Motional phase maps for estimating the effectiveness of granular dampers

This paper evaluates simple but general links between the operating dynamic motional phases and the non-linear energy dissipation characteristics of granular dampers. The Discrete Element Method is used to simulate a typical granular medium consisting of spherical particles in a cylindrical enclosure subjected to harmonic vibrations aligned both parallel and perpendicular with gravity. A set of equivalent experiments is conducted to verify the numerical model. A wide range of excitation frequency and amplitude are considered, to obtain many different motional phases, along with particle size and volume fill ratio. Granular motional phase maps are produced over amplitude-frequency plane that defines where the various motion phases are present providing rich information for the effectiveness of granular dampers. Findings show that high granular damping effectiveness is found in two distinct zones: where collective collisions with the enclosure are optimised and where fluidisation without convection is maximised. The most significant factors affecting these high effectiveness zones are identified and can be used to provide guidance for those seeking to design granular dampers to reduce vibrations in structures

(E)-N′-(2-Hydroxy­benzyl­idene)-2-(4-isobutyl­phen­yl)propanohydrazide

The title hydrazide compound, C20H24N2O2, exists in a trans configuration with respect to the acyclic C=N bond and an intra­molecular O—H⋯N hydrogen bond generates an S(6) ring motif. The mean plane through the formohydrazide unit is essentially planar [maximum deviation = 0.025 (2) Å], and forms dihedral angles of 24.45 (16) and 87.14 (16)° with the two benzene rings. In the crystal structure, inter­molecular N—H⋯O and C—H⋯O hydrogen bonds link neighbouring mol­ecules into extended chains along the c axis, which incorporate R 2 2(16) ring motifs. An inter­molecular C—H⋯π inter­action is also observed

TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. METHODS: The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. RESULTS: While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. CONCLUSIONS: Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis

Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF’s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF’s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD

The Neurotoxicity of DOPAL: Behavioral and Stereological Evidence for Its Role in Parkinson Disease Pathogenesis

BACKGROUND: The etiology of Parkinson disease (PD) has yet to be fully elucidated. We examined the consequences of injections of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite of dopamine, into the substantia nigra of rats on motor behavior and neuronal survival. METHODS/PRINCIPAL FINDINGS: A total of 800 nl/rat of DOPAL (1 µg/200 nl) was injected stereotaxically into the substantia nigra over three sites while control animals received similar injections of phosphate buffered saline. Rotational behavior of these rats was analyzed, optical density of striatal tyrosine hydroxylase was calculated, and unbiased stereological counts of the substantia nigra were made. The rats showed significant rotational asymmetry ipsilateral to the lesion, supporting disruption of dopaminergic nigrostriatal projections. Such disruption was verified since the density of striatal tyrosine hydroxylase decreased significantly (p<0.001) on the side ipsilateral to the DOPAL injections when compared to the non-injected side. Stereological counts of neurons stained for Nissl in pars compacta of the substantia nigra significantly decreased (p<0.001) from control values, while counts of those in pars reticulata were unchanged after DOPAL injections. Counts of neurons immunostained for tyrosine hydroxylase also showed a significant (p=0.032) loss of dopaminergic neurons. In spite of significant loss of dopaminergic neurons, DOPAL injections did not induce significant glial reaction in the substantia nigra. CONCLUSIONS: The present study provides the first in vivo quantification of substantia nigra pars compacta neuronal loss after injection of the endogenous toxin DOPAL. The results demonstrate that injections of DOPAL selectively kills SN DA neurons, suggests loss of striatal DA terminals, spares non-dopaminergic neurons of the pars reticulata, and triggers a behavioral phenotype (rotational asymmetry) consistent with other PD animal models. This study supports the "catecholaldehyde hypothesis" as an important link for the etiology of sporadic PD

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

The effect of particle surface roughness on granular energy dissipation performance

Granular materials can be effectively utilised to reduce structure-borne noise and structural vibrations. However, since granular damping shows non-linear characteristics and is affected by several different parameters such as particle shape, a granular damper should be designed considering the factors that may change granular energy dissipation behaviour. The particles used in a granular damper are generally assumed as having a certain geometric shape. However, particle surfaces can deviate from the pre-defined shape due to manufacturing limitations or wear during operation. This experimental study investigates the extent of particle surface distortion on the energy dissipation performance of a partially filled granular damper exposed to harmonic excitation parallel to the direction of gravity. The effect of the particle surface is evaluated over a range of amplitude and frequency conditions. Moulded and 3D printed spherical particles are used to indicate smooth and non-smooth particle shapes, respectively. In order to quantify the particle surface smoothness, a set of surface roughness measurements is carried out. A dissipated power measurement test rig is used to assess dissipative performances of smooth and non-smooth spherical particle types in a cylindrical granular damper enclosure

Influence of particle sphericity on granular dampers operating in the bouncing bed motional phase

This paper presents new research to determine the effect of particle shape on the energy dissipation in a granular damper operating in the bouncing bed motional phase. This is accomplished by conducting controlled experiments and validated Discrete Element Method (DEM) simulations for a broad collection of spheroidal particle shapes at vibration amplitudes of up to 50 g. The findings show that non-spherical particles significantly change the condition known as the “bouncing bed onset amplitude” which is the vibration amplitude at which granular damping is maximised. It is shown that the packing parameter known as the coordination number is an indicator of this change and that there is a correlation between the shear properties of the granular medium and the amplitude at which it delivers optimum energy dissipation. This paper also presents a sensitivity analysis specific to the bouncing bed phase which considers variations in particle modulus, density, restitution coefficient and friction. This shows that the observations about the effects of particle shape are valid over a broad range of conditions

Construction of motional phase maps for granular dampers

Harmonically vibrated granular media exhibit a variety of motional behaviours depending on amplitude, frequency, and vibration-to-gravity directional orientation. Motional behaviour defines the physical interactions of particles in the granular media and therefore the energy dissipation performance. A “phase map” that describes motional behaviour over broad ranges of frequency and amplitude is therefore a very useful tool in damper design. However, at present, identification of the operating motional conditions within the granular media has only been conducted by visual observation of the particles following a particle-level simulation or a specifically designed experiment. Because of this, design optimisation over a broad range of amplitude and frequency becomes costly. This paper aims to help reduce this cost through the development of approximate phase maps based on expected dissipative interactions of particles. Three-dimensional discrete element method simulations are conducted over a wide range of excitation intensities under two different vibration-to-gravity directional orientations (i.e., perpendicular, and parallel to the standard gravity direction) to allow the observation of as many motional phases as possible. The effect of particle size, volume filling ratio and particle shape on granular energy dissipation sources are also investigated