Design, synthesis and development of PDE5 inhibitors

This research project is concerned with the design, synthesis and development of new phosphodiesterase 5 (PDE5) inhibitors with improved selectivities and lower toxicities. Two series of a 5 member and a 6 member ring fused heterocyclic compounds were designed, and synthesized. By alteration of starting materials and fragments, two virtual libraries, each is consisted of close to hundred compounds, were obtained successfully. The screening of sexual stimulation activity with rabbits demonstrated both groups of compounds were able to stimulate rabbit penile erection significantly. The following toxicity studies revealed 2-(substituted-sulfonylphenyl)-imidazo [1,5-a]-1,3,5-triazine-4-(3H)-one group possessed an unacceptable toxicity with oral LD50 about 200mg/kg; while 2-(substituted-sulfonylphenyl)-pyrrolo[2,3-d]pyrimidin-4-one group showed an acceptable toxicity with oral LD50 over 2000mg/kg. The continued bioactivity studies showed yonkenafil, the representative of 2-(substituted-sulfonylphenyl)-pyrrolo[2,3-d]pyrimidin-4-one group, has a better selectivity towards PDE5 and PDE6 than sildenafil and a better overall profile of sexual stimulation on animals than sildenafil. Chronic toxicity studies of yonkenafil further confirmed yonkenafil did not cause any serious side effect and damage on animal models and most actions were explainable. Based on evidences of the above studies, yonkenafil were recommended to enter clinical trials by the regulation authority of China, SFDA. Currently yonkenafil has been through the Phase I clinical trials and ready to progress into Phase II. Hopefully, yonkenafil will provide an alternative to the ED patients in the future

Characterization of miniature fiber-optic Fabry-Perot interferometric sensors based on hollow silica tube

Sejatinya, Islam Nusantara bukanlah sesuatu yang baru. Penebalan kata “Nusantara” yang dikawinkan dengan “Islam” bukan hanya menegaskan nama, melainkan juga karakter untuk menunjukkan corak atau warna dari sebuah entitas yang heterogen. Keragaman sebagai salah satu tipologi Islam Nusantara adalah buah dari pergumulan panjang antara agama dan budaya; antara teks dengan konteks yang saling melengkapi satu sama lain sehingga menelurkan Islam yang ramah, inklusif dan fleksibel. Berangkat dari pijakan epistemologis dan historis, artikel ini coba menyuguhkan diskursus lama yang kembali mencuat di seputaran pertengahan tahun 2015 seiring dengan dihelatnya Muktamar dua ormas besar: NU dan Muhammadiyah. Hadirnya artikel ini sebetulnya juga ingin menjawab kasak-kusuk yang menuding bahwa Islam Nusantara hanya identik dengan kaum Nahdliyin. Sehingga term Islam Nusantara tidak lain dianggap sebagai nama baru dariIslam tradisionalis.Essentially, Islam Nusantara isn’t a new phenomenon. Bolding of both “Nusantara” with “Islam” not only affirmation about name but also character to show type or colour from the heterogenous entity. Diversity as one of Islam Nusantara typology is the result of a long struggle between religionand culture; between text and context that complement each other so that Islam spawned a friendly, inclusive and flexible. Start from the historical and epistemological approach, this article try to presents a classical discourse the back sticking around mid-2015 in line with the holding of the congress two major organizations: NU and Muhammadiyah. Actually, the presence o fthis article is also want to answer the rumors that accuse Islam Nusantara only synonymous with the Nahdliyin. Thus, Islam Nusantara considered as the new name of traditionalism Islam.</p

A Theory of Complex Adaptive Learning Based on an Intelligent Trading Probability Wave Equation

Complex adaptive learning is intelligent and crucial in living and inanimate complex systems. A complex system comprises many interacting individuals or units, shows hidden patterns as they interact, and widely occurs in almost every traditional discipline, from natural to social sciences. A recent study has demonstrated a so-called architected material capable of learning. It stimulates scientists to explore the mechanism of complex systems formulation. However, it is very challenging. Here the authors attempt to extract a universal rule or a law of complex adaptive learning subject to local dynamic equilibrium in complex systems from a trading volume-price probability wave equation and apply it to complex quantum systems as its application. It proves particles capable of intelligence-like properties in interactive coherence if the momentum force exerted on the complex quantum systems is non-localized. It is the cumulative probability of the moving particles observed in a time interval. Thus, it assumes that particles in complex quantum systems have a complex adaptive learning- or intelligence-like property in a reinforced coordinate, governed by the exact complex adaptive learning mechanism as that of traders in the complexity of the financial markets. With this assumption, the authors propose an innovative interpretation of entanglement in quantum mechanics. It concludes that quantum entanglement is not a state of the superposition of coherent states as the mainstream Copenhagen school of thought maintains. It is a coherent state in the interaction between two opposite, complementary, and variable forces. The authors look forward to the experimental results to examine its validity and further improve the theory until it is perfect, suggesting industrial production of entanglement resources in new technical routes availableComment: 22 pages in total (double spaces and including a title page and a popular summary), 2 figures, and 20 reference

