Great Potential For Further Studies Research Articles

A multihertz, kiloelectronvolt pulsed proton source from a laser irradiated continuous hydrogen cluster target

A high-repetition rate laser-driven proton source from a continuously operating cryogenic hydrogen cluster target is presented. We demonstrate a debris-free, Coulomb-explosion based acceleration in the 10s of kilo-electron-volt range with a stability of about 10% in a 5 Hz operation. This acceleration mechanism, delivering short pulse proton bursts, represents an ideal acceleration scheme for various applications, for example, in materials science or as an injector source in conventional accelerators. Furthermore, the proton energy can be tuned by varying the laser and/or cluster parameters. 3D numerical particle-in-cell simulations and an analytical model support the experimental results and reveal great potential for further studies, scaling up the proton energies, which can be realized with a simple modification of the target.

Discovery and structure-activity relationship of novel diphenylthiazole derivatives as BTK inhibitor with potent activity against B cell lymphoma cell lines

By the analysis of different binding modes with Bruton's tyrosine kinase (BTK), series of novel diphenylthiazole derivatives were rationally designed, synthesized and characterized. Biologically evaluation in biochemistry and cellular assay indicated that, compounds 5m, 5o, 6b, 6c, 6g, 6i, 7h, 7i, 7k, 7m, 7n, 7o and 7s exhibited improved potency against Ramos cell (IC50 = 1.36–8.60 μM) and Raji cell (IC50 = 1.20–14.04 μM) as compared with ibrutinib (IC50 = 14.69 and 15.99 μM, respectively). Especially, compounds 7m and 7n showed 10-time improved potency against Ramos cell viability over ibrutinib. Compound 6b improved 13-fold activity against Raji cell viability than ibrutinib. In addition, active compound 7o potently inhibited C481S mutant BTK with IC50 value of 0.061 μM. Apoptosis analysis of both Ramos and Raji cells indicated that 7o was remarkably more potent than CGI-1746 and ibrutinib. Compound 7o potently inhibited BTK Y223 phosphorylation in Raji cells, and arrested cell cycle progression in the G0/G1 phase in Raji and Ramos cells. This study expanded the structural diversity of BTK inhibitors and compound 7o was discovered as an active lead inhibitor with great potential for further studies.

The role of sodium oleate (NaOL) in the magnetic separation of pentlandite from serpentine using magnetic coating

The efficient separation of pentlandite from serpentine remains a challenging issue in the processing of nickel sulfide ores. In this study, selective magnetic coating-magnetic separation was employed to separate the pentlandite from serpentine with adding NaOL as a coagulant, which is different from the conventional flotation. The results indicate that it was very effective for their separation. Furthermore, the role of NaOL in the separation was evaluated in detail by means of adsorption tests, zeta potential measurements, Fourier transform infrared (FTIR) spectra analyses, solution chemistry calculations X-ray photoelectron (XPS) spectra analyses, and scanning electron microscopy-energy dispersive spectra (SEM-EDS) analyses. It turns out that NaOL can adsorb selectively onto the surfaces of pentlandite and magnetite through the Ni and Fe sites (serpentine was pre-depressed by sodium hexametaphosphate (NaHMP)) and form the hydrophobic surfaces between the two minerals. As a result, the pentlandite surface was selectively coated by the magnetite fines and then was separated from serpentine using magnetic separation. Therefore, our results provide an alternative technology for their separation and exhibit great potential for further study and applications.

An integrative approach combining ion mobility mass spectrometry, X-ray crystallography, and nuclear magnetic resonance spectroscopy to study the conformational dynamics of α1 -antitrypsin upon ligand binding.

Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whereas ion mobility (IM)-MS can report on conformational behavior of specific states. We used IM-MS to study a conformationally labile protein (α1-antitrypsin) that undergoes pathological polymerization in the context of point mutations. The folded, native state of the Z-variant remains highly polymerogenic in physiological conditions despite only minor thermodynamic destabilization relative to the wild-type variant. Various data implicate kinetic instability (conformational lability within a native state ensemble) as the basis of Z α1-antitrypsin polymerogenicity. We show the ability of IM-MS to track such disease-relevant conformational behavior in detail by studying the effects of peptide binding on α1-antitrypsin conformation and dynamics. IM-MS is, therefore, an ideal platform for the screening of compounds that result in therapeutically beneficial kinetic stabilization of native α1-antitrypsin. Our findings are confirmed with high-resolution X-ray crystallographic and nuclear magnetic resonance spectroscopic studies of the same event, which together dissect structural changes from dynamic effects caused by peptide binding at a residue-specific level. IM-MS methods, therefore, have great potential for further study of biologically relevant thermodynamic and kinetic instability of proteins and provide rapid and multidimensional characterization of ligand interactions of therapeutic interest.PDB Code(s): 4PYW

DISTRIBUTION OF CORDED WARE IN THE AREAS NORTH OF THE GULF OF FINLAND – AN UPDATE

Research of the Corded Ware phenomenon in the areas north of the Gulf of Finland has been scanty during the last several decades, and consequently outdated views, distribution maps, and numbers of finds still prevail. This paper aims to update data on the distribution of Corded Ware in Finland and Karelia (Russia), and to discuss the results in the context of the old research tradition, and to highlight some aspects of the northern Corded Ware. The current data shows that there are ca 360 Corded Ware settlement sites, 30 burial sites and over 1300 stray find locations of battle axes in the research area. Contrary to much of Europe the areas north of the Gulf of Finland accommodate a large amount of settlement sites but only a few burials. No singular reason for this can be pointed out but the most likely explanations include modest later land use at the locations, factors related to archaeological visibility and research methods, and also to local Corded Ware cultural practices. Despite certain shortcomings the northern Corded Ware material is exceptional and holds a great potential for further studies of the phenomenon, especially its domestic sphere and everyday practices.

