Search

The recent explosion of novel experimental protocols in the life sciences is providing glimpses into fundamental biological processes that previously remained inaccessible. The mechanisms underlying these processes are unique enough that understanding them often requires approaches beyond those traditionally associated with data-driven statistics. This thesis explores three such instances, in which borrowing ideas from geometry, probability theory and partial differential equations can lead to tangible improvements over existing methods, as well as new frameworks for future tasks. Our first analysis revolves around protein synthesis: the conversion of genes into viable polypeptides through what is known as translation. By exploiting the so-called Totally Asymmetric Simple Exclusion Process (TASEP) as a model of translation, we rephrase questions of biological interest in terms of Markov chains properties, which in turn we successfully tackle by deriving an adequate continuum limit of the TASEP. Analysis of this limiting process reveals a handful of key parameters that govern translation efficiency, whose roles we summarize in a concise set of design principles, and confirm on ribosome profiling data of yeast. Secondly, we direct attention to the task of gene expression deconvolution: recovering individual cell type contributions to the transcript abundances of an entire tissue. By embedding our deconvolution procedure into a full-likelihood framework, we not only provide provably optimal error guarantees, but also enable convenient model evaluation, adaptation and uncertainty quantification. We demonstrate this improved performance and flexibility on a variety of simulated and experimental bulk samples. And thirdly, motivated by detecting differential expression of genes across tissues, individuals or conditions, we investigate non-parametric two-sample testing. After identifying a broad family of statistics that includes as special cases Mann-Whitney’s U, Greenwood’s and Dixon’s, we employ combinatorial tools to quickly compute their null distributions’ moments to arbitrary precision. Combined with an equally fast and provably accurate solution to the related moment problem we thus arrive at a well-calibrated, versatile goodness-of-fit test with applicability beyond the gene expression setting. We showcase its power in various direct comparisons with a number of tests commonly used in practice.

This paper provides empirical evidence of the holiday effect in stock return and the implications of the holiday effect. The research finds that there are existing the high stock return before the Lunar new year on the Ho Chi Minh Stock Exchange during the period 2002-2018. This paper using the GARCH, Modified-GARCH, GARCH-M, and EGARCH models to test the holiday effect on stock return. The results indicate that there is evidence of holiday such as Chinese New Year in Vietnam which is called Lunar new year effect on stock return. Specifically, the stock return before the Lunar new year is usually higher than after the Lunar new year on the Ho Chi Minh Stock Exchange.

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1 alpha expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of gamma-aminobutyric acid (GABA) type A receptor-alpha 2 subunit (GABAR alpha 2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1 alpha in neurons. Along with this, GABAR alpha 2 expression was enhanced in the hippocampus of the PGC-1 alpha Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABAR alpha 2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1 alpha Tg mice compared with controls. To study whether drugs acting on PPAR gamma can affect GABAR alpha 2, we employed pioglitazone that elevated GABAR alpha 2 expression in primary cultured neurons. Similar results were obtained using the specific PPAR gamma agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1 alpha regulates GABAR alpha 2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABAR alpha 2 expression via the PPAR gamma/PGC-1 alpha system. Funding Agencies|EUEuropean Commission [H2020-MSCA-RISE-2016, 734791]; European Regional Development FundEuropean Commission [2014-2020-4-01.15-0012]; Liv and the Halsa Foundation; Academy of FinlandAcademy of FinlandEuropean Commission [290608]; Finska Lakaresallskapet; Magnus Ehrnrooth Foundation; Minerva Foundation; Estonian Research CouncilEstonian Research Council [PRG805]; Biocenter Finland; Helsinki Institute of Life Science

Red mud is a highly alkaline solid waste from the Bayer process for aluminum production. Red mud reservoirs are usually considered as a potential environmental risk. The treatment of red mud is costly due to the lack of an effective and economical treatment technology. On the other hand, the main components of red mud are Fe2O3, Al2O3, SiO2, and Na2O, which could be employed as a promising precursor for the preparation of various nanomaterials. In this study, we prepared activated red mud by thermal and acid treatment method and applied it for adsorption of H2S in air. The red mud was activated under different temperatures (i.e., 200, 400, 600, and 800 oC for 4 h), types of acid (i.e., H2SO4 and HCl), and acid concentrations (i.e., 0.5, 1.5, and 2.5 M). The produced materials were then applied for H2S removal in air with concentration of 90 – 110 mg/m3 using a fix-bed adsorption column test. Results showed that red mud activated at 800 oC and with 1.5 M H2SO4 solution had the highest adsorption capacity of 29.38 mg/g with an average removal efficiency of 80.2%. The effects of gas flow rate and initial H2S concentration were also investigated, and the highest removal capacity was achieved at an inlet concentration of 100 mg/m3 and flow rate of 1 L/min. Both Langmuir and Freundlich adsorption isotherms were employed for modelling the H2S adsorption by this material and the experimental result was more fitted with the Langmuir isotherm. The thermal desorption and recyclability test were also conducted for evaluating the practical application of activated red mud material and 200 oC was the suggested desorption temperature with 81.7% adsorption capacity recovery.

A Mach‐Zehnder interferometer (MZI) was built and modified to in situ monitor the deformation of polymers during the photocuring process. In this review, the working principle and method of operation of this MZI were explained together with the method of data analysis. As the examples for the utilization of this modified MZI, measurements of the deformation induced by photopolymerization was demonstrated for three different types of samples: homopolymer in the bulk state, miscible polymer blends and phase‐separated polymer blends. Finally, a concluding remark is provided for the usage of MZI in polymer research.

Parkinson's disease (PD) is a progressive neurodegenerative disorder causing movement disabilities and several non-motor symptoms in afflicted patients. Recent studies in animal models of PD and analyses of brain specimen from PD patients revealed an increase in the level and activity of the non-receptor tyrosine kinase Abelson (c-Abl) in dopaminergic neurons with phosphorylation of protein substrates, such as alpha-synuclein and the E3 ubiquitin ligase, Parkin. Most significantly inhibition of c-Abl kinase activity by small molecular compounds used in the clinic to treat human leukemia have shown promising neuroprotective effects in cell and animal models of PD. This has raised hope that similar beneficial outcome may also be observed in the treatment of PD patients by using c-Abl inhibitors. Here we highlight the background for the current optimism, reviewing c-Abl and its relationship to pathophysiological pathways prevailing in PD, as well as discussing issues related to the pharmacology and safety of current c-Abl inhibitors. Clearly more rigorously controlled and well-designed trials are needed before the c-Abl inhibitors can be used in the neuroclinic to possibly benefit an increasing number of PD patients.