Water and molecular chaperones act as weak links of protein folding networks: energy landscape and punctuated equilibrium changes point towards a game theory of proteins

Water molecules and molecular chaperones efficiently help the protein folding process. Here we describe their action in the context of the energy and topological networks of proteins. In energy terms water and chaperones were suggested to decrease the activation energy between various local energy minima smoothing the energy landscape, rescuing misfolded proteins from conformational traps and stabilizing their native structure. In kinetic terms water and chaperones may make the punctuated equilibrium of conformational changes less punctuated and help protein relaxation. Finally, water and chaperones may help the convergence of multiple energy landscapes during protein-macromolecule interactions. We also discuss the possibility of the introduction of protein games to narrow the multitude of the energy landscapes when a protein binds to another macromolecule. Both water and chaperones provide a diffuse set of rapidly fluctuating weak links (low affinity and low probability interactions), which allow the generalization of all these statements to a multitude of networks.Comment: 9 pages, 1 figur

Stability and geometry of silica nano-ribbons (SNRs): a first-principles study

Silica based materials are attractive because of their versatility and their unique structures and properties, which have led to numerous applications of silica in a range of fields. Recently, various low-dimensional silica materials have been synthesized experimentally. Here we present a first-principles study on the geometry and stability of novel low-dimensional silica nano-ribbons (SNRs) using density-functional theory (DFT) with van der Waals interactions (optB88-vdW). SNRs of various widths with different surface groups, and with the geometry of hexagonal rings and squares, were taken into consideration. An atomically flat ribbon with mixing squares and rings is also included. The calculations showed high stability for the single layer and bilayer silica ribbons, both containing hexagonal rings. The calculations also revealed a high flexibility of silica chains. The local structure and chemical bonding were carefully analyzed. Electronic band structure calculations showed an insulating nature of the SNRs with energy gaps of about 5.0 to 6.0 eV, which are determined by nonbonding and anti-bonding O 2p states

Preparation of χ\u3csup\u3e(2)\u3c/sup\u3e-inverted waveguides with poled polymers for efficient second-harmonic generation

Modal dispersion phase-matched second harmonic generation is demonstrated in polymer-based waveguides with a nonlinear optical core consisting of two side-chain polymers with different glass-transition temperatures. For an optimized overlap integral, a step like nonlinearity profile (chi (2)-inverted structure) is required across the core thickness. The chi(2)-inverted structure is achieved by two consecutive thermally assisted poling steps above and between the respective glass-transition temperatures, with an opposite poling field in the second poling step. The achieved chi(2)-inverted structure is monitored by in- situ electro-optic measurements and proved by electro-optic and second harmonic generation thermal analysis. Conversion efficiencies up to 7%/Wcm2 were achieved in first waveguide second-harmonic generation experiments. ©2005 Copyright SPIE - The International Society for Optical Engineering

Thomas Manns „Buddenbrooks“ und der Mythos zerfallender Familien

Erhart W. Thomas Manns „Buddenbrooks“ und der Mythos zerfallender Familien. In: Brinker-von der Heyde C, Scheuer H, eds. Familienmuster – Musterfamilien. Zur Konstruktion von Familie in der Literatur. Frankfurt a. M.: Peter Lang; 2004: 161-184

Polymer-based hybrid photonic integration for flexible PIC design

Recent developments in polymer-based photonic components allow for a novel PIC design approach bridging free-space optics, integrated optics and high-speed electronics

The protein import motor of mitochondria: a targeted molecular ratchet driving unfolding and translocation

Unfolding and import of preproteins into mitochondria are facilitated by a molecular motor in which heat shock protein 70 (Hsp70) in the matrix plays an essential role. Here we present two different experimental approaches to analyze mechanisms underlying this function of Hsp70. First, preproteins containing stretches of glutamic acid (polyE) or glycine (polyG) repeats in front of folded domains were imported into mitochondria. This occurred although Hsp70 cannot pull on these stretches to unfold the folded domains, since it does not bind to polyE and polyG. Secondly, preproteins containing titin immunoglobulin (Ig)-like domains were imported into mitochondria, despite the fact that forces of >200 pN are required to mechanically unfold these domains. Since molecular motors generate forces of ∼5 pN, Hsp70 could not promote unfolding of the Ig-like domains by mechanical pulling. Our observations suggest that Hsp70 acts as an element of a Brownian ratchet, which mediates unfolding and translocation of preproteins across the mitochondrial membranes

Risk of Venous Thromboembolism Among Patients with Atopic Dermatitis: A Cohort Study in a US Administrative Claims Database

Introduction: Atopic dermatitis (AD) is associated with risk factors for venous thromboembolism (VTE). However, the risk of VTE among this population is unknown. The aim of this study was to assess the risk of VTE among adults with AD and compare the risk vs. matched non-AD controls. Methods: This retrospective study used claims data from the IBM Watson MarketScan® Commercial Claims and Encounters, Medicare Supplemental, and Medicaid databases to identify adults aged 18 years or older with AD. Incidence rates (IR) per 100 person-years (PY) of VTE were reported for three cohorts: overall AD, moderate-to-severe AD, and non-AD controls matched by age, sex, and calendar time to the overall cohort. Cox proportional hazards regression was used to estimate hazard ratios (HR) for VTE risk. Results: Overall, 198,685 patients with AD were identified. Crude VTE IRs were 0.24 for AD overall, 0.31 for moderate-to-severe AD, and 0.25 for non-AD controls. VTE risk was similar in patients with AD vs. non-AD controls (partially adjusted HR 1.00, 95% confidence interval [CI] 0.92, 1.09). VTE risk was greater in patients with moderate-to-severe AD vs. non-AD controls in partially adjusted models (HR 1.24, 95% CI 1.13, 1.36), but not after adjustment for healthcare use and VTE risk factors (HR 0.95, 95% CI 0.85, 1.07). Conclusions: AD was not an independent risk factor for VTE, and the risk of VTE among patients with AD was low. These findings provide valuable context for understanding VTE risk among patients with AD, which is particularly relevant as advanced therapies for the treatment of moderate to severe AD, such as janus kinase inhibitors, become available

3D Photonic Integrated 4x4 Multi-Mode Interference Coupler

3D photonic integration introduces a new degree of freedom in the design of photonic integrated circuits (PICs) compared to standard 2D-like structures. Novel applications such as large-scale optical switching matrices, e.g. for top-of- rack cross connect switches in data centers, benefit from the additional design flexibility due to their waveguide crossing-free architecture and compact footprint. In this work, a novel 3D 4×4 multi-mode interference coupler (MMI) based on HHI’s polymer-based photonic integration platform PolyBoard is presented. The fabrication process of the PolyBoard platform allows for the realization of vertically stacked polymer waveguide layers. Cascading two of the presented 3D 4×4 MMIs will form the building block of future large-scale 3D switching matrices. The 3D 4×4 MMI structure comprises two waveguide layers separated by a distance of 7.2 μm, with two input and two output waveguides in each layer, and a multimode interference (MMI) section in between. The vertical MMI section serves as the interconnection between the different waveguide layers and distributes the incoming light from each input waveguide across the four output ports of the 4×4 MMI. Design rules and fabrication methodology of these novel structures are presented in detail. Preliminary measurements demonstrate the proof-of-concept indicating an insertion loss below 9.3 dB, including fiber-chip coupling loss and the 6 dB intrinsic loss