Connectable Components for Protein Design

Protein design requires reusable, trustworthy, and connectable parts in order to scale to complex challenges. The recent explosion of protein structures stored within the Protein Data Bank provides a wealth of small motifs we can harvest, but we still lack tools to combine them into larger proteins. Here I explore two approaches for connecting reusable protein components on two different length scales. On the atomic scale, I build an interactive search engine for connecting chemical fragments together. Protein fragments built using this search engine recapitulate native-like protein assemblies that can be integrated into existing protein scaffolds using backbone search engines such as MaDCaT. On the protein domain scale, I quantitatively dissect structural variations in two-component systems in order to extract general principles for engineering interfacial flexibility between modular four-helix bundles. These bundles exhibit large scissoring motions where helices move towards or away from the bundle axis and these motions propagate across domain boundaries. Together, these two approaches form the beginnings of a multiscale methodology for connecting reusable protein fragments where there is a constant interplay and feedback between design of atomic structure, secondary structure, and tertiary structure. Rapid iteration, visualization, and search glue these diverse length scales together into a cohesive whole

Sueño, vigilia y calidad de vida laboral

Los factores de riesgo psicosocial que tienen incidencia crítica sobre el trabajo y las organizaciones, son fenómenos ampliamente abordados y de interés general. No es posible delimitar este conglomerado teórico a un solo concepto; de allí la necesidad de tomar punto a punto las características para iniciar un desarrollo apropiado del tema. Gran cantidad de trabajadores han sido víctima de las consecuencias de no llevar a cabo un control minucioso sobre las tareas que se realizan día a día, y que mantienen en funcionamiento la estructura socioeconómica en la que esta inmerso, es por esto que el tema debe ser de especial atención y relevancia general. En el presente trabajo se aborda el tema de estrés laboral, estrés organizacional y otras patologías resultantes de la falta de control sobre variables como: jornadas laborales, rotación y cambio de turnos, en fin todos aquellos aspectos que van en detrimento de la salud del trabajador y, por ende, de la organización. La aplicación de programas de salud ocupacional no puede seguir siendo en nuestro entorno un instrumento subestimado si se quiere lograr éxito organizacional, es labor conjunta con los líderes y trabajadores, de otra forma se seguirá incurriendo en errores que alimentan un circulo vicioso que afecta directamente la productividad y el bienestar colectivo. El tema sueño y vigilia, es el centro de interés en este trabajo, ya que las repercusiones psicofisiològicas de un manejo inadecuado de estos, como se mostrará en el desarrollo de estas líneas, son graves y afectan directamente de manera negativa en la salud individual y puede llegar a generar conflicto en todo el sistema si no se atiende a tiempo. Este es un tema que debe ser estudiado con mayor amplitud si se quiere llegar a un control total sobre las variables que afectan la organización y la calidad de vida de los trabajadores

Drivers of Bird- Window Collisions in Florida International University’s Modesto A. Maidique Campus

Bird-window collisions are among the top leading causes of death for birds in North America. Studies have found primary drivers of bird-window collisions to be window area, building size, and presence of vegetation around the buildings. We hypothesized that higher window area and vegetation would increase birdwindow collisions, with an inverse relationship between number of stories and bird-window collisions. Surveys were conducted for 21 consecutive days around six buildings at Florida International University (FIU) in October 2014. Using ArcGIS, 50m buffers were created around each building to calculate percent vegetation and ImageJ was used to calculate percent window cover. We collected 10 bird carcasses and 13 feather piles assumed to represent bird-window collisions. Most of the collisions (8 out of 21) occurred at the building with the lowest percent vegetation and low window area. Our sample size limits our ability to make general conclusions, however, our data is a part of a larger collaborative project that includes over 30 campuses across North America. Results from this larger project could provide insight on whether the magnitude of bird-window collisions relates to landscape structure and functional connectivity

Spitzer UltRa Faint SUrvey Program (SURFS UP). II. IRAC-Detected Lyman-Break Galaxies at 6 < z < 10 Behind Strong-Lensing Clusters

We study the stellar population properties of the IRAC-detected $6 \lesssim z \lesssim 10$ galaxy candidates from the Spitzer UltRa Faint SUrvey Program (SURFS UP). Using the Lyman Break selection technique, we find a total of 16 new galaxy candidates at $6 \lesssim z \lesssim 10$ with $S/N \geq 3$ in at least one of the IRAC $3.6\mu$m and $4.5\mu$m bands. According to the best mass models available for the surveyed galaxy clusters, these IRAC-detected galaxy candidates are magnified by factors of $\sim 1.2$--$5.5$. We find that the IRAC-detected $6 \lesssim z \lesssim 10$ sample is likely not a homogeneous galaxy population: some are relatively massive (stellar mass as high as $4 \times 10^9\,M_{\odot}$) and evolved (age $\lesssim 500$ Myr) galaxies, while others are less massive ($M_{\text{stellar}}\sim 10^8\,M_{\odot}$) and very young ($\sim 10$ Myr) galaxies with strong nebular emission lines that boost their rest-frame optical fluxes. We identify two Ly$\alpha$ emitters in our sample from the Keck DEIMOS spectra, one at $z_{\text{Ly}\alpha}=6.76$ (in RXJ1347) and one at $z_{\text{Ly}\alpha}=6.32$ (in MACS0454). We show that IRAC $[3.6]-[4.5]$ color, when combined with photometric redshift, can be used to identify galaxies likely with strong nebular emission lines within certain redshift windows.Comment: ApJ in pres

Functional consequence of the MET-T1010I polymorphism in breast cancer.

