To Lyse or Not to Lyse: Transient-Mediated Stochastic Fate Determination in Cells Infected by Bacteriophages

Cell fate determination is usually described as the result of the stochastic dynamics of gene regulatory networks (GRNs) reaching one of multiple steady-states each of which corresponds to a specific decision. However, the fate of a cell is determined in finite time suggesting the importance of transient dynamics in cellular decision making. Here we consider cellular decision making as resulting from first passage processes of regulatory proteins and examine the effect of transient dynamics within the initial lysis-lysogeny switch of phage λ. Importantly, the fate of an infected cell depends, in part, on the number of coinfecting phages. Using a quantitative model of the phage λ GRN, we find that changes in the likelihood of lysis and lysogeny can be driven by changes in phage co-infection number regardless of whether or not there exists steady-state bistability within the GRN. Furthermore, two GRNs which yield qualitatively distinct steady state behaviors as a function of phage infection number can show similar transient responses, sufficient for alternative cell fate determination. We compare our model results to a recent experimental study of cell fate determination in single cell assays of multiply infected bacteria. Whereas the experimental study proposed a “quasi-independent” hypothesis for cell fate determination consistent with an observed data collapse, we demonstrate that observed cell fate results are compatible with an alternative form of data collapse consistent with a partial gene dosage compensation mechanism. We show that including partial gene dosage compensation at the mRNA level in our stochastic model of fate determination leads to the same data collapse observed in the single cell study. Our findings elucidate the importance of transient gene regulatory dynamics in fate determination, and present a novel alternative hypothesis to explain single-cell level heterogeneity within the phage λ lysis-lysogeny decision switch

Interference of an array of atom lasers

We report on the observation of interference of a series of atom lasers. A comb-like array of coherent atomic beams is generated by outcoupling atoms from distinct Bose-Einstein condensates confined in the independent sites of a mesoscopic optical lattice. The observed interference signal arises from the spatial beating of the overlapped atom laser beams, which is sampled over a vertical region corresponding to 2 ms of free fall time. The average relative de Broglie frequency of the atom lasers was measured.Comment: 3 figure

Stiffness of the Crystal-Liquid Interface in a Hard-Sphere Colloidal System Measured from Capillary Fluctuations

Face-centered cubic single crystals of $σ=1.55 μm$ diameter hard-sphere silica colloidal particles were prepared by sedimentation onto (100) and (110) oriented templates. The crystals had a wide interface with the overlaying liquid that was parallel to the template. The location of the interface was determined by confocal microscopic location of the particles, followed by identification of the crystalline and liquid phases by a bond-orientation order parameter. Fluctuations in the height of the interface about its average position were recorded for several hundred configurations. The interfacial stiffness $γ̃$ was determined from the slope of the inverse squared Fourier components of the height profile vs the square of the wave number, according to the continuum capillary fluctuation method. The offset of the fit from the origin could quantitatively be accounted for by gravitational damping of the fluctuations. For the (100) interface, $γ̃ =(1.3±0.3)k_{B}T/σ^{2}$; for the (110) interface, $γ̃ =(1.0±0.2)k_{B}T/σ^{2}$. The interfacial stiffness of both interfaces was found to be isotropic in the plane. This is surprising for the (110), where crystallography predicts twofold symmetry. Sedimentation onto a (111) template yielded a randomly stacked hexagonal crystal with isotropic $γ̃ =0.66k_{B}T/σ^{2}$. This value, however, is less reliable than the two others due to imperfections in the crystal.Engineering and Applied SciencesPhysic

An α2(Zα)5m\alpha^{2}(Z \alpha)^{5}m Contribution to the Hydrogen Lamb Shift from Virtual Light by Light Scattering

The radiative correction to the Lamb shift of order $\alpha^{2}(Z\alpha)^5m$ induced by the light by light scattering insertion in external photons is obtained. The new contribution turns out to be equal to $-0.122(2)\alpha^2(Z\alpha)^5/(\pi n^3)(m_r/m)^3m$. Combining this contribution with our previous results we obtain the complete correction of order $\alpha^{2}(Z\alpha)^5m$ induced by all diagrams with closed electron loops. This correction is $37.3(1)$ kHz and $4.67(1)$ kHz for the $1S$- and $2S$-states in hydrogen, respectively.Comment: pages, Penn State Preprint PSU/TH/142, February 199

Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers.

