338 research outputs found
Ab Initio Evidence for the Formation of Impurity d(3z^2-r^2) Holes in Doped La_{2-x}Sr_xCuO_4
Using the spin unrestricted Becke-3-Lee-Yang-Parr density functional, we
computed the electronic structure of explicitly doped La_{2-x}Sr_xCuO_4 (x =
0.125, 0.25, and 0.5). At each doping level, an impurity hole band is formed
within the undoped insulating gap. This band is well-localized to CuO_6
octahedra adjacent to the Sr impurities. The nature of the impurity hole is
A_{1g} in symmetry, formed primarily from the z^2 orbital on the Cu and p_z
orbitals on the apical O's. There is a strong triplet coupling of this hole
with the intrinsic B_{1g} Cu x^2-y^2/O1 p_{sigma} hole on the same site.
Optimization of the c coordinate of the apical O's in the doped CuO_6
octahedron lead to an asymmetric anti-Jahn-Teller distortion of the O2 atoms
toward the central Cu. In particular, the O2 atom between the Cu and Sr is
displaced 0.26 A while the O2 atom between the Cu and La is displaced 0.10 A.
Contrary to expectations, investigation of a 0.1 A enhanced Jahn-Teller
distortion of this octahedron does not force formation of an x^2-y^2 hole, but
instead leads to migration of the z^2 hole to the four other CuO_6 octahedra
surrounding the Sr impurity. This latter observation offers a simple
explanation for the bifurcation of the Sr-O2 distance revealed in x-ray
absorption fine structure data.Comment: Submitted to Phys. Rev. B. See http://www.firstprinciples.com for
more informatio
Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP
Elevation of intracellular calcium levels in the presence of normal
androgen levels has been implicated in apoptotic prostate cell death.
Since the androgen receptor (AR) plays a critical role in the regulation
of growth and differentiation of the prostate, it was of interest to
determine whether Ca2+ would affect the expression of androgen receptor
messenger RNA (mRNA) and protein, thus affecting the ability of androgens
to control prostate function. AR-positive human prostate cancer cells,
LNCaP, were incubated with either the calcium ionophore A23187 or the
intracellular endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin.
Subsequently, AR mRNA and protein levels were assessed by Northern and
Western blot analysis. Both A23187 and thapsigargin were found to
down-regulate steady state AR mRNA levels in a time- and dose-dependent
manner. AR mRNA began to decrease after 6-8 h of incubation with 10(-6) M
A23187 or 10(-7) M thapsigargin, reaching a nadir at 16 and 10 h of
incubation, respectively. In contrast, control mRNA (glyceraldehyde
3-phosphate dehydrogenase) did not change significantly during the
treatments with either A23187 or thapsigargin. AR protein levels were
found to be decreased after 12 h of incubation with either 10(-6) M A23187
or 10(-7) M thapsigargin. The decrease in AR mRNA and protein seemed to
precede apoptosis, since neither A23187 (24 h) nor thapsigargin (30 h) was
found to alter cell morphology within the treatment time. Cycloheximide
and actinomycin D were unable to change the calcium-mediated decrease in
AR mRNA, ruling out the necessity for de novo protein synthesis or a
change in mRNA stability. Moreover, the decrease in AR mRNA induced by
calcium does not seem to involve protein kinase C- or calmodulin-dependent
pathways, since inhibitors of these cellular components had no effect.
Nuclear run-on assays demonstrated little or no effects of either A23187
or thapsigargin treatment on AR gene transcription (8 h and 10 h). In
conclusion, these studies show that intracellular calcium seems to be a
potent regulator of AR gene expression in LNCaP cells
Comparison of Three CIDR Based Fixed-time AI Protocols for Beef Heifers
Several effective fixed-time AI (FTAI) protocols have been developed to facilitate AI while eliminating the need for estrus detection. Among these are the 5-d CO-Synch+CIDR (5d), PG 6-d CIDR (PG-CIDR), and 14-d CIDR-PG (CIDR-PG) protocols. While each of these protocols varies in duration and approach to synchronizing estrus and ovulation, each has been reported as an effective method to facilitate FTAI in beef heifers. Therefore, the objective of this study was to compare FTAI pregnancy rates in beef heifers synchronized with these three CIDR based protocols. Virgin beef heifers (n = 801) at four locations were synchronized with one of three protocols: 1) (5-day CO-Synch + CIDR) an injection of GnRH (100 μg; i.m.) and insertion of a CIDR on d -5, PG (25 mg; i.m.) and CIDR removal on d 0 with a second injection of PG (\u3e4 h after CIDR removal) on d 0 and FTAI at 72 h after CIDR removal, 2) (PG 6-day CIDR) PG (25 mg; i.m.) on d -9, GnRH (100 μg; i.m.) and insertion of a CIDR on d -6, PG and CIDR removal on d 0, and FTAI at 66 h after CIDR removal, or 3) (14-day CIDR-PG) a 14-day CIDR insert from d -30 to -16, PG (25 mg; i.m.) on d 0, and FTAI at 66 h after PG. All heifers received an injection of GnRH (100 μg; i.m.) concurrent with FTAI. Timing of treatment initiation was offset to allow all heifers to receive FTAI concomitantly and at random. Pregnancy success was determined between 35 and 40 d after FTAI by transrectal ultrasonography. Blood samples were collected approximately 12 d before the beginning of each protocol and at the initiation of each protocol to determine estrous cycling status (77%). Data were analyzed using the GLIMMIX procedures of SAS. Fixed-time AI pregnancy success did not differ between treatments (P = 0.13; 62.5%, 56.9%, and 53.3%, for 5-day CO-Synch + CIDR, PG 6-day CIDR, and 14-day CIDR-PG; respectively) or location (P = 0.16; 51.5%, 62.7%, 56.1%, and 58.6% for location 1, 2, 3, and 4; respectively). However, heifers that had reached puberty by initiation of synchronization had greater (P \u3c 0.01) pregnancy success compared to heifers that were prepubertal (60.7% and 47.3%; respectively). In summary, all three protocols had similar FTAI pregnancy success, and puberty status had the greatest impact on pregnancy success
Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors.
