On correlations and fluctuations of time-averaged densities and currents with general time-dependence

We present technical results required for the description and understand- ing of correlations and fluctuations of the empirical density and current as well as diverse time-integrated and time-averaged thermodynamic currents of diffusion pro- cesses with a general time dependence on all time scales. In particular, we generalize the results from arXiv:2105.10483 (Phys. Rev. Lett. , article in press), arXiv:2204.06553 (Phys. Rev. Research, article in press), and arXiv:2206.04034 to additive functionals with explicit time dependence and transient or non-ergodic overdamped diffusion. As an illustration we apply the results to two-dimensional harmonically confined over- damped diffusion in a rotational flow evolving from a non-stationary initial distribution

Feynman-Kac theory of time-integrated functionals: Itô versus functional calculus

The fluctuations of dynamical functionals such as the empirical density and current as well as heat, work and generalized currents in stochastic thermodynamics are often studied within the Feynman-Kac tilting formalism, which in the physics literature is typically derived by some form of Kramers-Moyal expansion. Here we derive the Feynman-Kac theory for general additive dynamical functionals directly via Itô calculus and via functional calculus, where the latter approach in fact appears to be new. Using Dyson series we then independently recapitulate recent results on steady-state (co)variances of general additive dynamical functionals derived in arXiv:2105.10483 and arXiv:2204.06553 directly from Itô calculus avoiding any tilting. We hope for our work to put the different approaches to stochastic functionals employed in the field on a common footing

Direct Route to Thermodynamic Uncertainty Relations

Thermodynamic uncertainty relations (TURs) bound the dissipation in non-equilibrium systems from below by fluctuations of an observed current. Contrasting the elaborate techniques employed in existing proofs, we here prove TURs directly from the Langevin equation. This establishes the TUR as an inherent property of overdamped stochastic equations of motion. By including current-density correlations we, moreover, derive a new sharpened TUR for transient dynamics. Our arguably simplest and most direct proof allows us to systematically determine conditions under which the different TURs saturate and thus allows for a more accurate thermodynamic inference

Coarse graining empirical densities and currents in continuous-space steady states

We present the conceptual and technical background required to describe and understand the correlations and fluctuations of the empirical density and current of steady-state diffusion processes on all time scales — observables central to statistical mechanics and thermodynamics on the level of individual trajectories. We focus on the important and non-trivial effect of a spatial coarse graining. Making use of a generalized time-reversal symmetry we provide deeper insight about the physical meaning of fluctuations of the coarse-grained empirical density and current, and explain why a systematic variation of the coarse-graining scale offers an efficient method to infer bounds on a system’s dissipation. Moreover, we discuss emerging symmetries in the statistics of the empirical density and current, and the statistics in the large deviations regime. More broadly our work promotes the application of stochastic calculus as a powerful direct alternative to Feynman-Kac theory and path-integral methods

Utilization of Polyspecific Antiserum for Specific Radioimmunoassays: Radioimmunoassays for Rat Fetuin and Bikunin Were Developed by Using Antiserum Against Total Rat Serum Proteins

Polyspecific antiserum against total rat serum proteins was used to develop specific and sensitive radioimmunoassays for fetuin and bikunin, two minor protein components of rat plasma. The radioimmunoassays proved to be highly useful to trace bikunin and fetuin in the course of developing isolation procedures, since neither specific functional assays nor monospecific antisera were available. The two examples demonstrate that, in general, it will be possible to develop a specific and sensitive radioimmunoassay with antiserum raised against a crude antigen preparation, such as a body fluid or a tissue extract, provided that a minute amount of pure antigen is available for preparing the radioiodinated antigen

Equation of state of cubic boron nitride at high pressures and temperatures

We report accurate measurements of the equation of state (EOS) of cubic boron nitride by x-ray diffraction up to 160 GPa at 295 K and 80 GPa in the range 500-900 K. Experiments were performed on single-crystals embedded in a quasi-hydrostatic pressure medium (helium or neon). Comparison between the present EOS data at 295 K and literature allows us to critically review the recent calibrations of the ruby standard. The full P-V-T data set can be represented by a Mie-Gr\"{u}neisen model, which enables us to extract all relevant thermodynamic parameters: bulk modulus and its first pressure-derivative, thermal expansion coefficient, thermal Gr\"{u}neisen parameter and its volume dependence. This equation of state is used to determine the isothermal Gr\"{u}neisen mode parameter of the Raman TO band. A new formulation of the pressure scale based on this Raman mode, using physically-constrained parameters, is deduced.Comment: 8 pages, 7 figure

TYK2 promotes malignant peripheral nerve sheath tumor progression through inhibition of cell death

