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The underlying biophysical principle governing the cytotoxicity of the oligomeric aggregates of β-amyloid (Aβ) peptides has long been an enigma. Here we show that the size of Aβ40oligomers can be actively controlled by incubating the peptides in reverse micelles. Our approach allowed for the first time a detailed comparison of the structures and dynamics of two Aβ40oligomers of different size, viz., 10 and 23 nm, by solid-state NMR. From the chemical shift data, we infer that the conformation of the residues from K16 to K28 are different between the 10-nm and 23-nm oligomers. We find that the 10-nm oligomers are more cytotoxic, and the molecular motions of their charged residues are more dynamic. Interestingly, the residue A21 exhibits an unusually high structural rigidity. Our data raise the interesting possibility that the cytotoxicity of Aβ40oligomers could also be correlated to the motional dynamics of the charged residues.

PDF file 105K, Supplementary methods and figure legends

PDF file 2097K, Knockdown of hTOP3alpha and p53, but not BLM, reduced cellular senescence and enhanced anchorage-independent growth of AGS cells

PDF file 2053K, DNA damage-induced expression of p53, p5315P and p21 is greatly reduced in hTOP3α-deficient cells

PDF file 1548KB, hTOP3alpha regulates TP53 mRNA and p53 protein stability

PDF file 3495K, Reduced expression of hTOP3alpha in renal and stomach tumor samples compared to the matched normal tissues

Purpose: Human DNA topoisomerase III alpha (hTOP3α) is involved in DNA repair surveillance and cell-cycle checkpoints possibly through formatting complex with tumor suppressors. However, its role in cancer development remained unsolved.Experimental Design: Coimmunoprecipitation, sucrose gradient, chromatin immunoprecipitation (ChIP), real time PCR, and immunoblotting analyses were performed to determine interactions of hTOP3α with p53. Paired cell lines with different hTOP3α levels were generated via ectopic expression and short hairpin RNA (shRNA)-mediated knockdown approaches. Cellular tumorigenic properties were analyzed using cell counting, colony formation, senescence, soft agar assays, and mouse xenograft models.Results: The hTOP3α isozyme binds to p53 and cofractionizes with p53 in gradients differing from fractions containing hTOP3α and BLM. Knockdown of hTOP3α expression (sh-hTOP3α) caused a higher anchorage-independent growth of nontumorigenic RHEK-1 cells. Similarly, sh-hTOP3α and ectopic expression of hTOP3α in cancer cell lines caused increased and reduced tumorigenic abilities, respectively. Genetic and mutation experiments revealed that functional hTOP3α, p53, and p21 are required for this tumor-suppressive activity. Mechanism-wise, ChIP data revealed that hTOP3α binds to the p53 and p21 promoters and positively regulates their expression. Two proteins affect promoter recruitments of each other and collaborate in p21 expression. Moreover, sh-hTOP3α and sh-p53 in AGS cells caused a similar reduction in senescence and hTOP3α mRNA levels were lower in gastric and renal tumor samples.Conclusion: We concluded that hTOP3α interacts with p53, regulates p53 and p21 expression, and contributes to the p53-mediated tumor suppression. Clin Cancer Res; 20(6); 1489–501. ©2014 AACR.

PDF file 1796K, Forced expression of hTOP3alpha induced expression of p5315P, p21 and {gamma}H2AX, but not ATM1981P under DNA damaging-agent stimulation

Climate change shapes human migration through the interaction of environmental changes with political, social, economic, and demographic drivers of mobility. Low-and middle-income countries bear the brunt of the health impacts of climate change and migration, despite their overall low contribution to greenhouse gas emissions. The CIHLMU Symposium 2021 aimed to explore the complex interconnections between climate change, migration and health from diverse global perspectives. A number of themes, such as the relationship between climate and trade, the role of technology, and the issue of responsibility were tackled. The speakers also highlighted the need for climate resilient health-systems, gender mainstreaming in climate strategies, collaboration between the Global North and South and urgently defining the ‘climate refugee’. It is crucial that the narrative around climate change moves from an environmental framing to encompass human health and migration within climate discussions and strategies.

