Two-pion exchange potential and the πN\pi N amplitude

We discuss the two-pion exchange potential which emerges from a box diagram with one nucleon (the spectator) restricted to its mass shell, and the other nucleon line replaced by a subtracted, covariant $\pi N$ scattering amplitude which includes $\Delta$, Roper, and $D_{13}$ isobars, as well as contact terms and off-shell (non-pole) dressed nucleon terms. The $\pi N$ amplitude satisfies chiral symmetry constraints and fits $\pi N$ data below $\sim$ 700 MeV pion energy. We find that this TPE potential can be well approximated by the exchange of an effective sigma and delta meson, with parameters close to the ones used in one-boson-exchange models that fit $NN$ data below the pion production threshold.Comment: 9 pages (RevTex) and 7 postscript figures, in one uuencoded gzipped tar fil

Feynman-Schwinger representation approach to nonperturbative physics

The Feynman-Schwinger representation provides a convenient framework for the cal culation of nonperturbative propagators. In this paper we first investigate an analytically solvable case, namely the scalar QED in 0+1 dimension. With this toy model we illustrate how the formalism works. The analytic result for the self energy is compared with the perturbative result. Next, using a $\chi^2\phi$ interaction, we discuss the regularization of various divergences encountered in this formalism. The ultraviolet divergence, which is common in standard perturbative field theory applications, is removed by using a Pauli-Villars regularization. We show that the divergence associated with large values of Feynman-Schwinger parameter $s$ is spurious and it can be avoided by using an imaginary Feynman parameter $is$.Comment: 26 pages, 9 figures, minor correctio

Warming Up Density Functional Theory

Density functional theory (DFT) has become the most popular approach to electronic structure across disciplines, especially in material and chemical sciences. Last year, at least 30,000 papers used DFT to make useful predictions or give insight into an enormous diversity of scientific problems, ranging from battery development to solar cell efficiency and far beyond. The success of this field has been driven by usefully accurate approximations based on known exact conditions and careful testing and validation. In the last decade, applications of DFT in a new area, warm dense matter, have exploded. DFT is revolutionizing simulations of warm dense matter including applications in controlled fusion, planetary interiors, and other areas of high energy density physics. Over the past decade or so, molecular dynamics calculations driven by modern density functional theory have played a crucial role in bringing chemical realism to these applications, often (but not always) with excellent agreement with experiment. This chapter summarizes recent work from our group on density functional theory at non-zero temperatures, which we call thermal DFT. We explain the relevance of this work in the context of warm dense matter, and the importance of quantum chemistry to this regime. We illustrate many basic concepts on a simple model system, the asymmetric Hubbard dimer

The influence of repeated injections on pharmacokinetics and biodistribution of different types of sterically stabilized immunoliposomes

AbstractSterically stabilized immunoliposomes (IL) with diameters of about 135 nm carrying mouse IgG, either coupled directly to the liposome surface, or linked to the terminal ends of grafted poly(ethylene glycol) (PEG) chains by a recently described conjugation procedure (Cyanur-PEG-PE), were intravenously injected into rats and the elimination kinetics and biodistribution were determined and compared with control liposomes. The amounts of conjugated antibodies were about 30 μg/μmol total lipid for all IL. In naive rats, plain pegylated liposomes displayed the longest blood circulation time, whereas the terminal-coupled IL exhibited the fastest elimination. Liposomes containing the underivatized anchor molecules circulate nearly as long as plain pegylated liposomes, indicating that the fast elimination of the IL can be attributed to the presence of antibodies.A second injection of identical liposomes 14 days after the first injection had a considerable influence on the pharmacokinetic parameters of the liposomes. The circulation time of plain pegylated liposomes drastically dropped by half and their uptake by the liver increased concomitantly, indicating that the PEG, upon repeated injection, ceases to function as an efficient barrier reducing opsonization and/or immune reactions. The circulation time of conventional IL was moderately reduced upon a second injection, whereas that of the terminally coupled IL was nearly unaffected. These differences among the IL demonstrate that the pharmacokinetic behavior of IL is strongly dependent on the antibody conjugation site on the liposome. The observed effects of repeated injections were similar for liposomes of 90-nm diameter. The phenomena described may have important implications for the repeated application of IL as drug carriers

Gut-microbe derived TMAO and its association with more progressed forms of AF:Results from the AF-RISK study

Introduction: The importance of gut microbiome in cardiovascular disease has been increasingly recognized. Trimethylamine N-oxide (TMAO) is a gut microbe-derived metabolite that is associated with cardiovascular disease, including atrial fibrillation (AF). The role of TMAO in clinical AF progression however remains unknown. Methods and results: In this study we measured TMAO and its precursor (betaine, choline, and L- carnitine) levels in 78 patients using plasma samples from patients that participated in the AF-RISK study. 56 patients suffered from paroxysmal AF and 22 had a short history of persistent AF. TMAO levels were significantly higher in patients with persistent AF, as compared to those with paroxysmal AF (median [IQR] 5.65 [4.7–9.6] m/z versus 4.31 [3.2–6.2] m/z, p < 0.05), while precursor levels did not differ. In univariate analysis, we observed that for every unit increase in TMAO, the odds for having persistent AF increased with 0.44 [0.14–0.73], p < 0.01. Conclusion: These results suggest that higher levels of TMAO are associated with more progressed forms of AF. We therefore hypothesize that increased TMAO levels may reflect disease progression in humans. Larger studies are required to validate these preliminary findings.Trial Registration number: Clinicaltrials.gov NCT01510210

Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs:Relevance to the diagnosis of pheochromocytoma

Background: Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives: To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). Animals: Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. Methods: Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively. Results: The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P &lt;.001) and NAI (P =.002). The PCC dogs had significantly higher pMN than HC dogs (P &lt;.001), but not higher than NAI dogs (P =.29). Using the upper reference limit, pNMN (&gt;3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (&gt;2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99). Conclusions and Clinical Importance: With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.</p

Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs:Relevance to the diagnosis of pheochromocytoma

Background: Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives: To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). Animals: Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. Methods: Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively. Results: The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P &lt;.001) and NAI (P =.002). The PCC dogs had significantly higher pMN than HC dogs (P &lt;.001), but not higher than NAI dogs (P =.29). Using the upper reference limit, pNMN (&gt;3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (&gt;2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99). Conclusions and Clinical Importance: With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.</p

Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs:Relevance to the diagnosis of pheochromocytoma

Background: Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives: To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). Animals: Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. Methods: Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively. Results: The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P &lt;.001) and NAI (P =.002). The PCC dogs had significantly higher pMN than HC dogs (P &lt;.001), but not higher than NAI dogs (P =.29). Using the upper reference limit, pNMN (&gt;3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (&gt;2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99). Conclusions and Clinical Importance: With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.</p

Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs:Relevance to the diagnosis of pheochromocytoma

Background: Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives: To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). Animals: Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. Methods: Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively. Results: The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P &lt;.001) and NAI (P =.002). The PCC dogs had significantly higher pMN than HC dogs (P &lt;.001), but not higher than NAI dogs (P =.29). Using the upper reference limit, pNMN (&gt;3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (&gt;2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99). Conclusions and Clinical Importance: With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.</p