The transition from a human diet based exclusively on wild plants and animals to one involving dependence on domesticated plants and animals beginning 10,000 to 11,000 y ago in Southwest Asia set ...into motion a series of profound health, lifestyle, social, and economic changes affecting human populations throughout most of the world. However, the social, cultural, behavioral, and other factors surrounding health and lifestyle associated with the foraging-to-farming transition are vague, owing to an incomplete or poorly understood contextual archaeological record of living conditions. Bioarchaeological investigation of the extraordinary record of human remains and their context from Neolithic Çatalhöyük (7100–5950 cal BCE), a massive archaeological site in south-central Anatolia (Turkey), provides important perspectives on population dynamics, health outcomes, behavioral adaptations, interpersonal conflict, and a record of community resilience over the life of this single early farming settlement having the attributes of a protocity. Study of Çatalhöyük human biology reveals increasing costs to members of the settlement, including elevated exposure to disease and labor demands in response to community dependence on and production of domesticated plant carbohydrates, growing population size and density fueled by elevated fertility, and increasing stresses due to heightened workload and greater mobility required for caprine herding and other resource acquisition activities over the nearly 12 centuries of settlement occupation. These changes in life conditions foreshadow developments that would take place worldwide over the millennia following the abandonment of Neolithic Çatalhöyük, including health challenges, adaptive patterns, physical activity, and emerging social behaviors involving interpersonal violence.
Objectives
The transition from foraging to farming is usually associated with unprecedented population densities coupled with an increase in fertility and population growth. However, little is known ...about the biological effects of such demographic changes during the Neolithic. In the present work, we test the relationship between diachronic changes in population size, relative exposure to developmental stressors, and patterns of dental fluctuating asymmetry in the Neolithic population of Çatalhöyük (Turkey, 7,100–5,950 cal BC).
Materials and Methods
We calculate fluctuating asymmetry of mesio‐distal and bucco‐lingual diameters of upper and lower permanent canines and first and second molars on a large (N = 259) sample representing adults of both sexes and various age classes.
Results
Results show only a moderate decrease of fluctuating asymmetry during the late phase of occupation of the site, possibly linked to a decrease in population density, and no differences in asymmetry between sexes.
Discussion
Though preliminary, our data reflect the presence of developmental stressors throughout the occupation of the site, albeit with a slight improvement in living conditions during the latest periods of occupation. At the same time, these data confirm the key role of diet as buffer against the detrimental effects of fluctuating demographic pressures on the biology of prehistoric human populations.
We compare the jet-path length and beam-energy dependence of the pion nuclear modification factor and a patton-jet nuclear modification factor at RHIC and LHC, and contrast the predictions based on a ...linear pQCD and a highly non-linear hybrid AdS holographic model of jet-energy loss. It is found that both models require a reduction of the jet-medium coupling from RHIC to LHC to account for the measured pion nuclear modification factor. In the case of the parton-jet nuclear modification factor, however, which serves as a lower bound for the LO jet nuclear modification factor of reconstructed jets, the extracted data can be characterized without a reduced jet-medium coupling at LHC energies. It is concluded that when the reconstructed jets are sensitive to both quarks and gluons and thus provide more information than the pion nuclear modification factor, their information regarding the jet-medium coupling is limited due to the superposition with NLO and medium effects. Hence, a detailed description of the underlying physics requires both the leading hadron and the reconstructed jet nuclear modification factor. Unfortunately, the results for both the pion and the parton-jet nuclear modification factor are insensitive to the jet-path dependence of the models considered.
By accentuating drug efficacy and impeding resistance mechanisms, combinatorial, multi‐agent therapies have emerged as key approaches in the treatment of complex diseases, most notably cancer. Using ...high‐throughput drug screens, we uncovered distinct metabolic vulnerabilities and thereby identified drug combinations synergistically causing a starvation‐like lethal catabolic response in tumor cells from different cancer entities. Domperidone, a dopamine receptor antagonist, as well as several tricyclic antidepressants (TCAs), including imipramine, induced cancer cell death in combination with the mitochondrial uncoupler niclosamide ethanolamine (NEN) through activation of the integrated stress response pathway and the catabolic CLEAR network. Using transcriptome and metabolome analyses, we characterized a combinatorial response, mainly driven by the transcription factors CHOP and TFE3, which resulted in cell death through enhanced pyrimidine catabolism as well as reduced pyrimidine synthesis. Remarkably, the drug combinations sensitized human organoid cultures to the standard‐of‐care chemotherapy paclitaxel. Thus, our combinatorial approach could be clinically implemented into established treatment regimen, which would be further facilitated by the advantages of drug repurposing.
