Nf1 haploinsufficiency alters myeloid lineage commitment and function, leading to deranged skeletal homeostasis

Although nullizygous loss of NF1 leads to myeloid malignancies, haploinsufficient loss of NF1 (Nf1) has been shown to contribute to osteopenia and osteoporosis which occurs in approximately 50% of neurofibromatosis type 1 (NF1) patients. Bone marrow mononuclear cells of haploinsufficient NF1 patients and Nf1(+/-) mice exhibit increased osteoclastogenesis and accelerated bone turnover; however, the culprit hematopoietic lineages responsible for perpetuating these osteolytic manifestations have yet to be elucidated. Here we demonstrate that conditional inactivation of a single Nf1 allele within the myeloid progenitor cell population (Nf1-LysM) is necessary and sufficient to promote multiple osteoclast gains-in-function, resulting in enhanced osteoclastogenesis and accelerated osteoclast bone lytic activity in response to proresorptive challenge in vivo. Surprisingly, mice conditionally Nf1 heterozygous in mature, terminally differentiated osteoclasts (Nf1-Ctsk) do not exhibit any of these skeletal phenotypes, indicating a critical requirement for Nf1 haploinsufficiency at a more primitive/progenitor stage of myeloid development in perpetuating osteolytic activity. We further identified p21Ras-dependent hyperphosphorylation of Pu.1 within the nucleus of Nf1 haploinsufficient myelomonocytic osteoclast precursors, providing a novel therapeutic target for the potential treatment of NF1 associated osteolytic manifestations

Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice

ASXL1 is mutated/deleted with high frequencies in multiple forms of myeloid malignancies, and its alterations are associated with poor prognosis. De novo ASXL1 mutations cause Bohring-Opitz syndrome characterized by multiple congenital malformations. We show that Asxl1 deletion in mice led to developmental abnormalities including dwarfism, anophthalmia, and 80% embryonic lethality. Surviving Asxl1(-/-) mice lived for up to 42 days and developed features of myelodysplastic syndrome (MDS), including dysplastic neutrophils and multiple lineage cytopenia. Asxl1(-/-) mice had a reduced hematopoietic stem cell (HSC) pool, and Asxl1(-/-) HSCs exhibited decreased hematopoietic repopulating capacity, with skewed cell differentiation favoring granulocytic lineage. Asxl1(+/-) mice also developed mild MDS-like disease, which could progress to MDS/myeloproliferative neoplasm, demonstrating a haploinsufficient effect of Asxl1 in the pathogenesis of myeloid malignancies. Asxl1 loss led to an increased apoptosis and mitosis in Lineage(-)c-Kit(+) (Lin(-)c-Kit(+)) cells, consistent with human MDS. Furthermore, Asxl1(-/-) Lin(-)c-Kit(+) cells exhibited decreased global levels of H3K27me3 and H3K4me3 and altered expression of genes regulating apoptosis (Bcl2, Bcl2l12, Bcl2l13). Collectively, we report a novel ASXL1 murine model that recapitulates human myeloid malignancies, implying that Asxl1 functions as a tumor suppressor to maintain hematopoietic cell homeostasis. Future work is necessary to clarify the contribution of microenvironment to the hematopoietic phenotypes observed in the constitutional Asxl1(-/-) mice

Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV

We report the STAR measurement of Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV. Using the event mixing technique, the Phi spectra and yields are obtained at mid-rapidity for five centrality bins in Au+Au collisions and for non-singly-diffractive p+p collisions. It is found that the Phi transverse momentum distributions from Au+Au collisions are better fitted with a single-exponential while the p+p spectrum is better described by a double-exponential distribution. The measured nuclear modification factors indicate that Phi production in central Au+Au collisions is suppressed relative to peripheral collisions when scaled by the number of binary collisions. The systematics of versus centrality and the constant Phi/K- ratio versus beam species, centrality, and collision energy rule out kaon coalescence as the dominant mechanism for Phi production.Comment: 6 pages, 3 figures, submitted to Phys. Rev. Let

Azimuthally sensitive Hanbury Brown-Twiss interferometry in Au+Au collisions at sqrt(s_{NN}) = 200 GeV

