Homogeneous nucleation: Comparison between two theories

The classical nucleation theory of Becker, D\"{o}ring and Zeldovich is compared with the Langer coarse-grained field approach to the nucleation phenomenon. Both formalisms have been applied to the condensation from a supersaturated vapor. It is shown that the nucleation rate derived in the classical theory can be expressed in a form equivalent to that of the field nucleation theory. This equivalence serves as an explanation of the puzzling fact that the numerical predictions of both theories for condensation of Xe and CO$_2$ are almost identical though the standard analytical expressions for the nucleation rates are different. The results obtained can help to link the theories of nucleation and their approximations.Comment: 12 pages, LaTeX, no figure

Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating

While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding); surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding). In contrast, inhibition of the nucleus accumbens (NAc), through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive

Screening and Molecular Analysis of Single Circulating Tumor Cells Using Micromagnet Array

Immunomagnetic assay has been developed to detect rare circulating tumor cells (CTCs), which shows clinical significance in cancer diagnosis and prognosis. The generation and fine-tuning of the magnetic field play essential roles in such assay toward effective single-cell-based analyses of target cells. However, the current assay has a limited range of field gradient, potentially leading to aggregation of cells and nanoparticles. Consequently, quenching of the fluorescence signal and mechanical damage to the cells may occur, which lower the system sensitivity and specificity. We develop a micromagnet-integrated microfluidic system for enhanced CTC detection. The ferromagnetic micromagnets, after being magnetized, generate localized magnetic field up to 8-fold stronger than that without the micromagnets, and strengthen the interactions between CTCs and the magnetic field. The system is demonstrated with four cancer cell lines with over 97% capture rate, as well as with clinical samples from breast, prostate, lung, and colorectal cancer patients. The system captures target CTCs from patient blood samples on a standard glass slide that can be examined using the fluorescence in-situ hybridization method for the single-cell profiling. All cells showed clear hybridization signals, indicating the efficacy of the compact system in providing retrievable cells for molecular studies

Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL

Abstract OBJECTIVE: The study goal was to assess the benefits and potential limitations in the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in the MRI diagnosis of CNS inflammatory diseases and primary CNS lymphoma. METHODS: Twenty patients with presumptive or known CNS lesions underwent MRI study. Eighteen patients received both gadolinium-based contrast agents (GBCAs) and 1 of 2 USPIO contrast agents (ferumoxytol and ferumoxtran-10) 24 hours apart, which allowed direct comparative analysis. The remaining 2 patients had only USPIO-enhanced MRI because of a renal contraindication to GBCA. Conventional T1- and T2-weighted MRI were acquired before and after contrast administration in all patients, and perfusion MRI for relative cerebral blood volume (rCBV) assessment was obtained in all 9 patients receiving ferumoxytol. RESULTS: USPIO-enhanced MRI showed an equal number of enhancing brain lesions in 9 of 18 patients (50%), more enhancing lesions in 2 of 18 patients (11%), and fewer enhancing lesions in 3 of 18 patients (17%) compared with GBCA-enhanced MRI. Four of 18 patients (22%) showed no MRI enhancement. Dynamic susceptibility-weighted contrast-enhanced perfusion MRI using ferumoxytol showed low rCBV (ratio <1.0) in 3 cases of demyelination or inflammation, modestly elevated rCBV in 5 cases of CNS lymphoma or lymphoproliferative disorder (range: 1.3-4.1), and no measurable disease in one case. CONCLUSIONS: This study showed that USPIO-enhanced brain MRI can be useful in the diagnosis of CNS inflammatory disorders and lymphoma, and is also useful for patients with renal compromise at risk of nephrogenic systemic fibrosis who are unable to receive GBCA

Dispersity-Driven Melting Transition in Two Dimensional Solids

We perform extensive simulations of $10^4$ Lennard-Jones particles to study the effect of particle size dispersity on the thermodynamic stability of two-dimensional solids. We find a novel phase diagram in the dispersity-density parameter space. We observe that for large values of the density there is a threshold value of the size dispersity above which the solid melts to a liquid along a line of first order phase transitions. For smaller values of density, our results are consistent with the presence of an intermediate hexatic phase. Further, these findings support the possibility of a multicritical point in the dispersity-density parameter space.Comment: In revtex format, 4 pages, 6 postscript figures. Submitted to PR

Academic Cancer Center Phase I Program Development

Multiple factors critical to the effectiveness of academic phase I cancer programs were assessed among 16 academic centers in the U.S. Successful cancer centers were defined as having broad phase I and I/II clinical trial portfolios, multiple investigator‐initiated studies, and correlative science. The most significant elements were institutional philanthropic support, experienced clinical research managers, robust institutional basic research, institutional administrative efforts to reduce bureaucratic regulatory delays, phase I navigators to inform patients and physicians of new studies, and a large cancer center patient base. New programs may benefit from a separate stand‐alone operation, but mature phase I programs work well when many of the activities are transferred to disease‐oriented teams. The metrics may be useful as a rubric for new and established academic phase I programs.This commentary assesses the factors necessary for the effectiveness of academic phase I cancer programs. The metrics presented here may be useful as a rubric for new and established programs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139928/1/onco12106-sup-0001-suppinfo1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139928/2/onco12106.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139928/3/onco12106-sup-0002-suppinfo2.pd

Multi-scale sequence correlations increase proteome structural disorder and promiscuity

Numerous experiments demonstrate a high level of promiscuity and structural disorder in organismal proteomes. Here we ask the question what makes a protein promiscuous, i.e., prone to non-specific interactions, and structurally disordered. We predict that multi-scale correlations of amino acid positions within protein sequences statistically enhance the propensity for promiscuous intra- and inter-protein binding. We show that sequence correlations between amino acids of the same type are statistically enhanced in structurally disordered proteins and in hubs of organismal proteomes. We also show that structurally disordered proteins possess a significantly higher degree of sequence order than structurally ordered proteins. We develop an analytical theory for this effect and predict the robustness of our conclusions with respect to the amino acid composition and the form of the microscopic potential between the interacting sequences. Our findings have implications for understanding molecular mechanisms of protein aggregation diseases induced by the extension of sequence repeats

David Hume on Banking and Hoarding

David Hume opposes banks and favors hoarding. The only bank he reluctantly approves of is a public, 100% reserve bank. Other banks increase money supply and prices, hindering exports and economic growth. For Hume, a 100% reserve public bank would lead to ‘‘the destruction of paper-credit’’ ([1752] 1985, p. 285), fostering economic growth instead by preventing inflation. Additionally, a 100% reserve bank hoards a large quantity of gold and silver, which is available in case of national emergency

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection