Spontaneous Switch Research Articles

Asymmetric nucleation processes in spontaneous mode switch of active matter

Flocking and vortical are two typical motion modes in active matter. Although it is known that the two modes can spontaneously switch between each other in a finite-size system, the switching dynamics remain elusive. In this work, by computer simulation of a two-dimensional Vicsek-like system with 1000 particles, we find from the perspective of the classical nucleation theory that the forward and backward switching dynamics are asymmetric: going from flocking to vortical is a one-step nucleation process, while the opposite is a two-step nucleation process, with the system staying in a metastable state before reaching the final flocking state.

Sequential co-reduction of nitrate and carbon dioxide enables selective urea electrosynthesis

Despite the recent achievements in urea electrosynthesis from co-reduction of nitrogen wastes (such as NO3−) and CO2, the product selectivity remains fairly mediocre due to the competing nature of the two parallel reduction reactions. Here we report a catalyst design that affords high selectivity to urea by sequentially reducing NO3− and CO2 at a dynamic catalytic centre, which not only alleviates the competition issue but also facilitates C−N coupling. We exemplify this strategy on a nitrogen-doped carbon catalyst, where a spontaneous switch between NO3− and CO2 reduction paths is enabled by reversible hydrogenation on the nitrogen functional groups. A high urea yield rate of 596.1 µg mg−1 h−1 with a promising Faradaic efficiency of 62% is obtained. These findings, rationalized by in situ spectroscopic techniques and theoretical calculations, are rooted in the proton-involved dynamic catalyst evolution that mitigates overwhelming reduction of reactants and thereby minimizes the formation of side products.

History-dependent changes to distribution of dominance phases in multistable perception.

Multistability - spontaneous switches of perception when viewing a stimulus compatible with several percepts - is often characterized by the distribution of durations of dominance phases. For continuous viewing conditions, these distributions are similar for various multistable displays and share two characteristic features: a Gamma-like distribution shape and dependence of dominance durations on the perceptual history. Both properties depend on a balance between self-adaptation (also conceptualized as a weakening stability prior) and noise. Prior experimental work and simulations that systematically manipulated displays showed that faster self-adaptation leads to a more "normal-like" distribution and, typically, to more regular dominance durations. We used a leaky integrator approach to estimate accumulated differences in self-adaptation between competing representations and used it as a predictor when fitting two parameters of a Gamma distribution independently. We confirmed earlier work showing that larger differences in self-adaptation led to a more "normal-like" distribution suggesting similar mechanisms that rely on the balance between self-adaptation and noise. However, these larger differences led to less regular dominance phases suggesting that longer times required for recovery from adaptation give noise more chances to induce a spontaneous switch. Our results also remind us that individual dominance phases are not "independent and identically distributed."

Abstract 114: Metabolic Adaptation During Obesity Is Associated With G Protein Switching By The Angiotensin At1a Receptor In Agrp Neurons

