Solid state NMR method development and studies of biological and biomimetic nanocomposites

This thesis describes application and development of advanced solid-state nuclear magnetic resonance techniques for complex materials, in particular organic-inorganic nanocomposites and thermoelectric tellurides. The apatite-collagen interface, essential for understanding the biomineralization process in bone and engineering the interface for controlled bio-mimetic synthesis and optimized mechanical properties, is buried within the nanocomposite of bone. We used multinuclear solid-state NMR to study the composition and structure of the interface. Citrate has been identified as the main organic molecule strongly bound to the apatite surface with a density of 1/(2 nm)2, covering 1/6 of the total surface area in bovine bone. Citrate provides more carboxylate groups, one of the key functional groups found to affect apatite nucleation and growth, than all the non-collagenous proteins all together in bone; thus we propose that citrate stabilizes apatite crystals at a very small thickness of ∼3 nm (4 unit cells) to increase bone fracture tolerance. The hypothesis has been confirmed in vitro by adding citrate in the bio-mimetic synthesis of polymer-hydroxyapatite nanocomposites. The results have shown that the size of hydroxyapatite nanocrystals decreases as increasing citrate concentration. With citrate concentrations comparable to that in body fluids, similar-sized nanocrystals as in bone have been produced. Besides the dimensions of the apatite crystals, the composition of bone also affects its bio-functional and macroscopic mechanical properties; therefore, our team also extended its effort to enhance the inorganic portion in our bio-mimetic synthesis from originally 15 wt% to current 50 wt% compared to 65 wt% in bovine bone, by using Lysine-Leucine hydroxyapatite nucleating diblock co-polypeptide, which forms a gel at very low concentration. In this thesis, various advanced solid state NMR techniques have been employed to characterize nanocomposites. Meanwhile, we have developed new methods to achieve broadband high resolution NMR and improve the accuracy of inter-nuclear distance measurements involving quadrupolar spins. Broadband high resolution NMR of spin-1/2 nuclei has been accomplished by the adaptation of the magic angle turning (MAT) method to fast magic angle spinning, termed fast MAT, by solving technical problems such as off-resonance effects. Fast MAT separates chemical shift anisotropy and isotropic chemical shifts over a spectral range of ∼1.8 γB1 without significant distortions. Fast MAT 125Te NMR has been applied to study technologically important telluride materials with spectra spreading up to 190 kHz. The signal-to-noise ratio of the spectra is significantly improved by using echo-matched Gaussian filtering in offline data processing. The accuracy of the measured distances between spin-1/2 and quadrupolar nuclei with methods such as SPIDER and REAPDOR has been improved by compensating for the fast longitudinal quadrupolar relaxation on the sub-millisecond with a modified S0 pulse sequence. Also, the T1Q effect on the spin coherence and its spinning speed dependency has been explored and documented with analytical and numerical simulations as well as experimental measurements

Low Growth Hormone Levels in Short-Stature Children with Pituitary Hyperplasia Secondary to Primary Hypothyroidism

Objective. The follow-up of GH levels in short-stature children with pituitary hyperplasia secondary to primary hypothyroidism (PPH) is reported in a few cases. We aimed to observe changes in GH secretion in short-stature children with PPH. Methods. A total of 11 short-stature children with PPH accompanied by low GH levels were included. They received levothyroxine therapy after diagnosis. Their thyroid hormones, IGF-1, PRL, and pituitary height were measured at baseline and 3 months after therapy. GH stimulation tests were performed at baseline and after regression of thyroid hormones and pituitary. Results. At baseline, they had decreased GH peak and FT3 and FT4 levels and elevated TSH levels. Decreased IGF-1 levels were found in seven children. Elevated PRL levels and positive thyroid antibodies were found in 10 children. The mean pituitary height was 14.3±3.8 mm. After 3 months, FT3, FT4, and IGF-1 levels were significantly increased (all p<0.01), and values of TSH, PRL, and pituitary height were significantly decreased (all p<0.001). After 6 months, pituitary hyperplasia completely regressed. GH levels returned to normal in nine children and were still low in two children. Conclusion. GH secretion can be resolved in most short-stature children with PPH

Fourier-transformed gauge theory models of three-dimensional topological orders with gapped boundaries

In this paper, we apply the method of Fourier transform and basis rewriting developed in arXiv:1910.13441 for the two-dimensional quantum double model of topological orders to the three-dimensional gauge theory model (with a gauge group $G$) of three-dimensional topological orders. We find that the gapped boundary condition of the gauge theory model is characterized by a Frobenius algebra in the representation category $\mathcal Rep(G)$ of $G$, which also describes the charge splitting and condensation on the boundary. We also show that our Fourier transform maps the three-dimensional gauge theory model with input data $G$ to the Walker-Wang model with input data $\mathcal Rep(G)$ on a trivalent lattice with dangling edges, after truncating the Hilbert space by projecting all dangling edges to the trivial representation of $G$. This Fourier transform also provides a systematic construction of the gapped boundary theory of the Walker-Wang model. This establishes a correspondence between two types of topological field theories: the extended Dijkgraaf-Witten and extended Crane-Yetter theories.Comment: 39 pages, 9 figure

