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Abstract:AbstractThe four books by Heinrich Wölfflin (Swiss, 1864–1945) that are owned by the Getty Research Institute are the author’s copies containing Wölfflin’s subsequent annotations. These books, along with a number of other books owned and annotated by Wölfflin and written by historians such as Jacob Burckhardt, are the subjects of this notice.

An undergraduate laboratory was developed as part of the Drugs for Neglected Diseases initiative’s Open Synthesis Network. This activity aimed to develop new compounds efficacious against visceral leishmaniasis. Students successfully synthesized, purified, and characterized ten different benzoxazole amides that were sent for biological testing against several protozoan parasites. Although all the benzoxazole amides had poor activity against L. donovani, several (2, 4, and 9) showed moderate activity against T. cruzi, T. b. rhodesiense, and T. b. bruceipaired with low cell cytotoxicity. This drug discovery laboratory activity made a measurable contribution to neglected tropical disease research and was an engaging and research-orientated experience for undergraduate students. Implementation of drug discovery laboratories across a range of student levels and backgrounds is highly achievable using existing laboratory equipment and a short investment in activity preparation and can be a sustainable course component.

ABSTRACTThis article demonstrates that the most celebrated building designed by Andrea Palladio, widely known as the Villa Rotonda and begun around 1566, was left only partially constructed at the time of the architect’s death in 1580 and that, as a villa design, it was neither perfect nor ideal. Drawing on detailed records of the construction work carried out in the 1590s, the article shows that much of the villa was constructed or altered after Palladio died, in significant part so as to deal with practical difficulties and deficiencies inherent in the design originally published in Palladio’s treatise. Scholars in general have come to recognise that the Villa Rotonda is something of a palimpsest. However, it has not been properly understood that the building was largely constructed not as an adjusted scheme devised by Palladio, but rather as a strategically revised concept for a villa developed after Palladio’s time by Vincenzo Scamozzi. This preserved something of the original scheme as a hilltop belvedere — especially its outward appearance as a domed and isolated block with four near-identical porticoes — but it adapted what had been built, which was far from complete, to a much more practical vision of the requirements of rural life. What was built during this later period then remained intact until the late eighteenth century.

‘Plainsmen’ (Reg. no. CV‐288, PI 698191) tall wheatgrass [Thinopyrum ponticum(Podp.) Z.‐W. Liu & R.‐C. Wang], also tested under the experimental designations NFTW6020 and Jose FYLD C1, was developed by the Noble Research Institute and released in 2014. A population was developed from selections from the cultivar ‘Jose’ for persistence under grazing and two cycles of selection for digestibility. The parents of Plainsmen were selected using within‐ and among‐family selection from this population based on autumn forage yield greater than 100% of the nursery mean. The heading date of Plainsmen in Ardmore, OK, is on average 5 d earlier than that of Jose. Seed size, as indicated by 1,000‐seed weight, of Plainsmen (4,724 mg) was greater than that of Jose (4,161 mg) and ‘Platte’ (3,143 mg). Persistence was improved by selection, with stands of Plainsmen ranging from 90 to 294% greater than stands of Jose across three locations. Total autumn forage yields of Plainsmen were greater by 45 and 53% than those of Jose at Iowa Park, TX, and Ardmore, OK, respectively. Crude protein and digestibility of Plainsmen and Jose were similar in both the autumn and spring, despite earlier maturity of Plainsmen. Seedling vigor, using a visual rating scale of 0–5, was greater for Plainsmen (4.3) than Jose (2.7). Plainsmen was released due to its improved autumn forage yield and persistence under grazing relative to Jose. Plainsmen tall wheatgrass was released due to its improved autumn forage yield and persistence under grazing.Plainsmen was developed from selections from the tall wheatgrass cultivar Jose.The parents of Plainsmen were selected using within‐ and among‐family selection.Fall forage yields of Plainsmen are higher than those of Jose.Plainsmen is more persistent under grazing than Jose tall wheatgrass.

