Validation of ankle strength measurements by means of a hand-held dynamometer in adult healthy subjects

Uniaxial Hand-Held Dynamometer (HHD) is a low-cost device widely adopted in clinical practice to measure muscle force. HHD measurements depend on operator’s ability and joint movements. The aim of the work is to validate the use of a commercial HHD in both dorsiflexion and plantarflexion ankle strength measurements quantifying the effects of HHD misplacements and unwanted foot’s movements on the measurements. We used an optoelectronic system and a multicomponent load cell to quantify the sources of error in the manual assessment of the ankle strength due to both the operator’s ability to hold still the HHD and the transversal components of the exerted force that are usually neglected in clinical routine. Results showed that foot’s movements and angular misplacements of HHD on sagittal and horizontal planes were relevant sources of inaccuracy on the strength assessment. Moreover, ankle dorsiflexion and plantarflexion force measurements presented an inaccuracy less than 2% and higher than 10%, respectively. In conclusion, the manual use of a uniaxial HHD is not recommend ed for the assessment of ankle plantarflexion strength; on the contrary, it can be allowed asking the operator to pay strong attention to the HHD positioning in ankle dorsiflexion strength measurements

Development of immunoassays for the investigation of peptide antibody interactions in array format

Antibodies perform a variety of important tasks in the immune system to protect us from diseases. They are trained to specifically target pathogens, which might be toxins, bacteria or viruses. However, they can also harm us by erroneously mark endogenous structures for degradation, which contributes to autoimmune diseases. Studying the immune response by determining, which antibodies are amplified during a successful immune reaction, and which part of the pathogen neutralizing antibodies are binding to, would help to develop new vaccine candidates and contribute to the common knowledge of the underlying mechanism. In addition to the information, what antibodies specifically bind to, it is of interest, in which concentration they are available in the blood and with which affinity they bind their target. Peptide arrays provide an ideal platform for the study of antibody-protein interactions, with the peptides mimicking antibody targets. Using a minute sample volume, several thousand peptides can be examined simultaneously. To study identified antibody-peptide interactions in terms of kinetics, on-line measurements in microfluidic channels, so called continuous flow assays, have to be performed. This work is divided into two main parts, covering the screening for epitopes and the development of an experimental setup to characterize the peptide-epitope interaction. In the first part, the immune response of healthy European individuals towards the tetanus, diphtheria and pertussis vaccination and two established epitopes (PALT(A)xET and PEFxGSxP) originating from enterovirus and probably Staphylococcus aureus, was investigated using peptide arrays. Vaccination specific antibodies were identified by determining their linear epitope in amino acid resolution. Therefore, the linear amino acid sequence of tetanus, diphtheria and pertussis toxin was synthesized in fragments (peptides) in array format onto a solid substrate and incubated with serum of 19 healthy European individuals. For the tetanus toxin, an epitope was identified (929ExxEVIVxK937), which was targeted by 8 out of 19 individuals. The amino acids crucial for antibody binding (the `antibody fingerprint\u27), were determined for this epitope, by substitution analysis. In a substitution, every amino acid is substituted by all of the other 19 amino acids while the rest of the sequence remains conserved. The antibody fingerprint can be determined, since the substitution of crucial amino acids leads to the loss of antibody binding. The `antibody fingerprints\u27 were found to be strongly conserved among individuals for the three investigated linear epitopes (929ExxEVIVxK937, PALT(A)xET and PEFxGSxP). Further, it was further verified by affinity batch chromatography and ELISA, that antibodies binding the identified epitope originating from the sequence of the tetanus toxin, also bind to the native tetanus toxin. This indicates, that the identified epitope is tetanus specific. For the mapping of the diphtheria toxin linear and cyclic peptides of different length were applied. Five prominent regions were identified in the mapping of cyclic peptides using pooled sera. For the pertussis toxin, three regions of interest could be identified, which also were reported in literature for their ability to induce toxin recognizing antibodies in rodents. However, no distinct antibody fingerprints could be determined for a variety of peptides covering the identified regions. Altogether, the homology in between fingerprints of different individuals targeting the same epitope (929ExxEVIVxK937, PALT(A)xET and PEFxGSxP) is striking, given the randomness of antibody formation. In the second part, an experimental setup was realized to incubate peptide arrays in an automated fashion in microfluidic channels to perform continuous flow assays. The interactions of fluorescently labelled antibodies with the peptides can be characterized via the detection of fluorescence using an epi-fluorescence setup design. For this purpose, fluorescence images are taken at short intervals and the increase of the fluorescence signal over time is determined. The fluorescence intensity of the fluorophore DL550 was found to be temperature dependent under assay conditions. However, for a constant temperature (24 +/- 0.1°C), the intensity can be approximated as being stable for 50 min of continuous exposure. For the fast production of peptide arrays needed during preliminary experiments, spotting of pre-synthesized peptides (bearing a C-terminal cysteine) on 3D-Maleimide surfaces was established. To have an additional label free imaging method at hand, VSI was established for the quality control of peptide arrays. Height profiles obtained by VSI did not significantly deviate from AFM measurements. Spots down to approximately 1 nm height can be resolved on a comparable large field of view of (1.74 x 1.31) mm within a minute. Two different approaches for the integration of peptide arrays into a microfluidic channel have been investigated. Molding channel structures in PDMS is a fast technique, but the channel design was determined to be restricted to have a minimum distance between channels to prevent leakage. By adding up to 2% of graphene particles to the PDMS prior to polymerization, the background fluorescence of PDMS was reduced by approximately 70%. The fabricated channel proved to be leak-tight up to a flow of 3 ml/min when screwed to a torque of 10 N/cm. However, the clamping led to a deformation of the PDMS channels. This results in non-homogeneous channel cross sections and is thus not apt for a concentration analysis, which requires a constant channel height. The second type of channel fabrication investigated is adhesive layer bonding using Ordyl SY355. It is the first approach to bond a glass substrate to a functionalized surface, used for micro array fabrication. This method has the potential to make microarrays available to other microsystem technologies. Fluidic in- and outlets are laser drilled into a glass substrate and the adhesive layer is applied and structured lithographically to form the walls of the channel. The parameter window for this lithographic process was determined to be quite broad with exposure doses ranging from (150-220) mJ/cm² and bonding pressures ranging from (220-735) N/cm². Process temperatures over 100°C were found to be critical, since damage of the functionalized surface occurred. The magnitude of fracture strength of the bond was estimated by random pulling tests to be about 305 +/- 50 N/cm². This results in a theoretical pressure resistance of ~ 4.9 bar and proved to be leak proof for a flow rate of up to 750 mL/min. The designed experimental setup, including the integration of peptide arrays into microfluidic channels, was shown to fulfill the requirements for performing continuous flow assays on peptide arrays. By conducting the calibration of fluorescence signal intensity to antibody concentration in a future project, the setup will be ready to further determine antibody titers

