Functions of X-linked miR-506 family in Reproduction

MicroRNAs (miRNAs) are ~22nt small non-coding RNAs that play a pivotal role in both development and adulthood physiology. Our lab has previously discovered that the miR-506 family, which consists of 22 miRNAs existing in 5 clusters expanding a ~62kb region near Slitrk2 and 1 cluster expanding a ~22kb region close to Fmr1 on the X chromosome in mice. Derived from the same ancestors, these miRNAs are preferentially expressed in the testis and have undergone rapid evolution with variable seed sequences, whereas the two protein-coding genes (Slitrk2 and Fmr1) flanking the 6 clusters remain highly conserved among all mammalian species. The quick evolution and testis preferential expression of these X-linked miRNAs strongly suggest that they are under selective pressure and play an important role in fine-tuning certain molecular events to ensure the production of high quality sperm. However, these hypotheses remain untested. My dissertation projects aimed to unveil the physiological roles of the miR-506 family miRNAs. Using the CRISPR-Cas-based genome editing technology, we deleted individual or 5 clusters of the miR-506 family in the mouse genome to analyzed potential phenotype. Interestingly, we found that ablation of one or two miRNAs, or even one cluster of several miRNAs did not generate any discernable defects in either spermatogenesis or male fertility. When we deleted four or five of the 6 miRNA clusters, we started to see some phenotype in these KO males, characterized by slightly reduced litter sizes and longer litter intervals despite normal testis weight and normal sperm counts. When the typical one male-one female mating scheme was used, the KO males were only subfertile. However, when a female was mated sequentially with either a wild type male first and a KO second, or a KO first followed by a WT male, no or much fewer pups were derived from the KO sperm, suggesting the KO sperm are less fit in fertilizing eggs. Indeed, in vitro fertilization assays showed that the KO sperm were less competitive in fertilizing wild type eggs. Our data suggest that sperm produced in the absence of these X-linked miRNAs are less fertile/competitive than wild-type sperm, suggesting that the miR-506 family miRNAs function to fine-tune certain molecular processes that render sperm better fitness. Among the miR-506 family, 6 miRNAs of the miR-465 cluster have similar seed sequences and are preferentially expressed in the testis. Surprisingly, loss of miR-465 cluster did not cause male fertility defects, but led to sex ratio bias among KO offspring, and the distorted sex ratio was found to result from female-biased lethality as early as embryonic day (E) 8.5. It turns out that miR-465 cluster miRNAs are also highly expressed in extra-embryonic tissues at E7.5. The female-biased lethality is likely due to dysregulation numerous target genes known critical for the survival of the female embryos, e.g., Alkbh1, a tRNA demethylation enzyme. Taken together, the data presented in this dissertation uncovered the physiological roles of the miR-506 family. Consistent with our previous reports, miRNAs tend to act as a group, and loss of function of one miRNA can be easily compensated by other members of the same cluster or the same family. Thus, inactivation of a single miRNA rarely leads to a discernable phenotype in mice. To reveal the true physiological role of miRNAs within one cluster or one family, simultaneous inactivation of most or all of the miRNAs is required

Explaining E-Tailers’ Source of Competitiveness: An Integrative Framework

E-tailers refer to small and medium size enterprises or individual entrepreneurs primarily conducting businesses on online shopping platforms. Although many works on e-marketplaces have been done, theory-driven studies that explain e-tailers’ source of competitiveness are relatively scarce. The current work developed an integrative theoretical model in which online social capital, structural assurance, and online word-of-month are proposed to affect e-tailers’ business performance. The current study offers implications on: 1) what are the unique sources of competitiveness for businesses operating in pure online environment; 2) how can the resource-scare e-tailers survive in their rivalry with large offline retailers

Accreting neutron stars and black holes

X-ray binary systems o↵er the best way to measure the masses of the accreting compact objects. Following the discovery of the narrow Bowen emission lines in the prototypical low-mass X-ray binary, Sco X-1, arising from the X-ray illuminated atmosphere of the donor star, the Bowen diagnostic has been used as a general tool to obtain dynamical information for persistent sources and/or transients during outburst. Here I exploit the Doppler tomography technique and develop Monte Carlo style bootstrap tests in order to obtain the most robust binary parameter constraints even in the low signal-to-noise ratio regime. Using a new set of analysis tools, I show that we can push the limit of observations to moderately faint (B ⇠ 19) persistent sources with 8-m class telescopes. The method has also been applied to the case of the accreting millisecond X-ray pulsar XTE J1814−338, where the Bowen technique played a crucial role in the derivation of the radial velocity of the secondary, K2. The resulting constraints on the binary component masses suggest the presence of a ‘redback’ millisecond pulsar in XTE J1814−338 during an X-ray quiescent state. Sco X-1 remains the most important Bowen blend system for benchmarking our method as well as a critical target for continuous gravitational wave searches. I provide revised constraints on key orbital parameters in direct support of continuous-wave observations of Sco X-1 in the Advanced- LIGO era. In light of the new constraints on orbital parameters, the ranges of search parameters T0 and Porb should be updated with the refined period and ephemeris. More importantly, the range for the projected semi-major axis (axsini) needs to be expanded in order to cover the full parameter space. In the last chapter, I present a summary of the method and the key results of its application to all 7 systems (including two transients). The list of Bowen targets can be expanded as new transient outbursts are detected, which may provide us with the opportunities to find stellar-mass black holes. Finally, I remark that the method developed in this thesis can be used to characterize other features in Doppler maps, e.g., the accretion disc and spiral arms

