The Dynamics of Hybrid Metabolic-Genetic Oscillators

The synthetic construction of intracellular circuits is frequently hindered by a poor knowledge of appropriate kinetics and precise rate parameters. Here, we use generalized modeling (GM) to study the dynamical behavior of topological models of a family of hybrid metabolic-genetic circuits known as "metabolators." Under mild assumptions on the kinetics, we use GM to analytically prove that all explicit kinetic models which are topologically analogous to one such circuit, the "core metabolator," cannot undergo Hopf bifurcations. Then, we examine more detailed models of the metabolator. Inspired by the experimental observation of a Hopf bifurcation in a synthetically constructed circuit related to the core metabolator, we apply GM to identify the critical components of the synthetically constructed metabolator which must be reintroduced in order to recover the Hopf bifurcation. Next, we study the dynamics of a re-wired version of the core metabolator, dubbed the "reverse" metabolator, and show that it exhibits a substantially richer set of dynamical behaviors, including both local and global oscillations. Prompted by the observation of relaxation oscillations in the reverse metabolator, we study the role that a separation of genetic and metabolic time scales may play in its dynamics, and find that widely separated time scales promote stability in the circuit. Our results illustrate a generic pipeline for vetting the potential success of a potential circuit design, simply by studying the dynamics of the corresponding generalized model

Topological Wilson-loop area law manifested using a superposition of loops

We introduce a new topological effect involving interference of two meson loops, manifesting a path-independent topological area dependence. The effect also draws a connection between quark confinement, Wilson-loops and topological interference effects. Although this is only a gedanken experiment in the context of particle physics, such an experiment may be realized and used as a tool to test confinement effects and phase transitions in quantum simulation of dynamic gauge theories.Comment: Superceding arXiv:1206.2021v1 [quant-ph

Intelligent Malingering in the Setting of Porphyria Variegata: A Rare Occurrence on Both Fronts

Malingering can be a difficult diagnosis to discern, especially in patients with well-crafted stories presenting with signs and symptoms that align directly with the literature. This can further become a challenge when a patient is malingering in the setting of a rare disease, where many complaints can be subjective in nature and not entirely testable by physical exam alone. Malingering is responsible for billions of dollars of healthcare waste every single year, and this report can serve as a guide of history elements, signs and symptoms to look out for with patients malingering in the setting of the porphyrias. It is important to recognize when patients are malingering, and when they are not, so that they may receive the appropriate care to help with their condition. This report can also serve as a guideline for what laboratory tests and studies to order in the setting of a suspected porphyria case, in order to confirm the diagnosis and get the patient the appropriate treatment regimen. Intelligent malingering is a growing problem, especially with the amount of access the general public has to medical information, and it is important for us to be able to identify when a patient is truly suffering from a rare disease and when they are malingering

Dynamics of Vortex Pair in Radial Flow

The problem of vortex pair motion in two-dimensional plane radial flow is solved. Under certain conditions for flow parameters, the vortex pair can reverse its motion within a bounded region. The vortex-pair translational velocity decreases or increases after passing through the source/sink region, depending on whether the flow is diverging or converging, respectively. The rotational motion of two corotating vortexes in a quiescent environment transforms into motion along a logarithmic spiral in the presence of radial flow. The problem may have applications in astrophysics and geophysics.Comment: 13 pages, 9 figure

Pregnancy associated plasma protein-A2: A novel biomarker for down syndrome

Introduction: In an effort to improve prenatal screening for Trisomy 21, we evaluated pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for Trisomy 21. Methods: Trisomy 21 and normal control mid-trimester placental samples were subjected to quantitative rt PCR analysis of seven genes we had previously found to be differentially expressed in Trisomy 21 placentae. The localization and differential expression of PAPP-A2 in second trimester placentae from normal and Trisomy 21 pregnancies was determined by immunohistochemistry. PAPP-A2 maternal serum protein levels in ten Trisomy 21 and ten diploid pregnancies were compared by Western blotting. Maternal serum PAPP-A2 levels were measured in 30 Down syndrome cases and 142 normal controls, using ELISA. Regression analysis was used to determine the correlation of PAPP-A2 with other existing markers of Trisomy 21. Results: PAPP-A2 (aka PLAC 3) mRNA and protein expression were both increased in Down syndrome placentae as compared to diploid placentae. PAPP-A2 was also increased in maternal serum from Down syndrome pregnancies as compared to diploid pregnancies. PAPP-A2 expression correlated weakly with established markers. Discussion: This work takes advantage of our previously performed systematic approach to the discovery of novel maternal serum biomarkers for Trisomy 21, using cDNA microarray analysis. Beginning with the validation of the microarray results, we have tracked PAPP-A2 overexpression in Down syndrome from placental mRNA to maternal serum protein. Conclusion: PAPP-A2 could serve as an additional maternal serum marker in prenatal screening for Trisomy 21. (C) 2014 Elsevier Ltd. All rights reserved

Richter Transformation in Chronic Lymphocytic Leukemia with Hypercalcemia and Acute Kidney Injury Presenting as Altered Mental Status: A Case Report

Introduction: Richter’s transformation is a deadly complication of chronic lymphocytic leukemia (CLL) associated with high mortality. This transformation involves the development of an aggressive, diffuse large B cell lymphoma in the setting of a chronic, underlying case of CLL. Although it is rare, Richter’s transformation is important to identify in patients with a history of CLL because of its significant mortality if left untreated. In the setting of CLL, there are many ways in which patients can present if they are currently undergoing a Richter’s transformation. Case Description: Patients may present with symptoms common to CLL which include but are not limited to fatigue, easy bruising, weight loss, etc., or they may present more unusually, as in the case that will be presented here: with altered mental status, fall, hypercalcemia and acute kidney injury (AKI). Discussion: With the current state of affairs due to COVID-19, it is also important to recognize the potential complications of patients with this disease state that are positive for COVID-19, leading to further complications such as disseminated intravascular coagulation (DIC). Recognizing these patients, and directing their care appropriately is important for their disease progression and outlook

Local/Non-Local Complementarity in Topological Effects

In certain topological effects the accumulation of a quantum phase shift is accompanied by a local observable effect. We show that such effects manifest a complementarity between non-local and local attributes of the topology, which is reminiscent but yet different from the usual wave-particle complementarity. This complementarity is not a consequence of non-commutativity, rather it is due to the non-canonical nature of the observables. We suggest that a local/non-local complementarity is a general feature of topological effects that are ``dual'' to the AB effect.Comment: 4 page

Raman scattering in a two-dimensional electron gas: Boltzmann equation approach

The inelastic light scattering in a 2-d electron gas is studied theoretically using the Boltzmann equation techniques. Electron-hole excitations produce the Raman spectrum essentially different from the one predicted for the 3-d case. In the clean limit it has the form of a strong non-symmetric resonance due to the square root singularity at the electron-hole frequency $\omega = vk$ while in the opposite dirty limit the usual Lorentzian shape of the cross section is reestablished. The effects of electromagnetic field are considered self-consistently and the contribution from collective plasmon modes is found. It is shown that unlike 3-d metals where plasmon excitations are unobservable (because of very large required transfered frequencies), the two-dimensional electron system gives rise to a low-frequency ($\omega \propto k^{1/2}$) plasmon peak. A measurement of the width of this peak can provide data on the magnitude of the electron scattering rate.Comment: 4 pages, 3 figures. to appear in Phys. Rev. B 59 (1999

Electron-phonon anomaly related to charge stripes: static stripe phase versus optimally-doped superconducting La1.85Sr0.15CuO4

Inelastic neutron scattering was used to study the Cu-O bond-stretching vibrations in optimally doped La1.85Sr0.15CuO4 (Tc = 35 K) and in two other cuprates showing static stripe order at low temperatures, i.e. La1.48Nd0.4Sr0.12CuO4 and La1.875Ba0.125CuO4. All three compounds exhibit a very similar phonon anomaly, which is not predicted by conventional band theory. It is argued that the phonon anomaly reflects a coupling to charge inhomogeneities in the form of stripes, which remain dynamic in superconducting La1.85Sr0.15CuO4 down to the lowest temperatures. These results show that the phonon effect indicating stripe formation is not restricted to a narrow region of the phase diagram around the so-called 1/8 anomaly but occurs in optimally doped samples as well.Comment: to appear in J. Low Temp. Phy

Model for the low-temperature magnetic phases observed in doped YBa_2Cu_3O_{6+x}

A classical statistical model for the antiferromagnetic (AFM) ordering of the Cu-spins in the CuO_2 planes of reduced YBa_2Cu_3O_{6+x} type materials is presented. The magnetic phases considered are the experimentally observed high-temperature AFI phase with ordering vector Q_I=(1/2,1/2,0), and the low-temperature phases: AFII with Q_II=(1/2,1/2,1/2) and intermediate TA (Turn Angle) phases TAI, TAII and TAIII with components of both ordering vectors. It is shown that the AFII and TA phases result from an effective ferromagnetic (FM) type coupling mediated by free spins in the CuO_x basal plane. Good agreement with experimental data is obtained for realistic model parameters.Comment: 11 pages, 2 Postscript figures, Submitted to Phys.Rev.Let