企业“扎堆”、技术升级与经济绩效 ——对中国开发区产业集聚的性质及其变迁的实证分析

Based on micro-firm data of development zones in Jiangsu Province along the Yangtze River, the effects of local factors special to development zones and of technology promotion on firm’s performance are tested, from which we try to illustrate the nature and dynamics of industrial clusters built on development zones. The results show that the primary reasons firms locate into development zones are not clustering benefits in general meaning brought by interactions among firms locally concentrated, but are the attraction of “policy rents” and the scale economy of infrastructure brought by government behaviors. Once located in the zone, the firm is doom to interact with local government as well as industry-related factors, and the clustering effects may emerge. Thus, the key to keep development zones’ competition sustainable, when governments’ bidding wars and policy adjustment fade away “policy rents” and scale economy of infrastructure, is to cultivate clustering effects

企业“扎堆”、技术升级与经济绩效 ——对中国开发区产业集聚的性质及其变迁的实证分析

Based on micro-firm data of development zones in Jiangsu Province along the Yangtze River, the effects of local factors special to development zones and of technology promotion on firm’s performance are tested, from which we try to illustrate the nature and dynamics of industrial clusters built on development zones. The results show that the primary reasons firms locate into development zones are not clustering benefits in general meaning brought by interactions among firms locally concentrated, but are the attraction of “policy rents” and the scale economy of infrastructure brought by government behaviors. Once located in the zone, the firm is doom to interact with local government as well as industry-related factors, and the clustering effects may emerge. Thus, the key to keep development zones’ competition sustainable, when governments’ bidding wars and policy adjustment fade away “policy rents” and scale economy of infrastructure, is to cultivate clustering effects

Astaxanthin protects against diabetic cardiomyopathy via activation of Akt pathway in H9c2 cells

Purpose: To investigate the cardioprotective action of astaxanthin, and to elucidate its underlying mechanism of action in H9c2 cells.Methods: Cell viability was determined by MTT assay. Intracellular reactive oxygen species (ROS) were evaluated using 2, 7-dichlorodihydro-fluorescein diacetate (H2DCFDA) staining. Cell apoptosis were assessed by determining caspase activities using colorimetric assay. The apoptotic cells were labelled with annexin V/PI staining and quantified by flow cytometry. Involvement of Akt signaling pathway was verified using western blot.Results: The results revealed that astaxanthin (5 and 10 μM) dose-dependently reversed high glucoseinduced cell viability loss in H9c2 cells (p &lt; 0.01 and p &lt; 0.001, respectively). Astaxanthin inhibited intracellular ROS production, decreased caspase 3 and caspase 9 activities in high glucose-challenged H9c2 cells in a concentration-related manner (p &lt; 0.05). Besides, astaxanthin markedly inhibited the number of apoptotic H9c2 cells induced by high glucose. Furthermore, western blot analysis demonstrated that astaxanthin upregulated the activation of Akt signaling.Conclusion: Astaxanthin may protect high glucose induced diabetic cardiomyopathy via activation of Akt pathway, and thus deserves further investigation as a cardioprotective agent.Keywords: Astaxanthin, Diabetic cardiomyopathy, Cardiomyocyte, Apoptosis, Akt pathwa

Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene

Benzo[a]pyrene (BaP) is a widespread potent carcinogen found in food, coal tar, cigarette smoke, and industrial smoke. Cigarette smoking is the leading cause of lung cancer, and the mutagenesis in smoking-associated lung cancer is determined by multiple factors, including nucleotide excision repair. We have developed a general method for genome-wide mapping of nucleotide excision repair at single-nucleotide resolution and applied it to generate repair maps of UV- and BaP-induced DNA damage in human. Results show a novel sequence specificity of BaP diol epoxide-deoxyguanosine repair. This general method can be used to study repair of all types of DNA damages that undergo nucleotide excision repair

Ecosystem multifunctionality and soil microbial communities in response to ecological restoration in an alpine degraded grassland

Linkages between microbial communities and multiple ecosystem functions are context-dependent. However, the impacts of different restoration measures on microbial communities and ecosystem functioning remain unclear. Here, a 14-year long-term experiment was conducted using three restoration modes: planting mixed grasses (MG), planting shrub with Salix cupularis alone (SA), and planting shrub with Salix cupularis plus planting mixed grasses (SG), with an extremely degraded grassland serving as the control (CK). Our objective was to investigate how ecosystem multifunctionality and microbial communities (diversity, composition, and co-occurrence networks) respond to different restoration modes. Our results indicated that most of individual functions (i.e., soil nutrient contents, enzyme activities, and microbial biomass) in the SG treatment were significantly higher than in the CK treatment, and even higher than MG and SA treatments. Compared with the CK treatment, treatments MG, SA, and SG significantly increased the multifunctionality index on average by 0.57, 0.23 and 0.76, respectively. Random forest modeling showed that the alpha-diversity and composition of bacterial communities, rather than fungal communities, drove the ecosystem multifunctionality. Moreover, we found that both the MG and SG treatments significantly improved bacterial network stability, which exhabited stronger correlations with ecosystem multifunctionality compared to fungal network stability. In summary, this study demonstrates that planting shrub and grasses altogether is a promising restoration mode that can enhance ecosystem multifunctionality and improve microbial diversity and stability in the alpine degraded grassland