ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs

Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced ‘browning’ in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow

Improved Machining Stability through Eddy Current Damping

Higher efficiency can be achieved during machining of thin-walled parts while maintaining quality of surface finish by damping part vibrations, thereby increasing the maximum chatter-free depth of cut over a range of spindle speeds. Models exist both to characterize the effect of damping in machining and to quantify the result of incorporating eddy current damping on a simple vibrating cantilever beam. Impact testing was performed on undamped and magnetically damped cantilever beams to quantify the amount of damping introduced by the magnet configuration being used. Machining tests were carried out on thin-floored compliant parts with and without magnetic damping. The use of magnets during machining resulted in cutting forces reduced by a factor of 10 and surface Ra being reduced by a factor of 25.ThesisMaster of Applied Science (MASc

Criteria for and Appropriateness of Renal Transplantation in Elderly Patients With End-Stage Renal Disease : A Literature Review and Position Statement on Behalf of the European Renal Association-European Dialysis and Transplant Association Descartes Working Group and European Renal Best Practice

During the last 20 years, waiting lists for renal transplantation (RT) have grown significantly older. However, elderly patients (ie ≥65 years of age) are still more rarely referred or accepted to waiting lists and, if enlisted, have less chances of actually receiving a kidney allograft, than younger counterparts. In this review, we looked at evidence for the benefits and risks of RT in the elderly trying to answer the following questions: Should RT be advocated for elderly patients? What should be the criteria to accept elderly patients on the waiting list for RT? What strategies might be used to increase the rate of RT in waitlisted elderly candidates? For selected elderly patients, RT was shown to be superior to dialysis in terms of patient survival. Virtually all guidelines recommend that patients should not be deemed ineligible for RT based on age alone, although a short life expectancy generally might preclude RT. Concerning the assessment of comorbidities in the elderly, special attention should be paid to cardiac evaluation and screening for malignancy. Comorbidity scores and frailty assessment scales might help the decision making on eligibility. Psychosocial issues should also be evaluated. To overcome the scarcity of organ donors, elderly RT candidates should be encouraged to consider expanded criteria donors and living donors, as alternatives to deceased standard criteria donors. It has been demonstrated that expanded criteria donor RT in patients 60 years or older is associated with higher survival rates than remaining on dialysis, whereas living donor RT is superior to all other options.Peer reviewe

A general theoretical formulation of deformation of steel structures exposed to fire

This paper presents a proposal for the formulation of a mathematical model of a fire resistance testing process for steel beams subject to bending, carried out experimentally in a test furnace. The model for the formulation was created with a balance method by describing with the fundamental laws of thermomechanics the phenomena occurring during the experiment analysed for the formulation. The viscoplastic behave our of steel at high temperatures was described with constitutive relationships proposed by Perzyna (which form the so-called “overload model”). The general mathematical model of the experiment analysed, obtained in the form of a system of differential equations, is discussed. The authors considered the impact of known physical properties of the test material and the impact of the results of the observations made during the research on the behaviour of individual terms of the model’s equations. Based on these considerations, simplifications were proposed which optimized the mathematical description and facilitated its adaptation to a special case. As a result of the investigation, a system of equation was obtained which described the processes present during the fire resistance test. It is postulated here to accept the system of equations as the mathematical model. Keywords: thermomechanical analysis, fire resistance test, viscoplastic constitutive laws, Perzyna mode

Computational design of syntheses leading to compound libraries or isotopically labelled targets

Although computer programs for retrosynthetic planning have shown improved and in some cases quite satisfactory performance in designing routes leading to specific, individual targets, no algorithms capable of planning syntheses of entire target libraries - important in modern drug discovery - have yet been reported. This study describes how network-search routines underlying existing retrosynthetic programs can be adapted and extended to multi-target design operating on one common search graph, benefitting from the use of common intermediates and reducing the overall synthetic cost. Implementation in the Chematica platform illustrates the usefulness of such algorithms in the syntheses of either (i) all members of a user-defined library, or (ii) the most synthetically accessible members of this library. In the latter case, algorithms are also readily adapted to the identification of the most facile syntheses of isotopically labelled targets. These examples are industrially relevant in the context of hitto-lead optimization and syntheses of isotopomers of various bioactive molecules