Gas Chromatography-Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies.

Thymoquinone (TQ) is the primary component of Nigella sativa L. (NS) oil, which is renowned for its potent hepatoprotective effects attributed to its antioxidant, anti-fibrotic, anti-inflammatory, anti-carcinogenic, and both anti- and pro-apoptotic properties. The aim of this work was to establish a method of measuring TQ in serum in order to investigate the pharmacokinetics of TQ prior to a targeted therapeutic application. In the first step, a gas chromatography-mass spectrometry method for the detection and quantification of TQ in an oily matrix was established and validated according to European Medicines Agency (EMA) criteria. For the assessment of the clinical application, TQ concentrations in 19 oil preparations were determined. Second, two serum samples were spiked with TQ to determine the TQ concentration after deproteinization using toluene. Third, one healthy volunteer ingested 1 g and another one 3 g of a highly concentrated NS oil 30 and 60 min prior to blood sampling for the determination of serum TQ level. After the successful establishment and validation of the measurement method, the highest concentration of TQ (36.56 g/L) was found for a bottled NS oil product (No. 1). Since a capsule is more suitable for oral administration, the product with the third highest TQ concentration (No. 3: 24.39 g/L) was used for all further tests. In the serum samples spiked with TQ, the TQ concentration was reliably detectable in a range between 5 and 10 µg/mL. After oral intake of NS oil (No. 3), however, TQ and/or its derivatives were not detectable in human serum. This discrepancy in detecting TQ after spiking serum or following oral ingestion may be attributed to the instability of TQ in biomatrices as well as its strong protein binding properties. A pharmacokinetics study was therefore not viable. Studies on isotopically labeled TQ in an animal model are necessary to study the pharmacokinetics of TQ using alternative modalities.

[Benign liver tumors : Diagnostics and treatment]. / Benigne Lebertumoren : Diagnostik und Behandlung.

Benign liver tumors are often detected during routine ultrasound examinations or as an incidental finding in radiological imaging. Only very few benign liver tumors are at risk of becoming malignant. In the majority of cases the differentiation from malignant tumors is currently carried out using imaging procedures. In a few cases of diagnostic uncertainty, a transcutaneous liver biopsy can lead to clarification. If the suspicion of malignancy is substantiated or this cannot be excluded with absolute certainty, the tumor should be removed by partial liver resection.

[Application of the Objective Structured Clinical Examination (OSCE) in German Medical Schools: An Inventory]. / Objective Structured Clinical Examination (OSCE) an Medizinischen Fakultäten in Deutschland ­ eine Bestandsaufnahme.

INTRODUCTION: The German medical licensing regulations, as amended by the government in 2002, now require the assessment of clinical skills in undergraduate medical education. As a result, the Objective Structured Clinical Examination (OSCE) was introduced as an assessment tool in many medical schools. This article provides a detailed inventory of the current application of the OSCE assessment in Germany. METHODS: From June to September 2015, the implementation of the OSCE in all 36 German medical schools was investigated using semi-structured telephone interviews and email correspondence. The areas of focus comprised implementation of the OSCE, and number and type of performance records according to the medical licensing regulations or involved disciplines. Following collection, data were analysed quantitatively and qualitatively. RESULTS: All medical schools (100%) participated in the survey. Nearly every school (94%) has introduced the OSCE into its assessment portfolio, however, to varying extents. For each location, the numbers range between 0 and 18 (M=4.7) performance records of the clinical science section assessed by OSCEs. The implementation of this assessment format includes most of the clinical performance records, but more than half (51.4%) of these cover surgery, internal medicine, emergency medicine, anaesthesiology, and orthopaedics. CONCLUSION: The results reported in this paper confirm the widespread introduction of the OSCE assessment in German medical schools. However, the implementation remains heterogeneous with respect to the scope, schools and individual disciplines involved in the process. In order to ensure extensive clinical competence of prospective physicians the application of the OSCE should be broadened. For this purpose, further information to convince medical school staff is still required.

Step Coalescence by Collective Motion at an Incommensurate Grain Boundary.

Using extended time series scanning transmission electron microscopy, we investigate structural fluctuations at an incommensurate grain boundary in Au. Atomic-resolution imaging reveals the coalescence of two interfacial steps, or disconnections, of different height via coordinated motion of atoms along close-packed directions. Numerical simulations uncover a transition pathway that involves constriction and expansion of a characteristic stacking fault often associated with grain boundaries in face-centered cubic materials. It is found that local atomic fluctuations by enhanced point defect diffusion may play a critical role in initiating this transition. Our results offer new insights into the collective motion of atoms underlying the lateral advance of steps that control the migration of faceted grain boundaries.

A theoretical study of lipid accumulation in the liver-implications for nonalcoholic fatty liver disease.

