Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials

Speaking rate and articulation rate of native speakers of Irish English

Previous studies have shown apparent difference in speaking rate and/or articulation rate between different dialects of English. In addition, native speakers of Irish English are perceived to be speaking very fast; however, there is very little information in the current literature regarding speech rate of speakers of this variety of English. Establishing regional norms might be needed for various reasons, such as speech intervention, if speakers of Irish English do have a higher speaking and articulation rates than individuals who speaks other English dialects. This study measured the speaking rate and articulation rate of 22 men and 22 women who were native speakers of Irish English. The study compared the speech rates between the male and female speakers, and across different speech tasks â first and second reading the Rainbow Passage and spontaneous speech elicited in a conversation. Overall, the male speakers seemed to speak faster than the females, although significant difference was found only in the articulation rate for the second reading of the passage. The speakers showed significantly higher speaking rate during passage reading than in conversation but the difference in articulation rate between the two tasks was not significant. Finally, the Irish English speakers in this study appeared to have relatively higher speech rates than most of the English dialects reported in previous studies

Steadily Increasing Star Formation Rates in Galaxies Observed at 3 <~ z <~ 5 in the CANDELS/GOODS-S Field

We investigate the star formation histories (SFHs) of high redshift (3 <~ z <~ 5) star-forming galaxies selected based on their rest-frame ultraviolet (UV) colors in the CANDELS/GOODS-S field. By comparing the results from the spectral-energy-distribution-fitting analysis with two different assumptions about the SFHs --- i.e., exponentially declining SFHs as well as increasing ones, we conclude that the SFHs of high-redshift star-forming galaxies increase with time rather than exponentially decline. We also examine the correlations between the star formation rates (SFRs) and the stellar masses. When the galaxies are fit with rising SFRs, we find that the trend seen in the data qualitatively matches the expectations from a semi-analytic model of galaxy formation. The mean specific SFR is shown to increase with redshift, also in agreement with the theoretical prediction. From the derived tight correlation between stellar masses and SFRs, we derive the mean SFH of star-forming galaxies in the redshift range of 3 <~ z <~ 5, which shows a steep power-law (with power alpha = 5.85) increase with time. We also investigate the formation timescales and the mean stellar population ages of these star-forming galaxies. Our analysis reveals that UV-selected star-forming galaxies have a broad range of the formation redshift. The derived stellar masses and the stellar population ages show positive correlation in a sense that more massive galaxies are on average older, but with significant scatter. This large scatter implies that the galaxies' mass is not the only factor which affects the growth or star formation of high-redshift galaxies.Comment: 31 pages, 8 figures, 2 table

Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction.

Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction

Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes.

Nitrogen-containing bisphosphonates (N-BPs) are the most widely used anti-resorptive agents in the treatment of bone-related diseases. N-BPs inhibit bone resorption by specifically targeting osteoclasts, bone-resorbing cells. However, soft tissue toxicity, such as oral or gastrointestinal (GI) ulcerations has frequently been reported in N-BP users, suggesting that N-BPs may also directly target cells other than osteoclasts. Previously, we reported that BPs inhibit proliferation without inducing the apoptosis of normal human oral keratinocytes (NHOKs). However, the molecular mechanisms through which N-BPs inhibit the proliferation of NHOKs are not yet fully understood. In this study, we performed gene expression profiling in N-BP-treated NHOKs and identified cyclin A2 as one of the most commonly downregulated genes. When the NHOKs were treated with N-BPs, we found that the level of cyclin A2 was suppressed in a dose- and time-dependent manner. In addition, the protein level of cyclin A2 was also significantly lower in oral epithelial cells in N-BP-treated oral mucosal tissue constructs. Cyclin A2 promoter reporter assay revealed that N-BPs inhibited the luciferase activity, indicating that the inhibition of cyclin A2 expression occurs at the transcriptional level. Furthermore, N-BPs did not alter the expression of cyclin A2 in normal human oral fibroblasts (NHOFs), suggesting that the effect of N-BPs on cyclin A2 expression may be cell-type specific. Thus, the findings of our study demonstrate that the inhibition of NHOK proliferation by N-BPs is mediated, at least in part, by the suppression of cyclin A2 expression at the transcriptional level, which may explain the underlying mechanisms of soft tissue toxicity by N-BPs

Cytological characterization and allelism testing of anther developmental mutants identified in a screen of maize male sterile lines.

Proper regulation of anther differentiation is crucial for producing functional pollen, and defects in or absence of any anther cell type result in male sterility. To deepen understanding of processes required to establish premeiotic cell fate and differentiation of somatic support cell layers a cytological screen of maize male-sterile mutants has been conducted which yielded 42 new mutants including 22 mutants with premeiotic cytological defects (increasing this class fivefold), 7 mutants with postmeiotic defects, and 13 mutants with irregular meiosis. Allelism tests with known and new mutants confirmed new alleles of four premeiotic developmental mutants, including two novel alleles of msca1 and single new alleles of ms32, ms8, and ocl4, and two alleles of the postmeiotic ms45. An allelic pair of newly described mutants was found. Premeiotic mutants are now classified into four categories: anther identity defects, abnormal anther structure, locular wall defects and premature degradation of cell layers, and/or microsporocyte collapse. The range of mutant phenotypic classes is discussed in comparison with developmental genetic investigation of anther development in rice and Arabidopsis to highlight similarities and differences between grasses and eudicots and within the grasses

Improving the Estimation of Star formation Rates and Stellar Population Ages of High-redshift Galaxies from Broadband Photometry