Obesity represents the single greatest impediment to continued improvements in hypertension and cardiovascular disease. Prolonged obesity is associated with “Resting Metabolic Rate (RMR) adaptation” (ie, reduced RMR relative to body composition), and RMR adaptation is proposed to explain resistance to weight loss / weight maintenance after obesity is established. Previously we showed that angiotensin II (ANG) Agtr1a (AT1A) receptors expressed in Agouti-related peptide (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) are required for integrative control of RMR. We hypothesize that changes in AT1A signaling in AgRP cells underlie the development of RMR adaptation. ARC slices from mice expressing tdTomato in AgRP cells ( Agrp -Cre x Ai9) were used for cell-attached voltage clamp recording of AgRP neurons. ANG inhibited ~33% of AgRP neurons via an AT1A-dependent mechanism (deemed a “Type 1i” response, which was inhibitable by losartan (LOS) or genetic deletion of AT1A; Firing rate; aCSF:0.85 ± 0.03 vs ANG:0.20 ± 0.04 vs ANG+LOS:0.91 ± 0.11 Hz, p<0.05) that was also blocked by the Gαi inhibitor, pertussis toxin (PTX), but not by the Gαq inhibitor, BIM-46187 (Δ Firing rate: PTX: -0.39 ± 0.09 Hz, p<0.05 vs BIM: 0.10 ± 0.09 Hz). After 10 weeks of high-fat feeding, roughly half of Type 1 cells exhibited a spontaneous switch from the ANG/AT1A-mediated inhibitory (Type 1i) response to an ANG/AT1A-mediated stimulatory response (“Type 1s”; Firing rate; aCSF: 0.86 ± 0.03 vs ANG:1.10 ± 0.12 vs ANG+LOS:0.82 ± 0.03 Hz, p<0.05), which was blocked by BIM-46187, but not by PTX (Δ Firing rate: PTX: 0.07 ± 0.06 Hz vs BIM: 0.49 ± 0.06 Hz, p<0.05). AAV delivery of Cre-inducible DREADDs into the ARC of lean Agtr1a -Cre mice was then used to study the effects of Gαi vs Gαq signaling in Type 1 AgRP cells upon RMR control. Activation of the Gαi-coupled hM4Di DREADD in AT1A-expressing cells of the ARC was sufficient to increase RMR (+25% from baseline, n=8-10, p<0.05), but activation of a Gαq-coupled DREADD had no effect. We conclude (i) that the AT1A receptor is expressed by a unique subtype of AgRP neuron; (ii) that inhibitory AT1A-Gαi signaling in the Type 1 AgRP cell stimulates RMR; and (iii) that loss of AT1A-Gαi coupling in these cells is sufficient to explain obesity-associated RMR adaptation.

The Third Dimension of Ferroelectric Domain Walls.

Ferroelectric domain walls are quasi-2D systems that show great promise for the development of nonvolatile memory, memristor technology, and electronic components with ultrasmall feature size. Electric fields, for example, can change the domain wall orientation relative to the spontaneous polarization and switch between resistive and conductive states, controlling the electrical current. Being embedded in a 3Dmaterial, however, the domain walls are not perfectly flat and can form networks, which leads to complex physical structures. In this work, the importance of the nanoscale structure for the emergent transport properties is demonstrated, studying electronic conduction in the 3D network of neutral and charged domain walls in ErMnO3 . By combining tomographic microscopy techniques and finite element modeling, the contribution of domain walls within the bulk is clarified and the significance of curvature effects for the local conduction is shown down to the nanoscale. The findings provide insights into the propagation of electrical currents in domain wall networks, reveal additional degrees of freedom for their control, and provide quantitative guidelines for the design of domain-wall-based technology.

Fabrication of superhydrophobic stainless-steel mesh for oil-water separation by jet electrodeposition

A method for fabricating superhydrophobic stainless-steel meshes based on magnetic field-assisted jet electrodeposition is proposed. Ferromagnetic nickel particles (Nip) were added to the electroplating solution to prepare Ni/Nip coatings with mountain-like rough structure on stainless-steel meshes, followed by application of a parallel magnetic field in the cathode region. Magnetic fields play an indispensable role in the preparation of coatings. Exposure to air for 6 days resulted in a spontaneous switch of the coating from superhydrophilicity to superhydrophobicity and exhibited superoleophilicity. X-ray photoelectron spectroscopy revealed that this transition in wettability was related to spontaneous adsorption of hydrocarbons in the air induced by the coating. Based on the superhydrophobicity and superoleophilicity of the as-prepared Ni/Nip-coated meshes, high-efficiency, high-throughput, and high-purity separation of oil-water mixtures was achieved with a 300-mesh mesh. Furthermore, the as-prepared meshes continue to exhibit a separation efficiency greater than 97.0% and stable reusability even after 50 repeated separations.