‘Chisholm’ (Reg. No. CV‐102, PI 686938) summer‐dormant (SD) tall fescue [Lolium arundinaceum(Schreb.) Darbysh.] is a forage‐type, synthetic cultivar developed from phenotypic selections for persistence in southern Oklahoma and north Texas from the cultivar Flecha. Chisholm was jointly developed, tested, and released in 2016 by the Noble Research Institute, LLC, Ardmore, OK, USA, GENTOS, Buenos Aires, Argentina, and Grasslanz Technology, Ltd., Palmerston North, New Zealand. Chisholm tall fescue is a mediterranean or SD ecotype characterized by productive growth in mild winters and dormancy during hot and dry summers. Chisholm differs (p< 0.05) from the SD cultivar Flecha by possessing a later heading date (4 d) and a more erect growth habit. Plants of Chisholm have wider (p< 0.05) flag and tiller leaf widths of 0.4 and 0.8 mm, respectively when compared to plants of Flecha. When tested in small plot grazing trials for persistence in southern Oklahoma and north Texas from 2011 to 2016, final stands of Chisholm were 23% greater (p< 0.05) than Flecha and the mediterranean cultivar Prosper when averaged across all locations, which is the justification for Chisholm's release. Chisholm is capable of producing high‐quality pasture from autumn through spring, thereby providing a perennial forage option for livestock producers to complement or replace the planting of winter annuals such as dual‐purpose wheat (Triticum aestivumL.). Chisholm is licensed to Warner Brothers Seed Company, Lawton, OK.

NFTW6001 (Reg. No. GP‐99; PI 676025) tall wheatgrass [Thinopyrum ponticum(Podp.) Barkworth & D.R. Dewey] germplasm, also tested under the designation Jose HDMD C2, was developed by the Samuel Roberts Noble Foundation and released in 2014. Selections were made from ‘Jose’ in north Texas for persistence and digestibility, followed by a second cycle of selection in southern Oklahoma emphasizing digestibility. The heading date of NFTW6001 in Ardmore, OK, is on average 7 d earlier than Jose. Persistence was improved by selection, based on greater stands of NFTW6001 (72%) compared with Jose (17%) at Vernon, TX. Total forage yield of NFTW6001 has equaled or exceeded (up to 607 kg ha− 1) the yield of Jose in Oklahoma. Despite its earlier maturity, digestibility and crude protein concentration of NFTW6001 in summer is equal to Jose. The digestibility and crude protein of NFTW6001 and Jose are similar in fall. NFTW6001 was released by the Noble Foundation's plant materials release committee due to its earlier maturity, improved forage yield, and persistence relative to Jose.

Patients with asymptomatic Type 2 Brugada ECG patterns are not often associated with the sinister cardiac presentations that are more often related to the Type 1 Brugada pattern. The use of implantable cardiac defibrillators (ICDs) are not recommended in this patient group.

AbstractThe four books by Heinrich Wölfflin (Swiss, 1864–1945) that are owned by the Getty Research Institute are the author’s copies containing Wölfflin’s subsequent annotations. These books, along with a number of other books owned and annotated by Wölfflin and written by historians such as Jacob Burckhardt, are the subjects of this notice.

Many Epichloëendophytes found in cool-season grasses are interspecific hybrids possessing much or all of the genomes of two or three progenitors. Here we characterize Epichloë canadensissp. nov., a hybrid species inhabiting the grass species Elymus canadensisnative to North America. Three distinct morphotypes were identified that were separated into two groups by molecular phylogenetic analysis. Sequence analysis of the translation elongation factor 1-α (tefA) and β-tubulin (tubB) genes revealed two copies in all isolates examined. Phylogenetic analyses indicated that allele 1 of each gene was derived from Epichloë amarillansand allele 2 from Epichloë elymi. This is the first documentation of an interspecific hybrid endophyte derived from parents of strictly North American origins. Alkaloid gene profiling using primers specific to genes in the peramine, loline, indole-diterpene and ergot alkaloid pathways may indicate chemotypic variation in the ergot alkaloid and loline pathways between the assigned morphotypes. All isolates have the gene enabling the production of peramine but lack genes in the indole-diterpene biosynthesis pathway. Morphology and phylogenetic evidence support the designation of isolates from El. canadensisas a new interspecific hybrid species.

