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Automatic differentiation (AD) is conventionally understood as a family of distinct algorithms, rooted in two “modes”—forward and reverse—which are typically presented (and implemented) separately. Can there be only one? Following up on the AD systems developed in the JAX and Dex projects, we formalize a decomposition of reverse-mode AD into (i) forward-mode AD followed by (ii) unzipping the linear and non-linear parts and then (iii) transposition of the linear part. To that end, we define a (substructurally) linear type system that can prove a class of functions are (algebraically) linear. Our main results are that forward-mode AD produces such linear functions, and that we can unzip and transpose any such linear function, conserving cost, size, and linearity. Composing these three transformations recovers reverse-mode AD. This decomposition also sheds light on checkpointing, which emerges naturally from a free choice in unzipping let expressions. As a corollary, checkpointing techniques are applicable to general-purpose partial evaluation, not just AD. We hope that our formalization will lead to a deeper understanding of automatic differentiation and that it will simplify implementations, by separating the concerns of differentiation proper from the concerns of gaining efficiency (namely, separating the derivative computation from the act of running it backward).

Invasive plants threaten biodiversity worldwide, but control of non-native species may affect native species in complex ways. Non-native tamarisk (Tamarix spp.) is widespread in western U.S. riparian environments, and tamarisk beetles (Diorhabda spp.), a tamarisk-specific herbivore, were subsequently introduced as biocontrol. The primary effect of biocontrol is defoliation and branch dieback, with repeated defoliation killing the plant. We investigated the initial stages of site recovery after biocontrol and how tamarisk decline affected birds, their arthropod prey, and microclimate. We compared avian community diversity and composition, arthropod abundance, humidity, and temperature at sites along the Virgin River in Nevada and Arizona, USA characterized as either mixed native vegetation, tamarisk-dominated, or tamarisk-dominated where the majority of tamarisk died from biocontrol. We compared avian communities sampled after biocontrol to counts at the same locations before biocontrol. Prior to biocontrol, community compositions of all but one site grouped together using unbiased clustering algorithms. Following biocontrol, tamarisk-dominated sites grouped separately, and mixed sites grouped with the pre-biocontrol cluster. Comparison of pre- and post-biocontrol communities showed 7 common species declined by ≥30% in dead tamarisk sites, while one species did so at mixed sites and 3 at tamarisk-dominated sites. Individual census points in dead tamarisk had significantly lower Simpson diversity than the same points censused before biocontrol, unless native vegetation was present, suggesting tamarisk death was the cause of dominant species abundance changes. Tamarisk-dominated sites were hotter and drier than sites with native vegetation and supported fewer non-tamarisk-obligate arthropods, consistent with the hypothesis that bird reductions were driven by changes in microclimate and prey abundance. How long these effects last will depend upon the rate of native vegetation recovery after biocontrol, therefore we recommend monitoring sites to determine the trajectory of vegetative recovery and considering the need and feasibility of active restoration in those sites with slow or no native regeneration.

Understanding how genes, drugs and neural circuits influence behavior requires the ability to effectively organize information about similarities and differences within complex behavioral datasets. Motion Sequencing (MoSeq) is an ethologically inspired behavioral analysis method that identifies modular components of three-dimensional mouse body language called ‘syllables’. Here, we show that MoSeq effectively parses behavioral differences and captures similarities elicited by a panel of neuroactive and psychoactive drugs administered to a cohort of nearly 700 mice. MoSeq identifies syllables that are characteristic of individual drugs, a finding we leverage to reveal specific on- and off-target effects of both established and candidate therapeutics in a mouse model of autism spectrum disorder. These results demonstrate that MoSeq can meaningfully organize large-scale behavioral data, illustrate the power of a fundamentally modular description of behavior and suggest that behavioral syllables represent a new class of druggable target. By analyzing hundreds of mice treated with a library of neuro- and psychoactive drugs, Wiltschko et al. show that Motion Sequencing can effectively discriminate and categorize drug effects and link molecular targets to behavioral syllables.

