Observation of PT phase transition in a simple mechanical system

If a Hamiltonian is PT symmetric, there are two possibilities: Either the eigenvalues are entirely real, in which case the Hamiltonian is said to be in an unbroken-PT-symmetric phase, or else the eigenvalues are partly real and partly complex, in which case the Hamiltonian is said to be in a broken-PT-symmetric phase. As one varies the parameters of the Hamiltonian, one can pass through the phase transition that separates the unbroken and broken phases. This transition has recently been observed in a variety of laboratory experiments. This paper explains the phase transition in a simple and intuitive fashion and then describes an extremely elementary experiment in which the phase transition is easily observed.Comment: 9 pages, 9 figure

Lived Cosmologies and Objectified Commodities: Reinventing the Traditional Art of India in a World of Cultural Tourism

This essay examines how the significance of ancient South Asian monuments is transformed when reframed by the practices of cultural tourism, which are grounded in the values of a modern, globalizing, economic cosmology. Ethnographic evidence collected on a visit to the archaeological park and museum at Sarnath, site of the Buddha's first discourse and home to some of the most celebrated masterpieces of ancient Indian sculpture, are here analyzed to support and illustrate a broader, social-constructivist argument about the representation of reality in Indian visual culture. I will argue that the version of 'reality' presupposed by modern economic practices, such as tourism, works to objectify ancient South Asian forms and meanings, previously precipitated out of older living practices, into reified, collectable entities. Such objects and their objectified meanings further contribute toward naturalizing and universalizing economically grounded projects of self-construction among the practitioners of an economic worldview, wherein the self is shaped by routines of production and consumption: I am what I do for a living and I am the goods—including here, the touristic experiences—that I collect. It is this economic cosmology that moves to the foreground when ancient Indian 'art' is re-presented and consumed in the form of tourism products. Meanwhile the cosmology of dharma is pushed into the background. I hope to persuade the reader that the 'cost' of doing this is too high to justify the narrow economic benefits

Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells.

Neomorphic mutations in NADP-dependent isocitrate dehydrogenases (IDH1 and IDH2) contribute to tumorigenesis in several cancers. Although significant research has focused on the hypermethylation phenotypes associated with (D)2-hydroxyglutarate (D2HG) accumulation, the metabolic consequences of these mutations may also provide therapeutic opportunities. Here we apply flux-based approaches to genetically engineered cell lines with an endogenous IDH1 mutation to examine the metabolic impacts of increased D2HG production and altered IDH flux as a function of IDH1 mutation or expression. D2HG synthesis in IDH1-mutant cells consumes NADPH at rates similar to de novo lipogenesis. IDH1-mutant cells exhibit increased dependence on exogenous lipid sources for in vitro growth, as removal of medium lipids slows growth more dramatically in IDH1-mutant cells compared with those expressing wild-type or enzymatically inactive alleles. NADPH regeneration may be limiting for lipogenesis and potentially redox homeostasis in IDH1-mutant cells, highlighting critical links between cellular biosynthesis and redox metabolism

Mucoadhesive polysaccharides modulate sodium retention, release and taste perception

The mucoadhesion between polymeric substances and mucosal membranes, widely exploited in the pharmaceutics industry to prolong drug residence, has been investigated as a means of retaining taste or aroma molecules in the oral cavity. This study shows that the mucoadhesive properties of carboxymethyl cellulose, a commonly used polysaccharide in the food and pharmaceutics industry, can modify retention, release and perception of sodium over time. A three-part study was designed coupling in vitro retention using ex vivo porcine tongue, sensory perception with a trained panel and in vivo retention of sodium ions in human volunteers. The findings suggest that although salt perception is stunted in samples containing a random coil, ionic, mucoadhesive thickener, the retention of sodium ions in the mouth is prolonged due to the mucoadhesive nature of the polysaccharide. Not only has this study-investigated mucoadhesion of liquid formulations in the oral cavity but it is also the first to link the mucoadhesive nature of a commonly used polysaccharide to the organoleptic properties of a food

Competing PT potentials and re-entrant PT symmetric phase for a particle in a box