Synopsis
This study identifies novel combinatorial drug treatments to induce death of different tumor cells, and defines the mechanisms of synergism between a mitochondrial uncoupler and antidepressants or dopamine receptor antagonists.
Mitochondrial uncoupler NEN synergized with tricyclic antidepressants (TCAs) and dopamine receptor antagonists to induce tumor cell death.
Synergistic cell death relied on the induction of the integrated stress response pathway and the catabolic CLEAR network.
Combinatorial drug treatment sensitized human pancreatic cancer organoids to Paclitaxel chemotherapy.
This study identifies novel combinatorial drug treatments to induce death of different tumor cells, and defines the mechanisms of synergism between a mitochondrial uncoupler and antidepressants or dopamine receptor antagonists.
The double-peak structure observed in soft-hard hadron correlations is commonly interpreted as a signature for a Mach cone generated by a supersonic jet interacting with the hot and dense medium ...created in ultrarelativistic heavy-ion collisions. We show that it can also arise due to averaging over many jet events in a transversally expanding background. We find that the jet-induced away-side yield does not depend on the details of the energy-momentum deposition in the plasma, the jet velocity, or the system size. Our claim can be experimentally tested by comparing soft-hard correlations induced by heavy-flavor jets with those generated by light-flavor jets.
A
bstract
Recent data on the high-
p
T
pion nuclear modification factor,
R
AA
(
p
T
), and its elliptic azimuthal asymmetry,
v
2
(
p
T
), from RHIC/BNL and LHC/CERN are analyzed in terms of a wide ...class of jet-energy loss models coupled to different (2+1)d transverse plus Bjorken expanding hydrodynamic fields. We test the consistency of each model by demanding a simultaneous account of the azimuthal, the transverse momentum, and the centrality dependence of the data at both 0.2 and 2.76 ATeV energies. We find a rather broad class of jet-energy independent energy-loss models
dE/dx
=
κ
(
T
)
x
z
T
2+
z
ζ
q
that, when coupled to bulk constrained temperature fields
T
(
x, t
), can account for the current data at the
χ
2
/
d
.
o
.
f
. <
2 level with different temperature-dependent jet-medium couplings,
κ
(
T
), and path-length dependence exponents 0 ≤
z
≤ 2. We extend previous studies by including a generic term, 0
< ζ
q
<
2 +
q
, to test different scenarios of energy-loss fluctuations. While a previously proposed AdS/CFT jet-energy loss model with a temperature-independent jet-medium coupling as well as a near-
T
c
dominated, pQCD-inspired energy-loss scenario are shown to be inconsistent with the LHC data, once the parameters are constrained by fitting to RHIC results, we find several new solutions with a temperature-dependent
κ
(
T
). We conclude that the current level of statistical and systematic uncertainties of the measured data does not allow a constraint on the path-length exponent
z
to a range narrower than 0 − 2.
Azimuthal jet tomography at RHIC and LHC Betz, Barbara; Gyulassy, Miklos
Nuclear physics. A,
November 2014, 2014-11-00, 2014-11-01, Letnik:
931, Številka:
C
Journal Article
Recenzirano
Odprti dostop
Results based on a generic jet-energy loss model that interpolates between running coupling pQCD-based and AdS/CFT-inspired holographic prescriptions are compared to recent data on the high-pT pion ...nuclear modification factor and the high-pT elliptic flow in nuclear collisions at RHIC and LHC. The jet-energy loss model is coupled to various (2+1)d (viscous hydrodynamic) fields. The impact of energy-loss fluctuations is discussed. While a previously proposed AdS/CFT jet-energy loss model with a temperature-independent jet-medium coupling is shown to be inconsistent with the LHC data, we find a rather broad class of jet-energy independent energy-loss models dE/dx=κ(T)xzT2+z that can account for the current data with different temperature-dependent jet-medium couplings κ(T) and path-length dependence exponents of 0≤z≤2.
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