Pursuits of wisdom Cooper, John M
2012., 20120527, 2012, 2012-05-27
eBook
This is a major reinterpretation of ancient philosophy that recovers the long Greek and Roman tradition of philosophy as a complete way of life--and not simply an intellectual discipline. ...Distinguished philosopher John Cooper traces how, for many ancient thinkers, philosophy was not just to be studied or even used to solve particular practical problems. Rather, philosophy--not just ethics but even logic and physical theory--was literally to be lived. Yet there was great disagreement about how to live philosophically: philosophy was not one but many, mutually opposed, ways of life. Examining this tradition from its establishment by Socrates in the fifth century BCE through Plotinus in the third century CE and the eclipse of pagan philosophy by Christianity,Pursuits of Wisdomexamines six central philosophies of living--Socratic, Aristotelian, Stoic, Epicurean, Skeptic, and the Platonist life of late antiquity.
The book describes the shared assumptions that allowed these thinkers to conceive of their philosophies as ways of life, as well as the distinctive ideas that led them to widely different conclusions about the best human life. Clearing up many common misperceptions and simplifications, Cooper explains in detail the Socratic devotion to philosophical discussion about human nature, human life, and human good; the Aristotelian focus on the true place of humans within the total system of the natural world; the Stoic commitment to dutifully accepting Zeus's plans; the Epicurean pursuit of pleasure through tranquil activities that exercise perception, thought, and feeling; the Skeptical eschewal of all critical reasoning in forming their beliefs; and, finally, the late Platonist emphasis on spiritual concerns and the eternal realm of Being.
Pursuits of Wisdomis essential reading for anyone interested in understanding what the great philosophers of antiquity thought was the true purpose of philosophy--and of life.
Tuberculosis is primarily a disease of the lung, and dissemination of the disease depends on productive infection of this critical organ. Upon aerosol infection with Mycobacterium tuberculosis (Mtb), ...the acquired cellular immune response is slow to be induced and to be expressed within the lung. This slowness allows infection to become well established; thus, the acquired response is expressed in an inflammatory site that has been initiated and modulated by the bacterium. Mtb has a variety of surface molecules that interact with the innate response, and this interaction along with the autoregulation of the immune response by several mechanisms results in less-than-optimal control of bacterial growth. To improve current vaccine strategies, we must understand the factors that mediate induction, expression, and regulation of the immune response in the lung. We must also determine how to induce both known and novel immunoprotective responses without inducing immunopathologic consequences.
Abstract
Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly ...penetrant contributors to severe Mendelian disorders. CADD is an integrative annotation built from more than 60 genomic features, and can score human single nucleotide variants and short insertion and deletions anywhere in the reference assembly. CADD uses a machine learning model trained on a binary distinction between simulated de novo variants and variants that have arisen and become fixed in human populations since the split between humans and chimpanzees; the former are free of selective pressure and may thus include both neutral and deleterious alleles, while the latter are overwhelmingly neutral (or, at most, weakly deleterious) by virtue of having survived millions of years of purifying selection. Here we review the latest updates to CADD, including the most recent version, 1.4, which supports the human genome build GRCh38. We also present updates to our website that include simplified variant lookup, extended documentation, an Application Program Interface and improved mechanisms for integrating CADD scores into other tools or applications. CADD scores, software and documentation are available at https://cadd.gs.washington.edu.
A Map of Local Adaptation in Arabidopsis thaliana Fournier-Level, A.; Korte, A.; Cooper, M. D. ...
Science (American Association for the Advancement of Science),
10/2011, Volume:
334, Issue:
6052
Journal Article
Peer reviewed
Local adaptation is critical for species persistence in the face of rapid environmental change, but its genetic basis is not well understood. Growing the model plant Arabidopsis thaliana in field ...experiments in four sites across the species' native range, we identified candidate loci for local adaptation from a genome-wide association study of lifetime fitness in geographically diverse accessions. Fitness-associated loci exhibited both geographic and climatic signatures of local adaptation. Relative to genomic controls, high-fitness alleles were generally distributed closer to the site where they increased fitness, occupying specific and distinct climate spaces. Independent loci with different molecular functions contributed most strongly to fitness variation in each site. Independent local adaptation by distinct genetic mechanisms may facilitate a flexible evolutionary response to changing environment across a species range.
