Characterization of the Active Site and Insight into the Binding Mode of the Anti-angiogenesis Agent Fumagillin to the Manganese(II)-Loaded Methionyl Aminopeptidase from \u3cem\u3eEscherichia coli\u3c/em\u3e

EPR spectra were recorded for methionine aminopeptidase from Escherichia coli (EcMetAP-I) samples (~2.5 mM) to which one and two equivalents of Mn(II) were added (the latter is referred to as [MnMn(EcMetAP-I)]). The spectra for each sample were indistinguishable except that the spectrum of [MnMn(EcMetAP-I)] was twice as intense. The EPR spectrum of [MnMn(EcMetAP-I)] exhibited the characteristic six-line g≈2 EPR signal of mononuclear Mn(II) with A av(55Mn)=9.3 mT (93 G) and exhibited Curie-law temperature dependence. This signal is typical of Mn(II) in a ligand sphere comprising oxygen and/or nitrogen atoms. Other features in the spectrum were observed only as the temperature was raised from that of liquid helium. The temperature dependences of these features are consistent with their assignment to excited state transitions in the S=1, 2 ... 5 non-Kramer’s doublets, due to two antiferromagnetically coupled Mn(II) ions with an S=0 ground state. This assignment is supported by the observation of a characteristic 4.5 mT hyperfine pattern, and by the presence of signals in the parallel mode consistent with a non-Kramers’ spin ladder. Upon the addition of the anti-angiogenesis agent fumagillin to [MnMn(EcMetAP-I)], very small changes were observed in the EPR spectrum. MALDI-TOF mass spectrometry indicated that fumagillin was, however, covalently coordinated to EcMetAP-I. Therefore, the inhibitory action of this anti-angiogenesis agent on EcMetAP-I appears to involve covalent binding to a polypeptide component at or near the active site rather than direct binding to the metal ions

Cyst fluid antibiotic concentrations in polycystic kidney disease: Differences between proximal and distal cysts

Cyst fluid antibiotic concentrations in polycystic kidney disease: Differences between proximal and distal cysts. The concentrations of several antibiotics were measured in the cyst fluid of six adult patients with polycystic kidney disease Seventy-nine cysts were aspirated at surgery or autopsy Sixty-one cysts could be categorized as arising from the proximal nephron and 16 from the distal nephron by cyst fluid to serum sodium ratios. Serum, urine, and cyst fluid were simultaneously analyzed for sodium, creatinine, and various antibiotics. Gentamicin, tobramycin, cephapirin, and ticarcillin were either undetectable or present in low concentrations in renal cysts. Cyst fluid antibiotic concentrations did not correlate with cyst volume or creatinine clearance. Cysts of proximal nephron origin had higher antibiotic concentrations than distal cysts. In one patient with normal renal function, inulin was undetectable in renal cysts after a continuous 36-hour i.v. infusion. Para-aminohippurate, however, was detected in the renal cysts of this patient. These data help explain the poor clinical response of infected renal cysts to antibiotic therapy. They also suggest that antibiotics and other solutes may enter cyst fluid across tubular cells in addition to entry by glomerular filtration.Concentration intra kystique d'antibiotiques dans la maladie poly kystique rénale: Différences entre les kystes proximaux et distaux. Les concentrations de plusieurs antibiotiques dans le liquide des kystes ont été mesurées chez six sujets adultes atteints de maladie polykystique. Soixante dix neuf kystes ont été ponctionnés pendant des interventions chirurgicales ou des autopsies. Soixante et un kystes ont pu être classés comme proximaux et seize comme distaux en fonction du rapport de concentration de sodium kyste/plasma. Des déterminations de concentration de sodium, de creatinine et de divers antibiotiques ont été réalisées simultanément pour le plasma, l'urine et le liquide des kystes. La gentamicine, la tobramycine, la cephapirine et la ticarcilline étaient soit non détectables soit à des concentrations très faibles dans les kystes. Les concentrations d'antibiotiques dans les kystes n'étaient pas corrélées avec le volume du kyste ou la clearance de la creatinine. Les kystes proximaux avaient des concentrations d'antibiotiques plus élevées que les kystes distaux. Chez un malade dont la fonction rénale était normale l'inuline n'était pas détectable dans les kystes après une perfusion continue de 36 heures. Le para-aminohippurate, cependant, a été détecté dans les mêmes kystes. Ces résultats permettent de comprendre la réponse clinique faible des kystes infectés au traitement antibiotique. Ils suggèrent aussi que les antibiotiques ainsi que d'autres substances dissoutes peuvent pénétrer dans les kystes à travers les cellules tubulaires en sus de la pénétration par filtration glomérulaire

A Synopsis of Interfacial Phenomena in Lithium-Based Polymer Electrolyte Electrochemical Cells

The interfacial regions between electrode materials, electrolytes and other cell components play key roles in the overall performance of lithium-based batteries. For cell chemistries employing lithium metal, lithium alloy or carbonaceous materials (i.e., lithium-ion cells) as anode materials, a "solid electrolyte interphase" (SEI) layer forms at the anode/electrolyte interface, and the properties of this "passivating" layer significantly affect the practical cell/battery quality and performance. A thin, ionically-conducting SEI on the electrode surface can beneficially reduce or eliminate undesirable side reactions between the electrode and the electrolyte, which can result in a degradation in cell performance. The properties and phenomena attributable to the interfacial regions existing at both anode and cathode surfaces can be characterized to a large extent by electrochemical impedance spectroscopy (EIS) and related techniques. The intention of the review herewith is to support the future development of lithium-based polymer electrolytes by providing a synopsis of interfacial phenomena that is associated with cell chemistries employing either lithium metal or carbonaceous "composite" electrode structures which are interfaced with polymer electrolytes (i.e., "solvent-free" as well as "plasticized" polymer-binary salt complexes and single ion-conducting polyelectrolytes). Potential approaches to overcoming poor cell performance attributable to interfacial effects are discussed

