Childhood obesity and its comorbidities continue to accelerate across the globe. Two-thirds of pregnant women are obese/overweight, as are 20% of preschoolers. Gestational diabetes mellitus (GDM) is ...escalating, affecting up to 1 in 5 pregnant women. The field of developmental origins of health and disease has begun to move beyond associations to potential causal mechanisms for developmental programming. Evidence across species compellingly demonstrates that maternal obesity, diabetes, and Western-style diets create a long-lasting signature on multiple systems, including infant stem cells, the early immune system, and gut microbiota. Such exposures accelerate adipogenesis, disrupt mitochondrial metabolism, and impair energy sensing, affecting neurodevelopment, liver, pancreas, and skeletal muscle. Attempts to prevent developmental programming have met with very limited success. A challenging level of complexity is involved in how the host genome, metabolome, and microbiome throughout pregnancy and lactation increase the offspring's risk of metabolic diseases across the life span. Considerable gaps in knowledge include the timing of exposure(s) and permanence or plasticity of the response, encompassing effects from both maternal and paternal dysmetabolism. Basic, translational, and human intervention studies targeting pathways that connect diet, microbiota, and metabolism in mothers with obesity/GDM and their infants are a critical unmet need and present new challenges for disease prevention in the next generation.
Five Ξ−p→ΛΛ two-body capture events in 12C and 14N emulsion nuclei, in which a pair of single-Λ hypernuclei is formed and identified by their weak decay, have been observed in (K−,K+) emulsion ...exposures at KEK and J-PARC. Applying a Ξ−-nucleus optical potential methodology to study atomic and nuclear transitions, we confirm that these capture events occur from Coulomb assisted 1pΞ− nuclear states. Long-range ΞN shell-model correlations are found essential to achieve consistency between the 12C and 14N events. The resulting Ξ-nuclear interaction is strongly attractive, with Ξ potential depth in nuclear matter VΞ≳20 MeV. Implications to multi-strangeness features of dense matter are outlined.
A depth of DΛ≈−28 MeV for the Λ-nucleus potential was confirmed in 1988 by studying Λ binding energies deduced from (π+,K+) spectra measured across the periodic table. Modern two-body hyperon-nucleon ...interaction models require additional interaction terms, most likely ΛNN three-body terms, to reproduce DΛ. Here we apply a suitably constructed Λ-nucleus density dependent optical potential to binding energy calculations of observed 1sΛ and 1pΛ states in the mass range 12≤A≤208. The resulting ΛNN contribution to DΛ, about 14 MeV repulsion at symmetric nuclear matter density ρ0=0.17 fm−3, makes DΛ increasingly repulsive at ρ≳3ρ0, leading possibly to little or no Λ hyperon content of neutron-star matter. This suggests in some models a stiff equation of state that may support two solar-mass neutron stars.
Exotic atoms provide a unique laboratory for studying strong interactions and nuclear medium effects at zero kinetic energy. Experimental and theoretical developments of the last decade in the study ...of exotic atoms and some related low-energy reactions are reviewed. The exotic atoms considered are of
π
-
,
K
-
,
p
¯
,
Σ
-
, and also the so far unobserved
Ξ
-
atoms. The analysis of these atomic systems consists of fitting density-dependent optical potentials
V
opt
=
t
(
ρ
)
ρ
to comprehensive sets of data of strong-interaction level shifts, widths and yields across the periodic table. These provide information on the in-medium hadron–nucleon
t matrix
t
(
ρ
)
over a wide range of densities up to central nuclear densities. For pions, the review focuses on the extraction of the
π
N
in-medium
s-wave interaction from pionic atoms, which include also the deeply bound
π
-
atomic states recently observed at GSI in isotopes of Sn and Pb. Also included are recent measurements at PSI of elastic scattering of
π
±
on Si, Ca, Ni and Zr at 21.5
MeV. The experimental results are analyzed in the context of chirally motivated
π
-nuclear potentials, and the evidence for partial restoration of chiral symmetry in dense nuclear matter is critically discussed. For antikaons, we review the evidence from
K
-
atoms, and also from low-energy
K
-
p
scattering and reaction data for and against a
deep
K
¯
-nucleus potential of 150–200
MeV attraction at nuclear matter density. The case for relatively narrow deeply bound
K
-
atomic states is made, essentially independent of the potential-depth issue. Recent experimental suggestions from KEK and DA
Φ
NE (Frascati) for signals of
K
¯
-nuclear deeply bound states are reviewed, and dynamical models for calculating binding energies and widths of
K
¯
-
nuclear states are discussed. For kaons we review the evidence, from
K
+
total and reaction cross section measurements at the AGS (BNL) on Li, C, Si and Ca at
p
lab
=
500
–
700
MeV
/
c
, for significant absorptivity of
t
KN
(
ρ
)
beyond that expected from
t
KN
free
within the impulse approximation. Attempts to explain the extra absorptivity for the relatively weak interaction of
K mesons in terms of a hypothetical exotic
S
=+
1
pentaquark
Θ
+
strength are reviewed. For antiprotons the exceptionally broad data base due to the recent results of the PS209 collaboration at CERN are analyzed, together with results of radiochemical experiments. We discuss the dependence of the phenomenological
p
¯
-nucleus interaction on the model adopted for the neutron density, showing how the neutron densities favored by our comprehensive analysis are compatible with densities from other sources, including our own analysis of pionic atoms. It is also shown how the strong absorptivity of the
p
¯
-nucleus interaction, which leads to the prediction of saturation of widths in deeply bound
p
¯
-atom states, also explains the observed saturation effects in low-energy
p
¯
annihilation on nuclei. For
Σ
hyperons we review the evidence, from continuum
Σ
-
hypernuclear
(
π
-
,
K
+
)
spectra obtained recently at KEK on C, Si, Ni, In and Bi, for substantial repulsion in the
Σ
-nucleus interaction, and the relationship to the inner repulsion established earlier from the density-dependence analysis of
Σ
-
atoms and by analyses of past
(
K
-
,
π
±
)
AGS experiments.
