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An intelligent component database for behavioral synthesis
This paper describes an intelligent component database system that delivers components to synthesis tools when given a set of attributes and constraints. Requirements of a component server are defined and an implementation is described. Our experiments demonstrate that such a component sever can replace component libraries and component catalogs with hundreds of pages
Water productivity in Zhanghe Irrigation System: issues of scale
Irrigation systemsWater productivityReservoirsWater useWater stressWater conservationRicePaddy fieldsCrop yield
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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
Spin-Kick Correlation in Neutron Stars: Alignment Conditions and Implications
Recent observations of pulsar wind nebulae and radio polarization profiles
revealed a tendency of the alignment between the spin and velocity directions
in neutron stars. We study the condition for spin-kick alignment using a toy
model, in which the kick consists of many off-centered, randomly-oriented
thrusts. Both analytical considerations and numerical simulations indicate that
spin-kick alignment cannot be easily achieved if the proto-neutron star does
not possess some initial angular momentum, contrary to some previous claims. To
obtain the observed spin-kick misalignment angle distribution, the initial spin
period of the neutron star must be smaller than the kick timescale. Typically,
an initial period of a hundred milliseconds or less is required.Comment: 17 pages, 8 figures. Accepted by Ap
Optimal Conclusive Discrimination of Two Non-orthogonal Pure Product Multipartite States Locally
We consider one copy of a quantum system prepared in one of two
non-orthogonal pure product states of multipartite distributed among separated
parties. We show that there exist protocols which obtain optimal probability in
the sense of conclusive discrimination by means of local operations and
classical communications(LOCC) as good as by global operations. Also, we show a
protocol which minimezes the average number of local operations. Our result
implies that two product pure multipartite states might not have the non-local
property though more than two can have.Comment: revtex, 3 pages, no figur
Optimization of Protein-Protein Interaction Measurements for Drug Discovery Using AFM Force Spectroscopy
Increasingly targeted in drug discovery, protein-protein interactions challenge current high throughput screening technologies in the pharmaceutical industry. Developing an effective and efficient method for screening small molecules or compounds is critical to accelerate the discovery of ligands for enzymes, receptors and other pharmaceutical targets. Here, we report developments of methods to increase the signal-to-noise ratio (SNR) for screening protein-protein interactions using atomic force microscopy (AFM) force spectroscopy. We have demonstrated the effectiveness of these developments on detecting the binding process between focal adhesion kinases (FAK) with protein kinase B (Akt1), which is a target for potential cancer drugs. These developments include optimized probe and substrate functionalization processes and redesigned probe-substrate contact regimes. Furthermore, a statistical-based data processing method was developed to enhance the contrast of the experimental data. Collectively, these results demonstrate the potential of the AFM force spectroscopy in automating drug screening with high throughput
Information-technology approach to quantum feedback control
Quantum control theory is profitably reexamined from the perspective of
quantum information, two results on the role of quantum information technology
in quantum feedback control are presented and two quantum feedback control
schemes, teleportation-based distant quantum feedback control and quantum
feedback control with quantum cloning, are proposed. In the first feedback
scheme, the output from the quantum system to be controlled is fed back into
the distant actuator via teleportation to alter the dynamics of system. The
result theoretically shows that it can accomplish some tasks such as distant
feedback quantum control that Markovian or Bayesian quantum feedback can't
complete. In the second feedback strategy, the design of quantum feedback
control algorithms is separated into a state recognition step, which gives
"on-off" signal to the actuator through recognizing some copies from the
cloning machine, and a feedback (control) step using another copies of cloning
machine. A compromise between information acquisition and measurement
disturbance is established, and this strategy can perform some quantum control
tasks with coherent feedback.Comment: 10 pages,submitte
Infrared spectroscopy of the charge ordering transition in NaCoO
We report infrared spectra of a NaCoO single crystal which
exhibits a sharp metal-insulator transition near 50 K due to the formation of
charge ordering. In comparison with x=0.7 and 0.85 compounds, we found that the
spectral weight associated with the conducting carriers at high temperature
increases systematically with decreasing Na contents. The charge ordering
transition only affects the optical spectra below 1000 cm. A hump near
800 cm develops below 100 K, which is accompanied by the appearance of
new lattice modes as well as the strong anti-resonance feature of phonon
spectra. At lower temperature , an optical gap develops at the
magnitude of 2, evidencing an insulating charge
density wave ground state. Our experimental results and analysis unequivocally
point towards the importance of charge ordering instability and strong
electron-phonon interaction in NaCoO system.Comment: 4 pages, 3 figure
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