Genética de la conservación para la recuperación de especies animales en peligro de extinción: revisión de los planes de recuperación de especies en peligro de extinción de Estados Unidos (1977–1998)

The utility of genetic data in conservation efforts, particularly in comparison to demographic information, is the subject of ongoing debate. Using a database of information surveyed from 181 US endangered and threatened species recovery plans, we addressed the following questions concerning the use of genetic information in animal recovery plans: I. What is the relative prominence of genetic vs. demographic data in recovery plan development? and, II. When are genetic factors viewed as a threat, and how do plans respond to genetic threats? In general, genetics appear to play a minor and relatively ill–defined part in the recovery planning process; demographic data are both more abundant and more requested in recovery plans, and tasks are more frequently assigned to the collection / monitoring of demographic rather than genetic information. Nonetheless, genetic threats to species persistence and recovery are identified in a substantial minority (22 %) of recovery plans, although there is little uniform response to these perceived threats in the form of specific proposed recovery or management tasks. Results indicate that better guidelines are needed to identify how and when genetic information is most useful for species recovery; we highlight specific contexts in which genetics may provide unique management information, beyond that provided by other kinds of data.La utilidad de los datos genéticos en los esfuerzos conservacionistas, en particular en comparación con la información demográfica, es objeto de un continuo debate. Utilizando una base de datos con información sobre los 181 planes de recuperación de especies amenazadas y en peligro de extinción de Estados Unidos, hemos estudiado las siguientes cuestiones referentes al uso de la información genética en los planes de recuperación de especies animales: I ¿Cuál es la importancia relativa de los datos genéticos en comparación con los demográficos en el desarrollo de los planes de recuperación? y II ¿Cuándo se considera que los factores genéticos constituyen una amenaza, y cómo responden los planes a esas amenazas genéticas? En general, parece que la genética sólo desempeña un papel menor y relativamente mal definido en el proceso de planificación de la recuperación de especies; los datos demográficos son más abundantes y más solicitados para la elaboración de planes de recuperación, y las acciones que se llevan a cabo con frecuencia se enfocan más a las recopilación/observación de los datos demográficos que a la obtención de información genética. No obstante, las amenazas genéticas para la supervivencia y recuperación de especies se indican como un importante factor minoritario (22 %) en los planes de recuperación, si bien la respuesta a esas amenazas mediante medidas de gestión o recuperación específicas es poco uniforme. Los resultados apuntan a que se necesitan unas directrices más claras para determinar cómo y cuándo resulta más útil la información genética para la recuperación de especies; hemos resaltado contextos concretos en los que la genética puede proporcionar una valiosísima fuente de información para la gestión de esas cuestiones, superior a la que se pueda obtener a partir de otros datos

Inference with interference between units in an fMRI experiment of motor inhibition

An experimental unit is an opportunity to randomly apply or withhold a treatment. There is interference between units if the application of the treatment to one unit may also affect other units. In cognitive neuroscience, a common form of experiment presents a sequence of stimuli or requests for cognitive activity at random to each experimental subject and measures biological aspects of brain activity that follow these requests. Each subject is then many experimental units, and interference between units within an experimental subject is likely, in part because the stimuli follow one another quickly and in part because human subjects learn or become experienced or primed or bored as the experiment proceeds. We use a recent fMRI experiment concerned with the inhibition of motor activity to illustrate and further develop recently proposed methodology for inference in the presence of interference. A simulation evaluates the power of competing procedures.Comment: Published by Journal of the American Statistical Association at http://www.tandfonline.com/doi/full/10.1080/01621459.2012.655954 . R package cin (Causal Inference for Neuroscience) implementing the proposed method is freely available on CRAN at https://CRAN.R-project.org/package=ci

A Halomethane thermochemical network from iPEPICO experiments and quantum chemical calculations

