•Cell-free therapy using MSC-CM can offer an exciting approach in regenerative medicine.•Therapeutic role of cytokine and growth factors present in MSC-CM in clinical studies.•Cell-free therapy ...offers a significant advantage over cells based therapy and other conventional pharmaceutics.
Mesenchymal Stem Cells (MSCs) have been shown to be a promising candidate for cell-based therapy. The therapeutic potential of MSCs, towards tissue repair and wound healing is essentially based on their paracrine effects. Numerous pre-clinical and clinical studies of MSCs have yielded encouraging results. Further, these cells have been shown to be relatively safe for clinical applications. MSCs harvested from numerous anatomical locations including the bone marrow, adipose tissue, Wharton’s jelly of the umbilical cord etc., display similar immunophenotypic profiles. However, there is a large body of evidence showing that MSCs secrete a variety of biologically active molecules such as growth factors, chemokines, and cytokines. Despite the similarity in their immunophenotype, the secretome of MSCs appears to vary significantly, depending on the age of the host and niches where the cells reside. Thus, by implication, proteomics-based profiling suggests that the therapeutic potential of the different MSC populations must also be different. Analysis of the secretome points to its influence on varied biological processes such as angiogenesis, neurogenesis, tissue repair, immunomodulation, wound healing, anti-fibrotic and anti-tumour for tissue maintenance and regeneration. Though MSC based therapy has been shown to be relatively safe, from a clinical standpoint, the use of cell-free infusions can altogether circumvent the administration of viable cells for therapy. Understanding the secretome of in vitro cultured MSC populations, by the analysis of the corresponding conditioned medium, will enable us to evaluate its utility as a new therapeutic option. This review will focus on the accumulating evidence that points to the therapeutic potential of the conditioned medium, both from pre-clinical and clinical studies. Finally, this review will emphasize the importance of profiling the conditioned medium for assessing its potential for cell-free therapy therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mesenchymal stem cells (MSCs) have immense potential for cell-based therapy of acute and chronic pathological conditions. MSC transplantation for cell-based therapy requires a substantial number of ...cells in the range of 0.5-2.5 × 10
cells/kg body weight of an individual. A prolific source of MSCs followed by in vitro propagation is therefore an absolute prerequisite for clinical applications. Umbilical cord tissue (UCT) is an abundantly available prolific source of MSC that are fetal in nature and have higher potential for ex-vivo expansion. However, the ex-vivo expansion of MSCs using a xenogeneic supplement such as fetal bovine serum (FBS) carries the risk of transmission of zoonotic infections and immunological reactions. We used platelet lysate (PL) as a xeno-free, allogeneic replacement for FBS and compared the biological and functional characteristics of MSC processed and expanded with PL and FBS by explant and enzymatic method. UCT-MSCs expanded using PL displayed typical immunophenotype, plasticity, immunomodulatory property and chromosomal stability. PL supplementation also showed 2-fold increase in MSC yield from explant culture with improved immunomodulatory activity as compared to enzymatically dissociated cultures. In conclusion, PL from expired platelets is a viable alternative to FBS for generating clinically relevant numbers of MSC from explant cultures over enzymatic method.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A
bstract
We present an analysis of the role that the quark-gluon plasma (QGP) resolution length, the minimal distance by which two nearby colored charges in a jet must be separated such that they ...engage with the plasma independently, plays in understanding the modification of jet substructure due to interaction with QGP. The shorter the resolution length of QGP, the better its resolving power. We identify a set of observables that are sen- sitive to whether jets are quenched as if they are single energetic colored objects or whether the medium that quenches them has the ability to resolve the internal structure of the jet. Using the hybrid strong/weak coupling model, we find that although the ungroomed jet mass is not suitable for this purpose (because it is more sensitive to effects coming from particles reconstructed as a part of a jet that originate from the wake that the jet leaves in the plasma), groomed observables such as the number of Soft Drop splittings
n
SD
, the momentum sharing fraction
z
g
, or the
groomed
jet mass are particularly well-suited to discriminate the degree to which the QGP medium resolves substructure within a jet. In order to find the optimal grooming strategy, we explore different cuts in the Lund plane that allow for a clear identification of the regions of Soft Drop phase space that enhance the differences in the jet substructure between jets in vacuum and quenched jets. Comparison with present data seems to disfavor an “infinite resolution length”, which is to say the hypothesis that the medium interacts with the jet as if it were a single energetic colored object. Our analysis indicates that as the precision of experimental measurements of jet substructure observables and the control over uncertainties in their calculation improves, it will become possible to use comparisons like this to constrain the value of the resolution length of QGP, in addition to seeing how the substructure of jets is modified via their passage through it.
