5-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway. The MTAP gene is frequently deleted in human cancers because of its chromosomal proximity to the tumor ...suppressor gene CDKN2A. By interrogating data from a large-scale short hairpin RNA–mediated screen across 390 cancer cell line models, we found that the viability of MTAP-deficient cancer cells is impaired by depletion of the protein arginine methyltransferase PRMT5. MTAP-deleted cells accumulate the metabolite methylthioadenosine (MTA), which we found to inhibit PRMT5 methyltransferase activity. Deletion of MTAP in MTAP-proficient cells rendered them sensitive to PRMT5 depletion. Conversely, reconstitution of MTAP in an MTAP-deficient cell line rescued PRMT5 dependence. Thus, MTA accumulation in MTAP–deleted cancers creates a hypomorphic PRMT5 state that is selectively sensitized toward further PRMT5 inhibition. Inhibitors of PRMT5 that leverage this dysregulated metabolic state merit further investigation as a potential therapy for MTAP/CDKN2A-deleted tumors.
Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs ...and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.
We present a catalog of galaxy clusters selected via their Sunyaev-Zel'dovich (SZ) effect signature from 2500 deg super(2) of South Pole Telescope (SPT) data. This work represents the complete sample ...of clusters detected at high significance in the 2500 deg super(2) SPT-SZ survey, which was completed in 2011. A total of 677 (409) cluster candidates are identified above a signal-to-noise threshold of xi = 4.5 (5.0). Ground- and space-based optical and near-infrared (NIR) imaging confirms overdensities of similarly colored galaxies in the direction of 516 (or 76%) of the xi > 4.5 candidates and 387 (or 95%) of the xi > 5 candidates; the measured purity is consistent with expectations from simulations. Of these confirmed clusters, 415 were first identified in SPT data, including 251 new discoveries reported in this work. We estimate photometric redshifts for all candidates with identified optical and/or NIR counterparts; we additionally report redshifts derived from spectroscopic observations for 141 of these systems. The mass threshold of the catalog is roughly independent of redshift above z ~ 0.25 leading to a sample of massive clusters that extends to high redshift. The median mass of the sample is M sub(500c)(rho sub(crit)) ~3.5 x 10 super(14) M sub(middot in circle) h super(-1) sub(70), the median redshift is z sub(med) = 0.55, and the highest-redshift systems are at z > 1.4. The combination of large redshift extent, clean selection, and high typical mass makes this cluster sample of particular interest for cosmological analyses and studies of cluster formation and evolution.
The electron-ion relaxation dynamics in warm dense iron were investigated by time-resolved x-ray absorption near-edge spectroscopy (XANES). A novel analysis, combining ab initio density functional ...theory (DFT) and two temperature model (TTM) simulations, was developed to calculate the x-ray absorption spectra as a function of delay time. Here we present experimental evidence of changes at the XAS L3 edge of iron that are consistent with the reduction of the electron-phonon coupling under warm dense matter conditions. The experimental results are in agreement with the model that takes both the electron (Te) and the ion temperature (Ti) dependence of the thermophysical properties into consideration, while models where either constant electron-phonon coupling factor (G) or only Te-dependent G are used do not agree with the observed relaxation dynamics of iron.
A novel multiuser scheduling and feedback strategy for the multiple-input multiple-output (MIMO) downlink is proposed in this paper. It achieves multiuser diversity gain without substantial feedback ...requirements. The proposed strategy uses per-antenna scheduling at the base station, which maps each transmit antenna at the base station (equivalently, a spatial channel) to a user. Each user has a number of receive antennas that is greater than or equal to the number of transmit antennas at the base station. Zero-forcing receivers are deployed by each user to decode the transmitted data streams. In this system, the base station requires users' channel quality on each spatial channel for scheduling. An opportunistic feedback protocol is proposed to reduce the feedback requirements. The proposed protocol uses a contention channel that consists of a fixed number of feedback minislots to convey channel state information. Feedback control parameters including the channel quality threshold and the random access feedback probability are jointly adjusted to maximize the average throughput performance of this system. Multiple receive antennas at the base station are used on the feedback channel to allow decoding multiple feedback messages sent simultaneously by different users. This further reduces the bandwidth of the feedback channel. Iterative search algorithms are proposed to solve the optimization for selection of these parameters under both scenarios that the cumulative distribution functions of users are known or unknown to the base station
In this paper, a novel relaying strategy that uses multiple-input multiple-output (MIMO) fixed relays with linear processing to support multiuser transmission in cellular networks is proposed. The ...fixed relay processes the received signal with linear operations and forwards the processed signal to multiple users creating a multiuser MIMO relay. This paper proposes upper and lower bounds on the achievable sum rate for this architecture assuming zero-forcing dirty paper coding at the base station, neglecting the direct links from the base station to the users, and with certain structure in the relay. These bounds are used to motivate an implementable multiuser precoding strategy that combines Tomlinson-Harashima precoding at the base station and linear signal processing at the relay, adaptive stream selection, and QAM modulation. Reduced complexity algorithms based on the sum rate lower bounds are used to select a subset of users. We compare the sum rates achieved by the proposed system architecture and algorithms with the sum rate upper bound and the sum rate achieved by the decode-and-forward relaying.