Rethinking the Pipeline of Demosaicing, Denoising and Super-Resolution

Incomplete color sampling, noise degradation, and limited resolution are the three key problems that are unavoidable in modern camera systems. Demosaicing (DM), denoising (DN), and super-resolution (SR) are core components in a digital image processing pipeline to overcome the three problems above, respectively. Although each of these problems has been studied actively, the mixture problem of DM, DN, and SR, which is a higher practical value, lacks enough attention. Such a mixture problem is usually solved by a sequential solution (applying each method independently in a fixed order: DM $\to$ DN $\to$ SR), or is simply tackled by an end-to-end network without enough analysis into interactions among tasks, resulting in an undesired performance drop in the final image quality. In this paper, we rethink the mixture problem from a holistic perspective and propose a new image processing pipeline: DN $\to$ SR $\to$ DM. Extensive experiments show that simply modifying the usual sequential solution by leveraging our proposed pipeline could enhance the image quality by a large margin. We further adopt the proposed pipeline into an end-to-end network, and present Trinity Enhancement Network (TENet). Quantitative and qualitative experiments demonstrate the superiority of our TENet to the state-of-the-art. Besides, we notice the literature lacks a full color sampled dataset. To this end, we contribute a new high-quality full color sampled real-world dataset, namely PixelShift200. Our experiments show the benefit of the proposed PixelShift200 dataset for raw image processing.Comment: Code is available at: https://github.com/guochengqian/TENe

Oblikovanje jestivih filmova iz proteina soje unakrsnim vezivanjem transglutaminazom iz bakterije Streptomyces

Soybean protein isolate (SPI) was used in the investigation of the formation of edible protein films through an enzymatic cross-linking method with a purified microbial transglutaminase (MTG) produced from a new effective strain Streptomyces sp. WZFF.L-M1 preserved in our laboratory, followed by the addition of glycerol and suitable heating and drying treatments. Cheaper partially-purified skimmed soybean protein powder (SSP) and whey protein isolates (WPI) were used as the substitutes partially replacing the expensive SPI products, and purified β-lactoglobulin was taken as the positive control of WPI. As a result, the three alternatives could also form highly efficient edible films under the optimal operation conditions. The films made with SPI alternatives, about 50 µm thin, had homogenous network structures, without any holes by direct observation with the naked eye. The tests of the properties of these films showed that they had high water-keeping capacity and strong elasticity, that the ultimate tensile strength (TS) and the elongation at break (Eb) had been remarkably increased (TS>5 MPa, Eb>50 %), and that the prevention rates against the permeability of water vapour and oxygen in the air were also upgraded more than 85 and 70 %, respectively.Izolat proteina soje upotrijebljen je pri oblikovanju jestivih filmova metodom unakrsnog vezivanja transglutaminaze iz novoga soja bakterije Streptomyces sp. WZFF.L-M1, uzgojenog u našem laboratoriju. Nakon dodavanja glicerola, film je zagrijan te osušen. Dio skupih izolata proteina soje zamijenjen je jeftinijim, djelomično pročišćenim obranim prahom proteina soje i izolatima proteina surutke, a pročišćenim β-laktoglobulinom dokazana je prisutnost izolata proteina surutke. Rezultati su pokazali da se u optimalnim uvjetima, upotrebom triju zamjenskih izolata, mogu proizvesti vrlo učinkoviti jestivi filmovi. Struktura filmova debljine oko 50 µm, dobivenih uporabom zamjenskih izolata, bila je homogena, bez okom vidljivih rupica. Rezultati ispitivanja pokazali su veliku moć zadržavanja vode i elastičnost tih filmova. Znatno je povećana granična čvrstoća (>5 MPa) i istezljivost (>50 %) te smanjena njihova propusnost na vodenu paru za 85 % i kisika za 70 %

Oblikovanje jestivih filmova iz proteina soje unakrsnim vezivanjem transglutaminazom iz bakterije Streptomyces

