Integration of energy crops into agricultural landscapes could promote sustainability if they are placed in ways that foster multiple ecosystem services and mitigate ecosystem disservices from ...existing crops. We conducted a modeling study to investigate how replacing annual energy crops with perennial energy crops along Wisconsin waterways could affect a variety of provisioning and regulating ecosystem services. We found that a switch from continuous corn production to perennial-grass production decreased annual income provisioning by 75%, although it increased annual energy provisioning by 33%, decreased annual phosphorous loading to surface water by 29%, increased below-ground carbon sequestration by 30%, decreased annual nitrous oxide emissions by 84%, increased an index of pollinator abundance by an average of 11%, and increased an index of biocontrol potential by an average of 6%. We expressed the tradeoffs between income provisioning and other ecosystem services as benefit-cost ratios. Benefit-cost ratios averaged 12.06 GJ of additional net energy, 0.84 kg of avoided phosphorus pollution, 18.97 Mg of sequestered carbon, and 1.99 kg of avoided nitrous oxide emissions for every $1,000 reduction in income. These ratios varied spatially, from 2- to 70-fold depending on the ecosystem service. Benefit-cost ratios for different ecosystem services were generally correlated within watersheds, suggesting the presence of hotspots--watersheds where increases in multiple ecosystem services would come at lower-than-average opportunity costs. When assessing the monetary value of ecosystem services relative to existing conservation programs and environmental markets, the overall value of enhanced services associated with adoption of perennial energy crops was far lower than the opportunity cost. However, when we monitized services using estimates for the social costs of pollution, the value of enhanced services far exceeded the opportunity cost. This disparity between recoverable costs and social value represents a fundamental challenge to expansion of perennial energy crops and sustainable agricultural landscapes.
Cockayne syndrome is a premature aging disease associated with numerous developmental and neurological abnormalities, and elevated levels of reactive oxygen species have been found in cells derived ...from Cockayne syndrome patients. The majority of Cockayne syndrome cases contain mutations in the ATP-dependent chromatin remodeler CSB; however, how CSB protects cells from oxidative stress remains largely unclear. Here, we demonstrate that oxidative stress alters the genomic occupancy of the CSB protein and increases CSB occupancy at promoters. Additionally, we found that the long-range chromatin-structure regulator CTCF plays a pivotal role in regulating sites of genomic CSB occupancy upon oxidative stress. We show that CSB directly interacts with CTCF in vitro and that oxidative stress enhances the CSB-CTCF interaction in cells. Reciprocally, we demonstrate that CSB facilitates CTCF-DNA interactions in vitro and regulates CTCF-chromatin interactions in oxidatively stressed cells. Together, our results indicate that CSB and CTCF can regulate each other's chromatin association, thereby modulating chromatin structure and coordinating gene expression in response to oxidative stress.
Objective To describe atopic dermatitis (AD) management patterns in children ≤36 months old as reported by pediatricians, dermatologists, and allergists in the US. Study design A ...nationally-representative survey was administered to pediatricians (n = 101), dermatologists (n = 26), and allergists (n = 26). Main outcomes included referrals to health care professionals, suggested/ordered laboratory tests, management approach (dietary, pharmacologic, or combination of both) by age, AD location, and severity. Results Significant differences were observed in referrals to healthcare professionals ( P < .001). Pediatricians more frequently referred to dermatologists than allergists in mild (52.4% vs 32.0%) and moderate/severe (60.6% vs 38.1%) cases. Dermatologists referred to allergists less frequently for mild (9.1%) than moderate/severe (40.7%) AD cases. Pediatricians (59%), allergists (61.5%), and dermatologists (26.9%) reported treating at least some of their patients with AD with dietary management (infant formula change) alone (with or without emollients). Soy-based formulas were often used. For mild AD, the most commonly reported first-line pharmacologic treatments included topical emollients, topical corticosteroids, and barrier repair topical therapy/medical devices. Over 80% of physicians used a dietary and pharmacologic combination approach. Dermatologists were most likely to manage AD symptoms with a pharmacologic-only approach. AD lesion location influenced pharmacologic treatment in >80% of physicians. Conclusions Significant and distinct differences in AD treatment approach exist among physicians surveyed. Most pediatricians and allergists use formula change as a management strategy in some patients, whereas dermatologists favor a pharmacologic approach. This diversity may result from inadequate evidence for a standard approach. Consistent methods for managing AD are needed.
