Identification of Natural Products as Potential Pharmacological Chaperones for Protein Misfolding Diseases

Defective protein folding and accumulation of misfolded proteins is associated with neurodegenerative, cardiovascular, secretory, and metabolic disorders. Efforts are being made to identify small-molecule modulators or structural-correctors for conformationally destabilized proteins implicated in various protein aggregation diseases. Using a metastable-reporter-based primary screen, we evaluated pharmacological chaperone activity of a diverse class of natural products. We found that a flavonoid glycoside ( C-10 , chrysoeriol-7-O-β-D-glucopyranoside) stabilizes metastable proteins, prevents its aggregation, and remodels the oligomers into protease-sensitive species. Data was corroborated with additional secondary screen with disease-specific pathogenic protein. In vitro and cell-based experiments showed that C-10 inhibits α-synuclein aggregation which is implicated in synucleinopathies-related neurodegeneration. C-10 interferes in its structural transition into β-sheeted fibrils and mitigates α-synuclein aggregation-associated cytotoxic effects. Computational modeling suggests that C-10 binds to unique sites in α-synuclein which may interfere in its aggregation amplification. These findings open an avenue for comprehensive SAR development for flavonoid glycosides as pharmacological chaperones for metastable and aggregation-prone proteins implicated in protein conformational diseases.     

Factorial design in optimization of the separation of uranium from yellowcake across a hollow fiber supported liquid membrane,with mass transport modeling

The extraction and stripping of uranium(VI) from other impurity elements in yellowcake was performed simultaneously in one stage by a hollow fiber supported liquid membrane. Uranium ions were selectively extracted from yellowcake using TBP as the extractant, while thorium and some rare earth elements were rejected in the raffinate. The optimization method was carried out using 3² factorial design. The concentration of nitric acid in the feed solution and the concentration of TBP in the liquid membrane were regarded as factors in the optimization. A mass transport model focusing on the boundary layer of the extraction side was also applied. The model can predict the concentration of uranium in the feed tank at different times. The validity of the developed model was statistically evaluated through a comparison with experimental data, and good agreement was obtained.     

Thermal Performance of a Closed-Loop Pulsating Heat Pipe With Multiple Heat Sources

A closed-loop pulsating heat pipe with multiple heat sources (CLPHP w/MHS) was invented to be used as a heat transfer medium between a number of heat sources to a single heat sink. However, an issue on the suitable heat source arrangement that causes the heat pipe to have the highest thermal performance was suspicious. The CLPHP w/MHS was made of a copper capillary tube with 32 turns. There were three heat sources with nonidentical input heat flux installed along a longitudinal axis in the evaporator section. Experimental investigations were conducted by permuting the heat sources into six unduplicated arrangements. For the vertical CLPHPs, the highest thermal performance is achieved when heat sources are arranged in consecutive order ascending from the lowest heat flux at the inlet of the evaporator section, since working fluid is promoted to circulate in complete one direction and then the heat can transfer more continuously. Finally, for the horizontal CLPHPs, the highest thermal performance is achieved when the heat sources are arranged in opposite order to the case of vertical CLPHPs, that is, descending from the highest heat flux, since working fluid pulsates with no intermission stop and this causes the heat transfer to be not interrupted.     

蓝青蛙酒廊与录音棚

Serie建筑师事务所是一个国际化事务所,涉及的领域包括建筑、城市的设计。事务所关注于当代城市中建筑类型的进化和变异以及这些智慧形式在空间解决方案上的应用。类型学式的研究,或者用他们的名词,“连续”（SERIES）的思考和探索（利用建筑类型的累积智慧）是Serie作品的关键。     

Interface state densities, low frequency noise and electron mobility in surface channel In0.53Ga0.47As n-MOSFETs with a ZrO2 gate dielectric

This paper reports on an investigation of interface state densities, low frequency noise and electron mobility in surface channel In_0.53Ga_0.47As n-MOSFETs with a ZrO₂ gate dielectric. Interface state density values of D_it ∼ 5 × 10¹² cm⁻² eV⁻¹ were extracted using sub-threshold slope analysis and charge pumping technique. The same order of magnitude of trap density was found from low frequency noise measurements. A peak effective electron mobility of 1200 cm²/Vs has been achieved. For these surface channel In_0.53Ga_0.47As n-MOSFETs, it was found that η parameter, an empirical parameter used to calculate the effective electric field, was ∼0.55, and is to be comparable to the standard value found in Si device.     

