The loss of indirect interactions leads to cascading extinctions of carnivores

Species extinctions are biased towards higher trophic levels, and primary extinctions are often followed by unexpected secondary extinctions. Currently, predictions on the vulnerability of ecological communities to extinction cascades are based on models that focus on bottom-up effects, which cannot capture the effects of extinctions at higher trophic levels. We show, in experimental insect communities, that harvesting of single carnivorous parasitoid species led to a significant increase in extinction rate of other parasitoid species, separated by four trophic links. Harvesting resulted in the release of prey from top-down control, leading to increased interspecific competition at the herbivore trophic level. This resulted in increased extinction rates of non-harvested parasitoid species when their host had become rare relative to other herbivores. The results demonstrate a mechanism for horizontal extinction cascades, and illustrate that altering the relationship between a predator and its prey can cause wide-ranging ripple effects through ecosystems, including unexpected extinctions.

LOSS OF GPRC5A ENHANCES SURVIVAL IN NORMAL AND MALIGNANT LUNG EPITHELIAL CELLS BY ELICITING PERSISTENT STAT3 ACTIVATION INDUCED BY AUTOCRINE LIF

Signal transduction and activator of transcription 3 (Stat3) is activated by cytokines and growth factors in many cancers. Persistent activation of Stat3 plays important role in cell growth, survival, and transformation through regulating its targeted genes. Previously, we found that mice with a deletion of the G protein-coupled receptor, family C, group 5, member a (Gprc5a) gene develop lung tumors indicating that Gprc5a is a tumor suppressor. In the present study, we examined he mechanism of Gprc5a-mediated tumor suppression. We found that epithelial cells from Gprc5a knockout mouse lung (Gprc5a-/- cells) survive better in vitro in medium deprived of exogenous growth factors and form more colonies in semi-solid medium than their counterparts from wildtype mice (Gprc5a+/+ cells). The phosphorylation of tyrosine 705 on Stat3 and the expression of Stat3-regulated anti-apoptotic genes Bcl-XL, Cryab, Hapa1a, and Mcl1 were higher in the Gprc5a-/- than in Gprc5a+/+ cells. In addition, their responses to Lif were different; Stat3 activation was persistent by Lif treatment in the Gprc5a-/- cells, but was transient in the Gprc5a+/+ cells. The persistent activation of Stat3 by Lif in Gprc5a-/- cells is due to a decreased level of Socs3 protein, a negative inhibitor of the Lif-Stat3 signaling. Restoration of Socs3 inhibited the persistent Stat3 activation in Gprc5a-/- cells. Lung adenocarcinoma cells isolated from Gprc5a-/- mice also exhibited autocrine Lif-mediated Stat3 activation. Treatment of Gprc5a-/- cells isolated from normal and tumor tissue with AG490, a Stat3 signaling inhibitor, or with dominant negative Stat3(Y705F) increased starvation-induced apoptosis and inhibited anchorage-independent growth. These results suggest that persistent Stat3 activation increased the survival and transformation of Gprc5a-/- lung cells. Thus, the tumor suppressive effects of Gprc5a are mediated, at least in part, by inhibition of Stat3 signaling through regulating the stability of the Socs3 protein.

Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer

Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD+-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int-/-) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC.

Peri-implant bone loss of dental implants with platform-switching design after 5 years of loading: a cross-sectional study

OBJECTIVE The aim of this cross-sectional study was to estimate bone loss of implants with platform-switching design and analyze possible risk indicators after 5 years of loading in a multi-centered private practice network. METHOD AND MATERIALS Peri-implant bone loss was measured radiographically as the distance from the implant shoulder to the mesial and distal alveolar crest, respectively. Risk factor analysis for marginal bone loss included type of implant prosthetic treatment concept and dental status of the opposite arch. RESULTS A total of 316 implants in 98 study patients after 5 years of loading were examined. The overall mean value for radiographic bone loss was 1.02 mm (SD ± 1.25 mm, 95% CI 0.90- 1.14). Correlation analyses indicated a strong association of peri-implant bone loss > 2 mm for removable implant-retained prostheses with an odds ratio of 53.8. CONCLUSION The 5-year-results of the study show clinically acceptable values of mean bone loss after 5 years of loading. Implant-supported removable prostheses seem to be a strong co-factor for extensive bone level changes compared to fixed reconstructions. However, these results have to be considered for evaluation of the included special cohort under private dental office conditions.