Abstract We present a catalog of 717 candidate galaxies at z > 8 selected from 125 square arcmin of NIRCam imaging as part of the JWST Advanced Deep Extragalactic Survey (JADES). We combine the full ...JADES imaging data set with data from the JWST Extragalactic Medium Survey and First Reionization Epoch Spectroscopic COmplete Survey (FRESCO) along with extremely deep existing observations from Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) for a final filter set that includes 15 JWST/NIRCam filters and five HST/ACS filters. The high-redshift galaxy candidates were selected from their estimated photometric redshifts calculated using a template-fitting approach, followed by visual inspection from seven independent reviewers. We explore these candidates in detail, highlighting interesting resolved or extended sources, sources with very red long-wavelength slopes, and our highest-redshift candidates, which extend to z phot ∼ 18. Over 93% of the sources are newly identified from our deep JADES imaging, including 31 new galaxy candidates at z phot > 12. We also investigate potential contamination by stellar objects, and do not find strong evidence from spectral energy distribution fitting that these faint high-redshift galaxy candidates are low-mass stars. Using 42 sources in our sample with measured spectroscopic redshifts from NIRSpec and FRESCO, we find excellent agreement to our photometric redshift estimates, with no catastrophic outliers and an average difference of 〈Δ z = z phot − z spec 〉 = 0.26. These sources comprise one of the most robust samples for probing the early buildup of galaxies within the first few hundred million years of the Universe’s history.
We present JADES JWST/NIRSpec spectroscopy of GN-z11, the most luminous candidate
z
> 10 Lyman break galaxy in the GOODS-North field with
M
UV
= −21.5. We derive a redshift of
z
= 10.603 (lower ...than previous determinations) based on multiple emission lines in our low and medium resolution spectra over 0.7 − 5.3 μm. We significantly detect the continuum and measure a blue rest-UV spectral slope of
β
= −2.4. Remarkably, we see spatially extended Lyman-
α
in emission (despite the highly neutral intergalactic medium expected at this early epoch), offset 555 km s
−1
redwards of the systemic redshift. From our measurements of collisionally excited lines of both low and high ionisation (including O
II
λ
3727, Ne
III
λ
3869, and C
III
λ
1909), we infer a high ionisation parameter (log
U
∼ −2). We detect the rarely seen N
IV
λ
1486 and N
III
λ
1748 lines in both our low and medium resolution spectra, with other high ionisation lines seen in the low resolution spectrum, such as He
II
(blended with O
III
) and C
IV
(with a possible P-Cygni profile). Based on the observed rest-UV line ratios, we cannot conclusively rule out photoionisation from an active galactic nucleus (AGN), although the high C
III
/He
II
and N
III
/He
II
ratios are compatible with a star formation explanation. If the observed emission lines are powered by star formation, then the strong N
III
λ
1748 observed may imply an unusually high
N
/
O
abundance. Balmer emission lines (H
γ
, H
δ
) are also detected, and if powered by star formation rather than an AGN, we infer a star formation rate of ∼20 − 30
M
⊙
yr
−1
(depending on the initial mass function) and low dust attenuation. Our NIRSpec spectroscopy confirms that GN-z11 is a remarkable galaxy with extreme properties seen 430 Myr after the Big Bang.
The PALLAS study investigated whether the addition of palbociclib, an oral CDK4/6 inhibitor, to adjuvant endocrine therapy (ET) improves invasive disease-free survival (iDFS) in early hormone ...receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In this analysis, we evaluated palbociclib exposure and discontinuation in PALLAS.
Patients with stage II-III HR+, HER2- disease were randomly assigned to 2 years of palbociclib with adjuvant ET versus ET alone. The primary objective was to compare iDFS between arms. Continuous monitoring of toxicity, dose modifications, and early discontinuation was performed. Association of baseline covariates with time to palbociclib reduction and discontinuation was analyzed with multivariable competing risk models. Landmark and inverse probability weighted per-protocol analyses were performed to assess the impact of drug persistence and exposure on iDFS.
Of the 5,743 patient analysis population (2,840 initiating palbociclib), 1,199 (42.2%) stopped palbociclib before 2 years, the majority (772, 27.2%) for adverse effects, most commonly neutropenia and fatigue. Discontinuation of ET did not differ between arms. Discontinuations for non-protocol-defined reasons were greater in the first 3 months of palbociclib, and in the first calendar year of accrual, and declined over time. No significant relationship was seen between longer palbociclib duration or ≥ 70% exposure intensity and improved iDFS. In the weighted per-protocol analysis, no improvement in iDFS was observed in patients receiving palbociclib versus not (hazard ratio 0.89; 95% CI, 0.72 to 1.11).
