697 research outputs found
Thermodynamic Properties of Dodecamethylpentasiloxane, Tetradecamethylhexasiloxane, and Decamethylcyclopentasiloxane
The Supporting Information is available free of charge on the ACS Publications website at https://pubs.acs.org/doi/abs/10.1021/acs.iecr.9b00608Siloxanes are widely used in the chemical industry and in process and power engineering. For example, they are used as working fluids of organic Rankine cycle power plants since 20 years ago. For the process design and optimization, thermodynamic properties, such as enthalpy, entropy, speed of sound, density, and vapor–liquid equilibrium, are required. While the properties of short-chained siloxanes, such as hexamethyldisiloxane (MM) or octamethylcyclotetrasiloxane (D4), have already been investigated comprehensively, information on thermophysical properties of higher order siloxanes is limited. Therefore, measurements on density and speed of sound in the liquid state of dodecamethylpentasiloxane (MD3M), tetradecamethylhexasiloxane (MD4M), and decamethylcyclopentasiloxane (D5) are presented here. On the basis of these measurements and other experimental data from the literature, new fundamental equations of state were developed for these three fluids. The equations are based on the Helmholtz energy and, thus, allow for the calculation of any thermodynamic state property by means of derivatives with respect to the natural variables, namely temperature and density. The obtained models also feature a correct extrapolation behavior in regions where no data are available in order to ensure the applicability of the equations to mixture models in the future. On the basis of the present equations of state and recently published equations for other siloxanes, the possibility of the siloxanes belonging to the group of Bethe–Zel’dovich–Thompson fluids is also investigated
Therapy sculpts the complex interplay between cancer and the immune system during tumour evolution
Cancer development is an evolutionary process. A key selection pressure is exerted by therapy, one of the few players in cancer evolution that can be controlled. As such, an understanding of how treatment acts to sculpt the tumour and its microenvironment and how this influences a tumour’s subsequent evolutionary trajectory is critical. In this review, we examine cancer evolution and intra-tumour heterogeneity in the context of therapy. We focus on how radiotherapy, chemotherapy and immunotherapy shape both tumour development and the environment in which tumours evolve and how resistance can develop or be selected for during treatment
Thermodynamic Properties of trans-1,3,3,3-tetrafluoropropene [R1234ze(E)]: Measurements of Density and Vapor Pressure and a Comprehensive Equation of State
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SRSF2 Is Essential For Hematopoiesis and Its Mutations Dysregulate Alternative RNA Splicing In MDS
Abstract
Myelodysplastic syndromes (MDS) are a group of neoplasms that are ineffective in generating multiple lineages of myeloid cells and have various risks to progress to acute myeloid leukemia. Recent genome-wide sequencing studies reveal that mutations in genes of splicing factors are commonly associated with MDS. However, the importance of these splicing factors in hematopoiesis has been unclear and the causal effect of their mutations on MDS development remains to be determined. One of these newly identified genes is SRSF2, and its mutations have been linked to poor survival among MDS patients. Interestingly, most of SRSF2 mutations occur at proline 95 and the majority of these mutations change this proline to histidine (P95H). Given that SRSF2 is a well-characterized splicing factor involved in both constitutive and regulated splicing, we hypothesize that SRSF2 plays an important role in normal hematopoiesis and the SRSF2 mutations induce specific changes in alternative splicing that favor disease progression. We first examined the role of SRSF2 in hematopoiesis by generating Srsf2 null mutation in mouse blood cells via crossing conditional Srsf2 knockout mice (Srsf2f/f) with blood cell-specific Cre transgenic mice (Vav-Cre). The mutant mice produced significantly fewer definitive blood cells (10% of wild type controls), exhibited increased apoptosis in the remaining blood cells, and died during embryonic development. Importantly, we detected no hematopoietic stem/progenitor cells (lineage-/cKit+) in E14 fetal livers of Vav-Cre/Srsf2f/f mice. These results indicate that SRSF2 is essential for hematopoiesis during embryonic development. We next examined the role of SRSF2 in adult hematopoiesis by injecting polyIC into mice that carry a polyIC inducible Cre expression