Green synthesis,characterisation and biological studies of AgNPs prepared using Shivlingi (Bryonia laciniosa) seed extract

Green synthesis of silver nanoparticles (AgNPs) using Shivlingi (Bryonia laciniosa) seed extract was carried out. Characterisation of synthesised nanoparticles was accomplished through the optical absorption and photoluminescence spectrum, X‐ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The XRD analysis further confirmed the size of nanoparticles ∼15 nm. TEM images revealed homogeneous spherical ∼10 nm Bryonia extract capped AgNPs. The biological studies indicated that both Bryonia seed extract and the nanoparticles lack anti‐microbial activity; however, the nanoparticles had better cytotoxicity and total antioxidant activity. The Lethal concentration (LC)₅₀ value of water extract and the nanoparticles were found to be 1091 and 592 μg/ml, respectively. The lower LC₅₀ of nanoparticles indicates that it is more cytotoxic than the crude extract. The results indicate that the Bryonia seed is safe to be used as a medicine and the formation of their nanoparticle has further enriched the chemical reactivity, energy absorption and biological mobility.Inspec keywords: silver, nanoparticles, nanomedicine, particle size, microorganisms, cellular biophysics, nanofabrication, photoluminescence, X‐ray diffraction, transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectra, Raman spectra, antibacterial activity, biochemistryOther keywords: green synthesis, biological studies, Shivlingi seed extraction, Bryonia laciniosa, silver nanoparticles, optical absorption, photoluminescence spectrum, X‐ray diffraction, transmission electron microscopy, scanning electron microscopy, SEM, Fourier transform infrared spectroscopy, Raman spectroscopy, XRD analysis, nanoparticle size, TEM images, homogeneous spherical images, antioxidant activity, water extraction, chemical reactivity, energy absorption, biological mobility, Ag     

High-efficiency HFSLM for silver-ion pertraction from pharmaceutical wastewater and mass-transport models

Hollow fiber supported liquid membrane (HFSLM) is a favorable technique for the pertraction of metal ions, especially at very low metal concentration. In this work, the pertraction of silver ions from acidic pharmaceutical wastewater via HFSLM was investigated. Pharmaceutical wastewater containing 30 mg/dm³ of silver ions and 120 mg/dm³ of ferric ions was subjected to HFSLM as a feed solution. LIX 84-I dissolved in organic solvent together with Na₂S₂O₃·5H₂O solution was selected for use as a liquid membrane and a receiving solution, respectively. The influence of ferric ions on the pertraction of silver ions was studied firstly using wastewater with normal ferric ion concentration and secondly using wastewater with ferric ion precipitation by phosphoric acid solution. The highest pertraction of silver ions was achieved by using 0.1 M of LIX 84-I and 0.5 M of Na₂S₂O₃·5H₂O solution at pH of feed and receiving solutions of 3.5 and 2. The flow rates of feed and receiving solutions were 0.2 dm³/min. 0.6 mg/dm³ of silver ions that remained in the wastewater was below the mandatory discharge limit. No effect of normal ferric ion concentration in the wastewater on silver ion pertraction was observed. The crucial parameters were defined to confirm the efficiency and reliability of the system. Finally, the controlling transport regime of silver ion pertraction across HFSLM was determined by the diffusion flux and reaction flux models.     

