Continuous-wave Cascaded-Harmonic Generation and Multi-Photon Raman Lasing in Lithium Niobate Whispering-Gallery Resonators

We report experimental demonstration of continuous-wave cascaded-harmonic generation and Raman lasing in a millimeter-scale lithium niobate whispering-gallery resonator pumped at a telecommunication-compatible infrared wavelength. Intensity enhancement through multiple recirculations in the whispering-gallery resonator and quasi phase-matching through a nonuniform crystal poling enable simultaneous cascaded-harmonic generation up to the fourth-harmonic accompanied by stimulated Raman, two-photon, three-photon, and four-photon Raman scattering corresponding the molecular vibrational wavenumbers 632 cm-1 and 255 cm-1 in z-cut lithium niobate at pump power levels as low as 200mW. We demonstrate simultaneous cascaded-harmonic generation and Raman lasing by observing the spectrum of the scattered light from the resonator and by capturing the image of the decoupled light from the resonator on a color CCD camera

CCAAT/Enhancer Binding Protein alpha uses distinct domains to prolong pituitary cells in the Growth 1 and DNA Synthesis phases of the cell cycle

BACKGROUND: A number of transcription factors coordinate differentiation by simultaneously regulating gene expression and cell proliferation. CCAAT/enhancer binding protein alpha (C/EBPα) is a basic/leucine zipper transcription factor that integrates transcription with proliferation to regulate the differentiation of tissues involved in energy balance. In the pituitary, C/EBPα regulates the transcription of a key metabolic regulator, growth hormone. RESULTS: We examined the consequences of C/EBPα expression on proliferation of the transformed, mouse GHFT1-5 pituitary progenitor cell line. In contrast to mature pituitary cells, GHFT1-5 cells do not contain C/EBPα. Ectopic expression of C/EBPα in the progenitor cells resulted in prolongation of both growth 1 (G1) and the DNA synthesis (S) phases of the cell cycle. Transcription activation domain 1 and 2 of C/EBPα were required for prolongation of G1, but not of S. Some transcriptionally inactive derivatives of C/EBPα remained competent for G1 and S phase prolongation. C/EBPα deleted of its leucine zipper dimerization functions was as effective as full-length C/EBPα in prolonging G1 and S. CONCLUSION: We found that C/EBPα utilizes mechanistically distinct activities to prolong the cell cycle in G1 and S in pituitary progenitor cells. G1 and S phase prolongation did not require that C/EBPα remained transcriptionally active or retained the ability to dimerize via the leucine zipper. G1, but not S, arrest required a domain overlapping with C/EBPα transcription activation functions 1 and 2. Separation of mechanisms governing proliferation and transcription permits C/EBPα to regulate gene expression independently of its effects on proliferation

Drug and Cell Type-Specific Regulation of Genes with Different Classes of Estrogen Receptor β-Selective Agonists

Estrogens produce biological effects by interacting with two estrogen receptors, ERα and ERβ. Drugs that selectively target ERα or ERβ might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERβ-selective compounds have been identified. One class of ERβ-selective agonists is represented by ERB-041 (WAY-202041) which binds to ERβ much greater than ERα. A second class of ERβ-selective agonists derived from plants include MF101, nyasol and liquiritigenin that bind similarly to both ERs, but only activate transcription with ERβ. Diarylpropionitrile represents a third class of ERβ-selective compounds because its selectivity is due to a combination of greater binding to ERβ and transcriptional activity. However, it is unclear if these three classes of ERβ-selective compounds produce similar biological activities. The goals of these studies were to determine the relative ERβ selectivity and pattern of gene expression of these three classes of ERβ-selective compounds compared to estradiol (E2), which is a non-selective ER agonist. U2OS cells stably transfected with ERα or ERβ were treated with E2 or the ERβ-selective compounds for 6 h. Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERβ-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile. FRET analysis showed that all compounds induced a similar conformation of ERβ, which is consistent with the finding that most genes regulated by the ERβ-selective compounds were similar to each other and E2. However, there were some classes of genes differentially regulated by the ERβ agonists and E2. Two ERβ-selective compounds, MF101 and liquiritigenin had cell type-specific effects as they regulated different genes in HeLa, Caco-2 and Ishikawa cell lines expressing ERβ. Our gene profiling studies demonstrate that while most of the genes were commonly regulated by ERβ-selective agonists and E2, there were some genes regulated that were distinct from each other and E2, suggesting that different ERβ-selective agonists might produce distinct biological and clinical effects

