A discrete time crystal (DTC) is a robust phase of driven systems that breaks the discrete time translation symmetry of the driving Hamiltonian. Recent experiments have observed DTC signatures in two ...distinct systems. Here we show nuclear magnetic resonance observations of DTC signatures in a third, strikingly different system: an ordered spatial crystal. We use a novel DTC echo experiment to probe the coherence of the driven system. Finally, we show that interactions during the pulse of the DTC sequence contribute to the decay of the signal, complicating attempts to measure the intrinsic lifetime of the DTC.
Can oxytocin treat autism? Young, Larry J; Barrett, Catherine E
Science,
02/2015, Letnik:
347, Številka:
6224
Journal Article
Recenzirano
Odprti dostop
We are still at an early stage of assessing oxytocin-based therapy for autism spectrum disorders
The U.S. Centers for Disease Control and Prevention estimates the prevalence of autism spectrum ...disorders (ASDs) to be 1 in 68 children in the United States, yet no drugs to treat the debilitating social deficits of ASD are available. Oxytocin, a natural brain peptide produced in the hypothalamus, has received considerable attention as a potential treatment for social deficits in ASD. Acute intranasal oxytocin temporarily enhances social cognition, empathy, and reciprocity in individuals with ASD (
1
). However, recent clinical trials have yielded mixed results, leaving the field questioning whether oxytocin can live up to the hype.
Who benefits from agricultural subsidies is an open question. Economic theory predicts that the entire subsidy incidence should be on the farmland owners. Using a complementary set of policy quasi ...experiments, I find that farmers who rent the land they cultivate capture 75 percent of the subsidy, leaving just 25 percent for landowners. This finding contradicts the prediction from neoclassical models. The standard prediction may not hold because of less than perfect competition in the farmland rental market; the share captured by landowners increases with local measures of competitiveness in the farmland rental market.
Evidence suggests that insulin delivery to skeletal muscle interstitium is the rate-limiting step in insulin-stimulated muscle glucose uptake and that this process is impaired by insulin resistance. ...In this review we examine the basis for the hypothesis that insulin acts on the vasculature at three discrete steps to enhance its own delivery to muscle: (1) relaxation of resistance vessels to increase total blood flow; (2) relaxation of pre-capillary arterioles to increase the microvascular exchange surface perfused within skeletal muscle (microvascular recruitment); and (3) the trans-endothelial transport (TET) of insulin. Insulin can relax resistance vessels and increase blood flow to skeletal muscle. However, there is controversy as to whether this occurs at physiological concentrations of, and exposure times to, insulin. The microvasculature is recruited more quickly and at lower insulin concentrations than are needed to increase total blood flow, a finding consistent with a physiological role for insulin in muscle insulin delivery. Microvascular recruitment is impaired by obesity, diabetes and nitric oxide synthase inhibitors. Insulin TET is a third potential site for regulating insulin delivery. This is underscored by the consistent finding that steady-state insulin concentrations in plasma are approximately twice those in muscle interstitium. Recent in vivo and in vitro findings suggest that insulin traverses the vascular endothelium via a trans-cellular, receptor-mediated pathway, and emerging data indicate that insulin acts on the endothelium to facilitate its own TET. Thus, muscle insulin delivery, which is rate-limiting for its metabolic action, is itself regulated by insulin at multiple steps. These findings highlight the need to further understand the role of the vascular actions of insulin in metabolic regulation.
STUDY QUESTION
Is first trimester phthalate exposure associated with anogenital distance (AGD), a biomarker of prenatal androgen exposure, in newborns?
SUMMARY ANSWER
Concentrations of diethylhexyl ...phthalate (DEHP) metabolites in first trimester maternal urine samples are inversely associated with AGD in male, but not female, newborns.
WHAT IS KNOWN ALREADY
AGD is a sexually dimorphic measure reflecting prenatal androgen exposure. Prenatal phthalate exposure has been associated with shorter male AGD in multiple animal studies. Prior human studies, which have been limited by small sample size and imprecise timing of exposure and/or outcome, have reported conflicting results.
STUDY DESIGN, SIZE, DURATION
The Infant Development and the Environment Study (TIDES) is a prospective cohort study of pregnant women recruited in prenatal clinics in San Francisco, CA, Minneapolis, MN, Rochester, NY and Seattle, WA in 2010–2012. Participants delivered 787 infants; 753 with complete data are included in this analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Any woman over 18 years old who was able to read and write English (or Spanish in CA), who was <13 weeks pregnant, whose pregnancy was not medically threatened and who planned to deliver in a study hospital was eligible to participate. Analyses include all infants whose mothers provided a first trimester urine sample and who were examined at or shortly after birth. Specific gravity (SpG) adjusted concentrations of phthalate metabolites in first trimester urine samples were examined in relation to genital measurements. In boys (N = 366), we obtained two measures of anogenital distance (AGD) (anoscrotal distance, or AGDAS and anopenile distance, AGDAP) as well as penile width (PW). In girls (N = 373), we measured anofourchette distance (AGDAF) and anoclitoral distance (AGDAC). We used multivariable regression models that adjusted for the infant's age at exam, gestational age, weight-for-length Z-score, time of day of urine collection, maternal age and study center.