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Stars form from cold molecular interstellar gas. As this is relatively rare in the local Universe, galaxies like the Milky Way form only a few new stars per year. Typical massive galaxies in the ...distant Universe formed stars an order of magnitude more rapidly. Unless star formation was significantly more efficient, this difference suggests that young galaxies were much more molecular-gas rich. Molecular gas observations in the distant Universe have so far largely been restricted to very luminous, rare objects, including mergers and quasars, and accordingly we do not yet have a clear idea about the gas content of more normal (albeit massive) galaxies. Here we report the results of a survey of molecular gas in samples of typical massive-star-forming galaxies at mean redshifts of about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current age. Our measurements reveal that distant star forming galaxies were indeed gas rich, and that the star formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy baryonic mass at z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher than in today’s massive spiral galaxies. The slow decrease between z 2 and z 1 probably requires a mechanism of semi-continuous replenishment of fresh gas to the young galaxies.
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Chronic inflammatory diseases of almost any cause are associated with bone loss. Bone loss is due to direct effects of inflammation, poor nutrition, reduced lean body mass, immobility and the effects ...of treatments, especially glucocorticoids. These mechanisms are complex and interrelated but are ultimately mediated through effects on the bone remodelling cycle. Inflammatory disease can increase bone resorption, decrease bone formation but most commonly impacts on both of these processes resulting in an uncoupling of bone formation from resorption in favour of excess resorption. This review will illustrate these interactions between inflammation and bone metabolism and discuss how these are, and might be, manipulated as therapies for inflammation related bone loss.
Soil structure (e.g. aggregation) has been recognized as a key element in the stabilization of soil organic matter. While aggregate bre akdown is assumed to expose the enclosed soil organic carbon ...(SOC) to preferential erosion and to accelerated decomposition, the link between the stability of soil aggregates and SOC exports from soils, has either been overlooked or unaccounted for, especially when developing carbon cycle models. This study compared SOC losses in particulate (POC), dissolved (DOC) and gaseous (GOC) forms to an indicator of the soil aggregate stability, the mean weight diameter of aggregates (MWD). SOC outputs were considered at 24 locations of a typical hillslope of the South African Highveld showing clayey to sandy soils. Both POC and DOC were evaluated in-situ under natural rains using 1×1m2 runoff plots while soil CO2 emissions were assessed in the laboratory from undisturbed 0–0.05m soil samples. MWD was finally compared to selected soil and terrain attributes for predictive purpose and as a means to further the understanding of SOC outputs from soils. MWD ranged between 1.4mm for unstable aggregates and 3.4mm for stable aggregates. The increase in aggregate stability resulted in a significant increase in POC and DOC concentrations in the eroded sediments (r=0.76) and in GOC losses from soils (r=0.91 when expressed as g C-CO2 per gram of soil; r=0.95 when as g C-CO2 per gram of soil carbon). In contrast, high aggregate stability induced low total DOC and POC losses (r=−0.81 and −0.77, respectively). The lower POC and DOC losses in the most stable soil aggregates were explained by increased soil infiltration by water and reduced transport by runoff, while the greater CO2 emissions correlated with high SOC concentration. Furthermore, there was a tendency for clayey soils which were fully covered by grass to present stable aggregates and thus to yield greater CO2 emissions but lower POC and DOC outputs than degraded sandy soils of low aggregate stability. Such a quantitative assessment of the role of soil aggregation on SOC outputs might enhance knowledge on organic matter persistence in soils, a prerequisite for developing more accurate global carbon cycle models. Finally further research is required to investigate the downslope to downstream fate of the eroded SOC and to develop land management strategies that aim at lessening carbon losses from soils while enhancing adaptation to climate change.
•POC and DOC content increased as the stability of soil aggregates increased.•Stable aggregates yielded low losses of particulate and dissolved carbon but high CO2 emissions.•Low particulate and dissolved losses were explained by increased soil infiltration by water and reduced transport by runoff.•High CO2 emissions correlated with high top-soil carbon content.
