MicroRNA detection on microsensor arrays by SPR imaging measurements with enzymatic signal enhancement.

We investigated sequence-specific and simultaneous microRNA (miRNA) detections by surface plasmon resonance (SPR) imaging measurements on SPR chips possessing an Au spot array modified with probe DNAs based on a miRNA-detection-selective SPR signal amplification method. MiRNAs were detected with the detection limit of the attomole level by SPR imaging measurements for different miRNA concentrations on a single chip. SPR signals were enhanced based on a combination process of sequence-specific hybridization of the miRNA to the probe DNAs, extension reaction of polyadenine (poly(A)) tails by poly(A) polymerase, binding of a ternary complex of T30-biotin/horseradish peroxidase (HRP)-biotin/streptavidin to the poly(A) tails, and the oxidation reaction of tetramethylbenzidine (TMB) on the HRP by providing a blue precipitate on the surface. This process sequence-specifically and dramatically amplified the SPR signals. This is a simple, cost-effective, and feasible signal amplification method based on the organic compound TMB instead of metal nanoparticles

Placing High-Redshift Quasars in Perspective: Unifying Distant Quasars with Their Lower Redshift Counterparts through Near-Infrared Spectroscopy

I present spectroscopic measurements for 260 sources from the Gemini Near Infrared Spectrograph–Distant Quasar Survey (GNIRS-DQS). Being the largest uniform, homogeneous survey of its kind, it represents a flux-limited sample of Sloan Digital Sky Survey (SDSS) quasars at 1.5 < z < 3.5. A combination of the GNIRS and SDSS spectra covers principal quasar diagnostic features, chiefly the C IV λ1549, Mg II λλ2798, 2803, Hβ λ4861, and [O III] λλ4959, 5007 emission lines, in each source. The spectral inventory is utilized primarily to develop prescriptions for obtaining more accurate and precise redshifts, black hole masses, and accretion rates for all quasars. Additionally, the measurements facilitate an understanding of the dependence of rest-frame ultraviolet–optical spectral properties of quasars on redshift, luminosity, and Eddington ratio, and test whether the physical properties of the quasar central engine evolve over cosmic time

Gemini Near Infrared Spectrograph - Distant Quasar Survey: Prescriptions for Calibrating UV-Based Estimates of Supermassive Black Hole Masses in High-Redshift Quasars

The most reliable single-epoch supermassive black hole mass ($M_{\rm BH}$) estimates in quasars are obtained by using the velocity widths of low-ionization emission lines, typically the H$\beta$ $\lambda4861$ line. Unfortunately, this line is redshifted out of the optical band at $z\approx1$, leaving $M_{\rm BH}$ estimates to rely on proxy rest-frame ultraviolet (UV) emission lines, such as C IV $\lambda1549$ or Mg II $\lambda2800$, which contain intrinsic challenges when measuring, resulting in uncertain $M_{\rm BH}$ estimates. In this work, we aim at correcting $M_{\rm BH}$ estimates derived from the C IV and Mg II emission lines based on estimates derived from the H$\beta$ emission line. We find that employing the equivalent width of C IV in deriving $M_{\rm BH}$ estimates based on Mg II and C IV provides values that are closest to those obtained from H$\beta$. We also provide prescriptions to estimate $M_{\rm BH}$ values when only C IV, only Mg II, and both C IV and Mg II are measurable. We find that utilizing both emission lines, where available, reduces the scatter of UV-based $M_{\rm BH}$ estimates by $\sim15\%$ when compared to previous studies. Lastly, we discuss the potential of our prescriptions to provide more accurate and precise estimates of $M_{\rm BH}$ given a much larger sample of quasars at $3.20 \lesssim z \lesssim 3.50$, where both Mg II and H$\beta$ can be measured in the same near-infrared spectrum.Comment: 19 pages (AASTeX 6.3.1), 9 figures, accepted for publication in Ap

Gemini Near Infrared Spectrograph -- Distant Quasar Survey: Augmented Spectroscopic Catalog and a Prescription for Correcting UV-Based Quasar Redshifts

