Highlights • Regional and network functional changes could be seen in the early stage of SCI. • Functional changes were associated with clinical symptom severity in SCI patients. • Functional ...reorganization may reflect a compensatory role in the recovery of SCI.
Central Asia is currently a semiarid‐arid region, dominated by the Westerlies. It is important to understand mechanisms of climate and precipitation changes here, as water availability in the region ...is crucial today and in the future. High‐resolution, absolutely‐dated oxygen isotope (δ18O) records of stalagmites from Kesang Cave characterize a dynamic precipitation history over most of the past 500,000 years. This record demonstrates, for the first time, that climate change in the region exhibits a processional rhythm with abrupt inceptions of low δ18O speleothem growth at times of high Northern Hemisphere summer insolation followed by gradual δ18O increases that track decreases of insolation. These observations and interpretations contrast with the interpretation of nearby, but higher elevation ice core records. The absolutely‐dated caveδ18O shifts can be used to correlate the regional climate variability by providing chronological marks. Combined with other paleoclimate records, the Kesang observations suggest that possible incursions of Asian summer monsoon rainfall or related moisture into the Kesang site and/or adjacent areas during the high insolation times may play an important role in changing orbital‐scale hydrology of the region. Based on our record, arid climate will prevail in this region for the next several millennia, providing that anthropogenic effects do not supersede natural processes.
Key Points
Speleothem records characterize 500 ka precipitation history in Central Asia
Climatic patterns in the Westerlies region are dominated by a precession rhythm
Asian Monsoon incursions may explain the hydrological change on precession scale
The stellar initial mass function (IMF) is commonly assumed to be an invariant probability density distribution function of initial stellar masses. These initial stellar masses are generally ...represented by the canonical IMF, which is defined as the result of one star formation event in an embedded cluster. As a consequence, the galaxy-wide IMF (gwIMF) should also be invariant and of the same form as the canonical IMF; gwIMF is defined as the sum of the IMFs of all star-forming regions in which embedded clusters form and spawn the galactic field population of the galaxy. Recent observational and theoretical results challenge the hypothesis that the gwIMF is invariant. In order to study the possible reasons for this variation, it is useful to relate the observed IMF to the gwIMF. Starting with the IMF determined in resolved star clusters, we apply the IGIMF-theory to calculate a comprehensive grid of gwIMF models for metallicities, Fe/H ∈ (−3, 1), and galaxy-wide star formation rates (SFRs), SFR ∈ (10−5, 105) M⊙ yr−1. For a galaxy with metallicity Fe/H < 0 and SFR > 1 M⊙ yr−1, which is a common condition in the early Universe, we find that the gwIMF is both bottom light (relatively fewer low-mass stars) and top heavy (more massive stars), when compared to the canonical IMF. For a SFR < 1 M⊙ yr−1 the gwIMF becomes top light regardless of the metallicity. For metallicities Fe/H > 0 the gwIMF can become bottom heavy regardless of the SFR. The IGIMF models predict that massive elliptical galaxies should have formed with a gwIMF that is top heavy within the first few hundred Myr of the life of the galaxy and that it evolves into a bottom heavy gwIMF in the metal-enriched galactic centre. Using the gwIMF grids, we study the SFR−Hα relation and its dependency on metallicity and the SFR. We also study the correction factors to the Kennicutt SFRK − Hα relation and provide new fitting functions. Late-type dwarf galaxies show significantly higher SFRs with respect to Kennicutt SFRs, while star-forming massive galaxies have significantly lower SFRs than hitherto thought. This has implications for gas-consumption timescales and for the main sequence of galaxies. We explicitly discuss Leo P and ultra-faint dwarf galaxies.
Aim
Emerging evidence from epidemiologic studies and basic science suggests a potential antitumour effect of metformin. However, whether metformin improves survival in cancer patients remains ...inconclusive.
Methods
A literature search was performed using the PubMed, EMbase and SciVerse Scopus databases. Pooled effect estimates were derived using a random‐effects meta‐analysis model.
Results
Of the 28 studies retrieved, the pooled effect estimates showed that metformin was associated with lower risk of all‐cause mortality in cancer patients with concurrent diabetes, particularly for breast pooled relative risk (RR) 0.70, 95% CI 0.55, 0.88; p = 0.003, colorectal (RR 0.70, 95% CI 0.59, 0.84; p < 0.001), ovarian (RR 0.44, 95% CI 0.30, 0.64; p < 0.001) and endometrial cancer (RR 0.49, 95% CI 0.32, 0.73; p = 0.001). In addition, metformin was associated with lower risks of cancer‐specific mortality.
Conclusions
The findings of this study support the hypothesis that metformin improves the survival for cancer patients with concurrent diabetes, particularly for breast, colorectal, ovarian, and endometrial cancer. Further investigation is warranted.
Abstract
We use state-of-the-art chemical models to track the cosmic evolution of the CNO isotopes in the interstellar medium of galaxies, yielding powerful constraints on their stellar initial mass ...function (IMF). We re-assess the relative roles of massive stars, asymptotic giant branch (AGB) stars and novae in the production of rare isotopes such as 13C, 15N, 17O and 18O, along with 12C, 14N and 16O. The CNO isotope yields of super-AGB stars, novae and fast-rotating massive stars are included. Having reproduced the available isotope enrichment data in the solar neighbourhood, and across the Galaxy, and having assessed the sensitivity of our models to the remaining uncertainties, e.g. nova yields and star formation history, we show that we can meaningfully constrain the stellar IMF in galaxies using C, O and N isotope abundance ratios. In starburst galaxies, where data for multiple isotopologue lines are available, we find compelling new evidence for a top-heavy stellar IMF, with profound implications for their star formation rates and efficiencies, perhaps also their stellar masses. Neither chemical fractionation nor selective photodissociation can significantly perturb globally averaged isotopologue abundance ratios away from the corresponding isotope ones, as both these processes will typically affect only small mass fractions of molecular clouds in galaxies. Thus, the Atacama Large Millimeter
Array now stands ready to probe the stellar IMF, and even the ages of specific starburst events in star-forming galaxies across cosmic time unaffected by the dust obscuration effects that plague optical/near-infrared studies.