Loss of Nogo-A-expressing neurons in a rat model of Parkinson's disease

The myelin-associated protein Nogo-A is among the most potent neurite growth inhibitors in the adult CNS. Recently, Nogo-A expression was demonstrated in a number of neuronal subpopulations of the adult and developing CNS but at present, little is known about the expression of Nogo-A in the nigrostriatal system, a brain structure severely affected in Parkinson's disease (PD). The present study sought to characterize the expression pattern of Nogo-A immunoreactive (ir) cells in the adult ventral mesencephalon of control rats and in the 6-hydroxydopamine (6-OHDA) rat model of PD. Immunohistochemical analyses of normal adult rat brain showed a distinct expression of Nogo-A in the ventral mesencephalon, with the highest level in the substantia nigra pars compacta (SNc) where it co-localized with dopaminergic neurons. Analyses conducted 1week and 1 month after unilateral striatal injections of 6-OHDA disclosed a severe loss of the number of Nogo-A-ir cells in the SNc. Notably, at 1week after treatment, more dopaminergic neurons expressing Nogo-A were affected by the 6-OHDA toxicity than Nogo-A-negative dopaminergic neurons. However, at later time points more of the surviving dopaminergic neurons expressed Nogo-A. In the striatum, both small and large Nogo-A-positive cells were detected. The large cells were identified as cholinergic interneurons. Our results suggest yet unidentified functions of Nogo-A in the CNS beyond the inhibition of axonal regeneration and plasticity, and may indicate a role for Nogo-A in PD.

Molecular consequences of the loss of 3'→5' exonuclease activity of DNA polymerases delta and epsilon

The DNA replication polymerases δ and ϵ have an inherent proofreading mechanism in the form of a 3'→5' exonuclease. Upon recognition of errant deoxynucleotide incorporation into DNA, the nascent primer terminus is partitioned to the exonuclease active site where the incorrectly paired nucleotide is excised before resumption of polymerization. The goal of this project was to identify the cellular and molecular consequences of an exonuclease deficiency. The proofreading capability of model system MEFs with EXOII mutations was abolished without altering polymerase function.^ It was hypothesized that 3'→5' exonucleases of polymerases δ and ϵ are critical for prevention of replication stress and important for sensitization to nucleoside analogs. To test this hypothesis, two aims were formulated: Determine the effect of the exonuclease active site mutation on replication related molecular signaling and identify the molecular consequences of an exonuclease deficiency when replication is challenged with nucleoside analogs.^ Via cell cycle studies it was determined that larger populations of exonuclease deficient cells are in the S-phase. There was an increase in levels of replication proteins, cell population growth and DNA synthesis capacity without alteration in cell cycle progression. These findings led to studies of proteins involved in checkpoint activation and DNA damage sensing. Finally, collective modifications at the level of DNA replication likely affect the strand integrity of DNA at the chromosomal level.^ Gemcitabine, a DNA directed nucleoside analog is a substrate of polymerases δ and ϵ and exploits replication to become incorporated into DNA. Though accumulation of gemcitabine triphosphate was similar in all cell types, incorporation into DNA and rates of DNA synthesis were increased in exonuclease defective cells and were not consistent with clonogenic survival. This led to molecular signaling investigations which demonstrated an increase in S-phase cells and activation of a DNA damage response upon gemcitabine treatment.^ Collectively, these data indicate that the loss of exonuclease results in a replication stress response that is likely required to employ other repair mechanisms to remove unexcised mismatches introduced into DNA during replication. When challenged with nucleoside analogs, this ongoing stress response coupled with repair serves as a resistance mechanism to cell death.^

Development and implementation of a dynamic heterogeneous proton equivalent anthropomorphic thorax phantom for the assessment of scanned proton beam therapy

