Showing papers by "Jun Lu published in 2007"
TL;DR: It is shown that global repression of miRNA maturation promotes cellular transformation and tumorigenesis, and abrogation of global miRNA processing promotes tumorigenisation.
Abstract: MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate the expression of target mRNA transcripts. Many of these target mRNA transcripts are involved in proliferation, differentiation and apoptosis, processes commonly altered during tumorigenesis. Recent work has shown a global decrease of mature miRNA expression in human cancers. However, it is unclear whether this global repression of miRNAs reflects the undifferentiated state of tumors or causally contributes to the transformed phenotype. Here we show that global repression of miRNA maturation promotes cellular transformation and tumorigenesis. Cancer cells expressing short hairpin RNAs (shRNAs) targeting three different components of the miRNA processing machinery showed a substantial decrease in steady-state miRNA levels and a more pronounced transformed phenotype. In animals, miRNA processing-impaired cells formed tumors with accelerated kinetics. These tumors were more invasive than control tumors, suggesting that global miRNA loss enhances tumorigenesis. Furthermore, conditional deletion of Dicer1 enhanced tumor development in a K-Ras-induced mouse model of lung cancer. Overall, these studies indicate that abrogation of global miRNA processing promotes tumorigenesis.
1,400 citations
TL;DR: The data show that expression of many microRNAs is altered in heart disease and that different types of heart disease are associated with distinct changes in microRNA expression.
Abstract: MicroRNAs are recently discovered regulators of gene expression and are becoming increasingly recognized as important regulators of heart function. Genome-wide profiling of microRNAs in human heart...
646 citations
TL;DR: It is shown that expression signatures of as few as two miRNAs could accurately discriminate ALL from AML, and that epigenetic regulation might play an important role in the regulation of expression of miRNAAs in acute leukemias.
Abstract: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas acute myeloid leukemia (AML) is the most common acute leukemia in adults. In general, ALL has a better prognosis than AML. To understand the distinct mechanisms in leukemogenesis between ALL and AML and to identify markers for diagnosis and treatment, we performed a large-scale genome-wide microRNA (miRNA, miR) expression profiling assay and identified 27 miRNAs that are differentially expressed between ALL and AML. Among them, miR-128a and -128b are significantly overexpressed, whereas let-7b and miR-223 are significantly down-regulated in ALL compared with AML. They are the most discriminatory miRNAs between ALL and AML. Using the expression signatures of a minimum of two of these miRNAs resulted in an accuracy rate of >95% in the diagnosis of ALL and AML. The differential expression patterns of these four miRNAs were validated further through large-scale real-time PCR on 98 acute leukemia samples covering most of the common cytogenetic subtypes, along with 10 normal control samples. Furthermore, we found that overexpression of miR-128 in ALL was at least partly associated with promoter hypomethylation and not with an amplification of its genomic locus. Taken together, we showed that expression signatures of as few as two miRNAs could accurately discriminate ALL from AML, and that epigenetic regulation might play an important role in the regulation of expression of miRNAs in acute leukemias.
485 citations
TL;DR: These findings demonstrate independent pathways mediating atonia and the EEG components of REM provide a basis for their occasional dissociation in pathological states, e.g. REM sleep behaviour disorder.
