An Upper Bound on Computation for the Anharmonic Oscillator

For a quantum system with energy E, there is a limitation in quantum computation which is identified by the minimum time needed for the state to evolve to an orthogonal state. In this paper, we will compute the minimum time of orthogonalization (i.e. quantum speed limit) for a simple anharmonic oscillator and find an upper bound on the rate of computations. We will also investigate the growth rate of complexity for the anharmonic oscillator by treating the anharmonic terms perturbatively. More precisely, we will compute the maximum rate of change of complexity and show that for even order perturbations, the rate of complexity increases while for the odd order terms it has a decreasing behavior.Comment: 9 pages, 5 figure

Proteomics of neurodegenerative diseases using novel online isoelectric point separation

The work presented in this thesis describes an instrument, developed for separation of proteins and peptides based on corresponding isoelectric point (pI) values, to empower mass spectrometry-based proteomics analysis. The main objectives are the instrument development and optimization, as well as clinical applications in biomarker discovery, particularly for neurodegenerative disorders. The thesis is based on five scientific papers that focus on three main stages; (i) development and optimization of the device for separation of proteins and peptides by pI that are well integrated with tandem mass spectrometry (ii) optimization of the device for intact blood plasma protein fractionation for application in biomarker discovery, and (iii) biomarker discovery in blood plasma for early diagnosis of Alzheimer disease. Within the first part of the work, a novel multiple-junction capillary isoelectric focusing fractionator (MJ-CIEF) is developed (Paper I). Subsequently, the resolving power and reproducibility of fractionation are improved, and in addition, a novel algorithm is developed to calculate the identified peptides’ pI (Paper II). Moreover, to achieve the aim of deep proteomics, a multi-parameter optimization of the LC-MS/MS pipeline is performed (Paper III). In the second part, an online desalinator is developed and coupled to the device, for direct buffer-exchange and isoelectric separation of intact human blood plasma/serum proteins. The developed pipeline achieves the increased depth of the proteome analysis and provides additional information on the pI of identified proteins, as another dimension of information in biomarker discovery by proteomics (Paper IV). The last part of the thesis is focused on the application of the developed method in biomarker discovery for early diagnosis of Alzheimer disease. A panel of new potential biomarkers is introduced based on the abundance changes, as well as shifts in the pI values. By means of the pI information, the protein concentration in a narrow pH range around 7.4 reveals increased levels in patients with progressive Alzheimer disease compared to stable ones. Proteome analysis of this particular pI region also suggests several potential proteins as biomarkers for early diagnosis of the disease (Paper V). Taken together, this thesis demonstrates emerging applications of peptides and proteins fractionation by pI in deep proteomics. The development of MJ-CIEF facilitates online separation of peptides and proteins from small amounts of samples in a fast format, automatable, cost-effective and compatible with mass spectrometry analysis. Further biomarker discovery in the narrow range of pH around 7.4 of blood proteome is suggested for early diagnosis of neurodegenerative diseases

Separation of Polypeptides by Isoelectric Point Focusing in Electrospray-Friendly Solution Using a Multiple-Junction Capillary Fractionator

We introduce an online multiple-junction capillary isoelectric focusing fractionator (OMJ-CIEF) for separation of biological molecules in solution by pI. In OMJ-CIEF, the separation capillary is divided into seven equal sections joined with each other via tubular Nafion membrane insertions. Each junction is communicated with its own external electrolytic buffer which is used both to supply electrical contact and for solvent exchange. The performance of the fractionator was explored using protein and peptide samples covering broad pI range. Separation was achieved in ionic and ampholytic buffers, including ammonium formate, ammonium hydroxide, histidine, and arginine. By maintaining electric potential across upstream segments of the capillary after the focusing stage, selective release of downstream analyte fractions could be achieved. The selective release mode circumvents the problem of peak broadening during mobilization and enables convenient comprehensive sampling for orthogonal separation methods. Using single-component ampholyte buffers with well-defined pI cutoff values, controlled separation of protein mixture into basic and acidic fractions was demonstrated. The device is cheap and easy to fabricate in-house, simple in operation, and straightforward in interfacing to hyphened analytical platforms. OMJ-CIEF has a potential of becoming a practical add-on unit in a wide range of bioanalytical setups, in particular as a first-dimension separation in mass spectrometry based proteomics or as a preparative tool for analyte purification, fractionation, and preconcentration

Membrane-Assisted Isoelectric Focusing Device As a Micropreparative Fractionator for Two-Dimensional Shotgun Proteomics

Recently, we introduced an online multijunction capillary isoelectric focusing (OMJ-CIEF) fractionator to fractionate proteins and peptides in electrospray-friendly solution. In this follow-up study, the original configuration of the fractionator was modified to improve the resolving power and reproducibility of separation. The major improvements include stabilization of the electrical current through the device using a voltage divider and stepwise elution of peptide zones in conjunction with the repeated refocusing of remaining peptides. Also, a novel algorithm was developed to calculate more accurately the pI values of peptides identified from experimental data. The standard deviation of calculated pI values for unmodified peptides from the theoretically predicted pI values was on average 0.21 pH units, which is more accurate than in standard-resolution gel-based methods. In order to characterize the analytical performance of the improved device, it was applied for the pI fractionation of yeast proteome digest into 18 fractions, with the collected fractions being analyzed by reverse-phase liquid chromatography coupled with tandem mass spectrometry. Approximately 37% of 20047 identified peptides were detected in only one fraction and 27% - in two fractions. On average, every peptide was found in 2.4 fractions. These results strongly indicate the suitability of the improved device as a first dimension of separation in multidimensional shotgun proteomics analysis, with a potential for fully automated workflow

Battling water limits to growth:lessons from water trends in the central plateau of Iran

Abstract The Zayandeh-Rud River Basin in the central plateau of Iran continues to grapple with water shortages due to a water-intensive development path made possible by a primarily supply-oriented water management approach to battle the water limits to growth. Despite inter-basin water transfers and increasing groundwater supply, recurring water shortages and associated tensions among stakeholders underscore key weaknesses in the current water management paradigm. There was an alarming trend of groundwater depletion in the basin’s four main aquifers in the 1993–2016 period as indicated by the results of the Mann-Kendall3 (MK3) test and Innovative Trend Analysis (ITA) of groundwater volume. The basin’s water resources declined by more than 6 BCM in 2016 compared to 2005 based on the equivalent water height (EWH) derived from monthly data (2002–2016) from the GRACE. The extensive groundwater depletion is an unequivocal evidence of reduced water availability in the face of growing basin-wide demand, necessitating water saving in all water use sectors. Implementing an integrated water resources management plan that accounts for evolving water supply priorities, growing demand and scarcity, and institutional changes is an urgent step to alleviate the growing tensions and preempt future water insecurity problems that are bound to occur if demand management approaches are delayed

Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response.

Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS).To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches--gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response