Direct and long-lasting effects elicited by repeated drug administration on 50-kHz ultrasonic vocalizations are regulated differently: Implications for the study of the affective properties of drugs of abuse

Several studies suggest that 50-kHz ultrasonic vocalizations (USVs) may indicate a positive affective state in rats, and these vocalizations are increasingly being used to investigate the properties of psychoactive drugs. Previous studies, however, have focused on dopaminergic psychostimulants and morphine, whereas little is known about how other drugs modulate 50-kHz USVs. To further elucidate the neuropharmacology of 50-kHz USVs, the present study characterized the direct and long-lasting effects of different drugs of abuse, by measuring the number of 50-kHz USVs and their 'trill' subtype emitted by adult male rats. Rats received repeated administrations of amphetamine (2 mg/kg, i.p.), 3,4-methylenedioxymethamphetamine (MDMA, 7.5 mg/kg, i.p.), morphine (7.5 mg/kg, s.c.), or nicotine (0.4 mg/kg, s.c.), on either consecutive or alternate days (five administrations in total) in a novel environment. Seven days later, rats were re-exposed to the drug-paired environment, subjected to USVs recording, and then challenged with the same drug. Finally, 7 d after the challenge, rats were repeatedly exposed to the drug-paired environment and vocalizations were measured. Amphetamine was the only drug to stimulate 50-kHz USVs and 'trill' subtype emission during administration and challenge. Conversely, all rats emitted 50-kHz USVs when re-exposed to the test cage, and this effect was most marked in morphine-treated rats, and less evident in nicotine-treated rats. This study demonstrates that the direct and long-lasting effects of drugs on 50-kHz USVs are regulated differently, providing a better understanding of the usefulness of these vocalizations in the study of psychoactive drugs

Development of a novel scheme for long-term body temperature monitoring: a review of benefits and applications

Body temperature is a health or disease marker that has been in clinical use for centuries. The threshold currently applied to define fever, with small variations, is 38 °C. However, current approaches do not provide a full picture of the thermoregulation process and its correlation with disease. This paper describes a new non-invasive body temperature device that improves the understanding of the pathophysiology of diseases by integrating a variety of temperature data from different body locations. This device enables to gain a deeper insight into fever, endogenous rhythms, subject activity and ambient temperature to provide anticipatory and more efficient treatments. Its clinical use would be a big step in the overcoming of the anachronistic febrile/afebrile dichotomy and walking towards a system medicine approach to certain diseases. This device has already been used in some clinical applications successfully. Other possible applications based on the device features and clinical requirements are also described in this paper.Cuesta Frau, D.; Varela Entrecanales, M.; Valor Pérez, R.; Vargas, B. (2015). Development of a novel scheme for long-term body temperature monitoring: a review of benefits and applications. Journal of Medical Systems. 39(4):1-7. doi:10.1007/s10916-015-0209-3S17394Gai, M., Merlo, I., Dellepiane, S., Cantaluppi, V., Leonardi, G., Fop, F., Guarena, C., Grassi, G., and Biancore, L., Glycemic pattern in diabetic patients on hemodialysis: Continuous Glucose Monitoring (CGM) analysis. Blood Purif. 38(1):68–73 , 2014.Kondziella, D., Friberg, C.K., Wellwood, I., Reiffurth, C., Fabricius, M., and Dreier, J.P.: Continuous EEG monitoring in aneurysmal subarachnoid hemorrhage: A systematic review. Neurocrit. Care (2014)Ciccone, A., Celani, M.G., Chiaramonte, R., Rossi, C., and Righetti, E., Continuous versus intermittent physiological monitoring for acute stroke. Cochrane Database Syst. Rev. 31, 2013.Kushimoto, S., Yamanouchi, S., Endo, T., Sato, T., Nomura, R., Fujita, M., Kudo, D., Omura, T., Miyagawa, N., and Sato, T., Body temperature abnormalities in non-neurological critically ill patients: A review of the literature. J. Intensive Care 2, 2014.Mc Callum, L., and Higgings, D., Measuring body temperature. Nursing Times 108:20–22, 2012.Varela, M., Ruiz-Esteban, R., Martinez-Nicolas, A., Cuervo-Arango, A., Barros, C., and Delgado, E.G., Catching the spike and tracking the flow: Holter-temperature monitoring in patients admitted in a general internal medicine ward. Int. J. Clin. Pract. 65(12):1283–1288, 2011.Lopes, F., Peres, D., Bross, A., Melot, C., and Vincent, J.L., Serial evaluation of the SOFA score to predict outcome in critically ill patients. J. Am. Med. Assoc. 286:1754–1758, 2001.Vincent, J.L., and Moreno, R., Clinical review: Scoring systems in the critically ill. Crit. Care, 14, 2010.Sund-Levander, M., and Grodzinsky, E., Time for a change to assess and evaluate body temperature in clinical practice. Int. J. Nurs. Pract. 15:241–249, 2009.Cuesta-Frau, D., Varela, M., Aboy, M., and Miro, P., Description of a portable wireless device for body temperature acquisition and analysis. Sensors 9(10):7648–7663, 2009.Varela, M., Cuesta-Frau, D., Madrid, J.A., Churruca, J., Miro-Matinez, P., Ruiz, R., and Marinez, C., Holter monitoring of central peripheral temperature: Possible uses and feasibility study in outpatient settings. J. Clin. Monit. Comput. 4(23):209–216, 2009.Jordan, J., Miro, P., Cuesta-Frau, D., Varela, M., and Vargas B.: Aplicacion de analisis multivariante para la deteccion de estados prefebriles en pacientes ingresados (in Spanish), XXXIV Congreso Nacional de Estadistica e Investigacion Operativa, Castellon (Spain) (2013)Richman, J., and Moorman, J.R., Physiological time-series analysis using approximate entropy and sample entropy. Am. J. Physiol. Heart Circ. Physiol. 278(6):H2039–2049, 2000.Young, P., Saxena, M., Eastwood, G.M., Bellomo, R., and Beasley, R., Fever and fever management among intensive care patients with known or suspected infection: A multicentre prospective cohort study. Crit. Care Resusc. 13:97–102 , 2011.Drewry, A.M., Fuller, B.M., Bailey, T.C., and Hotchkiss, R.S., Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile adult intensive care unit patients: A case-control study. Crit. Care,17, 2013.Musher, D., Fainstein, V., Young, E., and Pruett, T., Fever patterns. Their lack of significance. Arch. Intern. Med. 139(11):1225–8, 1979.Varela, M., Calvo, M., Chana, M., Gomez-Mestre, I., Asensio, R., and Galdos, P., Clinical implications of temperature curve complexity in critically ill patients. Crit. Care Med. 33(12):2764–2771, 2005.Varela, M., Churruca, J., Gonzalez, A., Martin, A., Ode, J., and Galdos, P., Temperature curve complexity predicts survival in critically ill patients. Am. J. Respir. Crit. Care Med. 174(3):290–298, 2006.Cuesta-Frau, D., Varela, M., Miro, P., Galdos, P., Abasolo, D., Hornero, R., and Aboy, M., Predicting survival in critical patients by use of body temperature regularity measurement based on Approximate Entropy. Med. Biol. Eng. Computing 45:671–678, 2007.Mackiowak, P. Temperature regulation and the pathogenesis of fever, Principles and Practice of Infectious Diseases, pp. 765–778. New York: Churchill Livingston Elsevier, 2010.Cherbuin N., and Brinkman C., Cognition is cool: Can hemispheric activation be assessed by tympanic membrane thermometry? Brain Cogn. 54:228–231, 2004