A hallmark of the nonalcoholic fatty liver disease is the accumulation of lipids. We developed a mathematical model of the hepatic lipid dynamics to simulate the fate of fatty acids in hepatocytes. Our model involves fatty acid uptake, lipid oxidation, and lipid export. It takes into account that storage of triacylglycerol within hepatocytes leads to cell enlargement reducing the sinusoids radius and impairing hepatic microcirculation. Thus oxygen supply is reduced, which impairs lipid oxidation. The analysis of our model revealed a bistable behavior (two stable steady states) of the system, in agreement with histological observations showing distinct areas of lipid accumulation in lobules. The first (healthy) state is characterized by intact lipid oxidation and a low amount of stored lipids. The second state in our model may correspond to the steatotic cell; it is marked by a high amount of stored lipids and a reduced lipid oxidation caused by impaired oxygen supply. Our model stresses the role of insufficient oxygen supply for the development of steatosis. We discuss implications of our results in regard to the experimental design aimed at exploring lipid metabolism reactions under steatotic conditions. Moreover, the model helps to understand the reversibility of lipid accumulation and predicts the reversible switch to show hysteresis. The system can switch from the steatotic state back to the healthy state by reduction of fatty acid uptake below the threshold at which steatosis started. The reversibility corresponds to the observation that caloric restriction can reduce the lipid content in the liver.

Highly monodisperse core-shell particles created by solid-state reactions.

The size distribution of particles, which is essential for many properties of nanomaterials, is equally important for the mechanical behaviour of the class of alloys whose strength derives from a dispersion of nanoscale precipitates. However, particle size distributions formed by solid-state precipitation are generally not well controlled. Here we demonstrate, through the example of core-shell precipitates in Al-Sc-Li alloys, an approach to forming highly monodisperse particle size distributions by simple solid-state reactions. The approach involves the use of a two-step heat treatment, whereby the core formed at high temperature provides a template for growth of the shell at lower temperature. If the core is allowed to grow to a sufficient size, the shell develops in a 'size focusing' regime, where smaller particles grow faster than larger ones. These results suggest strategies for manipulating precipitate size distributions in similar systems through simple variations in thermal treatments.

How similar are inbred rats? The influence of anatomical variations, shipment and sampling time on experimental surgery.

Variations among inbred rats in terms of anatomy and routine laboratory values can potentially blur surgical experimental results. Therefore, a retrospective analysis aiming at investigating hepatic and perihepatic anatomical variations, liver weight, body weight, liver weight/body weight ratio (LBWR), variations in routine laboratory values, and the influence of shipment and repeated sampling was performed. In our study, liver weight of rats seemed to be strain-specific. LBWR was weakly and negatively correlated with body weight in rats. A statistically significant difference in routine blood tests was found among normal rats grouped by different body weight or shipment. Weekly repeated sampling from the same rats revealed a statistically significant difference in a blood test. In conclusion, the fact that variation among rats or their environment can blur the results of a surgical experimental study should be kept in mind.

Hepatic arterial perfusion is essential for the spontaneous recovery from focal hepatic venous outflow obstruction in rats.

We previously observed that focal hepatic venous outflow obstruction recovered spontaneously by the formation of sinusoidal canals in a rat model of portal hyperperfusion. We aimed to investigate whether the lack of hepatic arterial perfusion aggravates parenchymal damage, decelerates recovery and influences the formation of sinusoidal canals after focal hepatic venous outflow obstruction. Rats were subjected to arterialized versus nonarterialized syngeneic liver transplantation after ligating the right median hepatic vein in the donor. Hepatic damage, microcirculation, regeneration and vascular remodeling were evaluated. In arterialized-recipients, confluent necrosis interspersed with viable periportal islands of hepatocytes, and vascularized sinusoidal canals with visible blood flow, surrounded by normal sinusoidal structure, were visible on postoperative day (POD) 2. Complete parenchymal recovery was consequently established by resorption of necrosis and hepatocyte proliferation, detected in viable portal islands and border zone. Lack of hepatic arterial perfusion caused complete necrosis in the obstruction zone without viable hepatocytes in the periportal area on POD2. Hepatocyte proliferation was only visible in the border zone. On POD28, perfused vascular structures, without neighboring normal sinusoidal structures, were observed in the scar-like area. Hepatic arterial perfusion determined the extent of hepatic necrosis, the formation of vascularized sinusoidal canals and the parenchymal recovery, after focal hepatic venous outflow obstruction.

A novel end-to-side anastomosis technique for hepatic rearterialization in rat orthotopic liver transplantation to accommodate size mismatches between vessels.

BACKGROUND/AIMS: We present our modification of a sutured arterial anastomosis in orthotopic rat liver transplantation as well as a literature survey and analysis of the existing techniques of rearterialization with regard to technical difficulties and potential limitations. METHODS: The donor common hepatic artery (CHA) was anastomosed to the enlarged lumen of the recipient proper hepatic artery (PHA), tailored to match the size of the donor CHA, with an end-to-side interrupted suture technique. Vascular patency of hepatic rearterialization was assessed both intraoperatively and at the time the liver grafts were harvested (postoperative days 2 and 28). The effect of arterialization on hepatic morphology was confirmed by histological examination and compared to nonarterialized rat orthotopic liver transplantation. RESULTS: The CHAs had a significantly larger diameter (up to 3-fold) compared to the PHAs, which represents a considerable size mismatch. The anastomosis procedure including the size adaptation required 15-25 min. All anastomoses were patent immediately, 5 min after rearterialization and at both harvest time points. The liver lobular architecture was intact in the rearterialized group, whereas a moderate degree of bile duct proliferation and portal/lobular lymphocytic infiltration were observed in the nonarterialized group. CONCLUSION: The new technique is a time-consuming and microsurgically challenging but universally applicable and robust procedure accommodating even a substantial mismatch in vessel diameter.