Background: Maternal nutrition influences fetal development and may permanently alter ("program") offspring body composition and metabolism, thereby influencing later risk of diabetes and cardiovascular (cardiometabolic) disease. The prevalence of cardiometabolic disease is rising rapidly in India. Objectives: To test the hypothesis that supplementing low-income Indian women with micronutrient-rich foods preconceptionally and during pregnancy has a beneficial impact on the children's body composition and cardiometabolic risk marker profiles. Methods: Follow-up of 1255 children aged 5-10 y whose mothers took part in the Mumbai Maternal Nutrition Project [Project "SARAS"; International Standard Randomised Controlled Trial Number (ISRCTN)62811278]. Mothers were randomly assigned to receive a daily micronutrient-rich snack or a control snack of lower micronutrient content, both made from local foods, in addition to normal diet, from before pregnancy until delivery. Children's body composition was assessed using anthropometry and DXA. Their blood pressure, plasma glucose, insulin, and lipid concentrations were measured. Outcomes were compared between allocation groups with and without adjustment for confounding factors. Results: Overall, 15% of children were stunted, 34% were wasted, and 3% were overweight. In the intention-To-Treat analysis, there were no differences in body composition or risk markers between children in the intervention and control groups. Among children whose mothers started supplementation ≥3 mo before conception (the "per protocol"sample) the intervention increased adiposity among girls, but not boys. BMI in girls was increased relative to controls by 2% (95% CI: 1, 4; P = 0.01); fat mass index by 10% (95% CI: 3, 18; P = 0.004); and percent fat by 7% (95% CI: 1, 13; P = 0.01) unadjusted, with similar results in adjusted models. Conclusions: Overall, supplementing women with micronutrient-rich foods from before pregnancy until delivery did not alter body composition or cardiometabolic risk markers in the children. Subgroup analyses showed that, if started ≥3 mo before conception, supplementation may increase adiposity among female children.

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) fails to consistently elicit tumor rejection. Manipulation of intrinsic factors that inhibit T cell effector function and neoantigen recognition may therefore improve TIL therapy outcomes. We previously identified the cytokine-induced SH2 protein (CISH) as a key regulator of T cell functional avidity in mice. Here, we investigate the mechanistic role of CISH in regulating human T cell effector function in solid tumors and demonstrate that CRISPR/Cas9 disruption of CISH enhances TIL neoantigen recognition and response to checkpoint blockade.Single-cell gene expression profiling was used to identify a negative correlation between high CISH expression and TIL activation in patient-derived TIL. A GMP-compliant CRISPR/Cas9 gene editing process was developed to assess the impact of CISH disruption on the molecular and functional phenotype of human peripheral blood T cells and TIL. Tumor-specific T cells with disrupted Cish function were adoptively transferred into tumor-bearing mice and evaluated for efficacy with or without checkpoint blockade.CISH expression was associated with T cell dysfunction. CISH deletion using CRISPR/Cas9 resulted in hyper-activation and improved functional avidity against tumor-derived neoantigens without perturbing T cell maturation. Cish knockout resulted in increased susceptibility to checkpoint blockade in vivo.CISH negatively regulates human T cell effector function, and its genetic disruption offers a novel avenue to improve the therapeutic efficacy of adoptive TIL therapy.This study was funded by Intima Bioscience, U.S. and in part through the Intramural program CCR at the National Cancer Institute.

We develop automatic differentiation (AD) procedures for reductions and scans—parameterized by arbitrary differentiable monoids—in a way that preserves parallelism, by rewriting them as other reductions and scans. This is in contrast with the literature and with existing AD systems, which are either general, but force sequential execution of the derivative program, or only include hand-crafted rules for a select few monoids (usually (0, +), (1, ×), (−∞, max) and (∞, min)) and thus lack the general flexibility of second-order languages.

