Naresuan University Journal
Not a member yet
39887 research outputs found
Sort by
The role of recovered envelope cues in the identification of temporal-fine-structure speech for hearing-impaired listeners
No full textNarrowband speech can be separated into fast temporal cues [temporal fine structure (TFS)], and slow amplitude modulations (envelope). Speech processed to contain only TFS leads to envelope recovery through cochlear filtering, which has been suggested to account for TFS-speech intelligibility for normal-hearing listeners. Hearing-impaired listeners have deficits with TFS-speech identification, but the contribution of recovered-envelope cues to these deficits is unknown. This was assessed for hearing-impaired listeners by measuring identification of disyllables processed to contain TFS or recovered-envelope cues. Hearing-impaired listeners performed worse than normal-hearing listeners, but TFS-speech intelligibility was accounted for by recovered-envelope cues for both groups
Au-catalyzed cross-coupling of arenes via double C–H activation
No full textThe first methodology for Au(I/III)-catalyzed oxidative cross-coupling of arenes via double C–H activation has been developed. The reaction is fully selective for the cross-coupling between electron-rich hetero-/carbocyclic arenes and electron-poor arenes bearing relatively acidic C–H bonds. The inherently high cross-selectivity of the system obviates the need for directing groups or a large excess of one of the coupling partners
The Quality of the Evidence According to GRADE Is Predominantly Low or Very Low in Oral Health Systematic Reviews.
No full textOBJECTIVES: The main objective was to assess the credibility of the evidence using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in oral health systematic reviews on the Cochrane Database of Systematic Reviews (CDSR) and elsewhere. STUDY DESIGN AND SETTING: Systematic Reviews or meta-analyses (January 2008-December 2013) from 14 high impact general dental and specialty dental journals and the Cochrane Database of Systematic Reviews were screened for meta-analyses. Data was collected at the systematic review, meta-analysis and trial level. Two reviewers applied and agreed on the GRADE rating for the selected meta-analyses. RESULTS: From the 510 systematic reviews initially identified 91 reviews (41 Cochrane and 50 non-Cochrane) were eligible for inclusion. The quality of evidence was high in 2% and moderate in 18% of the included meta-analyses with no difference between Cochrane and non-Cochrane reviews, journal impact factor or year of publication. The most common domains prompting downgrading of the evidence were study limitations (risk of bias) and imprecision (risk of play of chance). CONCLUSION: The quality of the evidence in oral health assessed using GRADE is predominantly low or very low suggesting a pressing need for more randomised clinical trials and other studies of higher quality in order to inform clinical decisions thereby reducing the risk of instituting potentially ineffective and/or harmful therapies
Commitments of Debt: Temporality and the Meanings of Aid Work in a Japanese NGO in Myanmar
No full textThe rise of debt as a mechanism of development troubles many scholars and aid practitioners. Contrary to these concerns, however, ethnographic research at a Japanese NGO in Myanmar showed that Japanese and Burmese aid workers found value in moral and monetary debt relations. In this article, I argue that these aid workers viewed indebtedness as a precondition for the making of voluntary actors, willing and committed to aid work. What they problematized was not indebtedness but, rather, competing understandings of the appropriate temporality of a debt’s repayment. The fault lines did not appear along cultural or moral-monetary boundaries; they existed in the ways that people conceptualized voluntary actors as emerging from either long-term forms of indebted gratitude or sequences of short-term contractual agreements. While the entrapment of the poor in cycles of debt remains an increasing concern in the world, I here ask how we might understand local aid workers’ professional commitments when they do not question indebtedness as a moral framework. [NGO, debt, gratitude, temporality, commitment,Myanmar
Photoactive composite films prepared from mixtures of polystyrene microgel dispersions and poly(3-hexylthiophene) solutions
No full textDoxycycline down-regulates DNA-PK and radiosensitizes tumor initiating cells: Implications for more effective radiation therapy.
No full textDNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by "chemical proteomics". In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline reduces DNA-PK protein expression by nearly 15-fold (> 90%). In accordance with these observations, we show that doxycycline functionally radio-sensitizes breast CSCs, by up to 4.5-fold. Moreover, we demonstrate that DNA-PK is highly over-expressed in both MCF7- and T47D-derived mammospheres. Interestingly, genetic or pharmacological inhibition of DNA-PK in MCF7 cells is sufficient to functionally block mammosphere formation. Thus, it appears that active DNA-repair is required for the clonal expansion of CSCs. Mechanistically, doxycycline treatment dramatically reduced the oxidative mitochondrial capacity and the glycolytic activity of cancer cells, consistent with previous studies linking DNA-PK expression to the proper maintenance of mitochondrial DNA integrity and copy number. Using a luciferase-based assay, we observed that doxycycline treatment quantitatively reduces the anti-oxidant response (NRF1/2) and effectively blocks signaling along multiple independent pathways normally associated with stem cells, including STAT1/3, Sonic Hedgehog (Shh), Notch, WNT and TGF-beta signaling. In conclusion, we propose that the efficacy of doxycycline as a DNA-PK inhibitor should be tested in Phase-II clinical trials, in combination with radio-therapy. Doxycycline has excellent pharmacokinetics, with nearly 100% oral absorption and a long serum half-life (18-22 hours), at a standard dose of 200-mg per day. In further support of this idea, we show that doxycycline effectively inhibits the mammosphere-forming activity of primary breast cancer samples, derived from metastatic disease sites (pleural effusions or ascites fluid). Our results also have possible implications for the radio-therapy of brain tumors and/or brain metastases, as doxycycline is known to effectively cross the blood-brain barrier. Further studies will be needed to determine if other tetracycline family members also confer radio-sensitivity
Precise measurements of the properties of the and states and observation of mass structures
No full text
Metabolomics investigation of recombinant mTNFaα production in Streptomyces lividans
No full textBACKGROUND: Whilst undergoing differentiation, Streptomyces produce a large quantity of hydrolytic enzymes and secondary metabolites, and it is this very ability that has focussed increasing interest on the use of these bacteria as hosts for the production of various heterologous proteins. However, within this genus, the exploration and understanding of the metabolic burden associated with such bio-products has only just begun. In this study our overall aim was to apply metabolomics approaches as tools to get a glimpse of the metabolic alterations within S. lividans TK24 when this industrially relevant microbe is producing recombinant murine tumour necrosis factor alpha (mTNFα), in comparison to wild type and empty (non-recombinant protein containing) plasmid-carrying strains as controls.\n\nRESULTS: Whilst growth profiles of all strains demonstrated comparable trends, principal component-discriminant function analysis of Fourier transform infrared (FT-IR) spectral data, showed clear separation of wild type from empty plasmid and mTNFα-producing strains, throughout the time course of incubation. Analysis of intra- and extra-cellular metabolic profiles using gas chromatography-mass spectrometry (GC-MS) displayed similar trends to the FT-IR data. Although the strain carrying the empty plasmid demonstrated metabolic changes due to the maintenance of the plasmid, the metabolic behaviour of the recombinant mTNFα-producing strain appeared to be the most significantly affected. GC-MS results also demonstrated a significant overflow of several organic acids (pyruvate, 2-ketoglutarate and propanoate) and sugars (xylitol, mannose and fructose) in the mTNFα-producing strain.\n\nCONCLUSION: The results obtained in this study have clearly demonstrated the metabolic impacts of producing mTNFα in S. lividans TK24, while displaying profound metabolic effects of harbouring the empty PIJ486 plasmid. In addition, the level of mTNFα produced in this study, further highlights the key role of media composition towards the efficiency of a bioprocess and metabolic behaviour of the host cells, which directly influences the yield of the recombinant product