Lastly, for
Ξ
hyperons we review prospects of measuring X-ray spectra in
Ξ
-
atoms and thereby extracting meaningful information on the
Ξ
-nucleus interaction. The significance of the latter to the physics of
Λ
Λ
hypernuclei and to extrapolation into multistrange hypernuclei are briefly reviewed.
Earlier work suggested that the in-medium πN threshold isovector amplitude b1(ρ) gets renormalized in pionic atoms by ∼30% away from its ρ=0 free-space value, relating such renormalization to the ...leading low-density decrease of the in-medium quark condensate <q¯q> and the pion decay constant fπ in terms of the pion-nucleon σ term σπN. Accepting the validity of this approach, we extracted σπN from a large-scale fit of pionic-atom level shift and width data across the periodic table. Our fitted value σπN=57±7 MeV is robust with respect to variation of πN interaction terms other than the isovector s-wave term with which σπN was associated. Higher order corrections to the leading order in density involve some cancellations, suggesting thereby only a few percent overall systematic uncertainty. The value of σπN derived here agrees with values obtained in several recent studies based on near-threshold πN phenomenology, but sharply disagrees with values obtained in recent direct lattice QCD calculations.
Herein we report the first study of the oxygen reduction reaction (ORR) catalyzed by a cofacial porphyrin scaffold accessed in high yield (overall 53%) using coordination-driven self-assembly with no ...chromatographic purification steps. The ORR activity was investigated using chemical and electrochemical techniques on monomeric cobalt(II) tetra(meso-4-pyridyl)porphyrinate (CoTPyP) and its cofacial analogue Ru8(η6-iPrC6H4Me)8(dhbq)4(CoTPyP)2OTf8 (Co Prism) (dhbq = 2,5-dihydroxy-1,4-benzoquinato, OTf = triflate) as homogeneous oxygen reduction catalysts. Co Prism is obtained in one self-assembly step that organizes six total building blocks, two CoTPyP units and four arene–Ru clips, into a cofacial motif previously demonstrated with free-base, Zn(II), and Ni(II) porphyrins. Turnover frequencies (TOFs) from chemical reduction (66 vs 6 h–1) and rate constants of overall homogeneous catalysis (k obs) determined from rotating ring–disk experiments (1.1 vs 0.05 h–1) establish a cofacial enhancement upon comparison of the activities of Co Prism and CoTPyP, respectively. Cyclic voltammetry was used to initially probe the electrochemical catalytic behavior. Rotating ring–disk electrode studies were completed to probe the Faradaic efficiency and obtain an estimate of the rate constant associated with the ORR.
The Strangeness S=−2 J-PARC E07 emulsion experiment published recently two new Ξ−–14N capture events, IRRAWADDY and IBUKI, identified by observing weak-decay sequences of pairs of single-Λ ...hypernuclei and interpreted as Ξ1s− and Ξ1p− nuclear bound states, respectively, with binding energies BΞ−1s=6.27±0.27 MeV and BΞ−1p=1.27±0.21 MeV. Ξ− capture events in emulsion play a major role in determining the Ξ-nuclear and the ΛΛ potential strengths. Here we question the assignment of a Ξ1s− nuclear bound state to IRRAWADDY and offer an alternative assignment as a near-threshold Ξ1p0–14C nuclear bound state, slightly admixed with a Ξ1p−–14N nuclear bound state component corresponding to IBUKI. We also question using IBUKI's BΞ−1p value as is to determine the Ξ-nuclear potential depth. Altogether, Ξ− capture events in 12C and 16O should prove less ambiguous than in 14N.
BRCA1 and BRCA2 mutations increase breast and ovarian cancer risks substantially enough to warrant risk reduction surgery, despite variable risk estimates. Underlying this variability are ...methodological issues, and also complex genetic and nongenetic effects. Although many modifying factors are unidentified, known factors can already be incorporated in individualised risk prediction.
The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, BRCA1/2 mutation carriers with pancreatic cancer may have ...distinct biologic outcomes.
Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data were collected. Disease-free survival and overall survival (OS) were analysed.
Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33-83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent primary resection. Out of 71 participants, 12 received experimental therapy; one patient had missing data, these 13 cases were excluded from OS analysis. Median OS for 58 patients was 14 months (95% CI 10-23 months). Median OS for patients with stage 1/2 disease has not been reached with 52% still alive at 60 months. Median OS for stage 3/4 was 12 months (95% CI 6-15). Superior OS was observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies (22 vs 9 months; P=0.039).
Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure.
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