Internal energy selected halomethane cations CH3Cl+, CH2Cl2+, CHCl3+, CH3F+, CH2F2+, CHClF2+ and CBrClF2+ were prepared by vacuum ultraviolet photoionization, and their lowest energy dissociation channel studied using imaging photoelectron photoion coincidence spectroscopy (iPEPICO). This channel involves hydrogen atom loss for CH3F+, CH2F2+ and CH3Cl+, chlorine atom loss for CH2Cl2+, CHCl3+ and CHClF2+, and bromine atom loss for CBrClF2+. Accurate 0 K appearance energies, in conjunction with ab initio isodesmic and halogen exchange reaction energies, establish a thermochemical network, which is optimized to update and confirm the enthalpies of formation of the sample molecules and their dissociative photoionization products. The ground electronic states of CHCl3+, CHClF2+ and CBrClF2+ do not confirm to the deep well assumption, and the experimental breakdown curve deviates from the deep well model at low energies. Breakdown curve analysis of such shallow well systems supplies a satisfactorily succinct route to the adiabatic ionization energy of the parent molecule, particularly if the threshold photoelectron spectrum is not resolved and a purely computational route is unfeasible. The ionization energies have been found to be 11.47 ± 0.01 eV, 12.30 ± 0.02 eV and 11.23 ± 0.03 eV for CHCl3, CHClF2 and CBrClF2, respectively. The updated 0 K enthalpies of formation, ∆fHo0K(g) for the ions CH2F+, CHF2+, CHCl2+, CCl3+, CCl2F+ and CClF2+ have been derived to be 844.4 ± 2.1, 601.6 ± 2.7, 890.3 ± 2.2, 849.8 ± 3.2, 701.2 ± 3.3 and 552.2 ± 3.4 kJ mol–1, respectively. The ∆fHo0K(g) values for the neutrals CCl4, CBrClF2, CClF3, CCl2F2 and CCl3F and have been determined to be –94.0 ± 3.2, –446.6 ± 2.7, –702.1 ± 3.5, –487.8 ± 3.4 and –285.2 ± 3.2 kJ mol–1, respectively

Semiparametric theory and empirical processes in causal inference

In this paper we review important aspects of semiparametric theory and empirical processes that arise in causal inference problems. We begin with a brief introduction to the general problem of causal inference, and go on to discuss estimation and inference for causal effects under semiparametric models, which allow parts of the data-generating process to be unrestricted if they are not of particular interest (i.e., nuisance functions). These models are very useful in causal problems because the outcome process is often complex and difficult to model, and there may only be information available about the treatment process (at best). Semiparametric theory gives a framework for benchmarking efficiency and constructing estimators in such settings. In the second part of the paper we discuss empirical process theory, which provides powerful tools for understanding the asymptotic behavior of semiparametric estimators that depend on flexible nonparametric estimators of nuisance functions. These tools are crucial for incorporating machine learning and other modern methods into causal inference analyses. We conclude by examining related extensions and future directions for work in semiparametric causal inference

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Chemical Kinetic Insights into the Octane Number and Octane Sensitivity of Gasoline Surrogate Mixtures

Gasoline octane number is a significant empirical parameter for the optimization and development of internal combustion engines capable of resisting knock. Although extensive databases and blending rules to estimate the octane numbers of mixtures have been developed and the effects of molecular structure on autoignition properties are somewhat understood, a comprehensive theoretical chemistry-based foundation for blending effects of fuels on engine operations is still to be developed. In this study, we present models that correlate the research octane number (RON) and motor octane number (MON) with simulated homogeneous gas-phase ignition delay times of stoichiometric fuel/air mixtures. These correlations attempt to bridge the gap between the fundamental autoignition behavior of the fuel (e.g., its chemistry and how reactivity changes with temperature and pressure) and engine properties such as its knocking behavior in a cooperative fuels research (CFR) engine. The study encompasses a total of 79 hydrocarbon gasoline surrogate mixtures including 11 primary reference fuels (PRF), 43 toluene primary reference fuels (TPRF), and 19 multicomponent (MC) surrogate mixtures. In addition to TPRF mixture components of iso-octane/n-heptane/toluene, MC mixtures, including n-heptane, iso-octane, toluene, 1-hexene, and 1,2,4-trimethylbenzene, were blended and tested to mimic real gasoline sensitivity. ASTM testing protocols D-2699 and D-2700 were used to measure the RON and MON of the MC mixtures in a CFR engine, while the PRF and TPRF mixtures' octane ratings were obtained from the literature. The mixtures cover a RON range of 0-100, with the majority being in the 70-100 range. A parametric simulation study across a temperature range of 650-950 K and pressure range of 15-50 bar was carried out in a constant-volume homogeneous batch reactor to calculate chemical kinetic ignition delay times. Regression tools were utilized to find the conditions at which RON and MON best correlate with simulated ignition delay times. Furthermore, temperature and pressure dependences were investigated for fuels with varying octane sensitivity. This analysis led to the formulation of correlations useful to the definition of surrogates for modeling purposes and allowed one to identify conditions for a more in-depth understanding of the chemical phenomena controlling the antiknock behavior of the fuels

Predicting HIV Pre-exposure Prophylaxis Efficacy for Women using a Preclinical Pharmacokinetic-Pharmacodynamic In Vivo Model

