Investigation of hydrostatic fluid forces in varying clearance turbomachinery seals

Varying clearance, rotor-following seals are a key technology for meeting the demands of increased machine flexibility for conventional power units. These seals follow the rotor through hydrodynamic or hydrostatic mechanisms. Forward-facing step (FFS) and Rayleigh step designs are known to produce positive fluid stiffness. However, there is very limited modeling or experimental data available on the hydrostatic fluid forces generated from either design. A quasi-one-dimensional (1D) method has been developed to describe both designs and validated using test data. Tests have shown that the FFS and the Rayleigh step design are both capable of producing positive film stiffness and there is little difference in hydrostatic force generation between the two designs. This means any additional hydrodynamic features in the Rayleigh step design should have a limited effect on hydrostatic fluid stiffness. The analytical model is capable of modeling both the inertial fluid forces and the viscous fluid losses, and the predictions are in good agreement with the test data

Detailed study on stiffness and load characteristics of film-riding groove types using design of experiments

In the application of film-riding sealing technology, there are various groove features that can be used to induce hydrodynamic lift. However, there is little guidance in selecting the relative parameter settings in order to maximize hydrodynamic load and fluid stiffness. In this study, two groove types are investigated—Rayleigh step and inclined groove. The study uses a design of experiments approach and a Reynolds equation solver to explore the design space. Key parameters have been identified that can be used to optimize a seal design. The results indicate that the relationship between parameters is not a simple linear relationship. It was also found that higher pressure drops hinder the hydrodynamic load and stiffness of the seal suggesting an advantage for using hydrostatic load support in such conditions

The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain

The function of the intrinsically disordered Unique domain of the Src family of tyrosine kinases (SFK), where the largest differences between family members are concentrated, remains poorly understood. Recent studies in c-Src have demonstrated that the Unique region forms transient interactions, described as an intramolecular fuzzy complex, with the SH3 domain and suggested that similar complexes could be formed by other SFKs. Src and Lyn are members of a distinct subfamily of SFKs. Lyn is a key player in the immunologic response and exists in two isoforms originating from alternative splicing in the Unique domain. We have used NMR to compare the intramolecular interactions in the two isoforms and found that the alternatively spliced segment interacts specifically with the so-called RT-loop in the SH3 domain and that this interaction is abolished when a polyproline ligand binds to the SH3 domain. These results support the generality of the fuzzy complex formation in distinct subfamilies of SFKs and its physiological role, as the naturally occurring alternative splicing modulates the interactions in this complex

A Novel Approach for Bisphosphonates: Ionic Liquids and Organic Salts from Zoledronic Acid

Novel ionic liquids and organic salts based on mono- or dianionic zoledronate and protonated superbases, choline and n-alkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Among the zoledronate-based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C3 OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.info:eu-repo/semantics/publishedVersio

Intramolecular fuzzy interactions involving intrinsically disordered domains

Structural disorder is an essential ingredient for function in many proteins and protein complexes. Fuzzy complexes describe the many instances where disorder is maintained as a critical element of protein interactions. In this minireview we discuss how intramolecular fuzzy interactions function in signaling complexes. Focussing on the Src family of kinases, we argue that the intrinsically disordered domains that are unique for each of the family members and display a clear fingerprint of long range interactions in Src, might have critical roles as functional sensor or effectors and mediate allosteric communication via fuzzy interactions

A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125

The activity of RING ubiquitin ligases (E3s) depends on an interaction between the RING domain and ubiquitin conjugating enzymes (E2), but posttranslational events or additional structural elements, yet largely undefined, are frequently required to enhance or regulate activity. Here, we show for the ubiquitin ligase RNF125 that, in addition to the RING domain, a C2HC Zn finger (ZnF) is crucial for activity, and a short linker sequence (Li2(120-128)) enhances activity. The contribution of these regions was first shown with truncated proteins, and the essential role of the ZnF was confirmed with mutations at the Zn chelating Cys residues. Using NMR, we established that the C2HC ZnF/Li2(120-128) region is crucial for binding of the RING domain to the E2 UbcH5a. The partial X-ray structure of RNF125 revealed the presence of extensive intramolecular interactions between the RING and C2HC ZnF. A mutation at one of the contact residues in the C2HC ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Thus, we identified the structural basis for an essential role of the C2HC ZnF and conclude that this domain stabilizes the RING domain, and is therefore required for binding of RNF125 to an E2

A myristoyl binding site in the SH3 domain modulates c-Src membrane anchoring

The c-Src oncogene is anchored to the cytoplasmic membrane through its N-terminal myristoylated SH4 domain. This domain is part of an intramolecular fuzzy complex with the SH3 and Unique domains. Here we show that the N-terminal myristoyl group binds to the SH3 domain in the proximity of the RT loop, when Src is not anchored to a lipid membrane. Residues in the so-called Unique Lipid Binding Region modulate this interaction. In the presence of lipids, the myristoyl group is released from the SH3 domain and inserts into the lipid membrane. The fuzzy complex with the SH4 and Unique domains is retained in the membrane-bound form, placing the SH3 domain close to the membrane surface and restricting its orientation. The apparent affinity of myristoylated proteins containing the SH4, Unique, and SH3 domains is modulated by these intramolecular interactions, suggesting a mechanism linking c-Src activation and membrane anchoring

