A Deep Multicolor Survey I. Imaging Observations and Catalog of Stellar Objects

We have used the KPNO 4-meter Mayall telescope to image 0.83 square degrees of sky in six fields at high galactic latitude in six filters spanning 3000-10000\AA\ to magnitude limits ranging from 22.1 to 23.8. We have assembled a catalog of 21,375 stellar objects detected in the fields for use primarily in conducting a multicolor search for quasars. This paper describes the data reduction techniques used on the CCD data, the methods used to construct the stellar object catalog, and the simulations performed to understand its completeness and contamination.Comment: To Appear in ApJ Supplement, 1996. 168k uuencoded gunzipped tarred tex file (requires aas2pp4.sty and tighten.sty) and 4 PostScript figures. Also available at http://astro.as.arizona.edu/~pathall/astro.html#preprint

A Deep Multicolor Survey II. Initial Spectroscopy and Comparison With Expected Quasar Number Counts

We have used the KPNO 4-meter Mayall telescope to image 0.83 square degrees of sky in six fields at high galactic latitude in six filters spanning 3000-10000\AA\ to magnitude limits ranging from 22.1 to 23.8. As a first use of this database, we have conducted a multicolor survey for quasars. We discuss various methods of selecting outliers in different color-color diagrams and multicolor space that have been used to identify quasars at all redshifts from their colors alone. We discuss the initial results of our program of spectroscopic identification which has so far resulted in the identification of over forty faint quasars, including one at z$>$4, a similar number of compact narrow-emission-line galaxies, and a number of unusual and potentially interesting stars. We use these spectroscopic results, along with extensive simulations of quasar spectra, to study the efficiency of our candidate selection procedures. Finally, we compare the number counts of our quasars and quasar candidates to the expected numbers based on previous studies of the quasar luminosity function. The agreement of our observations with these expectations is good in most cases. However, we do estimate that our survey contains more quasars with B$<$21 and z$<$2.3 than expected from the results of Koo \& Kron (1988) and more z$>$3 quasars than expected from the results of Warren, Hewett, \& Osmer (1994), both at the 3$\sigma$\ level. Additional spectroscopic observations will be required to confirm or refute these excesses.Comment: To appear in ApJ Vol. 462, May 20, 1996. 87k gunzipped uuencoded PostScript file. Figures (2750k) available from http://astro.as.arizona.edu/~pathall/astro.html#preprints or via anonymous ftp to ftp://gemini.tuc.noao.edu/pub/phall/ or by email to [email protected]

Schaffnerella Rediscovered! (Gramineae, Chloridoideae)

From 1876 to 1880 in San Luis Potosí, Mexico, J. G. Schaffner made the first collections of a small grass that later was named Schaffnerella gracilis (Chloridoideae). The monotypic genus apparently was not encountered again by botanists until 2001, when, during a targeted search, we discovered it in the Sierra de San Miguelito growing along the Río Potosino, ca. 6 air km southwest of the city of San Luis Potosí. Most of the 100-150 plants encountered along a 3-km stretch of the Río Potosino above the village of Escalerillas and reservoir EI Potosino were growing in a moist alluvium of rock and sand. Historically known to occur some 10 km or more downstream near Morales, a village at the western edge of the city of San Luis Potosí, S. gracilis has been impacted adversely by the creation of dams. Much additional field work is required to determine the geographic range and frequency of the species. Also needed are life history and population-level studies

Barrier-to-autointegration factor 1 protects against a basal cGAS-STING response

Although the pathogen recognition receptor pathways that activate cell-intrinsic antiviral responses are well delineated, less is known about how the host regulates this response to prevent sustained signaling and possible immune-mediated damage. Using a genome-wide CRISPR-Cas9 screening approach to identify host factors that modulate interferon-stimulated gene (ISG) expression, we identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1), a previously described inhibitor of retrovirus integration, as a modulator of basal cell-intrinsic immunity. Ablation of Banf1 by gene editing resulted in chromatin activation near host defense genes with associated increased expression of ISGs, includin

Interactive influences of ozone and climate on streamflow of forested watersheds

The capacity of forests to mitigate global climate change can be negatively influenced by tropospheric ozone that impairs both photosynthesis and stomatal control of plant transpiration, thus affecting ecosystem productivity and watershed hydrology. We have evaluated individual and interactive effects of ozone and climate on late season streamflow for six forested watersheds (38–970 000 ha) located in the Southeastern United States. Models were based on 18–26 year data records for each watershed and involved multivariate analysis of interannual variability of late season streamflow in response to physical and chemical climate during the growing season. In all cases, some combination of ozone variables significantly improved model performance over climate-only models. Effects of ozone and ozone × climate interactions were also consistently negative and were proportional to variations in actual ozone exposures, both spatially across the region and over time. Conservative estimates of the influence of ozone on the variability (R2) of observed flow ranged from 7% in the area of lowest ozone exposure in West Virginia to 23%in the areas of highest exposure in Tennessee. Our results are supported by a controlled field study using free-air concentration enrichment methodology which indicated progressive ozone-induced loss of stomatal control over tree transpiration during the summer in mixed aspen-birch stands. Despite the frequent assumption that ozone reduces tree water loss, our findings support increasing evidence that ozone at near ambient concentrations can reduce stomatal control of leaf transpiration, and increase water use. Increases in evapotranspiration and associated streamflow reductions in response to ambient ozone exposures are expected to episodically increase the frequency and severity of drought and affect flow-dependent aquatic biota in forested watersheds. Regional and global models of hydrologic cycles and related ecosystem functions should consider potential interactions of ozone with climate under both current and future warmer and ozone-enriched climatic conditions

Feedback control architecture and the bacterial chemotaxis network.