Alfalfa (Medicago sativaL.) is a high‐quality forage legume that may have potential to improve net returns to stocker cattle producers in the southern Great Plains. The objective of this 3‐yr field study was to compare the agronomic and economic performance of alfalfa grazing systems under two management strategies. Treatments were (i) continuous stocking for the entire growing season, referred to as full‐season grazing; and (ii) a late‐season rest, which was continuous stocking of alfalfa until 1 August. Steers (250 ± 25 kg initial body weight) were weighed every 28 d during each grazing season, and stocking rates were adjusted with put‐and‐take steers based on forage mass. In each 28‐d grazing period, forage mass and total gain (TG) were measured, allowing calculation of average daily gain (ADG). Animals had ADG of 0.93 and 1.05 kg d−1and TG of 449 and 379 kg ha−1on alfalfa for the full‐season grazing treatment and the late‐season rest (August termination), respectively. The 3‐yr average production cost ($278 ha−1) did not differ between the two management treatments; however, expected net return was greater (P< 0.01) for the full‐season alfalfa grazing treatment ($314 ha−1) compared to the 1 August termination date ($145 ha−1). Therefore, a late‐season rest from grazing was not economically beneficial to grazing alfalfa in this 3‐yr experiment, and grazing alfalfa with summer stockers may be a viable option for producers in the southern Great Plains.

Pandemic, epidemic and endemic infectious diseases are united by a common problem: how do we rapidly and cost-effectively identify potential pharmacological interventions to treat infections? Given the large number of emerging and neglected infectious diseases and the fact that they disproportionately afflict the poorest members of the global society, new ways of thinking are required to develop high productivity discovery systems that can be applied to a large number of pathogens. The growing availability of parasite genome data provides the basis for developing methods to prioritize, a priori potential drug targets and analyze the pharmacological landscape of an infectious disease. Thus the overall objective of infectious disease informatics is to enable the rapid generation of plausible, novel medical hypotheses of testable pharmacological experiments, by uncovering undiscovered relationships in the wealth of biomedical literature and databases that were collected for other purposes. In particular our goal is to identify potential drug targets present in a pathogen genome and prioritize which pharmacological experiments are most likely to discover drug-like lead compounds rapidly against a pathogen (i.e. which specific compounds and drug targets should be screened, in which assays and where they can be sourced). An integral part of the challenge is the development and integration of methods to predict druggability, essentiality, synthetic lethality and polypharmocology in pathogen genomes, while simultaneously integrating the inevitable issues of chemical tractability and the potential for acquired drug resistance from the start.

Use of cool‐season perennial grasses may decrease annual establishment cost and improve returns to stocker cattle producers. The objective of this 5‐yr field study was to compare the performance of two stocker cattle grazing forage systems: cool‐season annual (rye [Secale cerealeL.]–annual ryegrass [Lolium multiflorumLam.]) vs. cool‐season perennial tall fescue [Schedonorus arundinaceus(Schreb.) Dumort; formerly Festucaarundinacea Schreb., ‘Texoma’], with a nontoxic endophyte (MaxQ II). Paddocks of four replicates consisted of a cereal rye and annual ryegrass mixture that was planted annually in early September 2005 through 2009, whereas tall fescue was planted once in late September 2005. Steers (273 ± 55 kg initial body weight) were weighed every 28 d of each grazing season, and stocking rates were adjusted with put‐and‐take steers based on forage mass. In each 28‐d grazing period, forage mass, forage nutritive value, and stocker average daily gain (ADG) and total gain (TG) were measured. Animals performed well in both systems with ADG of 1.05 and 0.93 kg d−1, and TG of 491 and 349 kg ha−1for rye–annual ryegrass and tall fescue, respectively. The 5‐yr average annual production cost was less for the tall fescue system ($336 ha−1) than for the rye–annual ryegrass system ($455 ha−1). The assumed amortization of the tall fescue was especially influential on net return; with a 5‐yr amortization, net return was greater for the rye–annual ryegrass ($279 ha−1) than for the tall fescue ($217 ha−1) system, but with 12‐yr amortization, the net return of these two systems was identical.

In this second of a series of papers on spatially resolved star formation, we investigate the impact of the density-morphology relation of galaxies on the spatial variation of star formation (SF) and its dependence on environment. We find that while a density-morphology relation is present for the sample, it cannot solely explain the observed suppression of SF in galaxies in high-density environments. We also find that early-type and late-type galaxies exhibit distinct radial star formation rate (SFR) distributions, with early types having an SFR distribution that extends further relative to the galaxy scale length, compared to late types at all densities. We find that a suppression of SF in the highest density environments is found in the highest star-forming galaxies for both galaxy types. This suppression occurs in the innermost regions in late types (r [?] 0.125 Petrosian radii), and further out in radius in early types (0.125 Petrosian radii < r [?] 0.25 Petrosian radii). When the full sample is considered no clear suppression of SF is detected, indicating that the environmental trends are driven only by the highest SF galaxies. We demonstrate that the density-morphology relation alone cannot account for the suppression of SF in the highest density environments. This points to an environmentally governed evolutionary mechanism that affects the SF in the innermost regions in both early- and late-type galaxies. We suggest that this is a natural consequence of the "downsizing" of SF in galaxies.

There is interest in Canada wildrye (CWR, Elymus canadensisL.) and Virginia wildrye (VWR, E. virginicusL.) for conservation and forage uses. Our objectives were to identify a set of molecular markers to assess genetic structure within and diversity among populations of CWR and VWR from the Southern Great Plains and to determine if these populations had an associated fungal endophyte. Nine CWR and five VWR populations and two barley (Hordeum vulgareL.) cultivars were genotyped using simple sequence repeat (SSR) markers isolated from tall fescue [Lolium arundinaceum(Schreb.) Darbysh.] expressed sequence tags (TF ESTs). Scorable fragments were produced by 31% of TF EST‐SSRs tested, thus identifying a set of SSR markers for wildrye. Populations grouped into three clusters consisting of (i) three wild populations, one plant introduction, and two commercial sources of CWR; (ii) all VWR populations and three CWR plant introductions; and (iii) barley cultivars. Clustering indicated possible gene flow between CWR and VWR. Genetic variation within populations was minimal and comparable to that of the barley cultivars. Thus, unlike many ancestral cultivars and landraces of self‐pollinated crops, CWR and VWR populations consisted of essentially pure lines and can be handled as such in a breeding program. Potentially sexual and asexual epichloëendophytes were found in several populations, indicating the need to account for endophytes in breeding and germplasm conservation efforts of wildrye.

For a mass-selected sample of 66544 galaxies with photometric redshifts (z phot) from the Cosmic Evolution Survey (COSMOS), we examine the evolution of star-formation activity as a function of stellar mass in galaxies. We estimate the cosmic star-formation rates (SFRs) over the range 0.2 < z phot < 1.2, using the rest-frame 2800 A flux (corrected for extinction). We find the mean SFR to be a strong function of the galactic stellar mass at any given redshift, with massive systems (log(M/M )>10.5) contributing less (by a factor of [?]5) to the total star-formation rate density (SFRD). Combining data from the COSMOS and Gemini Deep Deep Survey, we extend the SFRD-z relation as a function of stellar mass to z [?] 2. For massive galaxies, we find a steep increase in the SFRD-z relation to z [?] 2; for the less-massive systems, the SFRD which also increases from z = 0 to 1 levels off at z [?] 1. This implies that the massive systems have had their major star-formation activity at earlier epochs (z > 2) than the lower-mass galaxies. We study changes in the SFRDs as a function of both redshift and stellar mass for galaxies of different spectral types. We find that the slope of the SFRD-z relation for different spectral types of galaxies is a strong function of their stellar mass. For low- and intermediate-mass systems, the main contribution to the cosmic SFRD comes from the star-forming galaxies while, for more-massive systems, the evolved galaxies are the most dominant population.