DEVELOPMENT AND IMPLEMENTATION OF A DYNAMIC HETEROGENEOUS PROTON EQUIVALENT ANTHROPOMORPHIC THORAX PHANTOM FOR THE ASSESSMENT OF SCANNED PROTON BEAM THERAPY by James Leroy Neihart, B.S. APPROVED: ______________________________David Followill, Ph.D. ______________________________Peter Balter, Ph.D. ______________________________Narayan Sahoo, Ph.D. ______________________________Kenneth Hess, Ph.D. ______________________________Paige Summers, M.S. APPROVED: ____________________________ Dean, The University of Texas Graduate School of Biomedical Sciences at Houston DEVELOPMENT AND IMPLEMENTATION OF A DYNAMIC HETEROGENEOUS PROTON EQUIVALENT ANTHROPOMORPHIC THORAX PHANTOM FOR THE ASSESSMENT OF SCANNED PROTON BEAM THERAPY A THESIS Presented to the Faculty of The University of Texas Health Science Center at Houston andThe University of TexasMD Anderson Cancer CenterGraduate School of Biomedical Sciences in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE by James Leroy Neihart, B.S. Houston, Texas Date of Graduation August, 2013 Acknowledgments I would like to acknowledge my advisory committee members, chair David Followill, Ph.D., Peter Balter, Ph.D, Narayan Sahoo, Ph.D., Kenneth Hess, Ph.D., Paige Summers M.S. and, for their time and effort contributed to this project. I would additionally like to thank the faculty and staff at the PTC-H and the RPC who assisted in many aspects of this project. Falk Pӧnisch, Ph.D. for his breath hold proton therapy treatment expertise, Matt Palmer and Jaques Bluett for proton dosimetry assistance, Matt Kerr for verification plan assistance, Carrie Amador, Nadia Hernandez, Trang Nguyen, Andrea Molineu, Lynda McDonald for TLD and film dosimetry assistance. Finally, I would like to thank my wife and family for their support and encouragement during my research and studies. Development and implementation of a dynamic heterogeneous proton equivalent anthropomorphic thorax phantom for the assessment of scanned proton beam therapy By: James Leroy Neihart, B.S. Chair of Advisory Committee: David Followill, Ph.D Proton therapy has been gaining ground recently in radiation oncology. To date, the most successful utilization of proton therapy is in head and neck cases as well as prostate cases. These tumor locations do not suffer from the resulting difficulties of treatment delivery as a result of respiratory motion. Lung tumors require either breath hold or motion tracking, neither of which have been assessed with an end-to-end phantom for proton treatments. Currently, the RPC does not have a dynamic thoracic phantom for proton therapy procedure assessment. Additionally, such a phantom could be an excellent means of assessing quality assurance of the procedures of proton therapy centers wishing to participate in clinical trials. An eventual goal of this phantom is to have a means of evaluating and auditing institutions for the ability to start clinical trials utilizing proton therapy procedures for lung cancers. Therefore, the hypothesis of this study is that a dynamic anthropomorphic thoracic phantom can be created to evaluate end-to-end proton therapy treatment procedures for lung cancer to assure agreement between the measured and calculated dose within 5% / 5 mm with a reproducibility of 2%. Multiple materials were assessed for thoracic heterogeneity equivalency. The phantom was designed from the materials found to be in greatest agreement. The phantom was treated in an end-to-end treatment four times, which included simulation, treatment planning and treatment delivery. Each treatment plan was delivered three times to assess reproducibility. The dose measured within the phantom was compared to that of the treatment plan. The hypothesis was fully supported for three of the treatment plans, but failed the reproducibility requirement for the most aggressive treatment plan.

Abundance and sizes of European oak species (Quercus petraea (Matt.) Liebl., Quercus robur L.) in dependence of neighborhood and environmental factors

Quercus robur L. (pedunculate oak) and Quercus petraea (Matt.) Liebl. (sessile oak) are two European oak species of great economic and ecological importance. Even though both oaks have wide ecological amplitudes of suitable growing conditions, forests dominated by oaks often fail to regenerate naturally. The regeneration performance of both oak species is assumed to be subject to a variety of variables that interact with one another in complex ways. The novel approach of this research was to study the effect of many ecological variables on the regeneration performance of both oak species together and identify key variables and interactions for different development stages of the oak regeneration on a large scale in the field. For this purpose, overstory and regeneration inventories were conducted in oak dominated forests throughout southern Germany and paired with data on browsing, soil, and light availability. The study was able to verify the assumption that the occurrence of oak regeneration depends on a set of variables and their interactions. Specifically, combinations of site and stand specific variables such as light availability, soil pH and iron content on the one hand, and basal area and species composition of the overstory on the other hand. Also browsing pressure was related to oak abundance. The results also show that the importance of variables and their combinations differs among the development stages of the regeneration. Light availability becomes more important during later development stages, whereas the number of oaks in the overstory is important during early development stages. We conclude that successful natural oak regeneration is more likely to be achieved on sites with lower fertility and requires constantly controlling overstory density. Initially sufficient mature oaks in the overstory should be ensured. In later stages, overstory density should be reduced continuously to meet the increasing light demand of oak seedlings and saplings.