Construction sites consisting of soft soils may require ground improvement to prevent excessive settlements or bearing capacity type failures and shear movements, which results in construction delays ...and premature failures. Among the various ground improvement techniques, the Geosynthetic Reinforced Piled Embankment Systems (GRPES) provide a practical and efficient solution due to the low cost and short construction times. Most of the piled embankments are constructed on end bearing piles. At large depths of foundation soil, floating piles are more economical and technically feasible than the end bearing piles. The design of floating piles involves complex soil–structure interaction and there are no clear uniform guidelines available for the design of embankments supported on floating piles. This paper presents the results of numerical investigation into the performance of geosynthetic reinforced embankments supported on end bearing as well as floating piles considering the pile–soil and geosynthetic–soil interaction. 3-D Column models are employed to carry out the parametric studies on factors such as the development of arching, skin friction distribution along the pile length and axial force distribution. Full three-dimensional analyses are carried out to study the overall behavior of the GRPES system and the results obtained from the analyses were compared with those from British Standard BS8006-2010. The results indicated that the use of floating piles could considerably reduce the settlements and the embankment load transferred through the piles to the foundation soil is found to depend very much on the length of the piles. This aspect needs to be accounted for while calculating the arching factor in the empirical equations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The term ‘elasticity’ seems to conjure different images in different minds. After a discussion of the various interpretations of elasticity espoused by the pioneers, we discuss the notions of Cauchy ...elastic and Green elastic bodies, and whether Cauchy elastic bodies that are not Green elastic are reasonable from a physical standpoint. We then discuss a class of models, more general than classical Cauchy elastic bodies, and we find that such bodies need not be Green elastic. While a stored energy can be associated with these materials, the stress is not derivable from the stored energy. One can delineate conditions under which these models are thermodynamically consistent in that they meet the second law of thermodynamics; more precisely, the general class of bodies that is being described is incapable of dissipation1 in any process whatsoever. These models not only add to the repertoire of the elasticians in modeling solids that are incapable of dissipation, but also they seem to provide an opportunity for a genuinely new approach to the study of problems that result in singularities within the classical theory of linearized elasticity, such as that encountered in the rupturing and fracturing of solids. The generalized framework also provides a rational basis for developing linearized theories within which the linearized strain bears a non-linear relationship to the stress.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
A thermodynamic framework has been developed for a class of amorphous polymers used in fused deposition modeling (FDM), in order to predict the residual stresses and the accompanying distortion of ...the geometry of the printed part (warping). When a polymeric melt is cooled, the inhomogeneous distribution of temperature causes spatially varying volumetric shrinkage resulting in the generation of residual stresses. Shrinkage is incorporated into the framework by introducing an isotropic volumetric expansion/contraction in the kinematics of the body. We show that the parameter for shrinkage also appears in the systematically derived rate-type constitutive relation for the stress. The solidification of the melt around the glass transition temperature is emulated by drastically increasing the viscosity of the melt. In order to illustrate the usefulness and efficacy of the constitutive relation that has been developed, we consider four ribbons of polymeric melt stacked on top of each other such as those extruded using a flat nozzle: each layer laid instantaneously and allowed to cool for one second before another layer is laid on it. Each layer cools, shrinks and warps until a new layer is laid, at which time the heat from the newly laid layer flows into the previous laid layer and heats up the bottom layers. The residual stresses of the existing and newly laid layers readjust to satisfy equilibrium. Such mechanical and thermal interactions amongst layers result in a complex distribution of residual stresses. The plane strain approximation predicts nearly equibiaxial tensile stress conditions in the core region of the solidified part, implying that a preexisting crack in that region is likely to propagate and cause failure of the part during service. The free-end of the interface between the first and the second layer is subjected to the largest magnitude of combined shear and tension in the plane with a propensity for delamination.