Crystalline ionic solutions

Systems of crystalline ionic solutions containing impurity cations and associated compensation defects are described. Interactions between aliovalent ions and compensation defects give rise to configuration partition functions which predict a distribution in ion-defect pair separation distances at low temperatures. At elevated temperatures such ion-defect pairs dissociate, and the concept of pair formation more appropriately gives way to the concept of pair correlation functions. The relative sizes of the aliovalent ion and the host ion which it replaces are seen to exert a pronounced effect on pair distribution. Salient features of the theory are applied to the KCl: Sr2+, NaCl: Mn2+, NaCl: Sr2+, LiCl: Mn2+ and (alkaline-earth halide): (rareearth)3+ systems. While the high-temperature treatment lends itself to comparisons with the Debye-Hückel theory for electrolytes, the low-temperature pair distribution theory is shown to be valid chiefly because of the specific nature of the crystalline ionic solutions

Development and Application of an Integrated Approach toward NASA Airspace Systems Research

The National Aeronautics and Space Administration's (NASA) Airspace Systems Program is contributing air traffic management research in support of the 2025 Next Generation Air Transportation System (NextGen). Contributions support research and development needs provided by the interagency Joint Planning and Development Office (JPDO). These needs generally call for integrated technical solutions that improve system-level performance and work effectively across multiple domains and planning time horizons. In response, the Airspace Systems Program is pursuing an integrated research approach and has adapted systems engineering best practices for application in a research environment. Systems engineering methods aim to enable researchers to methodically compare different technical approaches, consider system-level performance, and develop compatible solutions. Systems engineering activities are performed iteratively as the research matures. Products of this approach include a demand and needs analysis, system-level descriptions focusing on NASA research contributions, system assessment and design studies, and common systemlevel metrics, scenarios, and assumptions. Results from the first systems engineering iteration include a preliminary demand and needs analysis; a functional modeling tool; and initial system-level metrics, scenario characteristics, and assumptions. Demand and needs analysis results suggest that several advanced concepts can mitigate demand/capacity imbalances for NextGen, but fall short of enabling three-times current-day capacity at the nation s busiest airports and airspace. Current activities are focusing on standardizing metrics, scenarios, and assumptions, conducting system-level performance assessments of integrated research solutions, and exploring key system design interfaces

A reduced version of the NMC DERF 2 data set

The National Meterological Center (NMC) Dynamical Extended Range Forecast (DERF 2) data represents a major computational effort to better ascertain the potential for extended range forecasts and to develop a strategy for performing operational extended range forecasts using dynamical models. A major stumbling block for using this data has been the sheer volume of data that must be processed to perform even simple calculations. The product of the data reduction described is a manageable data set that fits comfortably on five magnetic tapes or on one compact disc. The document outlines the data reduction process of the second phase of DERF data. It contains the description of the fields and the resolution of both the original and final fields. In order to assist the users of this data set, maps of selected fields, using both the original truncation at rhomboidal 30 and the truncation of the final data at triangular 20, are displayed

New Strategies for Exploring RNA's 2′-OH Expose the Importance of Solvent during Group II Intron Catalysis

AbstractThe 2′-hydroxyl group contributes inextricably to the functional behavior of many RNA molecules, fulfilling numerous essential chemical roles. To assess how hydroxyl groups impart functional behavior to RNA, we developed a series of experimental strategies using an array of nucleoside analogs. These strategies provide the means to investigate whether a hydroxyl group influences function directly (via hydrogen bonding or metal ion coordination), indirectly (via space-filling capacity, inductive effects, and sugar conformation), or through interactions with solvent. The nucleoside analogs span a broad range of chemical diversity, such that quantitative structure activity relationships (QSAR) now become possible in the exploration of RNA biology. We employed these strategies to investigate the spliced exons reopening (SER) reaction of the group II intron. Our results suggest that the cleavage site 2′-hydroxyl may mediate an interaction with a water molecule

Characterization of mouse orofacial pain and the effects of lesioning TRPV1-expressing neurons on operant behavior

<p>Abstract</p> <p>Background</p> <p>Rodent models of orofacial pain typically use methods adapted from manipulations to hind paw; however, limitations of these models include animal restraint and subjective assessments of behavior by the experimenter. In contrast to these methods, assessment of operant responses to painful stimuli has been shown to overcome these limitations and expand the breadth of interpretation of the behavioral responses. In the current study, we used an operant model based on a reward-conflict paradigm to assess nociceptive responses in three strains of mice (SKH1-Hr^hr, C57BL/6J, TRPV1 knockout). We previously validated this operant model in rats and hypothesized in this study that wild-type mice would demonstrate a similar thermal stimulus-dependent response and similar operant pain behaviors. Additionally, we evaluated the effects on operant behaviors of mice manipulated genetically (e.g., TRPV1 k.o.) or pharmacologically with resiniferatoxin (RTX), a lesioning agent for TRPV1-expressing neurons. During the reward-conflict task, mice accessed a sweetened milk reward solution by voluntarily position their face against a neutral or heated thermode (37–55°C).</p> <p>Results</p> <p>As the temperature of the thermal stimulus became noxiously hot, reward licking events in SKH1-Hr^hrand C57BL/6J mice declined while licking events in TRPV1 k.o. mice were insensitive to noxious heat within the activation range of TRPV1 (37–52°C). All three strains displayed nocifensive behaviors at 55°C, as indicated by a significant decrease in reward licking events. Induction of neurogenic inflammation by topical application of capsaicin reduced licking events in SKH1-Hr^hrmice, and morphine rescued this response. Again, these results parallel what we previously documented using rats in this operant system. Following intracisternal treatment with RTX, C57BL/6J mice demonstrated a block of noxious heat at both 48 and 55°C. RTX-treated TRPV1 k.o. mice and all vehicle-treated mice displayed similar reward licking events as compared to the pre-treatment baseline levels. Both TRPV1 k.o. and RTX-treated C57BL/6J had complete abolishment of eye-wipe responses following corneal application of capsaicin.</p> <p>Conclusion</p> <p>Taken together, these results indicate the benefits of using the operant test system to investigate pain sensitivity in mice. This ability provides an essential step in the development of new treatments for patients suffering from orofacial pain disorders.</p

Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

PurposeTumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).Patients and methodsTavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done.ResultsThe combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses.ConclusionsThe combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors

Performance of the double multilayer monochromator on the NSLS wiggler beam line X25

A tunable, double multilayer x-ray monochromator has recently been implemented on the National Synchrotron Light Source (NSLS) X25 wiggler beam line. It is based on a parallel pair of tungsten-boron-carbide multilayer films grown on silicon substrates and purchased from Osmic, Inc. of Troy, Michigan, USA. It acts as an optional alternative to the conventional double silicon crystal monochromator, and uses the same alignment mechanism. Two other NSLS beam lines also have had this kind of monochromator installed recently, following the lead of the NSLS X20C IBM/MIT beam line which has used a double multilayer monochromator for several years. Owing to the 100 times broader bandwidth of a multilayer x-ray monochromator, compared with a silicon monochromator, the multilayer monochromator has the obvious advantage of delivering 100 times the flux of a silicon monochromator, and thereby makes more efficient use of the continuous synchrotron radiation spectrum, yet preserves the narrow collimation of the incident synchrotron beam. In particular, multilayer x-ray bandwidths, on the order of 1%, are well-matched to x-ray undulator linewidths. Performance results for the X25 multilayer monochromator are presented, comparing it with the silicon monochromator. Of note is its short- and long-term performance as an x-ray monochromator delivering the brightness of the wiggler source in the presence of the high-power white beam. Detailed measurements of its spatial beam profile and wavelength dispersion have been made, and it is shown how its resolution could be improved when desired. Finally, its peculiar, anisotropic resolution function in reciprocal space, and its bearing upon x-ray crystallography and scattering experiments, will be discussed, and highlighted by the results of a protein crystallography experiment. © 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87844/2/71_1.pd

An Improved Photometric Calibration of the Sloan Digital Sky Survey Imaging Data

We present an algorithm to photometrically calibrate wide field optical imaging surveys, that simultaneously solves for the calibration parameters and relative stellar fluxes using overlapping observations. The algorithm decouples the problem of "relative" calibrations, from that of "absolute" calibrations; the absolute calibration is reduced to determining a few numbers for the entire survey. We pay special attention to the spatial structure of the calibration errors, allowing one to isolate particular error modes in downstream analyses. Applying this to the Sloan Digital Sky Survey imaging data, we achieve ~1% relative calibration errors across 8500 sq.deg. in griz; the errors are ~2% for the u band. These errors are dominated by unmodelled atmospheric variations at Apache Point Observatory. These calibrations, dubbed "ubercalibration", are now public with SDSS Data Release 6, and will be a part of subsequent SDSS data releases.Comment: 16 pages, 17 figures, matches version accepted in ApJ. These calibrations are available at http://www.sdss.org/dr

Improving the prediction of hepatocellular carcinoma in cirrhotic patients with an arterially-enhancing liver mass

In the United States, cirrhotic patients with known or suspected hepatocellular carcinoma (HCC) are prioritized for liver transplantation. Noninvasive criteria for the diagnosis of HCC rely on arterial enhancement of a mass. The aim of this study was to determine whether clinical, laboratory, and / or radiologic data can improve the prediction of HCC in cirrhotic patients with an arterially-enhancing mass. Between May 2002 and June 2003, dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of consecutive patients with liver cirrhosis and a solid mass were reviewed by 2 radiologists blinded to the clinical diagnosis. Clinical, laboratory, and radiologic data were recorded for all patients. A total of 94 patients with cirrhosis and an arterially-enhancing liver mass were studied, 66 (70%) of whom had HCC. Alpha-fetoprotein (AFP) >20 ng/mL ( P = .029), tumor size >2 cm ( P = .0018), and delayed hypointensity ( P = .0001) were independent predictors of HCC. Delayed hypointensity of an arterially-enhancing mass had a sensitivity of 89% and a specificity of 96% for HCC. The presence of delayed hypointensity was the only independent predictor of HCC among patients with arterially-enhancing lesions <2 cm (odds ratio, 6.3; 95% confidence interval [CI], 1.8-13), with a sensitivity of 80% and a specificity of 95%. In conclusion, delayed hypointensity of an arterially-enhancing mass was the strongest independent predictor of HCC, regardless of the size of the lesion. If additional studies confirm our results, the noninvasive criteria utilized to make a diagnosis of HCC should be revised. (Liver Transpl 2005;11:281–289.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35287/1/20357_ftp.pd