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Most human transcription factors bind a small subset of potential genomic sites and often use different subsets in different cell types. To identify mechanisms that govern cell-type-specific ...transcription factor binding, we used an integrative approach to study estrogen receptor α (ER). We found that ER exhibits two distinct modes of binding. Shared sites, bound in multiple cell types, are characterized by high-affinity estrogen response elements (EREs), inaccessible chromatin, and a lack of DNA methylation, while cell-specific sites are characterized by a lack of EREs, co-occurrence with other transcription factors, and cell-type-specific chromatin accessibility and DNA methylation. These observations enabled accurate quantitative models of ER binding that suggest tethering of ER to one-third of cell-specific sites. The distinct properties of cell-specific binding were also observed with glucocorticoid receptor and for ER in primary mouse tissues, representing an elegant genomic encoding scheme for generating cell-type-specific gene regulation.
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•Two types of estrogen receptor α binding sites: shared and cell specific•Shared sites are encoded in the genome as high-affinity estrogen response elements•Cell-specific sites rely on interacting factors and depend on genomic context•Cell-specific binding is predicted from DNA sequence and chromatin accessibility
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Abstract
This paper provides an update of our previous scaling relations between galaxy-integrated molecular gas masses, stellar masses, and star formation rates (SFRs), in the framework of the star ...formation main sequence (MS), with the main goal of testing for possible systematic effects. For this purpose our new study combines three independent methods of determining molecular gas masses from CO line fluxes, far-infrared dust spectral energy distributions, and ∼1 mm dust photometry, in a large sample of 1444 star-forming galaxies between
z
= 0 and 4. The sample covers the stellar mass range log(
M
*
/
M
⊙
) = 9.0–11.8, and SFRs relative to that on the MS,
δ
MS = SFR/SFR(MS), from 10
−1.3
to 10
2.2
. Our most important finding is that all data sets, despite the different techniques and analysis methods used, follow the same scaling trends, once method-to-method zero-point offsets are minimized and uncertainties are properly taken into account. The molecular gas depletion time
t
depl
, defined as the ratio of molecular gas mass to SFR, scales as (1 +
z
)
−0.6
× (
δ
MS)
−0.44
and is only weakly dependent on stellar mass. The ratio of molecular to stellar mass
μ
gas
depends on (
1
+
z
)
2.5
×
(
δ
MS
)
0.52
×
(
M
*
)
−
0.36
, which tracks the evolution of the specific SFR. The redshift dependence of
μ
gas
requires a curvature term, as may the mass dependences of
t
depl
and
μ
gas
. We find no or only weak correlations of
t
depl
and
μ
gas
with optical size
R
or surface density once one removes the above scalings, but we caution that optical sizes may not be appropriate for the high gas and dust columns at high
z
.
The extragalactic background light (EBL) is of fundamental importance both for understanding the entire process of galaxy evolution and for γ-ray astronomy, but the overall spectrum of the EBL ...between 0.1 and 1000 μm has never been determined directly from galaxy spectral energy distribution (SED) observations over a wide redshift range. The evolving, overall spectrum of the EBL is derived here utilizing a novel method based on observations only. This is achieved from the observed evolution of the rest-frame K-band galaxy luminosity function up to redshift 4, combined with a determination of galaxy-SED-type fractions. These are based on fitting Spitzer Wide-Area Infrared Extragalactic Survey (SWIRE) templates to a multiwavelength sample of about 6000 galaxies in the redshift range from 0.2 to 1 from the All-wavelength Extended Groth Strip International Survey (AEGIS). The changing fractions of quiescent galaxies, star-forming galaxies, starburst galaxies and active galactic nucleus (AGN) galaxies in that redshift range are estimated, and two alternative extrapolations of SED types to higher redshifts are considered. This allows calculation of the evolution of the luminosity densities from the ultraviolet (UV) to the infrared (IR), the evolving star formation rate density of the Universe, the evolving contribution to the bolometric EBL from the different galaxy populations including AGN galaxies and the buildup of the EBL. Our EBL calculations are compared with those from a semi-analytic model, another observationally based model and observational data. The EBL uncertainties in our modelling based directly on the data are quantified, and their consequences for attenuation of very-high-energy γ-rays due to pair production on the EBL are discussed. It is concluded that the EBL is well constrained from the UV to the mid-IR, but independent efforts from IR and γ-ray astronomy are needed in order to reduce the uncertainties in the far-IR.
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