We investigate the effects of competition between two complex, $\mathcal{PT}$-symmetric potentials on the $\mathcal{PT}$-symmetric phase of a "particle in a box". These potentials, given by $V_Z(x)=iZ\mathrm{sign}(x)$ and $V_\xi(x)=i\xi[\delta(x-a)-\delta(x+a)]$, represent long-range and localized gain/loss regions respectively. We obtain the $\mathcal{PT}$-symmetric phase in the $(Z,\xi)$ plane, and find that for locations $\pm a$ near the edge of the box, the $\mathcal{PT}$-symmetric phase is strengthened by additional losses to the loss region. We also predict that a broken $\mathcal{PT}$-symmetry will be restored by increasing the strength $\xi$ of the localized potential. By comparing the results for this problem and its lattice counterpart, we show that a robust $\mathcal{PT}$-symmetric phase in the continuum is consistent with the fragile phase on the lattice. Our results demonstrate that systems with multiple, $\mathcal{PT}$-symmetric potentials show unique, unexpected properties.Comment: 7 pages, 3 figure

Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery

Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors

B-Type Natriuretic Peptide in Pregnant Women With Heart Disease

ObjectivesThe objectives of this study were to examine: 1) B-type natriuretic peptide (BNP) response to pregnancy in women with heart disease; and 2) the relationship between BNP levels and adverse maternal cardiac events during pregnancy.BackgroundPregnancy imposes a hemodynamic stress on the heart. BNP might be a useful biomarker to assess the ability of the heart to adapt to the hemodynamic load of pregnancy.MethodsThis was a prospective study of women with structural heart disease seen at our center. Serial clinical data and plasma BNP measurements were obtained during the first trimester, third trimester, and after delivery (>6 weeks).ResultsSeventy-eight pregnant women were studied; 66 women with heart disease (age 31 ± 5 years), and 12 healthy women (age 33 ± 5 years). During pregnancy, the median peak BNP level was higher in women with heart disease compared with control subjects (median 79, interquartile range 51 to 152 pg/ml vs. median 35, interquartile range 21 to 43 pg/ml, p < 0.001). In women with heart disease, those with subaortic ventricular dysfunction had higher BNP levels (p = 0.03). A BNP >100 pg/ml was measured in all women with events during pregnancy (n = 8). Sixteen women had increased BNP levels during pregnancy but did not have clinical events. None of the women with BNP ≤100 pg/ml had events. BNP ≤100 pg/ml had a negative predictive value of 100% for identifying events during pregnancy.ConclusionsMany pregnant women with heart disease have increased BNP levels during pregnancy. Incorporating serial BNP levels in into clinical practice can be helpful, specifically in adjudicating suspected adverse cardiac events during pregnancy

Prescription and Other Medication Use in Pregnancy

OBJECTIVE: To characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy. METHODS: In a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined. RESULTS: Of the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication). CONCLUSION: In this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common

Mutation-related magnetization-transfer, not axon density, drives white matter differences in premanifest Huntington disease:Evidence from in vivo ultra-strong gradient MRI

White matter (WM) alterations have been observed in Huntington disease (HD) but their role in the disease-pathophysiology remains unknown. We assessed WM changes in premanifest HD by exploiting ultra-strong-gradient magnetic resonance imaging (MRI). This allowed to separately quantify magnetization transfer ratio (MTR) and hindered and restricted diffusion-weighted signal fractions, and assess how they drove WM microstructure differences between patients and controls. We used tractometry to investigate region-specific alterations across callosal segments with well-characterized early- and late-myelinating axon populations, while brain-wise differences were explored with tract-based cluster analysis (TBCA). Behavioral measures were included to explore disease-associated brain-function relationships. We detected lower MTR in patients' callosal rostrum (tractometry: p = .03; TBCA: p = .03), but higher MTR in their splenium (tractometry: p = .02). Importantly, patients' mutation-size and MTR were positively correlated (all p-values < .01), indicating that MTR alterations may directly result from the mutation. Further, MTR was higher in younger, but lower in older patients relative to controls (p = .003), suggesting that MTR increases are detrimental later in the disease. Finally, patients showed higher restricted diffusion signal fraction (FR) from the composite hindered and restricted model of diffusion (CHARMED) in the cortico-spinal tract (p = .03), which correlated positively with MTR in the posterior callosum (p = .033), potentially reflecting compensatory mechanisms. In summary, this first comprehensive, ultra-strong gradient MRI study in HD provides novel evidence of mutation-driven MTR alterations at the premanifest disease stage which may reflect neurodevelopmental changes in iron, myelin, or a combination of these