Abstract: Rapid eye movement (REM) sleep is a behavioural state characterized by activation of the cortical and hippocampal EEG, rapid eye movements and muscle atonia. For the past 30 years, the most widely accepted neural circuitry model for the regulation of REM sleep has emphasized reciprocal inhibitory interactions between pontine brainstem monoaminergic and cholinergic neurons. In general support of the reciprocal interaction model, neuropharmacological studies have shown that cholinergic agonists promote REM sleep and muscarinic antagonists and monoamines inhibit REM sleep. It has nevertheless proven difficult to reconcile both the theoretical framework of this model and the pharmacological data with the fact that selective lesions of either cholinergic or monoaminergic (noradrenergic, serotoninergic or dopaminergic) nuclei in the brainstem have relatively limited effects on REM sleep. Recent work by our laboratory has revealed the presence of non-cholinergic and non-monoaminergic mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum that may form the neuroanatomical basis of the switching circuitry for REM sleep. These findings posit a REM switching circuitry model that is analogous to an electronic 'flip-flop' switch. In this flip-flop switch arrangement, GABAergic REM-on neurons (located in the sublaterodorsal tegmental nucleus (SLD)) inhibit GABAergic REM-off neurons (located in the ventrolateral periaqueductal grey matter (vlPAG) and lateral pontine tegmentum (LPT)) and vice versa. In the REM-on area are two populations of glutamatergic neurons, the first of which projects to the basal forebrain and regulates EEG components of REM sleep and the second of which projects to the ventromedial medulla and spinal cord and regulates atonia during REM sleep. Our findings demonstrating independent pathways mediating atonia and the EEG components of REM provide a basis for their occasional dissociation in pathological states, e.g. REM sleep behaviour disorder.
173 citations
TL;DR: It is found that overexpression of miR-128a and b in ALL was at least partly associated with hypomethylation, rather than amplification of DNA locus copy, which will enhance the understanding of the biological role of these miRNAs and their targets in leukemogenesis, and in determining the lineage fate of acute leukemia.
125 citations
TL;DR: The crystal structure of a large C-terminal fragment of human Daam1 containing the FH2 domain has weak actin assembly activity as compared with other mammalian formins, but mutations that disrupt the beta-strand lock increase activity about tenfold to a level comparable to other formins.
100 citations
TL;DR: The use of ALD for making nanostructured materials is exemplified by many ways: making of nanolaminates, deposition of thin films inside nanopores, as well as coating of nanofibers and nanorods as discussed by the authors.
77 citations
TL;DR: It is hypothesize that barbiturate anesthetics and related agents microinjected into the MPTA enhance the inhibitory response of local GABAA‐R‐bearing neurons to endogenous GABA released at baseline during wakefulness, ultimately leading to loss of consciousness.
Abstract: Anesthesia, slow-wave sleep, syncope, concussion and reversible coma are behavioral states characterized by loss of consciousness, slow-wave cortical electroencephalogram, and motor and sensory suppression. We identified a focal area in the rat brainstem, the mesopontine tegmental anesthesia area (MPTA), at which microinjection of pentobarbital and other GABA(A) receptor (GABA(A)-R) agonists reversibly induced an anesthesia-like state. This effect was attenuated by local pre-treatment with the GABA(A)-R antagonist bicuculline. Using neuroanatomical tracing we identified four pathways ascending from the MPTA that are positioned to mediate electroencephalographic synchronization and loss of consciousness: (i) projections to the intralaminar thalamic nuclei that, in turn, project to the cortex; (ii) projections to several pontomesencephalic, diencephalic and basal forebrain nuclei that project cortically and are considered parts of an ascending "arousal system"; (iii) a projection to other parts of the subcortical forebrain, including the septal area, hypothalamus, zona incerta and striato-pallidal system, that may indirectly affect cortical arousal and hippocampal theta rhythm; and (iv) modest projections directly to the frontal cortex. Several of these areas have prominent reciprocal projections back to the MPTA, notably the zona incerta, lateral hypothalamus and frontal cortex. We hypothesize that barbiturate anesthetics and related agents microinjected into the MPTA enhance the inhibitory response of local GABA(A)-R-bearing neurons to endogenous GABA released at baseline during wakefulness. This modulates activity in one or more of the identified ascending neural pathways, ultimately leading to loss of consciousness.
75 citations
TL;DR: Amorphous or cubic Gd2O3 thin films were grown from tris ( 2,3-dimethyl-2-butoxy)gadolinium( III), Gd [OC(CH3)(2)CH(CH 3)(2))(3)], and H2O precursors at 350 degrees C as discussed by the authors.