PMCID: PMC3088647This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance

Detection of retained microbubbles in carotid arteries with real-time low mechanical index imaging in the setting of endothelial dysfunction

ObjectivesWe sought to determine if intravenously injected microbubbles would be retained by the carotid arteries (CAs) in the setting of endothelial dysfunction (ED) using a linear transducer equipped with a low mechanical index pulse sequence scheme (PSS).BackgroundMicrobubbles normally pass freely through large and small vessels but are retained in regions with ED. New high-frequency low mechanical index PSS can potentially be utilized to image these retained microbubbles.MethodsIntravenous albumin- and lipid-encapsulated microbubbles were administered in seven pigs while imaging the CAs before and after a 20% intralipid infusion to induce hypertriglyceridemia. The degree of microbubble retention was quantified by measuring endothelial acoustic intensity (AI) after clearance of free-flowing microbubbles. Microbubble adherence was also evaluated after selective balloon injury of the CAs. The CA diameter responses to acetylcholine were quantified.ResultsAfter induction of hypertriglyceridemia, adherence of albumin-encapsulated microbubbles was visually evident in all CAs, and endothelial AI increased significantly (p < 0.001 compared with baseline). The CA responses to acetylcholine went from vasodilation at baseline to vasoconstriction during hypertriglyceridemia. Endothelial AI also increased in the balloon-stretched vessels (p < 0.01 compared with uninjured vessels) after albumin-encapsulated microbubble injection, with a ring of microbubbles selectively adhering to the injured segment. This retention was not observed with lipid-encapsulated microbubbles. Scanning electron microscopy confirmed that albumin-coated microbubbles adhered to endothelial cells.ConclusionsRetention of intravenously injected albumin microbubbles occurs in the setting of both global and regional ED in large vessels and can be noninvasively imaged with high-frequency low mechanical index PSS

A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma

Introduction Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC. Methods A total of 27 previously treated patients (16 with thymoma and 11 with TC) with advanced, unresectable disease were treated with pemetrexed, 500 mg/m2, intravenously every 3 weeks for a maximum of six cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12, and steroid prophylaxis. Results The median number of cycles administered was 6 (range 1–6). Nine patients with a total of 14 events had grade 3 toxicities; no grade 4 toxicities were noted. In 26 fully evaluable patients, two complete and three partial responses (according to the Response Evaluation Criteria in Solid Tumors) were documented (all in patients with stage IVA thymoma, except for one partial response with stage IVA TC). A total of 14 patients completed the full six cycles of treatment, 7 patients progressed while undergoing therapy, 5 patients discontinued therapy because of intolerance, and 1 patient discontinued therapy because of progressive Morvan syndrome. The median progression-free survival time for all patients was 10.6 months (12.1 months for those with thymoma versus 2.9 months for those with TC). With 23 deaths at data cutoff, the median overall survival time was 28.7 months (46.4 months for those with thymoma versus 9.8 months for those with TC). Conclusions Pemetrexed is an active agent in this heavily pretreated population of patients with recurrent thymic malignancies, especially thymoma

Reversal of aging-induced increases in aortic stiffness by targeting cytoskeletal protein-protein interfaces

Background: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening. Methods and Results: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome-wide association study of carotid-femoral pulse wave velocity. Common genetic variation in the N-WASP (WASL) locus is associated with carotid-femoral pulse wave velocity (rs600420, P=0.0051). Thus, we tested the hypothesis that decoy proteins designed to disrupt the interaction of cytoskeletal proteins such as N-WASP with its binding partners in the vascular smooth muscle cytoskeleton could decrease ex vivo stiffness of aortas from a mouse model of aging. A synthetic decoy peptide construct of N-WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin-vinculin interfaces similarly decreased aging-induced ex vivo active stiffness by on-target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound-targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness. Conclusions: We conclude that decoy peptides targeted to vascular smooth muscle cytoskeletal protein-protein interfaces and microbubble packaged can decrease aortic stiffness ex vivo. Our results provide proof of concept at the ex vivo level that decoy peptides targeted to cytoskeletal protein-protein interfaces may lead to substantive dynamic modulation of aortic stiffness

Telehealth and Mobile Health Applied To IntegratedBehavioral Care: OpportunitiesFor Progress In New Hampshire

This paper is an accompanying document to a webinar delivered on May 16, 2017, for the New Hampshire Citizens Health Initiative (Initiative). As integrated behavioral health efforts in New Hampshire gain traction, clinicians, administrators, payers, and policy makers are looking for additional efficiencies in delivering high quality healthcare. Telehealth and mobile health (mHealth) have the opportunity to help achieve this while delivering a robust, empowered patient experience. The promise of video-based technology was first made in 1964 as Bell Telephone shared its Picturephone® with the world. This was the first device with audio and video delivered in an integrated technology platform. Fast-forward to today with Skype, FaceTime, and webinar tools being ubiquitous in our personal and business lives, but often slow to be adopted in the delivery of medicine. Combining technology-savvy consumers with New Hampshire’s high rate of electronic health record (EHR) technology adoption, a fairly robust telecommunications infrastructure, and a predominately rural setting, there is strong foundation for telehealth and mHealth expansion in New Hampshire’s integrated health continuum