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161.
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163.
Rutland CS Polo-Parada L Ehler E Alibhai A Thorpe A Suren S Emes RD Patel B Loughna S 《Development (Cambridge, England)》2011,138(18):3955-3966
The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal development and cardiac function. Most cases of atrial septal defects and cardiomyopathy are not associated with a known causative gene, suggesting that further analysis into candidate genes is required. Expression studies localised eMYH in the developing chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner and functional studies were carried out using electrical and calcium signalling methodologies. Knockdown in the early embryo led to abnormal atrial septal development and heart enlargement. Intriguingly, action potentials of the eMYH knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy chain knockdowns and controls. Although myofibrillogenesis appeared normal, in knockdown hearts the tissue integrity was affected owing to apparent focal points of myocyte loss and an increase in cell death. An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy. 相似文献
164.
Microspheres of tramadol hydrochloride (TM) for oral delivery were prepared by complex coacervation method without the use
of chemical cross-linking agents such as glutaraldehyde to avoid the toxic reactions and other undesirable effects of the
chemical cross-linking agents. Alternatively, ionotropic gelation was employed by using sodium-tripolyphosphate as cross-linking
agent. Chitosan and gelatin B were used as polymer and copolymer, respectively. All the prepared microspheres were subjected
to various physicochemical studies, such as drug–polymer compatibility by thin layer chromatography (TLC) and Fourier transform
infrared (FTIR) spectroscopy, surface morphology by scanning electron microscopy, frequency distribution, drug entrapment
efficiency, in vitro drug release characteristics and release kinetics. The physical state of drug in the microspheres was determined by differential
scanning calorimetry (DSC) and X-ray diffractometry (XRD). TLC and FTIR studies indicated no drug–polymer incompatibility.
All the microspheres showed initial burst release followed by a fickian diffusion mechanism. DSC and XRD analysis indicated
that the TM trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. From
the preliminary trials, it was observed that it may be possible to formulate TM microspheres by using biodegradable natural
polymers such as chitosan and gelatin B to overcome the drawbacks of TM and to increase the patient compliance. 相似文献
165.
As stipulated by ICH Q8 R2 (1), prediction of critical process parameters based on process modeling is a part of enhanced, quality by design approach to
product development. In this work, we discuss a Bayesian model for the prediction of primary drying phase duration. The model
is based on the premise that resistance to dry layer mass transfer is product specific, and is a function of nucleation temperature.
The predicted duration of primary drying was experimentally verified on the lab scale lyophilizer. It is suggested that the
model be used during scale-up activities in order to minimize trial and error and reduce costs associated with expensive large
scale experiments. The proposed approach extends the work of Searles et al. (2) by adding a Bayesian treatment to primary drying modeling. 相似文献
166.
Temporal development of roots is key to the understanding of root system architecture of plants which influences nutrient uptake, anchorage and plant competition. Using time lapse imaging we analyzed developmental patterns of length, growth angle, depth and curvature of Phaseolus basal roots from emergence till 48 h in two genotypes, and TLP19 with contrasting growth angles. In both genotypes all basal roots appeared almost simultaneously, but their growth rates varied which accounted for differences in root length. The growth angles of the basal roots fluctuated rapidly during initial development due to oscillatory root growth causing local bends. Beyond 24 h, as the root curvature stabilized, so did the growth angle. Therefore growth angle of basal roots is not a very reliable quantity for characterizing root architecture, especially during early seedling development. Comparatively, tip depth is a more robust measure of vertical distribution of the basal roots even during early seedling development.Key words: B98311basal root, kinematics, root architecture, root growth, spatiotemporal analysis, root imagingVertical and horizontal placements of the roots in the soil influence plant performance through acquisition of below ground resources like water and nutrients, plant anchorage and intra- and inter-plant competition.1–4 Therefore the architecture of the root system plays important roles in regulating plant growth and yield, especially under abiotic stresses.5 As a seedling grows to become a mature plant, the root architecture develops continuously in response to various cues e.g., genotypic, environmental, hormonal, etc. Therefore studies of root architecture of plants of different ages are important for understanding the influence of these cues in regulating plant growth.The root scaffold of a plant is comprised of different types of roots with different functions. A mature common bean (Phaseolus vulgaris L.) plant has root system consisting of primary, adventitious, lateral and basal roots. Among these, the basal roots are typically the earliest emerging secondary roots from the hypocotyl6 forming a major