Abstract: Amorphous or cubic Gd2O3 thin films were grown from tris ( 2,3-dimethyl-2-butoxy)gadolinium( III) , Gd [OC(CH3)(2)CH(CH3)(2))(3)], and H2O precursors at 350 degrees C. As-deposited Gd2O3 films grown on etched (H-terminated) Si(100) exhibited better leakage current-voltage characteristics as well as lower flatband voltage shift than films grown on SiO2/ Si substrates. Interface trap densities were lower in Al/Gd2O3/ hydrofluoric acid (HF)-etched Si samples annealed at rather high temperatures.
40 citations
TL;DR: In this article, low-temperature x-ray diffraction, susceptibility, specific heat, and thermal conductivity results both on single crystal and polycrystalline samples were presented.
Abstract: We present low-temperature x-ray diffraction, susceptibility, specific heat, and thermal conductivity results both on single crystal and polycrystalline $\mathrm{Mn}{\mathrm{V}}_{2}{\mathrm{O}}_{4}$ The single crystal sample exhibits two transitions: a spin ordering (ferrimagnetic) transition at ${T}_{\mathrm{SO}}=56\phantom{\rule{03em}{0ex}}\mathrm{K}$ and an orbital ordering transition at ${T}_{\mathrm{OO}}=52\phantom{\rule{03em}{0ex}}\mathrm{K}$ The structural change and phase separation at ${T}_{\mathrm{OO}}$ suggest that the transition is first order With applied magnetic fields, both ${T}_{\mathrm{SO}}$ and ${T}_{\mathrm{OO}}$ increase and ${T}_{\mathrm{OO}}$ disappears with $H\ensuremath{\geqslant}05\phantom{\rule{03em}{0ex}}\mathrm{T}$ The polycrystalline sample just exhibits one transition at $55\phantom{\rule{03em}{0ex}}\mathrm{K}$ The difference between the single crystal and polycrystalline samples is due to the nonstoichiometric polycrystalline sample
38 citations
TL;DR: The structural and electrical behavior of the films were somewhat precursor-dependent, revealing better insulating properties in the films grown from oxygen-containing precursors as discussed by the authors, which showed lower leakage compared to ZrO"2.
TL;DR: In this paper, the magnetic phase diagram of single crystalline (single crystalline) molecules was determined by measuring the magnetic susceptibility, specific heat, dielectric constant, and thermal conductivity.
Abstract: The magnetic phase diagram of single crystalline ${\mathrm{Ho}}_{1\ensuremath{-}x}{\mathrm{Y}}_{x}\mathrm{Mn}{\mathrm{O}}_{3}$ below ${T}_{N}$ is determined by measuring the magnetic susceptibility $(\ensuremath{\chi})$, specific heat $({C}_{p})$, dielectric constant $(\ensuremath{\epsilon})$, and thermal conductivity $(\ensuremath{\kappa})$. Y doping enhances the $P{\underset{}{6}}_{3}c\underset{}{m}$ magnetic phase below ${T}_{\mathrm{SR}}$ and therefore increases ${T}_{\mathrm{SR}}$; only the $P{\underset{}{6}}_{3}c\underset{}{m}$ phase exists below ${T}_{N}$ for $x\ensuremath{\geqslant}0.9$ samples. Y doping also reduces the $P{6}_{3}cm$ phase below ${T}_{2}$. The anomaly around ${T}_{\mathrm{SR}}$ appears in the dielectric constant but is absent in $\ensuremath{\chi}$ and ${C}_{p}$ for ${\mathrm{Ho}}_{0.3}{\mathrm{Y}}_{0.7}\mathrm{Mn}{\mathrm{O}}_{3}$ and ${\mathrm{Ho}}_{0.2}{\mathrm{Y}}_{0.8}\mathrm{Mn}{\mathrm{O}}_{3}$ samples, which indicates that the multiferroicity at ${T}_{\mathrm{SR}}$ for $\mathrm{Ho}\mathrm{Mn}{\mathrm{O}}_{3}$ is not necessarily related to the ${\mathrm{Ho}}^{3+}$ spin ordering. Specific heat measurements show that the large electronic specific heat $(\ensuremath{\gamma})$ of $\mathrm{Ho}\mathrm{Mn}{\mathrm{O}}_{3}$ is related to the disorder of ${\mathrm{Ho}}^{3+}$ spins, and is correlated with the relief of frustration in the Mn sublattice. The thermal conductivity data support an enhanced spin-lattice interaction due to strong spin fluctuations in the geometrically frustrated Mn-spin system.
TL;DR: Findings are consistent with the hypothesis that MAT could play a significant role in the molecular mechanism by which TETA extracts CuII from the systemic compartment in diabetic subjects.
Abstract: Triethylenetetramine (TETA), a selective Cu(II)-chelator used in the treatment of Wilson's disease, is now undergoing clinical trials for the treatment of heart failure in diabetes. Despite decades of clinical use, knowledge of its pharmacology in human subjects remains incomplete. Here, we first used liquid chromatography-mass spectrometry (LC-MS) to detect and identify major metabolites of TETA in human plasma and urine, and then used this method to measure concentrations of TETA and its metabolites in the urine of healthy and diabetic subjects who were administered increasing doses (300, 600, 1200, and 2400 mg) of TETA orally. Twenty-four-hour urine collections were performed before and after dosing participants. Two major metabolites of TETA were detected in human urine, N(1)-acetyltriethylenetetramine (MAT) and N(1),N(10)-diacetyltriethylenetetramine, the latter being novel. Both metabolites were verified with synthetic standards by LC-MS. The proportion of unchanged TETA excreted as a fraction of total urinary drug-derived molecules was significantly higher in healthy than in matched diabetic subjects, consistent with a higher rate of TETA metabolism in the latter. TETA-evoked increases in urinary Cu excretion in nondiabetic subjects were more closely correlated with parent drug concentrations than in diabetic subjects, whereas, by contrast, urinary Cu was more closely associated with the sum of TETA and MAT. These findings are consistent with the hypothesis that MAT could play a significant role in the molecular mechanism by which TETA extracts Cu(II) from the systemic compartment in diabetic subjects.
TL;DR: In this article, the atomic layer deposition growth of tungsten nitride films was demonstrated using the precursors W2(NMe2)6 and ammonia with substrate temperatures between 150 and 250 °C.
Abstract: The atomic layer deposition growth of tungsten nitride films was demonstrated using the precursors W2(NMe2)6 and ammonia with substrate temperatures between 150 and 250 °C At 180 °C, surface saturative growth was achieved with W2(NMe2)6 pulse lengths of ≥20 s The growth rates were between 074 and 081 A cycle−1 at substrate temperatures between 180 and 210 °C Growth rates of 057 and 096 A cycle−1 were observed at 150 and 220 °C, respectively In a series of films deposited at 180 °C, the film thicknesses varied linearly with the number of deposition cycles Films grown at 180 and 210 °C exhibited resistivity values between 810 and 4600 μΩ cm Time-of-flight elastic recoil detection analysis on tungsten nitride films containing a protective AlN overlayer demonstrated slightly nitrogen-rich films relative to W2N, with compositions of W10N082C013O026H033 at 150 °C, W10N074C020O033H028 at 180 °C, and W10N082C033O018H023 at 210 °C In the absence of an AlN overlayer, the oxygen and hydrogen levels were much higher, suggesting that the films degrade in the presence of ambient atmosphere The as-deposited films were amorphous Amorphous films containing a protective AlN overlayer were annealed to 600–800 °C under a nitrogen atmosphere X-Ray diffraction patterns suggested that crystallization does not occur at or below 800 °C Similar annealing of films that did not contain the AlN overlayer afforded X-ray diffraction patterns that were consistent with orthorhombic WO3 Atomic force microscopy showed root-mean-square surface roughnesses of 09, 08, and 07 nm for films deposited at 150, 180, and 210 °C, respectively
TL;DR: This liquid chromatography-mass spectrometry method was successfully applied to measure TETA, MAT and DAT in plasma and urine of humans receiving oral drug treatment.
