2,564 research outputs found
Milling plant and soil material in plastic tubes over-estimates carbon and under-estimates nitrogen concentrations
Peer reviewedPostprin
Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.
To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo
Effects of temperature on thick branes and the fermion (quasi-)localization
Following Campos's work [Phys. Rev. Lett. 88, 141602 (2002)], we investigate
the effects of temperature on flat, de Sitter (dS), and anti-de Following
Campos's work [Phys. Rev. Lett. \textbf{88}, 141602 (2002)], we investigate the
effects of temperature on flat, de Sitter (dS), and anti-de Sitter (AdS) thick
branes in five-dimensional (5D) warped spacetime, and on the fermion
(quasi-)localization. First, in the case of flat brane, when the critical
temperature reaches, the solution of the background scalar field and the warp
factor is not unique. So the thickness of the flat thick brane is uncertain at
the critical value of the temperature parameter, which is found to be lower
than the one in flat 5D spacetime. The mass spectra of the fermion Kaluza-Klein
(KK) modes are continuous, and there is a series of fermion resonances. The
number and lifetime of the resonances are finite and increase with the
temperature parameter, but the mass of the resonances decreases with the
temperature parameter. Second, in the case of dS brane, we do not find such a
critical value of the temperature parameter. The mass spectra of the fermion KK
modes are also continuous, and there is a series of fermion resonances. The
effects of temperature on resonance number, lifetime, and mass are the same
with the case of flat brane. Last, in the case of AdS brane, {the critical
value of the temperature parameter can less or greater than the one in the flat
5D spacetime.} The spectra of fermion KK modes are discrete, and the mass of
fermion KK modes does not decrease monotonically with increasing temperature
parameter.Comment: 24 pages, 15 figures, published versio
Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden
Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression
Eta Carinae and the Luminous Blue Variables
We evaluate the place of Eta Carinae amongst the class of luminous blue
variables (LBVs) and show that the LBV phenomenon is not restricted to
extremely luminous objects like Eta Car, but extends luminosities as low as
log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses
as low as ~10-15 Msun. We present a census of S Doradus variability, and
discuss basic LBV properties, their mass-loss behaviour, and whether at maximum
light they form pseudo-photospheres. We argue that those objects that exhibit
giant Eta Car-type eruptions are most likely related to the more common type of
S Doradus variability. Alternative atmospheric models as well as
sub-photospheric models for the instability are presented, but the true nature
of the LBV phenomenon remains as yet elusive. We end with a discussion on the
evolutionary status of LBVs - highlighting recent indications that some LBVs
may be in a direct pre-supernova state, in contradiction to the standard
paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova
imposters" (eds R. Humphreys and K. Davidson) new version submitted to
Springe
Quantum-Dot Light-Emitting Diodes with Nitrogen-Doped Carbon Nanodot Hole Transport and Electronic Energy Transfer Layer
Electroluminescence efficiency is crucial for the application of quantum-dot light-emitting diodes (QD-LEDs) in practical devices. We demonstrate that nitrogen-doped carbon nanodot (N-CD) interlayer improves electrical and luminescent properties of QD-LEDs. The N-CDs were prepared by solution-based bottom up synthesis and were inserted as a hole transport layer (HTL) between other multilayer HTL heterojunction and the red-QD layer. The QD-LEDs with N-CD interlayer represented superior electrical rectification and electroluminescent efficiency than those without the N-CD interlayer. The insertion of N-CD layer was found to provoke the Forster resonance energy transfer (FRET) from N-CD to QD layer, as confirmed by time-integrated and - resolved photoluminescence spectroscopy. Moreover, hole-only devices (HODs) with N-CD interlayer presented high hole transport capability, and ultraviolet photoelectron spectroscopy also revealed that the N-CD interlayer reduced the highest hole barrier height. Thus, more balanced carrier injection with sufficient hole carrier transport feasibly lead to the superior electrical and electroluminescent properties of the QD-LEDs with N-CD interlayer. We further studied effect of N-CD interlayer thickness on electrical and luminescent performances for high-brightness QD-LEDs. The ability of the N-CD interlayer to improve both the electrical and luminescent characteristics of the QD-LEDs would be readily exploited as an emerging photoactive material for high-efficiency optoelectronic devices.ope
Cloning and Characterization of a Putative TAC1 Ortholog Associated with Leaf Angle in Maize (Zea mays L.)