Quasars at $z~{\gtrsim}~1$ most often have redshifts measured from rest-frame ultraviolet emission lines. One of the most common such lines, C IV ${\lambda}1549$, shows blueshifts up to ${\approx}~5000~\rm{km~s^{-1}}$, and in rare cases even higher. This blueshifting results in highly uncertain redshifts when compared to redshift determinations from rest-frame optical emission lines, e.g., from the narrow [O III] ${\lambda}5007$ feature. We present spectroscopic measurements for 260 sources at $1.55~{\lesssim}~z~{\lesssim}~3.50$ having $-28.0~{\lesssim}~M_i~{\lesssim}~-30.0$ mag from the Gemini Near Infrared Spectrograph - Distant Quasar Survey (GNIRS-DQS) catalog, augmenting the previous iteration which contained 226 of the 260 sources whose measurements are improved upon in this work. We obtain reliable systemic redshifts based on [O III] ${\lambda}5007$ for a subset of 121 sources which we use to calibrate prescriptions for correcting UV-based redshifts. These prescriptions are based on a regression analysis involving C IV full-width-at-half-maximum intensity and equivalent width, along with the UV continuum luminosity at a rest-frame wavelength of 1350 A. Applying these corrections can improve the accuracy and the precision in the C IV-based redshift by up to ${\sim}~850~\rm{km~s^{-1}}$ and ${\sim}~150~\rm{km~s^{-1}}$, respectively, which correspond to ${\sim}~8.5$ Mpc and ${\sim}~1.5$ Mpc in comoving distance at $z~=~2.5$. Our prescriptions also improve the accuracy of the best available multi-feature redshift determination algorithm by ${\sim}~100~\rm{km~s^{-1}}$, indicating that the spectroscopic properties of the C IV emission line can provide robust redshift estimates for high-redshift quasars. We discuss the prospects of our prescriptions for cosmological and quasar studies utilizing upcoming large spectroscopic surveys.Comment: 20 pages (AASTeX 6.3.1), 8 figures, accepted for publication in Ap

Placing high-redshift quasars in perspective: A catalog of spectroscopic properties from the gemini near infrared spectrograph-distant quasar survey

We present spectroscopic measurements for 226 sources from the Gemini Near Infrared Spectrograph-Distant Quasar Survey (GNIRS-DQS). Being the largest uniform, homogeneous survey of its kind, it represents a fluxlimited sample (mi≤19.0 mag, H≤16.5 mag) of Sloan Digital Sky Survey (SDSS) quasars at 1.5 ≤ z ≤ 3.5 with a monochromatic luminosity (λLλ) at 5100 Å in the range of 1044-1046 erg s-1. A combination of the GNIRS and SDSS spectra covers principal quasar diagnostic features, chiefly the C IV λ1549, Mg II λλ2798, 2803, Hβ λ4861, and [O III] λλ4959, 5007 emission lines, in each source. The spectral inventory will be utilized primarily to develop prescriptions for obtaining more accurate and precise redshifts, black hole masses, and accretion rates for all quasars. Additionally, the measurements will facilitate an understanding of the dependence of rest-frame ultraviolet-optical spectral properties of quasars on redshift, luminosity, and Eddington ratio, and test whether the physical properties of the quasar central engine evolve over cosmic time.Fil: Matthews, Brandon M.. University of North Texas; Estados UnidosFil: Shemmer, Ohad. University of North Texas; Estados UnidosFil: Dix, Cooper. University of North Texas; Estados UnidosFil: Brotherton, Michael S.. University of Wyoming; Estados UnidosFil: Myers, Adam D.. University of Wyoming; Estados UnidosFil: Andruchow, Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Brandt, W.N.. State University of Pennsylvania; Estados UnidosFil: Ferrero, Gabriel A.. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Gallagher, S.C.. The University Of Western Ontario; CanadáFil: Green, Richard. University of Arizona; Estados UnidosFil: Lira, Paulina. Universidad de Chile.; ChileFil: Plotkin, Richard M.. University of Nevada. Deparment of Physics; Estados UnidosFil: Richards, Gordon T.. Drexel University; Estados UnidosFil: Runnoe, Jessie C.. Vanderbilt University; Estados UnidosFil: Schneider, Donald P.. State University of Pennsylvania; Estados UnidosFil: Shen, Yue. University of Illinois at Urbana; Estados UnidosFil: Strauss, Michael A.. University of Princeton; Estados UnidosFil: Wills, Beverley J.. University of Texas at Austin; Estados Unido

The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma.

CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently inhibited cellular CHK1 activity (IC50 30-220 nM) and enhanced gemcitabine and SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft models. Mouse oral bioavailability was complete (100%) with extensive tumor exposure. Genotoxic-induced CHK1 activity (pS296 CHK1) and cell cycle arrest (pY15 CDK1) were inhibited both in vitro and in human tumor xenografts by CCT245737, causing increased DNA damage and apoptosis. Uniquely, we show CCT245737 enhanced gemcitabine antitumor activity to a greater degree than for higher doses of either agent alone, without increasing toxicity, indicating a true therapeutic advantage for this combination. Furthermore, development of a novel ELISA assay for pS296 CHK1 autophosphorylation, allowed the quantitative measurement of target inhibition in a RAS mutant human tumor xenograft of NSCLC at efficacious doses of CCT245737. Finally, CCT245737 also showed significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma. In conclusion, CCT245737 is a new CHK1 inhibitor clinical development candidate scheduled for a first in man Phase I clinical trial, that will use the novel pS296 CHK1 ELISA to monitor target inhibition

Shedding New Light on Weak Emission-Line Quasars in the CIV_{\rm IV}-Hβ\beta Parameter Space

Weak emission-line quasars (WLQs) are a subset of Type 1 quasars that exhibit extremely weak Ly$\alpha +$N V $\lambda$1240 and/or C IV $\lambda$1549 emission lines. We investigate the relationship between emission-line properties and accretion rate for a sample of 230 `ordinary' Type 1 quasars and 18 WLQs at $z < 0.5$ and $1.5 < z < 3.5$ that have rest-frame ultraviolet and optical spectral measurements. We apply a correction to the H$\beta$-based black-hole mass ($M_{\rm BH}$) estimates of these quasars using the strength of the optical Fe II emission. We confirm previous findings that WLQs' $M_{\rm BH}$ values are overestimated by up to an order of magnitude using the traditional broad emission-line region size-luminosity relation. With this $M_{\rm BH}$ correction, we find a significant correlation between H$\beta$-based Eddington luminosity ratios and a combination of the rest-frame C IV equivalent width and C IV blueshift with respect to the systemic redshift. This correlation holds for both ordinary quasars and WLQs, which suggests that the two-dimensional C IV parameter space can serve as an indicator of accretion rate in all Type 1 quasars across a wide range of spectral properties.Comment: 17 pages (AASTeX 6.3.1), 5 figures, accepted for publication in Ap

Cell-Type Specific Expression of a Dominant Negative PKA Mutation in Mice

We employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any cell-type that expresses Cre recombinase. The mouse line carries a mutant Prkar1a allele encoding a glycine to aspartate substitution at position 324 in the carboxy-terminal cAMP-binding domain (site B). This mutation produces a dominant negative RIα regulatory subunit (RIαB) and leads to inhibition of PKA activity. Insertion of a loxP-flanked neomycin cassette in the intron preceding the site B mutation prevents expression of the mutant RIαB allele until Cre-mediated excision of the cassette occurs. Embryonic stem cells expressing RIαB demonstrated a reduction in PKA activity and inhibition of cAMP-responsive gene expression. Mice expressing RIαB in hepatocytes exhibited reduced PKA activity, normal fasting induced gene expression, and enhanced glucose disposal. Activation of the RIαB allele in vivo provides a novel system for the analysis of PKA function in physiology

Recovery of Barotrauma Injuries in Chinook Salmon, Oncorhynchus tshawytscha from Exposure to Pile Driving Sound

Juvenile Chinook salmon, Oncorhynchus tshawytscha, were exposed to simulated high intensity pile driving signals to evaluate their ability to recover from barotrauma injuries. Fish were exposed to one of two cumulative sound exposure levels for 960 pile strikes (217 or 210 dB re 1 µPa2·s SELcum; single strike sound exposure levels of 187 or 180 dB re 1 µPa2⋅s SELss respectively). This was followed by an immediate assessment of injuries, or assessment 2, 5, or 10 days post-exposure. There were no observed mortalities from the pile driving sound exposure. Fish exposed to 217 dB re 1 µPa2·s SELcum displayed evidence of healing from injuries as post-exposure time increased. Fish exposed to 210 dB re 1 µPa2·s SELcum sustained minimal injuries that were not significantly different from control fish at days 0, 2, and 10. The exposure to 210 dB re 1 µPa2·s SELcum replicated the findings in a previous study that defined this level as the threshold for onset of injury. Furthermore, these data support the hypothesis that one or two Mild injuries resulting from pile driving exposure are unlikely to affect the survival of the exposed animals, at least in a laboratory environment