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials

Pollen segmentation and feature evaluation for automatic classification in bright-field microscopy

14 págs.; 10 figs.; 7 tabs.; 1 app.© 2014 Elsevier B.V. Besides the well-established healthy properties of pollen, palynology and apiculture are of extreme importance to avoid hard and fast unbalances in our ecosystems. To support such disciplines computer vision comes to alleviate tedious recognition tasks. In this paper we present an applied study of the state of the art in pattern recognition techniques to describe, analyze, and classify pollen grains in an extensive dataset specifically collected (15 types, 120 samples/type). We also propose a novel contour-inner segmentation of grains, improving 50% of accuracy. In addition to published morphological, statistical, and textural descriptors, we introduce a new descriptor to measure the grain's contour profile and a logGabor implementation not tested before for this purpose. We found a significant improvement for certain combinations of descriptors, providing an overall accuracy above 99%. Finally, some palynological features that are still difficult to be integrated in computer systems are discussed.This work has been supported by the European project APIFRESH FP7-SME-2008-2 ‘‘Developing European standards for bee pollen and royal jelly: quality, safety and authenticity’’ and we would like to thank to Mr. Walter Haefeker, President of the European Professional Beekeepers Association (EPBA). J. Victor Marcos is a ‘‘Juan de la Cierva’’ research fellow funded by the Spanish Ministry of Economy and Competitiveness. Rodrigo Nava thanks Consejo Nacional de Ciencia y Tecnología (CONACYT) and PAPIIT Grant IG100814.Peer Reviewe

From X-ray dips to eclipse: Witnessing disk reformation in the recurrent nova USco

The 10th recorded outburst of the recurrent eclipsing nova USco was observed simultaneously in X-ray, UV, and optical by XMM-Newton on days 22.9 and 34.9 after outburst. Two full passages of the companion in front of the nova ejecta were observed, witnessing the reformation of the accretion disk. On day 22.9, we observed smooth eclipses in UV and optical but deep dips in the X-ray light curve which disappeared by day 34.9, then yielding clean eclipses in all bands. X-ray dips can be caused by clumpy absorbing material that intersects the line of sight while moving along highly elliptical trajectories. Cold material from the companion could explain the absence of dips in UV and optical light. The disappearance of X-ray dips before day 34.9 implies significant progress in the formation of the disk. The X-ray spectra contain photospheric continuum emission plus strong emission lines, but no clear absorption lines. Both continuum and emission lines in the X-ray spectra indicate a temperature increase from day 22.9 to day 34.9. We find clear evidence in the spectra and light curves for Thompson scattering of the photospheric emission from the white dwarf. Photospheric absorption lines can be smeared out during scattering in a plasma of fast electrons. We also find spectral signatures of resonant line scattering that lead to the observation of the strong emission lines. Their dominance could be a general phenomenon in high-inclination systems such as Cal87.Comment: Submitted to ApJ. 16 pages, 16 figure

Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites

Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species

Calibration and in orbit performance of the reflection grating spectrometer onboard XMM-Newton

Context: XMM-Newton was launched on 10 December 1999 and has been operational since early 2000. One of the instruments onboard XMM-Newton is the reflection grating spectrometer (RGS). Two identical RGS instruments are available, with each RGS combining a reflection grating assembly (RGA) and a camera with CCDs to record the spectra. Aims: We describe the calibration and in-orbit performance of the RGS instrument. By combining the preflight calibration with appropriate inflight calibration data including the changes in detector performance over time, we aim at profound knowledge about the accuracy in the calibration. This will be crucial for any correct scientific interpretation of spectral features for a wide variety of objects. Methods: Ground calibrations alone are not able to fully characterize the instrument. Dedicated inflight measurements and constant monitoring are essential for a full understanding of the instrument and the variations of the instrument response over time. Physical models of the instrument are tuned to agree with calibration measurements and are the basis from which the actual instrument response can be interpolated over the full parameter space. Results: Uncertainties in the instrument response have been reduced to < 10% for the effective area and < 6 mA for the wavelength scale (in the range from 8 A to 34 A. The remaining systematic uncertainty in the detection of weak absorption features has been estimated to be 1.5%. Conclusions: Based on a large set of inflight calibration data and comparison with other instruments onboard XMM-Newton, the calibration accuracy of the RGS instrument has been improved considerably over the preflight calibrations.Comment: Accepted for publication in Astronomy and Astrophysics, Astronomical instrumentation sectio

PI3K Pathway Mutations and PTEN Levels in Primary and Metastatic Breast Cancer

The purpose of this work was to determine whether there are differences in PIK3CA mutation status and PTEN protein expression between primary and matched metastatic breast tumors as this could influence patient management. Fifty-micron paraffin sections were used for DNA extraction and 3-micron slides for immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH). ER, PR and HER2 IHC were repeated in a central laboratory for both primary and metastasis. PTEN levels were assessed by IHC and PI3K pathway mutations detected by a mass spectroscopy-based approach. Median age was 48 years (range, 30 to 83 years). Tumor subtype included 72% hormone receptor-positive/HER2-negative, 20% HER2-positive, and less than 7.8% triple receptor negative. Tissues were available for PTEN IHC in 46 primary tumors and 52 metastases. PTEN was lost in 14 (30%) primary tumors and 13 (25%) metastases. There were 5 cases of PTEN loss and eight cases of PTEN gain from primary to metastasis (26% discordance). Adequate DNA was obtained on 46 primary tumors and on 50 metastases for PIK3CA analysis. PIK3CA mutations were detected in 19 (40%) of primary tumors and 21 (42%) of metastases. There were five cases of PIK3CA mutation loss, and four cases of mutation gain (18% discordance). There was an increase of the level of PIK3CA mutations in four cases, and decrease in one from primary to metastasis. There is a high level of discordance in PTEN level, PIK3CA mutations, and receptor status between primary and metastatic disease that may influence patient selection and response to PI3K-targeted therapies