We present the results of a systematic study of the shape of the pion distribution in coordinate space at freeze-out in Au+Au collisions at RHIC using two-pion Hanbury Brown-Twiss (HBT) interferometry. Oscillations of the extracted HBT radii vs. emission angle indicate sources elongated perpendicular to the reaction plane. The results indicate that the pressure and expansion time of the collision system are not sufficient to completely quench its initial shape.Comment: 6 pages, 4 figures, published versio

ρ\u3csup\u3e0\u3c/sup\u3e production and possible modification in Au + Au and p + p collisions at √s\u3csub\u3eNN\u3c/sub\u3e = 200 GeV

We report results on ρ(770)0→π+π− production at midrapidity in p+p and peripheral Au+Au collisions at √sNN=200  GeV. This is the first direct measurement of ρ(770)0→π+π− in heavy-ion collisions. The measured ρ0 peak in the invariant mass distribution is shifted by ∼40  MeV/c2 in minimum bias p+p interactions and ∼70  MeV/c2 in peripheral Au+Au collisions. The ρ0 mass shift is dependent on transverse momentum and multiplicity. The modification of the ρ0 meson mass, width, and shape due to phase space and dynamical effects are discussed

Distributions of Charged Hadrons Associated with High Transverse Momentum Particles in pp and Au+Au Collisions at √s\u3csub\u3eNN\u3c/sub\u3e = 200 GeV

Charged hadrons in 0.15⊥\u3c4  GeV/c associated with particles of ptrig⊥\u3e4  GeV/c are reconstructed in pp and Au+Au collisions at √sNN=200  GeV. The associated multiplicity and p⊥magnitude sum are found to increase from pp to central Au+Au collisions. The associated p⊥distributions, while similar in shape on the nearside, are significantly softened on the awayside in central Au+Au relative to pp and not much harder than that of inclusive hadrons. The results, consistent with jet quenching, suggest that the awayside fragments approach equilibration with the medium traversed

Distributions of charged hadrons associated with high transverse momentum particles in pp and Au plus Au collisions at root(S)(NN)=200 GeV

Charged hadrons in 0.15 4 GeV/c are reconstructed in pp and Au+Au collisions at root s(NN)=200 GeV. The associated multiplicity and p(perpendicular to) magnitude sum are found to increase from pp to central Au+Au collisions. The associated p(perpendicular to) distributions, while similar in shape on the nearside, are significantly softened on the awayside in central Au+Au relative to pp and not much harder than that of inclusive hadrons. The results, consistent with jet quenching, suggest that the awayside fragments approach equilibration with the medium traversed

rho(0) production and possible modification in Au+Au and p+p collisions at root S-NN=200 GeV

We report results on rho(770)(0)-->pi(+)pi(-) production at midrapidity in p+p and peripheral Au+Au collisions at roots(NN)=200 GeV. This is the first direct measurement of rho(770)(0)-->pi(+)pi(-) in heavy-ion collisions. The measured rho(0) peak in the invariant mass distribution is shifted by similar to40 MeV/c(2) in minimum bias p+p interactions and similar to70 MeV/c(2) in peripheral Au+Au collisions. The rho(0) mass shift is dependent on transverse momentum and multiplicity. The modification of the rho(0) meson mass, width, and shape due to phase space and dynamical effects are discussed

Batch Process Monitoring Based on Multisubspace Multiway Principal Component Analysis and Time-Series Bayesian Inference

Multiway principal component analysis (MPCA), which is a dimensionality reduction method for process variables, has been widely used to monitor batch and fed-batch processes. However, three main factors affect the performance of MPCA monitoring: The future status of the online batch has to be predicted, the discarded principal components with small variance might contain useful information, and self-correlation and industrial noise exist in process data. Thus, a new batch process monitoring method based on multisubspace multiway principal component analysis and time-series Bayesian inference through a moving window is developed. The feasibility and effectiveness of the proposed batch process monitoring method is demonstrated using a numerical process and the fed-batch penicillin fermentation process, and its performance is compared with that of the MPCA. The results show that the proposed method is more accurate in detecting different types of batch process faults