Tuning intermolecular interactions in di-octyl substituted polyfluorene via hydrostatic pressure

Polyfluorenes (PFs) represent a unique class of poly para-phenylene based blue-emitting polymers with intriguing structure-property relationships. Slight variations in the choice of functionalizing side chains result in dramatic differences in the inter- and intra-chain structures in PFs. We present photoluminescence (PL) and Raman scattering studies of bulk samples and thin films of dioctyl-substituted PF (PF8) under hydrostatic pressure. The bulk sample was further thermally annealed at 1.9 GPa. The PL vibronics of the as-is sample red-shift at an average rate of 26 meV/GPa. The thermally annealed sample is characterized by at least two phase transitions at 1.1 GPa and 4.2 GPa, each of which has a different pressure coefficient for PL vibronics. The Huang-Rhys factor, a measure of the electron-phonon interaction, is found to increase with increasing pressures signaling a higher geometric relaxation of the electronic states. The Raman peaks harden with increasing pressures; the intra-ring C-C stretch frequency at 1600 cm$^{-1}$ has a pressure coefficient of 7.2 cm$^{-1}$/GPa and exhibits asymmetric line shapes at higher pressures, characteristic of a strong electron-phonon interaction. The optical properties of PF8 under high pressure are further contrasted with those of a branched side chain substituted PF.Comment: 22 pages, 10 figure

Exercise and manual auricular acupuncture: a pilot assessor-blind randomised controlled trial. (The acupuncture and personalised exercise programme (APEP) Trial)

<p>Abstract</p> <p>Background</p> <p>Evidence supports the use of exercise for chronic low back pain (CLBP); however, adherence is often poor due to ongoing pain. Auricular acupuncture is a form of pain relief involving the stimulation of points on the outer ear corresponding with specific body parts. It may be a useful adjunct to exercise in managing CLBP; however, there is only limited evidence to support its use with this patient group.</p> <p>Methods/Design</p> <p>This study was designed to test the feasibility of an assessor-blind randomised controlled trial which assess the effects on clinical outcomes and exercise adherence of adding manual auricular acupuncture to a personalised and supervised exercise programme (PEP) for CLBP. No sample size calculation has been carried out as this study aims to identify CLBP referral rates within the catchment area of the study site. The researchers aim to recruit four cohorts of n = 20 participants to facilitate a power analysis for a future randomised controlled trial. A computer generated random allocation sequence will be prepared centrally and used to allocate participants by cohort to one of the following interventions: 1) six weeks of PEP <it>plus </it>manual auricular acupuncture; 2) six weeks of PEP alone. Both groups will also complete a further six weeks of self-paced exercise with telephone follow-up support. In addition to a baseline and exit questionnaire at the beginning and end of the study, the following outcomes will be collected at baseline, and after 7, 13 and 25 weeks: pain frequency and bothersomeness, back-specific function, objective assessment and recall of physical activity, use of analgesia, perceived self-efficacy, fear avoidance beliefs, and beliefs about the consequences of back pain. Since this is a feasibility study, significance tests will not be presented, and treatment effects will be represented by point estimates and confidence intervals. For each outcome variable, analysis of covariance will be performed on the data, conditioning on the baseline value.</p> <p>Discussion</p> <p>The results of this study investigating the adjuvant effects of auricular acupuncture to exercise in managing CLBP will be used to inform the design of a future multi-centre randomised controlled trial.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN94142364.</p

RNA Polymerase II Pausing Downstream of Core Histone Genes Is Different from Genes Producing Polyadenylated Transcripts

