ENGINEERING ADVANCED MATERIAL PROPERTIES FOR POLYMERIC MATERIALS THROUGH MISCIBLE AND IMMISCIBLE ADDITIVES

This dissertation focuses on engineering polymeric formulations using strategically selected additives or novel processes to achieve advanced material properties. The first chapter reviews the state-of-the-art impact modification and discusses micro-mechanics associated with soft particle toughening of polymeric materials. We present an analytical solution to elucidate the effect of concentration of rubbery domains on matrix yielding and energy absorption. Soft particle toughening relies on particle size, interparticle spacing, and concentration of rubbery phase. The second chapter demonstrates developing impact modified stereolithography (SLA) resins for the superior energy absorption of the SLA printed thermosets. SLA resins are engineered using additives that remain miscible in the uncured resin but undergo RIPS to generate rubbery domains after photopolymerization. SLA resins containing 15% of the identified impact modifier generates rubbery domains of appropriate size (57 nm) and inter-particle spacing (33 nm) to provide the most significant, order of magnitude, improvement in the impact properties irrespective of the print layer orientation and print layer thickness. The third chapter describes new strategies to obtain non-spherical rubbery domains for the next-generation impact modification. Firstly, blending of two different block copolymers with polypropylene is investigated to achieve non-spherical domains. Alternatively, elastomeric adducts are prepared via reactive mixing to realize non-spherical rubbery domains for polyoxymethylene. Impact properties of engineered polypropylene formulations show a strong dependence on particle size and shape under quasi-static room temperature as well as high strain, low temperatures (extreme conditions). The fourth chapter describes multifunctional organophosphorus additives for high Tg epoxy networks which achieve both enhanced mechanical and flame-retardant properties. These molecular additives remain miscible in the cured epoxy networks and participate in the mechanisms of fortification and flame inhibition. Herein, a systematic investigation of the effect of dimethyl methyl phosphonate (DMMP) on the mechanical and heat release properties of both conventional and inherently low flammability epoxy resins is presented. The integration of DMMP into epoxy networks produces materials with outstanding flame retardance and increased stiffness

Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1−/− mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1−/− mice is also significantly decreased relative to that from wild-type mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1−/− mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1

Design and construction of a point-contact spectroscopy rig with lateral scanning capability

The design and realization of a cryogenic rig for point-contact spectroscopy measurements in the needle-anvil configuration is presented. Thanks to the use of two piezoelectric nano-positioners, the tip can move along the vertical ($z$) and horizontal ($x$) direction and thus the rig is suitable to probe different regions of a sample \textit{in situ}. Moreover, it can also form double point-contacts on different facets of a single crystal for achieving, e.g., an interferometer configuration for phase-sensitive measurements. For the latter purpose, the sample holder can also host a Helmholtz coil for applying a small transverse magnetic field to the junction. A semi-rigid coaxial cable can be easily added for studying the behavior of Josephson junctions under microwave irradiation. The rig can be detached from the probe and thus used with different cryostats. The performance of this new probe has been tested in a Quantum Design PPMS system by conducting point-contact Andreev reflection measurements on Nb thin films over large areas as a function of temperature and magnetic field.Comment: 7 pages, 7 figures, published in Rev. Sci. Instru

A percutaneous needle biopsy technique for sampling the supraclavicular brown adipose tissue depot of humans.

Brown adipose tissue (BAT) has been proposed as a potential target tissue against obesity and its related metabolic complications. Although the molecular and functional characteristics of BAT have been intensively studied in rodents, only a few studies have used human BAT specimens due to the difficulty of sampling human BAT deposits. We established a novel positron emission tomography and computed tomography-guided Bergström needle biopsy technique to acquire human BAT specimens from the supraclavicular area in human subjects. Forty-three biopsies were performed on 23 participants. The procedure was tolerated well by the majority of participants. No major complications were noted. Numbness (9.6%) and hematoma (2.3%) were the two minor complications noted, which fully resolved. Thus, the proposed biopsy technique can be considered safe with only minimal risk of adverse events. Adoption of the proposed method is expected to increase the sampling of the supraclavicular BAT depot for research purposes so as to augment the scientific knowledge of the biology of human BAT

The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum.