Farseer-NMR: automatic treatment, analysis and plotting of large, multi-variable NMR data

We present Farseer-NMR (https ://git.io/vAueU), a software package to treat, evaluate and combine NMR spectroscopic data from sets of protein-derived peaklists covering a range of experimental conditions. The combined advances in NMR and molecular biology enable the study of complex biomolecular systems such as flexible proteins or large multibody complexes, which display a strong and functionally relevant response to their environmental conditions, e.g. the presence of ligands, site-directed mutations, post translational modifications, molecular crowders or the chemical composition of the solution. These advances have created a growing need to analyse those systems' responses to multiple variables. The combined analysis of NMR peaklists from large and multivariable datasets has become a new bottleneck in the NMR analysis pipeline, whereby information-rich NMR-derived parameters have to be manually generated, which can be tedious, repetitive and prone to human error, or even unfeasible for very large datasets. There is a persistent gap in the development and distribution of software focused on peaklist treatment, analysis and representation, and specifically able to handle large multivariable datasets, which are becoming more commonplace. In this regard, Farseer-NMR aims to close this longstanding gap in the automated NMR user pipeline and, altogether, reduce the time burden of analysis of large sets of peaklists from days/weeks to seconds/minutes. We have implemented some of the most common, as well as new, routines for calculation of NMR parameters and several publication-quality plotting templates to improve NMR data representation. Farseer-NMR has been written entirely in Python and its modular code base enables facile extension

From Dusty Filaments to Cores to Stars: An Infrared Extinction Study of Lupus 3

We present deep NIR observations of a dense region of Lupus 3 obtained with ESO's NTT and VLT. Using the NICE method we construct a dust extinction map of the cloud, which reveals embedded globules, a dense filament, and a dense ring structure. We derive dust column densities and masses for the entire cloud and for the individual structures therein. We construct radial extinction profiles for the embedded globules and find a range of profile shapes from relatively shallow profiles for cores with low peak extinctions, to relatively steep profiles for cores with high extinction. Overall the profiles are similar to those of pressure truncated isothermal spheres of varying center-to-edge density contrast. We apply Bonnor-Ebert analysis to compare the density profiles of the embedded cores in a quantitative manner and derive physical parameters such as temperatures, central densities, and external pressures. We examine the stability of the cores and find that two cores are likely stable and two are likely unstable. One of these latter cores is known to harbor an active protostar. Finally, we discuss the relation between an emerging cluster in Lupus 3 and the ring structure identified in our extinction map. Assuming that the ring is the remnant of the core within which the cluster originally formed we estimate that a star formation efficiency of ~ 30% characterized the formation of the small cluster. Our observations of Lupus 3 suggest an intimate link between the structure of a dense core and its state of star forming activity. The dense cores are found to span the entire range of evolution from a stable, starless core of modest central concentration, to an unstable, star-forming core which is highly centrally concentrated, to a significantly disrupted core from which a cluster of young stars is emerging.Comment: Accepted for publication in the Astrophysical Journal. Go to http://cfa-www.harvard.edu/~clada/ or http://cfa-www.harvard.edu/~pteixeir/ a version with higher resolution figure

Ancient mitochondrial genomes from the Argentinian Pampas inform the early peopling of the Southern Cone of South America

The Southern Cone of South America (SCSA) is a key region for investigations about the peopling of the Americas. However, little is known about the eastern sector, the Argentinian Pampas. We analyzed 18 mitochondrial genomes?7 of which are novel?from human skeletal remains from 3 Early to Late Holocene archaeological sites. The Pampas present a distinctive genetic makeup compared to other Middle to Late Holocene pre-Columbian SCSA populations. We also report the earliest individuals carrying SCSA-specific mitochondrial haplogroups D1j and D1g fromEarly andMiddle Holocene, respectively. Using these deep calibration time points in Bayesian phylogenetic reconstructions, we suggest that the first settlers of the Pampas were part of a single and rapid dispersal 15,600 years ago. Finally, we propose that present-day genetic differences between the Pampas and the rest of the SCSA are due to founder effects, genetic drift, and a partial population replacement 9,000 years ago.Fil: Roca Rada, Xavier. Centre For Ancient Dna, University Of Adelaide; AustraliaFil: Politis, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Messineo, Pablo Geronimo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Scheifler, Nahuel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Scabuzzo, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Entre Ríos. Universidad Nacional de Entre Ríos. Centro de Investigaciones y Transferencia de Entre Ríos; ArgentinaFil: Gonzalez, Mariela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano. Universidad Nacional del Centro de la Provincia de Buenos Aires. Investigaciones Arqueológicas y Paleontológicas del Cuaternario Pampeano; ArgentinaFil: Harkins, Kelly M.. University of California; Estados UnidosFil: Reich, David. Harvard Medical School; Estados UnidosFil: Souilmi, Yassine. University of Adelaide; AustraliaFil: Teixeira, Joao C. T.. University of Adelaide; AustraliaFil: Llamas, Bastien. University of Adelaide; AustraliaFil: Fehren Schmitz, Lars. University of California; Estados Unido