We explore methods to improve the estimates of star formation rates and mean stellar population ages from broadband photometry of high redshift star-forming galaxies. We use synthetic spectral templates with a variety of simple parametric star formation histories to fit broadband spectral energy distributions. These parametric models are used to infer ages, star formation rates and stellar masses for a mock data set drawn from a hierarchical semi-analytic model of galaxy evolution. Traditional parametric models generally assume an exponentially declining rate of star-formation after an initial instantaneous rise. Our results show that star formation histories with a much more gradual rise in the star formation rate are likely to be better templates, and are likely to give better overall estimates of the age distribution and star formation rate distribution of Lyman break galaxies. For B- and V-dropouts, we find the best simple parametric model to be one where the star formation rate increases linearly with time. The exponentially-declining model overpredicts the age by 100 % and 120 % for B- and V-dropouts, on average, while for a linearly-increasing model, the age is overpredicted by 9 % and 16 %, respectively. Similarly, the exponential model underpredicts star-formation rates by 56 % and 60 %, while the linearly-increasing model underpredicts by 15 % 22 %, respectively. For U-dropouts, the models where the star-formation rate has a peak (near z ~ 3) provide the best match for age -- overprediction is reduced from 110 % to 26 % -- and star-formation rate -- underprediction is reduced from 58 % to 22 %. We classify different types of star-formation histories in the semi-analytic models and show how the biases behave for the different classes. We also provide two-band calibration formulae for stellar mass and star formation rate estimations.Comment: 28 pages, 7 figures, minor changes; published in Ap

The use of complementary and alternative medicine among california adults with and without cancer.

This article examines the extent and correlates of complementary and alternative medicine (CAM) use among a population-based sample of California adults that is highly diverse in terms of sociodemographic characteristics and health status. As a follow-up to a state-wide health survey of 55,428 people, 9187 respondents were interviewed by phone regarding their use of 11 different types of CAM providers, special diets, dietary supplements, mind-body interventions, self-prayer and support groups. The sample included all participants in the initial survey who reported a diagnosis of cancer, all the non-white respondents, as well as a random sample of all the white respondents. The relation of CAM use to the respondents' demographic characteristics and health status is assessed. CAM use among Californians is generally high, and the demographic factors associated with high rates of CAM use are the same in California as have been found in other studies. Those reporting a diagnosis of cancer and those who report other chronic health problems indicate a similar level of visits to CAM providers. However, those with cancer are less likely to report using special diets, and more likely to report using support groups and prayer. Health status, gender, ethnicity and education have an independent impact upon CAM use among those who are healthy as well as those who report suffering from chronic health problems, although the precise relation varies by the type of CAM used

Evaluation of 4 Outcomes Measures in Microtia Treatment: Exposures, Infections, Aesthetics, and Psychosocial Ramifications.

BackgroundIn craniofacial microsomia, microtia and canal atresia pose formidable reconstructive challenges. We review our institutional experience in treating microtia and atresia to identify variables associated with 4 outcomes measures: complications, surgical revisions, aesthetic outcomes, and psychosocial function.MethodsCraniofacial microsomia patients treated at the University of California Los Angeles Craniofacial Clinic between 2008 and 2014 greater than 13 years of age (n = 68) were reviewed for microtia and atresia treatment and outcomes.ResultsIn total, 91.2% of patients diagnosed with craniofacial microsomia presented with microtia, affecting 75 ears. Both a male and right-sided predominance were observed. Fifty-six patients (90.3%) underwent autologous external ear reconstruction at an average age of 8.5 years. Age, type of incision, and size of cartilage framework did not predict total number of surgeries or complications. Severity of ear anomalies correlated with increased number of surgeries (P &lt; 0.001) and decreased aesthetic outcomes (P &lt; 0.001) but not complications. In total, 87.1% of patients with microtia had documented hearing loss, of which the majority were conductive and 18.5% were mixed sensorineural and conductive. Hearing deficits were addressed in 70.4% of patients with external hearing aids, bone anchored hearing aids, or canaloplasty. Of all variables, improvement of psychosocial function was correlated only to hearing loss treatment of any type (P = 0.01).ConclusionsOn evaluation of surgical and patient characteristics, severity of microtia predicted the total number of surgical revisions performed and aesthetic ratings. In addition, we found that the only factor that correlated with improved patient and parent-reported psychosocial outcomes was treatment of hearing loss

Evaluating Semi-Analytic Halo Merging Histories

We evaluate the accuracy of semi-analytic merger-trees by comparing them with the merging histories of dark-matter halos in N-body simulations, focusing on the joint distribution of the number of progenitors and their masses. We first confirm that the halo mass function as predicted directly by the Press-Schechter (PS) model deviates from the simulations by up to 50% depending on the mass scale and redshift, while the means of the projected distributions of progenitor number and mass for a halo of a given mass are more accurately predicted by the Extended PS model. We then use the full merger trees to study the joint distribution as a function of redshift and parent-halo mass. We find that while the deviation of the mean quantities due to the inaccuracy of the Extended PS model partly propagates into the higher moments of the distribution, the merger-tree procedure does not introduce a significant additional source of error. In particular, certain properties of the merging history such as the mass ratio of the progenitors and the total accretion rate are reproduced quite accurately for galaxy sized halos (\sim 10^{12}\msun), and less so for larger masses. We conclude that although there could be $\sim 50$ deviations in the absolute numbers and masses of progenitors and in the higher order moment of these distributions, the relative properties of progenitors for a given halo are reproduced fairly well by the merger trees. They can thus provide a useful framework for modelling galaxy formation once the above-mentioned limitations are taken into account.Comment: 10 pages including 9 figures, submitted to MNRA