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise most commonly in the setting of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome. Despite aggressive multimodality therapy, outcomes are dismal and most patients die within 5 years of diagnosis. Prior genomic studies in our laboratory identified tyrosine kinase 2 (TYK2) as a frequently mutated gene in MPNST. Herein, we explored the function of TYK2 in MPNST pathogenesis. METHODS: Immunohistochemistry was utilized to examine expression of TYK2 in MPNSTs and other sarcomas. To establish a role for TYK2 in MPNST pathogenesis, murine and human TYK2 knockdown and knockout cells were established using shRNA and CRISPR/Cas9 systems, respectively. RESULTS: We have demonstrated that TYK2 was highly expressed in the majority of human MPNSTs examined. Additionally, we demonstrated that knockdown of Tyk2/TYK2 in murine and human MPNST cells significantly increased cell death in vitro. These effects were accompanied by a decrease in the levels of activated Stats and Bcl-2 as well as an increase in the levels of Cleaved Caspase-3. In addition, Tyk2-KD cells demonstrated impaired growth in subcutaneous and metastasis models in vivo. CONCLUSION: Taken together, these data illustrate the importance of TYK2 in MPNST pathogenesis and suggest that the TYK2 pathway may be a potential therapeutic target for these deadly cancers

Scattering fingerprints of two-state dynamics

Particle transport in complex environments such as the interior of living cells is often (transiently) non-Fickian or anomalous, that is, it deviates from the laws of Brownian motion. Such anomalies may be the result of small-scale spatio-temporal heterogeneities in, or viscoelastic properties of, the medium, molecular crowding, etc. Often the observed dynamics displays multi-state characteristics, i.e. distinct modes of transport dynamically interconverting between each other in a stochastic manner. Reliably distinguishing between single- and multi-state dynamics is challenging and requires a combination of distinct approaches. To complement the existing methods relying on the analysis of the particle's mean squared displacement, position- or displacement-autocorrelation function, and propagators, we here focus on 'scattering fingerprints' of multi-state dynamics. We develop a theoretical framework for two-state scattering signatures—the intermediate scattering function and dynamic structure factor—and apply it to the analysis of simple model systems as well as particle-tracking experiments in living cells. We consider inert tracer-particle motion as well as systems with an internal structure and dynamics. Our results may generally be relevant for the interpretation of state-of-the-art differential dynamic microscopy experiments on complex particulate systems, as well as inelastic or quasielastic neutron (incl. spin-echo) and x-ray scattering probing structural and dynamical properties of macromolecules, when the underlying dynamics displays two-state transport

“I see myself as a STEM person”: Exploring high school students’ self-identification with STEM

In the literature, STEM identity tends to be characterized either as students' relationship with the STEM field “as a whole,” or their relationship with a particular STEM area, such as science. With this study, we add to the existing scholarship by characterizing the profiles of students who identified themselves as “STEM people.” A 52-item questionnaire was administered to 1004 students aged 12–16 from high schools in and around Barcelona, Spain. To profile different groups of students, we performed a hierarchical cluster analysis that included responses relating to participants' interest, competence, self-efficacy, and aspirations to different STEM and non-STEM areas. Our analysis generated six different clusters, which we interpreted as ranging from positive to negative self-identification with STEM. Our particular interest was in the two clusters we interpreted as exhibiting positive STEM identity (C1 and C2). The analysis suggested that there were two different ways of considering oneself as a STEM person. Students who self-identified as STEM people were either more inclined toward technology and engineering (C1) or science (C2), particularly in terms of their aspirations. These two clusters were also strongly gendered, with C1 being dominated by boys and C2 by girls. Although our findings suggest the existence of a conscious “sense of STEM identity,” we suggest that students who self-identified as STEM people may have ascribed different meanings to the STEM based on their preferences. As such, this study questions the suitability of studying STEM identity “as a whole” without also considering how students relate to individual STEM and non-STEM areas

First-passage statistics of colloids on fractals: Theory and experimental realization

In nature and technology, particle dynamics frequently occur in complex environments, for example in restricted geometries or crowded media. These dynamics have often been modeled invoking a fractal structure of the medium although the fractal structure was only indirectly inferred through the dynamics. Moreover, systematic studies have not yet been performed. Here, colloidal particles moving in a laser speckle pattern are used as a model system. In this case, the experimental observations can be reliably traced to the fractal structure of the underlying medium with an adjustable fractal dimension. First-passage time statistics reveal that the particles explore the speckle in a self-similar, fractal manner at least over four decades in time and on length scales up to 20 times the particle radius. The requirements for fractal diffusion to be applicable are laid out, and methods to extract the fractal dimension are established