N=1/2 gauge theory and its instanton moduli space from open strings in R-R background

We derive the four dimensional N=1/2 super Yang-Mills theory from tree-level computations in RNS open string theory with insertions of closed string Ramond-Ramond vertices. We also study instanton configurations in this gauge theory and their ADHM moduli space, using systems of D3 and D(-1) branes in a R-R background.Comment: 29 pages, 6 figures, JHEP class (included

NGR Tumor-Homing Peptides : Structural Requirements for Effective APN (CD13) Targeting

Acknowledgements We thank The Development Trust, University of Aberdeen, for financial support and a fellowship to M.P.Peer reviewedPublisher PD

Instanton calculus in R-R background and the topological string

We study a system of fractional D3 and D(-1) branes in a Ramond-Ramond closed string background and show that it describes the gauge instantons of N=2 super Yang-Mills theory and their interactions with the graviphoton of N=2 supergravity. In particular, we analyze the instanton moduli space using string theory methods and compute the prepotential of the effective gauge theory exploiting the localization methods of the instanton calculus showing that this leads to the same information given by the topological string. We also comment on the relation between our approach and the so-called Omega-background.Comment: 38 pages, 2 figures, JHEP class (included); final version to be pubished in JHE

The molecular gas content of the Pipe Nebula I. Direct evidence of outflow-generated turbulence in B59?

The Pipe Nebula is a molecular cloud hosting the B59 region as its only active star-forming clump. While the particular importance of outflows in active star forming regions is subject of debate, the quiet nature of the gas in B59 makes it a good site to directly see the impact of protostellar feedback on the quiescent dense gas. Using HARP at the JCMT, we mapped the B59 region with the J=3-2 transition of 12CO to study the kinematics and energetics of the outflows, and 13CO and C18O to study the overall dynamics of the ambient cloud, the physical properties of the gas, and the hierarchical structure of the region. The B59 region has a total of 30Msun of cold and quiescent material, mostly gravitationally bound, with narrow line widths throughout. Such low levels of turbulence in non-star-forming sites of B59 are indicative of the intrinsic initial conditions of the cloud. On the other hand, close to the forming protostars the impact of the outflows is observed as a localised increase of both line widths from 0.3 to 1 km/s, and 13CO excitation temperatures by 2-3K. The impact of the outflows is also evident in the low column density material which shows signs of being pushed, shaped and carved by the outflow bow shocks as they pierce their way out of the cloud. Much of this structure is readily apparent in a dendrogram analysis of the cloud. The low mass of B59 together with its intrinsically quiescent gas and small number of protostars, allows the identification of specific regions where the outflows from the embedded sources interact the dense gas. Our study suggests that outflows are an important mechanism for injecting and sustaining supersonic turbulence at sub-parsec size scales. We find that less than half of the outflow energy is deposited as turbulent energy of the gas, however this turbulent energy is sufficient to slow down the collapse of the region.Comment: Accepted for publication in A&

