SIRT1 DEFICIENCY COMPROMISES MOUSE EMBRYONIC STEM CELL DIFFERENTIATION, AND EMBRYONIC AND ADULT HEMATOPOIESIS IN THE MOUSE

Indiana University-Purdue University Indianapolis (IUPUI)SIRT1 (Sirtuin 1) is a founding member of a family of seven proteins and histone deacetylases. It is involved in cellular resistance to stress, metabolism, differentiation, aging, and tumor suppression. SIRT1-/- mice demonstrate embryonic and postnatal development defects. We examined hematopoietic and endothelial cell differentiation of SIRT1-/- mouse embryonic stem (mES) cells in vitro, and hematopoietic progenitors in SIRT1+/+, SIRT1+/-, and SIRT1-/- mice. SIRT1-/- ES cells exhibited markedly delayed/immature formation of blast colony-forming cells (BL-CFCs). When individual blast colonies were analyzed for hematopoietic and endothelial potential, replated SIRT1-/- BL-CFC possessed limited hematopoietic potential, whereas endothelial potential was essentially unaltered. The ability of SIRT1-/- ES cells to form primitive erythroid progenitors was not only delayed but greatly decreased. Moreover, after differentiation of SIRT1-/- mES cells, there were also significant decreases in granulocyte-macrophage (CFU-GM) and multipotential (CFU-GEMM) progenitor cells. Differentiation delay/defects were associated with delayed capacity to switch off Oct4, Nanog and Fgf5, decreased β-H1 globin, β-major globin, and Scl gene expression and reduced activation of the Erk1/2 pathway upon SIRT1-/- ES cell commitment. Reintroduction of WT SIRT1 into SIRT1-/- cells partially rescued the primitive erythroid progenitor formation of SIRT1-/- cells and the expression of hemoglobin genes, Hbb-bh1 and Hbb-b1, suggesting that the defect of hematopoietic commitment is due to deletion of SIRT1, and not to genetic drifting of SIRT1-/- cells. To confirm the requirement for SIRT1 for normal development of hematopoietic progenitor cells, we assessed embryonic and adult hematopoiesis in SIRT1+/+, SIRT1+/- and SIRT1-/- mice. Yolk sacs from SIRT1 mutant embryos generated fewer primitive erythroid precursors compared to wild-type (WT) and heterozygous mice. Moreover, knockout of SIRT1 decreased primary bone marrow hematopoietic progenitor cells (HPCs) in 5 week and 12 month old mice, which was especially notable at lower (5%) O2 tension. In addition these progenitors survived less well in vitro under conditions of delayed growth factor addition. Taken together, these results demonstrate that SIRT1 plays a role in ES cell hematopoietic differentiation and mouse hematopoiesis

Quantum entangled Sagnac interferometer

SU(1,1) interferometer (SUI) is a novel type of interferometer that uses directly entangled quantum fields for sensing phase change. For rotational sensing, Sagnac geometry is usually adopted. However, because SUI depends on the phase sum of the two arms, traditional Sagnac geometry, when applied to SUI, will result in null signal. In this paper, we modify the traditional Sagnac interferometer by nesting SU(1,1) interferometers inside. We show that the rotational signal comes from two parts labeled as "classical" and "quantum", respectively, and the quantum part, where quantum entangled fields are used for sensing, has rotational signal enhanced by a factor related to the gain of the SUI.Comment: 5 pages, 3 figure

SIRT1 positively regulates autophagy and mitochondria function in embryonic stem cells under oxidative stress

SIRT1, an NAD-dependent deacetylase, plays a role in regulation of autophagy. SIRT1 increases mitochondrial function and reduces oxidative stress, and has been linked to age-related reactive oxygen species (ROS) generation, which is highly dependent on mitochondrial metabolism. H2O2 induces oxidative stress and autophagic cell death through interference with Beclin 1 and the mTOR signaling pathways. We evaluated connections between SIRT1 activity and induction of autophagy in murine (m) and human (h) embryonic stem cells (ESCs) upon ROS challenge. Exogenous H2 O2 (1 mM) induced apoptosis and autophagy in wild-type (WT) and Sirt1-/- mESCs. High concentrations of H2O2 (1 mM) induced more apoptosis in Sirt1-/-, than in WT mESCs. However, addition of 3-methyladenine, a widely used autophagy inhibitor, in combination with H2O2 induced more cell death in WT than in Sirt1-/- mESCs. Decreased induction of autophagy in Sirt1-/- mESCs was demonstrated by decreased conversion of LC3-I to LC3-II, lowered expression of Beclin-1, and decreased LC3 punctae and LysoTracker staining. H2O2 induced autophagy with loss of mitochondrial membrane potential and disruption of mitochondrial dynamics in Sirt1-/- mESCs. Increased phosphorylation of P70/85-S6 kinase and ribosomal S6 was noted in Sirt1-/- mESCs, suggesting that SIRT1 regulates the mTOR pathway. Consistent with effects in mESCs, inhibition of SIRT1 using Lentivirus-mediated SIRT1 shRNA in hESCs demonstrated that knockdown of SIRT1 decreased H2O2-induced autophagy. This suggests a role for SIRT1 in regulating autophagy and mitochondria function in ESCs upon oxidative stress, effects mediated at least in part by the class III PI3K/Beclin 1 and mTOR pathways