Extracellular accumulation of β amyloid peptides of 40 (Aβ40) and 42 residues (Aβ42) has been considered as one of the hallmarks in the pathology of Alzheimer’s disease. In this work, we are able to prepare oligomeric aggregates of Aβ with uniform size and high structural homogeneity. Our experimental design is to incubate Aβ peptides in reverse micelles (RMs) so that the peptides could aggregate only through a single nucleation process and the size of the oligomers is confined by the physical dimension of the reverse micelles. The hence obtained Aβ oligomers (AβOs) are 23 nm in diameter and they belong to the category of high molecular-weight (MW) oligomers. The solid-state NMR data revealed that Aβ40Os adopt the structural motif of β-loop-β but the chemical shifts manifested that they are structurally different from low-MW AβOs and mature fibrils. From the thioflavin-T results, we found that high-MW Aβ42Os can seed the fibrillization of Aβ40 monomers. Our protocol allows performing cross-seeding experiments among oligomeric species. By comparing the chemical shifts of Aβ40Os cross seeded by Aβ42Os and those of Aβ40Os prepared in the absence of Aβ42Os, we observed that the structures of E11, K16, and E22 were altered, whereas the backbone conformation of the β-sheet region near the C-terminus is structurally invariant. The use of reverse micelles allows hitherto the most detailed characterization of the structural variability of Aβ40Os.

Ethanol-tolerant Arthrobacter simplex is desirable since ethanol facilitates hydrophobic substrates dissolution on an industrial scale. Herein, alterations in compatible solutes were investigated under ethanol stress. The results showed that the amount of trehalose and glycerol increased while that of glutamate and proline decreased. The trehalose protectant role was verified and its concentration was positively related to the degree of cell tolerance. otsA, otsB and treS, three trehalose biosynthesis genes in A. simplex, also enhanced Escherichia coli stress tolerance, but the increased tolerance was dependent on the type and level of the stress. A. simplex strains accumulating trehalose showed a higher productivity in systems containing more ethanol and substrate because of better viability. The underlying mechanisms of trehalose were involved in better cell integrity, higher membrane stability, stronger reactive oxygen species scavenging capacity and higher energy level. Therefore, trehalose was a general protectant and the upregulation of its biosynthesis by genetic modification enhanced cell stress tolerance, consequently promoted productivity.

Helicobacter pylori neutrophil-activating protein (HP-NAP)-induced production of reactive oxygen species (ROS) by neutrophils and monocytes is regulated by pertussis toxin (PTX)-sensitive G proteins, whereas HP-NAP-induced cytokine secretion by monocytes is mediated by Toll-like receptor 2 (TLR2). However, it is unclear whether TLR2 participates in HP-NAP-induced cytokine secretion by neutrophils. Here, all-trans retinoic acid (ATRA)-induced differentiated HL-60 cells were first employed as a neutrophil model to investigate the molecular mechanisms underlying neutrophil responses to HP-NAP. HP-NAP-induced ROS production in ATRA-induced differentiated HL-60 cells is mediated by the PTX-sensitive heterotrimeric G protein-dependent activation of extracellular signal-regulated kinase 1/2 and p38-mitogen-activated protein kinase, which is consistent with the findings reported for human neutrophils. Next, whether TLR2 participated in HP-NAP-induced secretion of interleukin-8 (IL-8) was investigated in neutrophils and ATRA-induced differentiated HL-60 cells. In both cells, TLR2 participated in HP-NAP-induced IL-8 secretion but not HP-NAP-induced ROS production. Interestingly, PTX-sensitive G proteins also contributed to the HP-NAP-induced secretion of IL-8 from neutrophils and the differentiated HL-60 cells. Our ELISA-based binding assay further revealed the competitive binding of Pam3CSK4, a TLR2 agonist, and HP-NAP to TLR2, which suggests the presence of specific and direct interactions between HP-NAP and TLR2. Thus, HP-NAP directly interacts with and activates TLR2 to induce IL-8 secretion in neutrophils and ATRA-induced differentiated HL-60 cells.

