Intranasal Mice Model to Study the role of Bordetella pertussis antigens in Immunity

699-702Pertussis known as whooping cough is a highly contagious disease. Whole cell pertussis vaccine is the most economical and effective strategy for preventing and controlling pertussis. The efficacy of whole cell vaccine is ascertained most commonly by intracerebral challenge assay, but it does not reflect the true efficacy of vaccine as Pertussis essentially is a respiratory disease. Therefore, in order to mimic the natural infection, intranasal challenge model in mice was developed. In intranasal challenge assay mice were immunized with vaccine and challenged through intranasal route. Mice lungs were dissected and examined for bacterial count. The degree of count was related to efficacy of vaccine, higher count indicated low efficacy and low count pointed to better efficacy

Disclination vortices in elastic media

The vortex-like solutions are studied in the framework of the gauge model of disclinations in elastic continuum. A complete set of model equations with disclination driven dislocations taken into account is considered. Within the linear approximation an exact solution for a low-angle wedge disclination is found to be independent from the coupling constants of the theory. As a result, no additional dimensional characteristics (like the core radius of the defect) are involved. The situation changes drastically for 2\pi vortices where two characteristic lengths, l_\phi and l_W, become of importance. The asymptotical behaviour of the solutions for both singular and nonsingular 2\pi vortices is studied. Forces between pairs of vortices are calculated.Comment: 13 pages, published versio

An elastoplastic theory of dislocations as a physical field theory with torsion

We consider a static theory of dislocations with moment stress in an anisotropic or isotropic elastoplastical material as a T(3)-gauge theory. We obtain Yang-Mills type field equations which express the force and the moment equilibrium. Additionally, we discuss several constitutive laws between the dislocation density and the moment stress. For a straight screw dislocation, we find the stress field which is modified near the dislocation core due to the appearance of moment stress. For the first time, we calculate the localized moment stress, the Nye tensor, the elastoplastic energy and the modified Peach-Koehler force of a screw dislocation in this framework. Moreover, we discuss the straightforward analogy between a screw dislocation and a magnetic vortex. The dislocation theory in solids is also considered as a three-dimensional effective theory of gravity.Comment: 38 pages, 6 figures, RevTe

Regge Calculus in Teleparallel Gravity

In the context of the teleparallel equivalent of general relativity, the Weitzenbock manifold is considered as the limit of a suitable sequence of discrete lattices composed of an increasing number of smaller an smaller simplices, where the interior of each simplex (Delaunay lattice) is assumed to be flat. The link lengths between any pair of vertices serve as independent variables, so that torsion turns out to be localized in the two dimensional hypersurfaces (dislocation triangle, or hinge) of the lattice. Assuming that a vector undergoes a dislocation in relation to its initial position as it is parallel transported along the perimeter of the dual lattice (Voronoi polygon), we obtain the discrete analogue of the teleparallel action, as well as the corresponding simplicial vacuum field equations.Comment: Latex, 10 pages, 2 eps figures, to appear in Class. Quant. Gra

Quantum thermodynamics at critical points during melting and solidification processes

We systematically explore and show the existence of finite-temperature continuous quantum phase transition (CTQPT) at a critical point, namely, during solidification or melting such that the first-order thermal phase transition is a special case within CTQPT. Infact, CTQPT is related to chemical reaction where quantum fluctuation (due to wavefunction transformation) is caused by thermal energy and it can occur maximally for temperatures much higher than zero Kelvin. To extract the quantity related to CTQPT, we use the ionization energy theory and the energy-level spacing renormalization group method to derive the energy-level spacing entropy, renormalized Bose-Einstein distribution and the time-dependent specific heat capacity. This work unambiguously shows that the quantum phase transition applies for any finite temperatures.Comment: To be published in Indian Journal of Physics (Kolkata

Dizajniranje, sinteza, kinetika hidrolize i farmakodinamski profili konjugata aceklofenaka s histidinom i alaninom

The gastrointestinal toxicity associated with aceclofenac can be reduced by condensing its carboxylic acid group with methyl esters of amino acids like histidine and alanine to give amide linkage by the Schotten-Baumann method. Physicochemical characterization of the conjugates was carried out by various analytical and spectral methods. The synthesized conjugates were also subjected to in vitro hydrolysis in simulated gastric fluid (SGF) at pH 1.2, simulated intestinal fluid (SIF) at pH 7.4 and SIF + 80 % human plasma at pH 7.4. The release of free aceclofenac from histidine and alanine conjugated aceclofenac showed negligible hydrolysis in SGF compared to SIF. This indicated that the conjugates do not break in stomach, but release aceclofenac in SIF. Both synthesized conjugates showed excellent pharmacological response and encouraging hydrolysis rate in SIF and SIF + 80 % human plasma. Marked reduction of the ulcer index and comparable increase in analgesic and anti-inflammatory activities were obtained in both cases compared to aceclofenac alone. These findings suggest that the conjugates are better in action compared to the parent drug and have fewer gastrointestinal side-effects.Gastrointestinalna toksičnost aceklofenaka može se umanjiti kondenzacijom karboksilne skupine aceklofenaka s metilnim esterima aminokiselina poput histidina i alanina, pri čemu se stvaraju nove amidne veze po Schotten-Baumannovoj metodi. Fizikokemijska karakterizacija konjugata provedena je različitim analitičkim i spektralnim metodama. Nadalje, praćena je hidroliza sintetiziranih konjugata in vitro u simuliranoj gastričnoj tekućini (SGF) pri pH 1,2, simuliranoj intestinalnoj tekućini (SIF) pri pH 7,4 i simuliranoj intestinalnoj tekućini s 80 % humane plazme pri pH 7,4. Oslobađanje aceklofenaka iz konjugata s histidinom, odnosno alaninom, bilo je zanemarivo u SGF-u, u odnosu na oslobađanje u SIF-u. To ukazuje da su konjugati stabilni u želucu, dok se u SIF-u iz njih oslobađa aceklofenak. Oba konjugata daju izvrstan farmakološki odgovor i zadovoljavajući stupanj hidrolize u SIF-u i smjesi SIF-a i humane plazme. Oba konjugata pokazala su značajno smanjenu ulcerogenost i pojačano analgetsko i protuupalno djelovanje u odnosu na aceklofenak. Rezultati ukazuju na prednost konjugata u odnosu na samu ljekovitu tvar

Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer.

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis. The tumorigenicity of each model has been linked to different molecular pathways, and there is no common molecular mechanism shared among them. According to our hypothesis that genome level heterogeneity is a key to cancer evolution, we expect to reveal that the common link of tumorigenicity between these diverse models is elevated genome diversity. Spectral karyotyping (SKY) was used to compare the degree of karyotypic heterogeneity displayed in various sublines of these five models. The cell population diversity was determined by scoring type and frequencies of clonal and non-clonal chromosome aberrations (CCAs and NCCAs). The tumorigenicity of these models has been separately analyzed. As expected, the highest level of NCCAs was detected coupled with the strongest tumorigenicity among all models analyzed. The karyotypic heterogeneity of both benign hyperplastic lesions and premalignant dysplastic tissues were further analyzed to support this conclusion. This common link between elevated NCCAs and increased tumorigenicity suggests an evolutionary causative relationship between system instability, population diversity, and cancer evolution. This study reconciles the difference between evolutionary and molecular mechanisms of cancer and suggests that NCCAs can serve as a biomarker to monitor the probability of cancer progression

Innovative method for rapid detection of falsified COVID-19 vaccines through unopened vials using handheld Spatially Offset Raman Spectroscopy (SORS)

Preventing, detecting, and responding to substandard and falsified vaccines is of critical importance for ensuring the safety, efficacy, and public trust in vaccines. This is of heightened importance in context of public health crisis, such as the COVID-19 pandemic, in which extreme world-wide shortages of vaccines provided a fertile ground for exploitation by falsifiers. Here, a proof-of-concept study explored the feasibility of using a handheld Spatially Offset Raman Spectroscopy (SORS) device to authenticate COVID-19 vaccines through rapid analysis of unopened vaccine vials. The results show that SORS can verify the chemical identity of dominant excipients non-invasively through vaccine vial walls. The ability of SORS to identify potentially falsified COVID-19 vaccines was demonstrated by measurement of surrogates for falsified vaccines contained in vaccine vials. In all cases studied, the SORS technique was able to differentiate between surrogate samples from the genuine COVISHIELD™ vaccine. The genuine vaccines tested included samples from six batches across two manufacturing sites to account for any potential variations between batches or manufacturing sites. Batch and manufacturing site variations were insignificant. In conjunction with existing security features, for example on labels and packaging, SORS provided an intrinsic molecular fingerprint of the dominant excipients of the vaccines. The technique could be extended to other COVID-19 and non-COVID-19 vaccines, as well as other liquid medicines. As handheld and portable SORS devices are commercially available and widely used for other purposes, such as airport security, they are rapidly deployable non-invasive screening tools for vaccine authentication.</p

The Einsteinian T(3)-Gauge Approach and the Stress Tensor of the Screw Dislocation in the Second Order: Avoiding the Cut-off at the Core

A translational gauge approach of the Einstein type is proposed for obtaining the stresses that are due to non-singular screw dislocation. The stress distribution of second order around the screw dislocation is classically known for the hollow circular cylinder with traction-free external and internal boundaries. The inner boundary surrounds the dislocation's core, which is not captured by the conventional solution. The present gauge approach enables us to continue the classically known quadratic stresses inside the core. The gauge equation is chosen in the Hilbert--Einstein form, and it plays the role of non-conventional incompatibility law. The stress function method is used, and it leads to the modified stress potential given by two constituents: the conventional one, say, the `background' and a short-ranged gauge contribution. The latter just causes additional stresses, which are localized. The asymptotic properties of the resulting stresses are studied. Since the gauge contributions are short-ranged, the background stress field dominates sufficiently far from the core. The outer cylinder's boundary is traction-free. At sufficiently moderate distances, the second order stresses acquire regular continuation within the core region, and the cut-off at the core does not occur. Expressions for the asymptotically far stresses provide self-consistently new length scales dependent on the elastic parameters. These lengths could characterize an exteriority of the dislocation core region.Comment: 34 pages, LaTe