Practical Type Inference for the GADT Type System

Generalized algebraic data types (GADTs) are a type system extension to algebraic data types that allows the type of an algebraic data value to vary with its shape. The GADT type system allows programmers to express detailed program properties as types (for example, that a function should return a list of the same length as its input), and a general-purpose type checker will automatically check those properties at compile time. Type inference for the GADT type system and the properties of the type system are both currently areas of active research. In this dissertation, I attack both problems simultaneously by exploiting the symbiosis between type system research and type inference research. Deficiencies of GADT type inference algorithms motivate research on specific aspects of the type system, and discoveries about the type system bring in new insights that lead to improved GADT type inference algorithms. The technical contributions of this dissertation are therefore twofold: in addition to new GADT type system properties (such as the prevalence of pointwise type information flow in GADT patterns, a generalized notion of existential types, and the effects of enforcing the GADT branch reachability requirement), I will also present a new GADT type inference algorithm that is significantly more powerful than existing algorithms. These contributions should help programmers use the GADT type system more effectively, and they should also enable language implementers to provide better support for the GADT type system

Personal Exposure to Submicrometer Particles and Heart Rate Variability in Human Subjects

We conducted a study on two panels of human subjects—9 young adults and 10 elderly patients with lung function impairments—to evaluate whether submicrometer particulate air pollution was associated with heart rate variability (HRV). We measured these subjects’ electrocardiography and personal exposure to number concentrations of submicrometer particles with a size range of 0.02–1 μm (NC(0.02–1)) continuously during daytime periods. We used linear mixed-effects models to estimate the relationship between NC(0.02–1) and log(10)-transformed HRV, including standard deviation of all normal-to-normal intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF, 0.04–0.15 Hz), and high frequency (HF, 0.15–0.40 Hz), adjusted for age, sex, body mass index, tobacco exposure, and temperature. For the young panel, a 10,000-particle/cm(3) increase in NC(0.02–1) with 1–4 hr moving average exposure was associated with 0.68–1.35% decreases in SDNN, 1.85–2.58% decreases in r-MSSD, 1.32–1.61% decreases in LF, and 1.57–2.60% decreases in HF. For the elderly panel, a 10,000-particle/cm(3) increase in NC(0.02–1) with 1–3 hr moving average exposure was associated with 1.72–3.00% decreases in SDNN, 2.72–4.65% decreases in r-MSSD, 3.34–5.04% decreases in LF, and 3.61–5.61% decreases in HF. In conclusion, exposure to NC(0.02–1) was associated with decreases in both time-domain and frequency-domain HRV indices in human subjects

Effects of Particle Size Fractions on Reducing Heart Rate Variability in Cardiac and Hypertensive Patients

It is still unknown whether the associations between particulate matter (PM) and heart rate variability (HRV) differ by particle sizes with aerodynamic diameters between 0.3 μm and 1.0 μm (PM(0.3–1.0)), between 1.0 μm and 2.5 μm (PM(1.0–2.5)), and between 2.5 μm and 10 μm (PM(2.5–10)). We measured electrocardiographics and PM exposures in 10 patients with coronary heart disease and 16 patients with either prehypertension or hypertension. The outcome variables were standard deviation of all normal-to-normal (NN) intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF; 0.04–0.15 Hz), high frequency (HF; 0.15–0.40 Hz), and LF:HF ratio for HRV. The pollution variables were mass concentrations of PM(0.3–1.0), PM(1.0–2.5), and PM(2.5–10). We used linear mixed-effects models to examine the association between PM exposures and log(10)-transformed HRV indices, adjusting for key personal and environmental attributes. We found that PM(0.3–1.0) exposures at 1- to 4-hr moving averages were associated with SDNN and r-MSSD in both cardiac and hypertensive patients. For an interquartile increase in PM(0.3–1.0), there were 1.49–4.88% decreases in SDNN and 2.73–8.25% decreases in r-MSSD. PM(0.3–1.0) exposures were also associated with decreases in LF and HF for hypertensive patients at 1- to 3-hr moving averages except for cardiac patients at moving averages of 2 or 3 hr. By contrast, we found that HRV was not associated with either PM(1.0–2.5) or PM(2.5–10). HRV reduction in susceptible population was associated with PM(0.3–1.0) but was not associated with either PM(1.0–2.5) or PM(2.5–10)