Fungal predatory behavior on nematodes has evolved independently in all major fungal lineages. The basidiomycete oyster mushroom Pleurotus ostreatus is a carnivorous fungus that preys on nematodes to supplement its nitrogen intake under nutrient-limiting conditions. Its hyphae can paralyze nematodes within a few minutes of contact, but the mechanism had remained unclear. We demonstrate that the predator–prey relationship is highly conserved between multiple Pleurotus species and a diversity of nematodes. To further investigate the cellular and molecular mechanisms underlying rapid nematode paralysis, we conducted genetic screens in Caenorhabditis elegans and isolated mutants that became resistant to P. ostreatus. We found that paralysis-resistant mutants all harbored loss-of-function mutations in genes required for ciliogenesis, demonstrating that the fungus induced paralysis via the cilia of nematode sensory neurons. Furthermore, we observed that P. ostreatus caused excess calcium influx and hypercontraction of the head and pharyngeal muscle cells, ultimately resulting in rapid necrosis of the entire nervous system and muscle cells throughout the entire organism. This cilia-dependent predatory mechanism is evolutionarily conserved in Pristionchus pacificus, a nematode species estimated to have diverged from C. elegans 280 to 430 million y ago. Thus, P. ostreatus exploits a nematode-killing mechanism that is distinct from widely used anthelmintic drugs such as ivermectin, levamisole, and aldicarb, representing a potential route for targeting parasitic nematodes in plants, animals, and humans.

Resistance to the current therapies is the main clinical challenge in the treatment of lethal metastatic prostate cancer (mPCa). Developing novel therapeutic approaches with effective regimes and minimal side effects for this fatal disease remain a priority in prostate cancer study. In the present study, we demonstrated that a traditional Chinese medicine, quality-assured Ganoderma tsugae ethanol extract (GTEE), significantly suppressed cell growth and metastatic capability and caused cell cycle arrest through decreasing expression of cyclins in mPCa cells, PC-3 and DU145 cells. GTEE also induced caspase-dependent apoptosis in mPCa cells. We further showed the potent therapeutic efficacy of GTEE by inhibiting subcutaneous PC-3 tumor growth in a xenograft model. The in vitro and in vivo efficacies on mPCa cells were due to blockade of the PI3K/Akt and MAPK/ERK signaling pathways associated with cancer cell growth, survival and apoptosis. These preclinical data provide the molecular basis for a new potential therapeutic approach toward the treatment of lethal prostate cancer progression.

Conventional antitumor therapy is often complicated by the emergence of the so-called cancer stem cells (CSCs), which are characterized by low metabolic rates and high resistance to almost all existing therapies. Many problems of clinical oncology and a poor efficacy of current treatments in particular are ascribed to CSCs. Therefore, it is important to develop new compounds capable of eliminating both rapidly proliferating tumor cells and standard treatment-resistant CSCs. Curaxins have been demonstrated to manifest various types of antitumor activity. Curaxins simultaneously affect at least three key molecular cascades involved in tumor development, including the p53, NF-κB, and HSF1 metabolic pathways. In addition, studies of some curaxins indicate that they can inhibit the transcriptional induction of the genes for matrix metalloproteinases 1 and 8 (MMP1 and MMP8); the PI3K/AKT/mTOR signaling cascades; cIAP-1 (apoptosis protein 1) inhibitor activity; topoisomerase II; and a number of oncogenes, such as c-MYC and others. In vivo experiments have shown that the CSC population increases on gemcitabine monotherapy and is reduced on treatment with curaxin CBL0137. The data support the prospective use of FACT inhibitors as new anticancer drugs with multiple effects on cell metabolism.

This study examines whether an institution's research resources affect its centrality and relationships in international collaboration among 606 astronomical institutions worldwide. The findings support our theoretical hypotheses that an institution's research resources are positively related to its central position in the network. Astronomical institutions with superior resources, such as being equipped with international observational facilities and having substantial research manpower, tend to have more foreign partners high degree centrality and play an influential role high betweenness centrality in the international collaboration network. An institution becomes more and more active in international collaborations as its research population expands. In terms of the relationship, which is captured by an actor institution's co-authorship preference for each partner in the network, the effect of research resources is not as significant as expected. We found that astronomical institutions are not necessarily preferentially co-authoring with partners that have better research resources. In addition, this study indicates that geographic closeness or "geographic proximity" largely affects the occurrence of international collaboration. The investigated institutions apparently prefer partners from neighboring countries. This finding gives an indication of the phenomenon of "regional homophily" in the international collaboration network.