part of the mature root system. We have recently demonstrated important differences in architectural traits of the basal roots of common bean in the early seedling stage between two contrasting class of genotypes and how auxin-ethylene interplay regulates these traits.7 While this study of basal roots at a fixed time allows assessment and comparison of root development up to that point of time, investigation of the temporal events of emergence and growth of the basal roots is important and complementary to the understanding of their architectural traits. Therefore in the present study, we examined the detailed developmental patterns of basal roots through time lapse imaging in two genotypes.We chose two bean genotypes with contrasting basal root growth angles (BRGA) relative to the gravity— producing basal roots of smaller BRGA (41.7° ± 14°) and TLP19 having roots of larger BRGA (56.4° ± 18°). B983118 The germinated seedling with 2–3 cm radical was transferred to the blue germination paper (Anchor Paper Co., St. Paul, MN), which was suspended in nutrient solution7 inside a growth chamber (ACMAS Technocracy Limited, Delhi, India) maintained at 25 ± 1°C. Time lapse photography was carried out for 48 h at 30 min intervals using Nikon D200 digital camera fitted with a macro lens to obtain high resolution digital images of the roots. Imaging started from the visibility of the protrusions of emerging basal root along the root-shoot interface. A computer program was developed in Matlab® 7.8 (Mathworks, Natick) to analyze the images semi-automatically. From every image the computer program identified the basal roots using contrast of color between the roots (mostly white) and the germination paper (blue). Root midlines were determined following the methodology of Miller et al.9 and smoothed using the method of overlapping polynomials. Length of the midline is root length. The angle between gravity and the line connecting the root tip to the base is BRGA.7 The vertical distance of the root tip from the base of the lowest emerging root along the gravity vector is tip depth. From the midline, root curvature was also determined using the equation
(1)
where [x(x), y(s)] is coordinate of any point along the root midline, s is normalized distance along the midline, and the primes denote derivatives with respect to s. Here positive curvature signifies bending upward and vice versa. 相似文献
167.
Chatterjee P Basu S Kundu M Nasipuri M Plewczynski D 《Journal of molecular modeling》2011,17(9):2191-2201
Secondary structure prediction is a crucial task for understanding the variety of protein structures and performed biological
functions. Prediction of secondary structures for new proteins using their amino acid sequences is of fundamental importance
in bioinformatics. We propose a novel technique to predict protein secondary structures based on position-specific scoring
matrices (PSSMs) and physico-chemical properties of amino acids. It is a two stage approach involving multiclass support vector
machines (SVMs) as classifiers for three different structural conformations, viz., helix, sheet and coil. In the first stage, PSSMs obtained from PSI-BLAST and five specially selected physicochemical properties
of amino acids are fed into SVMs as features for sequence-to-structure prediction. Confidence values for forming helix, sheet and coil that are obtained from the first stage SVM are then used
in the second stage SVM for performing structure-to-structure prediction. The two-stage cascaded classifiers (PSP_MCSVM) are trained with proteins from RS126 dataset. The classifiers
are finally tested on target proteins of critical assessment of protein structure prediction experiment-9 (CASP9). PSP_MCSVM
with brainstorming consensus procedure performs better than the prediction servers like Predator, DSC, SIMPA96, for randomly
selected proteins from CASP9 targets. The overall performance is found to be comparable with the current state-of-the art. PSP_MCSVM source code, train-test datasets and supplementary files are available freely in public domain at: and 相似文献
168.
Basu A 《Statistics in biosciences》2011,3(1):6-27
Instrumental variables methods (IV) are widely used in the health economics literature to adjust for hidden selection biases
in observational studies when estimating treatment effects. Less attention has been paid in the applied literature to the
proper use of IVs if treatment effects are heterogeneous across subjects. Such a heterogeneity in effects becomes an issue
for IV estimators when individuals’ self-selected choices of treatments are correlated with expected idiosyncratic gains or
losses from treatments. We present an overview of the challenges that arise with IV estimators in the presence of effect heterogeneity
and self-selection and compare conventional IV analysis with alternative approaches that use IVs to directly address these
challenges. Using a Medicare sample of clinically localized breast cancer patients, we study the impact of breast-conserving
surgery and radiation with mastectomy on 3-year survival rates. Our results reveal the traditional IV results may have masked
important heterogeneity in treatment effects. In the context of these results, we discuss the advantages and limitations of
conventional and alternative IV methods in estimating mean treatment-effect parameters, the role of heterogeneity in comparative
effectiveness research and the implications for diffusion of technology. 相似文献
169.
170.
Sayantari Ghosh Kamakshi Sureka Bhaswar Ghosh Indrani Bose Joyoti Basu Manikuntala Kundu 《BMC systems biology》2011,5(1):18