We present a novel programming language design that attempts to combine the clarity and safety of high-level functional languages with the efficiency and parallelism of low-level numerical languages. We treat arrays as eagerly-memoized functions on typed index sets, allowing abstract function manipulations, such as currying, to work on arrays. In contrast to composing primitive bulk-array operations, we argue for an explicit nested indexing style that mirrors application of functions to arguments. We also introduce a fine-grained typed effects system which affords concise and automatically-parallelized in-place updates. Specifically, an associative accumulation effect allows reverse-mode automatic differentiation of in-place updates in a way that preserves parallelism. Empirically, we benchmark against the Futhark array programming language, and demonstrate that aggressive inlining and type-driven compilation allows array programs to be written in an expressive, "pointful" style with little performance penalty., Comment: 31 pages with appendix, 11 figures. A conference submission is still under review

Our aim was to evaluate the effect of antibiotic exposure on bacterial pathogen yield in patients with diabetic foot osteomyelitis. In a retrospective cohort study, we evaluated 142 patients admitted to the hospital with diabetic foot osteomyelitis which confirmed by histologic evaluation. Histologic criteria for osteomyelitis included the presence of an inflammatory response, bone necrosis, and/or bone fragmentation. We compared bacterial pathogens in patients that received antibiotics before bone culture (n=114) and patients that did not receive antibiotics (n=28), as well as bacterial yield based on the duration of antibiotic exposure. We used the chi square test to compare antibiotic exposure and culture yield. There was not a significant difference in culture yield in patients that received antibiotics (77.9%) and patients that did not (85.7%, p=0.58). There was no difference in patients that received antibiotics for ≥4 days (n=56, 71.4%), 1-3 days (n=58, 84.5%) and no antibiotics (85.7%, p=0.15). In conclusion, the results of bacterial recovery were similar in patients regardless of the length of antibiotic treatment. Antibiotic exposure did not change the bacterial yield, the type of bacteria or the number of bacteria. In patients with suspected diabetic foot osteomyelitis, there is no evidence to support withholding antibiotics prior to obtaining a bone biopsy. Disclosure L.A. Lavery: Advisory Panel; Self; Acelity, Bayer AG. Consultant; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Smith & Nephew. E.C. Ryan: None. D.H. Truong: None. M.J. Johnson: None. J. La Fontaine: None. P.A. Crisologo: None.

The western population of the yellow-billed cuckoo (Coccyzus americanus) was recently listed as threatened under the federal Endangered Species Act. Yellow-billed cuckoo conservation efforts require the identification of features and area requirements associated with high quality, riparian forest habitat at spatial scales that range from nest microhabitat to landscape, as well as lower-suitability areas that can be enhanced or restored. Spatially explicit models inform conservation efforts by increasing ecological understanding of a target species, especially at landscape scales. Previous yellow-billed cuckoo modelling efforts derived plant-community maps from aerial photography, an expensive and oftentimes inconsistent approach. Satellite models can remotely map vegetation features (e.g., vegetation density, heterogeneity in vegetation density or structure) across large areas with near perfect repeatability, but they usually cannot identify plant communities. We used aerial photos and satellite imagery, and a hierarchical spatial scale approach, to identify yellow-billed cuckoo breeding habitat along the Lower Colorado River and its tributaries. Aerial-photo and satellite models identified several key features associated with yellow-billed cuckoo breeding locations: (1) a 4.5 ha core area of dense cottonwood-willow vegetation, (2) a large native, heterogeneously dense forest (72 ha) around the core area, and (3) moderately rough topography. The odds of yellow-billed cuckoo occurrence decreased rapidly as the amount of tamarisk cover increased or when cottonwood-willow vegetation was limited. We achieved model accuracies of 75–80% in the project area the following year after updating the imagery and location data. The two model types had very similar probability maps, largely predicting the same areas as high quality habitat. While each model provided unique information, a dual-modelling approach provided a more complete picture of yellow-billed cuckoo habitat requirements and will be useful for management and conservation activities.

