A CA1 pyramidal neuron in the rodent hippocampus integrates inputs from as many as 30,000 synapses distributed over hundreds of microns, making synaptic integration an intricate spatio-temporal computation. Crucial to this computation, is the timing of synaptic inputs at the axo-somatic integration site. Consequently, it would be beneficial if co-incident proximal and distal inputs arrive simultaneously at the axo-somatic integration site. This, however, is a challenge considering that spatially dispersed inputs have to propagate varying distances, leading to location-dependent temporal differences at the soma. Here we show that CA1 pyramidal neurons have an intrinsic biophysical mechanism in the form of a gradient of HCN channels that actively counteracts location-dependent temporal differences of dendritic inputs at the soma. HCN channels, due to their slow kinetics and unusual gating properties, impart an inductive reactance to the neuronal membrane properties. Using multi-site whole cell recordings, we show that this gradient of inductive reactance actively compensates for the location-dependent capacitive delay of dendritic inputs. This leads to a response synchrony of spatially dispersed inputs at the soma. This response synchrony is optimum for oscillatory signals in the theta frequency range (4-12 Hz). Using computational modeling we show that the characteristic sigmoidal distribution of HCN channels in CA1 neurons is crucial for the efficient and exclusive transfer of these synchronous theta frequencies from dendrite to the soma. To understand the significance of this oscillatory synchrony during synaptic integration, we used the dynamic clamp technique to simulate different temporal patterns of synaptic input in the dendrites of CA1 neurons. Our results reveal that this oscillatory synchrony is best harnessed by theta and gamma (40-140 Hz) frequency synaptic input patterns in CA1 neurons. Gamma and theta oscillations are associated with synchronizing activity across space in the hippocampal network. Our results thus identify a novel mechanism by which this synchrony extends to activity within single pyramidal neurons with complex dendritic arbors. / text

This thesis focuses on the radiation mechanisms of non-thermal X-rays and soft gamma-rays of two types of thousands year old spin-down powered pulsars. The thousands year old pulsars have distinct radiation behaviors from the middle-aged gamma-ray pulsars. In the magnetosphere of the pulsar, the particles are accelerated by the electric field resulting from the rotation of the neutron star. These accelerated particles move along the magnetic field lines and emit GeV gamma-ray curvature photons. For the middle-aged pulsars, most of the curvature photons, whose observed spectra are described well by power law with exponential cut-off, can escape out of the light cylinder. In X-ray band, the middle-aged pulsars usually have black body radiation with a weak non-thermal component described by power law. On the other hand, for the thousands-year-old pulsars, the curvature spectra in GeV band, which obey power law with exponential cut-off, are smeared out by the pair creation or missed by the line of sight. The secondary pairs generated by pair creation processes spiral around the magnetic field lines and emit synchrotron photons, and the young pulsars have stronger non-thermal X-ray and soft gamma-ray radiation than the middle-aged ones. Seven young pulsars have been studied here, they are the Crab pulsar, PSRs B0540-69, B1509-58, J1846-0258, J1811-1925, J1617-5055 and J1930+1852. These seven fall into two categories: the Crab-like pulsars and soft gamma-ray pulsars. The Crab-like pulsars include the Crab pulsar and the Giant Crab PSR B0540-69, and the soft gamma-ray pulsars include the other five. The main difference between the two types of young pulsars is that the Crab-like pulsars’ spectra peak at E ≤ 1MeV while the soft gamma-ray pulsars’ spectra (in units of MeV/cm2/s) peak at E ∼ 10MeV. Their spectra also have different photon indices in X-ray band. The physics behind is two different pair creations, the photon-photon pair creation and the magnetic pair creation. The former happens when a high energy photon collides with a soft photon, and the latter happens when a high energy photon penetrates through strong perpendicular magnetic field. In the outer gap of the pulsar, a large mount of pairs are generated around the null charge surface via photon-photon pair creation, and the electric field separates the two charges to move in opposite directions. Therefore, there are outflow and inflow of particles in the magnetosphere, whose curvature photons are converted to pairs by photon-photon pair creation and magnetic pair creation respectively. For the Crab-like pulsar, the non-thermal X-rays and soft gamma-rays are emitted by the outgoing secondary pairs generated by photon-photon pair creation in the outer magnetosphere; for the soft gamma-ray pulsar, the radiating secondary pairs are generated below the null charge surface by the magnetic pair creation. / published_or_final_version / Physics / Doctoral / Doctor of Philosophy

