-depth case analysis of two multi-national companies in the consumer goods industry. Internally developed and externally acquired technologies by firms in the last 15 years are plotted using qualitative and quantitative indicators on pre-designed templates. Technologies for all three sustainability dimensions, namely, environmental, social and economic, get mapped and the impact assessed. The analysis finds a sustainability transition landscape reflecting the use of protected (patents, trademarks, designs) and unprotected technologies (open innovation) to generate impacts like production efficiency, consumption reduction, emission reduction, reduce-recycle-reuse among others. Companies implementing sustainable technologies do observe positive impacts. Implementation of reduce-reuse- recycle (3R)-based technologies enhance the achievement of sustainable development targets. Furthermore, the use of trademarks seems common in differentiating their technologies and identities. The last section uses these and other results to comment on the role of managing intellectual property and harnessing the effect of technological innovations in sustainability transition.

A Nonsmooth Extension of Samuelson’s Multiplier-Accelerator Model

Petri T. Piiroinen and Srinivasan Raghavenadra. International Journal of Bifurcation and Chaos, Vol. 29, No. 10 (2019) 1930027 pp. 01-15, DOI: 10.1142/S0218127419300271

Dynamical-systems approaches have historically been used in business-cycle theory to generate sustained oscillations in macroeconomic variables. We aim to contribute to this literature by extending the original Samuelson multiplier-accelerator model with a discontinuous stabilization policy in terms of government expenditure. We show that the nonsmoothness yields…

Working Papers

Policy Review: Humanure Application in Agriculture: Emerging Policy Concerns and Recommendations

Girija R - Research Scholar, Divecha Centre for Climate Change, IISc; Working Paper 01A/12/2019, pp. 01-07

This Policy brief highlights the challenges in agriculture and provides recommendations with respect to the identified problem – hurdles in reusing humanure in agriculture. It presents evidence and experience, through research results and findings from the field on application of human excreta-based soil inputs in agriculture in order to make informed decisions.

Policy Review: National Design Policy of India, 2007 and Science, Technology and Innovation Policy of India, 2013

Kumari M C - Research Scholar, Centre for Product Design & Manufacturing, IISc; Working Paper 06A/10/2019, pp. 01-11

The word design is used to refer to design solutions, design activity, design stage, and the domain itself. It is used as a noun and a verb. “Design is to design a design to produce a design.”– is a line often used to show the shifts of its meaning. Design cuts across various domains, while materialising as products, processes, and services. Heskett categories design…

Policy Review: The Winds of Change in India’s Wind Sector - Guidelines for Tariff Based Competitive Bidding for Procurement of Power from Grid-Connected Large Wind Power Projects

Anasuya Gangopadhyay - Research Scholar, Divecha Centre for Climate Change, IISc; Working Paper 05A/10/2019, pp. 01-07

The policy titled ‘Guidelines for Tariff Based Competitive Bidding for Procurement of Power from Grid-Connected Large Wind Power Projects’ was released on 7 December 2017. In India, till the year 2017, wind power was promoted through various tax benefits, incentives [like Accelerated Depreciation (AD) and Generation Based Incentives (GBI)] and preferential… 

Policy Review:Annotation of the Draft National Policy for Micro and Mini-Grids, 2016

Soumya Deep Das - Research Scholar, National Institute of Advanced Studies; Working Paper 04A/10/2019, pp. 01-09

Electricity is one of the prime movers in the National economic growth rate, catalyst in generating new skilled manpower and an important indicator to measure poverty alleviation. It is a well-known fact that with higher energy consumption results in higher economic growth, but it also creates a negative impact on our environment through rising anthropogenic…

Kalyāṇ – a Voyage through Dēśa and Kāla | Part-II

Achintya Prahlad - Postdoctoral Fellow, Ashoka University; Working Paper 02A/10/2019, pp. 01-40

This article explores the rāga system in Indian music, in the specific context of a prominent family of rāgas known as Kalyāṇ. It explores their structure, with attention to its historical evolution and geographical variation. Part 1 deals with the period from the 16th to the 18th century, while part 2 deals with the later period…

Kalyāṇ – a Voyage through Dēśa and Kāla | Part-I

Achintya Prahlad - Postdoctoral Fellow, Ashoka University; Working Paper 01A/10/2019. pp. 01-30

This article explores the rāga system in Indian music, in the specific context of a prominent family of rāgas known as Kalyāṇ. It explores their structure, with attention to its historical evolution and geographical variation. Part 1 deals with the period from the 16th to the 18th century, while part 2 deals with the later period…

Close Menu