Electrically controlled valley polarization in 2D buckled honeycomb structures

Generating and manipulating valley polarization in a controlled method is significant. The inherently broken centrosymmetry of the buckled honeycomb structures gives it both ferroelectricity and valley degree of freedom, which provides an opportunity to realize electrically controlled valley polarization. In the first step, we explored the origin of buckling. The hexagonal structure is polar due to buckling of the surface, but the degree of buckling and the energy barrier to switching electric polarization are determined not solely by the chemical composition. We combined the electronegativity difference, bond length and the distribution of charge density to describe quantificationally the polarity of chemical bonds. It shows the characteristics of relatively long bond-length but relatively small electronegativity-difference. For exploring the ferroelectricity of buckling structures and the behavior of ferroelectric (FE) control of the valley degree of freedom, the [Formula: see text]-GaP is used as a model system to elucidate the strain effect on FE behavior and the magnetic proximity effect on the polarization and switching of valley. We found that the spontaneous polarization is positively correlated with the electronegativity difference within a certain range, and the compression strain can effectively manipulate spontaneous polarization and switch barrier. A combination of the magnetic proximity effect and the inversion of electric polarization can generate and switch valley polarization effectively.

Pupil constriction via the parasympathetic pathway precedes perceptual switch of ambiguous stimuli

Perceptual rivalry of ambiguous stimuli reflects the interaction of neural activity among multiple cortical regions. However, it remains unclear what drives a spontaneous perceptual alteration. We hypothesized that increased fluctuations in spontaneous neural activity due to arousal reduction drive the perceptual switch. Here, we show that the pupils shrank a few seconds prior to the onset of the spontaneous perceptual switch. Such pupil constriction was not observed before the exogenous perceptual switch. Pharmacological experiments confirmed that the pupil constriction disappeared when the peripheral parasympathetic pathway (pupil sphincter muscle) was blocked, but it remained intact when the peripheral sympathetic pathway (pupil dilator muscle) was manipulated. Furthermore, rapid pupil dilations with behavioral response are also mediated by the peripheral parasympathetic pathway. The present findings suggested that transient arousal drops, as denoted by the autonomic nervous modulation of pupil size, are involved in inducing the spontaneous perceptual switch of bistable stimuli.

Interplay between Swampland and Bayesian Machine Learning in constraining cosmological models

Constraints on a dark energy dominated Universe are obtained from an interplay Bayesian (Probabilistic) Machine Learning and string Swampland criteria. Unlike in previous studies, here, the field traverse itself has been used to constraint the theory and reveal its connection to the Swampland approach. The field traverse based Bayesian (Probabilistic) Learning approach is applied to two toy models. A parametrization of the Hubble constant is used for the first model, while a parametrization of the deceleration parameter is considered for the second one. The results obtained here allow to estimate how the high-redshift behavior of the Universe will affect the low-redshift one. Moreover, the adopted approach may highlight, in the future, the borders of the Swampland for the low-redshift Universe and help to develop new string-theory motivated dark energy models. The most important message from our study is a hint that the string Swampland criteria might be in tension with recent observations indicating that phantom dark energy cannot be in the Swampland. Finally, another interesting result obtained in our study is a spontaneous sign switch in the dark energy equation of state parameter when the field traverses are in the zin [0,5] redshift range, a remarkable phenomenon requiring further analysis.

Implementation of pharmacist-managed early switch from intravenous to oral therapy using electronic identification at a tertiary academic hospital

