Data Cleaning, Preliminary Summary and Evaluation of Diagnostic Criteria of T-Cell Data in a Juvenile Onset Diabetes Cohort

Type 1 diabetes mellitus (T1DM) is an autoimmune disease manifested by an autoimmune attack on pancreatic beta-islet cells. T1DM can occur at any age. However, it is most often diagnosed in children, adolescents, or young adults. My thesis is derived from a large longitudinal study of Juvenile Onset Diabetes (JOD) at Children’s Hospital of Pittsburgh. The objectives are: 1) Data cleaning and preliminary summary of the cohort with respect to T-cell data. 2) Evaluating the T-cell data criteria used for the prediction of the diabetes. An extensive data examination was made for accuracy and consistency. A preliminary summary of the stimulation index (SI) for the test analytes and the number of positive antigens was performed by demographic sub-groups, HLA-DQ serotype, and follow up time. Using the ROC analysis, an evaluation of diagnosis test performance based on two different criteria was performed. The JOD dataset had few errors with an error rate under 0.5%. The accuracy and consistency of the data is good. New onsets and first degree relatives (FDRs) nonconverters had a relatively stable SI as well as positive antigen tests results. The SI level and positive test results are higher in new onsets when compared with FDRs. FDR-converters (those subsequently developing diabetes) prior to using insulin have SIs and number of positive antigens similar to FDR-nonconverters; and FDR-converters after starting insulin have results similar to new onsets. The recommended SI cutoff of 1.5 indicating positive response appears reasonable. However, the cutoff still may be optimized for better prediction. Evidence suggests that a lower cutoff within 1.25 to 1.5 may be better and the number of positive antigens could move from ≥4 to greater than 5 or 6. Public health significance: Development of a better understanding of the pattern of T-cell response in diabetes and non-diabetic children, and those progressing to diabetes, may give us tools to predict the early onset of disease. It is this point in time where therapeutic intervention could be focused to help stem the development of T1DM or to dramatically reduce its severity

Entry Flow and Heat Transfer of Laminar and Turbulent Forced Convection of Nanofluids in a Pipe and a Channel

This thesis presents a numerical investigation of laminar and turbulent fluid flow and convective heat transfer of nanofluids in the entrance and fully developed regions of flow in a channel and a pipe. In recent years, nanofluids have attracted attention as promising heat transfer fluids in many industrial processes due to their high thermal conductivity. Nanofluids consist of a suspension of nanometer-sized particles of higher thermal conductivity in a liquid such as water. The thermal conductivity of nanoparticles is typically an order-of-magnitude higher than the base liquid, which results in a significant increase in the thermal performance of the nanofluid even with a small percentage of nanoparticles (~4% by volume) in the base liquid. In this study, Al2O3, CuO and carbon nanotube (CNT) nanoparticles with the particle concentration ranging from 0 to 4 % by volume suspended in water are considered as nanofluids. Entrance flow field and heat transfer of nanofluids in a channel and pipe are computed using the commercially available software ANSYS FLUENT 14.5. Both constant wall temperature and constant heat flux boundary conditions are considered. An unstructured two-dimensional mesh is generated by the software ICEM. For turbulent flow simulations, two-equation k-epsilon, standard k-omega and SST k-omega models as well as the one-equation Spalart-Allmaras models are employed. The results are validated and compared using the experimental data and other empirical correlations available in the literature. The entrance length of laminar and turbulent flows in a circular pipe and channel are calculated and compared with the established correlations in the literature. The effect of particle concentrations, Reynolds number and type of the nanoparticles on the forced convective heat transfer performance are estimated and discussed in detail. The results show significant improvement in heat transfer performance of nanofluids, especially the CNT nanofluids, compared to the conventional base fluids

How the Transition Region Along the Cascadia Megathrust Influences Coseismic Behavior: Insights From 2‐D Dynamic Rupture Simulations

There is a strong need to model potential rupture behaviors for the next Cascadia megathrust earthquake. However, there exists significant uncertainty regarding the extent of downdip rupture and rupture speed. To address this problem, we study how the transition region (i.e., the gap), which separates the locked from slow‐slip regions, influences coseismic rupture propagation using 2‐D dynamic rupture simulations governed by a slip‐weakening friction law. We show that rupture propagation through the gap is strongly controlled by the amount of accumulated tectonic initial shear stress and gap friction level. A large amplitude negative dynamic stress drop is needed to arrest downdip rupture. We also observe downdip supershear rupture when the gradient in effective normal stress from the locked to slow‐slip regions is dramatic. Our results justify kinematic rupture models that extend below the gap and suggests the possibility of high‐frequency energy radiation during the next Cascadia megathrust earthquake.Plain Language SummaryHow large, deep, and damaging a future earthquake will be depends on factors such as energy release that must be constrained by precise observations of previous earthquakes in the same area. But such data are rarely available. Instead, computer models of earthquakes guided by the laws of physics can provide us with estimates of potential ground shaking for a future event. In our study, we design two‐dimensional earthquake simulations for the Cascadia fault below the northwestern United States coast and test different hypotheses for how stress may be accumulating at depth along this fault. Our models focus on a portion of the fault referred to as the “gap.” The gap physically separates a shallow region that slips during large earthquakes from a deeper region that experiences intermittent slip between large earthquakes. A gap region similar to that in Cascadia is also found in Japan, Mexico, and around other active faults worldwide. We find that our simulated rupture is able to extend to deeper regions at faster speeds given the current understanding of stress levels and earthquake fault friction in the gap. While this work represents only a first step toward understanding how stresses and friction influence how the Cascadia fault might slip, it lays the foundation for modeling more complex physics that can help scientists better predict shaking from seismic waves.Key PointsWe examine dynamic source effects on along‐dip rupture propagation for a Cascadia megathrust earthquakeSimulated earthquake rupture is able to penetrate through the transition zone and reach the deeper slow‐slip regionOur results underscore the potential for a deeper downdip rupture and faster rupture speed than previously assumed in kinematic modelsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148357/1/grl58609.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148357/2/grl58609_am.pd