Soybean protein isolate (SPI) was used in the investigation of the formation of edible protein films through an enzymatic cross-linking method with a purified microbial transglutaminase (MTG) produced from a new effective strain Streptomyces sp. WZFF.L-M1 preserved in our laboratory, followed by the addition of glycerol and suitable heating and drying treatments. Cheaper partially-purified skimmed soybean protein powder (SSP) and whey protein isolates (WPI) were used as the substitutes partially replacing the expensive SPI products, and purified β-lactoglobulin was taken as the positive control of WPI. As a result, the three alternatives could also form highly efficient edible films under the optimal operation conditions. The films made with SPI alternatives, about 50 µm thin, had homogenous network structures, without any holes by direct observation with the naked eye. The tests of the properties of these films showed that they had high water-keeping capacity and strong elasticity, that the ultimate tensile strength (TS) and the elongation at break (Eb) had been remarkably increased (TS>5 MPa, Eb>50 %), and that the prevention rates against the permeability of water vapour and oxygen in the air were also upgraded more than 85 and 70 %, respectively.Izolat proteina soje upotrijebljen je pri oblikovanju jestivih filmova metodom unakrsnog vezivanja transglutaminaze iz novoga soja bakterije Streptomyces sp. WZFF.L-M1, uzgojenog u našem laboratoriju. Nakon dodavanja glicerola, film je zagrijan te osušen. Dio skupih izolata proteina soje zamijenjen je jeftinijim, djelomično pročišćenim obranim prahom proteina soje i izolatima proteina surutke, a pročišćenim β-laktoglobulinom dokazana je prisutnost izolata proteina surutke. Rezultati su pokazali da se u optimalnim uvjetima, upotrebom triju zamjenskih izolata, mogu proizvesti vrlo učinkoviti jestivi filmovi. Struktura filmova debljine oko 50 µm, dobivenih uporabom zamjenskih izolata, bila je homogena, bez okom vidljivih rupica. Rezultati ispitivanja pokazali su veliku moć zadržavanja vode i elastičnost tih filmova. Znatno je povećana granična čvrstoća (>5 MPa) i istezljivost (>50 %) te smanjena njihova propusnost na vodenu paru za 85 % i kisika za 70 %

Amphibian Species Contribute Similarly to Taxonomic, but not Functional and Phylogenetic Diversity: Inferences from Amphibian Biodiversity on Emei Mountain

Understanding the relationships between species, communities, and biodiversity are important challenges in conservation ecology. Current biodiversity conservation activities usually focus on species that are rare, endemic, distinctive, or at risk of extinction. However, empirical studies of whether such species contribute more to aspects of biodiversity than common species are still relatively rare. The aim of the present study was to assess the contribution of individual amphibian species to different facets of biodiversity, and to test whether species of conservation interest contribute more to taxonomic, functional, and phylogenetic diversity than do species without special conservation status. To answer these questions, 19 000 simulated random communities with a gradient of species richness were created by shuffling the regional pool of species inhabiting Emei Mountain. Differences of diversity values were then computed before and after removing individual species in these random communities. Our results indicated that although individual species contributed similarly to taxonomic diversity, their contribution to functional and phylogenetic diversity was more idiosyncratic. This was primarily driven by the diverse functional attributes of species and the differences in phylogenetic relationships among species. Additionally, species of conservation interest did not show a significantly higher contribution to any facet of biodiversity. Our results support the claims that the usefulness of metrics based only on species richness is limited. Instead, assemblages that include species with functional and phylogenetic diversity should be protected to maintain biodiversity

Variation of Al species during water treatment:correlation with treatment efficiency under varied hydraulic conditions

The concentration of hydrolyzed coagulant ion species is a key factor in determining drinking water treatment efficiency. Direct correlation of water treatment efficiency with changes in species during coagulation has not been addressed. We investigated the correlation under different hydraulic conditions and water treatment efficiencies including changes in removal of turbidity, ultraviolet adsorption at 254 nm (UV254) and dissolved organic carbon (DOC). Results highlighted that Al species (monomeric species as Ala, medium polymeric species as Alb and colloidal species as Alc) behaved differently during coagulation and treatment efficiencies were affected. When varying the mixing speed, the removal of Alc species had a strong negative correlation with water treatment efficiency but under other hydraulic conditions positive correlations were found. The removal of Ala species was positively correlated with water treatment efficiency, but under other hydraulic conditions the low abundance of Ala species meant the correlation was difficult to observe. The Alb species were significantly and positively correlated with water treatment efficiency with the highest correlation coefficient (R2) of 0.87. The correlation of metallic species with removal efficiencies of the DOC and the UV254 produced higher R2 values. Correlation of the rate of removal of Alb species with the removal efficiencies of the DOC or the UV254 was better than for Alc. HIGHLIGHTS Hydrolyzed coagulant ion species is considered as one of key factors in determining drinking water treatment efficiency.; Drinking water treatment efficiency is often correlated with the distribution species in coagulant rather than water.; The variation of the species removal was investigated in the coagulation system.; Under varied hydraulic conditions a positive response in correlation was presented.