Background Diabetes mellitus affects up to 14% of Americans. Infection of the diabetic foot is a common complication, which may lead to amputation. If infection extends to involve bone, the risk of amputation is increased 4-fold. Presence of osteomyelitis at the histopathologic margin of resection portends a poor prognosis in osteomyelitis outside the setting of the diabetic foot. We aimed to assess the association of a positive histopathologic margin with the outcome of osteomyelitis in the diabetic foot. Methods Medical records were reviewed for all patients who underwent below-ankle amputation for osteomyelitis of the diabetic foot. Patients who had at least 1 year of follow-up, a histopathologic diagnosis of osteomyelitis, and a comment on whether the margin was involved were included. Results Thirty-nine of 66 (59%) cases had remission of osteomyelitis at 12 months. When comparing cases with remission with those who experienced recurrence in the 12 months of follow-up, there were no statistically significant differences in age, glycosylated hemoglobin, duration of antimicrobial therapy, Infectious Diseases Society of America class, or presence of osteomyelitis at the histopathologic margin. Among cases with a negative histopathologic margin, 29/48 (60.4%) were free of disease at 1 year, compared with 10/18 (55.6%) cases with a positive histopathologic margin (P = .72). Remission was significantly more frequent in cases undergoing amputation at the digit level (66.7%) compared with amputation at the metatarsal level (40.7%) (P = .045). Conclusions Osteomyelitis of the diabetic foot at the histopathologic margin of resection was not associated with increased risk of treatment failure. Resection at the level of the digit was associated with a lower risk of failure than at the metatarsal level.

© 2019 Elsevier Ltd The establishment and naturalization of non-native Russian olive (Elaeagnus angustifolia)in southwestern US riparian habitats is hypothesized to have negative implications for native flora and fauna. Despite the potential for Russian olive establishment in new riparian habitats, much of its ecology remains unclear. Arid river systems are important stopover sites and breeding grounds for birds, including some endangered species, and understanding how birds use Russian olive habitats has important implications for effective non-native species management. We compared native bird use of sites that varied in the amount of Russian olive and mixed native/non-native vegetation along the San Juan River, UT, USA. From presence/absence surveys conducted in 2016 during the breeding season, we found 1)fewer bird species and functional groups used Russian olive habitats and 2)the composition of species within Russian olive habitats was different from the composition of species in mixed native/non-native habitats. Our results suggest Russian olive may support different bird compositions during the breeding season and as Russian olive continues to naturalize, bird communities may change. Finally, we highlight the paucity of research surrounding Russian olive ecology and stress the need for rigorous studies to improve our understanding of Russian olive ecology.

Aim: The objective of the study was to evaluate the effect of the Erbium-Yttrium aluminum garnet (YAG) laser on diabetic foot ulcer that had not responded to standard care. Methods: We retrospectively evaluated 23 patients with c non-healing diabetic foot ulcers that received at least four weeks of standard wound care, demonstrated poor healing response, and were subsequently treated with YAG laser. We measure the percent wound area reduction (PWAR) for the 4 weeks prior to initiating laser therapy and the PWAR for 4 weeks following the initiation of laser therapy. YAG laser treatment consisted of two components: debridement and re-surfacing. The laser settings were the same for all treatments. We used pair t-test to compare pre versus post wound area reduction. Results: During the 4-week period prior to the initiation of laser therapy, the average PWAR was -32.1%. During this time, the diabetic foot ulcers increased in area. After treatment with YAG laser, after 4 weeks the average PWAR was 63.5% (p 50% PAR at 4 weeks and 45.8% of patients healed by 12 weeks. Conclusion: YAG laser therapy accelerated DFU healing in a cohort of patients with ulcers that had been unresponsive to standard of care therapy. Disclosure M.J. Johnson: None. L.A. Lavery: Consultant; Self; Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Medline Industries, Inc. Research Support; Self; Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Osiris Therapeutics, Inc.

Background: Rodent hippocampal population codes represent important spatial information about the environment during navigation. Computational methods have been developed to uncover the neural representation of spatial topology embedded in rodent hippocampal ensemble spike activity. New method: We extend our previous work and propose a novel Bayesian nonparametric approach to infer rat hippocampal population codes during spatial navigation. To tackle the model selection problem, we leverage a Bayesian nonparametric model. Specifically, we apply a hierarchical Dirichlet process-hidden Markov model (HDP-HMM) using two Bayesian inference methods, one based on Markov chain Monte Carlo (MCMC) and the other based on variational Bayes (VB). Results: The effectiveness of our Bayesian approaches is demonstrated on recordings from a freely behaving rat navigating in an open field environment. Comparison with existing methods: The HDP-HMM outperforms the finite-state HMM in both simulated and experimental data. For HPD-HMM, the MCMC-based inference with Hamiltonian Monte Carlo (HMC) hyperparameter sampling is flexible and efficient, and outperforms VB and MCMC approaches with hyperparameters set by empirical Bayes. Conclusion: The Bayesian nonparametric HDP-HMM method can efficiently perform model selection and identify model parameters, which can used for modeling latent-state neuronal population dynamics., National Institutes of Health (U.S.) (Grant R01-MH06197), National Institutes of Health (U.S.) (Grant TR01-GM10498), National Institutes of Health (U.S.) (Grant ONR-MURI N00014-10-1-0936)