Compatibility of liquid deproteinized natural rubber having epoxy group (LEDPNR)/poly (L‐lactide) blend

Reaction after mixing of liquid epoxidized natural rubber/poly(L ‐lactide) blend was performed to enhance the compatibility of the blend. The liquid epoxidized natural rubber was prepared by epoxidation of deproteinized natural rubber with peracetic acid in latex stage followed by depolymerization with peroxide and propanal. The resulting liquid deproteinized natural rubber having epoxy group (LEDPNR) was mixed with poly(L ‐lactide) (PLLA) to investigate the compatibility of the blend through differential scanning calorimetry, optical light microscopy, and NMR spectroscopy. After heating the blend at 473 K for 20 min, glass transition temperature (T_g) of LEDPNR in LEDPNR/PLLA blend increased from 251 to 259 K, while T_g and melting temperature (T_m) of PLLA decreased from 337 to 332 K and 450 to 445 K, respectively, suggesting that the compatibility of LEDPNR/ PLLA blend was enhanced by a reaction between the epoxy group of LEDPNR and the ester group of PLLA. The reaction was proved by high‐resolution solid‐state ¹³C NMR spectroscopy. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Surface modification of textured silicon and its wetting behaviour

Textured silicon (Si) substrate were prepared using various texturing methods both chemical and physical and their water contact angle, surface topography and Raman spectra were studied and investigated. The effect of plasma and chemical treatment on micro/nanostructure and roughness of the surface with and without deposition of Octadecyltrichlorosilane (ODTS, Cl₃Si (CH₃)₁₇), self-assembled monolayer (SAM) is investigated for achieving higher water contact angle (θ_c). The importance of synergism of texturing with deposition of ODTS SAM in preparing superhydrophobic silicon surfaces has been discussed. It is shown that superhydrophobic silicon surfaces can be achieved on silicon surfaces by coating with ODTS, irrespective of whether it is textured or not, polished or unpolished, provided a chemical treatment is given to the surface prior to the ODTS coating.     

Relating spatial patterns of fractional land cover to savanna vegetation morphology using multi-scale remote sensing in the Central Kalahari

Understanding, monitoring, and managing savanna ecosystems requires characterizing both functional and structural properties of vegetation. From a functional perspective, in savannas, quantitative estimation of fractional cover of photosynthetic vegetation (f_PV), non-photosynthetic vegetation (f_NPV), and bare soil (f_BS) is important as it relates to carbon dynamics and ecosystem function. On the other hand, vegetation morphology classes describe the structural properties of the ecosystem. Due to high functional diversity and structural heterogeneity in savannas, accurately characterizing both these properties using remote sensing is methodologically challenging. While mapping both fractional cover and vegetation morphology classes are important research themes within savanna remote sensing, very few studies have considered systematic investigation of their spatial association across different spatial resolutions. Focusing on the semi-arid savanna ecosystem in the Central Kalahari, this study utilized f_PV, f_NPV, and f_BS derived in situ and estimated from spectral unmixing of high- (GeoEye-1), medium- (Landsat TM), and coarse- (MODIS) spatial resolution imagery to investigate: (i) the impact of reducing spatial resolution on both magnitude and accuracy of fractional cover; and (ii) how fractional-cover magnitude and accuracy are spatially associated with savanna vegetation morphology classes. Endmembers for Landsat TM and GeoEye-1 were derived from the image based on purity measures; for MODIS (MCD43A4), the challenge of finding spectral endmembers was addressed following an empirical multi-scale hierarchical approach. GeoEye-1-derived fractional estimates showed comparatively closest agreement with in situ measurements and were used to evaluate Landsat TM and MODIS. Overall results indicate that increasing pixel size caused consistent increases in variance of and error in fractional-cover estimates. Even at coarse spatial resolution, f_PV was estimated with higher accuracy compared with f_NPV and f_BS. Assessment considering vegetation morphology of samples revealed both morphology- and cover-specific differences in accuracy. At larger pixel sizes, in areas with dominant woody vegetation, f_PV was overestimated at the cost of mainly underestimating f_BS; in contrast, in areas with dominant herbaceous vegetation, f_NPV was overestimated with a corresponding underestimation of both f_PV and f_BS. These results underscore that structural and functional heterogeneity in semi-arid savanna both impact retrieval of fractional cover, suggesting that comprehensive remote sensing of savannas needs to take both structure and cover into account.