During transcription along nucleosomal DNA, RNA polymerase II (Pol II) pauses at multiple positions and induces formation of multiple intermediates that aid in maintaining proper chromatin structure. To describe the kinetics of this multiple-step reaction, we utilized a computational model-based approach and KinTek Explorer software to analyze the time courses. Here we describe the stepwise protocol for analysis of the kinetics of transcription through a nucleosome that provides the rate constants for each step of this complex process. We also present an example where this time-resolved approach was applied to study the mechanism of histone chaperone FACT action during Pol II transcription through a single nucleosome by comparing the rate constants derived in the presence or in the absence of FACT.

Protumor factor FACT is removed from transcribed genes by anticancer drugs curaxins., Human FACT (facilitates chromatin transcription) is a multifunctional protein complex that has histone chaperone activity and facilitates nucleosome survival and transcription through chromatin. Anticancer drugs curaxins induce FACT trapping on chromatin of cancer cells (c-trapping), but the mechanism of c-trapping is not fully understood. Here, we show that in cancer cells, FACT is highly enriched within the bodies of actively transcribed genes. Curaxin-dependent c-trapping results in redistribution of FACT from the transcribed chromatin regions to other genomic loci. Using a combination of biochemical and biophysical approaches, we have demonstrated that FACT is bound to and unfolds nucleosomes in the presence of curaxins. This tight binding to the nucleosome results in inhibition of FACT-dependent transcription in vitro in the presence of both curaxins and competitor chromatin, suggesting a mechanism of FACT trapping on bulk nucleosomes (n-trapping).

FAcilitates Chromatin Transcription (FACT) has been considered essential for transcription through chromatin mostly based on cell-free experiments. However, FACT inactivation in cells does not cause a significant reduction in transcription. Moreover, not all mammalian cells require FACT for viability. Here we synthesize information from different organisms to reveal the core function(s) of FACT and propose a model that reconciles the cell-free and cell-based observations. We describe FACT structure and nucleosomal interactions, and their roles in FACT-dependent transcription, replication and repair. The variable requirements for FACT among different tumor and non-tumor cells suggests that various FACT-dependent processes have significantly different levels of relative importance in different eukaryotic cells. We propose that the stability of chromatin, which might vary among different cell types, dictates these diverse requirements for FACT to support cell viability. Since tumor cells are among the most sensitive to FACT inhibition, this vulnerability could be exploited for cancer treatment.

Efficient overcoming of the nucleosomal barrier and accurate maintenance of associated histone marks during chromatin replication are essential for normal functioning of the cell. Recent studies revealed new protein factors and histone modifications contributing to overcoming the nucleosomal barrier, and suggested an important role for DNA looping in survival of the original histones during replication. These studies suggest new possible mechanisms for transmitting the histone code to next generations of cells.

This study employs social network analysis to identify institutions with strong international collaborative relationships in astronomical research. We find that the strongest ties tend to link institutions across continents in research collaboration. However, the effect of geographic factors is still notable in light of the fact that most of the institutions in the largest subgroup are located in Europe. Examination of the network position, measured by degree centrality, indicates that homophily is more common than heterophily in the network. A relatively high number of relational ties are observed among institutions that have similar levels of network centrality. Mutual relations are prevalent among central institutions, while strong mutual solidarity exists between institutions on the periphery of the network. This study shows a general unstable international collaborative relationship among astronomical institutions. While more and more institutions have linked up in research collaboration, many of them keep relatively weak ties. Institutions tend not remain in the same subgroup, but link to different partners over time.

Purpose: Human DNA topoisomerase III alpha (hTOP3α) is involved in DNA repair surveillance and cell-cycle checkpoints possibly through formatting complex with tumor suppressors. However, its role in cancer development remained unsolved. Experimental Design: Coimmunoprecipitation, sucrose gradient, chromatin immunoprecipitation (ChIP), real time PCR, and immunoblotting analyses were performed to determine interactions of hTOP3α with p53. Paired cell lines with different hTOP3α levels were generated via ectopic expression and short hairpin RNA (shRNA)-mediated knockdown approaches. Cellular tumorigenic properties were analyzed using cell counting, colony formation, senescence, soft agar assays, and mouse xenograft models. Results: The hTOP3α isozyme binds to p53 and cofractionizes with p53 in gradients differing from fractions containing hTOP3α and BLM. Knockdown of hTOP3α expression (sh-hTOP3α) caused a higher anchorage-independent growth of nontumorigenic RHEK-1 cells. Similarly, sh-hTOP3α and ectopic expression of hTOP3α in cancer cell lines caused increased and reduced tumorigenic abilities, respectively. Genetic and mutation experiments revealed that functional hTOP3α, p53, and p21 are required for this tumor-suppressive activity. Mechanism-wise, ChIP data revealed that hTOP3α binds to the p53 and p21 promoters and positively regulates their expression. Two proteins affect promoter recruitments of each other and collaborate in p21 expression. Moreover, sh-hTOP3α and sh-p53 in AGS cells caused a similar reduction in senescence and hTOP3α mRNA levels were lower in gastric and renal tumor samples. Conclusion: We concluded that hTOP3α interacts with p53, regulates p53 and p21 expression, and contributes to the p53-mediated tumor suppression. Clin Cancer Res; 20(6); 1489–501. ©2014 AACR.