Uncovering landscape values and micro-geographies of meanings with the go-along method

Benefiting from recent developments in landscape anthropology, the objective of this research is to explore the landscape experiences and values of residents of a small city in the Greater Montreal area (Quebec, Canada). Given the lack of local knowledge, there is an urgent need for developing innovative and productive methods for revealing the implicit meanings attached to places and for facilitating community input and participation. Drawn from the mobile methodologies paradigm, the so-called go-along method, which consists of conducting on-site and mobile interviews, was chosen for its potential to generate place-bound narratives and reveal landscape values. While showing room for improvement, the go-along method proved to be original and productive for reaching the objectives of our research as it allows for revealing micro-geographies of meanings. In the analysis stage, we combined all the data produced into one single comprehensive interface so as to create a nexus of narrative, geographic and visual data. The results show that the residents’ knowledge is undeniably rich and relevant for understanding the diverse values which people have of landscapes. The exercise of bringing locals to express their perceptions and preoccupations in regards to their living environment thus constitutes a valuable complement to the traditional expert perspective. As such, the go-along method merits becoming an integral part of land management practices and offers great potential for further studies in landscape and urban planning.

Identification of Nonlinear Systems Using Parallel Laguerre-NN Model

In this paper, a nonlinear system identification framework using parallel linear-plus-neural networks model is developed. The framework is established by combining a linear Laguerre filter model and a nonlinear neural networks (NN) model in a parallel structure. The main advantage of the proposed parallel model is that by having a linear model as the backbone of the overall structure, reasonable models will always be obtained. In addition, such structure provides great potential for further study on extrapolation benefits and control. Similar performance of proposed method with other conventional nonlinear models has been observed and reported, indicating the effectiveness of the proposed model in identifying nonlinear systems.

In vitro activities of ABT-773 and other antimicrobials against human mycoplasmas.

The in vitro susceptibilities of 103 Mycoplasma pneumoniae isolates, 14 Mycoplasma hominis isolates, 12 Mycoplasma fermentans isolates, and 24 Ureaplasma species to ABT-773, an investigational ketolide, and seven other agents were determined. For M. pneumoniae, the ABT-773 MIC at which 90% of isolates are inhibited (MIC(90); <or=0.001 microg/ml) was comparable to those of azithromycin, clarithromycin, and erythromycin and at least 128-fold lower than those of levofloxacin, gatifloxacin, moxifloxacin, and doxycycline. For M. fermentans, the ABT-773 MIC(90) (<or=0.008 microg/ml) was 2- to 128-fold lower than those of all other agents tested. For M. hominis, the ABT-773 MIC(90) (0.031 microg/ml) was equivalent to that of moxifloxacin, 2-fold lower than those of gatifloxacin and clindamycin, and 16-fold lower than that of levofloxacin. ABT-773 was equally active against doxycycline-susceptible and doxycycline-resistant organisms. The ABT-773 MICs (0.016 microg/ml) for Ureaplasma species were the lowest of those of any drug tested. The MIC(90) was 4- to 64-fold lower than those of clarithromycin, azithromycin, and erythromycin and >or=16-fold lower than those of all three fluoroquinolones. Minimal bactericidal concentrations determined for a subgroup of organisms were <or=0.063 micro g/ml for M. pneumoniae and 0.25 microg/ml for M. fermentans, but they were several dilutions higher for M. hominis and Ureaplasma spp. ABT-773 has great potential for further study for the treatment of infections due to mycoplasmas and ureaplasmas.

Temporal variation in tooth fracture among Rancho La Brea dire wolves

ABSTRACT Canis dirus preserved in the late Pleistocene Rancho La Brea tar seep deposits display a remarkably high incidence of teeth broken in life as compared with modern species. This might reflect greater carcass utilization in the Pleistocene relative to the present. Here we compare tooth fracture frequencies in C. dirus between two localities at Rancho La Brea, Pit 13 (about 15 ka) and Pit 61/67 (about 12 ka). Results indicate that Pit 13 C. dirus exhibited heavier tooth wear and fractured their teeth about three times more often than those of the younger Pit 61/67. This might reflect a difference in diet between the two periods or a greater preservation of older individuals (which are more likely to have broken teeth) in Pit 13. To test for differences in the mortality profiles of the two pits, we estimated individual age C. dirus from pulp cavity dimensions of lower canine teeth, as measured from radiographs of preserved mandibles. We first verified the validity of the approach using a sample of extant Canis latrans that had been previously aged using cementum counts. Pulp cavity analysis of the C. dirus indicated no significant difference between pits in the age structure of the preserved populations. Consequently, it appears that feeding behavior of C. dirus differed in the latest Pleistocene in that bone consumption declined. Pulp cavity analysis has great potential for further studies of population parameters, such as mortality profiles, of extinct carnivorans. It is easy, non-destructive, and provides a continuum of age values rather than discrete categories.