Atmospheric and Oceanographic Forcing Impact Particle Flux Composition and Carbon Sequestration in the Eastern Mediterranean Sea: A Three-Year Time-Series Study in the Deep Ierapetra Basin.

Sinking particles are a critical conduit for the export of organic material from surface waters to the deep ocean. Despite their importance in oceanic carbon cycling, little is known about the biotic composition and seasonal variability of sinking particles reaching abyssal depths. Herein, sinking particle flux data, collected in the deep Ierapetra Basin for a three-year period (June 2010 to June 2013), have been examined at the light of atmospheric and oceanographic parameters and main mass components (lithogenic, opal, carbonates, nitrogen, and organic carbon), stable isotopes of particulate organic carbon (POC) and source-specific lipid biomarkers. Our aim is to improve the current understanding of the dynamics of particle fluxes and the linkages between atmospheric dynamics and ocean biogeochemistry shaping the export of organic matter in the deep Eastern Mediterranean Sea. Overall, particle fluxes showed seasonality and interannual variability over the studied period. POC fluxes peaked in spring April-May 2012 (12.2 mg m−2 d−1) related to extreme atmospheric forcing. Summer export was approximately fourfold higher than mean wintertime, fall, and springtime (except for the episodic event of spring 2012), fueling efficient organic carbon sequestration. Lipid biomarkers indicate a high relative contribution of natural and anthropogenic, marine- and land-derived POC during both spring (April-May) and summer (June-July) reaching the deep-sea floor. Moreover, our results highlight that both seasonal and episodic pulses are crucial for POC export, while the coupling of extreme weather events and atmospheric deposition can trigger the influx of both marine labile carbon and anthropogenic compounds to the deep Levantine Sea. Finally, the comparison of time series data of sinking particulate flux with the corresponding biogeochemical parameters data previously reported for surface sediment samples from the deep-sea shed light on the benthic-pelagic coupling in the study area. Thus, this study underscores that accounting the seasonal and episodic pulses of organic carbon into the deep sea is critical in modeling the depth and intensity of natural and anthropogenic POC sequestration, and for a better understanding of the global carbon cycle

Instantons in N=2 magnetized D-brane worlds

In a toroidal orbifold of type IIB string theory we study instanton effects in N=2 super Yang-Mills theories engineered with systems of wrapped magnetized D9 branes and Euclidean D5 branes. We analyze the various open string sectors in this brane system and study the 1-loop amplitudes described by annulus diagrams with mixed boundary conditions, explaining their role in the stringy instanton calculus. We show in particular that the non-holomorphic terms in these annulus amplitudes precisely reconstruct the appropriate Kahler metric factors that are needed to write the instanton correlators in terms of purely holomorphic variables. We also explicitly derive the correct holomorphic structure of the instanton induced low energy effective action in the Coulomb branch.Comment: 40 pages, 5 figures, JHEP class. Some footnotes added and typos corrected. Version published in JHE

Instanton effects in N=1 brane models and the Kahler metric of twisted matter

We consider locally consistent systems of magnetized D9 branes on an orbifolded six-torus which support N=1 gauge theories. In such realizations, the matter multiplets arise from "twisted" strings connecting different stacks of branes. The introduction of Euclidean 5 branes (E5) wrapped on the six-dimensional compact space leads to instanton effects. For instance, if the system is engineered so as to yield SQCD, a single E5 brane may account for the ADS/TVY superpotential. We discuss the subtle interplay that exists between the annuli diagrams with an E5 boundary and the holomorphicity properties of the effective low-energy action of the N=1 theory. The consistency of this picture allows to obtain information on the Kahler metric of the chiral matter multiplets arising from twisted strings.Comment: 33 pages, 4 figures. V2: improved discussion, clarifyng comments and references added. Version to be published in JHE

N=1/2 quiver gauge theories from open strings with R-R fluxes

We consider a four dimensional N=1 gauge theory with bifundamental matter and a superpotential, defined on stacks of fractional branes. By turning on a flux for the R-R graviphoton field strength and computing open string amplitudes with insertions of R-R closed string vertices, we introduce a non-anticommutative deformation and obtain the N=1/2 version of the theory. We also comment on the appearance of a new structure in the effective Lagrangian.Comment: 30 pages, 5 figures, JHEP class (included); some comments and a reference adde