MAKING WAR ON JUPITER PLUVIUS THE CULTURE AND SCIENCE OF RAINMAKING IN THE SOUTHERN GREAT PLAINS, 1870-1913

For two weeks in August 1891, the grounds of the C Ranch in rural West Texas thundered with the sound of explosions, as a federal government- sponsored expeditionary force hurled hundreds of pounds of heavy ordnance against an invisible enemy. In command of this unusual operation was General Robert Dyrenforth, who with $9,000 of congressional funding in pocket was doing his utmost to find out whether, as a bit of folk wisdom ran, the furious tumult and aerial concussions of battle could somehow cause rain. From tiny western hamlets to the metropolises of the East, Americans were fascinated by the sensational experiments. In magazines, newspapers, and journals, some scoffed at what they saw as a fool\u27s errand and an egregious waste of public funds, while others were equally certain of the reality of the connection and regarded the potential windfall great enough to justifY any expense. Scientists in particular were almost unanimously doubtful (and occasionally hostile), and made their views clear in the scholarly organs of their profession. In the end, the experiments failed to prove a definitive connection; indeed, as many had predicted all along, sober assessments of the data yielded little to suggest any causal link between explosions and rainfall. Yet, curiously, this was by no means the end of the theory. Over the course of two decades, a colorful cast of characters, from an eccentric self-titled general to a millionaire cereal magnate-cum-social engineer, typified a stubborn core of devoted believers. Each attempted to prove (or make practical use of) the theory by discharging various weapons and explosives at the sky, hoping that raindrops would come down in exchange

MAKING WAR ON JUPITER PLUVIUS THE CULTURE AND SCIENCE OF RAINMAKING IN THE SOUTHERN GREAT PLAINS, 1870-1913

For two weeks in August 1891, the grounds of the C Ranch in rural West Texas thundered with the sound of explosions, as a federal government- sponsored expeditionary force hurled hundreds of pounds of heavy ordnance against an invisible enemy. In command of this unusual operation was General Robert Dyrenforth, who with $9,000 of congressional funding in pocket was doing his utmost to find out whether, as a bit of folk wisdom ran, the furious tumult and aerial concussions of battle could somehow cause rain. From tiny western hamlets to the metropolises of the East, Americans were fascinated by the sensational experiments. In magazines, newspapers, and journals, some scoffed at what they saw as a fool\u27s errand and an egregious waste of public funds, while others were equally certain of the reality of the connection and regarded the potential windfall great enough to justifY any expense. Scientists in particular were almost unanimously doubtful (and occasionally hostile), and made their views clear in the scholarly organs of their profession. In the end, the experiments failed to prove a definitive connection; indeed, as many had predicted all along, sober assessments of the data yielded little to suggest any causal link between explosions and rainfall. Yet, curiously, this was by no means the end of the theory. Over the course of two decades, a colorful cast of characters, from an eccentric self-titled general to a millionaire cereal magnate-cum-social engineer, typified a stubborn core of devoted believers. Each attempted to prove (or make practical use of) the theory by discharging various weapons and explosives at the sky, hoping that raindrops would come down in exchange

Stimulation of Mitochondrial Biogenesis through Induction Of cGMP Promotes Recovery of Mitochondrial and Renal Function Following Acute Kidney Injury

Mitochondrial damage and dysfunction are major pathophysiological mechanisms underlying acute kidney injury (AKI). Following various forms of AKI, mitochondrial biogenesis, the de novo generation of new, functional mitochondria, is suppressed. Pharmacological stimulation of PPARγ-coactivator-1α (PGC-1α), the master regulator of mitochondrial biogenesis, promotes recovery of mitochondrial and renal function after AKI. The primary goals of this project were the evaluation of renal cGMP as a modulator of mitochondrial biogenesis in AKI, and the assessment of phosphodiesterase (PDE) inhibitors and guanylyl cyclase (GC) activators as novel agents to induce mitochondrial biogenesis and promote renal recovery. cGMP has been demonstrated to stimulate mitochondrial biogenesis and function. Both cGMP generation through guanylyl cyclase and degradation through PDEs are highly regulated processes. Compounds that regulate cGMP levels, including the PDE3 inhibitors cilostamide and trequinsin, and the PDE5 inhibitor sildenafil, increased mitochondrial gene expression, and elevated mitochondrial respiration in renal proximal tubule cell (RPTC) cultures. Furthermore, these compounds increased renal cortical mitochondrial gene expression and mtDNA copy number in naïve mice. PDE4 inhibitors, which regulate only cAMP levels had no effect. Treatment of mice with sildenafil in a folic acid model of AKI promoted recovery of mitochondrial gene expression, increased mtDNA content, and reduced expression of the tubular injury marker, kidney injury molecule-1 (KIM-1). An occurrence of AKI is a strong risk factor for the development of chronic kidney disease (CKD) and end stage renal disease (ESRD). Following folic acid-induced AKI, mice developed renal fibrosis and early signs of CKD. These changes were associated with a chronic suppression of mitochondrial gene expression and mtDNA copy number. Treatment of mice with trequinsin or sildenafil failed to restore mitochondrial gene expression, and failed to prevent the progression of fibrosis. Induction of cGMP through activation of guanylyl cyclase by the compound BAY 58-2667 increased mitochondrial respiration in RPTC, and additionally, increased mitochondrial gene and protein expression, and mtDNA copy number in mouse renal cortex. Daily treatment of mice with BAY 58-2667 beginning 24 h after renal ischemia-reperfusion (I/R) injury promoted renal functional and morphological recovery at 144 h after reperfusion. Renal inflammation and oxidative stress were also reduced. Renal recovery was associated with recovery of mitochondrial gene and protein expression, and mtDNA content in the renal cortex. Taken together, we have demonstrated that cGMP is a regulator of mitochondrial biogenesis in the kidney, and activation of mitochondrial biogenesis through modulators of cGMP can promote recovery of renal function following AKI. PDE inhibitors and guanylyl cyclase activators represent novel therapeutics that warrant further evaluation as potential interventions to treat AKI and other diseases characterized by mitochondrial dysfunction. To provide a platform for clinical evaluation of mitochondrial biogenics in renal disease in humans, we examined urinary ATP synthase subunit beta and urinary mtDNA as non-invasive biomarkers of renal mitochondrial dysfunction. These markers were shown to be efficacious as diagnostic and/or prognostic biomarkers of renal damage and mitochondrial dysfunction, and will aid in future development of mitochondrial-targeted renal therapies

The Relation between Galaxy Structure and Spectral Type: Implications for the Buildup of the Quiescent Galaxy Population at 0.5<z<2.0

We present the relation between galaxy structure and spectral type, using a K-selected galaxy sample at 0.5<z<2.0. Based on similarities between the UV-to-NIR spectral energy distributions, we classify galaxies into 32 spectral types. The different types span a wide range in evolutionary phases, and thus -- in combination with available CANDELS/F160W imaging -- are ideal to study the structural evolution of galaxies. Effective radii (R_e) and Sersic parameters (n) have been measured for 572 individual galaxies, and for each type, we determine R_e at fixed stellar mass by correcting for the mass-size relation. We use the rest-frame U-V vs. V-J diagram to investigate evolutionary trends. When moving into the direction perpendicular to the star-forming sequence, in which we see the Halpha equivalent width and the specific star formation rate (sSFR) decrease, we find a decrease in R_e and an increase in n. On the quiescent sequence we find an opposite trend, with older redder galaxies being larger. When splitting the sample into redshift bins, we find that young post-starburst galaxies are most prevalent at z>1.5 and significantly smaller than all other galaxy types at the same redshift. This result suggests that the suppression of star formation may be associated with significant structural evolution at z>1.5. At z<1, galaxy types with intermediate sSFRs (10^{-11.5}-10^{-10.5} yr^-1) do not have post-starburst SED shapes. These galaxies have similar sizes as older quiescent galaxies, implying that they can passively evolve onto the quiescent sequence, without increasing the average size of the quiescent galaxy population.Comment: 7 pages, 5 figures; Accepted for publication in ApJ

Ionization behavior of the histidine residue in the catalytic triad of serine proteases

α-Lytic protease is a homologue of the mammalian serine proteases such as trypsin, chymotrypsin, and elastase, and its single histidine residue belongs to the Asp-His-Ser catalytic triad. This single histidine residue has been selectively enriched in the C-2 carbon with 13C. Magnetic resonance studies of the chemical shift and coupling constant (1Jch) behavior of this nucleus as a function of pH suggest that the imidazole ring is neutral above pH 5 and therefore that the group which is known to ionize with pKa near 6.7 must be the aspartic acid residue. Implications of these new pKa assignments for the catalytic mechanism of serine proteases are discussed and include the absence of any need to separate charge during catalysis. The histidine residue plays two roles. (a) It insulates the aspartic acid from an aqueous environment and accordingly raises its pKa. (b) It serves as a bidentate base to accept a proton from the serine at one of its nitrogens and concertedly transfer a proton from its other nitrogen to the buried carboxylate anion during formation of the tetrahedral intermediate