Book Reviews

The purpose of this book is, to quote from the preface, to present a clear, accurate, and impartial study of the law in the hope of offering assistance to those who are attempting to choose a career or who are about to enter upon the profession. This necessitates a review of the nature of the law, present day legal conditions, personal and educational requirements, the dangers and disadvantages incident to practice, the high professional demands made upon the lawyer, the varied fields of service open to him, his probable earnings and emoluments,--in a word, all that has a distinct and important bearing upon the law as a vocation

Degradation of Airway Secretory Cell Mucin Granules Is Dependent on Lysosome Activity

Inflammatory airway diseases (e.g. COPD and asthma) are associated with mucous cell metaplasia and mucin hypersecretion, resulting in symptoms such as shortness of breath and cough. However, how secretory cells remove excess mucin granules is poorly understood. Previous research suggests that intracellular degradation pathways, such as autophagy, are involved in the degradation of mucin granules during resolution of mucous cell metaplasia. We thus hypothesized that the elimination of excess mucin granules is dependent on lysosome-mediated degradation in airway secretory cells. Calu-3 cells, an airway epithelial cell line containing abundant mucin granules, were treated with inhibitors of lysosome acidification (Bafilomycin A1) and lysosome enzyme activity (Pepstatin E64d). We found statistically significant increases in the levels of secretory mucin, MUC5AC, by mucin blot, suggesting that the lysosome mediates the elimination of mucin granules. In addition, by immunoblot we observed an increase in the autophagosome markers, LC3-II and SQSTM1, with lysosome inhibition using Bafilomycin A1, indicating an accumulation of autophagosomes and a role for autophagy in the degradation of mucin granules. However, after transfecting Calu-3 cells with a ubiquitin-hemagglutinin tag plasmid to examine the role of the proteasome in the degradation of mucin granules, we observed that our transfection efficiency was low, making it difficult to detect the hemagglutinin epitope by immunoblots. Nevertheless, we found that MUC5AC levels preliminarily increase with the inhibition of the proteasome using MG-132, suggesting a potential role for the proteasome in the degradation of mucin granules. Thus, we can conclude that inhibition of the lysosome increases MUC5AC levels, demonstrating that the lysosome mediates the degradation of mucin granules in airway secretory cells. In addition, while we were not able to conclude that the proteasome is involved in the degradation of mucin granules with certainty, our preliminary data suggests that it is possible that the ubiquitin-proteasome system is involved in the degradation of mucin due to the observed increase in MUC5AC levels with MG-132.https://digitalcommons.unmc.edu/surp2022/1039/thumbnail.jp

Measuring Symmetry in Real-World Scenes Using Derivatives of the Medial Axis Radius Function

Symmetry has been shown to be an important principle that guides the grouping of scene information. Previously, we have described a method for measuring the local, ribbon symmetry content of line-drawings of real-world scenes (Rezanejad, et al., MODVIS 2017), and we demonstrated that this information has important behavioral consequences (Wilder, et al., MODIVS 2017). Here, we describe a continuous, local version of the symmetry measure, that allows for both ribbon and taper symmetry to be captured. Our original method looked at the difference in the radius between successive maximal discs along a symmetric axis. The number of radii differences in a local region that exceeded a threshold, normalized by the number of total differences, was used as the symmetry score at an axis point. We now use the derivative of the radius function along the symmetric axis between two contours, which allows for a continuous method of estimating the score which does not need a threshold. By replacing the first derivative with a second derivative, we can generalize this method to allow pairs of contours which taper with respect to one another, to express high symmetry. Such situations arise, for example, when parallel lines in the 3D world project onto a 2D image. This generalization will allow us to determine the relative importance of taper and ribbon symmetries in natural scenes

Book Reviews

Professor Hicks has done for a few great lawyers and \u27a few great books what it is hoped he may do for many more lawyers and many more books. Out of his full and intimate knowledge of the literature of our profession he has gathered and presented to us in most entertaining fashion the human as well as the intellectual and professional characteristics of a full half dozen men, each of whom holds a somewhat unique place in the development of Anglo-Saxon law

A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.

Synthetic protein switches controlled with user-defined inputs are powerful tools for studying and controlling dynamic cellular processes. To date, these approaches have relied primarily on intermolecular regulation. Here we report a computationally guided framework for engineering intramolecular regulation of protein function. We utilize this framework to develop chemically inducible activator of RAS (CIAR), a single-component RAS rheostat that directly activates endogenous RAS in response to a small molecule. Using CIAR, we show that direct RAS activation elicits markedly different RAS-ERK signaling dynamics from growth factor stimulation, and that these dynamics differ among cell types. We also found that the clinically approved RAF inhibitor vemurafenib potently primes cells to respond to direct wild-type RAS activation. These results demonstrate the utility of CIAR for quantitatively interrogating RAS signaling. Finally, we demonstrate the general utility of our approach in design of intramolecularly regulated protein tools by applying it to the Rho family of guanine nucleotide exchange factors

Ozone depletion, greenhouse gases, and climate change

This symposium was organized to study the unusual convergence of a number of observations, both short and long term that defy an integrated explanation. Of particular importance are surface temperature observations and observations of upper atmospheric temperatures, which have declined significantly in parts of the stratosphere. There has also been a dramatic decline in ozone concentration over Antarctica that was not predicted. Significant changes in precipitation that seem to be latitude dependent have occurred. There has been a threefold increase in methane in the last 100 years; this is a problem because a source does not appear to exist for methane of the right isotopic composition to explain the increase. These and other meteorological global climate changes are examined in detail

z~7 galaxy candidates from NICMOS observations over the HDF South and the CDF-S and HDF-N GOODS fields

We use ~88 arcmin**2 of deep (>~26.5 mag at 5 sigma) NICMOS data over the two GOODS fields and the HDF South to conduct a search for bright z>~7 galaxy candidates. This search takes advantage of an efficient preselection over 58 arcmin**2 of NICMOS H-band data where only plausible z>~7 candidates are followed up with NICMOS J-band observations. ~248 arcmin**2 of deep ground-based near-infrared data (>~25.5 mag, 5 sigma) is also considered in the search. In total, we report 15 z-dropout candidates over this area -- 7 of which are new to these search fields. Two possible z~9 J-dropout candidates are also found, but seem unlikely to correspond to z~9 galaxies. The present z~9 search is used to set upper limits on the prevalence of such sources. Rigorous testing is undertaken to establish the level of contamination of our selections by photometric scatter, low mass stars, supernovae (SNe), and spurious sources. The estimated contamination rate of our z~7 selection is ~24%. Through careful simulations, the effective volume available to our z>~7 selections is estimated and used to establish constraints on the volume density of luminous (L*(z=3), or -21 mag) galaxies from these searches. We find that the volume density of luminous star-forming galaxies at z~7 is 13_{-5}^{+8}x lower than at z~4 and >25x lower (1 sigma) at z~9 than at z~4. This is the most stringent constraint yet available on the volume density of >~L* galaxies at z~9. The present wide-area, multi-field search limits cosmic variance to <20%. The evolution we find at the bright end of the UV LF is similar to that found from recent Subaru Suprime-Cam, HAWK-I or ERS WFC3/IR searches. The present paper also includes a complete summary of our final z~7 z-dropout sample (18 candidates) identified from all NICMOS observations to date (over the two GOODS fields, the HUDF, galaxy clusters).Comment: 13 pages, 6 figures, 6 tables, accepted for publication in the Astrophysical Journal, replaced to match accepted version, see http://firstgalaxies.org/astronomers-area/ for a link to a complete reduction of the NICMOS observations over the two GOODS field