Despite observed rates of discontinuation in PALLAS, analyses suggest that the lack of significant iDFS difference between arms was not directly related to inadequate palbociclib exposure. However, the discontinuation rate illustrates the challenge of introducing novel adjuvant treatments, and the need for interventions to improve persistence with oral cancer therapies.
The lignin biosynthetic pathway is highly conserved in angiosperms, yet pathway manipulations give rise to a variety of taxon-specific outcomes. Knockout of lignin-associated
-
:
(
) in herbaceous ...species mainly reduces guaiacyl (G) lignin and enhances cell wall saccharification. Here we show that CRISPR-knockout of
in poplar (
×
) preferentially reduced syringyl (S) lignin, with negligible effects on biomass recalcitrance. Concordant with reduced S-lignin was downregulation of
-
(
). Lignification was largely sustained by 4CL5, a low-affinity paralog of 4CL1 typically with only minor xylem expression or activity. Levels of caffeate, the preferred substrate of 4CL5, increased in line with significant upregulation of
Upregulation of
-
-
and downregulation of
are consistent with preferential funneling of 4CL5 products toward G-lignin biosynthesis at the expense of S-lignin. Thus, transcriptional and metabolic adaptations to
-knockout appear to have enabled 4CL5 catalysis at a level sufficient to sustain lignification. Finally, genes involved in sulfur assimilation, the glutathione-ascorbate cycle, and various antioxidant systems were upregulated in the mutants, suggesting cascading responses to perturbed thioesterification in lignin biosynthesis.
Why do states delegate certain tasks and responsibilities to international organizations rather than acting unilaterally or cooperating directly? Furthermore, to what extent do states continue to ...control IOs once authority has been delegated? Examining a variety of different institutions including the World Trade Organization, the United Nations and the European Commission, this book explores the different methods that states employ to ensure their interests are being served, and identifies the problems involved with monitoring and managing IOs. The contributors suggest that it is not inherently more difficult to design effective delegation mechanisms at international level than at domestic level and, drawing on principal-agent theory, help explain the variations that exist in the extent to which states are willing to delegate to IOs. They argue that IOs are neither all evil nor all virtuous, but are better understood as bureaucracies that can be controlled to varying degrees by their political masters.
We report the discovery of a remarkable Ly
α
emitting galaxy at
z
= 7.2782, JADES-GS+53.16746−27.7720 (shortened to JADES-GS-z7-LA), with rest-frame equivalent width, EW
0
(Ly
α
) = 388.0 ± 88.8 Å ...and UV magnitude −17.0. The spectroscopic redshift is confirmed via rest-frame optical lines O
II
, H
β
and O
III
in its JWST/NIRSpec Micro-Shutter Assembly (MSA) spectrum. The Ly
α
line is detected in both lower resolution (
R
∼ 100) PRISM as well as medium resolution (
R
∼ 1000)
G
140
M
grating spectra. The line spread function-deconvolved Ly
α
full width at half maximum in the grating is 383.9 ± 56.2 km s
−1
and the Ly
α
velocity offset compared to the systemic redshift is 113.3 ± 80.0 km s
−1
, indicative of very little neutral gas or dust within the galaxy. We estimate the Ly
α
escape fraction to be > 70%. JADES-GS-z7-LA has a O
III
/O
II
ratio (O32) of 11.1 ± 2.2 and a (O
III
+ O
II
)/H
β
ratio (R23) of 11.2 ± 2.6, consistent with low metallicity and high ionization parameters. Deep NIRCam imaging also revealed a close companion source (separated by 0.23″), which exhibits similar photometry to that of JADES-GS-z7-LA, with a photometric excess in the
F
410
M
NIRCam image consistent with O
III
+ H
β
emission at the same redshift. The spectral energy distribution of JADES-GS-z7-LA indicates a “bursty” star formation history, with a low stellar mass of ≈10
7
M
⊙
. Assuming that the Ly
α
transmission through the intergalactic medium is the same as its measured escape fraction, an ionized region of size > 1.5 pMpc is needed to explain the high Ly
α
EW and low velocity offset compared to systemic seen in JADES-GS-z7-LA. Owing to its UV-faintness, we show that it is incapable of single-handedly ionizing a region large enough to explain its Ly
α
emission. Therefore, we suggest that JADES-GS-z7-LA (and possibly the companion source) may be a part of a larger overdensity, presenting direct evidence of overlapping ionized bubbles at
z
> 7.
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