TL;DR: In this paper, the formation of epitaxial Al2O3 thin films on 4H-SiC was found to be strongly dependent on the film thickness, and an abrupt interface was observed in films up to 200 A.
Abstract: The formation of epitaxial γ-Al2O3 thin films on 4H-SiC was found to be strongly dependent on the film thickness. An abrupt interface was observed in films up to 200 A thick with an epitaxial relationship of γ-Al2O3(111)‖4H-SiC(0001) and γ-Al2O3(44¯0)‖4H-SiC(112¯0). The in-plane alignment between the film and the substrate is nearly complete for γ-Al2O3 films up to 115 A thick, but quickly diminishes in thicker films. The films are found to be slightly strained laterally in tension; the strain increases with thickness and then decreases in films thicker than 200 A, indicating strain relaxation which is accompanied by increased misorientation. By controlling the structure of ultrathin Al2O3 films, metal–oxide–semiconductor capacitors with Al2O3 gate dielectrics on 4H-SiC were found to have a very low leakage current density, suggesting suitability of Al2O3 for SiC device integration.
TL;DR: In this article, a silicon carbide layer was synthesized by 40-keV C12+ implantation of a p-type (100) Si wafer at a fluence of 6.5×1017 ions∕cm2 at an elevated temperature.
Abstract: Ion beam synthesis using high-fluence carbon ion implantation in silicon in combination with subsequent or in situ thermal annealing has been shown to be able to form nanocrystalline cubic SiC (3C-SiC) layers in silicon. In this study, a silicon carbide layer was synthesized by 40-keV C12+ implantation of a p-type (100) Si wafer at a fluence of 6.5×1017 ions∕cm2 at an elevated temperature. The existence of the implanted carbon in Si substrate was investigated by time-of-flight energy elastic recoil detection analysis. The SiC layer was subsequently irradiated by 10–30 MeV I127 ions to a very low fluence of 1012 ions∕cm2 at temperatures from 80 to 800 °C to study the effect on the crystallization of the SiC layer. Infrared spectroscopy and Raman scattering measurement were used to monitor the formation of SiC and detailed information about the SiC film properties was obtained by analyzing the peak shape of the Si-C stretching mode absorption. The change in crystallinity of the synthesized layer was probed ...
TL;DR: In this article, high-resolution transmission electron microscopy images were used to confirm that the abrupt interface of the as-deposited films with the 4H-SiC substrate was preserved during crystallization, indicating no interfacial reaction.
Abstract: Al2O3 thin films were grown on 4H-SiC (0001) by thermal atomic layer deposition and were crystallized to the γ-Al2O3 phase by rapid thermal annealing in N2 at 1100°C. The films were found to be chemically stable during processing based on x-ray photoelectron spectroscopy. The change in film structure was initially confirmed by reflection high-energy electron diffraction. As shown by high-resolution transmission electron microscopy images, the abrupt interface of the as-deposited films with the 4H-SiC substrate was preserved during crystallization, indicating no interfacial reaction. Selected area electron diffraction and synchrotron-based x-ray diffraction established an epitaxial relationship of γ-Al2O3 (111) ‖ 4H-SiC (0001) and in-plane orientation of γ-Al2O3 (11¯0) ‖ 4H-SiC (112¯0). No other alumina phases or orientations were observed and no in-plane misorientation was observed in the 27A Al2O3 films. The full width at half maximum of the γ-Al2O3 (222) rocking curve is 0.056°, indicating a lack of mos...
TL;DR: In this paper, 3C-SiC is directly formed during implantation, and the subsequent high-temperature annealing enhances the quality of the poly-crystalline SiC.
TL;DR: In this article, the behavior of low-temperature spin dynamics can be explained by the hierarchical model, where memory effect and slow magnetic relaxation, the typical characteristics of the spin-glass-like phase, occur below the blocking temperature of 45 K in samples with high Mn concentration, while ferromagnetic order remains up to 360 K.