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The stone columns (or granular piles) are increasingly being used as ground reinforcement elements for supporting a wide variety of structures including buildings and flexible structures. The stone ...columns derive their load capacity from the confinement offered by the surrounding soil. In very soft soils this lateral confinement may not be adequate and the formation of the stone column itself may be doubtful. Wrapping the individual stone columns with suitable geosynthetic is one of the ideal forms of improving the performance of stone columns. This type of encasement by geosynthetic makes the stone columns stiffer and stronger. In addition, encasement prevents the lateral squeezing of stones in to the surrounding clay soil and vice versa, preserves drainage function of the stone column and frictional properties of the aggregates. In spite of many advantages, the behavior and the mechanism of the geosynthetic encased stone columns is not thoroughly understood. This paper investigates the qualitative and quantitative improvement of individual load capacity of stone column by encasement through laboratory model tests conducted on stone columns installed in clay bed prepared in controlled condition in a large scale testing tank. The load tests were performed on single as well as group of stone columns with and without encasement. Tests were performed with different geosynthetics for the encasement of stone column. The results from the load tests indicated a clear improvement in the load capacity of the stone column due to encasement. The increase in the axial load capacity depends very much upon the modulus of the encasement and the diameter of the stone column. The increase in the stress concentration on the stone columns due to encasement was also measured in the tests. The results from the tests were used to develop the design guidelines for the design of geosynthetic encasement for the given load and settlement.
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DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The classical linearized approximation to describe the elastic response of solids is the most widely used model in solid mechanics. This approximate model is arrived at by assuming that the norm of ...the displacement gradient is sufficiently small so that one can neglect the square of the norm in terms of the norm. Recent experimental results on Titanium and Gum metal alloys, among other alloys, indicate with unmistakable clarity a nonlinear relationship between the strain and the stress in the range of strain wherein one would have to use the classical linearized theory of elasticity, namely wherein the square of the norm of the strain can be ignored with regard to the value of the strain, leading to a dilemma concerning the modeling of the response, as the classical nonlinear Cauchy elastic model would collapse to the linearized elastic model in this range. A novel and important generalization of the theory of elastic materials has been suggested by Rajagopal in Appl Math 48: 279–319,
2003
and Zeit Angew Math Phys 58: 309–317,
2007
that allows for an approximation wherein the linearized strain can be a nonlinear function of the stress. In this paper, we show how this new theory can be used to describe the new experiments on Titanium and Gum metal alloys and also clarify several issues concerning the domain of application of the classical linearized theory.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Medical image processing has a strong footprint in radio diagnosis for the detection of diseases from the images. Several computer-aided systems were researched in the recent past to assist the ...radiologist in diagnosing liver diseases and reducing the interpretation time. The aim of this paper is to provide an overview of the state-of-the-art techniques in computer-assisted diagnosis systems to predict benign and malignant lesions using computed tomography images.
The research articles published between 1998 and 2020 obtained from various standard databases were considered for preparing the review. The research papers include both conventional as well as deep learning-based systems for liver lesion diagnosis. The paper initially discusses the various hepatic lesions that are identifiable on computed tomography images, then the computer-aided diagnosis systems and their workflow. The conventional and deep learning-based systems are presented in stages wherein the various methods used for preprocessing, liver and lesion segmentation, radiological feature extraction and classification are discussed.
The review suggests the scope for future, work as efficient and effective segmentation methods that work well with diverse images have not been developed. Furthermore, unsupervised and semi-supervised deep learning models were not investigated for liver disease diagnosis in the reviewed papers. Other areas to be explored include image fusion and inclusion of essential clinical features along with the radiological features for better classification accuracy.
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•A comprehensive review of conventional and deep learning based CAD systems for liver lesion diagnosis.•Provides an overview of the various technical as well as medical aspects associated with hepatic lesion diagnosis.•The articles published in the last two decades were analyzed in the review.•The various limitations of the current systems along with directions for future research are outlined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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