Background Posttraumatic Stress Disorder (PTSD) is a disabling illness suffered by many Veterans returning from war. Some Veterans believe that cannabis may be therapeutic for PTSD. The purpose of this study was to better understand the association between cannabis use and PTSD symptoms. Methods The study was a matched case-control cross-sectional evaluation of the psychiatric and sociocultural associations of cannabis use in Veterans with probable PTSD. Patient self-report measures were examined comparing cannabis users (cases) to non-users (controls) who were case-matched on age and gender. Results Results indicated that there were no significant differences between cases and controls in mean PTSD Checklist-Civilian version (PCL-C) scores (59.2 and 59.1, respectively). There was also no association between PTSD scores and frequency of cannabis use. It was also observed that cases were more likely to be non-Caucasian, financially challenged, and unmarried. Limitations The sample is a convenience sample of Veterans being referred for a clinical assessment and therefore, sampling biases may limit the generalizability of the results to other populations including Veterans not seeking health care in the Veterans Affairs (VA) system. Conclusions The results do not support the theory that cannabis use would be associated with less severe PTSD symptoms. Results do suggest important sociocultural differences in cannabis users compared to controls.

Category: Arthroscopy; Midfoot/Forefoot Introduction/Purpose: Refractory pain to the fourth and fifth tarsometatarsal (TMT) joint is a source of disability and functional impairment. The etiology of fourth and fifth TMT joint pain may be attributed to injury, post-traumatic arthritis, or arthrofibrosis, however, the principal pathologies associated with pain in the absence of arthritis are not well elucidated. The purpose of this study is to characterize arthroscopic pathology associated with chronic refractory pain to the fourth and fifth TMT joints with and without arthritis. Methods: We retrospectively examined 25 patients that underwent arthroscopic surgery of the fourth and fifth TMT joints for refractory pain at our academic institution between 2015 - 2020. Patients were placed in supine position, thigh tourniquet placed, prepped and draped in standard sterile fashion. The fourth and fifth TMT joints were accessed medially through a portal between the third and fourth TMT joint and laterally through a portal lateral to the fifth TMT joint. A 30° 2.5mm arthroscope was used as well as 2.5mm aggressive soft tissue shaver. Intraoperative fluoroscopy was use to confirm location of the arthroscope and shaver. The intraoperative findings were recorded into the medical record. We used the Outerbridge classification for chondral lesions, the Kellgren Lawrence (KL) radiographic classification for osteoarthritis, and described intraarticular pathologies as acute hypertrophic synovitis, chronic synovial fibrosis, hyaline bands, meniscoid bodies, loose joint bodies, arthrofibrosis. Results: Twenty-three fourth TMT joints and 26 fifth TMT joints, in 25 patients, underwent arthroscopic surgery for refractory pain. Average age was 62.6+-8.3 years. Average body mass index was 31.0+-5.0 kg/m2. All patients had pain with piano-key test. Twelve patients with arthritis to first through third TMT joints and eight patients to second through third TMT joints required arthrodesis. Approximately, 71.4% of TMT joints presented with radiographic evidence of arthritis and 28.6% of TMT joints were absent of radiographic signs of arthritis. The soft tissue pathology observed in patients without radiographic evidence of arthritis was arthrofibrosis (87.5%), chronic synovial fibrosis (75.0%), and acute hypertrophic synovitis (62.5%). Frequency plot of soft tissue pathologies, Outerbridge classification and KL radiographic classification for arthritis are shown in Figure 1. Conclusion: This is the first study to report arthroscopic findings associated with refractory pain of the fourth and fifth TMT joints with and without arthritis. These findings provide information regarding pathologies associated with fourth and fifth TMT joints pain and subsequent treatment.