We use the photometric information contained in individual pixels of 44,964 ( 0.019 < z < 0.125 and - 23.5 < Mr < [?] 20.5) galaxies in the Fourth Data Release (DR4) of the Sloan Digital Sky Survey to investigate the effects of environment on galaxy star formation (SF). We use the pixel-z technique, which combines stellar population synthesis models with photometric redshift template fitting on the scale of individual pixels in galaxy images. Spectral energy distributions are constructed, sampling a wide range of properties such as age, star formation rate (SFR), dust obscuration, and metallicity. By summing the SFRs in the pixels, we demonstrate that the distribution of total galaxy SFR shifts to lower values as the local density of surrounding galaxies increases, as found in other studies. The effect is most prominent in the galaxies with the highest SF, and we see the break in the SFR-density relation at a local galaxy density of [?]0.05 (Mpc h[?]1)[?]3. Since our method allows us to spatially resolve the SF distribution within galaxies, we can calculate the mean SFR of each galaxy as a function of radius. We find that on average the mean SFR is dominated by SF in the central regions of galaxies, and that the trend for suppression of SFR in high-density environments is driven by a reduction in this nuclear SF. We also find that the mean SFR in the outskirts is largely independent of environmental effects. This trend in the mean SFR is shared by galaxies which are highly star forming, while those which are weakly star forming show no statistically significant correlation between their environment and the mean SFR at any radius.

The private biomedical research industry has brought significant benefits to patients and has been a major factor in the transformation of the course and treatment of disease over the past half century. It is estimated that over 90% of the medicines in use today have been discovered or developed by the industry. Successful medicines bring revenues to the companies who research and develop them through long-term at-risk investment; the ensuing returns through medicine sales are a key element in sustaining a virtuous circle in the traditional drug research and development (R&D) model. However, late-stage attrition, along with increasing development costs, are now challenging companies and the current R&D model. As a consequence, biopharmaceutical companies are under ever increasing pressure to develop new R&D models.The private biomedical research industry has brought significant benefits to patients and has been a major factor in the transformation of the course and treatment of disease over the past half century. It is estimated that over 90% of the medicines in use today have been discovered or developed by the industry. Successful medicines bring revenues to the companies who research and develop them through long-term at-risk investment; the ensuing returns through medicine sales are a key element in sustaining a virtuous circle in the traditional drug research and development (R&D) model. However, late-stage attrition, along with increasing development costs, are now challenging companies and the current R&D model. As a consequence, biopharmaceutical companies are under ever increasing pressure to develop new R&D models.

Strong constraints on the cosmic star formation history (SFH) have recently been established using ultraviolet and far-infrared measurements, refining the results of numerous measurements over the past decade. The data show a compellingly consistent picture of the SFH out to redshift z [?] 6, with especially tight constraints for z [?] 1. We fit these data with simple analytical forms and derive conservative uncertainties. Since the z [?] 1 SFH data are quite precise, we investigate the sequence of assumptions and corrections that together affect the SFH normalization to test their accuracy, both in this redshift range and beyond. As lower limits on this normalization, we consider the evolution in stellar and metal mass densities, and supernova rate density, finding it unlikely that the SFH normalization is much lower than indicated by our direct fit. As a corresponding upper limit on the SFH normalization, we consider the Super-Kamiokande limit on the electron antineutrino (img1.gife) flux from past core-collapse supernovae, which applies primarily to z [?] 1. We find consistency with the SFH only if the neutrino temperatures from supernova events are relatively modest. Constraints on the assumed initial mass function (IMF) also become apparent. The traditional Salpeter IMF, assumed for convenience by many authors, is known to be a poor representation at low stellar masses ([?]1 M), and we show that recently favored IMFs are also constrained. In particular, somewhat shallow, or top-heavy, IMFs may be preferred, although they cannot be too top-heavy. To resolve the outstanding issues, improved data are called for on the supernova rate density evolution, the ranges of stellar masses leading to core-collapse and type Ia supernovae, and the antineutrino and neutrino backgrounds from core-collapse supernovae.