A novel method for comparison of arterial remodeling in hypertension: Quantification of arterial trees and recognition of remodeling patterns on histological sections

Remodeling of spatially heterogeneous arterial trees is routinely quantified on tissue sections by averaging linear dimensions, with lack of comparison between different organs and models. The impact of experimental models or hypertension treatment modalities on organ-specific vascular remodeling remains undefined. A wide variety of arterial remodeling types has been demonstrated for hypertensive models, which include differences across organs. The purpose of this study was to reassess methods for measurement of arterial remodeling and to establish a morphometric algorithm for standard and comparable quantification of vascular remodeling in hypertension in different vascular beds. We performed a novel and comprehensive morphometric analysis of terminal arteries in the brain, heart, lung, liver, kidney, spleen, stomach, intestine, skin, skeletal muscle, and adrenal glands of control and Goldblatt hypertensive rats on routinely processed tissue sections. Mean dimensions were highly variable but grouping them into sequential 5 μm intervals permitted creation of reliable linear regression equations and complex profiles. Averaged arterial dimensions demonstrated seven remodeling patterns that were distinct from conventional inward-outward and hypertrophic-eutrophic definitions. Numerical modeling predicted at least nineteen variants of arterial spatial conformations. Recognition of remodeling variants was not possible using averaged dimensions, their ratios, or the remodeling and growth indices. To distinguish remodeling patterns, a three dimensional modeling was established and tested. The proposed algorithm permits quantitative analysis of arterial remodeling in different organs and may be applicable for comparative studies between animal hypertensive models and human hypertension. Arterial wall tapering is the most important factor to consider in arterial morphometry, while perfusion fixation with vessel relaxation is not necessary. Terminal arteries in organs undergo the same remodeling pattern in Goldblatt rats, except for organs with hemodynamics affected by the arterial clip. The existing remodeling nomenclature should be replaced by a numerical classification applicable to any type of arterial remodeling

The Carnegie Supernova Project: Analysis of the First Sample of Low-Redshift Type-Ia Supernovae

We present the analysis of the first set of low-redshift Type Ia supernovae (SNe Ia) by the Carnegie Supernova Project. Well-sampled, high-precision optical (ugriBV) and near-infrared (NIR; YJHKs) light curves obtained in a well-understood photometric system are used to provide light-curve parameters, and ugriBVYJH template light curves. The intrinsic colors at maximum light are calibrated to compute optical--NIR color excesses for the full sample, thus allowing the properties of the reddening law in the host galaxies to be studied. A low value of Rv~1.7, is derived when using the entire sample of SNe. However, when the two highly reddened SNe in the sample are excluded, a value Galactic standard of Rv~3.2 is obtained. The colors of these two events are well matched by a reddening model due to circumstellar dust. The peak luminosities are calibrated using a two-parameter linear fit to the decline rates and the colors, or alternatively, the color excesses. In both cases, dispersions in absolute magnitude of 0.12--0.16 mag are obtained, depending on the filter-color combination. In contrast to the results obtained from color excesses, these fits give Rv~1--2, even when the two highly reddened SNe are excluded. This discrepancy suggests that, beyond the "normal" interstellar reddening produced in the host galaxies, there is an intrinsic dispersion in the colors of SNe Ia which is correlated with luminosity but independent of the decline rate. Finally, a Hubble diagram is produced by combining the results of the fits for each filter. The resulting scatter of 0.12 mag appears to be limited by peculiar velocities as evidenced by the strong correlation between the distance-modulus residuals among the different filters. The implication is that the actual precision of SN Ia distances is 3--4%.Comment: 76 pages, 20 figures, accepted for publication in A

The Carnegie Supernova Project. I. Third Photometry Data Release of Low-redshift Type Ia Supernovae and Other White Dwarf Explosions