unit. Unexpectedly, after multiple polyIC treatments, the Srsf2f/f mice stayed alive during several months of observation. Time course genotyping analyses of polyIC treated mice revealed an increased rate of incomplete Srsf2 deletion in peripheral blood cells. These observations suggest that Srsf2 ablation did not cause immediate cell lethality in differentiated blood cells, but the gene is indispensable for the function of blood stem/progenitor cells. Since mutations of splicing factors are generally heterozygous in MDS patients, we also examined mice with Srsf2+/- blood cells. No obvious defect of hematopoiesis was observed under normal conditions or in response to stress with 5-FU treatment and sublethal irradiation. To gain molecular insight into the splicing activity of MDS-associated mutant forms of SRSF2, we performed large-scale alternative splicing surveys by using RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing (RASL-seq) previously developed in our lab, which offers a robust and cost-effective platform for splicing profiling. Compared to vector transduction controls, we found that overexpression of both wild type and P95H SRSF2 induced many, but distinct changes in alternative splicing in lineage-negative bone marrow cells, and importantly, we noted several changes in genes with known roles in hematopoietic malignancies that were uniquely induced by the mutant SRSF2. To further link the mutations to altered splicing in MDS patients, we also applied RASL-seq to a large number of MDS patient samples with or without mutations in SRSF2 or other splicing regulators. The data revealed a specific set of alternative splicing events that are commonly linked to MDS with splicing factor mutations. These findings strongly suggest that many of these mutations in splicing regulators are gain-of-function mutations that are causal to MDS. In conclusion, we report that SRSF2 plays an essential role in hematopoietic stem/progenitor cells and that the MDS-associated mutations in SRSF2 have a dominant effect on RNA alternative splicing. These findings provide functional information and molecular basis of SRSF2 and its MDS-related mutations in hematopoiesis and related clinical disorders.
Disclosures:
No relevant conflicts of interest to declare
Implementation of a coherent real-time noise radar system
The utilisation of continuous random waveforms for radar, that is, noise radar, has been extensively studied as a candidate for low probability of intercept operation. However, compared with the more traditional pulse-Doppler radar, noise radar systems are significantly more complicated to implement, which is likely why few systems exist. If noise radar systems are to see the light of day, system design, implementation, limitations etc., must be investigated. Therefore, the authors examine and detail the implementation of a real-time noise radar system on a field programmable gate array. The system is capable of operating with 100% duty cycle, 200\ua0MHz bandwidth, and 268\ua0ms integration time while processing a range of about 8.5\ua0km. Additionally, the system can perform real-time moving target compensation to reduce cell migration. System performance is primarily limited by the memory bandwidth of the off-chip dynamic random access memory
Fragmented Territories: Incomplete Enclosures and Agrarian Change on the Agricultural Frontier of Samlaut District, North-West Cambodia
peer reviewedIn Cambodia, the interactions between large-scale land investment and land titling gathered particular momentum in 2012–13, when the government initiated an unprecedented upland land titling programme in an attempt to address land tenure insecurity where large-scale land investment overlaps with land appropriated by peasants. This paper is based on a spatially explicit ethnography of land rights conducted in the Samlaut district of north-west Cambodia – a former Khmer Rouge resistance stronghold – in a context where the enclosures are both incomplete and entangled with post-war, socially embedded land tenure systems. We discuss how this new pattern of fragmentation affects the prevailing dynamics of agrarian change. We argue that it has introduced new forms of exclusion and a generalized perception of land tenure uncertainty that is managed by peasants through the actualization of hybrid land tenure arrangements borrowing from state rules and local consensus. In contrast with common expectations about land formalization, the process reinforces the patterns of social differentiation initiated by land rent capture practices of early migrants and pushes more vulnerable peasants into seeking wage labour and resorting to job migration
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