BACKGROUND: Modifying plant architecture to increase photosynthesis efficiency and reduce shade avoidance response is very important for further yield improvement when crops are grown in high density. Identification of alleles controlling leaf angle in maize is needed to provide insight into molecular mechanism of leaf development and achieving ideal plant architecture to improve grain yield. METHODOLOGY/PRINCIPAL FINDINGS: The gene cloning was done by using comparative genomics, and then performing real-time polymerase chain reaction (RT-PCR) analysis to assay gene expression. The gene function was validated by sequence dissimilarity analysis and QTL mapping using a functional cleaved amplified polymorphism (CAP). CONCLUSIONS: The leaf angle is controlled by a major quantitative trait locus, ZmTAC1 (Zea mays L. Leaf Angle Control 1). ZmTAC1 has 4 exons encoding a protein with 263 amino acids, and its domains are the same as those of the rice OsTAC1 protein. ZmTAC1 was found to be located in the region of qLA2 by using the CAP marker and the F(2:3) families from the cross between Yu82 and Shen137. Real-time PCR analysis revealed ZmTAC1 expression was the highest in the leaf-sheath pulvinus, less in the leaf and shoot apical meristem, and the lowest in the root. A nucleotide difference in the 5'-untranslated region (UTR) between the compact inbred line Yu82 ("CTCC") and the expanded inbred line Shen137 ("CCCC") influences the expression level of ZmTAC1, further controlling the size of the leaf angle. Sequence verification of the change in the 5'-UTR revealed ZmTAC1 with "CTCC" was present in 13 compact inbred lines and ZmTAC1 with "CCCC" was present in 18 expanded inbred lines, indicating ZmTAC1 had been extensively utilized in breeding with regard to the improvement of the maize plant architecture
Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer
<p>Abstract</p> <p>Background</p> <p>Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women.</p> <p>Methods</p> <p>A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry.</p> <p>Results</p> <p>Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer.</p> <p>Conclusion</p> <p>Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy.</p
Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies
<p>Abstract</p> <p>Background</p> <p>YN968D1 (Apatinib) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies.</p> <p>Methods</p> <p>This dose-escalation study was conducted according to the Chinese State Food and Drug Administration (SFDA) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death.</p> <p>Results</p> <p>Forty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension (69.5%, 29 grade 1-2 and 3 grade 3-4), proteinuria (47.8%, 16 grade 1-2 and 6 grade 3-4), and hand-foot syndrome (45.6%, 15 grade 1-2 and 6 grade 3-4). Among the thirty-seven evaluable patients, PR was noted in seven patients (18.9%), SD 24 (64.9%), with a disease control rate of 83.8% at 8 weeks.</p> <p>Conclusions</p> <p>The recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations.</p> <p>Trial registration</p> <p>ClinicalTrials.gov unique identifier: NCT00633490</p
Differential cross sections and spin density matrix elements for the reaction gamma p -> p omega
High-statistics differential cross sections and spin density matrix elements
for the reaction gamma p -> p omega have been measured using the CLAS at
Jefferson Lab for center-of-mass (CM) energies from threshold up to 2.84 GeV.
Results are reported in 112 10-MeV wide CM energy bins, each subdivided into
cos(theta_CM) bins of width 0.1. These are the most precise and extensive omega
photoproduction measurements to date. A number of prominent structures are
clearly present in the data. Many of these have not previously been observed
due to limited statistics in earlier measurements
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