Overutilization of intravenous (IV) medications can result in drug shortages, which is one of the major health care crisis, in addition to increasing costs, length of hospital stays (LOS) and the associated complications. We hypothesized that IV therapy was overused at our hospital where oral (PO) was applicable, and that the implementation of IV-PO protocol could result in a cost-effective practice. Hence, we aimed at assessing impact and outcomes of implementing such a protocol.A single center, prospective quasi-interventional study conducted at tertiary academic hospital. A protocol was implemented targeting 17 medications, with educational sessions to medical staff during a 5-month phase. IV orders of 48 h or more, among adult patients at medical or surgical wards with no contraindication to PO route were eligible. Once eligible, pharmacists send interventions using hospital’s computerized order entry system, and physicians’ responses were monitored on daily basis. Efficacy was estimated by percentage of switch recommendations that resulted in effective switch to PO medication. Cost-minimization analysis was used for course cost between the control phase and intervention phase. Length of hospital stay (LOS), readmissions within 90 days and in-hospital mortality were analyzed as secondary outcomes.During intervention phase, 781 patients had at least one IV order switched to PO. Gastric acid-reducing agents (GARAs) accounted for the most IV prescriptions (50.4%), followed by antibiotics (39.6%). Pharmacists carried out 2677 interventions to which switch recommendations were issued in 1185 (44.3%). Primary switch recommendations (N = 677) led to effective switch in 60.7% cases. These included per protocol switch (8.9%), switch to another PO (2.5%), spontaneous switch by physician (17.6%) and IV discontinuation (31.8%). The overall efficacy was estimated as 62.8%. The intervention was associated with reduced IV consumption from 4,574–18,597 vials in control phase to 3,654–15,546 vials in intervention phase, which resulted in overall cost saving of 50,960.8 SAR ($13,589.5), with an average monthly cost saving of 10,192.2 SAR ($2,717.9).Pharmacist-managed early switch from IV-PO therapy, with physicians’ education, showed significant reduction in IV medication use in our hospital. By reducing unnecessary IV use, this strategy enabled considerable cost savings, besides the potential advantages of convenience and safety.

Graduated dark energy: Observational hints of a spontaneous sign switch in the cosmological constant

We study the cosmological constant ($\Lambda$) in the standard $\Lambda$CDM model by introducing the \textit{graduated dark energy} (gDE) characterised by a minimal dynamical deviation from the null inertial mass density of the $\Lambda$ in the form $\rho_{\rm inert}\propto \rho^{\lambda}<0$ with $\lambda<1$ being a ratio of two odd integers, for which its energy density $\rho$ dynamically takes negative values in the finite past. For large negative values of $\lambda$, it creates a phenomenological model described by a smooth function that approximately describes the $\Lambda$ spontaneously switching sign in the late universe to become positive today. We confront the model with the latest combined observational data sets of PLK+BAO+SN+$H$. It is striking that the data predict bimodal posterior probability distributions for the parameters of the model along with large negative $\lambda$ values; the new maximum significantly excludes the $\Lambda$, and the old maximum contains the $\Lambda$. The improvement in the goodness of fit for the $\Lambda$ reaches highly significant levels, $\Delta\chi_{\rm min}^2=6.4$ for the new maxima, while it remains at insignificant levels, $\Delta\chi_{\rm min}^2\lesssim0.02$, for the old maxima. We show that, in contrast to the old maxima, which do not distinguish from the $\Lambda$, the new maxima agree with the model-independent $H_0$ measurements, high-precision Ly-$\alpha$ data, and model-independent $Omh^2$ diagnostic estimates. Our results provide strong hints of a spontaneous sign switch in the cosmological constant and lead us to conjecture that the universe has transitioned from AdS vacua to dS vacua, at a redshift $z\approx 2.32$ and triggered the late-time acceleration, and suggests looking for such mechanisms in string theory constructions.

Testing ovarian cancer cell lines to train dogs to detect ovarian cancer from blood plasma: A pilot study