Effects of Low‐Velocity Fault Damage Zones on Long‐Term Earthquake Behaviors on Mature Strike‐Slip Faults

Mature strike‐slip faults are usually surrounded by a narrow zone of damaged rocks characterized by low seismic wave velocities. Observations of earthquakes along such faults indicate that seismicity is highly concentrated within this fault damage zone. However, the long‐term influence of the fault damage zone on complete earthquake cycles, that is, years to centuries, is not well understood. We simulate aseismic slip and dynamic earthquake rupture on a vertical strike‐slip fault surrounded by a fault damage zone for a thousand‐year timescale using fault zone material properties and geometries motivated by observations along major strike‐slip faults. The fault damage zone is approximated asan elastic layer with lower shear wave velocity than the surrounding rock. We find that dynamic wave reflections, whose characteristics are strongly dependent on the width and the rigidity contrast of the fault damage zone, have a prominent effect on the stressing history of the fault. The presence of elastic damage can partially explain the variability in the earthquake sizes and hypocenter locations along a single fault, which vary with fault damage zone depth, width and rigidity contrast from the host rock. The depth extent of the fault damage zone has a pronounced effect on the earthquake hypocenter locations, and shallower fault damage zones favor shallower hypocenters with a bimodal distribution of seismicity along depth. Our findings also suggest significant effects on the hypocenter distribution when the fault damage zone penetrates to the nucleation sites of earthquakes, likely being influenced by both lithological (material) and rheological (frictional) boundaries.Plain Language SummaryLarge strike‐slip earthquakes tend to create a zone of fractured network surrounding the main fault. This zone, referred to as a fault damage zone, becomes highly localized as the fault matures, with a width of few hundred meters. The influence of this fault damage zone on earthquake characteristics remains elusive since we do not have enough long‐term observations along a single fault. We use numerical simulations to examine the behavior of earthquake nucleation and rupture dynamics on a fault surrounded by a damage zone over a thousand‐year timescale. Our simulations reveal that the reflection of seismic waves from the fault damage zone boundaries leads to complexity in earthquake sequences, such as variability in earthquake locations and sizes. We also show that a shallowfault damage zone produces shallower earthquakes with the earthquake depths centered around two locations (bimodal), as opposed to a deep fault damage zone with the earthquake depths centered around a single location (unimodal). Our study suggests that imaging the geometry and physical properties of fault damage zones could potentially give us clues about depths of future earthquakes and improve earthquake probabilistic hazard assessment.Key PointsFully dynamic earthquake cycle simulations show persistent heterogeneous stress distribution generated by fault zone wavesFaults surrounded by low‐velocity damage zones lead to more complexities in earthquakelocation, size, and slip patternsBoth lithology and rheology influence the depth distribution of seismicity, with shallow fault damage zones exhibiting bimodal distributionPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156497/2/jgrb54370.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156497/1/jgrb54370_am.pd

Earthquake ruptures modulated by waves in damaged fault zones

Faults are usually surrounded by damaged zones of lower elastic moduli and seismic wave velocities than their host rocks. If the interface between the damaged rocks and host rocks is sharp enough, earthquakes happening inside the fault zone generate reflected waves and head waves, which can interact with earthquake ruptures and modulate rupture properties such as rupture speed, slip rate, and rise time. We find through 2–D dynamic rupture simulations the following: (1) Reflected waves can induce multiple slip pulses. The rise time of the primary pulse is controlled by fault zone properties, rather than by frictional properties. (2) Head waves can cause oscillations of rupture speed and, in a certain range of fault zone widths, a permanent transition to supershear rupture with speeds that would be unstable in homogeneous media. (3) Large attenuation smears the slip rate function and delays the initial acceleration of rupture speed but does not affect significantly the rise time or the period of rupture speed oscillations. (4) Fault zones cause a rotation of the background stress field and can induce plastic deformations on both extensional and compressional sides of the fault. The plastic deformations are accumulated both inside and outside the fault zone, which indicates a correlation between fault zone development and repeating ruptures. Spatially periodic patterns of plastic deformations are formed due to oscillating rupture speed, which may leave a permanent signature in the geological record. Our results indicate that damaged fault zones with sharp boundaries promote multiple slip pulses and supershear ruptures

