Liver Cancer Stem Cells

Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers for each of the liver cell types, production of corresponding monoclonal antibodies and cell sorting techniques have together revolutionized the characteristics of normal stem cells. In hepatocarcinogenesis, multiple signaling transduction pathways, important for stem cell proliferation and differentiations, are deregulated. Strategies are being developed to identify and characterize the liver cancer stem cells. Targeting liver cancer stem cells may bring hope to curing hepatocellular carcinoma

Measurement Axis Searching Model for Terrestrial Laser Scans Registration

Nowadays, terrestrial Lidar scans can cover rather a large area; the point densities are strongly varied because of the line-of-sight measurement principle in potential overlaps with scans taken from different viewpoints. Most of the traditional methods focus on registration algorithm and ignore searching model. Sometimes the traditional methods are directly used to align two point clouds; a large critically unsolved problem of the large biases will be created in areas distant from the overlaps while the local overlaps are often aligned well. So a novel measurement axis searching model (MASM) has been proposed in this paper. The method includes four steps: (1) the principal axis fitting, (2) the measurement axis generation, (3) low-high-precision search, and (4) result generation. The principal axis gives an orientation to the point cloud; the search scope is limited by the measurement axis. The point cloud orientation can be adjusted gradually until the achievement of the global optimum using low- and high-precision search. We perform some experiments with simulated point clouds and real terrestrial laser scans. The results of simulated point clouds have shown the processing steps of our method, and the results of real terrestrial laser scans have shown the sensitivity of the approach with respect to the indoor and outdoor scenes

A Sparse Representation Speech Denoising Method Based on Adapted Stopping Residue Error

A sparse representation speech denoising method based on adapted stopping residue error was presented in this paper. Firstly, the cross-correlation between the clean speech spectrum and the noise spectrum was analyzed, and an estimation method was proposed. In the denoising method, an over-complete dictionary of the clean speech power spectrum was learned with the K-singular value decomposition (K-SVD) algorithm. In the sparse representation stage, the stopping residue error was adaptively achieved according to the estimated cross-correlation and the adjusted noise spectrum, and the orthogonal matching pursuit (OMP) approach was applied to reconstruct the clean speech spectrum from the noisy speech. Finally, the clean speech was re-synthesised via the inverse Fourier transform with the reconstructed speech spectrum and the noisy speech phase. The experiment results show that the proposed method outperforms the conventional methods in terms of subjective and objective measure

Performance of a Large-area GEM Detector Read Out with Wide Radial Zigzag Strips

A 1-meter-long trapezoidal Triple-GEM detector with wide readout strips was tested in hadron beams at the Fermilab Test Beam Facility in October 2013. The readout strips have a special zigzag geometry and run along the radial direction with an azimuthal pitch of 1.37 mrad to measure the azimuthal phi-coordinate of incident particles. The zigzag geometry of the readout reduces the required number of electronic channels by a factor of three compared to conventional straight readout strips while preserving good angular resolution. The average crosstalk between zigzag strips is measured to be an acceptable 5.5%. The detection efficiency of the detector is (98.4+-0.2)%. When the non-linearity of the zigzag-strip response is corrected with track information, the angular resolution is measured to be (193+-3) urad, which corresponds to 14% of the angular strip pitch. Multiple Coulomb scattering effects are fully taken into account in the data analysis with the help of a stand-alone Geant4 simulation that estimates interpolated track errors.Comment: 30 pages, 28 figures, submitted to NIM

Towards engineering hormone-binding globulins as drug delivery agents.

The treatment of many diseases such as cancer requires the use of drugs that can cause severe side effects. Off-target toxicity can often be reduced simply by directing the drugs specifically to sites of diseases. Amidst increasingly sophisticated methods of targeted drug delivery, we observed that Nature has already evolved elegant means of sending biological molecules to where they are needed. One such example is corticosteroid binding globulin (CBG), the major carrier of the anti-inflammatory hormone, cortisol. Targeted release of cortisol is triggered by cleavage of CBG's reactive centre loop by elastase, a protease released by neutrophils in inflamed tissues. This work aimed to establish the feasibility of exploiting this mechanism to carry therapeutic agents to defined locations. The reactive centre loop of CBG was altered with site-directed mutagenesis to favour cleavage by other proteases, to alter the sites at which it would release its cargo. Mutagenesis succeeded in making CBG a substrate for either prostate specific antigen (PSA), a prostate-specific serine protease, or thrombin, a key protease in the blood coagulation cascade. PSA is conspicuously overproduced in prostatic hyperplasia and is, therefore, a good way of targeting hyperplastic prostate tissues. Thrombin is released during clotting and consequently is ideal for conferring specificity to thrombotic sites. Using fluorescence-based titration assays, we also showed that CBG can be engineered to bind a new compound, thyroxine-6-carboxyfluorescein, instead of its physiological ligand, cortisol, thereby demonstrating that it is possible to tailor the hormone binding site to deliver a therapeutic drug. In addition, we proved that the efficiency with which CBG releases bound ligand can be increased by introducing some well-placed mutations. This proof-of-concept study has raised the prospect of a novel means of targeted drug delivery, using the serpin conformational change to combat the problem of off-target effects in the treatment of diseases.The research was funded by the Wellcome Trust (http://www.wellcome.ac.uk/) grant no. 082961/Z/07/Z to RJR and was facilitated by a Wellcome Trust Strategic Award to the Cambridge Institute for Medical Research. WLC was supported by the Singapore government’s Agency for Science, Technology and Research (http://www.astar.edu.sg/). AZ was supported by a Senior Research Fellowship from the British Heart Foundation (http://www.bhf.org.uk). RJR is supported by a Principal Research Fellowship from the Wellcome Trust.This is the final published version. It originally appeared in PLOS ONE at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0113402