Characterization of flow-pattern and heat transfer of micro flat heat pipes

Paper presented to the 10th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Florida, 14-16 July 2014.In this study, thermal performance and flow visualization of a double layer flat micro vapor chamber are carried out. Two micro vapor chambers having pin fin and pin fin array support structure were fabricated and tested. The micro vapor chambers were composed of silicon and glass wafers having an overall size of 35 mm × 40 mm × 1.525 mm. Test results show that both the pin fin and pin fin array vapor chambers show appreciably lower thermal resistance as compared to the solid silicon counterpart, the thermal resistance of the pin fin vapor chamber is about 52-60% of the solid silicon whereas the corresponding thermal resistance of pin fin array is only 17-20 % of the solid silicon. The thermal resistance of the pin fin vapor chamber is moderately increased with the increase of supplied power whereas opposite trend is encountered for the pin fin array. The phenomenon is associated with the influence of dry-out phenomenon. It is found that the pin fin array vapor chamber is still in function even for an upside-down arrangement. The thermal resistance, however, is reduced with the rise of tilt angle, and the vertical arrangement gives the lowest thermal resistance. However, the thermal resistance is considerably increased if the heat source is placed upwards, and the corresponding thermal resistance for an upside-down heat source can be threefold higher than that of the vertical arrangement.dc201

Anti-inflammatory effects of bitongling granules are mediated through the suppression of miR-21/p38 MAPK/TLR4/NF-κB signaling in H9C2 rat cardiac cells exposed to lipopolysaccharides

Purpose: To assess the protective effects of bitongling granules on H9C2 cells exposed to lipopolysaccharides (LPS) in the management of rheumatoid arthritis (RA)-induced myocardial inflammation.Methods: The effects of bitongling granule (BTLG) drug-containing serum were assessed in myocarditis models established in rat cardiac cells. MicroRNA-21 (miR-21) levels were evaluated by qRT-PCR while MTT assays were performed to assess cell viability. ELISA assay was used to evaluate tumor necrosis factor α (TNF-α), interleukin 17 (IL-17) and interleukin 6 (IL-6) levels in cell culture supernatants. Apoptosis was determined by flow cytometry (FCM). Quantitative mitogen-activated protein kinase (MAPK)/p38, toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB)/p65 levels were evaluated by western blot and immunofluorescenceResults: BTLG increased cardiac cell activity and exhibited anti-inflammatory effect. It also inhibited LPS-induced H9C2 apoptosis and suppressed p65 NF-κB phosphorylation (p-p65 NF-κB), TLR4, and p38 MAPK phosphorylation (p-p38 MAPK). BTLG also reduced miR-21 expression, and the overexpression of the miR-21 inhibitor in H9C2 suppressed apoptosis. Moreover, p-p38 MAPK, TLR4 and p-p65 NF-κB expression were down-regulated in miR-21 inhibitor transfected H9C2s. The inhibition of p38/TLR4/ NF-κB signaling might have occurred via the suppression of miR-21 by BTLG.Conclusion: The results show that BTLG inhibits the inflammatory reaction involved in p38MAPK/TLR4/ NF-κB signaling pathway and can prevent RA-induced cardiac disease, suggesting that BTLP treatment may be beneficial for the management of arthritic cardiomyopathy

The extremely small body size of Williamson’s mouse deer (Tragulus williamsoni) allows coexistence with sympatric larger ungulates through temporal avoidance

