13C NMR spectra of 3-substituted phlorophenone compounds

The ¹³C NMR spectra of a series of 3-allyl-, 3-prenyl- and 3-benzyl-phlorophenone compounds are reported. Relative substituent effects are discussed.     

Enhancement of finite Reynolds number effects: Inner-outer sublayer interaction in the turbulent boundary layer

Residual Reynolds number effects in the established data for the velocity profile in turbulent boundary layers (and in pipe or channel flows) are found to be remarkably large. We combine two eddy-viscosity models (with overlapping validity in the inertial sublayer) and show (both analytically and numerically) that this enhancement (which involves a viscous correlation length) arises from inner-outer sublayer interaction.     

A unified treatment of single component replacement models

In this paper we discuss a general framework for single component replacement models. This framework is based on the regenerative structure of these models and by using results from renewal theory a unified presentation of the discounted and average finite and infinite horizon cost models is given. Finally, some well-known replacement models are discussed, and making use of the previous results an easy derivation of their cost functions is presented.     

On the path integral for diffusion in curved spaces

The Onsager-Machlup Lagrangian for diffusion processes in curved spaces is determined by evaluating the covariant path integral by means of a spectral analysis of smooth trajectories in Riemannian normal coordinates. The Lagrangian involves a novel curvature scalar potential term $\text{v=?}\text{(}\text{1}\text{8}\text{)}\text{R}$. The present treatment replaces an earlier one.     

Rayleigh curve and coercive force of thin MnBi films

Statistical Rayleigh-curve theory is applied to thin evaporated MnBi films in order to obtain information concerning the density of wall pinning centra. The treatment results in a prediction of the coercive forceH _c and the average distance between adjacent wall pinning centra, 2L ₀. The coercive forceH _cis also measured experimentally. The results of the two methods are in good agreement with each other. The influence of dislocations on the coercive force is discussed briefly.     

A functional Stieltjes measure and generalized diffusion processes

The sum over paths for a generalized Wiener diffusion process has been presented in a previous paper on the basis of the concept of time-local gaussian processes. This well-defined functional sum leads to a functional integral for the probability of passing from an initial state to some final state of the system. A mathematical ambiguity remained in the freedom to choose the diffusion function in the measure anywhere between the so-called prepoint for each infinitesimal transition. In the present paper we will demonstrate, for the generalized diffusion process, how a logical extension of functional integration in the sense of Stieltjes quite naturally leads to an unambiguous formulation which has the special and interesting property of being form-invariant under nonlinear transformations according to the rules of ordinary differential calculus.     

Activity‐Based Probes for 15‐Lipoxygenase‐1

Human 15‐lipoxygenase‐1 (15‐LOX‐1) plays an important role in several inflammatory lung diseases, such as asthma, COPD, and chronic bronchitis, as well as various CNS diseases, such as Alzheimer's disease, Parkinson's disease, and stroke. Activity‐based probes of 15‐LOX‐1 are required to explore the role of this enzyme further and to enable drug discovery. In this study, we developed a 15‐LOX‐1 activity‐based probe for the efficient activity‐based labeling of recombinant 15‐LOX‐1. 15‐LOX‐1‐dependent labeling in cell lysates and tissue samples was also possible. To mimic the natural substrate of the enzyme, we designed activity‐based probes that covalently bind to the active enzyme and include a terminal alkene as a chemical reporter for the bioorthogonal linkage of a detectable functionality through an oxidative Heck reaction. The activity‐based labeling of 15‐LOX‐1 should enable the investigation and identification of this enzyme in complex biological samples, thus opening up completely new opportunities for drug discovery.     

Histone Deacetylase 3-Directed PROTACs Have Anti-inflammatory Potential by Blocking Polarization of M0-like into M1-like Macrophages

Macrophage polarization plays a crucial role in inflammatory processes. The histone deacetylase 3 (HDAC3) has a deacetylase-independent function that can activate pro-inflammatory gene expression in lipopolysaccharide-stimulated M1-like macrophages and cannot be blocked by traditional small-molecule HDAC3 inhibitors. Here we employed the proteolysis targeting chimera (PROTAC) technology to target the deacetylase-independent function of HDAC3. We developed a potent and selective HDAC3-directed PROTAC, P7 , which induces nearly complete HDAC3 degradation at low micromolar concentrations in both THP-1 cells and human primary macrophages. P7 increases the anti-inflammatory cytokine secretion in THP-1-derived M1-like macrophages. Importantly, P7 decreases the secretion of pro-inflammatory cytokines in M1-like macrophages derived from human primary macrophages. This can be explained by the observed inhibition of macrophage polarization from M0-like into M1-like macrophage. In conclusion, we demonstrate that the HDAC3-directed PROTAC P7 has anti-inflammatory activity and blocks macrophage polarization, demonstrating that this molecular mechanism can be targeted with small molecule therapeutics.     

Role of tension and twist in single-molecule DNA condensation

Using magnetic tweezers, we study in real time the condensation of single DNA molecules under tension. We find that DNA condensation occurs via discrete nucleated events. By measuring the influence of an imposed twist, we show that condensation is initiated by the formation of a plectonemic supercoil. This demonstrates a strong interplay between the condensation transition and externally imposed mechanical constraints.