Resistance to the current therapies is the main clinical challenge in the treatment of lethal metastatic prostate cancer (mPCa). Developing novel therapeutic approaches with effective regimes and minimal side effects for this fatal disease remain a priority in prostate cancer study. In the present study, we demonstrated that a traditional Chinese medicine, quality-assured Ganoderma tsugae ethanol extract (GTEE), significantly suppressed cell growth and metastatic capability and caused cell cycle arrest through decreasing expression of cyclins in mPCa cells, PC-3 and DU145 cells. GTEE also induced caspase-dependent apoptosis in mPCa cells. We further showed the potent therapeutic efficacy of GTEE by inhibiting subcutaneous PC-3 tumor growth in a xenograft model. The in vitro and in vivo efficacies on mPCa cells were due to blockade of the PI3K/Akt and MAPK/ERK signaling pathways associated with cancer cell growth, survival and apoptosis. These preclinical data provide the molecular basis for a new potential therapeutic approach toward the treatment of lethal prostate cancer progression.

Maintenance of nucleosomal structure in the cell nuclei is essential for cell viability, regulation of gene expression and normal aging. Our previous data identified a key intermediate (a small intranucleosomal DNA loop, Ø-loop) that is likely required for nucleosome survival during transcription by RNA polymerase II (Pol II) through chromatin, and suggested that strong nucleosomal pausing guarantees efficient nucleosome survival. To evaluate these predictions, we analysed transcription through a nucleosome by different, structurally related RNA polymerases and mutant yeast Pol II having different histone-interacting surfaces that presumably stabilize the Ø-loop. The height of the nucleosomal barrier to transcription and efficiency of nucleosome survival correlate with the net negative charges of the histone-interacting surfaces. Molecular modeling and analysis of Pol II-nucleosome intermediates by DNase I footprinting suggest that efficient Ø-loop formation and nucleosome survival are mediated by electrostatic interactions between the largest subunit of Pol II and core histones.

The study explores the international collaboration network consisting of 606 astronomical institutions through the analysis of international coauthored papers published in six journals in astronomy and astrophysics from 2001 to 2009. It shows that the Istituto Nazionale di Astrofisica (INAF) and European Southern Observatory (ESO) are the most notable actors, with the highest values of centrality in the network, while Japan Meteorological Agency (JMA) is the only institution that is completely separated from others. It is observed that national academies in major countries, international organizations, and large observatories are more likely to be the central actors. Yet some world-famous astronomical institutions, such as CfA, NASA, and Caltech, are identified as remarkable actors in the network, they show no strikingly high scores in the centrality measures. Overall, astronomical institutions' network position varies with time; nevertheless, not all of institutions present considerable changes during the investigation periods. While some institutions moved from central to relative peripheral positions, or in the opposite direction, the institutions which are positioned at the very center of the network tend to be stable over time.

Nucleosomes present a strong, sequence-dependent barrier for moving replisomes and can survive during DNA replication in vitro., Efficient overcoming and accurate maintenance of chromatin structure and associated histone marks during DNA replication are essential for normal functioning of the daughter cells. However, the molecular mechanisms of replication through chromatin are unknown. We have studied traversal of uniquely positioned mononucleosomes by T7 replisome in vitro. Nucleosomes present a strong, sequence-dependent barrier for replication, with particularly strong pausing of DNA polymerase at the +(31–40) and +(41–65) regions of the nucleosomal DNA. The exonuclease activity of T7 DNA polymerase increases the overall rate of progression of the replisome through a nucleosome, likely by resolving nonproductive complexes. The presence of nucleosome-free DNA upstream of the replication fork facilitates the progression of DNA polymerase through the nucleosome. After replication, at least 50% of the nucleosomes assume an alternative conformation, maintaining their original positions on the DNA. Our data suggest a previously unpublished mechanism for nucleosome maintenance during replication, likely involving transient formation of an intranucleosomal DNA loop.