Repeat elements can be dysregulated at a genome-wide scale in human diseases. For example, in Ewing sarcoma, hundreds of inert GGAA repeats can be converted into active enhancers when bound by EWS-FLI1. Here we show that fusions between EWS and GGAA-repeat-targeted engineered zinc finger arrays (ZFAs) can function at least as efficiently as EWS-FLI1 for converting hundreds of GGAA repeats into active enhancers in a Ewing sarcoma precursor cell model. Furthermore, a fusion of a KRAB domain to a ZFA can silence GGAA microsatellite enhancers genome wide in Ewing sarcoma cells, thereby reducing expression of EWS-FLI1-activated genes. Remarkably, this KRAB-ZFA fusion showed selective toxicity against Ewing sarcoma cells compared with non-Ewing cancer cells, consistent with its Ewing sarcoma-specific impact on the transcriptome. These findings demonstrate the value of ZFAs for functional annotation of repeats and illustrate how aberrant microsatellite activities might be regulated for potential therapeutic applications
Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer
Cefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS) such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1(dissimilarity) and f2(similarity) factors using a reference brand of cefuroxime axetil. Significant differences (p<0.05) in dissolution rate were recorded with the change in concentration of SLS in different media. Test formulation T3 containing 1% SLS was found to be best optimized formulation based on assay, disintegration, dissolution and similarity and dissimilarity factors
Cherenkov radiation emitted by ultrafast laser pulses and the generation of coherent polaritons
We report on the generation of coherent phonon polaritons in ZnTe, GaP and
LiTaO using ultrafast optical pulses. These polaritons are coupled modes
consisting of mostly far-infrared radiation and a small phonon component, which
are excited through nonlinear optical processes involving the Raman and the
second-order susceptibilities (difference frequency generation). We probe their
associated hybrid vibrational-electric field, in the THz range, by
electro-optic sampling methods. The measured field patterns agree very well
with calculations for the field due to a distribution of dipoles that follows
the shape and moves with the group velocity of the optical pulses. For a
tightly focused pulse, the pattern is identical to that of classical Cherenkov
radiation by a moving dipole. Results for other shapes and, in particular, for
the planar and transient-grating geometries, are accounted for by a convolution
of the Cherenkov field due to a point dipole with the function describing the
slowly-varying intensity of the pulse. Hence, polariton fields resulting from
pulses of arbitrary shape can be described quantitatively in terms of
expressions for the Cherenkov radiation emitted by an extended source. Using
the Cherenkov approach, we recover the phase-matching conditions that lead to
the selection of specific polariton wavevectors in the planar and transient
grating geometry as well as the Cherenkov angle itself. The formalism can be
easily extended to media exhibiting dispersion in the THz range. Calculations
and experimental data for point-like and planar sources reveal significant
differences between the so-called superluminal and subluminal cases where the
group velocity of the optical pulses is, respectively, above and below the
highest phase velocity in the infrared.Comment: 13 pages, 11 figure
High-Accuracy X-Ray Diffraction Analysis of Phase Evolution Sequence During Devitrification of Cu50Zr50 Metallic Glass
Real-time high-energy X-ray diffraction (HEXRD) was used to investigate the crystallization kinetics and phase selection sequence for constant-heating-rate devitrification of fully amorphous Cu50Zr50, using heating rates from 10 K/min to 60 K/min (10 °C/min to 60 °C/min). In situ HEXRD patterns were obtained by the constant-rate heating of melt-spun ribbons under synchrotron radiation. High-accuracy phase identification and quantitative assessment of phase fraction evolution though the duration of the observed transformations were performed using a Rietveld refinement method. Results for 10 K/min (10 °C/min) heating show the apparent simultaneous formation of three phases, orthorhombic Cu10Zr7, tetragonal CuZr2 (C11b), and cubic CuZr (B2), at 706 K (433 °C), followed immediately by the dissolution of the CuZr (B2) phase upon continued heating to 789 K (516 °C). Continued heating results in reprecipitation of the CuZr (B2) phase at 1002 K (729 °C), with the material transforming completely to CuZr (B2) by 1045 K (772 °C). The Cu5Zr8 phase, previously reported to be a devitrification product in C50Zr50, was not observed in the present study
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