Neutrosophic soft sets forecasting model for multi-attribute time series

Traditional time series forecasting models mainly assume a clear and definite functional relationship between historical values and current/future values of a dataset. In this paper, we extended current model by generating multi-attribute forecasting rules based on consideration of combining multiple related variables. In this model, neutrosophic soft sets (NSSs) are employed to represent historical statues of several closely related attributes in stock market such as volumes, stock market index and daily amplitudes

Antioxidant and antidiabetic properties of Chinese and Indian bitter melons (Momordica charantia L.)

Bitter melon (Momordica charantia L.) has been used for anti-diabetes treatment for decades. Indian and Chinese bitter melons (BM) are two commonly produced cultivars in the US market. This study has comparatively evaluated the effects of two processing methods (fresh and freeze-drying) on Chinese and Indian BM by measuring their bioactivity in terms of total phenolic content (TPC), total triterpene content (TTC), antioxidant activity, and antidiabetic properties using the DPPH free radical scavenging and reducing power assays, and the α-amylase and α-glucosidase inhibition assays. The TPC (GAE mg/g dw) in freeze-dried BM were 6.03 and 6.09, and in fresh BM were 4.81 and 4.83 for Indian and Chinese BM, respectively. The TTC (OAE mg/g dw) in Indian BM were 7.25 and 5.63, and in Chinese BM were 5.88 and 3.87 for fresh and freeze-dried samples, respectively. TPC and TTC in the freeze-dried BM samples were significantly higher than that in the fresh ones (p \u3c 0.05). The DPPH IC50 of India BM was significantly lower than that of Chinese BM (p \u3c 0.05). All BM samples ranged from 9.18 to 18.6 mg/ml. The reducing power was significantly different between Indian and Chinese BM (p \u3c 0.01) for fresh samples, but after freeze-drying, there was no detectable difference in reducing power (p ≥ 0.05). The Indian BM showed a significantly stronger α-glucosidase inhibition effect as compared to the Chinese BM. TTC was positively correlated with reducing power (p \u3c 0.05). TPC was negatively correlated with α-amylase inhibition efficiency (p \u3c 0.05)

Structural basis for the specificity of renin-mediated angiotensinogen cleavage.

The renin-angiotensin cascade is a hormone system that regulates blood pressure and fluid balance. Renin-mediated cleavage of the angiotensin I peptide from the N terminus of angiotensinogen (AGT) is the rate-limiting step of this cascade; however, the detailed molecular mechanism underlying this step is unclear. Here, we solved the crystal structures of glycosylated human AGT (2.30 Å resolution), its encounter complex with renin (2.55 Å), AGT cleaved in its reactive center loop (RCL; 2.97 Å), and spent AGT from which the N-terminal angiotensin peptide was removed (2.63 Å). These structures revealed that AGT undergoes profound conformational changes and binds renin through a tail-into-mouth allosteric mechanism that inserts the N terminus into a pocket equivalent to a hormone-binding site on other serpins. These changes fully extended the N-terminal tail, with the scissile bond for angiotensin release docked in renin's active site. Insertion of the N terminus into this pocket accompanied a complete unwinding of helix H of AGT, which, in turn, formed key interactions with renin in the complementary binding interface. Mutagenesis and kinetic analyses confirmed that renin-mediated production of angiotensin I is controlled by interactions of amino acid residues and glycan components outside renin's active-site cleft. Our findings indicate that AGT adapts unique serpin features for hormone delivery and binds renin through concerted movements in the N-terminal tail and in its main body to modulate angiotensin release. These insights provide a structural basis for the development of agents that attenuate angiotensin release by targeting AGT's hormone binding pocket