Development of Organic Carbon Monoxide prodrugs

Carbon monoxide (CO) is an endogenously produced gasotransmitter in mammals and may have signaling roles in bacteria as well. It has many recognized therapeutic effects. A significant challenge in this field is the development of pharmaceutically acceptable forms of CO delivery with controllable and tunable release rates. Our lab has designed a series of organic CO prodrugs as prototypes of “carbon monoxide in a pill.” In the first project, a series of such CO prodrugs was synthesized to examine the structure-release rate in aqueous solution at neutral pH. CO prodrugs with triggered release mechanisms are highly desirable for targeted delivery. In the second project, we focused on the development of reactive oxygen species ROS-sensitive CO prodrugs, which selectively deliver CO to cells with elevated ROS levels and sensitize cancer cells to chemotherapy. CO prodrugs as such could serve as powerful tools for targeted delivery to disease sites with elevated ROS levels and for exploring the therapeutic applications of CO. In the third project, we focused on metal-free CO prodrugs with dual-responsive endogenous triggers, which have the advantage of controlled activation at the desired site of action. These CO prodrugs afford highly selective release profiles as compared to others with no or a single trigger. In addition, one representative CO prodrug showed significant anti-inflammatory effects both in vitro and in a LPS-simulated systemic inflammation models, suggesting its possible application in treating systemic inflammatory conditions. The prodrug also conferred very pronounced protective effects against LPS-induced acute liver injury. These results firmly established such CO prodrugs as either research tools or candidate compounds for the treatment of systemic inflammation or other inflammation-related organ injuries

Does enterprise risk management benefit manufacturing firms? Evidence from China

It is observed that Enterprise risk management (ERM) framework has been adopted by some manufacturing firms in China in the past years. To investigate the effectiveness of ERM, data of A-share listed manufacturing firms in Shanghai and Shenzhen stock exchange during 2010-2019 are adopted from Wind database and CSMAR database, two large domestic databases, to examine the impact of ERM on value of manufacturing firms. Treatment effects model and genenralised method of moments (GMM) are employed to derive the empirical results. Our results show that adoption of ERM can add value to the firms, and firms benefitmore from high-quality ERM program. Furthermore, the impact of ERM seems to be more significant among the manufacturing firms with smaller scale, or stronger institutional shareholding, or international business. Our findings encourage the manufacturing firms to implement ERM program and improve the program to achieve its targets

Asymptotic properties of spiked eigenvalues and eigenvectors of signal-plus-noise matrices with their applications

This paper is to consider a general low-rank signal plus noise model in high dimensional settings. Specifically, we consider the noise with a general covariance structure and the signal to be at the same magnitude as the noise. Our study focuses on exploring various asymptotic properties related to the spiked eigenvalues and eigenvectors. As applications, we propose a new criterion to estimate the number of clusters, and investigate the properties of spectral clustering

Real-time frequency measurement based on parallel pipeline FFT for time-stretched acquisition system

Real-time frequency measurement for non-repetitive and statistically rare signals are challenging problems in the electronic measurement area, which places high demands on the bandwidth, sampling rate, data processing and transmission capabilities of the measurement system. The time-stretching sampling system overcomes the bandwidth limitation and sampling rate limitation of electronic digitizers, allowing continuous ultra-high-speed acquisition at refresh rates of billions of frames per second. However, processing the high sampling rate signals of hundreds of GHz is an extremely challenging task, which becomes the bottleneck of the real-time analysis for non-stationary signals. In this work, a real-time frequency measurement system is designed based on a parallel pipelined FFT structure. Tens of FFT channels are pipelined to process the incoming high sampling rate signals in sequence, and a simplified parabola fitting algorithm is implemented in the FFT channel to improve the frequency precision. The frequency results of these FFT channels are reorganized and finally uploaded to an industrial personal computer for visualization and offline data mining. A real-time transmission datapath is designed to provide a high throughput rate transmission, ensuring the frequency results are uploaded without interruption. Several experiments are performed to evaluate the designed real-time frequency measurement system, the input signal has a bandwidth of 4 GHz, and the repetition rate of frames is 22 MHz. Experimental results show that the frequency of the signal can be measured at a high sampling rate of 20 GSPS, and the frequency precision is better than 1 MHz.Comment: 11 pages, 14 figure