Recent restrictions on uranium mining within the Grand Canyon watershed have drawn attention to scientific data gaps in evaluating the possible effects of ore extraction to human populations as well as wildlife communities in the area. Tissue contaminant concentrations, one of the most basic data requirements to determine exposure, are not available for biota from any historical or active uranium mines in the region. The Canyon Uranium Mine is under development, providing a unique opportunity to characterize concentrations of uranium and other trace elements, as well as radiation levels in biota, found in the vicinity of the mine before ore extraction begins. Our study objectives were to identify contaminants of potential concern and critical contaminant exposure pathways for ecological receptors; conduct biological surveys to understand the local food web and refine the list of target species (ecological receptors) for contaminant analysis; and collect target species for contaminant analysis pri...

SummaryComplex animal behaviors are likely built from simpler modules, but their systematic identification in mammals remains a significant challenge. Here we use depth imaging to show that 3D mouse pose dynamics are structured at the sub-second timescale. Computational modeling of these fast dynamics effectively describes mouse behavior as a series of reused and stereotyped modules with defined transition probabilities. We demonstrate this combined 3D imaging and machine learning method can be used to unmask potential strategies employed by the brain to adapt to the environment, to capture both predicted and previously hidden phenotypes caused by genetic or neural manipulations, and to systematically expose the global structure of behavior within an experiment. This work reveals that mouse body language is built from identifiable components and is organized in a predictable fashion; deciphering this language establishes an objective framework for characterizing the influence of environmental cues, genes and neural activity on behavior.Video Abstract

The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation. Finally, we show that the Nhp10 module of INO80 plays an auto-inhibitory role, tuning INO80's switch-like response to flanking DNA. Our results indicate that INO80 is a highly processive remodeling motor that is tightly regulated by both substrate cues and non-catalytic subunits.

Introduction The time series of vital signs, such as heart rate (HR) and blood pressure (BP), can exhibit complex dynamic behaviors as a result of internally and externally induced changes in the state of the underlying control systems (Peng et al . 1995; Ivanov et al . 1999; Costa et al . 2002). For instance, time series of BP can exhibit oscillations on the order of seconds (e.g., due to the variations in sympathovagal balance), to minutes (e.g., as a consequence of fever, blood loss, or behavioral factors), to hours (e.g., due to humoral variations, sleep-wake cycle, or circadian effects) (Mancia 2012; Parati et al . 2013). A question of interest is whether “similar” dynamical patterns can be automatically identified across a heterogeneous patient cohort, and be used for prognosis of patients' health and progress. In this work, we present a Bayesian nonparametric switching Markov processes framework with conditionally linear dynamics to learn phenotypic dynamic behaviors from vital sign time series of a patient cohort, and use the learned dynamics to characterize the changing physiological states of patients for critical-care bed-side monitoring (Lehman et al . 2012, 2013, 2014a; Nemati 2012). We assume that although the underlying dynamical system may be nonlinear and nonstationary and the stochastic noise components can be non-Gaussian, the dynamics can be approximated by a collection of linear dynamical systems (Nemati 2012; Nemati et al . 2012). Each such linear “dynamic” (or mode) is a time-dependent rule that describes how the future state of the system evolves from its current state, centered around a given system equilibrium point. Therefore, an ideal algorithm would be able to identify time series segments that follow a “similar” dynamic, and would switch to a different mode upon a change in the state of the underlying system. We explore several variants of the Bayesian nonparametric approach to discovery of shared dynamics among patients via switching Markov processes: hierarchical Dirichlet process (HDP) autoregressive hidden Markov model (HDP-AR-HMM) (Teh et al . 2006; Fox et al . 2008), an explicit-duration HDP-based hidden semi-Markov model (HDP-AR-HSMM) (Johnson & Willsky 2013a), and the beta process autoregressive HMM (BP-AR-HMM) (Fox 2009; Fox et al . 2009, 2014).

