Recent Progress in Pharmaceutical Therapies for Castration-Resistant Prostate Cancer

Since 2010, six drugs have been approved for the treatment of castration-resistant prostate cancer, i.e., CYP17 inhibitor Abiraterone, androgen receptor antagonist Enzalutamide, cytotoxic agent Cabazitaxel, vaccine Sipuleucel-T, antibody Denosumab against receptor activator of nuclear factor kappa B ligand and radiopharmaceutical Alpharadin. All these drugs demonstrate improvement on overall survival, expect for Denosumab, which increases the bone mineral density of patients under androgen deprivation therapy and prolongs bone-metastasis-free survival. Besides further CYP17 inhibitors (Orteronel, Galeterone, VT-464 and CFG920), androgen receptor antagonists (ARN-509, ODM-201, AZD-3514 and EZN-4176) and vaccine Prostvac, more drug candidates with various mechanisms or new indications of launched drugs are currently under evaluation in different stages of clinical trials, including various kinase inhibitors and platinum complexes. Some novel strategies have also been proposed aimed at further potentiation of antitumor effects or reduction of side effects and complications related to treatments. Under these flourishing circumstances, more investigations should be performed on the optimal combination or the sequence of treatments needed to delay or reverse possible resistance and thus maximize the clinical benefits for the patients

Ambient Sound Helps: Audiovisual Crowd Counting in Extreme Conditions

Visual crowd counting has been recently studied as a way to enable people counting in crowd scenes from images. Albeit successful, vision-based crowd counting approaches could fail to capture informative features in extreme conditions, e.g., imaging at night and occlusion. In this work, we introduce a novel task of audiovisual crowd counting, in which visual and auditory information are integrated for counting purposes. We collect a large-scale benchmark, named auDiovISual Crowd cOunting (DISCO) dataset, consisting of 1,935 images and the corresponding audio clips, and 170,270 annotated instances. In order to fuse the two modalities, we make use of a linear feature-wise fusion module that carries out an affine transformation on visual and auditory features. Finally, we conduct extensive experiments using the proposed dataset and approach. Experimental results show that introducing auditory information can benefit crowd counting under different illumination, noise, and occlusion conditions. The dataset and code will be released. Code and data have been made availabl

Mitigating Coherent Noise by Balancing Weight-2 ZZ-Stabilizers

Physical platforms such as trapped ions suffer from coherent noise where errors manifest as rotations about a particular axis and can accumulate over time. We investigate passive mitigation through decoherence free subspaces, requiring the noise to preserve the code space of a stabilizer code, and to act as the logical identity operator on the protected information. Thus, we develop necessary and sufficient conditions for all transversal $Z$-rotations to preserve the code space of a stabilizer code, which require the weight-$2$ $Z$-stabilizers to cover all the qubits that are in the support of some $X$-component. Further, the weight-$2$ $Z$-stabilizers generate a direct product of single-parity-check codes with even block length. By adjusting the size of these components, we are able to construct a large family of QECC codes, oblivious to coherent noise, that includes the $[[4L^2, 1, 2L]]$ Shor codes. Moreover, given $M$ even and any $[[n,k,d]]$ stabilizer code, we can construct an $[[Mn, k, \ge d]]$ stabilizer code that is oblivious to coherent noise. If we require that transversal $Z$-rotations preserve the code space only up to some finite level $l$ in the Clifford hierarchy, then we can construct higher level gates necessary for universal quantum computation. The $Z$-stabilizers supported on each non-zero $X$-component form a classical binary code C, which is required to contain a self-dual code, and the classical Gleason's theorem constrains its weight enumerator. The conditions for a stabilizer code being preserved by transversal $2\pi/2^l$ $Z$-rotations at $4 \le l \le l_{\max} <\infty$ level in the Clifford hierarchy lead to generalizations of Gleason's theorem that may be of independent interest to classical coding theorists.Comment: Jingzhen Hu and Qingzhong Liang contributed equally to this work. The paper was accepted to IEEE Transactions on Information Theory. The ISIT paper is available as an ancillary fil

HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells

Reendothelialization involves endothelial progenitor cell (EPC) homing, proliferation, and differentiation, which may be influenced by fluid shear stress and local flow pattern. This study aims to elucidate the role of laminar flow on embryonic stem (ES) cell differentiation and the underlying mechanism. We demonstrated that laminar flow enhanced ES cell–derived progenitor cell proliferation and differentiation into endothelial cells (ECs). Laminar flow stabilized and activated histone deacetylase 3 (HDAC3) through the Flk-1–PI3K–Akt pathway, which in turn deacetylated p53, leading to p21 activation. A similar signal pathway was detected in vascular endothelial growth factor–induced EC differentiation. HDAC3 and p21 were detected in blood vessels during embryogenesis. Local transfer of ES cell–derived EPC incorporated into injured femoral artery and reduced neointima formation in a mouse model. These data suggest that shear stress is a key regulator for stem cell differentiation into EC, especially in EPC differentiation, which can be used for vascular repair, and that the Flk-1–PI3K–Akt–HDAC3–p53–p21 pathway is crucial in such a process

Cotton WATs Modulate SA Biosynthesis and Local Lignin Deposition Participating in Plant Resistance Against Verticillium dahliae

