914 research outputs found
Cholesteryl isobutylcarbonate
Cholesteryl isobutylcarbonate, C 32H 54O 3, contains two molecules (A and B) in the asymmetric unit. The isobutylcarbonate chain of molecule A and the isoprenoid tail of molecule B are each conformationally disordered over two positions. The two distinct molecules form separate stacks along the screw axes so that they are arranged in an antiparallel array, forming monolayers with a thickness of d 001 = 19.412 A. The central regions of the monolayers are characterized by efficient molecular packing and are separated by interface regions, which are more loosely packed.open4
Anticathepsin D Antibody-Sepharose Chromatography of Human Cathepsin D
Cathepsin D was isoilated from human tissues by anticatheipsin
D antibo:dy-Serpharose 4B .chromatoigraphy. Caithepsin D,
rele1ased from the immunoaffinity column formed one precipitin
line with specif.ic antibody in immwnod:Lffusion and in immunoe1ectropholl1esis.
The isolated proteinase is shown to be prure
cathepsin D by actiivity and by inhibition with peipstatin.
The quanititative determinati.on o:f cathepsin D in human
tissue, taiken by bio.psy from sco,Uotic patients 1rl ivery small
amount, is desert.bed.
It was demonstrated that cathepsin D from human muscle
and human gingival fluid was indistinguishable in immunodiffus
ion from the human liver catheps iirl D
Robust Quantitative Susceptibility Mapping via Approximate Message Passing
Purpose: It is challenging to recover magnetic susceptibility in the presence
of phase errors, which may be caused by noise or strong local-susceptibility
shifts in cases of brain hemorrhage and calcification. We propose a Bayesian
formulation for quantitative susceptibility mapping (QSM) where a customized
Gaussian-mixture distribution is used to model the long-tailed noise
distribution.
Theory: Complex exponential functions of the phase are used as nonlinear
measurements. Wavelet coefficients of the susceptibility map are modeled by the
Laplace distribution. Measurement noise is modeled by a two-component
Gaussian-mixture distribution, where the second component is reserved to model
the noise outliers. The susceptibility map and distribution parameters are
jointly recovered using approximate message passing (AMP).
Methods: The proposed AMP with built-in parameter estimation (AMP-PE) is
compared with the state-of-the-art nonlinear L1-QSM and MEDI approaches that
adopt the L1-norm and L2-norm data-fidelity terms respectively. They are tested
on the simulated and in vivo datasets.
Results: On the simulated Sim2Snr1 dataset, AMP-PE achieved the lowest NRMSE
and SSIM, MEDI achieved the lowest HFEN. On the in vivo datasets, AMP-PE is
more robust and better at preserving structural details and removing streaking
artifacts in the hemorrhage cases than L1-QSM and MEDI.
Conclusion: By leveraging a customized Gaussian-mixture noise prior, AMP-PE
achieves better performance in challenging cases of brain hemorrhage and
calcification. It is equipped with built-in parameter estimation, which avoids
subjective bias from the usual visual-tuning step of in vivo reconstruction.Comment: Keywords: Approximate message passing, Compressive sensing, Parameter
estimation, QS
Model-based T1, T2* and Proton Density Mapping Using a Bayesian Approach with Parameter Estimation and Complementary Undersampling Patterns
Purpose: To achieve automatic hyperparameter estimation for the joint
recovery of quantitative MR images, we propose a Bayesian formulation of the
reconstruction problem that incorporates the signal model. Additionally, we
investigate the use of complementary undersampling patterns to determine
optimal undersampling schemes for quantitative MRI.
Theory: We introduce a novel nonlinear approximate message passing framework,
referred to as ``AMP-PE'', that enables the simultaneous recovery of
distribution parameters and quantitative maps.
Methods: We employed the variable flip angle multi-echo (VFA-ME) method to
acquire measurements. Both retrospective and prospective undersampling
approaches were utilized to obtain Fourier measurements using variable-density
and Poisson-disk patterns. Furthermore, we extensively explored various
undersampling schemes, incorporating complementary patterns across different
flip angles and/or echo times.