From 1994–1996 we investigated effects of Brown-headed Cowbird (Molothrus ater) parasitism on Black-throated Sparrow (Amphispiza bilineata) nesting success in the Verde Valley of central Arizona. Of 56 Black-throated Sparrow nests, 52% were parasitized. Black-throated Sparrows appear to respond to natural parasitism by accepting the cowbird egg, deserting the nest, or burying the cowbird egg. Removal and damage of host eggs by female cowbirds effectively reduced clutch size from an average of 3.4 to 1.9 eggs. Because of this reduced clutch size, Black-throated Sparrow reproductive success was significantly lower in parasitized nests (0.2 young fledged/ nest) as compared to nonparasitized nests (1.6 young fledged/nest). When comparing cowbird parasitism between two habitat types, we found significantly higher parasitism frequencies in crucifixion-thorn (Canotia holacantha) versus creosote-bush (Larrea divaricata) habitat. We argue that this difference in parasitism is due to the greater number of ...

Chromatin remodeling complexes are molecular motors that catalyze diverse structural rearrangements of the genetic material in eukaryotic cells. One such motor, human ACF, is involved in many fundamental gene regulatory processes, including transcriptional activation and repression. ACF is composed of a motor subunit called SNF2h, which is shared with several other remodeling complexes, and a non-catalytic subunit called Acf1. Both SNF2h alone and the ACF complex slide nucleosomes, the basic unit of chromatin, along DNA. Despite the prevalence of ACF and related complexes in genomic regulation, much remains unclear about the mechanism of their sliding activity. SNF2h and Acf1 contain a number of “moving parts” that contribute to significant conformational rearrangements of the enzyme during the remodeling cycle, making them challenging to study by ensemble methods. SNF2h and ACF also dimerize on nucleosomes, further complicating their study in asynchronous populations. Single-molecule techniques are therefore particularly well-suited to investigating such a system. We use single-molecule FRET to observe SNF2h and ACF remodeling individual nucleosomes, to address the following questions: (1) How does the Acf1 accessory subunit modify the basic motor properties of SNF2h, especially in terms of processivity, directional commitment, and remodeling efficiency? (2) How do the “moving” parts of SNF2h combine to regulate the basic activity of the motor? (3) How is protomer coordination achieved across the nucleosome to avoid a tug of war, since enzyme monomers do not directly contact each other?

We consider recovering the salient feature subset for distinguishing between two probability models from i.i.d. samples. Identifying the salient set improves discrimination performance and reduces complexity. The focus in this work is on the high-dimensional regime where the number of variables d, the number of salient variables k and the number of samples n all grow. The definition of saliency is motivated by error exponents in a binary hypothesis test and is stated in terms of relative entropies. It is shown that if n grows faster than max{ck log((d-k)/k), exp(c′k)} for constants c, c′, then the error probability in selecting the salient set can be made arbitrarily small. Thus, n can be much smaller than d. The exponential rate of decay and converse theorems are also provided. An efficient and consistent algorithm is proposed when the distributions are graphical models which are Markov on trees.

A primary constraint on effective conservation of migratory animals is our inability to track individuals through their annual cycle. One such animal is the endangered southwestern subspecies of the Willow Flycatcher, which is difficult to distinguish from conspecifics. Identifying wintering regions used by the endangered subspecies would be an important step in formulating an effective conservation strategy. Our objective was to use stable isotope ratios as a means of identifying wintering sites of Southwestern Willow Flycatchers. We analyzed stable isotope ratios of carbon, nitrogen, and hydrogen from feathers of breeding and wintering Willow Flycatchers. Based on winter samples, we document a positive trend in hydrogen isotope ratios across latitude. We also found that Willow Flycatchers use C4 food webs south of 8 degrees N latitude, but we found no evidence of use of C4 food webs farther north. Nitrogen stable isotope ratios of feathers showed no discernable geographic variation. Discriminant function analyses, based on stable isotope ratios of wintering Willow Flycatchers, were only useful (50% accurate) for assigning individuals to winter regions if the regions were large and the threshold probability for assignment was relatively high. When using these discriminant functions, most breeding samples of Southwestern Willow Flycatchers were assigned to two wintering regions: central Mexico and Ecuador. We think that assignment of Southwestern Willow Flycatchers to Ecuador is unrealistic. Given the large percentages of samples that could not be classified with certainty, we are not confident that these two regions are truly more likely to harbor wintering Southwestern Willow Flycatchers than other winter regions. We think our inconclusive results are due primarily to weak and nonlinear gradients in isotope ratios across the winter range of Willow Flycatchers.