This study investigates the trend of global concentration in scientific research and technological innovation around the world. It accepts papers and patents as appropriate data for revealing the development and status of science and technology respectively. The performance of these outputs in production and citation impact is taken into consideration in the analysis. The findings suggest that both papers and patents are geographically concentrated on a small number of countries, including the United States, the United Kingdom, Japan, Germany, and France. China has made great progress in paper production and citation impact, and Taiwan and Korea have experienced a rapid growth in patents over the past years. The degree of concentration dramatically decreases when the data from the United States are excluded, indicating the effects of the U.S.’s participation on the concentration. Patents show a higher degree of concentration than papers. With time-varying aspects taken into consideration, the study indicates that the degree of concentration of papers and patents has gradually decreased over time. The concentration of patents has declined more slowly than that of papers. This decrease of the concentration is mainly due to the reduction of the predominant role of the U.S. in world R&D output.

The present study analyzes bibliometric characteristics of Taiwan's highly cited papers published from 2000 to 2009. During this period, Taiwan ranked within the top 30 countries by number of highly cited papers, defined in Thomson Reuters' Essential Science Indicators (ESI) as those that rank in the top 1 % by citations for their category and year of publication. Taiwan made notable progress in world-class research in the two consecutive 5-year periods 2000---2004 and 2005---2009. For the group of highly cited papers from Taiwan, USA, China, Germany, and Japan were the top collaborating countries over the decade. In recent years, Taiwan has increasingly collaborated with European countries whose output of highly cited papers is relatively high and increasing, rather than with its neighboring countries in Asia. Overall, Taiwan produced highly cited papers in all the 22 ESI subject categories during the 10-year period. Taiwan's output of highly cited papers was greatest in the categories of Engineering, Clinical Medicine, and Physics, while those in Agricultural Sciences and Mathematics exceeded the expected output level in relative terms. More detailed analyses would be useful for a holistic understanding of Taiwan's research landscape and their progress in world-class research, combining both bibliometric and non-bibliometric data, such as researcher mobility, research grants, and output from internationally-collaborated research programs.

Both Al–Zn alloy and Mg–Al–Zn alloy are considered as high damping and light materials. This study investigated the effects of the structure and the composition on the vibration fracture characteristics of the Al–xZn alloy and the Mg–xAl–Zn alloy under resonance. For Al–xZn (x = 7, 11, 49, and 83 wt.%) alloys, under both constant force and initial-deflection conditions, the 7Zn specimen showed the greatest vibration life. For Mg–xAl–Zn (x = 3, 6, and 9 wt.%) alloys, experimental results indicate that the AZ31-F as-extruded samples showed a greater vibration life, while high Al fully annealed samples (AZ91-O) had greater vibration fracture resistance under constant force conditions.

Background Helicobacter pylori neutrophil-activating protein (HP-NAP) is involved in H. pylori-induced gastric inflammation. Due to its immunogenic and immunomodulatory properties, HP-NAP has been used for developing vaccines against H. pylori infection and new drugs for cancer therapy. Results Here, we provide a simple process for high-yield production of HP-NAP by applying one-step negative chromatography to purify recombinant HP-NAP expressed in Escherichia coli (E. coli). In our E. coli expression system, recombinant HP-NAP constitutes nearly 70% of the total protein. Overexpressed recombinant HP-NAP is almost completely soluble upon cell lysis at pH 9.5. Under the optimal condition at pH 8.0, recombinant HP-NAP with purity higher than 95% can be obtained from E. coli by collecting the unbound fraction using diethylaminoethyl (DEAE) Sephadex resin in batch mode. The overall yield of HP-NAP from a 50-ml E. coli culture is ~19 mg. The purified HP-NAP folds into a multimer with a secondary structure of α-helix and is able to trigger the production of reactive oxygen species by neutrophils. Conclusions Purification of recombinant HP-NAP overexpressed in E. coli using DEAE Sephadex negative mode batch chromatography is an efficient method for high-yield production of highly pure HP-NAP in its native state. The purified HP-NAP is useful for various clinical applications including vaccine development, diagnosis, and new drug development.

