Structure of the novel membrane-coating material in proton-secreting epithelial cells and identification as an H+ATPase.

Specialized proton-secreting cells known collectively as mitochondria-rich cells are found in a variety of transporting epithelia, including the kidney collecting duct (intercalated cells) and toad and turtle urinary bladders. These cells contain a population of characteristic tubulovesicles that are believed to be involved in the shuttling of proton pumps (H+ATPase) to and from the plasma membrane. These transporting vesicles have a dense, studlike material coating the cytoplasmic face of their limiting membranes and similar studs are also found beneath parts of the plasma membrane. We have recently shown that this membrane coat does not contain clathrin. The present study was performed to determine the structure of this coat in rapidly frozen and freeze-dried tissue, and to determine whether the coat contains a major membrane protein transported by these vesicles, a proton pumping H+ATPase. The structure of the coat was examined in proton-secreting, mitochondria-rich cells from toad urinary bladder epithelium by rapidly freezing portions of apical membrane and associated cytoplasm that were sheared away from the remainder of the cell using polylysine-coated coverslips. Regions of the underside of these apical membranes as large as 0.2 micron2 were decorated by studlike projections that were arranged into regular hexagonal arrays. Individual studs had a diameter of 9.5 nm and appeared to be composed of multiple subunits arranged around a central depression, possibly representing a channel. The studs had a density of approximately 16,800 per micron2 of membrane. Similar arrays of studs were also found on vesicles trapped in the residual band of cytoplasm that remained attached to the underside of the plasma membrane, but none were seen in adjacent granular cells. To determine whether these arrays of studs contained H+ATPase molecules, we examined a preparation of affinity-purified bovine medullary H+ATPase, using the same technique, after incorporation of the protein eluted from a monoclonal antibody affinity column into phospholipid liposomes. The affinity-purified protein was shown to be capable of ATP-dependent acidification. In such preparations, large paracrystalline arrays of studs identical in appearance to those seen in situ were found. The dimensions of the studs as well as the number per square micrometer of membrane were identical to those of toad bladder mitochondria-rich cells: 9.5 nm in diameter, 16,770 per micron2 of membrane.(ABSTRACT TRUNCATED AT 400 WORDS

Synthesis and late-stage functionalization of complex molecules through C-H fluorination and nucleophilic aromatic substitution.

We report the late-stage functionalization of multisubstituted pyridines and diazines at the position α to nitrogen. By this process, a series of functional groups and substituents bound to the ring through nitrogen, oxygen, sulfur, or carbon are installed. This functionalization is accomplished by a combination of fluorination and nucleophilic aromatic substitution of the installed fluoride. A diverse array of functionalities can be installed because of the mild reaction conditions revealed for nucleophilic aromatic substitutions (S(N)Ar) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution versus the rates for competitive processes provides a framework for planning this functionalization sequence. This process is illustrated by the modification of a series of medicinally important compounds, as well as the increase in efficiency of synthesis of several existing pharmaceuticals

Research on digital transducer principles. Volume 7 - Dielectric properties of thin polymer films, 1 July 1967 - 30 June 1968

Dielectric properties of thin films of polymerized oil-metal-silicon structure

Constraining the primordial initial mass function with stellar archaeology

We present a new near-field cosmological probe of the initial mass function (IMF) of the first stars. Specifically, we constrain the lower-mass limit of the Population III (Pop III) IMF with the total number of stars in large, unbiased surveys of the Milky Way. We model the early star formation history in a Milky Way-like halo with a semi-analytic approach, based on Monte-Carlo sampling of dark matter merger trees, combined with a treatment of the most important feedback mechanisms. Assuming a logarithmically flat Pop III IMF and varying its low mass limit, we derive the number of expected survivors of these first stars, using them to estimate the probability to detect any such Pop III fossil in stellar archaeological surveys. Following our analysis, the most promising region to find possible Pop III survivors is the stellar halo of the Milky Way, which is the best target for future surveys. We find that if no genuine Pop III survivor is detected in a sample size of $4 \times 10^6$ ($2 \times 10^7$) halo stars with well-controlled selection effects, then we can exclude the hypothesis that the primordial IMF extended down below $0.8 M_\odot$ at a confidence level of 68% (99%). With the sample size of the Hamburg/ESO survey, we can tentatively exclude Pop III stars with masses below $0.65 M_\odot$ with a confidence level of 95%, although this is subject to significant uncertainties. To fully harness the potential of our approach, future large surveys are needed that employ uniform, unbiased selection strategies for high-resolution spectroscopic follow-up.Comment: 19 pages, 14 figures, published in MNRA

The Path I Took from Farquhar College of Arts and Science to the Field of Pharmacy and Business

The road to becoming a pharmacist has been a rewarding experience. The challenges that I have encountered along the way have made me a better person and a better healthcare professional. I am about to finish my last clinical rotation and will graduate with both my Doctorate of Pharmacy and Masters of Business Administration in May 2015. It seems like yesterday that I was in the Farquhar College of Arts and Sciences, pursuing a degree in biology. This presentation will highlight some insights and stories I had on the path to becoming a pharmacist and dual enrolling in the H. Wayne Huizenga School of Business and Entrepreneurship for my MBA. I will also discuss key lessons I learned along the way to reaching my career goals some of which will include: • Don’t let your grades or your peers grades prevent you from applying to grad schools • Show interest in your desired field • Scheduling will save your life • Librarians are your best frien

RTG/science instrument radiation interactions for deep space probes, phase 2, 3, and 4

Assessment of interference to scientific instruments onboard RTG powered spacecraft caused by radiation emanating from RTG unit with application to Pioneer F/G space probe

Industrial Freeform Generation of Microtools by Laser Micro Sintering

Precision tools with structural resolution reaching the 20 micrometer range can be generated on an industrial scale by “laser micro sintering”. Components featuring aspect ratios above 12 and a roughness Ra down to 1.5 micrometers have already been produced from sub micrometer grained metal powders. The components can be generated either firmly attached to a substrate or fixed in an easily separable mode. If supporting structures are employed, undercuts up to 90° are feasible, without, a process parameter dependent maximum angles of undercut below 90° are obtained. The process has been introduced into the market, labeled microSINTERING by 3D-Micromac AG.Mechanical Engineerin

How an improved implementation of H2 self-shielding influences the formation of massive stars and black holes

High redshift quasars at z>6 have masses up to ~$10^9$ M$_\odot$. One of the pathways to their formation includes direct collapse of gas, forming a supermassive star, precursor of the black hole seed. The conditions for direct collapse are more easily achievable in metal-free haloes, where atomic hydrogen cooling operates and molecular hydrogen (H2) formation is inhibited by a strong external UV flux. Above a certain value of UV flux (J_crit), the gas in a halo collapses isothermally at ~$10^4$ K and provides the conditions for supermassive star formation. However, H2 can self-shield, reducing the effect of photodissociation. So far, most numerical studies used the local Jeans length to calculate the column densities for self-shielding. We implement an improved method for the determination of column densities in 3D simulations and analyse its effect on the value of J_crit. This new method captures the gas geometry and velocity field and enables us to properly determine the direction-dependent self-shielding factor of H2 against photodissociating radiation. We find a value of J_crit that is a factor of two smaller than with the Jeans approach (~2000 J_21 vs. ~4000 J_21). The main reason for this difference is the strong directional dependence of the H2 column density. With this lower value of J_crit, the number of haloes exposed to a flux >J_crit is larger by more than an order of magnitude compared to previous studies. This may translate into a similar enhancement in the predicted number density of black hole seeds.Comment: 14 pages, 12 figures, published in MNRA

Decomposition of stochastic properties within images using non-parametric methods

This paper discusses the application of three different nonparametric methods for decomposing images into regions which exhibit special stochastic properties, together with the constituent components of the stochastic. These are: (1) order statistics in connection with steps in the empirical estimated distribution functions; (2) detection of stochastic information within an image by hypothesis testing; and (3) rank order statistics to decompose the different types of stochastic within an image. The decomposition is used to isolate different image regions and to estimate the processes which are the constituent stochastic components. In order to achieve this, decisions based upon membership relations are employed and adapted thresholds used. The thresholds are obtained by the ordering of terms calculated by stochastic estimation methods together with one of the aforementioned technique