Trees and water: smallholder agroforestry on irrigated lands in Northern India

Trees / Populus deltoids / Agroforestry / Afforestation / Reforestation / Models / Water use / Water balance / Evapotranspiration / Precipitation / Remote sensing / Irrigation requirements / India

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Molecular Epidemiology of HIV-1 Subtypes in India: Origin and Evolutionary History of the Predominant Subtype C

This thesis describes the translational genomics of HIV-1subtype C in India from its origin to therapeutic response with the aim to improve our knowledge for better therapeutic and preventive strategies to combat HIV/AIDS. In a systemic approach, we identified the molecular phylogeny of HIV-1 subtypes circulating in India and the time to most recent common ancestors (tMRCA) of predominant HIV-1 subtype C strains. Additionally, this thesis also studied drug resistance mutations in children, adolescents and adults, the role of host factors in evolution of drug resistance, and population dynamics of viremia and viral co-receptor tropism in perinatal transmission. Finally, the long term therapeutic responses on Indian national first-line antiretroviral therapy were also studied. In Paper I, we reported an increase in the HIV-1 recombinant forms in the HIV-1 epidemiology using a robust subtyping methodology. While the study confirmed HIV- 1 subtype C as a dominant subtype, its origin was dated back to the early 1970s from a single or few genetically related strains from South Africa, whereafter, it has evolved independently. In Paper II, the lethal hypermutations due to the activity of human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (hA3G) was significantly associated with antiretroviral therapy (ART) failure in Indian HIV-1 subtype C patients. The presence of M184I and M230I mutations were observed due to the editing of hA3G in the proviral compartment but stop codons were also found in the open reading frames and the same drug resistance mutations were absent in plasma virus. Therefore, it is unlikely that the viral variants which exhibit hypermutated sequences and M184I and/or M230I will mature and expand in vivo and hence are unlikely to have any clinical significance. The high concordance of drug resistance genotyping in the plasma and proviral compartments in therapy-naïve patients, gives weight to the idea of using whole blood for surveillance of drug resistance mutations which precludes logistic challenges of cold chain transport. In Papers III and IV, we identified a substantial proportion of HIV-1 subtype C perinatally-infected older children who had a high burden of plasma viremia but also had high CD4+ T-cell counts. In addition, older children with HIV-1 subtype C infection presented a high prevalence of predicted X4 and R5/X4 tropic strains which indicates that HIV-1 subtype C strains required longer duration of infection and greater disease progression to co-receptor transition from R5- to X4-tropic strains (IV). Our studies also indicate that transmitted drug resistance is low among Indian HIV-1 infected children, adolescents (III) and adults (II). In Paper V, in a longitudinal cohort study, a good long-term response to the Indian national first-line therapy for a median of nearly four years with 2.8% viral failure, indicating the overall success of the Indian ART program. Our study also showed that three immunologically well patients with virological rebound and major viral drug resistance mutations (M184V, K103N and Y181C) during one study visit had undetectable viral load at their next visit. These findings suggest that use of multiple parameters like patients’ immunological (CD4+ T-cell count), virological (viral load) and drug resistance data should all be used to optimize the treatment switch to second line therapy. In conclusion, this translational genomics study enhances our knowledge about the HIV-1 subtype C strains circulating in India which are genetically distinct from prototype African subtype C strains. Considerably more research using appropriate models need to be performed to understand the phenotypic and biological characteristics of these strains to guide efficient disease intervention and management strategies

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model

Supernova Pointing Capabilities of DUNE

The determination of the direction of a stellar core collapse via its neutrino emission is crucial for the identification of the progenitor for a multimessenger follow-up. A highly effective method of reconstructing supernova directions within the Deep Underground Neutrino Experiment (DUNE) is introduced. The supernova neutrino pointing resolution is studied by simulating and reconstructing electron-neutrino charged-current absorption on 4040Ar and elastic scattering of neutrinos on electrons. Procedures to reconstruct individual interactions, including a newly developed technique called ``brems flipping'', as well as the burst direction from an ensemble of interactions are described. Performance of the burst direction reconstruction is evaluated for supernovae happening at a distance of 10 kpc for a specific supernova burst flux model. The pointing resolution is found to be 3.4 degrees at 68% coverage for a perfect interaction-channel classification and a fiducial mass of 40 kton, and 6.6 degrees for a 10 kton fiducial mass respectively. Assuming a 4% rate of charged-current interactions being misidentified as elastic scattering, DUNE's burst pointing resolution is found to be 4.3 degrees (8.7 degrees) at 68% coverage

The DUNE Far Detector Interim Design Report, Volume 3: Dual-Phase Module

The DUNE IDR describes the proposed physics program and technical designs of the DUNE far detector modules in preparation for the full TDR to be published in 2019. It is intended as an intermediate milestone on the path to a full TDR, justifying the technical choices that flow down from the high-level physics goals through requirements at all levels of the Project. These design choices will enable the DUNE experiment to make the ground-breaking discoveries that will help to answer fundamental physics questions. Volume 3 describes the dual-phase module's subsystems, the technical coordination required for its design, construction, installation, and integration, and its organizational structure

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model.Comment: Contribution to Snowmass 202

Snowmass Neutrino Frontier: DUNE Physics Summary

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of $\delta_{CP}$. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter.Comment: Contribution to Snowmass 202

Identification and reconstruction of low-energy electrons in the ProtoDUNE-SP detector

Measurements of electrons from $\nu_e$ interactions are crucial for the Deep Underground Neutrino Experiment (DUNE) neutrino oscillation program, as well as searches for physics beyond the standard model, supernova neutrino detection, and solar neutrino measurements. This article describes the selection and reconstruction of low-energy (Michel) electrons in the ProtoDUNE-SP detector. ProtoDUNE-SP is one of the prototypes for the DUNE far detector, built and operated at CERN as a charged particle test beam experiment. A sample of low-energy electrons produced by the decay of cosmic muons is selected with a purity of 95%. This sample is used to calibrate the low-energy electron energy scale with two techniques. An electron energy calibration based on a cosmic ray muon sample uses calibration constants derived from measured and simulated cosmic ray muon events. Another calibration technique makes use of the theoretically well-understood Michel electron energy spectrum to convert reconstructed charge to electron energy. In addition, the effects of detector response to low-energy electron energy scale and its resolution including readout electronics threshold effects are quantified. Finally, the relation between the theoretical and reconstructed low-energy electron energy spectrum is derived and the energy resolution is characterized. The low-energy electron selection presented here accounts for about 75% of the total electron deposited energy. After the addition of lost energy using a Monte Carlo simulation, the energy resolution improves from about 40% to 25% at 50~MeV. These results are used to validate the expected capabilities of the DUNE far detector to reconstruct low-energy electrons.Comment: 19 pages, 10 figure