ABSTRACT We present cosmological parameter constraints obtained from galaxy clusters identified by their Sunyaev-Zel'dovich effect signature in the 2500 square-degree South Pole Telescope Sunyaev ...Zel'dovich (SPT-SZ) survey. We consider the 377 cluster candidates identified at with a detection significance greater than five, corresponding to the 95% purity threshold for the survey. We compute constraints on cosmological models using the measured cluster abundance as a function of mass and redshift. We include additional constraints from multi-wavelength observations, including Chandra X-ray data for 82 clusters and a weak lensing-based prior on the normalization of the mass-observable scaling relations. Assuming a spatially flat ΛCDM cosmology, we combine the cluster data with a prior on H0 and find and , with the parameter combination . These results are in good agreement with constraints from the cosmic microwave background (CMB) from SPT, WMAP, and Planck, as well as with constraints from other cluster data sets. We also consider several extensions to ΛCDM, including models in which the equation of state of dark energy w, the species-summed neutrino mass, and/or the effective number of relativistic species ( ) are free parameters. When combined with constraints from the Planck CMB, H0, baryon acoustic oscillation, and SNe, adding the SPT cluster data improves the w constraint by 14%, to .
Objective
Coacervates are inevitably formed on scalp on using hair washing products. Our goal was to analyse the coacervates in detail to identify the part responsible for scalp stimulation.
Methods
...Shampoo that increases coacervate formation was applied to in vitro skin and was washed. The residue was then analysed using Fourier transform infrared spectroscopy–focal plane array (FTIR‐FPA) and X‐ray photoelectron microscopy (XPS). And HaCaT cells were used for irritant test of coacervate.
Results
Through this research, it was confirmed that the coacervate was a macromolecule structurally similar to a cationic polymer and contains an anionic surfactant. Its anionic surfactant was structurally semi‐stable so that it released onto scalp when it absorbs moisture.
Conclusion
Coacervate releases sulphate bonding into the matrix when it is exposed to water. Thus, the scalp stimulation would be expected.
Résumé
Objectif
Des coacervats sont inévitablement formés sur le cuir chevelu lors de l'utilisation de produits de lavage des cheveux. Notre objectif était d'analyser les coacervats en détail pour identifier la partie responsable de l'irritation du cuir chevelu.
Methodes
Un shampoo qui augmente la formation de coacervats a été appliqué sur la peau in vitro et a été lavé. Le résidu a ensuite été analysé à l'aide de la spectroscopie infrarouge à transformée de Fourier au plan focal (FTIR‐FPA), et de la microscopie à photoélectrons X (XPS). Les cellules HaCaT ont été utilisées pour le test d'irritation du coacervat.
Resultats
Grâce à cette recherche, il a été confirmé que le coacervat est une macromolécule structurellement similaire à un polymère cationique et contient un agent tensio‐actif anionique. Son tensioactif anionique était structurellement semi‐stable de sorte qu'il relargue sur le cuir chevelu quand il absorbe de l'humidité.
Conclusion
Le coacervat libère la liaison de sulfate dans la matrice quand il est exposé à l'eau. Ainsi, l'irritation du cuir chevelu est attendue.
This study aimed to evaluate the scalp irritation effects of shampoos that form coacervates. We believe that our study makes a significant contribution to the literature because the structure of coacervates was evaluated as well as the possible mechanism of irritation.
Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure, which if left untreated, is invariably fatal. Conventional therapies with immunosuppressive therapy or allogeneic ...hematopoietic stem cell transplantation (HSCT) are highly effective. HSCT can offer a greater outcome in younger patients who have an available HLA match-related donor. Recent studies showing the addition of antithymocyte globulin (ATG) to the conditioning regimen improves engraftment and reduces the risk of graft-versus-host disease (GVHD).There are currently two ATG preparations in the USA, equine (or horse) and rabbit ATG. These agents are pharmacologically distinct, having significant differences in their pharmacokinetics and in vivo immunosuppressive effects N Engl J Med 365(5):430-438, 2011. Here, we report a case of two monozygotic twins with constitutional SAA that evolved to myelodysplastic syndrome (MDS) who both underwent allogeneic peripheral blood stem cell transplantation (PBSC) from the same single HLA antigen mismatched sibling donor with the only difference in the transplant regimen being the type of ATG used in the preparative regimen; one twin received horse ATG and the other received rabbit ATG during conditioning. This report emphasizes that dramatic differences in donor T cell chimerism and clinical outcomes including GVHD can occur as a consequence of the type of ATG that is utilized in the transplant conditioning regimen. These differences highlight that these agents should not be considered interchangeable drugs when used in this setting.
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