The efficacy of HIV pre-exposure prophylaxis (PrEP) relies on adherence and may also depend on the route of HIV acquisition. Clinical studies of systemic tenofovir disoproxil fumarate (TDF) PrEP revealed reduced efficacy in women compared to men with similar degrees of adherence. To select the most effective PrEP strategies, preclinical studies are critically needed to establish correlations between drug concentrations (pharmacokinetics [PK]) and protective efficacy (pharmacodynamics [PD]). We utilized an in vivo preclinical model to perform a PK-PD analysis of systemic TDF PrEP for vaginal HIV acquisition. TDF PrEP prevented vaginal HIV acquisition in a dose-dependent manner. PK-PD modeling of tenofovir (TFV) in plasma, female reproductive tract tissue, cervicovaginal lavage fluid and its intracellular metabolite (TFV diphosphate) revealed that TDF PrEP efficacy was best described by plasma TFV levels. When administered at 50 mg/kg, TDF achieved plasma TFV concentrations (370 ng/ml) that closely mimicked those observed in humans and demonstrated the same risk reduction (70%) previously attained in women with high adherence. This PK-PD model mimics the human condition and can be applied to other PrEP approaches and routes of HIV acquisition, accelerating clinical implementation of the most efficacious PrEP strategies

LDRD final report on high power broadly tunable Mid-IR quantum cascade lasers for improved chemical species detection.

The goal of our project was to examine a novel quantum cascade laser design that should inherently increase the output power of the laser while simultaneously providing a broad tuning range. Such a laser source enables multiple chemical species identification with a single laser and/or very broad frequency coverage with a small number of different lasers, thus reducing the size and cost of laser based chemical detection systems. In our design concept, the discrete states in quantum cascade lasers are replaced by minibands made of multiple closely spaced electron levels. To facilitate the arduous task of designing miniband-to-miniband quantum cascade lasers, we developed a program that works in conjunction with our existing modeling software to completely automate the design process. Laser designs were grown, characterized, and iterated. The details of the automated design program and the measurement results are summarized in this report

State and local governments plan for development of most land vulnerable to rising sea level along the US Atlantic coast

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of IOP Publishing for personal use, not for redistribution. The definitive version was published in Environmental Research Letters 4 (2009): 044008, doi:10.1088/1748-9326/4/4/044008.Rising sea level threatens existing coastal wetlands. Overall ecosystems could often survive by migrating inland, if adjacent lands remained vacant. On the basis of 131 state and local land use plans, we estimate that almost 60% of the land below 1 m along the US Atlantic coast is expected to be developed and thus unavailable for the inland migration of wetlands. Less than 10% of the land below 1 m has been set aside for conservation. Environmental regulators routinely grant permits for shore protection structures (which block wetland migration) on the basis of a federal finding that these structures have no cumulative environmental impact. Our results suggest that shore protection does have a cumulative impact. If sea level rise is taken into account, wetland policies that previously seemed to comply with federal law probably violate the Clean Water Act

LDRD final report on continuous wave intersubband terahertz sources.

There is a general lack of compact electromagnetic radiation sources between 1 and 10 terahertz (THz). This a challenging spectral region lying between optical devices at high frequencies and electronic devices at low frequencies. While technologically very underdeveloped the THz region has the promise to be of significant technological importance, yet demonstrating its relevance has proven difficult due to the immaturity of the area. While the last decade has seen much experimental work in ultra-short pulsed terahertz sources, many applications will require continuous wave (cw) sources, which are just beginning to demonstrate adequate performance for application use. In this project, we proposed examination of two potential THz sources based on intersubband semiconductor transitions, which were as yet unproven. In particular we wished to explore quantum cascade lasers based sources and electronic based harmonic generators. Shortly after the beginning of the project, we shifted our emphasis to the quantum cascade lasers due to two events; the publication of the first THz quantum cascade laser by another group thereby proving feasibility, and the temporary shut down of the UC Santa Barbara free-electron lasers which were to be used as the pump source for the harmonic generation. The development efforts focused on two separate cascade laser thrusts. The ultimate goal of the first thrust was for a quantum cascade laser to simultaneously emit two mid-infrared frequencies differing by a few THz and to use these to pump a non-linear optical material to generate THz radiation via parametric interactions in a specifically engineered intersubband transition. While the final goal was not realized by the end of the project, many of the completed steps leading to the goal will be described in the report. The second thrust was to develop direct THz QC lasers operating at terahertz frequencies. This is simpler than a mixing approach, and has now been demonstrated by a few groups with wavelengths spanning 65-150 microns. We developed and refined the MBE growth for THz for both internally and externally designed QC lasers. Processing related issues continued to plague many of our demonstration efforts and will also be addressed in this report