Research challenges and opportunities in blockchain and cryptocurrencies

The blockchain is the underlying technology of the Bitcoin cryptocurrency, and it has created much excitement in the technology and research communities. A blockchain is a distributed ledger collectively maintained by a peer‐to‐peer network of participants who in Bitcoin are known as miners. This key innovation enables cryptocurrencies such as Bitcoin to operate in a decentralized manner with no intermediaries such as financial institutions. But the blockchain can be used to record things other than cryptocurrency transactions. While many of the concepts of Bitcoin build on what have been around since the 1980s and 1990s, the designer(s) of it have made important assumptions that make it work along with the use of an incentive protocol, leading to a major breakthrough from traditional academic thinking. In this paper, we present the state‐of‐the‐art of blockchain and cryptocurrencies along with research challenges and opportunities that would be of interest to researchers getting into this exciting field

X-ray diffraction of crystallization of copper (II) chloride for improved energy utilization in hydrogen production

Crystallization is an effective method to recover solids from solution, due to its relatively low energy utilization, low material requirements and lower cost compared to other alternatives. Hence, crystallization is of particular interest in the thermochemical copper-chlorine cycle for hydrogen production as an energy-saving means to extract solid CuCl2 from its aqueous solution. It has been determined from experiments that there is a range of concentrations that will demonstrate crystallization. If the initial concentration exceeds the upper bound of this range, the solution will be saturated and instantly become paste-like without forming crystals. Conversely, if the initial concentrations fall below the lower bound of a specified range, the solution will remain liquid upon cooling. As a result, it has been observed that crystallization does not occur for HCl concentrations below 3 M and above 9 M. Also, it has been found that anhydrous CuCl2 does not crystallize under any of the conditions tested. To analyze the composition of the recovered solids, X-ray diffraction (XRD) was employed. The samples were also analyzed using thermogravimetric analysis (TGA) in order to determine their thermochemical properties such as melting and decomposition temperatures. The stationary point on the TGA curve was found to be around 462 °C which is below the normal melting temperature of CuCl2. Also, the vaporization of the samples was found to be approximately 600 °C

Expression and function of the LIM homeobox containing genes Lhx3 and Lhx4 in the mouse placenta

The LIM homeobox containing genes of the LIM-3 group, Lhx3 and Lhx4 , are critical for normal development. Both genes are involved in the formation of the pituitary and the motoneuron system and loss of either gene causes perinatal lethality. Previous studies had shown that Lhx3 is overexpressed in hyperplastic placentas of mouse interspecies hybrids. To determine the role of LHX3 in the mouse placenta, we performed expression and function analyses. Our results show that Lhx3 exhibits specific spatial and temporal expression in the mouse placenta. However, deletion of Lhx3 does not produce a placental phenotype. To test whether this is due to functional substitution by Lhx4 , we performed a phenotype analysis of Lhx3 −/−; Lhx4 −/− double-mutant placentas. A subset of Lhx3 −/−; Lhx4 −/− placentas exhibited abnormal structure of the labyrinth. However, absence of both LIM-3 genes did not interfere with placental transport nor consistently with expression of target genes such as Gnrhr . Thus, LHX3 and LHX4 appear to be dispensable for placental development and function. Developmental Dynamics 237:1517-1525, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58577/1/21546_ftp.pd

BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin

Because mouse embryonic stem cells (mESCs) do not contribute to the formation of extraembryonic placenta when they are injected into blastocysts, it is believed that mESCs do not differentiate into trophoblast whereas human embryonic stem cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic protein 4 (BMP4) in vitro. To test whether mESCs have the potential to differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a defined monolayer culture condition. The expression of trophoblast-specific transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was specifically upregulated in the BMP4-treated differentiated cells, and these cells expressed trophoblast markers. These results suggest that BMP4 treatment in defined culture conditions enabled mESCs to differentiate into trophoblast. This differentiation was inhibited by serum or leukemia inhibitory factor, which are generally used for mESC culture. In addition, we studied the mechanism underlying BMP4-directed mESC differentiation into trophoblast. Our results showed that BMP4 activates the Smad pathway in mESCs inducing Cdx2 expression, which plays a crucial role in trophoblast differentiation, through the binding of Smad protein to the Cdx2 genomic enhancer sequence. Our findings imply that there is a common molecular mechanism underlying hESC and mESC differentiation into trophoblast