Ovarian cancer is known as a “silent killer” because of its nonspecific symptoms and generally late diagnosis due to the lack of reliable early detection tools. Medical detection canines have been shown to recognize the odor profile of malignant tumors of many types, including ovarian cancer, and may be utilized to help produce a much-needed early detection system for ovarian cancer. One significant drawback, however, is that to train detection canines on the odor signature of ovarian cancer, different samples or sets of samples must be used in every training session so that the canines do not begin to recognize an individual patient's odor signature or attune to patient-specific noncancerous olfactory cues. Therefore, numerous patient-derived samples must be obtained and stored for use in the training process. Ovarian cancer cell lines may be able to solve this obstacle, as they have low sample-to-sample variability and do not present patient-specific confounding olfactory cues. In this study, we attempted to train three medical detection dogs to alert to an ovarian cancer cell line (OVKATE) but not the culture media or nonmalignant cultured fallopian tube cells. Only one dog was able to discriminate between OVKATE and culture media and was able to be tested on other ovarian cancer cell lines (OVCAR-4, OVCAR-8, and SK-OV-3). The dog's responses suggest a common or related olfactory signature of malignant ovarian cancer cell lines. We then tested whether an OVKATE-trained dog recognized the blood plasma of patients with confirmed ovarian cancer. We did not find strong evidence that the dog recognized the blood plasma of a patient with confirmed ovarian cancer within three testing trials, with the dog only hesitating at the target odor, suggesting that while training on the cell lines may prepare medical dedication canines to recognize the blood plasma of patient with ovarian cancer, it is not a spontaneous switch to blood plasma. Despite this outcome, the behavior of the dog led us to believe that this method could help further the use of medical detection canines to inform the production of early detection tools for ovarian cancer, which would lead to earlier diagnoses and more favorable outcomes from therapy.

Differentially expressed genes during spontaneous lytic switch of Marek's disease virus in lymphoblastoid cell lines determined by global gene expression profiling.

Marek’s disease virus (MDV), an alphaherpesvirus of poultry, causes Marek’s disease and is characterized by visceral CD4+TCRαβ+ T-cell lymphomas in susceptible hosts. Immortal cell lines harbouring the viral genome have been generated from ex vivo cultures of MD tumours. As readily available sources of large numbers of cells, MDV-transformed lymphoblastoid cell lines (LCLs) are extremely valuable for studies of virus–host interaction. While the viral genome in most cells is held in a latent state, minor populations of cells display spontaneous reactivation identifiable by the expression of lytic viral genes. Spontaneous reactivation in these cells presents an opportunity to investigate the biological processes involved in the virus reactivation. For detailed characterization of the molecular events associated with reactivation, we used two lymphoblastoid cell lines derived from lymphomas induced by pRB1B-UL47eGFP, a recombinant MDV engineered to express enhanced green fluorescent protein (EGFP) fused with the UL47. We used fluorescence-activated cell sorting to purify the low-frequency EGFP-positive cells with a spontaneously activating viral genome from the majority EGFP-negative cells and analysed their gene expression profiles by RNA-seq using Illumina HiSeq2500. Ingenuity pathway analysis on more than 2000 differentially expressed genes between the lytically infected (EGFP-positive) and latently infected (EGFP-negative) cell populations identified the biological pathways involved in the reactivation. Virus-reactivating cells exhibited differential expression of a significant number of viral genes, with hierarchical differences in expression levels. Downregulation of a number of host genes including those directly involved in T-cell activation, such as CD3, CD28, ICOS and phospholipase C, was also noticed in the LCL undergoing lytic switch.

Keep flexible – Keep switching! The influence of forced task switching on voluntary task switching

Goal directed behavior depends on a dynamic balance between cognitive flexibility and stability. Identifying factors that modulate the balance between these control states is therefore of major interest for the understanding of human action control. In two experiments we used a hybrid paradigm combining forced- and free-choice task switching and measured spontaneous voluntary switch rate (VSR) as an indicator of cognitive flexibility. In Experiment 1 participants were free to choose a given task on 75%, 50%, or 25% of all trials. In the remaining forced-choice trials task repetitions and switches were roughly equally distributed. Results showed that VSR increases with increasing proportion of forced choices. To clarify whether the frequency of forced choices per se or the frequency of forced task switches in particular drives this effect we conducted Experiment 2. In a fully orthogonal between design participants were free to choose a given task on 75% or 25% of all trials with a predetermined switch rate in the remaining forced-choice trials of 75% or 25%, respectively. Results revealed an interaction of both manipulations: The highest VSR was found for the combination of 75% forced-choice trials with 75% forced switch rate, while VSR for 75% forced-choice trials with 25% forced switch rate was still higher than VSRs in both conditions with 25% forced-choice trials. This suggests that a context of frequent forced task switching changes global control parameters towards more flexible behavior.