Equivalent dose, dose rate and age determination of cobble surfaces in the Antarctic

Most current methods of reconstructing past sea levels within Antarctica rely on radiocarbon dating. However, radiocarbon dating is limited by the availability of material for dating and problems inherent with radiocarbon reservoirs in Antarctic marine systems. Here we report on the success of a new approach to dating raised beach deposits in Antarctica for the purpose of reconstructing past sea levels. This new approach is the use of optically stimulated luminescence (OSL) on quartz-grains obtained from the underside of cobbles within raised beaches and boulder pavements. We obtained eight OSL dates from three sites along the shores of Maxwell Bay in the South Shetland Islands of the Antarctic Peninsula. These dates are internally consistent and fit well with previously published radiocarbon ages obtained from the same deposits. In addition, when the technique was applied to a modern beach, it resulted in an age of zero. Our results suggest that this method will provide a valuable tool in the reconstruction of past sea levels in Antarctica and other coarse-grained beach deposits across the globe.

Qualitative behaviour of L1 and L2 standard deviation in insulations measurements according to standard UNE EN ISO 140-4

Knowledge of the uncertainty of measurement of testing results is important when results have to be compared with limits and specifications. In the measurement of sound insulation following standards UNE EN ISO 140-4 the uncertainty of the final magnitude is mainly associated to the average sound pressure levels L1 and L2 measured. A parameter that allows us to quantify the spatial variation of the sound pressure level is the standard deviation of the pressure levels measured at different points of the room. In this work, for a wide number of measurements following standards UNE EN ISO 140-4 we analyzed qualitatively the behaviour of the standard deviation for L1 and L2. The study of sound fields in enclosed spaces is very difficult. There are a wide variety of rooms with different sound fields depending on factors as volume, geometry and materials. In general, we observe that the L1 and L2 standard deviations contain peaks and dips independent on characteristics of the rooms at single frequencies that could correspond to critical frequencies of walls, floors and windows or even to temporal alterations of the sound field. Also, in most measurements according to UNE EN ISO 140-4 a large similitude between L1 and L2 standard deviation is found. We believe that such result points to a coupled system between source and receiving rooms, mainly at low frequencies the shape of the L1 and L2 standard deviations is comparable to the velocity level standard deviation on a wall

Decelerated mass loss of Hurd and Johnsons Glaciers, Livingston Island, Antarctic Peninsula

A new 10 year surface mass balance (SMB) record of Hurd and Johnsons Glaciers, Livingston Island, Antarctica, is presented and compared with earlier estimates on the basis of local and regional meteorological conditions and trends.Since Johnsons is a tidewater glacier, we also include a calving flux calculation to estimate its total mass balance. The average annual SMB over the 10 year observation period 2002–11 is –0.15�0.10 m w.e. for Hurd Glacier and 0.05�0.10 m w.e. for Johnsons Glacier. Adding the calving losses to the latter results in a total mass balance of –0.09�0.10 m w.e. There has been a deceleration of the mass losses of these glaciers from 1957–2000 to 2002–11, which have nearly halved for both glaciers. We attribute this decrease in the mass losses to a combination of increased accumulation in the region and decreased melt. The increased accumulation is attributed to larger precipitation associated with the recent deepening of the circumpolar pressure trough, while the melt decrease is associated with lower summer surface temperatures during the past decade.