Verticillium wilt, caused by Verticillium dahliae, seriously limits cotton production. It is difficult to control this pathogen damage mainly due to the complexity of the molecular mechanism of plant resistance to V. dahliae. Here, we identified three homologous cotton Walls Are Thin (WAT) genes, which were designated as GhWAT1, GhWAT2, and GhWAT3. The GhWATs were predominantly expressed in the roots, internodes, and hypocotyls and induced by infection with V. dahliae and treatment with indole-3-acetic acid (IAA) and salicylic acid (SA). GhWAT1-, GhWAT2-, or GhWAT3-silenced plants showed a comparable phenotype and level of resistance with control plants, but simultaneously silenced three GhWATs (GhWAT123-silenced), inhibited plant growth and increased plant resistance to V. dahliae, indicating that these genes were functionally redundant. In the GhWAT123-silenced plants, the expression of SA related genes was significantly upregulated compared with the control, resulting in an increase of SA level. Moreover, the histochemical analysis showed that xylem development was inhibited in GhWAT123-silenced plants compared with the control. However, lignin deposition increased in the xylem of the GhWAT123-silenced plants compared to the control, and there were higher expression levels of lignin synthesis- and lignifications-related genes in the GhWAT123-silenced plants. Collectively, the results showed that GhWATs in triple-silenced plants acts as negative regulators of plant resistance against V. dahliae. The potential mechanism of the WATs functioning in the plant defence can modulate the SA biosynthesis and lignin deposition in the xylem

Assessment of gene order computing methods for Alzheimer’s disease

This article was originally published by BMC Medical Genomics in 2013. doi:10.1186/1755-8794-6-S1-S8Background: Computational genomics of Alzheimer disease (AD), the most common form of senile dementia, is a nascent field in AD research. The field includes AD gene clustering by computing gene order which generates higher quality gene clustering patterns than most other clustering methods. However, there are few available gene order computing methods such as Genetic Algorithm (GA) and Ant Colony Optimization (ACO). Further, their performance in gene order computation using AD microarray data is not known. We thus set forth to evaluate the performances of current gene order computing methods with different distance formulas, and to identify additional features associated with gene order computation. Methods: Using different distance formulas- Pearson distance and Euclidean distance, the squared Euclidean distance, and other conditions, gene orders were calculated by ACO and GA (including standard GA and improved GA) methods, respectively. The qualities of the gene orders were compared, and new features from the calculated gene orders were identified. Results: Compared to the GA methods tested in this study, ACO fits the AD microarray data the best when calculating gene order. In addition, the following features were revealed: different distance formulas generated a different quality of gene order, and the commonly used Pearson distance was not the best distance formula when used with both GA and ACO methods for AD microarray data. Conclusion: Compared with Pearson distance and Euclidean distance, the squared Euclidean distance generated the best quality gene order computed by GA and ACO methods.The work was supported by the BWH Radiology and MGH Psychiatry research funds (to X. Huang) and the Technology Innovation fund (No. 09zz028) of Key Developing Program from Education Department of Sichuan Province, ChinaPearson distanc

A Genome-wide Microsatellite Polymorphism Database for the Indica and Japonica Rice

Microsatellite (MS) polymorphism is an important source of genetic diversity, providing support for map-based cloning and molecular breeding. We have developed a new database that contains 52 845 polymorphic MS loci between indica and japonica, composed of ample Class II MS markers, and integrated 18 828 MS loci from IRGSP and genetic markers from RGP. Based on genetic marker positions on the rice genome (http://rise.genomics.org.cn/rice2/index.jsp ), we determined the approximate genetic distances of these MS loci and validated 100 randomly selected markers experimentally with 90% success rate. In addition, we recorded polymorphic MS positions in indica cv. 9311 that is the most important paternal parent of the two-line hybrid rice in China. Our database will undoubtedly facilitate the application of MS markers in genetic researches and marker-assisted breeding. The data set is freely available from www.wigs.zju.edu.cn/achievment/polySSR

Variasi Temperatur Pencampuran Terhadap Parameter Marshall Pada Campuran Lapis Aspal Beton

This study was conducted to determine the effect of temperature variations on the mixing processof the asphalt concrete AC-WC (Asphalt Concrete-Wearing Course) subtle gradations in themiddle limit and lower limit of the Marshall parameters with reference to specifications of BinaMarga, 2010.From the results of experiments conducted that the optimum asphalt content is used to middle limitusing a asphalt content of 5,7% and 6,8% for the lower limit after that mixing was done usingtemperature variation of 120 o C, 130 o C, 140 o C, 150 o C, and 160 o C.To a mixture of Laston AC-WC subtle gradations middle limit grading 5,7% asphalt contentmixing temperature using a temperature of 120 o C, 130 o C, 140 o C, 150 o C, 160 o C and still meet allstandards of marshall parameters. Ideal mixing temperature variations in the middle limit ofmixing temperature 150 o C-160 o C. While the lower limit to the level of 6,8% asphalt contentmixing temperatures between 120 o C-160 o C did not meet the specifications, because the MQ valuebelow the minimum value of 250 kg / mm

Manipulations of phenylnorbornyl palladium species for multicomponent construction of a bridged polycyclic privileged scaffold

Hexahydromethanocarbazole is a privileged scaffold in the discovery of new drugs and photoactive organic materials due to its good balance between structural complexity and minimized entropy penalty upon receptor binding. To address the difficulty of synthesizing this highly desirable bridged polycyclic scaffold, we designed a convenient multicomponent reaction cascade as intercepted Heck addition/C-H activation/C-palladacycle formation/electrophilic attack of ANP/N-palladacycle formation/Buchwald amination. A distinguishing feature of this sophisticated strategy is the successive generation of two key phenylnorbornyl palladium species to control the reaction flow towards desired products. DFT calculations further reveal the crucial roles of Cs2CO3 and 5,6-diester substitutions on the norbornene reactant in preventing multiple side-reactions. This innovative method exhibits a broad scope with good yields, and therefore will enable the construction of natural-product-like compound libraries based on hexahydromethanocarbazole