Both Al-Zn alloy and Mg-Al-Zn alloy have been considered as high damping and light materials. For practical use, this study investigated the effects of the structure and the composition on the vibration fracture characteristics of the Al-xZn alloy and the Mg-xAl-Zn alloy under resonance. For Al-xZn (x=7, 11, 49, 83wt%) alloys, under both constant force and initial-deflection conditions, the 7Zn showed the greatest vibration life. For Mg-xAl-Zn (x=3, 6, 9wt%) alloys, experimental results indicate that the AZ31-F as-extruded samples showed a greater vibration life, while high Al fully-annealed samples (AZ91-O) had greater vibration fracture resistance under constant force conditions.

Publications have been regarded as the most significant output indicating the research performance of universities. This paper uses ISI Essential Science Indicators (ESI) database to investigate the academic performance of research-oriented universities in Taiwan, adopting the bibliometric method from both quantitative and qualitative perspectives. The data cover the time span for 11 years from 1993 to 2003. The performance indicators applied in this study includes the number of papers, the number of citations, the average citations per paper, the number of highly cited papers, the number of hot papers, and the number of top papers. The research performance and the strength of those universities are revealed in this study, and it is found that National Taiwan University leads among these universities though each university still shows strengths in various specific fields.

This study investigated the vibration fracture behavior of two Mg–Zn–Al alloys, AZ31 and AZ61 in as-extruded and as-annealed states. The effects of deformation twins, precipitates and Al concentration on vibration properties were examined. As-extruded AZ31 specimens showed a longer vibration life than the others, mainly because of better damping capacity and a lack of intergranular Mg17Al12 precipitates.

This paper uses United States patent classification analysis to study the development of core technologies and key industries in Taiwan over the last 25 years, from 1978 to 2002. After counting the number of Taiwan-held United States granted utility patents, the authors divide the years into three phases: from 1978 to 1994, with less than 500 patents each year; from 1995 to 1999, with 500-2,500 patents each year; from 2000 to 2002, with annual patents greater than 2,500. The results show that for both Taiwan’s core technologies and key industries, there was a great diversity at the first phase, while a mainstream forms and matures at the second and the third phases. However, industrial development at the third phase was more concentrated and focused than previous ones. Overall, Taiwan has clearly moved from a manufacturing-based economy to an innovation-based one, with its focus on high-tech industries during the previous 25 years.

Efficient maintenance of chromatin structure during passage of RNA polymerase II (Pol II) is critical for cell survival and functioning. Moderate-level transcription of eukaryotic genes by Pol II is accompanied by nucleosome survival, extensive exchange of histones H2A/H2B and minimal exchange of histones H3/H4. Complementary in vitro studies have shown that transcription through chromatin by single Pol II complexes is uniquely coupled with nucleosome survival via formation of a small intranucleosomal DNA loop (O-loop) containing the transcribing enzyme. In contrast, transient displacement and exchange of all core histones are observed during intense transcription. Indeed, multiple transcribing Pol II complexes can efficiently overcome the high nucleosomal barrier and displace the entire histone octamer in vitro. Thus, various Pol II complexes can remodel chromatin to different extents. The mechanisms of nucleosome survival and displacement during transcription and the role of DNA-histone interactions and various factors during this process are discussed. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.

Context-aware systems in smart space environments must be aware of the context of their surroundings and adapt to changes in highly dynamic environments. Data management of contextual information is different from traditional approaches because the contextual information is dynamic, transient, and fallible in nature. Consequently, the capability to detect context inconsistency and maintain consistent contextual information are two key issues for context management. We propose an ontology-based model for representing, deducing, and managing consistent contextual information. In addition, we use ontology reasoning to detect and resolve context inconsistency problems, which will be described in a Smart Alarm Clock scenario.

In an urban area, the demand for taxis is not always matched up with the supply. This paper proposes mining historical data to predict demand distributions with respect to contexts of time, weather, and taxi location. The four-step process consists of data filtering, clustering, semantic annotation, and hotness calculation. The results of three clustering algorithms are compared and demonstrated in a web mash-up application to show that context-aware demand prediction can help improve the management of taxi fleets.