In recent years, online retailers (also called e-tailers) have started allowing manufacturers direct access to their customers while charging a fee for providing this access, a format commonly ...referred to as agency selling. In this paper, we use a stylized theoretical model to answer a key question that e-tailers are facing: When should they use an agency selling format instead of using the more conventional reselling format? We find that agency selling is more efficient than reselling and leads to lower retail prices; however, the e-tailers end up giving control over retail prices to the manufacturer. Therefore, the reaction by the manufacturer, who makes electronic channel pricing decisions based on their impact on demand in the traditional channel (brick-and-mortar retailing), is an important factor for e-tailers to consider. We find that when sales in the electronic channel lead to a negative effect on demand in the traditional channel, e-tailers prefer agency selling, whereas when sales in the electronic channel lead to substantial stimulation of demand in the traditional channel, e-tailers prefer reselling. This preference is mediated by competition between e-tailers—as competition between them increases, e-tailers prefer to use agency selling. We also find that when e-tailers benefit from positive externalities from the sales of the focal product (such as additional profits from sales of associated products), retail prices may be lower under reselling than under agency selling, and the e-tailers prefer reselling under some conditions for which they would prefer agency selling without the positive externalities.
This paper was accepted by Chris Forman, information systems.
The North China Plain (NCP) is a region with high level of seismic hazard. Previous Global Positioning System measurements, however, have shown a near absence of present‐day crustal deformation. ...Using updated Global Positioning System data covering three blocks of the eastern China, we discover that interseismic deformation in the NCP takes place in an ~1,100 km wide left‐lateral shear zone of roughly east‐west orientation. The 6.0 ± 1.3 mm/yr interseismic left‐lateral shear over the NCP results in contemporary deformation that is eventually accommodated by earthquake ruptures of right‐lateral strike‐slip along the north‐northeast trending faults and anticlockwise block rotates. We suggest that rapid eastward motion of the rigid South China block, with respect to the rigid Amurian block, has created a left‐lateral shear couple to twist the nonrigid NCP to form the contemporary deformation.
Key Points
North China Plain is a region with high‐level of earthquake hazard but absence of detectable crustal deformation
Interseismic deformation of the NCP takes place in an ~1,100 km wide left‐lateral shear zone of roughly east‐west orientation
Permanent right‐lateral slips and block rotates on the NNE‐trending faults accommodate the left‐lateral transient shearing
We reevaluate the hadronic vacuum polarisation contributions to the muon magnetic anomaly and to the running of the electromagnetic coupling constant at the
Z
-boson mass. We include newest
e
+
e
-
→
...hadrons
cross-section data together with a phenomenological fit of the threshold region in the evaluation of the dispersion integrals. The precision in the individual datasets cannot be fully exploited due to discrepancies that lead to additional systematic uncertainty in particular between BABAR and KLOE data in the dominant
π
+
π
-
channel. For the muon
(
g
-
2
)
/
2
, we find for the lowest-order hadronic contribution
(
694.0
±
4.0
)
·
10
-
10
. The full Standard Model prediction differs by
3.3
σ
from the experimental value. The five-quark hadronic contribution to
α
(
m
Z
2
)
is evaluated to be
(
276.0
±
1.0
)
·
10
-
4
.
Kidney transplant injury occurs with ischemia and alloimmunity. Members of the receptor interacting protein kinase family (RIPK1,3) are key regulators of “necroptosis,” a newly recognized, regulated ...form of necrosis. Necroptosis and apoptosis death appear to be counterbalanced as caspase‐8 inhibition can divert death from apoptosis to necrosis. Inhibition of necroptosis in donor organs to limit injury has not been studied in transplant models. In this study, necroptosis was triggered in caspase inhibited tubular epithelial cells (TEC) exposed to tumor necrosis factor alpha in vitro, while RIPK1 inhibition with necrostatin‐1 or use of RIPK3−/− TEC, prevented necroptosis. In vivo, short hairpin RNA silencing of caspase‐8 in donor B6 mouse kidneys increased necroptosis, enhanced high‐mobility group box 1 release, reduced renal function and accelerated rejection when transplanted into BALB/c recipients. Using ethidium homodimer perfusion to assess necrosis in vivo, necrosis was abrogated in RIPK3−/− kidneys postischemia. Following transplantation, recipients receiving RIPK3−/− kidneys had longer survival (p = 0.002) and improved renal function (p = 0.03) when compared to controls. In summary, we show for the first time that RIPK3‐mediated necroptosis in donor kidneys can promote inflammatory injury, and has a major impact on renal ischemia–reperfusion injury and transplant survival. We suggest inhibition of necroptosis in donor organs may similarly provide a major clinical benefit.
Inhibition of donor kidney receptor‐interacting protein kinase–mediated necroptosis reduces inflammatory injury and prolongs allograft survival. See editorial by Mannon on page 2785 and minireview by Linkermann et al on page 2797.
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