The Yellow Sea Surface Cold Patches in Warm Seasons

An important hydrographic phenomenon in the Yellow Sea is the surface cold patches (SCP) in warm seasons, among which the most conspicuous are the Shandong SCP, Subei SCP, and Mokpo SCP. Previous studies based on monthly mean fields propose that these patches result from the collaboration of tidal mixing and tidal induced upwelling. While this is true for patches like the Shandong SCP, the monthly mean tidal mixing and upwelling alone cannot explain all their formations. In this study, through a detailed analysis of their patterns over a spring-neap tidal cycle, it is found that the Subei and Mokpo SCPs show distinct spring-neap variations. During the neap tide phase, strong stratification is established, and hence the cold patches in these two areas may be greatly weakened or even suppressed, while during the spring tide phase, the surface temperature reaches its minimum. That is to say, for these two SCPs, besides the well-accepted mechanisms, the effect of spring-neap tidal variation must be taken into account

Pulse-like ruptures induced by low-velocity fault zones

Low-velocity fault zones (LVFZs) are found in most mature faults. They are usually 100–400 m wide and have ~20%–60% wave velocity reductions relative to the country rock. To study the effect of LVFZs on earthquake rupture and the radiated wavefield, we conducted two-dimensional (2-D) simulations of dynamic rupture on faults that bisect a LVFZ, considering a range of velocity reductions and widths. Most earthquakes apparently have slip rise times much shorter than their overall rupture duration. A number of dynamic mechanisms for such pulse-like ruptures have been proposed, including frictional self-healing, fault strength heterogeneities, and bimaterial effects. We find that ruptures in LVFZs with strong enough wave velocity contrast behave as pulses. These pulses are generated by fault locking induced by waves reflected from the boundaries of the LVFZ. This mechanism of pulse generation is robust to variations of initial stress, smoothness of the LVFZ structure, rupture mode, and exclusion of frictional healing. Moreover, we find that LVFZs can generate complex rupture patterns. LVFZs with low-velocity reduction induce multiple rupture fronts involving coexisting pulses and cracks. LVFZs with certain widths can accelerate the transition to supershear rupture speed. These additional effects of LVFZs on dynamic rupture can contribute to the complexity of high-frequency ground motions

Detection and Genetic Analysis of Porcine Bocavirus

Porcine Bocavirus (PBoV) has been reported to be associated with postweaning multisystemic wasting syndrome and pneumonia in pigs. In this study, a survey was conducted to evaluate the prevalence of PBoV in slaughter pigs, sick pigs, asymptomatic pigs and classical swine fever virus (CSFV) eradication plan herds in five provinces of China (Henan, Liaoning, Shandong, Hebei and Tianjin) by means of PCR targeting NS1 gene of PBoV. Among the total of 403 tissue samples, 11.41% were positive for PBoV. The positive rates of spleen (20.75%) and inguinal lymph node (27.18%) are higher than those of other organs. PCR products of twenty PBoV positive samples from slaughter pigs were sequenced for phylogenetic analysis. The result revealed that PBoV could be divided into 6 groups (PBoV-a~PBoV-f). All PBoV sequenced in this study belong to PBoV-a–PBoV-d with 90.1% to 99% nucleotide identities. Our results exhibited significant genetic diversity of PBoV and suggested a complex prevalence of PBoV in Chinese swine herds. Whether this diversity of PBoV has a significance to pig production or even public health remains to be further studied

Is Centralized Training with Decentralized Execution Framework Centralized Enough for MARL?

Centralized Training with Decentralized Execution (CTDE) has recently emerged as a popular framework for cooperative Multi-Agent Reinforcement Learning (MARL), where agents can use additional global state information to guide training in a centralized way and make their own decisions only based on decentralized local policies. Despite the encouraging results achieved, CTDE makes an independence assumption on agent policies, which limits agents to adopt global cooperative information from each other during centralized training. Therefore, we argue that existing CTDE methods cannot fully utilize global information for training, leading to an inefficient joint-policy exploration and even suboptimal results. In this paper, we introduce a novel Centralized Advising and Decentralized Pruning (CADP) framework for multi-agent reinforcement learning, that not only enables an efficacious message exchange among agents during training but also guarantees the independent policies for execution. Firstly, CADP endows agents the explicit communication channel to seek and take advices from different agents for more centralized training. To further ensure the decentralized execution, we propose a smooth model pruning mechanism to progressively constraint the agent communication into a closed one without degradation in agent cooperation capability. Empirical evaluations on StarCraft II micromanagement and Google Research Football benchmarks demonstrate that the proposed framework achieves superior performance compared with the state-of-the-art counterparts. Our code will be made publicly available