Study on the Hydration Behaviour of the Coral Sand Powder- Ground-Granulated Blast Furnace Slag-Portland Cement Ternary System

Recently, the studies on the application of coral sand in concrete construction attracted wide attention, especially in China. Coral sand and coral sand powder (CSP) can be used as fine aggregate and mineral admixture in concrete, respectively. The main component of CSP is calcium carbonate (CaCO3), up to 96%. However, the utilization of CSP in cement mortar will cause performance degradation. Ground-Granulated Blast Furnace Slag (BFS) be used to improve the property of CSP-Portland cement mortar. In this study, the coral sand powder-blast furnace slag-Portland cement (CSP-BFS-PC) ternary system had been used to produce cement paste and mortar. The hydration product of the CSP-BFS-PC ternary system are researched fundamentally by X-ray diffraction, and compressive strength are tested at different curing age. The results show that CSP can suppress consumption of C3A. 15wt.% BFS can offset the strength loss of cement mortar due to the substitution of CSP for cement (CSP less than 15wt.%), especially 7-28 days

MCP-induced protein 1 mediates the minocycline-induced neuroprotection against cerebral ischemia/reperfusion injury in vitro and in vivo

Background: Minocycline, a broad-spectrum tetracycline antibiotic, has shown anti-inflammatory and neuroprotective effects in ischemic brain injury. The present study seeks to determine whether monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified modulator of inflammatory reactions, is involved in the cerebral neuroprotection conferred by minocycline treatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of minocycline-induced ischemic brain tolerance. Methods: Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h in male C57BL/6 mice and MCPIP1 knockout mice followed by 24-or 48-h reperfusion. Twelve hours before ischemia or 2 h after MCAO, mice were injected intraperitoneally with 90 mg/kg of minocycline hydrochloride. Thereafter, the animals were injected twice a day, at a dose of 90 mg/kg after ischemia until sacrificed. Transcription and expression of MCPIP1 gene was monitored by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. The neurobehavioral scores, infarction volumes, and proinflammatory cytokines in brain and NF-.B signaling were evaluated after ischemia/reperfusion. Results: MCPIP1 protein and mRNA levels significantly increased in mouse brain undergoing minocycline pretreatment. Minocycline treatment significantly attenuated the infarct volume, neurological deficits, and upregulation of proinflammatory cytokines in the brain of wild type mice after MCAO. MCPIP1-deficient mice failed to evoke minocycline-treatment-induced tolerance compared with that of the control MCPIP1-deficient group without minocycline treatment. Similarly, in vitro data showed that minocycline significantly induced the expression of MCPIP1 in primary neuron-glial cells, cortical neurons, and reduced oxygen glucose deprivation (OGD)-induced cell death. The absence of MCPIP1 blocked minocycline-induced protection on neuron-glial cells and cortical neurons treated with OGD. Conclusions: Our in vitro and in vivo studies demonstrate that MCPIP1 is an important mediator of minocyclineinduced protection from brain ischemia

The Compressive Strength of Cement–Slag–Calcium Sulphoaluminate Ternary System

At present, there is an increasing interest on the use of calcium sulphoaluminate (C4A3$) in cement. In this paper, pure mineral of sulphoaluminate (C4A3$) was prepared in laboratory. Different dosages of steel slag and C4A3$were blended into cement. The aim of this paper is to investigate the compressive strength of this ternary system. The test results show that the addition of C4A3$ can improve the strength of cement. Larger C4A3$dosage (7$ dosage is 5%. In ternary system, C4A3$ has no obvious improvement, while 5% dosage could improve the strength a little

GCSA Codes with Noise Alignment for Secure Coded Multi-Party Batch Matrix Multiplication

A secure multi-party batch matrix multiplication problem (SMBMM) is considered, where the goal is to allow a master to efficiently compute the pairwise products of two batches of massive matrices, by distributing the computation across S servers. Any X colluding servers gain no information about the input, and the master gains no additional information about the input beyond the product. A solution called Generalized Cross Subspace Alignment codes with Noise Alignment (GCSA-NA) is proposed in this work, based on cross-subspace alignment codes. The state of art solution to SMBMM is a coding scheme called polynomial sharing (PS) that was proposed by Nodehi and Maddah-Ali. GCSA-NA outperforms PS codes in several key aspects - more efficient and secure inter-server communication, lower latency, flexible inter-server network topology, efficient batch processing, and tolerance to stragglers. The idea of noise alignment can also be combined with N-source Cross Subspace Alignment (N-CSA) codes and fast matrix multiplication algorithms like Strassen's construction. Moreover, noise alignment can be applied to symmetric secure private information retrieval to achieve the asymptotic capacity