On subsurface fracture opening and closure

Understanding of subsurface fracture opening and closure is of great importance to oil/gas production, geothermal energy extraction, radioactive waste disposal, and carbon sequestration and storage. Fracture opening and closure involve a complex set of thermal, hydrologic, mechanical and chemical (THMC) processes. In this paper, a fully coupled THMC model for fracture opening and closure is formulated by explicitly accounting for the stress concentration on aperture surface, stress-activated mineral dissolution, pressure solution at contacting asperities, and channel flow dynamics. A model analysis, together with reported laboratory observations, shows that a tangential surface stress created by a far-field compressive normal stress may play an important role in controlling fracture aperture evolution in a stressed geologic medium, a mechanism that has not been considered in any existing models. Based on the model analysis, a necessary condition for aperture opening has been derived. The model provides a reasonable explanation for many salient features of fracture evolution in laboratory experiments, including a spontaneous switch from a permeability reduction to a permeability increase in a static limestone experiment. The work may also help develop a new method for estimating in-situ stress in a reservoir.

Time to lack of persistence with pharmacological treatment among patients with current depressive episodes: a natural study with 1-year follow-up.

IntroductionMedication nonadherence remains a big challenge for depressive patients. This study aims to assess and compare the medication persistence between unipolar depression (UD) and bipolar depression (BD).MethodsA total of 146 UD and 187 BD patients were recruited at their first index prescription. Time to lack of persistence with pharmacological treatment (defined as a gap of at least 60 days without taking any medication) was calculated, and clinical characteristics were collected. Final diagnosis was made at the end of 1-year follow-up.ResultsA total of 101 (69.2%) UD and 126 (67.4%) BD patients discontinued the treatment, with a median duration of 36 days and 27 days, respectively. No significant difference was found between UD and BD in terms of time to lack of persistence with pharmacological treatment. The highest discontinuation rate (>40%) occurred in the first 3 months for both groups of patients. For UD patients, those with a higher risk of suicide (odds ratio [OR] =0.696, P=0.035) or comorbidity of any anxiety disorder (OR =0.159, P<0.001) were less likely to prematurely drop out (drop out within the first 3 months), while those with onset in the summer (OR =4.702, P=0.049) or autumn (OR =7.690, P=0.012) were more likely to prematurely drop out than those with onset in the spring (OR =0.159, P<0.001). For BD patients, being female (OR =2.250, P=0.012) and having a history of spontaneous remission or switch to hypomania (OR =2.470, P=0.004) were risk factors for premature drop out, while hospitalization (OR =0.304, P=0.023) and misdiagnosis as UD (OR =0.283, P<0.001) at the first index prescription were protective factors.LimitationConservative definition of nonadherence, low representativeness of sample.ConclusionTreatment discontinuation was frequently seen in patients with UD or BD, especially in the first 3 months of treatment. In spite of the similar pattern of medication persistence, UD and BD differ from each other in predictors of premature drop out.

Bitcoin and entrepreneurship: breaking the network effect

This paper explores the question of whether the market process is capable of bringing about a spontaneous monetary switch to a new currency in the presence of strong network effects of the incumbent currency as well as the absence of contingencies such as extreme inflation or political instability. It does so by examining current happenings around Bitcoin. It finds that two mechanisms stand out: the coordinating efforts of the profit-maximizing entrepreneur as well as the ability to use the old and the new currency simultaneously. Specifically, it finds that marginal decisions made by rational agents merely seeking to maximize net private benefit irrespective of the network effect, be it entrepreneurs or users of the new currency, are capable of setting in motion a switch to a new currency. Whether or not these mechanisms play out fully in the case of Bitcoin still remains to be seen.

