SEARCHING FOR GENETIC DETERMINANTS FOR SODIUM LITHIUM COUNTERTRANSPORT, AN INTERMEDIATE TRAIT FOR ESSENTIAL HYPERTENSION

Essential hypertension (EH) is a major risk factor for cardiovascular disorders, the leading cause of death in the United States. Given its great public health impact, it is crucial to understand the genetic basis of EH. EH is highly heterogeneous and to use an intermediate phenotype of EH, sodium lithium countertransport (SLC), will provide substantial advantage for disease genes discovery. We proposed two approaches to explore the genes for SLC.The first study examined the relationship between SLC and a positional candidate gene, SLC34A2, which is linked to SLC in baboon. We sequenced gene SLC34A2 in baboon and human. Strong homology was established in exonic organization and sequence between human and baboon SLC34A2 genes and extensive variation in both species was identified. Association studies between SLC and SLC34A2 were carried out in 1856 RFHS phase II individuals and 634 baboons. Significant association of SLC with human SNP rs3775909 (p=0.03) in SLC34A2 and haplotype block 2 (p<0.005) were observed. Strong evidence for association of SLC with SLC34A2 was found for baboon SNP Asn136Asn (p=0.0001). Consistent findings in two different species implied that SLC34A2 may be one of the genes involved in SLC. However, linkage analyses conditional on genotypes of baboon Asn136Asn suggest that Asn136Asn is not the primarily functional site for SLC. We conclude that SLC34A2 is associated with SLC, though it may not be the major effect gene.In second study, we integrated gene expression micrarray with linkage analysis to search for genes for SLC. Two independent microarrays (U133A and U133_plus_2.0) were used to identify the differentially expressed genes in high verse low SLC groups. Five genes, IER3, ARHGAP15, CD47, CDKAL1 and PRKRA, were among top 1% of differentially expressed genes in both arrays and also mapped to linkage region for SLC in RFHS Phase II population. A follow-up association study for IER3 shows that SNP rs8512 is significantly associated with SBP (p=0.002) and DBP (p=0.0008), and SNP rs2284174 has marginal association with SLC (p=0.055) and SBP (p=0.085). In conclusion, we identified some interesting susceptible genes for SLC by combining gene expression profiling and linkage study

Probing the Diffuse Lyman-alpha Emission on Cosmological Scales: Ly{\alpha} Emission Intensity Mapping Using the Complete SDSS-IV eBOSS Survey

Based on the Sloan Digital Sky Survey Data Release 16, we have detected the large-scale structure of Ly$\alpha$ emission in the Universe at redshifts $z = 2$--3.5 by cross-correlating quasar positions and Ly$\alpha$ emission imprinted in the residual spectra of luminous red galaxies. We apply an analytical model to fit the corresponding Ly$\alpha$ surface brightness profile and multipoles of the redshift-space quasar-Ly$\alpha$ emission cross-correlation function. The model suggests an average cosmic Ly$\alpha$ luminosity density of ${6.6_{-3.1}^{+3.3}}\times 10^{40} {\rm erg\, s^{-1} cMpc^{-3}}$, a $\sim 2\sigma$ detection with a median value about 8--9 times those estimated from deep narrowband surveys of Ly$\alpha$ emitters at similar redshifts. Although the low signal-to-noise ratio prevents us from a significant detection of the Ly$\alpha$ forest-Ly$\alpha$ emission cross-correlation, the measurement is consistent with the prediction of our best-fit model from quasar-Ly$\alpha$ emission cross-correlation within current uncertainties. We rule out the scenario that these Ly$\alpha$ photons mainly originate from quasars. We find that Ly$\alpha$ emission from star-forming galaxies, including contributions from that concentrated around the galaxy centers and that in the diffuse Ly$\alpha$ emitting halos, is able to explain the bulk of the the Ly$\alpha$ luminosity density inferred from our measurements. Ongoing and future surveys can further improve the measurements and advance our understanding of the cosmic Ly$\alpha$ emission field.Comment: Accepted for Publication in ApJS; 21 pages, 15 figures, 2 table

A multiple-time-step integration algorithm for particle-resolved simulation with physical collision time

In this paper, we present a multiple-time-step integration algorithm (MTSA) for particle collisions in particle-resolved simulations. Since the time step required for resolving a collision process is much smaller than that for a fluid flow, the computational cost of the traditional soft-sphere model by reducing the time step is quite high in particle-resolved simulations. In one state-of-the-art methodology, collision time is stretched to several times the flow solver time step for the fluid to adapt to the sudden change in particle motion. However, the stretched collision time is not physical, the hydrodynamic force may be severely underestimated during a stretched collision, and the simulation of sediment transport may be sensitive to the stretched collision time. The proposed MTSA adopts different time steps to resolve fluid flow, fluid-particle interaction, and particle collision. We assessed the MTSA for particle-wall collisions as well as particle-particle collisions, determined the optimal iteration number in the algorithm, and obtained excellent agreements with experimental measurements and reference simulations. The computational cost of the MTSA can be reduced to about one order of magnitude less than that using the traditional soft-sphere model with almost the same accuracy. The MTSA was then implemented in a particle-resolved simulation of sediment transport with thousands of particles. {By comparing the results obtained using the MTSA and a version of the stretching collision time algorithm similar to Costa et al.(2015), we found that stretching the collision time reduced particle stiffness, weakened particle entrainment, and affected some turbulence and particle statistics

