Quality Assurance in Biobanking for Pre-Clinical Research

It is estimated that not less than USD 28 billion are spent each year in the USA alone on irreproducible pre-clinical research, which is not only a fundamental loss of investment and resources but also a strong inhibitor of efficiency for upstream processes regarding the translation towards clinical applications and therapies. The issues and cost of irreproducibility has mainly been published on pre-clinical research. In contrast to pre-clinical research, test material is often being transferred into humans in clinical research. To protect treated human subjects and guarantee a defined quality standard in the field of clinical research, the manufacturing and processing infrastructures have to strictly follow and adhere to certain (inter-)national quality standards. It is assumed and suggested by the authors that by an implementation of certain quality standards within the area of pre-clinical research, billions of USD might be saved and the translation phase of promising pre-clinical results towards clinical applications may substantially be improved. In this review, we discuss how an implementation of a quality assurance (QA) management system might positively improve sample quality and sustainability within pre-clinically focused biobank infrastructures. Biobanks are frequently positioned at the very beginning of the biomedical research value chain, and, since almost every research material has been stored in a biobank during the investigated life cycle, biobanking seems to be of substantial importance from this perspective. The role model of a QA-regulated biobank structure can be found in biobanks within the context of clinical research organizations such as in regenerative medicine clusters

Magnetic moment of welded HTS samples: dependence on the current flowing through the welds

We present a method to calculate the magnetic moments of the high-temperature superconducting (HTS) samples which consist of a few welded HTS parts. The approach is generalized for the samples of various geometrical shapes and an arbitrary number of welds. The obtained relations between the sample moment and the density of critical current, which flows through the welds, allow to use the magnetization loops for a quantitative characterization of the weld quality in a wide range of temperatures and/or magnetic fields.Comment: RevTeX4, 4 pages, 2 figures. Submitted to Supercond. Sci. Techno

Growth-related profiles of remanent flux in bulk melt-textured YBaCuO crystal magnetized by pulsed fields

We have studied the remanent magnetic flux distribution in bulk melt-textured YBa2Cu3O7 (YBCO) crystals after their magnetization in quasi-static and pulsed magnetic fields up to 6T. It has been shown that, provided that the magnetic pulse is sharp enough and its amplitude much exceeds the twice penetration magnetic field, the pulse magnetization technique becomes extremely sensitive to the sample inhomogeneities. Using this method with appropriate parameters of the magnetic pulse, we have particularly demonstrated that the growth of YBCO crystals in the growth sectors (GSs) responds for a macroscopic arrangement of weaks links -- they mostly appear inside of GSs, but not along the GS boundaries.Comment: 8 pages in LaTeX2e, 5 figures. Revised version, submitted to Supercond. Sci. Techno

Studies of cracking behavior in melt-processed YBCO bulk superconductors

An important phenomenon in bulk superconductors fabricated by top-seeded-melt growth (TSMG) is the formation of cracks due to the inherent brittleness of the YBa2Cu3O7-δ (Y-123) phase matrix. These form during the fabrication of the superconducting monolith and play an important role in the limitation of current flow. However, cracks may also form during cooling cycles of the sample to liquid nitrogen temperatures. In this investigation, macrocracks along the c-direction, in particular were analyzed microscopically before and after cooling. In addition we attempt to resolve the c-axis macrocrack formation pattern using the magnetoscan technique

Inter- and intragrain currents in bulk melt-grown YBaCuO rings

A simple contactless method suitable to discern between the intergrain (circular) current, which flows in the thin superconducting ring, and the intragrain current, which does not cross the weakest link, has been proposed. At first, we show that the intergrain current may directly be estimated from the magnetic flux density $B(\pm z_0)$ measured by the Hall sensor positioned in the special points $\pm z_0$ above/below the ring center. The experimental and the numerical techniques to determine the value $z_0$ are discussed. Being very promising for characterization of a current flowing across the joints in welded YBaCuO rings (its dependencies on the temperature and the external magnetic field as well as the time dissipation), the approach has been applied to study corresponding properties of the intra- and intergrain currents flowing across the $a$-twisted grain boundaries which are frequent in bulk melt-textured YBaCuO samples. We present experimental data related to the flux penetration inside a bore of MT YBaCuO rings both in the non-magnetized, virgin state and during the field reversal. The shielding properties and their dependence on external magnetic fields are also studied. Besides, we consider the flux creep effects and their influence on the current re-distribution during a dwell.Comment: 13 pages, 16 figures (EPS), RevTeX4. In the revised version, corrections to perturbing effects near the weak links are introduced, one more figure is added. lin

A Novel Magnetoscan Setup

Due to a modification in the original magnetoscan setup, a significant improvement in resolution was obtained. The paper focuses on experimental results which should support the idea of the new setup using two magnets with opposite direction of magnetization. This contribution to the characterization techniques of melt-grown bulk superconductors should promote the easy installation of this technique in industry. The improved magnetoscan technique may further help to investigate growth-induced inhomogeneities of the top-seeded-melt-growth process in the submillimeter range, and it offers new possibilities to the characterization of smaller structures such as superconducting films or coated conductors.Comment: 7 pages, 7 figure

Identification of DNA methylation changes at cis-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing

Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important cis-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation

Measurement of the magnetic field inside the holes of a drilled bulk high-Tc superconductor

We use macroscopic holes drilled in a bulk YBCO superconductor to probe its magnetic properties in the volume of the sample. The sample is subjected to an AC magnetic flux with a density ranging from 30mT to 130mT and the flux in the superconductor is probed by miniature coils inserted in the holes. In a given hole, three different penetration regimes can be observed: (i) the shielded regime, where no magnetic flux threads the hole; (ii) the gradual penetration regime, where the waveform of the magnetic field has a clipped sine shape whose fundamental component scales with the applied field; and (iii) the flux concentration regime, where the waveform of the magnetic field is nearly a sine wave, with an amplitude exceeding that of the applied field by up to a factor of two. The distribution of the penetration regimes in the holes is compared with that of the magnetic flux density at the top and bottom surfaces of the sample, and is interpreted with the help of optical polarized light micrographs of these surfaces. We show that the measurement of the magnetic field inside the holes can be used as a local characterization of the bulk magnetic properties of the sample

Vortex Dynamics at the transition to the normal state in YBCO films

We propose a description of the vortex dynamics in YBCO films from the critical to the normal states. This description supposes that the vortex motion is thermally activated along the twin boundaries of the films. The discontinuity observed in the current-voltage curves at the transition to the normal state is explained by the sudden increase in the dissipated power rate due to vortex depinning. However, near the critical temperature, this phenomenon does not occur because the vortex activation energy is near zero. We also show how the current at the transition to the normal state can be computed from the current-voltage curves measured at low currents. The predictions of this description are compared to the data published by Gonzalez et al. [Phys.Rev.B68,054514 (2003)]

Myeloid Cells Contribute to Tumor Lymphangiogenesis

The formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation