Identification and inhibitory properties of a novel Ca(2+)/calmodulin antagonist.

We developed a high-throughput yeast-based assay to screen for chemical inhibitors of Ca(2+)/calmodulin-dependent kinase pathways. After screening two small libraries, we identified the novel antagonist 125-C9, a substituted ethyleneamine. In vitro kinase assays confirmed that 125-C9 inhibited several calmodulin-dependent kinases (CaMKs) competitively with Ca(2+)/calmodulin (Ca(2+)/CaM). This suggested that 125-C9 acted as an antagonist for Ca(2+)/CaM rather than for CaMKs. We confirmed this hypothesis by showing that 125-C9 binds directly to Ca(2+)/CaM using isothermal titration calorimetry. We further characterized binding of 125-C9 to Ca(2+)/CaM and compared its properties with those of two well-studied CaM antagonists: trifluoperazine (TFP) and W-13. Isothermal titration calorimetry revealed that binding of 125-C9 to CaM is absolutely Ca(2+)-dependent, likely occurs with a stoichiometry of five 125-C9 molecules to one CaM molecule, and involves an exchange of two protons at pH 7.0. Binding of 125-C9 is driven overall by entropy and appears to be competitive with TFP and W-13, which is consistent with occupation of similar binding sites. To test the effects of 125-C9 in living cells, we evaluated mitogen-stimulated re-entry of quiescent cells into proliferation and found similar, although slightly better, levels of inhibition by 125-C9 than by TFP and W-13. Our results not only define a novel Ca(2+)/CaM inhibitor but also reveal that chemically unique CaM antagonists can bind CaM by distinct mechanisms but similarly inhibit cellular actions of CaM.

THE LESSER-KNOWN PIANO CHAMBER MUSIC OF CAMILLE SAINT-SAENS: A RECORDING PROJECT

Throughout his long and industrious lifetime, Camille Saint-Saens (1835-1921) devoted himself unconditionally to music both as a composer and a performer. Saint-Saens was a self-described traditionalist and musical purist, yet his works are distinctly expressive and imaginative, and they reflect the composer's own unique musical language which incorporates recognizably modem traits such as chromaticism and frequent modulation. As a performer, Saint-Saens preferred to premiere his own works and often included his chamber music in his concert programs. Regarded primarily as a symphonic composer in the present day, however, his extensive and varied collection of chamber music works is sadly neglected. Six varied small-ensemble works with piano from his chamber music repertoire have been selected for study and recording for this project: Piano Trio No. 1 in F Major, Op. 18 (1864); Sonata for Cello and Piano No. 1 inC Minor, Op. 32 (1872); two pieces for two pianos, Le Rouet d'Omphale (The Spinning Wheel ofOmphale), Op. 31 (1871) and Phaeton, Op. 39 (1874); piano duet Konig Harald Haifagar (King Harald Haarfager), Op. 59 (1880); and a wind quartet, Caprice sur des airs Danois et Russes (Caprice on Danish and Russian Airs) for Flute, Oboe, Clarinet and Piano, Op. 79 (1887). Analyses of the forms and harmonic structures of these compositions will be included in this dissertation paper as well as studies from the viewpoint of Saint-Saens' compositional style, ensemble characteristics, and writing for the piano. The recordings for this project were made in four sessions in LeFrak Concert Hall at Queens College, the City University of New York. On September 24, 2003, Op. 31, Op. 39 and Op. 59 were recorded with Professor Morey Ritt, piano. On March 2, 2004, Op. 18 was recorded with Elena Rojas, violin, and Clare Liu, cello, and on March 15, 2004, Op. 32 was recorded, also with Ms. Liu. The Caprice, Op. 79 was recorded on June 27, 2008 with Laura Conwesser, flute; Randall Wolfgang, oboe; and Steve Hartman, clarinet. The recordings may be found on file in the library at the University of Maryland, College Park.

A comprehensive simulation study of slotted CSMA/CA for IEEE 802.15.4 wireless sensor networks

In this paper, we analyze the performance limits of the slotted CSMA/CA mechanism of IEEE 802.15.4 in the beacon-enabled mode for broadcast transmissions in WSNs. The motivation for evaluating the beacon-enabled mode is due to its flexibility for WSN applications as compared to the non-beacon enabled mode. Our analysis is based on an accurate simulation model of the slotted CSMA/CA mechanism on top of a realistic physical layer, with respect to the IEEE 802.15.4 standard specification. The performance of the slotted CSMA/CA is evaluated and analyzed for different network settings to understand the impact of the protocol attributes (superframe order, beacon order and backoff exponent) on the network performance, namely in terms of throughput (S), average delay (D) and probability of success (Ps). We introduce the concept of utility (U) as a combination of two or more metrics, to determine the best offered load range for an optimal behavior of the network. We show that the optimal network performance using slotted CSMA/CA occurs in the range of 35% to 60% with respect to an utility function proportional to the network throughput (S) divided by the average delay (D).

Pen and sunlight sketches of scenery reached by the Grand Trunk Railway and connections : including Niagara Falls, Thousand Islands, Rapids of the Saint Lawrence, Montreal, Quebec, and the mountains of New England.--

At head of title: "The tourist route of America".

Electrical Development Company of Ontario certificate of stock ownership, ca. 1910.

The Electrical Development Company of Ontario was created in 1903. It was one of three private power companies that had water power leases with the Niagara Parks Commission, but was the only one that was financed with Canadian capital. The company built the Toronto Power Generating Station at Niagara Falls beginning in 1906, and the power house was completed in 1913. During the construction, there was much debate about whether the utility should remain privately operated or become a public utility. In 1920, the company became part of the public utility.

Letter addressed by Benjamin Bates (bearer of the memorial) to a Member of the Legislature, ca. 1812.

Benjamin Bates was a member of the Religious Society of Friends, and served as Clerk of the Society at the time that the Memorial and Petition was written.

Letter addressed by Benjamin Bates (bearer of the memorial) to a Member of the Legislature, ca. 1812.

Benjamin Bates was a member of the Religious Society of Friends, and served as Clerk of the Society at the time that the Memorial and Petition was written.