Statistical Methods and Analysis for Human Genetic Copy Number Variation and Homozygosity Mapping

Single nucleotide polymorphism (SNP) arrays are used primarily for genetic association studies, with data being analyzed in most cases one SNP at a time. Several other applications of SNP arrays, however, involve integration of data over multiple markers for a single individual. Two such applications of SNP arrays are studies of copy number variants (CNVs) and regions of homozygosity or identity by descent. Hidden Markov models are a common approach to both of these problems, but other methods have been used as well. In this dissertation I address several methodological issues related to these two types of analysis, and also apply the methods to several datasets. The purpose of my studies in CNVs is to better detect and analyze CNVs. A major concern for all copy number variation (CNV) calling algorithms is their reliability and repeatability. I use family data as a verification standard to evaluate CNV calling strategies and methods. I make recommendations for how CNV calls can be used in genome-wide association studies. I then apply them to analyze CNVs in studies of psychiatric disorders and birth outcomes. Results from these studies have the potential for great public health significance, because they can lead to better understanding of the genetic etiology and eventually to better markers for disease screening and diagnosis. Homozygosity mapping is a powerful method to map genes for rare recessive disorders. However, current methods are not ideal, especially when using high density SNP array data from consanguineous families. This study develops improved methods for homozygosity mapping using dense SNP data, and thus will improve the ability of geneticists to find genetic causes of rare recessive diseases. Many of these rare disorders are life-threatening; identification of the disease genes may help with early diagnosis and treatment

The growth of non-c-axis-oriented ferroelectric BLT thin films on silicon using ZnO buffer layer

Lanthanum-doped bismuth titanate (BLT) thin films were grown on buffered Si substrates using a RF magnetron sputtering system. Electrically conducting ZnO layers were used as an effective buffer layer to facilitate the growth of the ferroelectric thin films. X-ray diffraction data shows the Aurivilius phase structure with the highest diffraction peak (1 1 7), indicating non-c-axis-oriented microstructure. Random oriented plate-like grains were observed using scanning electron microscopy. The ferroelectric nature of the film was proved by ferroelectric domain switching under an electrical field

Target Selection and Annotation for the Structural Genomics of the Amidohydrolase and Enolase Superfamilies

To study the substrate specificity of enzymes, we use the amidohydrolase and enolase superfamilies as model systems; members of these superfamilies share a common TIM barrel fold and catalyze a wide range of chemical reactions. Here, we describe a collaboration between the Enzyme Specificity Consortium (ENSPEC) and the New York SGX Research Center for Structural Genomics (NYSGXRC) that aims to maximize the structural coverage of the amidohydrolase and enolase superfamilies. Using sequence- and structure-based protein comparisons, we first selected 535 target proteins from a variety of genomes for high-throughput structure determination by X-ray crystallography; 63 of these targets were not previously annotated as superfamily members. To date, 20 unique amidohydrolase and 41 unique enolase structures have been determined, increasing the fraction of sequences in the two superfamilies that can be modeled based on at least 30% sequence identity from 45% to 73%. We present case studies of proteins related to uronate isomerase (an amidohydrolase superfamily member) and mandelate racemase (an enolase superfamily member), to illustrate how this structure-focused approach can be used to generate hypotheses about sequence-structure-function relationships

An H{\alpha} Impression of Ly{\alpha} Galaxies at z≃6z\simeq6 with Deep JWST/NIRCam Imaging

We present a study of seven spectroscopically confirmed Ly{\alpha} emitting galaxies at redshift $z\simeq6$ using the James Webb Space Telescope (JWST) NIRCam images. These galaxies, with a wide range of Ly{\alpha} luminosities, were recently observed in a series of NIRCam broad- and medium-bands. We measure the continuum and H{\alpha} line properties of the galaxies using the combination of the NIRCam photometry and archival Hubble Space Telescope imaging data. We find that galaxies with bluer UV continuum slopes likely have higher escape fractions of Ly{\alpha} photons. We also find that galaxies with higher Ly{\alpha} line emission tend to produce ionizing photons more efficiently. The most Ly{\alpha}-luminous galaxy in the sample has a high ionizing photon production efficiency of log$_{10} \xi_{\rm ion, 0}$ (Hz erg$^{-1}$) > 26. Our results support that Ly{\alpha} galaxies may have served as an important contributor to the cosmic reionization. Blue and bright Ly{\alpha} galaxies are also excellent targets for JWST follow-up spectroscopic observations.Comment: 10 pages, 4 figures, 2 tables, submitted to ApJ

Vibration characteristics and environmental responses of different vehicle-track-ballast coupling systems in subway operation

The vibration characteristics of two ballast beds are analyzed in this study from five aspects including the amplitude-frequency characteristic curve of foundation reaction. This study also shows that the maximum ground Z vibration level caused by a normal monolithic ballast bed structure is 75 dB. The range of its vibration influence during daytime is approximately 30 m. The maximum ground Z vibration level caused by a rubber floating slab track structure is 52 dB, whereas that caused by a steel spring floating slab track structure is 57 dB. The maximum damping amount in horizontal speed of a rubber floating slab track structure is 74 %, whereas the reduction of vertical ground vibration speed and acceleration is 92 % and 93 %, respectively. The reduction in Z level is 37 %. The horizontal speed reduction in a steel spring floating slab track structure is 71 %, whereas the reduction of ground vertical vibration speed and acceleration is 83 % and 84 %, respectively. The reduction in Z level is 29 %