Proactive measures of governmental debt guarantees to facilitate Public-Private Partnerships project

Governmental Debt Guarantees (GDGs) are often used to encourage involvement by promoters and financial institutions in Public-Private Partnerships (PPP) projects. However, even after demonstrating the bankability of a project and reducing debt cost, the success of the project may be prevented by the lack of long-term commitment from shareholders. Equity contributions by promoters in the project company may be recovered from earnings on short-term construction activities. Based on lesson learned from early PPP projects with GDG, the hold-up problem for government in the view of transaction cost economic (TCE) theory may worsen if the designed contractual structure does not adequately manage opportunistic behaviours from promoters. This study empirically examined the effects of a structured GDG mechanism with particular complementary measures applied in joint projects to develop the Taipei Mass Rapid Transit (MRT) stations. A GDG game model was then applied to bridge the theoretical gap based on the Taipei MRT experience. The analysis shows that requiring the promoter to provide sufficient equity and ensuring the commitment of the lender to provide the loan are the appropriate proactive measures. This study demonstrates its practical value for policy makers by combining case study, TCE and game theory in contractual issues

Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectional promoter in an evolutionarily conserved manner

BACKGROUND: Despite of the fact that mammalian genomes are far more spacious than prokaryotic genomes, recent nucleotide sequencing data have revealed that many mammalian genes are arranged in a head-to-head orientation and separated by a small intergenic sequence. Extensive studies on some of these neighboring genes, in particular homologous gene pairs, have shown that these genes are often co-expressed in a symmetric manner and regulated by a shared promoter region. Here we report the identification of two non-homologous brain disease-related genes, with one coding for a serine protease inhibitor (SERPINI1) and the other for a programmed cell death-related gene (PDCD10), being tightly linked together by an asymmetric bidirectional promoter in an evolutionarily conserved fashion. This asymmetric bidirectional promoter, in cooperation with some cis-acting elements, is responsible for the co-regulation of the gene expression pattern as well as the tissue specificity of SERPINI1 and PDCD10. RESULTS: While SERPINI1 is predominantly expressed in normal brain and down-regulated in brain tumors, PDCD10 is ubiquitously expressed in all normal tissues but its gene transcription becomes aberrant in different types of cancers. By measuring the luciferase activity in various cell lysates, their 851-bp intergenic sequence was shown to be capable of driving the reporter gene expression in either direction. A 175-bp fragment from nt 1 to 175 in the vicinity of PDCD10 was further determined to function as a minimal bidirectional promoter. A critical regulatory fragment, from nt 176-473 outside the minimal promoter in the intergenic region, was identified to contain a strong repressive element for SERPINI1 and an enhancer for PDCD10. These cis-acting elements may exist to help coordinate the expression and regulation of the two flanking genes. CONCLUSION: For all non-homologous genes that have been described to be closely adjacent in the mammalian genomes, the intergenic region of the head-to-head PDCD10-SERPINI1 gene pair provides an interesting and informative example of a complex regulatory system that governs the expression of both genes not only through an asymmetric bidirectional promoter, but also through fine-tuned regulations with some cis-acting elements

Occupational hand dermatitis among cement workers in Taiwan

Background/PurposeOccupational dermatitis among cement workers is a major occupational health concern. The two most important occupational hazards for cement workers are irritant and allergic cement contact dermatitis. The objective of this study was to investigate the severity of occupational cement contact dermatitis and the common allergens among cement workers in Taiwan.MethodsA total of 97 cement workers from the Cement Workers’ Association of Tainan City and County participated in this study. A structured questionnaire was used to evaluate the demographic data and work-related activities of these cement workers. A complete skin examination was conducted, and skin manifestations were assessed by a dermatologist. Allergens from European Standard Tray (Chemotechnique Diagnostic AB, Sweden) with a total of 25 substances were used for patch testing.ResultsOur results showed that 65 out of 97 cement workers were suffering from occupational cement hand contact dermatitis. The most affected skin area was the hand. Thickening of the dorsal surface of the hand, especially around the metacarpophalangeal joint area, and hyperkeratosis of the palm were the major skin manifestations. The results of the patch test showed that 24 out of 97 were allergic to potassium dichromate, nine were allergic to thiuram mix, nine were allergic to fragrance mix and seven were allergic to cobalt chloride. The final diagnosis, based on the results of the skin examination and the patch test, showed that 43 of 97 cement workers had irritant cement contact dermatitis and 22 had allergic cement contact dermatitis.ConclusionWe conclude that occupational cement hand dermatitis among cement workers is an important and severe issue in Taiwan, and the most common allergens among cement workers are potassium dichromate, thiuram mix, fragrance mix and cobalt chloride. The high positive rate of chromium hypersensitivity among cement workers reflects the urgency to regulate the addition of ferrous sulfate to cement in Taiwan

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR

Organic Electrochemical Transistors/SERS-Active Hybrid Biosensors Featuring Gold Nanoparticles Immobilized on Thiol-Functionalized PEDOT Films

In this study we immobilized gold nanoparticles (AuNPs) onto thiol-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) films as bioelectronic interfaces (BEIs) to be integrated into organic electrochemical transistors (OECTs) for effective detection of dopamine (DA) and also as surface-enhanced Raman scattering (SERS)—active substrates for the selective detection of p-cresol (PC) in the presence of multiple interferers. This novel PEDOT-based BEI device platform combined (i) an underlying layer of polystyrenesulfonate-doped PEDOT (PEDOT:PSS), which greatly enhanced the transconductance and sensitivity of OECTs for electrochemical sensing of DA in the presence of other ascorbic acid and uric acid metabolites, as well as amperometric response toward DA with a detection limit (S/N = 3) of 37 nM in the linear range from 50 nM to 100 μM; with (ii) a top interfacial layer of AuNP-immobilized three-dimensional (3D) thiol-functionalized PEDOT, which not only improved the performance of OECTs for detecting DA, due to the signal amplification effect of the AuNPs with high catalytic activity, but also enabled downstream analysis (SERS detection) of PC on the same chip. We demonstrate that PEDOT-based 3D OECT devices decorated with a high-density of AuNPs can display new versatility for the design of next-generation biosensors for point-of-care diagnostics

The histone H3K36 demethylase Rph1/KDM4 regulates the expression of the photoreactivation gene PHR1

The dynamics of histone methylation have emerged as an important issue since the identification of histone demethylases. We studied the regulatory function of Rph1/KDM4 (lysine demethylase), a histone H3K36 demethylase, on transcription in Saccharomyces cerevisiae. Overexpression of Rph1 reduced the expression of PHR1 and increased UV sensitivity. The catalytically deficient mutant (H235A) of Rph1 diminished the repressive transcriptional effect on PHR1 expression, which indicates that histone demethylase activity contributes to transcriptional repression. Chromatin immunoprecipitation analysis demonstrated that Rph1 was associated at the upstream repression sequence of PHR1 through zinc-finger domains and was dissociated after UV irradiation. Notably, overexpression of Rph1 and H3K36A mutant reduced histone acetylation at the URS, which implies a crosstalk between histone demethylation and acetylation at the PHR1 promoter. In addition, the crucial checkpoint protein Rad53 acted as an upstream regulator of Rph1 and dominated the phosphorylation of Rph1 that was required for efficient PHR1 expression and the dissociation of Rph1. The release of Rph1 from chromatin also required the phosphorylation at S652. Our study demonstrates that the histone demethylase Rph1 is associated with a specific chromatin locus and modulates histone modifications to repress a DNA damage responsive gene under control of damage checkpoint signaling