Exact spin polarization of massive and massless particles in relativistic fluids at global equilibrium

We present the exact form of the spin polarization vector and the spin density matrix of massive and massless free particles of any spin and helicity at general global equilibrium in a relativistic fluid with non-vanishing thermal vorticity, thus extending the known expression at the linear order. The exact form is obtained by means of the analytic continuation of the relativistic density operator to imaginary thermal vorticity and the resummation of the obtained series. The phenomenological implications for the polarization of the $\Lambda$ hyperon in relativistic heavy-ion collisions are addressed.Comment: 14 pages + 3 pages appendices. 2 figure

Erectile dysfunction and its management in patients with diabetes mellitus

Diabetes can be described as a syndrome of multiple closely related conditions induced by a chronic state of hyperglycaemia resulting from defective insulin secretion, insulin action or both. Chronic complications associated with diabetes (including neuropathy, vascular disease, nephropathy and retinopathy) are common, and of these, erectile dysfunction (ED) deserves special attention. ED and its correlation with cardiovascular disease require careful evaluation and appropriate treatment. PDE5 inhibitors (PDE5is) are an important tool for the treatment of ED, with new drugs coming onto the market since the late 90s. This review offers an overview of PDE5is and their use in treating ED in diabetes. We underline the differences between different types of PDE5i, focusing on available doses, duration of action, T ½, side effects and selectivity profiles in relation to patients with diabetes. We also discuss the link between diabetes and ED in presence of various associated cofactors (obesity, hypertension and its pharmacological treatments, atherosclerosis, hyperhomocysteinaemia, neuropathy, nephropathy, hypogonadism and depression). Finally a number of past and ongoing clinical trials on the use of PDE5is in patients with diabetes are presented to offer an overview of the appropriate treatment of ED in this condition

The Economic Consequences of the Covid-19 First Wave and the New International Scenarios. An Historical Dimension

The Covid-19 crisis is urging scholars to ponder the perspectives of the globalization process which started at the end of the XXth Century. The pandemic is creating a sense of insecurity and uncertainty which has few precedents in the current age, pervading wider and wider sectors of the population. Moving from the analysis of the first wave of the pandemic (March 2020), this essay proposes a model of analysis of the effects of the pandemic by framing the economic emergency produced by it from a historical and theoretical perspective. The paper will also try to indicate the traits and the model of a new economic paradigm: the birth of a new globalization that would surely feature competitions between its biggest geoeconomics areas, but that would also offer the opportunity to promote novel perspectives for development and to achieve a brand-new convergence between the private and public interest

Extraction of the microscopic properties of quasi-particles using deep neural networks

We use deep neural networks (DNN) to obtain the microscopic characteristics of partons in terms of dynamical degrees of freedom on the basis of an off-shell quasiparticle description. We aim to infer masses and widths of quasi-gluons, up/down, and strange quarks using constraints on the macroscopic thermodynamic observables obtained by the first-principles calculations lattice QCD. In this work, we use 3 independent dimensionless thermodynamic observables from lQCD for minimization. First, we train our DNN using the DQPM (Dynamical QuasiParticle Model) Ansatz for the masses and widths. Furthermore, we use the DNN capabilities to generalize this Ansatz, to evaluate which quasiparticle characteristics are desirable to describe different thermodynamic functions simultaneously. To evaluate consistently the microscopic properties obtained by the DNN in the case of off-shell quarks and gluons, we compute transport coefficients using the spectral function within Kubo-Zubarev formalism in different setups. In particular, we make a comprehensive comparison in the case of the dimensionless ratios of shear viscosity over entropy density $\eta/s$ and electric conductivity over temperature $\sigma_Q/T$, which provide additional constraints for the parameter generalization of the considered models.Comment: 22 pages, 20 figure

The Economic Consequences of the Covid-19 First Wave and the New International Scenarios. An Historical Dimension

The Covid-19 crisis is urging scholars to ponder the perspectives of the globalization process which started at the end of the XXth Century. The pandemic is creating a sense of insecurity and uncertainty which has few precedents in the current age, pervading wider and wider sectors of the population. Moving from the analysis of the first wave of the pandemic (March 2020), this essay proposes a model of analysis of the effects of the pandemic by framing the economic emergency produced by it from a historical and theoretical perspective. The paper will also try to indicate the traits and the model of a new economic paradigm: the birth of a new globalization that would surely feature competitions between its biggest geoeconomics areas, but that would also offer the opportunity to promote novel perspectives for development and to achieve a brand-new convergence between the private and public interest