Recent genome-wide chromatin immunoprecipitation coupled high throughput sequencing (ChIP-seq) analyses performed in various eukaryotic organisms, analysed RNA Polymerase II (Pol II) pausing around the transcription start sites of genes. In this study we have further investigated genome-wide binding of Pol II downstream of the 3′ end of the annotated genes (EAGs) by ChIP-seq in human cells. At almost all expressed genes we observed Pol II occupancy downstream of the EAGs suggesting that Pol II pausing 3′ from the transcription units is a rather common phenomenon. Downstream of EAGs Pol II transcripts can also be detected by global run-on and sequencing, suggesting the presence of functionally active Pol II. Based on Pol II occupancy downstream of EAGs we could distinguish distinct clusters of Pol II pause patterns. On core histone genes, coding for non-polyadenylated transcripts, Pol II occupancy is quickly dropping after the EAG. In contrast, on genes, whose transcripts undergo polyA tail addition [poly(A)+], Pol II occupancy downstream of the EAGs can be detected up to 4–6 kb. Inhibition of polyadenylation significantly increased Pol II occupancy downstream of EAGs at poly(A)+ genes, but not at the EAGs of core histone genes. The differential genome-wide Pol II occupancy profiles 3′ of the EAGs have also been confirmed in mouse embryonic stem (mES) cells, indicating that Pol II pauses genome-wide downstream of the EAGs in mammalian cells. Moreover, in mES cells the sharp drop of Pol II signal at the EAG of core histone genes seems to be independent of the phosphorylation status of the C-terminal domain of the large subunit of Pol II. Thus, our study uncovers a potential link between different mRNA 3′ end processing mechanisms and consequent Pol II transcription termination processes

Responsiveness and minimal clinically important difference for pain and disability instruments in low back pain patients

BACKGROUND: The choice of an evaluative instrument has been hampered by the lack of head-to-head comparisons of responsiveness and the minimal clinically important difference (MCID) in subpopulations of low back pain (LBP). The objective of this study was to concurrently compare responsiveness and MCID for commonly used pain scales and functional instruments in four subpopulations of LBP patients. METHODS: The Danish versions of the Oswestry Disability Index (ODI), the 23-item Roland Morris Disability Questionnaire (RMQ), the physical function and bodily pain subscales of the SF36, the Low Back Pain Rating Scale (LBPRS) and a numerical rating scale for pain (0–10) were completed by 191 patients from the primary and secondary sectors of the Danish health care system. Clinical change was estimated using a 7-point transition question and a numeric rating scale for importance. Responsiveness was operationalised using standardardised response mean (SRM), area under the receiver operating characteristic curve (ROC), and cut-point analysis. Subpopulation analyses were carried out on primary and secondary sector patients with LBP only or leg pain +/- LBP. RESULTS: RMQ was the most responsive instrument in primary and secondary sector patients with LBP only (SRM = 0.5–1.4; ROC = 0.75–0.94) whereas ODI and RMQ showed almost similar responsiveness in primary and secondary sector patients with leg pain (ODI: SRM = 0.4–0.9; ROC = 0.76–0.89; RMQ: SRM = 0.3–0.9; ROC = 0.72–0.88). In improved patients, the RMQ was more responsive in primary and secondary sector patients and LBP only patients (SRM = 1.3–1.7) while the RMQ and ODI were equally responsive in leg pain patients (SRM = 1.3 and 1.2 respectively). All pain measures demonstrated almost equal responsiveness. The MCID increased with increasing baseline score in primary sector and LBP only patients but was only marginally affected by patient entry point and pain location. The MCID of the percentage change score remained constant for the ODI (51%) and RMQ (38%) specifically and differed in the subpopulations. CONCLUSION: RMQ is suitable for measuring change in LBP only patients and both ODI and RMQ are suitable for leg pain patients irrespectively of patient entry point. The MCID is baseline score dependent but only in certain subpopulations. Relative change measured using the ODI and RMQ was not affected by baseline score when patients quantified an important improvement