Direct pulsed laser crystallization of nanocrystals for absorbent layers in photovoltaics: Multiphysics simulation and experiment

Direct pulsed laser crystallization (DPLC) of nanoparticles of photoactive material-Copper Indium Selenide (nanoCIS) is investigated by multiphysics simulation and experiments. Laser interaction with nanoparticles is fundamentally different from their bulk counterparts. A multiphysics electromagnetic-heat transfer model is built to simulate DPLC of nanoparticles. It is found smaller photoactive nanomaterials (e.g., nanoCIS) require less laser fluence to accomplish the DPLC due to their stronger interactions with incident laser and lower melting point. The simulated optimal laser fluence is validated by experiments observation of ideal microstructure. Selectivity of DPLC process is also confirmed by multiphysics simulation and experiments. The combination effects of pulse numbers and laser intensity to trigger laser ablation are investigated in order to avoid undesired results during multiple laser processing. The number of pulse numbers is inversely proportional to the laser fluence to trigger laser ablation. (C) 2013 AIP Publishing LLC

The Molecular Determinants of NEDD8 Specific Recognition by Human SENP8

Although neuronal-precursor-cell-expressed developmentally downregulated protein-8 (NEDD8) and ubiquitin share the highest level of sequence identity and structural similarity among several known ubiquitin-like proteins, their conjugation to a protein leads to distinct biological consequences. In the study, we first identified the NEDD8 protein of Chlamydomonas reinhardtii (CrNEDD8) and discovered that CrNEDD8 is fused at the C-terminus of a ubiquitin moiety (CrUb) in a head-to-tail arrangement. This CrUb-CrNEDD8 protein was termed CrRUB1 (related to ubiquitin 1) by analogy with a similar protein in Arabidopsis thaliana (AtRUB1). Since there is high sequence identity in comparison to the corresponding human proteins (97% for ubiquitin and 84% for NEDD8), a His-CrRUB1-glutathione S-transferase (GST) fusion construct was adopted as the alternative substrate to characterize the specificity of NEDD8-specific peptidase SENP8 for CrNEDD8. The data showed that SENP8 only cleaved the peptide bond beyond the di-glycine motif of CrNEDD8 and His-RUB1 was subsequently generated, confirming that SENP8 has exquisite specificity for CrNEDD8 but not CrUb. To further determine the basis of this specificity, site-directed mutagenesis at earlier reported putative molecular determinants of NEDD8 specific recognition by SENP8 was performed. We found that a single N51E mutation of CrNEDD8 completely inhibited its hydrolysis by SENP8. Conversely, a single E51N mutation of CrUb enabled this ubiquitin mutant to undergo hydrolysis by SENP8, revealing that a single residue difference at the position 51 contributes substantially to the substrate selectivity of SENP8. Moreover, the E51N/R72A double mutant of the CrUb subdomain can further increase the efficiency of cleavage by SENP8, indicating that the residue at position 72 is also important in substrate recognition. The E51N or R72A mutation of CrUb also inhibited the hydrolysis of CrUb by ubiquitin-specific peptidase USP2. However, USP2 cannot cleave the N51E/A72R double mutant of the CrNEDD8 subdomain, suggesting that USP2 requires additional recognition sites

Antitumor agents 294. Novel E-ring-modified camptothecin–4β-anilino-4′-O-demethyl-epipodophyllotoxin conjugates as DNA topoisomerase I inhibitors and cytotoxic agents

Two conjugates (1 and 2) of camptothecin (CPT) and 4β-anilino-4′-O-demethylepipodophyllotoxin were previously shown to exert antitumor activity through inhibition of topoisomerase I (topo I). In this current study, two novel conjugates (1E and 2E) with an open E-ring in the CPT moiety were first synthesized and evaluated for biological activity in comparison with their intact E-ring congeners. This novel class of CPT derivatives exhibits its antitumor effect against CPT-sensitive and -resistant cells, in part, by inhibiting topo I-linked DNA (TLD) religation. An intact E-ring was not essential for the inhibition of TLD religation, although conjugates with an open E-ring were less potent than the closed ring analogs. This lower religation potency resulted in decreased formation of protein-linked DNA breaks (PLDBs), and hence, less cell growth inhibition. In addition to their impact on topo I, conjugates 1E, 2, and 2E exhibited a minor inhibitory effect on topo II-induced DNA cleavage. The novel structures of 1E and 2E may present scaffolds for further development of dual function topo I and II inhibitors with improved pharmacological profiles and physicochemical properties

Is the incipient Chinese civil society playing a role in regenerating historic urban areas? Evidence from Nanjing, Suzhou and Shanghai