Experimental Lithium-Ion Battery Developed for Demonstration at the 2007 NASA Desert Research and Technology Studies (D-RATS) Program

The NASA Glenn Research Center (GRC) Electrochemistry Branch designed and built five lithium-ion battery packs for demonstration in spacesuit simulators as a part of the 2007 Desert Research and Technology Studies (D-RATS) activity at Cinder Lake, Arizona. The experimental batteries incorporated advanced, NASA-developed electrolytes and included internal protection against over-current, overdischarge and over-temperature. The 500-g experimental batteries were designed to deliver a constant power of 22 W for 2.5 hr with a minimum voltage of 13 V. When discharged at the maximum expected power output of 38.5 W, the batteries operated for 103 min of discharge time, achieving a specific energy of 130 Wh/kg. This report summarizes design details and safety considerations. Results for field trials and laboratory testing are summarized

Assessment of Lithium-based Battery Electrolytes Developed under the NASA PERS Program

Recently, NASA formally completed the Polymer Energy Rechargeable System (PERS) Program, which was established in 2000 in collaboration with the Air Force Research Laboratory (AFRL) to support the development of polymer-based, lithium-based cell chemistries and battery technologies to address the next generation of aerospace applications and mission needs. The goal of this program was to ultimately develop an advanced, space-qualified battery technology, which embodied a solid polymer electrolyte (SPE) and complementary components, with improved performance characteristics that would address future aerospace battery requirements. Programmatically, the PERS initiative exploited both interagency collaborations to address common technology and engineering issues and the active participation of academia and private industry. The initial program phases focused on R&D activities to address the critical technical issues and challenges at the cell level. A variety of cell and polymeric electrolyte concepts were pursued as part of the development efforts undertaken at numerous governmental, industrial and academic laboratories. Numerous candidate electrolyte materials were developed, synthesized and optimized for evaluation. Utilizing the component screening facility and the "standardized" test procedures developed at the NASA Glenn Research Center, electrochemical screening and performance evaluations of promising candidate materials were completed. This overview summarizes test results for a variety of candidate electrolyte materials that were developed under the PERS Program. Electrolyte properties are contrasted and compared to the original project goals, and the strengths and weaknesses of the electrolyte chemistries are discussed. Limited cycling data for full-cells using lithium metal and vanadium oxide electrodes are also presented. Based on measured electrolyte properties, the projected performance characteristics and temperature limitations of batteries utilizing the advanced electrolytes and components have been estimated. Limitations for the achievement of practical performance levels are also discussed, as well as needs for future research and development

Quantum privacy amplification and the security of quantum cryptography over noisy channels

Existing quantum cryptographic schemes are not, as they stand, operable in the presence of noise on the quantum communication channel. Although they become operable if they are supplemented by classical privacy-amplification techniques, the resulting schemes are difficult to analyse and have not been proved secure. We introduce the concept of quantum privacy amplification and a cryptographic scheme incorporating it which is provably secure over a noisy channel. The scheme uses an `entanglement purification' procedure which, because it requires only a few quantum Controlled-Not and single-qubit operations, could be implemented using technology that is currently being developed. The scheme allows an arbitrarily small bound to be placed on the information that any eavesdropper may extract from the encrypted message.Comment: 13 pages, Latex including 2 postcript files included using psfig macro

Comparison of Environmental Assessments of Two Proposed Harbor Expansions on the Mississippi River

The National Environmental Policy Act of 1969 requires federally funded projects to be evaluated for environmental impact to determine if a complete environmental impact statement must be prepared. Such an environmental assessment must also be included in any feasibility study for harbor enlargement and bank stabilization measures under the Water Resources Development Act. Population increases, coupled with economic growth from increased agricultural and industrial productivity, have resulted in increased Mississippi River barge transportation needs for Arkansas and Missouri. We report here two such environmental assessments of planned harbor expansions of the New Madrid County and Pemiscot County ports in the Missouri bootheel along the Mississippi River. We evaluated the environmental settings, presence of wetlands, and the presence of hazardous, toxic or radioactive wastes (HTRW) at the two sites. The results of these evaluations were used to determine the possible significant resources and impacts (including endangered species) associated with harbor expansion at the two sites. No significant HTRW were present or likely to be encountered during construction at either site. However, differences in 1) the environmental settings (open high banks vs. bottomland forest), 2) significant resources (historical accounts of least tern colonies at one site), and 3) presence of wetland habitat at one site may preclude or reduce the level of one or both harbor expansions. Careful consideration of possible environmental impacts may help guide the choice of sites for similar harbor expansions in Arkansas

On the role of entanglement in quantum computational speed-up

For any quantum algorithm operating on pure states we prove that the presence of multi-partite entanglement, with a number of parties that increases unboundedly with input size, is necessary if the quantum algorithm is to offer an exponential speed-up over classical computation. Furthermore we prove that the algorithm can be classically efficiently simulated to within a prescribed tolerance \eta even if a suitably small amount of global entanglement (depending on \eta) is present. We explicitly identify the occurrence of increasing multi-partite entanglement in Shor's algorithm. Our results do not apply to quantum algorithms operating on mixed states in general and we discuss the suggestion that an exponential computational speed-up might be possible with mixed states in the total absence of entanglement. Finally, despite the essential role of entanglement for pure state algorithms, we argue that it is nevertheless misleading to view entanglement as a key resource for quantum computational power.Comment: Main proofs simplified. A few further explanatory remarks added. 22 pages, plain late