Research on the coexistence of congeneric species is essential for understanding community assemblages. Smaller competitors are expected to avoid larger ones, either spatially or temporally, to reduce interspecific competition. According to the spatial scaling law, the greater the difference in body size, the weaker the competitive interactions of the competitors. However, this is not confirmed in the guild of tropical forest ungulates. In this study, we assessed the competitive interactions of Williamson’s mouse deer (Tragulus williamsoni), an endangered species and one of the smallest ungulates in the world, with sympatric larger ungulates. We hypothesized that: 1) because of its extremely small body size, competition with the larger ungulates would be relatively weak, allowing spatial co-existence but still requiring temporal avoidance, and 2) the strength of avoidance would increases with decreasing differences in body size. We set up 238 camera traps from January 2017 to January 2021 to survey Williamson’s mouse deer and the sympatric larger ungulate species, that is, northern red muntjac (Muntiacus vaginalis), wild boar (Sus scrofa), Chinese serow (Capricornis milneedwardsii), and sambar (Rusa unicolor), in the protected areas of Mengla County, southwestern China. We then performed spatio-temporal analyses, including occupancy models, daily activity patterns, and a time interval analysis. Spatially, there was no significant avoidance. Temporally, Williamson’s mouse deer had different daily activity patterns and direct temporal avoidance of all larger ungulate species. The lack of spatial avoidance and strong temporal avoidance supported our first hypothesis, but the stronger avoidance of much larger species ran counter to our second hypothesis. Our results revealed the coexistence mechanism between Williamson’s mouse deer and sympatric larger ungulates and suggested that the difference in body size is limited in explaining the competitive interactions of tropical forest ungulates due to the effects of multiple ecological processes. This deepens our understanding of the relationship between species trait differences and community assembly in tropical forest ecosystems

Clonal spread of multidrug-resistant Acinetobacter baumannii in eastern Taiwan

Background and PurposeThis study was conducted to investigate the molecular epidemiology and antimicrobial susceptibility of multidrug-resistant (MDR) Acinetobacter baumannii to three types of antibiotics.MethodsOne hundred and thirty-four specimens of MDR A baumannii were collected from three branches (Taipei, Dalin, and Hualien branches) of Buddhist Tzu Chi Hospital, which are located in northern, southern, and eastern Taiwan, during 2007. Genotyping was performed by pulsed-field gel electrophoresis. Antibiotic susceptibilities to colistin, rifampicin, and tigecycline were determined. The synergistic effects of rifampin and colistin were also evaluated.ResultsAntibiotic susceptibility testing showed that 10.4%, 47.8% and 45.5% of the MDR A baumannii isolates are resistant to colistin, rifampicin, and tigecycline, respectively. A majority of the rifampicin-resistant isolates (62.7%) were found in the Haulien branch, whereas 62.2% of tigecycline-resistant isolates were found in the Taipei branch. The combination of colistin and rifampicin had a synergistic effect on all of the isolates. Genotyping by pulsed-field gel electrophoresis identified 17, 23, and 11 pulsotypes in the Taipei, Dalin, and Haulien branches, respectively. Furthermore, 74.5% of isolates in the Haulien branch were identified as one of three pulsotypes. Among 37 rifampicin-resistant and 22 tigecycline-resistant MDR A baumannii isolates found in the Haulien branch, 51.3% (19/37) and 50% (11/22) of the isolates belonged to the same clone, respectively.ConclusionThis study confirms the high prevalence of resistance to rifampicin and tigecycline in MDR A baumannii in the three hospitals that were studied, and the high proportion of identical strains that exist in eastern Taiwan

Directed Evolution of a Lysosomal Enzyme with Enhanced Activity at Neutral pH by Mammalian Cell-Surface Display

SummaryHuman β-glucuronidase, due to low intrinsic immunogenicity in humans, is an attractive enzyme for tumor-specific prodrug activation, but its utility is hindered by low activity at physiological pH. Here we describe the development of a high-throughput screening procedure for enzymatic activity based on the stable retention of fluorescent reaction product in mammalian cells expressing properly folded glycoproteins on their surface. We utilized this procedure on error-prone PCR and saturation mutagenesis libraries to isolate β-glucuronidase tetramers that were up to 60-fold more active (kcat/Km) at pH 7.0 and were up to an order of magnitude more effective at catalyzing the conversion of two structurally disparate glucuronide prodrugs to anticancer agents. The screening procedure described here can facilitate investigation of eukaryotic enzymes requiring posttranslational modifications for biological activity