Not available / text

Lithium ion batteries, due to their relatively high energy density, are now widely used as the power source for portable electronics. Commercial lithium ion cells currently employ layered LiCoO₂ as a cathode but only 50% of its theoretical capacity can be utilized. The factors that cause the limitation are not fully established in the literature. With this perspective, prompt gamma-ray activation analysis (PGAA) has been employed to determine the hydrogen content in various oxide cathodes that have undergone chemical extraction of lithium (delithiation). The PGAA data is complemented by data obtained from atomic absorption spectroscopy (AAS), redox titration, thermogravimetric analysis (TGA), and mass spectroscopy to better understand the capacity limitations and failure mechanisms of lithium ion battery cathodes. As part of this work, the PGAA facility has been redesigned and reconstructed. The neutron and gamma-ray backgrounds have been reduced by more than an order of magnitude. Detection limits for elements have also been improved. Special attention was given to the experimental setup including potential sources of error and system calibration for the detection of hydrogen. Spectral interference with hydrogen arising from cobalt was identified and corrected for. Limits of detection as a function of cobalt mass present in a given sample are also discussed. The data indicates that while delithiated layered Li[subscript 1-x]CoO₂, Li[subscript 1-x]Ni[subscript 1/3]Mn[subscript 1/3]Co[subscript 1/3]O₂, and Li[subscript 1-x]Ni[subscript 0.5]Mn[subscript 0.5]O₂ take significant amounts of hydrogen into the lattice during deep extraction, orthorhombic Li[subscript 1-x]MnO₂, spinel Li[subscript 1-x]Mn₂O₄, and olivine Li[subscript 1-x]FePO₄ do not. Layered LiCoO₂, LiNi[subscript 0.5]Mn[subscript 0.5]O₂, and LiNi[subscript 1/3]Mn[subscript 1/3]Co[subscript 1/3]O₂ have been further analyzed to assess their relative chemical instabilities while undergoing stepped chemical delithiation. Each system takes increasing amounts of protons at lower lithium contents. The differences are attributed to the relative chemical instabilities of the various cathodes that could be related to the position of the transition metal band and the top of the O²-:2p band. Chemically delithiated layered Li[Li[subscript 0.17]Mn[subscript 0.33]Co[subscript0.5-y]Ni[subscript y]]O₂ cathodes have also been characterized. The first charge and discharge capacities decrease with increasing nickel content. The decrease in the capacity with increasing nickel content is due to a decrease in the lithium content present in the transition metal layer and a consequent decrease in the amount of oxygen irreversibly lost during the first charge. / text

Leishmaniasis is a spectrum of diseases caused by several species of protozoan parasites belonging to the genus, Leishmania. The disease, which is transmitted by Sandflies, ranges from self-healing cutaneous lesions to the life-threatening visceral leishmaniasis. Cutaneous leishmaniasis, caused by L. major, is the most common form of the disease. With no vaccine available for use in humans, cutaneous leishmaniasis remains a global public health problem. Since understanding the factors that regulate effective immunity to cutaneous leishmaniasis is critical for the development of an affective vaccine and treatment strategies, the overall aim of my thesis was to decipher the host and pathogen factors that regulate immunity in cutaneous leishmaniasis. Firstly, I show that parasite dose affects the expansion of different T cell subsets following L. major infection; with low dose infection inducing more CD8+ T cells while high dose infection induced more CD4+ T cells. However, although CD8+ T cells were important for optimal primary immunity following low dose infection, they where dispensable during secondary immunity. Secondly, I found that blockade of LIGHT, (lymphotoxin like, exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes) significantly impaired DC maturation, expression of co-stimulatory molecules, and early cytokine production (IL-12 and IFN-γ) following L. major infection. Interestingly, LIGHT was completely dispensable during secondary immunity in wild type mice but was critical for effective secondary immunity in CD40 deficient mice. Thirdly,I compared disease progression and immune response in CD40 and CD40L deficient mice infected with L. major under identical experimental conditions. I found significant differences in disease progression and immune response between CD40KO and CD40L KO mice infected with virulent L. major and treated with recombinant IL-12. My data revealed a novel pathway (CD40L-Mac-1 interaction) for IL-12 production and resistance to Leishmania major. Collectively, this thesis provides novel insights into the mechanisms involved in the development and maintenance of protective immunity against cutaneous leishmaniasis, which could lead to the development of a more efficient and effective immunotherapeutic and/or vaccination strategies against the disease. / October 2015

Gamma-ray bursts (GRBs) are relativistic explosions which originate at cosmological distances, and are among the most luminous transients in the universe. Following the prompt gamma-ray emission, a fading synchrotron "afterglow" is detectable at lower energies. While long-duration GRBs (duration > 2 sec) are linked to the deaths of massive stars, the progenitors of short-duration GRBs (duration < 2 sec) have remained elusive. Theoretical predictions formulated over the past two decades have suggested that they are the mergers of two compact objects, involving either two neutron stars (NS-NS) or a neutron star and a black hole (NS-BH). Such merging systems are also important to understand because they are premier candidates for gravitational wave detections with upcoming facilities and are considered likely sites of heavy element nucleosynthesis. The launch of the Swift satellite in 2004, with its rapid multi-wavelength monitoring and localization capabilities, led to the first discoveries of short GRB afterglows and therefore robust associations to host galaxies. At a Swift detection rate of ~8 events per year, the growing number of well-localized short GRBs enables comprehensive population studies of their afterglows and environments for the first time. In this thesis, I undertake a multi-wavelength observational campaign to address testable predictions for the progenitors of short GRBs. From their local environments, I show that short GRBs explode in diffuse regions of their host galaxies and are weakly correlated with the distribution of stellar mass and star formation in their host galaxies. I study the host galaxy demographics for the entire population and find that ~20-40% of short GRBs originate from elliptical galaxies, implying an older stellar progenitor. From their afterglows, I present evidence that some short GRBs are collimated in narrow jets of ~5-10 degrees, directly affecting the true energy scale and event rate. Finally, taking advantage of a decade of broad-band afterglow observations at radio through X-ray wavelengths, I find that short GRBs have median isotropic-equivalent energies of ~10^51 erg and that their local environments have low densities, ~10^-3-10^-2 cm^-3. Taken together, this thesis comprises several lines of independent evidence to demonstrate that short GRBs originate from the mergers of two compact objects, and also provides the first constraints on the explosion properties for a large sample of events. With the direct detection of gravitational waves from compact object mergers on the horizon, these studies provide necessary inputs to inform the next decade of joint electromagnetic-gravitational wave search strategies. / Astronomy

published_or_final_version / Physics / Master / Master of Philosophy

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