Estudio acústico de la iglesia Santa María del Castillo

En el presente proyecto se ha realizado un estudio sobre las condiciones acústicas de la iglesia Santa María del Castillo, ubicada en la localidad de Campo Real, al sureste de Madrid. Se trata de una iglesia construida entre los siglos XIV y XVII en diferentes fases, rica en características arquitectónicas correspondientes a varios estilos, tales como el gótico, el renacentista y el barroco. Reconocida en 1981 por sus valores arquitectónicos como Monumento Histórico–Artístico. A partir de unas completas mediciones del interior de la iglesia, se ha realizado un modelo tridimensional del mismo como base para la simulación mediante el software de simulación acústica EASE versión 4.3. Para conseguir que este modelo se asemeje a la realidad, se han realizado medidas del ruido de fondo en el interior de la iglesia en diferentes condiciones ambientales. Además se han creado mediante el software los coeficientes de absorción correspondientes a cada material presente en el interior de la iglesia y se han tenido en cuenta las características de los altavoces utilizados en la megafonía del recinto. El modelo en 3D obtenido caracteriza completamente las condiciones acústicas de la iglesia Santa María del Castillo, y nos sirve para valorar cómo es el sonido en el interior de la misma. Para ello obtenemos valores de diferentes parámetros acústico realizando simulaciones. Parámetros como el tiempo de reverberación y el nivel de presión sonora nos dan una idea general de cómo es el campo sonoro en el interior del recinto. Otros parámetros como el ALCons y el STI nos dan información sobre la inteligibilidad de la palabra en el recinto en el que se está realizando el estudio. Finalmente basándonos en los resultados obtenidos de la simulación se sacan conclusiones sobre las características acústicas de este recinto. La iglesia estudiada no es un recinto apropiado para la palabra y/o la música, además el predominio del campo reverberante sobre el campo directo es claro, esto es debido a las dimensiones del recinto y la poca absorción de los diferentes materiales empleados en su construcción, que son bastante reflexivos al sonido. ABSTRACT The present project undertakes the acoustic study of the church Santa María del Castillo. The church is the main temple of Campo Real, in the south-east of Madrid. It was built over different phases between the 14th and the 17th centuries and therefore, the presence of several architectural styles makes the church of Campo Real an interesting aim for this study. The building was recognised as Historic-Artistic Monument for its architectural value in 1981. Complete measurements from inside of the church were taken to build a computational 3D model which has been used to perform acoustic simulations of the church with the software EASE (Version 4.3). Noise measurements have been taken inside the church at different ambient conditions and they have been used to improve the reliability of the computational model. Furthermore, the model has been provided with software generated absorption coefficients and the characteristics of the actual loudspeakers have been taken into account. The 3D model created characterises all the acoustic conditions of the church Santa María del Castillo and allows the study of the sound properties inside the temple. Parameters such as reverberation time and sound pressure level were calculated performing simulations so the sound field inside the building can be described. Other parameters such as the Articulation Loss of Consonants (ALCons) and the Speech Transmission Index (STI) were studied to derive information about intelligibility inside the church. Finally, based on the results obtained by the simulation, I expose my conclusions about the acoustic characteristics of the building. The main conclusion derived from the present study is that the temple is not an appropriate place for voice or music listening due to the dimensions and the characteristics of the materials used in the construction since they are highly reflective to sound. The reverberant field predominates over the whole audience area in comparison with the direct field.

Influence of loudspeaker directivity and measurement geometry on direct acoustic levels over façades for acoustic insulation tests with the International Standard ISO 140-5

The International Standard ISO 140-5 on field measurements of airborne sound insulation of façades establishes that the directivity of the measurement loudspeaker should be such that the variation in the local direct sound pressure level (ΔSPL) on the sample is ΔSPL < 5 dB (or ΔSPL < 10 dB for large façades). This condition is usually not very easy to accomplish nor is it easy to verify whether the loudspeaker produces such a uniform level. Direct sound pressure levels on the ISO standard façade essentially depend on the distance and directivity of the loudspeaker used. This paper presents a comprehensive analysis of the test geometry for measuring sound insulation and explains how the loudspeaker directivity, combined with distance, affects the acoustic level distribution on the façade. The first sections of the paper are focused on analysing the measurement geometry and its influence on the direct acoustic level variations on the façade. The most favourable and least favourable positions to minimise these direct acoustic level differences are found, and the angles covered by the façade in the reference system of the loudspeaker are also determined. Then, the maximum dimensions of the façade that meet the conditions of the ISO 140-5 standard are obtained for the ideal omnidirectional sound source and the piston radiating in an infinite baffle, which is chosen as the typical radiation pattern for loudspeakers. Finally, a complete study of the behaviour of different loudspeaker radiation models (such as those usually utilised in the ISO 140-5 measurements) is performed, comparing their radiation maps on the façade for searching their maximum dimensions and the most appropriate radiation configurations.