Numerical simulation and experimental investigation of diesel fuel reforming over a Pt/CeO₂-Al₂O₃ catalyst

In order to benefit from a realistic hydrogen production device equipped on a vehicle, issues with the effects of the process parameters on H2 and CO yield need to be resolved. In this study, a reduced mechanism for n-heptane (as a surrogate diesel) reforming over a Pt/CeO2-Al2O3 catalyst is adopted to investigate the effects of the process parameters on H2 and CO yield, and the preferred process parameters are concluded. In addition, the comparison of reforming bench tests of diesel fuel and n-heptane under typical diesel engine operating conditions is conducted. The n-heptane reforming simulation results show that the maximum H2 and CO yield moves toward unity with the decreased GHSV and increased reaction temperature, and the GHSV of 10,000 1/h, O2/C ratio of 0.6 and reaction temperature of 500 °C is preferable. The contrast experiments reveal that the change trend of H2 and CO yield displays consistence, although the difference of the average H2 and CO yield results is obvious. The characteristics of n-heptane reforming can represent H2 and CO yield features of diesel fuel reforming at typical reaction temperatures in a way

Developmental trajectories of reading development and impairment from ages 3 to 8 years in Chinese children

Early prediction of reading disabilities in Chinese is important for early remediation efforts. In this 6-year longitudinal study, we investigated the early cognitive predictors of reading skill in a statistically representative sample of Chinese children from Beijing.Two hundred sixty-one (261) native Chinese children were administered seven language-related skills over three years between the ages of 3 and 6 years. Performances on these skills were then examined in relation to subsequent word reading accuracy and fluency. Individual differences in developmental profiles across tasks were then estimated using growth mixture modeling.Four developmental trajectories were classified – the typical (control), catch-up (with low initial cognitive performances but adequate subsequent reading), literacy-related-cognitive-delay (with difficulties in morphological awareness, phonological awareness, and speeded naming and subsequent word recognition), and language-delay (relatively low across all tasks) groups.Findings suggest that the combination of phonological awareness, rapid naming and morphological awareness are essential in the early prediction of later reading difficulties in Chinese children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79090/1/j.1469-7610.2010.02311.x.pd

Milk fat globule membrane promotes brain development in piglets by enhancing the connection of white matter fiber trace

IntroductionBrain development during infancy is crucial for later health and development. Although Milk Fat Globule Membrane (MFGM) has been demonstrated to enhance brain development, further investigation is needed to determine the optimal dose.MethodsIn this study, 80 piglets aged 2 days were randomly assigned to four groups: Control group, MFGM-L (1.74 g MFGM per 100 g diet), MFGM-M (4.64 g MFGM per 100 g diet), and MFGM-H (6.09 g MFGM per 100 g diet). Daily body weight and milk intake of the piglets were recorded until 31 days postnatal. Learning and memory abilities were evaluated using the spatial T-maze test on day 15. MRI analysis was conducted to assess functional and structural changes in brain tissues. Additionally, mRNA and protein expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF-3) in the hippocampus and prefrontal cortex were evaluated.ResultsThe results indicated that the MFGM supplemented diet significantly improved the accuracy of the piglets in the T-maze test, with the MFGM-L group exhibiting the best performance. MRI showed no volumetric differences in the gray and white matter between the groups. However, the fractional anisotropy in the left and right hippocampus of piglets in the MFGM-L group was significantly higher than in the other three groups. Furthermore, there was a strong correlation between the accuracy of the T-maze test and hippocampal fractional anisotropy.DiscussionThe MFGM supplemented diet also increased the expression of BDNF in the cerebral cortex. However, the changes in BDNF were not consistent with the results of the T-maze test. In conclusion, adding 1.74 g MFGM per 100 g diet can significantly improve neonatal piglets’ learning and memory abilities, potentially by enhancing the connection of white matter fiber bundles in the brain