FGF4 Independent Derivation of Trophoblast Stem Cells from the Common Vole

The derivation of stable multipotent trophoblast stem (TS) cell lines from preimplantation, and early postimplantation mouse embryos has been reported previously. FGF4, and its receptor FGFR2, have been identified as embryonic signaling factors responsible for the maintenance of the undifferentiated state of multipotent TS cells. Here we report the derivation of stable TS-like cell lines from the vole M. rossiaemeridionalis, in the absence of FGF4 and heparin. Vole TS-like cells are similar to murine TS cells with respect to their morphology, transcription factor gene expression and differentiation in vitro into derivatives of the trophectoderm lineage, and with respect to their ability to invade and erode host tissues, forming haemorrhagic tumours after subcutaneous injection into nude mice. Moreover, vole TS-like cells carry an inactive paternal X chromosome, indicating that they have undergone imprinted X inactivation, which is characteristic of the trophoblast lineage. Our results indicate that an alternative signaling pathway may be responsible for the establishment and stable proliferation of vole TS-like cells

Placental overgrowth in mice lacking the imprinted gene Ipl

The Ipl (Tssc3) gene lies in an extended imprinted region of distal mouse chromosome 7, which also contains the Igf2 gene. Expression of Ipl is highest in placenta and yolk sac, where its mRNA is derived almost entirely from the maternal allele. Ipl encodes a small cytoplasmic protein with a pleckstrin-homology (PH) domain. We constructed two lines of mice with germ-line deletions of this gene (Ipl(neo) and Ipl(loxP)) and another line deleted for the similar but nonimprinted gene Tih1. All three lines were viable. There was consistent overgrowth of the Ipl-null placentas, with expansion of the spongiotrophoblast. These larger placentas did not confer a fetal growth advantage; fetal size was normal in Ipl nulls with the Ipl(neo) allele and was decreased slightly in nulls with the Ipl(loxP) allele. When bred into an Igf2 mutant background, the Ipl deletion partially rescued the placental but not fetal growth deficiency. Neither fetal nor placental growth was affected by deletion of Tih1. These results show a nonredundant function for Ipl in restraining placental growth. The data further indicate that Ipl can act, at least in part, independently of insulin-like growth factor-2 signaling. Thus, genomic imprinting regulates multiple pathways to control placental size

Trophoblast expression of fms-like tyrosine kinase 1 is not required for the establishment of the maternal–fetal interface in the mouse placenta

Fms-like tyrosine kinase 1 (Flt1)/vascular endothelial growth factor (VEGF) receptor 1, a receptor for VEGF-A and placental growth factor, is expressed in the spongiotrophoblast layer that segregates the maternal and fetal vasculature in the mouse placenta. A soluble form of Flt1 (sFlt1) produced in the mouse and human placenta can also be detected in the maternal blood. Levels of maternal sFlt1 are elevated in preeclampsia, suggesting that placental sFlt1 plays roles in regulating the maternal vasculature during pregnancy. However, it remains to be determined whether placental Flt1/sFlt1 serves as a regulator of VEGF-A activity in the placenta per se. Here, we investigated the placental development in Flt1-deficient mice. Flt1 is expressed in a subpopulation of ectoplacental cone cells and later marks the spongiotrophoblast cells, peri/endovascular trophoblast cells, and trophoblast glycogen cells. The labyrinth of Flt1(lacZ/lacZ) placentae lacked the fetal capillary network because of a defect in allantoic mesoderm invasion. To address whether the absence of Flt1 in the trophoblast alone affects placental development, we investigated chimeric placentae comprised of Flt1(lacZ/lacZ) trophoblast and Flt1(+)(/)(+) mesoderm, generated by tetraploid aggregation. Fetal growth was supported normally, and no defect in the formation of placental circulation into the maternal spiral artery or invasion of peri/endovascular trophoblast was detected. These findings indicate that trophoblast-derived Flt1/sFlt1 is dispensable for the initial establishment of the maternal–fetal interface in the mouse placenta. Targeting maternal sFlt1 levels for treatment of preeclampsia may thus be possible without affecting the proper formation of the placenta