MAIN RESULTS AND THE ROLE OF CHANCE
Three metabolites of DEHP were significantly and inversely associated with both measures of boys' AGD. Associations (β, 95% confidence interval (CI)) between AGDAS and (log10) SpG-adjusted phthalate concentrations were: −1.12 (−2.16, −0.07) for mono-2-ethylhexyl phthalate (MEHP), −1.43, (−2.49, −0.38) for mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and −1.28 (−2.29, −0.27) for mono-2-ethyl-5-hydroxyhexyl (MEHHP). Associations were of similar magnitude for AGDAP. Associations were weaker and not statistically significant for PW. No other phthalate metabolites were associated with any genital measurement in boys. No phthalate metabolites were associated with either AGD measure in girls.
LIMITATIONS, REASONS FOR CAUTION
Exposure assessment was based on a single first trimester urine sample, which may have introduced exposure misclassification. In addition, significant between-center differences suggest that this measurement is difficult to standardize.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings are consistent with multiple rodent studies and most human studies which were far smaller. The data we report here suggest that even at current low levels, environmental exposure to DEHP can adversely affect male genital development resulting in reproductive tract changes that may impact reproductive health later in life. These findings have important implications for public policy since most pregnant women are exposed to this ubiquitous chemical.
STUDY FUNDING/COMPETING INTEREST(S)
Funding for TIDES was provided by the following grants from the National Institute of Environmental Health Sciences: R01ES016863-04 and R01 ES016863-02S4. The authors report no conflict of interest.
While there are a growing number of human pluripotent stem cell repositories, genetic diversity remains limited in most collections and studies. Here, we discuss the importance of incorporating ...diverse ancestries in these models to improve equity and accelerate biological discovery.
Nanosuspensions in drug delivery Rabinow, Barrett E
Nature reviews. Drug discovery,
09/2004, Letnik:
3, Številka:
9
Journal Article
Recenzirano
A surprisingly large proportion of new drug candidates emerging from drug discovery programmes are water insoluble, and therefore poorly bioavailable, leading to abandoned development efforts. These ...so-called 'brickdust' candidates can now be rescued by formulating them into crystalline nanosuspensions. In the process of overcoming issues involving solubility, additional pharmacokinetic benefits of the drugs so formulated have come to be appreciated. As such, insolubility issues of the past have provoked a paradigm change, which now offers novel solutions for innovative drugs of the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Number
concentrations of ice-nucleating particles (NINP) in the Arctic
were derived from ground-based filter samples. Examined samples had been
collected in Alert (Nunavut, northern Canadian ...archipelago on Ellesmere
Island), Utqiaġvik, formerly known as Barrow (Alaska), Ny-Ålesund
(Svalbard), and at the Villum Research Station (VRS; northern Greenland). For
the former two stations, examined filters span a full yearly cycle. For VRS,
10 weekly samples, mostly from different months of one year, were included.
Samples from Ny-Ålesund were collected during the months from March until
September of one year. At all four stations, highest concentrations were
found in the summer months from roughly June to September. For those stations
with sufficient data coverage, an annual cycle can be seen. The spectra of
NINP observed at the highest temperatures, i.e., those obtained
for summer months, showed the presence of INPs that nucleate ice up to
−5 ∘C. Although the nature of these highly ice-active INPs could
not be determined in this study, it often has been described in the
literature that ice activity observed at such high temperatures originates
from the presence of ice-active material of biogenic origin. Spectra observed
at the lowest temperatures, i.e., those derived for winter months, were on
the lower end of the respective values from the literature on Arctic INPs or
INPs from midlatitude continental sites, to which a comparison is presented
herein. An analysis concerning the origin of INPs that were ice active at
high temperatures was carried out using back trajectories and satellite
information. Both terrestrial locations in the Arctic and the adjacent sea
were found to be possible source areas for highly active INPs.
Despite efforts to increase gender diversity in science, technology, engineering, mathematics and medicine (STEMM), men continue to hold most tenured and leadership positions. Moreover, the specific ...population shifts and timelines which may be required to achieve gender parity have not been well delineated. It is obvious that if women are statistically underrepresented in a field, then men must be statistically overrepresented: however, male overrepresentation and related gender-based advantages are rarely mentioned in conversations about gender equality. It is important that actions to address both overrepresentation and underrepresentation are elements of any strategy that seeks to move STEMM fields closer to gender parity.
Models of spreading processes over nontrivial networks are commonly motivated by modeling and analysis of biological networks, computer networks, and human contact networks. However, learning the ...spread parameters of such models has not yet been explored in detail, and the models have not been validated by real data. In this paper, we present several different spread models from the literature and explore their relationships to each other; for one of these processes, we present a sufficient condition for asymptotic stability of the healthy equilibrium, show that the condition is necessary and sufficient for uniqueness of the healthy equilibrium, and present necessary and sufficient conditions for estimating the spread parameters. Finally, we employ two real data sets, one from John Snow's seminal work on cholera epidemics in London in the 1850s and the other one from the United States Department of Agriculture, to validate an approximation of a well-studied network-dependent susceptible-infected-susceptible model.
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