Temperature dependence of spontaneous switch-on and switch-off of laser cavity solitons in vertical-cavity surface-emitting lasers with frequency-selective feedback

A systematic experimental and numerical investigation of the conditions for the spontaneous formation of laser cavity solitons in broad-area vertical-cavity surface-emitting lasers with frequency-selective feedback by a volume Bragg grating is reported. It is shown that the switching thresholds are controlled by a combination of frequency shifts induced by ambient temperature and Joule heating. The gain level has only a minor influence on the threshold but controls mainly the power of the solitons. At large initial detuning and high threshold gain, the first observed structure can be a high order soliton. In real devices spatial disorder in the cavity length causes a pinning of solitons and a dispersion of thresholds. The experimental observations are in good agreement with numerical simulations taking into account disorder and the coupling of gain and cavity resonance due to Joule heating. In particular, we demonstrate that the existence of the traps explain the spontaneous switch on of the solitons, but do not modify the soliton shape significantly, i.e. the observed solitons are a good approximation of the ones expected in a homogeneous system.

Unrelated toxin-antitoxin systems cooperate to induce persistence.

Persisters are drug-tolerant bacteria that account for the majority of bacterial infections. They are not mutants, rather, they are slow-growing cells in an otherwise normally growing population. It is known that the frequency of persisters in a population is correlated with the number of toxin–antitoxin systems in the organism. Our previous work provided a mechanistic link between the two by showing how multiple toxin–antitoxin systems, which are present in nearly all bacteria, can cooperate to induce bistable toxin concentrations that result in a heterogeneous population of slow- and fast-growing cells. As such, the slow-growing persisters are a bet-hedging subpopulation maintained under normal conditions. For technical reasons, the model assumed that the kinetic parameters of the various toxin–antitoxin systems in the cell are identical, but experimental data indicate that they differ, sometimes dramatically. Thus, a critical question remains: whether toxin–antitoxin systems from the diverse families, often found together in a cell, with significantly different kinetics, can cooperate in a similar manner. Here, we characterize the interaction of toxin–antitoxin systems from many families that are unrelated and kinetically diverse, and identify the essential determinant for their cooperation. The generic architecture of toxin–antitoxin systems provides the potential for bistability, and our results show that even when they do not exhibit bistability alone, unrelated systems can be coupled by the growth rate to create a strongly bistable, hysteretic switch between normal (fast-growing) and persistent (slow-growing) states. Different combinations of kinetic parameters can produce similar toxic switching thresholds, and the proximity of the thresholds is the primary determinant of bistability. Stochastic fluctuations can spontaneously switch all of the toxin–antitoxin systems in a cell at once. The spontaneous switch creates a heterogeneous population of growing and non-growing cells, typical of persisters, that exist under normal conditions, rather than only as an induced response. The frequency of persisters in the population can be tuned for a particular environmental niche by mixing and matching unrelated systems via mutation, horizontal gene transfer and selection.

Flow regimes in a vertical drop shaft with a sharp-edged intake

The results of an experimental analysis are provided concerning the hydraulic behaviour of a vertical drop shaft with a sharp-edged circular intake, also taking into account a peculiar venting system consisting of a coaxial vertical pipe, projecting within the drop shaft with different plunging lengths. Three different flow regimes are experienced: a “weir flow” for low head values, where an air–water mixture at the atmospheric pressure can be observed; a “pressurized flow” for high head values, where water flows in a pressurized regime along the shaft; a “transitional flow” for intermediate water head values, consisting of a continuous, spontaneous switch between weir flow and pressurized flow with consequent water head variation for a fixed discharge. Pressurized flow regime is analytically explained, so that a head–discharge relation can be provided both for the non-vented and for the vented configurations, with specific assumptions about intake losses.