Abstract: Zincblende Mn-rich Mn(Ga)As nanoclusters embedded in GaAs matrices are fabricated by in situ postgrowth annealing diluted magnetic semiconductor (Ga,Mn)As films with Mn concentration ranging from 2.6% to 8% at 650 degrees C. Magnetization measurements show that memory effect and slow magnetic relaxation, the typical characteristics of the spin-glass-like phase, occur below the blocking temperature of 45 K in samples with high Mn concentration, while for samples with low Mn concentration, ferromagnetic order remains up to 360 K. The behavior of low-temperature spin dynamics can be explained by the hierarchical model. (c) 2007 American Institute of Physics.
TL;DR: In this article, a high amount of boron in the range of 1 x 10(20)-1x 10(21) cm(-3) in selective epitaxial growth of Si1-xGex (x = 0.15-0.315) layers for recessed or elevated source/drain junc
Abstract: Incorporation of high amount of boron in the range of 1 x 10(20)-1 x 10(21) cm(-3) in selective epitaxial growth (SEG) of Si1-xGex (x = 0.15-0.315) layers for recessed or elevated source/drain junc ...
TL;DR: A validated method for the determination of triethylenetetramine, a selective copper-chelator currently undergoing clinical trials for the treatment of diabetic heart failure, and its two major metabolites in human serum using HPLC is reported.
TL;DR: In this paper, the authors measured the IC(B, isin) behavior of high current density Nb3Sn conductors under applied tensile strain in high magnetic field.
Abstract: The measurement of critical current of superconducting conductors under applied tensile strain in high magnetic field [IC(B, isin) is essential for the application of Nb3Sn composite conductor in high field superconducting magnets. The large bore 20 T DC magnet at the NHMFL along with a device designed to apply tensile strain allows the IC(B, isin) measurement of about 100 mm long straight Nb3Sn composite wire. The superconducting wires are soldered to dog-bone shaped backing plates made of different materials. Our results show that the backing plate materials have significant effects on the measured IC(B, isin) behaviors. This paper also reports our recent experimental results on high current density Nb3Sn conductors.
TL;DR: In this paper, the microstructure and critical current of the superconductors with respect to the strain of various Nb3Sn supercondors are characterized and other relevant properties are also measured and related to the fabrication, design and micro-structure of the conductors.
Abstract: Nb3Sn superconductors are examined to select proper conductors for hybrid magnets outserts (that is a superconductor solenoid wound on the outside of a Bitter magnet) at the National High Magnetic Field Laboratory. The materials are subject to both thermal and mechanical stresses when in service. The stresses are complex due to the thermal contraction of the conduit applying extra stresses to the conductors. The final thermal stress levels can be well beyond the yield stress of some components in the superconductor composite and therefore plastic flow occurs in these components, such as Cu stabilizer and Cu-Sn matrix. If the plastic deformation strain is large, deformation strain in Nb3Sn superconductor filaments can be difficult to estimate. The differences in conductor design also render the estimation of the strain status difficult. It is well documented that the critical current is strongly affected by strain in the Nb3Sn superconductors. Therefore, we have characterized the microstructure and critical current of the superconductors with respect to the strain of various Nb3Sn superconductors. Other relevant properties are also measured and related to the fabrication, design and microstructure of the conductors. This paper reports our efforts in characterization of the Nb3Sn superconductors for hybrid magnets.
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TL;DR: In this paper, the intrinsic ferromagnetism of (Ga,Cr)As epilayers with all the necessary properties in accordance with that of a diluted magnetic semiconductor, especially the hysteresis characteristics, was investigated.
Abstract: To clarify whether or not (Ga,Cr)As is an intrinsic diluted magnetic semiconductor, a systematic study of the magnetic circular dichroism (MCD) was carried out for a series of (Ga,Cr)As epilayers grown by the low-temperature molecular-beam epitaxy technique. The present work provides unambiguous evidence for the intrinsic ferromagnetism of the (Ga,Cr)As epilayers with all the necessary properties in accordance with that of a diluted magnetic semiconductor, especially the hysteresis characteristics, which is opened up in the magnetic field dependence of MCD.