Phase Dependent Hanbury-Brown and Twiss effect

Hanbury-Brown and Twiss (HBT) effect is the foundation for stellar intensity interferometry. However, it is a phase insensitive two-photon interference effect. In this paper, we extend the HBT interferometer by mixing two phase-coherent input fields with coherent auxiliary fields before intensity correlation measurement and achieve phase sensitive two-photon interference so as to measure the complete complex second-order coherence function of the input fields. This practical scheme paves the way for synthetic aperture imaging for astronomical applications in optical regime. Pulsed input fields is also tested for potential remote sensing and ranging applications. We discuss the condition to implement recently proposed entanglement-based telescopy scheme with the more realistic cw broadband anti-bunched light fields.Comment: 5 pages, 6 figure

Interstellar: Using Halide's Scheduling Language to Analyze DNN Accelerators

We show that DNN accelerator micro-architectures and their program mappings represent specific choices of loop order and hardware parallelism for computing the seven nested loops of DNNs, which enables us to create a formal taxonomy of all existing dense DNN accelerators. Surprisingly, the loop transformations needed to create these hardware variants can be precisely and concisely represented by Halide's scheduling language. By modifying the Halide compiler to generate hardware, we create a system that can fairly compare these prior accelerators. As long as proper loop blocking schemes are used, and the hardware can support mapping replicated loops, many different hardware dataflows yield similar energy efficiency with good performance. This is because the loop blocking can ensure that most data references stay on-chip with good locality and the processing units have high resource utilization. How resources are allocated, especially in the memory system, has a large impact on energy and performance. By optimizing hardware resource allocation while keeping throughput constant, we achieve up to 4.2X energy improvement for Convolutional Neural Networks (CNNs), 1.6X and 1.8X improvement for Long Short-Term Memories (LSTMs) and multi-layer perceptrons (MLPs), respectively.Comment: Published as a conference paper at ASPLOS 202

A Dispersive Analysis on the f0(600)f_0(600) and f0(980)f_0(980) Resonances in γγ→π+π−,π0π0\gamma\gamma\to\pi^+\pi^-, \pi^0\pi^0 Processes

We estimate the di-photon coupling of $f_0(600)$, $f_0(980)$ and $f_2(1270)$ resonances in a coupled channel dispersive approach. The $f_0(600)$ di-photon coupling is also reinvestigated using a single channel $T$ matrix for $\pi\pi$ scattering with better analyticity property, and it is found to be significantly smaller than that of a $\bar qq$ state. Especially we also estimate the di-photon coupling of the third sheet pole located near $\bar KK$ threshold, denoted as $f_0^{III}(980)$. It is argued that this third sheet pole may be originated from a coupled channel Breit-Wigner description of the $f_0(980)$ resonance.Comment: 24 pages and 13 eps figures. A nuerical bug in previous version is fixed. Some results changed. References and new figures added. Version to appear in Phys. Rev.

The influence of economic factors on the sustainable energy consumption: evidence from China

Recently, sustainable energy consumption has been a significant factor in reducing environmental degradation due to the high economic growth, and this phenomenon demands more attention of scholars and policymakers. Thus, the current literature examines the impact of economic factors such as economic growth, foreign direct investment (FDI), inflation, and population growth on sustainable energy consumption (SEC), particularly in renewable energy consumption (REC) in China. This study used secondary data collection methods extracted from world development indicators (WDI), incorporating stationary tests like Phillips-Perron (PP) and Augmented Dickey-Fuller (ADF) to check the unit root of the constructs. The time-series data involved are from 1981 to 2019. The autoregressive distributed lag (ARDL) model was utilized to examine the association among the variables. The results indicated that economic growth, FDI, inflation, and population growth were positively associated with SEC in China. This study provides the guidelines to the policymakers to develop policies related to the SEC

Circulating tissue factor-positive procoagulant microparticles in patients with type 1 diabetes

Aim: To investigate the count of circulating tissue factor-positive (TF+) procoagulant microparticles (MPs) in patients with type 1 diabetes mellitus (T1DM). Methods: This case-control study included patients with T1DM and age and sex-matched healthy volunteers. The counts of phosphatidylserine-positive (PS+) MPs and TF(+)PS(+)MPs and the subgroups derived from different cell types were measured in the peripheral blood sample of the two groups using multicolor flow cytometric assay. We compared the counts of each MP between groups as well as the ratio of the TF(+)PS(+)MPs and PS(+)MPs (TF(+)PS(+)MPs/PS(+)MPs). Results: We recruited 36 patients with T1DM and 36 matched healthy controls. Compared with healthy volunteers, PS(+)MPs, TF(+)PS(+)MPs and TF(+)PS(+)MPs/PS(+)MPs were elevated in patients with T1DM (PS(+)MPs: 1078.5 +/- 158.08 vs 686.84 +/- 122.04/mu L, P &lt;0.001; TF(+)PS(+)MPs: 202.10 +/- 47.47 vs 108.33 +/- 29.42/mu L, P &lt;0.001; and TF(+)PS(+)MPs/PS(+)MPs: 0.16 +/- 0.04 vs 0.19 +/- 0.05, P = 0.004), mostly derived from platelet, lymphocytes and endothelial cells. In the subgroup analysis, the counts of total and platelet TF(+)PS(+)MPs were increased in patients with diabetic retinopathy (DR) and with higher HbA1c, respectively. Conclusion: Circulating TF(+)PS(+)MPs and those derived from platelet, lymphocytes and endothelial cells were elevated in patients with T1DM.De tre första författarna delar förstaförfattarskapet.</p