BackgroundGene expression is controlled at multiple levels, including transcription, stability, translation, and degradation. Over the years, it has become apparent that Plasmodium falciparum exerts limited transcriptional control of gene expression, while at least part of Plasmodium's genome is controlled by post-transcriptional mechanisms. To generate insights into the mechanisms that regulate gene expression at the post-transcriptional level, we undertook complementary computational, comparative genomics, and experimental approaches to identify and characterize mRNA-binding proteins (mRBPs) in P. falciparum.ResultsClose to 1000 RNA-binding proteins are identified by hidden Markov model searches, of which mRBPs encompass a relatively large proportion of the parasite proteome as compared to other eukaryotes. Several abundant mRNA-binding domains are enriched in apicomplexan parasites, while strong depletion of mRNA-binding domains involved in RNA degradation is observed. Next, we experimentally capture 199 proteins that interact with mRNA during the blood stages, 64 of which with high confidence. These captured mRBPs show a significant overlap with the in silico identified candidate RBPs (p < 0.0001). Among the experimentally validated mRBPs are many known translational regulators active in other stages of the parasite's life cycle, such as DOZI, CITH, PfCELF2, Musashi, and PfAlba1-4. Finally, we also detect several proteins with an RNA-binding domain abundant in Apicomplexans (RAP domain) that is almost exclusively found in apicomplexan parasites.ConclusionsCollectively, our results provide the most complete comparative genomics and experimental analysis of mRBPs in P. falciparum. A better understanding of these regulatory proteins will not only give insight into the intricate parasite life cycle but may also provide targets for novel therapeutic strategies

Cross-correlation between PlanckPlanck CMB lensing potential and galaxy catalogues from HELP

We present the study of cross-correlation between Cosmic Microwave Background (CMB) gravitational lensing potential map released by the \textit{Planck} collaboration and photometric redshift galaxy catalogues from the \textit{Herschel} Extragalactic Legacy Project (HELP), divided into four sky patches: NGP, \textit{Herschel} Stripe-82, and two halves of SGP field, covering in total $\sim 660$ deg$^{2}$ of the sky. We estimate the galaxy linear bias parameter, $b_{0}$, from joint analysis of cross-power spectrum and galaxy auto-power spectrum using Maximum Likelihood Estimation technique to obtain values ranging from $0.70 \pm 0.01$ for SGP Part-2 to $1.02 \pm 0.02$ for SGP Part-1 field. We also estimate the amplitude of cross-correlation and find the values spanning from $0.67 \pm 0.18$ for SGP Part-2 to $0.80 \pm 0.23$ for SGP Part-1 field, respectively. For NGP and SGP Part-1 fields the amplitude is consistent with the expected value for the standard cosmological model within $\sim 1\,\sigma$, while for \textit{Herschel} Stripe-82 and SGP Part-2 we find the amplitude to be smaller than expected with $\sim 1.5\,\sigma$ and $\sim 2\,\sigma$ deviation, respectively. We perform several tests on various systematic errors to study the reason for the deviation, however, value of the amplitude turns out to be robust with respect to these errors. The only significant change in the amplitude is observed when we replace the minimum-variance CMB lensing map, used in the baseline analysis, by the lensing map derived from the CMB temperature map with deprojected thermal Sunyaev-Zeldovich signal.Comment: 15 pages, 13 figures, Published in MNRA

Differential Ballistic Response of Aramid-Glass Fibre Laminates to Soft and Hard Shots .

Ballistic perfonnance of all-glass, all-aramid and aramid-glass fibre-reinforced phenolic resincomposite laminates has been evaluated against 0.30 in. calibre soft ball and hard armour piercing (AP) bullets. It is observed that mass effective ness of glass fibre phenolic composites against impacts by APbullets can be improved by aramid fibre'reinforcement in the back of laminate. The perfonnance of a ramid phenolic composites against ball ammunition can be improved by hybridisation with glass fibre reinforcement at the front

The multifunctional autophagy pathway in the human malaria parasite, Plasmodium falciparum.

Autophagy is a catabolic pathway typically induced by nutrient starvation to recycle amino acids, but can also function in removing damaged organelles. In addition, this pathway plays a key role in eukaryotic development. To date, not much is known about the role of autophagy in apicomplexan parasites and more specifically in the human malaria parasite Plasmodium falciparum. Comparative genomic analysis has uncovered some, but not all, orthologs of autophagy-related (ATG) genes in the malaria parasite genome. Here, using a genome-wide in silico analysis, we confirmed that ATG genes whose products are required for vesicle expansion and completion are present, while genes involved in induction of autophagy and cargo packaging are mostly absent. We subsequently focused on the molecular and cellular function of P. falciparum ATG8 (PfATG8), an autophagosome membrane marker and key component of the autophagy pathway, throughout the parasite asexual and sexual erythrocytic stages. In this context, we showed that PfATG8 has a distinct and atypical role in parasite development. PfATG8 localized in the apicoplast and in vesicles throughout the cytosol during parasite development. Immunofluorescence assays of PfATG8 in apicoplast-minus parasites suggest that PfATG8 is involved in apicoplast biogenesis. Furthermore, treatment of parasite cultures with bafilomycin A 1 and chloroquine, both lysosomotropic agents that inhibit autophagosome and lysosome fusion, resulted in dramatic morphological changes of the apicoplast, and parasite death. Furthermore, deep proteomic analysis of components associated with PfATG8 indicated that it may possibly be involved in ribophagy and piecemeal microautophagy of the nucleus. Collectively, our data revealed the importance and specificity of the autophagy pathway in the malaria parasite and offer potential novel therapeutic strategies