BACKGROUND: Ticagrelor is an oral P2Y12 inhibitor that is used with aspirin to reduce the risk of ischemic events among patients with acute coronary syndromes or previous myocardial infarction. Spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with ticagrelor, as with other antiplatelet drugs. The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. A rapid-acting reversal agent would be useful. METHODS: In this randomized, double-blind, placebo-controlled, phase 1 trial, we evaluated intravenous PB2452, a monoclonal antibody fragment that binds ticagrelor with high affinity, as a ticagrelor reversal agent. We assessed platelet function in healthy volunteers before and after 48 hours of ticagrelor pretreatment and again after the administration of PB2452 or placebo. Platelet function was assessed with the use of light transmission aggregometry, a point-of-care P2Y12 platelet-reactivity test, and a vasodilator-stimulated phosphoprotein assay. RESULTS: Of the 64 volunteers who underwent randomization, 48 were assigned to receive PB2452 and 16 to receive placebo. After 48 hours of ticagrelor pretreatment, platelet aggregation was suppressed by approximately 80%. PB2452 administered as an initial intravenous bolus followed by a prolonged infusion (8, 12, or 16 hours) was associated with a significantly greater increase in platelet function than placebo, as measured by multiple assays. Ticagrelor reversal occurred within 5 minutes after the initiation of PB2452 and was sustained for more than 20 hours (P\u3c0.001 after Bonferroni adjustment across all time points for all assays). There was no evidence of a rebound in platelet activity after drug cessation. Adverse events related to the trial drug were limited mainly to issues involving the infusion site. CONCLUSIONS: In healthy volunteers, the administration of PB2452, a specific reversal agent for ticagrelor, provided immediate and sustained reversal of the antiplatelet effects of ticagrelor, as measured by multiple assays. (Funded by PhaseBio Pharmaceuticals; ClinicalTrials.gov number, NCT03492385.)

Thermalization of coupled atom-light states in the presence of optical collisions

The interaction of a two-level atomic ensemble with a quantized single mode electromagnetic field in the presence of optical collisions (OC) is investigated both theoretically and experimentally. The main accent is made on achieving thermal equilibrium for coupled atom-light states (in particular dressed states). We propose a model of atomic dressed state thermalization that accounts for the evolution of the pseudo-spin Bloch vector components and characterize the essential role of the spontaneous emission rate in the thermalization process. Our model shows that the time of thermalization of the coupled atom-light states strictly depends on the ratio of the detuning and the resonant Rabi frequency. The predicted time of thermalization is in the nanosecond domain and about ten times shorter than the natural lifetime at full optical power in our experiment. Experimentally we are investigating the interaction of the optical field with rubidium atoms in an ultra-high pressure buffer gas cell under the condition of large atom-field detuning comparable to the thermal energy in frequency units. In particular, an observed detuning dependence of the saturated lineshape is interpreted as evidence for thermal equilibrium of coupled atom-light states. A significant modification of sideband intensity weights is predicted and obtained in this case as well.Comment: 14 pages, 12 figures; the content was edite

Improved Theory of the Muonium Hyperfine Structure

Terms contributing to the hyperfine structure of the muonium ground state at the level of few tenths of kHz have been evaluated. The $\alpha^2 (Z\alpha)$ radiative correction has been calculated numerically to the precision of 0.02 kHz. Leading $\ln (Z\alpha )$ terms of order $\alpha^{4-n} (Z\alpha)^n , n=1,2,3,$ and some relativistic corrections have been evaluated analytically. The theoretical uncertainty is now reduced to 0.17 kHz. At present, however, it is not possible to test QED to this precision because of the 1.34 kHz uncertainty due to the muon mass.Comment: 11 pages + 2 figures (included), RevTeX 3.0, CLNS 94/127

Tunneling out of a time-dependent well

Solutions to explicit time-dependent problems in quantum mechanics are rare. In fact, all known solutions are coupled to specific properties of the Hamiltonian and may be divided into two categories: One class consists of time-dependent Hamiltonians which are not higher than quadratic in the position operator, like i.e the driven harmonic oscillator with time-dependent frequency. The second class is related to the existence of additional invariants in the Hamiltonian, which can be used to map the solution of the time-dependent problem to that of a related time-independent one. In this article we discuss and develop analytic methods for solving time-dependent tunneling problems, which cannot be addressed by using quadratic Hamiltonians. Specifically, we give an analytic solution to the problem of tunneling from an attractive time-dependent potential which is embedded in a long-range repulsive potential. Recent progress in atomic physics makes it possible to observe experimentally time-dependent phenomena and record the probability distribution over a long range of time. Of special interest is the observation of macroscopical quantum-tunneling phenomena in Bose-Einstein condensates with time-dependent trapping potentials. We apply our model to such a case in the last section.Comment: 11 pages, 3 figure

Phytochemical screening and biological activity studies of five South African indigenous medicinal plants

Different extracts and fractions of five selected indigenous South African medicinal plants, namely, Cissampelos capensis, Geranium incanum and three Gethyllis species, were subjected to phytochemical screening and testing for cytotoxicity using the brine shrimp lethality bioassay, and antimicrobial activity assays against nine microbes, which included three fungal species, three Gram negative and three Gram positive bacteria.The majority of the extracts tested positive for the presence of tannins, phenolics and flavonoids, while in selected cases, phytochemical tests suggested the presence of essential oils, glycosides or alkaloids. The methanol extract of Gethyllis gregoriana displayed the highest cytotoxicity levels. Generally, the highest levels of biological activity were shown to reside in the methanolic extracts, while hexane extracts revealed very low to zero activity. The total tertiary alkaloid (TTA) of C. capensis was mostly active against Bacillus subtilis, a Gram +ve bacteria. The trends observed for the cytotoxicity assay were in agreement with those observed for the antimicrobial assay