We present final natural-system optical (ugriBV) and near-infrared (YJH) photometry of 134 supernovae (SNe) with probable white dwarf progenitors that were observed in 2004-2009 as part of the first stage of the Carnegie Supernova Project (CSP-I). The sample consists of 123 Type Ia SNe, 5 Type Iax SNe, 2 super-Chandrasekhar SN candidates, 2 Type Ia SNe interacting with circumstellar matter, and 2 SN 2006bt-like events. The redshifts of the objects range from to 0.0835; the median redshift is 0.0241. For 120 (90%) of these SNe, near-infrared photometry was obtained. Average optical extinction coefficients and color terms are derived and demonstrated to be stable during the five CSP-I observing campaigns. Measurements of the CSP-I near-infrared bandpasses are also described, and near-infrared color terms are estimated through synthetic photometry of stellar atmosphere models. Optical and near-infrared magnitudes of local sequences of tertiary standard stars for each supernova are given, and a new calibration of Y-band magnitudes of the Persson et al. standards in the CSP-I natural system is presented.Fil: Krisciunas, Kevin. Texas A&M University; Estados UnidosFil: Contreras, Carlos. University Aarhus; Dinamarca. Las Campanas Observatory; ChileFil: Burns, Christopher R.. Las Campanas Observatory; ChileFil: Phillips, M. M.. Las Campanas Observatory; ChileFil: Stritzinger, Maximilian D.. Las Campanas Observatory; Chile. University Aarhus; DinamarcaFil: Morrell, Nidia Irene. Las Campanas Observatory; ChileFil: Hamuy, Mario. Universidad de Chile; ChileFil: Anais, Jorge. Las Campanas Observatory; ChileFil: Boldt, Luis. Las Campanas Observatory; ChileFil: Busta, Luis. Las Campanas Observatory; ChileFil: Campillay, Abdo. Las Campanas Observatory; ChileFil: Castellón, Sergio. Las Campanas Observatory; ChileFil: Folatelli, Gaston. Las Campanas Observatory; Chile. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Freedman, Wendy L.. University of Chicago; Estados UnidosFil: González, Consuelo. Las Campanas Observatory; ChileFil: Hsiao, Eric Y.. Florida State University; Estados Unidos. University Aarhus; Dinamarca. Las Campanas Observatory; ChileFil: Krzeminski, Wojtek. Las Campanas Observatory; ChileFil: Persson, Sven Eric. Carnegie Observatories;Fil: Roth, Miguel. Gmto Corporation; Chile. Las Campanas Observatory; ChileFil: Salgado, Francisco. Leiden Observatory Research Institute; . Las Campanas Observatory; ChileFil: Serón, Jacqueline. Las Campanas Observatory; Chile. Cerro Tololo Inter American Observatory; ChileFil: Suntzeff, Nicholas B.. Texas A&M University; Estados UnidosFil: Torres, Simón. Soar Telescope; Chile. Las Campanas Observatory; ChileFil: Filippenko, Alexei V.. University of California at Berkeley; Estados UnidosFil: Li, Weidong. University of California at Berkeley; Estados UnidosFil: Madore, Barry F.. Jet Propulsion Laboratory, California Institute Of Technology; . Las Campanas Observatory; ChileFil: DePoy, D.L.. Texas A&M University; Estados UnidosFil: Marshall, Jennifer L.. Texas A&M University; Estados UnidosFil: Rheault, Jean Philippe. Texas A&M University; Estados UnidosFil: Villanueva, Steven. Texas A&M University; Estados Unidos. Ohio State University; Estados Unido

Francisella tularensis Transmission by Solid Organ Transplantation, 20171.

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation

Genomic Profiling of Two Histologically Distinct Rare Urothelial Cancers in a Clinical Setting to Identify Potential Therapeutic Options for Treatment and Management of Disease.