Results: AMP-PE adopts a model-based joint recovery strategy, it outperforms
the -norm minimization approach that follows a decoupled recovery
strategy. A comparison with an existing joint-recovery approach further
demonstrates the advantageous outcomes of AMP-PE. For quantitative
mapping using VFA-ME, employing identical k-space sampling patterns across
different echo times produced the best performance. Whereas for and
proton density mappings, using complementary sampling patterns across different
flip angles yielded the best performance.
Conclusion: AMP-PE is equipped with built-in parameter estimation, and works
naturally in clinical settings with varying acquisition protocols and scanners.
It also achieves improved performance by combining information from the MR
signal model and the sparse prior on images
Novel bi- and trifunctional inhibitors of tumor-associated proteolytic systems
Serine proteases, cysteine proteases, and matrix metalloproteinases (MMPs) are involved in cancer cell invasion and metastasis. Recently, a recombinant bifunctional inhibitor (chCysuPA(19-31)) directed against cysteine proteases and the urokinasetype plasminogen activator (uPA)/plasmin serine protease system was generated by introducing the uPA receptor (uPAR)binding site of uPA into chicken cystatin (chCysWT). In the present study, we designed and recombinantly produced multifunctional inhibitors also targeting MMPs. The inhibitors comprise the Nterminal inhibitory domain of human TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) or TIMP-3, fused to chCysuPA(19-31) or chCysWT. As demonstrated by various techniques, these fusion proteins effectively interfere with all three targeted protease systems. In in vitro Matrigel invasion assays, the addition of recombinant inhibitors strongly reduced invasion of ovarian cancer cells (OVMZ-6\#8). Additionally, OVMZ 6\#8 cells were stably transfected with expression plasmids encoding the various inhibitors. Synthesis and secretion of the inhibitors was verified by a newly developed ELISA, which selectively detects the recombinant proteins. Invasive capacity of inhibitorproducing cells was significantly reduced compared to vectortransfected control cells. Thus, these novel, compact, and smallsize inhibitors directed against up to three different tumorassociated proteolytic systems may represent promising agents for prevention of tumor cell migration and metastasis
Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel γ-secretase substrates
BACKGROUND: The mammalian Vps10p sorting receptor family is a group of 5 type I membrane homologs (Sortilin, SorLA, and SorCS1-3). These receptors bind various cargo proteins via their luminal Vps10p domains and have been shown to mediate a variety of intracellular sorting and trafficking functions. These proteins are highly expressed in the brain. SorLA has been shown to be down regulated in Alzheimer's disease brains, interact with ApoE, and modulate Aβ production. Sortilin has been shown to be part of proNGF mediated death signaling that results from a complex of Sortilin, p75(NTR )and proNGF. We have investigated and provide evidence for γ-secretase cleavage of this family of proteins. RESULTS: We provide evidence that these receptors are substrates for presenilin dependent γ-secretase cleavage. γ-Secretase cleavage of these sorting receptors is inhibited by γ-secretase inhibitors and does not occur in PS1/PS2 knockout cells. Like most γ-secretase substrates, we find that ectodomain shedding precedes γ-secretase cleavage. The ectodomain cleavage is inhibited by a metalloprotease inhibitor and activated by PMA suggesting that it is mediated by an α-secretase like cleavage. CONCLUSION: These data indicate that the α- and γ-secretase cleavages of the mammalian Vps10p sorting receptors occur in a fashion analogous to other known γ-secretase substrates, and could possibly regulate the biological functions of these proteins
The HI content of star-forming galaxies at z = 0.24
We use observations from the Giant Metrewave Radio Telescope (GMRT) to
measure the atomic hydrogen gas content of star-forming galaxies at z = 0.24
(i.e. a look-backtime of ~3 Gyr). The sample of galaxies studied were selected
from Halpha-emitting field galaxies detected in a narrow-band imaging survey
with the Subaru Telescope. The Anglo-Australian Telescope was used to obtain
precise optical redshifts for these galaxies. We then coadded the HI 21 cm
emission signal for all the galaxies within the GMRT spectral line data cube.
From the coadded signal of 121 galaxies, we measure an average atomic
hydrogen gas mass of (2.26 +- 0.90)*10^9 solar masses. We translate this HI
signal into a cosmic density of neutral gas at z = 0.24 of Omega_gas = (0.91 +-
0.42)*10^-3. This is the current highest redshift at which Omega_gas has been
constrained from 21 cm emission and our value is consistent with that estimated
from damped Lyman-alpha systems around this redshift. We also find that the
correlations between the Halpha luminosity and the radio continuum luminosity
and between the star formation rate and the HI gas content in star-forming
galaxies at z = 0.24 are consistent with the correlations found at z = 0. These
two results suggest that the star formation mechanisms in field galaxies ~3 Gyr
ago were not substantially different from the present, even though the star
formation rate is 3 times higher.Comment: 11 pages, contains 9 figures and 1 table. Accepted for publishing in
MNRAS 2007 January 22. Received 2007 January 22; in original form 2006
November 3
Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: Evidence for a proximal role in Alzheimer's disease
Alzheimer's disease (AD) is the most prevalent form of dementia, resulting in progressive neuronal death and debilitating damage to brain loci that mediate memory and higher cognitive function. While pathogenic genetic mutations have been implicated in approximately 2% of AD cases, the proximal events that underlie the common, sporadic form of the disease are incompletely understood. Converging lines of evidence from human neuropathology, basic biology, and genetics have implicated loss of the multifunctional receptor LR11 (also known as SORLA and SORL1) in AD pathogenesis. Cell-based studies suggest that LR11 reduces the formation of beta-amyloid (Abeta), the molecule believed to be a primary toxic species in AD. Recently, mutant mice deficient in LR11 were shown to upregulate murine Abeta in mouse brain. In the current study, LR11-deficient mice were crossed with transgenic mice expressing autosomal-dominant human AD genes, presenilin-1 (PS1DeltaE9) and amyloid precursor protein (APPswe). Here, we show that LR11 deficiency in this AD mouse model significantly increases Abeta levels and exacerbates early amyloid pathology in brain, causing a forward shift in disease onset that is LR11 gene dose-dependent. Loss of LR11 increases the processing of the APP holo-molecule into alpha-, beta-, and gamma-secretase derived metabolites. We propose that LR11 regulates APP processing and Abeta accumulation in vivo and is of proximal importance to the cascade of pathological amyloidosis. The results of the current study support the hypothesis that control of LR11 expression may exert critical effects on Alzheimer's disease susceptibility in humans
Fatty Acid Copper(II) Carboxylates with Nicotinamide - Characterization and Fungicidal Activity. Crystal Structures of Two Heptanoate Forms and Nonanoate
Several new compounds of the composition Cu2(OOCCnH2n+1)4
(nia)2 (nia = nicotinamide; n = 6 to 11) were synthesized, characterized and tested for fungicidal activity. Crystal structure determinations revealed dinuclear structures of the copper(II) acetate hydrate type for compounds [Cu2(OOCC6H13)4(nia)2]-A (1A), [Cu2(OOCC6H13)4(nia)2]-B (1B) and [Cu2(OOCC8H17)4(nia)2] (3).
Other applied characterization methods indicate dimeric structures for ali synthesized compounds [μeff (298 K) = 1.43-1.50 BM; characteristic band in UV-Vis spectra in the region λ = 350-400 nm]. The same conclusion may also be deduced from the IR (Δ = νasym(COO-) - νsym(COO-) = 183-189 cm-1) and EPR spectra, though some differences were observed for heptanoate modification 1A, probably due to a different hydrogen bonding scheme. Screening for fungicidal activity against the wood-rotting fungus Trametes versicolor (L. ex Fr.) Pilat shows that the compounds dissolved in DMSO completely stop mycelium growth at a concentration of 1.0 × 10-3 mol L-1. Some of them (n = 8, 9, 10) show strong activity also in more diluted Solutions (1.0 × 10-4 mol L-1)
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