Urban regeneration in Western countries can count on a long-lasting tradition of experiences in which civil society has played a fundamental role in counterbalancing the system of power, resulting in profound urban governance readjustments. This has been the result of the increasing centrality of horizontal alliances between citizens and associations involved in urban affairs since the late 1960s in the West. Similar theoretical frameworks have been applied in China. However, these have frequently resulted in conceptual shortcuts that depict civil society as immature or lacking and the state as authoritarian. This paper will explore whether these categories are still entirely valid to urban regeneration in China. While the regime has traditionally prevented horizontal linkages of associations in urban governance (supporting their vertical integration to ensure a certain degree of soft control), there are signs of change. In particular, three cases of urban regeneration in historic areas will be used to discuss the changing role played by civil society in China. The ultimate goal is to examine whether horizontal linkages across groups of heterogeneous citizens are arising at the micro-level of urban governance

Polycythemia vera as a presentation of renal angiomyolipoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Angiomyolipoma is a common benign renal tumor composed of thick-walled blood vessels, smooth muscle, and adipose tissue. It may be found incidentally during workup for suspected renal disease. Although angiomyolipoma may present as a palpable, tender renal mass with flank pain and gross or microscopic hematuria, many patients are asymptomatic. Erythrocytosis is an unusual presentation, and malignant transformation may be suspected. This report describes a rare case of a woman diagnosed with renal angiomyolipoma and polycythemia vera. The report discusses the differential diagnosis using erythropoietin, erythropoietin-receptor and Janus kinase 2.</p> <p>Case presentation</p> <p>A 79-year-old Chinese woman was diagnosed with erythrocytosis according to World Health Organization criteria. An upper left renal pole angiomyolipoma was successfully ablated after multiple phlebotomy treatments. Red cell count immediately returned to normal, but gradually increased after 4 months. Polycythemia vera was finally diagnosed by positive mutation of Janus kinase 2 and negative erythropoietin protein expression. Her clinical symptoms improved with regular phlebotomy and hydroxyurea treatment.</p> <p>Conclusion</p> <p>Concurrent occurence of angiomyolipoma and polycythemia vera is rare. Polycythemia vera can be easily missed. Polycythemia vera can be confirmed with high specificity and sensitivity by the acquired somatic mutation. Surgical intervention for this renal tumor should be avoided unless malignancy or renal cell carcinoma is suspected or to prevent spontaneous rupture of larger tumors.</p

Screening for eukaryotic signal transduction and Mycobacterium isocitrate lyase inhibitor from actinomycetes and fungi of dipterocarp rain forests at Imabak Valey, Sabah, Malaysia

A diversity of actinomycetes and fungi was isolated from various sites during the Imbak Valley Scientific Expedition 2000. A total of 144 soil samples were collected under trees that have been identified to species or genus level. Imbak Valley is a lowland dipterocarp forest, which is interestingly dominated by Dryobalanops beccarii. Isolation of Streptomyces and non-Streptomyces actinomycetes on HV medium and other specific isolation media for non-Streptomyces yielded 203 isolates from 89 soil samples. Morphological characterisation of the isolated actinomycetes was carried out based on aerial mycelium colour, substrate mycelium colour and diffusible pigment production on oatmeal medium. Nine strains of fungi were isolated from the six soil samples plated on PDA medium. All actinomycetes isolates were grown under aerobic condition in liquid culture and extracted with acetone, and used for screening against proteins involved eukaryotic signal transduction. Yeast MAPK kinase and MAP kinase phosphatase were some of the targeted proteins used in this research. MKK1P386 and MKK1P386-MSG5 mutant yeasts were used to screen for these inhibitors, as these yeast kinase and phosphatase have homologous proteins in the MAP kinase signal transduction pathway in human. No inhibitors in the extracts were found in these screenings. Type 1 protein serine/ threonine phosphatase (GLC7) in yeast was used to screen inhibitors against PP1 inhibitors and no inhibitor was found. None of the fungal extracts showed any inhibitory activities in all the screening systems. No Ras/Raf inhibitor was found in the in vivo Ras/Raf interaction with the yeast two-hybrid screening system, which used to screen for inhibitor against Ras/ Raf protein interaction inhibitor. There were 11 actinomycetes extracts that showed toxicity against yeast strain LZ (transformant of Ras/ Raf). H7667, a Streptomycete toxic to yeast is further screened for inhibitors of the GSK3-beta pathway. H7763, a Streptomyces species that showed positive in the primary screen for inhibitor of isocitrate lyase (ICL) which is not itaconic acid (known ICL inhibitor). H7240 showed the strongest susceptibility towards the resin in which the concentration of 5g/l of resin is sufficient to produce growth inhibition of the bacteria