Molecular profiling of urothelial cancers for therapeutic and prognostic potential has been very limited due to the absence of cancer-specific targeted therapies. We describe here 2 clinical cases with a histological diagnosis of an invasive sarcomatoid and a poorly differentiated carcinoma favoring urothelial with some neuroendocrine differentiation, two of the rarer types of urothelial cancers, which were evaluated for mutations in 212 genes for single-nucleotide variants and copy-number variants and 53 genes for fusions associated with solid tumors. In both cases, we identified variants in 2 genes, Case Rep Oncol 2018 Mar 27; 11(1):196-205

The Peculiar SN 2005hk: Do Some Type Ia Supernovae Explode as Deflagrations?

We present extensive u'g'r'i'BVRIYJHKs photometry and optical spectroscopy of SN 2005hk. These data reveal that SN 2005hk was nearly identical in its observed properties to SN 2002cx, which has been called ``the most peculiar known type Ia supernova.'' Both supernovae exhibited high ionization SN 1991T-like pre-maximum spectra, yet low peak luminosities like SN 1991bg. The spectra reveal that SN 2005hk, like SN 2002cx, exhibited expansion velocities that were roughly half those of typical type Ia supernovae. The R and I light curves of both supernovae were also peculiar in not displaying the secondary maximum observed for normal type Ia supernovae. Our YJH photometry of SN 2005hk reveals the same peculiarity in the near-infrared. By combining our optical and near-infrared photometry of SN 2005hk with published ultraviolet light curves obtained with the Swift satellite, we are able to construct a bolometric light curve from ~10 days before to ~60 days after B maximum. The shape and unusually low peak luminosity of this light curve, plus the low expansion velocities and absence of a secondary maximum at red and near-infrared wavelengths, are all in reasonable agreement with model calculations of a 3D deflagration which produces ~0.25 M_sun of 56Ni.Comment: Accepted by PASP, to appear in April 2007 issue, 63 pages, 16 figures, 11 table

Reduction of aldehydes and hydrogen cyanide yields in mainstream cigarette smoke using an amine functionalised ion exchange resin

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is a well recognized cause of diseases such as lung cancer, chronic obstructive pulmonary disease and cardiovascular disease. Of the more than 5000 identified species in cigarette smoke, at least 150 have toxicological activity. For example, formaldehyde and acetaldehyde have been assigned as Group 1 and Group 2B carcinogens by IARC, and hydrogen cyanide has been identified as a respiratory and cardiovascular toxicant. Active carbon has been shown to be an effective material for the physical adsorption of many of the smoke volatile species. However, physical adsorption of acetaldehyde, formaldehyde and also hydrogen cyanide from smoke is less effective using carbon. Alternative methods for the removal of these species from cigarette smoke are therefore of interest. A macroporous, polystyrene based ion-exchange resin (Diaion^®CR20) with surface amine group functionality has been investigated for its ability to react with aldehydes and HCN in an aerosol stream, and thus selectively reduce the yields of these compounds (in particular formaldehyde) in mainstream cigarette smoke.</p> <p>Results</p> <p>Resin surface chemistry was characterized using vapour sorption, XPS, TOF-SIMS and ¹⁵N NMR. Diaion^®CR20 was found to have structural characteristics indicating weak physisorption properties, but sufficient surface functionalities to selectively remove aldehydes and HCN from cigarette smoke. Using 60 mg of Diaion^®CR20 in a cigarette cavity filter gave reductions in smoke formaldehyde greater than 50% (estimated to be equivalent to >80% of the formaldehyde present in the smoke vapour phase) independent of a range of flow rates. Substantial removal of HCN (>80%) and acetaldehyde (>60%) was also observed. The performance of Diaion^®CR20 was found to be consistent over a test period of 6 months. The overall adsorption for the majority of smoke compounds measured appeared to follow a pseudo-first order approximation to second order kinetics.</p> <p>Conclusions</p> <p>This study has shown that Diaion^®CR20 is a highly selective and efficient adsorbent for formaldehyde, acetaldehyde and HCN in cigarette smoke. The reductions for these compounds were greater than those achieved using an active carbon. The results also demonstrate that chemisorption can be an effective mechanism for the removal of certain vapour phase toxicants from cigarette smoke.</p

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras