Calibrating evanescent-wave penetration depths for biological TIRF microscopy

Roughly half of a cells proteins are located at or near the plasma membrane. In this restricted space the cell senses its environment, signals to its neighbors and ex-changes cargo through exo- and endocytotic mechanisms. Ligands bind to receptors, ions flow across channel pores, and transmitters and metabolites are transported against con-centration gradients. Receptors, ion channels, pumps and transporters are the molecular substrates of these biological processes and they constitute important targets for drug discovery. Total internal reflection fluorescence microscopy suppresses background from cell deeper layers and provides contrast for selectively imaging dynamic processes near the basal membrane of live-cells. The optical sectioning of total internal reflection fluorescence is based on the excitation confinement of the evanescent wave generated at the glass-cell interface. How deep the excitation light actually penetrates the sample is difficult to know, making the quantitative interpretation of total internal reflection fluorescence data problematic. Nevertheless, many applications like super-resolution microscopy, colocalization, fluorescence recovery after photobleaching, near-membrane fluorescence recovery after photobleaching, uncaging or photo-activation-switching, as well as single-particle tracking require the quantitative interpretation of evanescent-wave excited images. Here, we review existing techniques for characterizing evanescent fields and we provide a roadmap for comparing total internal reflection fluorescence data across images, experiments, and laboratories.Comment: 18 text pages, 7 figures and one supplemental figur

Mathematical investigation of diabetically impaired ultradian oscillations in the glucose-insulin regulation

We study the effect of diabetic deficiencies on the production of an oscillatory ultradian regime using a deterministic nonlinear model which incorporates two physiological delays. It is shown that insulin resistance impairs the production of oscillations by dampening the ultradian cycles. Four strategies for restoring healthy regulation are explored. Through the introduction of an instantaneous glucose-dependent insulin response, explicit conditions for the existence of periodic solutions in the linearised model are formulated, significantly reducing the complexity of identifying an oscillatory regime. The model is thus shown to be suitable for representing the effect of diabetes on the oscillatory regulation and for investigating pathways to reinstating a physiological healthy regime

Amplitude and frequency variation in nonlinear glucose dynamics with multiple delays via periodic perturbation

Characterising the glycemic response to a glucose stimulus is an essential tool for detecting deficiencies in humans such as diabetes. In the presence of a constant glucose infusion in healthy individuals, it is known that this control leads to slow oscillations as a result of feedback mechanisms at the organ and tissue level. In this paper, we provide a novel quantitative description of the dependence of this oscillatory response on the physiological functions. This is achieved through the study of a model of the ultradian oscillations in glucose-insulin regulation which takes the form of a nonlinear system of equations with two discrete delays. While studying the behaviour of solutions in such systems can be mathematically challenging due to their nonlinear structure and non-local nature, a particular attention is given to the periodic solutions of the model. These arise from a Hopf bifurcation which is induced by an external glucose stimulus and the joint contributions of delays in pancreatic insulin release and hepatic glycogenesis. The effect of each physiological subsystem on the amplitude and period of the oscillations is exhibited by performing a perturbative analysis of its periodic solutions. It is shown that assuming the commensurateness of delays enables the Hopf bifurcation curve to be characterised by studying roots of linear combinations of Chebyshev polynomials. The resulting expressions provide an invaluable tool for studying the interplay between physiological functions and delays in producing an oscillatory regime, as well as relevant information for glycemic control strategies

Ultradian rhythms in glucose regulation: A mathematical assessment

Glucose regulation is an essential function of the human body which enables energy to be effectively utilized by the brain, organs and muscles. This regulation operates in a cyclic manner, in different periodic regimes. Indeed, ultradian rhythms with a period of 70 to 150 minutes have been clinically observed in healthy patients under various glucose stimulation patterns. Various models of these oscillations in plasma glucose and insulin have shown that the presence of two delays in hepatic glycogenesis and pancreatic insulin secretion provide a pathway for explaining these oscillations. The efficacy of this control is typically reduced in the presence of diabetes. In this contribution, we adopt the presence and the accurate tuning of ultradian rhythms as a criterion for healthy glucose regulation. We then investigate a model with two delays of these ultradian rhythms which incorporates parameters accounting for insulin sensitivity and insulin secretion. Additionally, the effect of diabetic deficiencies on this feedback loop is explored by quantifying the joint contribution of delays and diabetic parameters on the limit cycle of this model, which is generated through a Hopf bifurcation. Strategies for restoring an oscillatory regime in a physiologically appropriate range are discussed. Finally, a simple polynomial model of the oscillations is introduced to give further insight into the influence of each physiological subsystem. The approach provides a quantified relationship between diabetic impairments and the plasma glucose-insulin feedback loop

Radiation reaction for spinning bodies in effective field theory. I. Spin-orbit effects

We compute the leading post-Newtonian (PN) contributions at linear order in the spin to the radiation-reaction acceleration and spin evolution for binary systems, which enter at fourth PN order. The calculation is carried out, from first principles, using the effective field theory framework for spinning compact objects, in both the Newton-Wigner and covariant spin supplementary conditions. A nontrivial consistency check is performed on our results by showing that the energy loss induced by the resulting radiation-reaction force is equivalent to the total emitted power in the far zone, up to so-called “Schott terms.” We also find that, at this order, the radiation reaction has no net effect on the evolution of the spins. The spin-spin contributions to radiation reaction are reported in a companion paper

Radiation reaction for spinning bodies in effective field theory. II. Spin-spin effects

We compute the leading post-Newtonian (PN) contributions at quadratic order in the spins to the radiation-reaction acceleration and spin evolution for binary systems, entering at four-and-a-half PN order. Our calculation includes the backreaction from finite-size spin effects, which is presented for the first time. The computation is carried out, from first principles, using the effective field theory framework for spinning extended objects. At this order, nonconservative effects in the spin-spin sector are independent of the spin supplementary conditions. A nontrivial consistency check is performed by showing that the energy loss induced by the resulting radiation-reaction force is equivalent to the total emitted power in the far zone. We find that, in contrast to the spin-orbit contributions (reported in a companion paper), the radiation reaction affects the evolution of the spin vectors once spin-spin effects are incorporated

Increase in presentations with new-onset psychiatric disorders in a psychiatric emergency department in Berlin, Germany during the second wave of the COVID-19 pandemic – a retrospective cross-sectional study

Introduction: While numerous studies have identified an increase in symptoms of depression as well as anxiety and distress due to the COVID-19 pandemic, relatively few studies have investigated the new-onset of psychiatric diseases during the pandemic. Methods: This study focuses on the number of psychiatric new-onset diagnoses in a psychiatric emergency department (pED) in Berlin, Germany during the second wave of the pandemic (i.e. from 09/15/2020 to 03/01/2021 = COVID-19-period) compared to pre-pandemic times (09/15/2019 to 03/01/2020 = control period). We focused on diagnostic subgroups and performed logistic regression analysis to investigate potential risk groups based on covariables such as age, gender, homelessness, attending in police custody and familial relationship. Results: Overall, there was a 59.7% increase in new-onset psychiatric diagnoses during the COVID-19-period. Increases in the following diagnoses were observed: new-onset of substance-related and addictive disorders (+192.5%), depressive disorders (+115.8%), schizophrenia spectrum and psychotic disorders (+113.3%) and anxiety disorders (+63.6%). These diagnostic subgroups, together with attending in police custody, were found to predict pED presentations with new-onset during the COVID-19-period. Interestingly, in the group of new-onset psychiatric diseases in the COVID-19-period, higher amounts of job loss and living alone as well as a relative decrease in familial relationships were observed. Discussion: COVID-19 infections and post-COVID-19 syndrome are unlikely to have played a substantial role in the increase of new-onset diseases in this study. Conclusion: Our findings underline the role of indirect factors in new-onset of psychiatric diseases during the pandemic and should be a caveat for future pandemic control policies

Suicidality in psychiatric emergency department situations during the first and the second wave of COVID-19 pandemic

Psychiatric patients are prone to mental health deterioration during the Covid-19 pandemic. Little is known about suicidality in psychiatric patients during the Covid-19 pandemic. This study is a retrospective chart review of psychiatric emergency department (pED) presentations with present or absent suicidality (5634 pED attendances, 4110 patients) in an academic pED in Berlin, Germany. Poisson regression analysis was performed on the effect of Covid-19 period on suicidality (suicidal ideation (SI), suicide plans (SP) or suicide attempt (SA)) during the first (3/2/2020-5/24/2020 "first-wave") and second (9/15/2020-3/1/2021 "second-wave") wave of the Covid-19 pandemic compared to the same periods one year earlier. During the first-wave the number of pED visits per person with SI, SP and SA was higher compared to one year earlier (SI RR = 1.614; p = 0.016; SP RR = 2.900; p = 0.004; SA RR = 9.862; p = 0.003). SI and SP were predicted by interaction between substance use disorder (SUD) and second-wave (SI RR = 1.305, p = 0.043; SP RR = 1.645, p = 0.018), SA was predicted by interaction between borderline personality disorder (BPD) and second-wave (RR = 7.128; p = 0.012). Suicidality increased during the first-wave of Covid-19 pandemic in our sample. In the second-wave this was found in patients with SUD and BPD. These patients may be at particular risk of suicidality during the Covid-19 pandemic