Carbon nanotubes as nanoscale mass conveyors.

The development of manipulation tools that are not too 'fat' or too 'sticky' for atomic scale assembly is an important challenge facing nanotechnology. Impressive nanofabrication capabilities have been demonstrated with scanning probe manipulation of atoms and molecules on clean surfaces. However, as fabrication tools, both scanning tunnelling and atomic force microscopes suffer from a loading deficiency: although they can manipulate atoms already present, they cannot efficiently deliver atoms to the work area. Carbon nanotubes, with their hollow cores and large aspect ratios, have been suggested as possible conduits for nanoscale amounts of material. Already much effort has been devoted to the filling of nanotubes and the application of such techniques. Furthermore, carbon nanotubes have been used as probes in scanning probe microscopy. If the atomic placement and manipulation capability already demonstrated by scanning probe microscopy could be combined with a nanotube delivery system, a formidable nanoassembly tool would result. Here we report the achievement of controllable, reversible atomic scale mass transport along carbon nanotubes, using indium metal as the prototype transport species. This transport process has similarities to conventional electromigration, a phenomenon of critical importance to the semiconductor industry.

Effect and risk of AEE788, a dual tyrosine kinase inhibitor, on regeneration in a rat liver resection model.

BACKGROUND: AEE788, a dual tyrosine kinase inhibitor, has antiproliferative effects on diverse tumor models in mice. We aimed to investigate whether AEE788 blocks liver regeneration and causes drug-related side effects. METHODS: Rats treated orally with 50 mg/kg AEE788 or solvent every 2 days were subjected to 70% partial hepatectomy (PH) and sacrificed on postoperative days 1, 2, 7, and 28. Liver regeneration was evaluated using liver weight to body weight ratio, BrdU-staining, mitotic index, and PCR for PCNA (proliferating cell nuclear antigen). Side effects on the gastrointestinal system and liver were assessed using clinical chemistry, histology, silver staining, and immunohistochemistry. Plasma and liver tissue levels of AEE788 were measured using spectrometry. RESULTS: AEE788 treatment did not inhibit liver regeneration. No obvious drug-related systemic or hepatic side effects were observed. Restoration of liver architecture during liver regeneration was not obviously impaired, even after 4 weeks' AEE788 treatment. After a 1-week treatment, AEE788 concentrations in plasma and liver tissue in the PH group were 3-fold and 8-fold higher than the non-PH group, respectively. CONCLUSION: Its antiproliferative properties, good tolerance, and lack of inhibition on liver regeneration make AEE788 a potential candidate for clinical study with oncological PH, but one that carries the risk of overexposure in the early postoperative phase.

Observations of pentagonally twinned precipitate needles of germanium in aluminum.

Unusual pentagonally twinned precipitates were observed in a high-resolution transmission electron microscopy study of needle-shaped germanium particles in aluminum. Although commonly found in small particles formed on substrates, such twinning has not been seen in precipitates grown in the solid state. The morphologies and orientation relationships are consistent with symmetry principles.

[Benign liver tumors : Diagnostics and treatment]. / Benigne Lebertumoren : Diagnostik und Behandlung.

Benign liver tumors are often detected during routine ultrasound examinations or as an incidental finding in radiological imaging. Only very few benign liver tumors are at risk of becoming malignant. In the majority of cases the differentiation from malignant tumors is currently carried out using imaging procedures. In a few cases of diagnostic uncertainty, a transcutaneous liver biopsy can lead to clarification. If the suspicion of malignancy is substantiated or this cannot be excluded with absolute certainty, the tumor should be removed by partial liver resection.

[Knowledge, trust, and the decision to donate organs : A comparison of medical students and students of other disciplines in Germany]. / Wissen, Vertrauen und Entscheidung zur Organspende : Ein Vergleich zwischen Medizinstudenten und Studenten anderer Fachrichtungen.

BACKGROUND: Following the organ transplant scandal in Germany in 2011, the willingness to donate organs postmortem decreased dramatically. This was explained by a loss of confidence in the German organ donation system. OBJECTIVES: The aim of this study was to evaluate the relationship between knowledge, trust, and fear in respect to organ donation and the explicit willingness to potentially act as an organ donor by comparing medical students to students of other disciplines. MATERIAL AND METHODS: We conducted a Facebook-based online survey (June-July 2013). The participating students were divided into two groups according to their discipline: medical students and other students. Based on questions covering different aspects of organ donation, a knowledge, trust, and fear score was established and calculated. The answers were related to an explicitly expressed decision to donate organs as expressed in a signed organ donor card. RESULTS: In total, 2484 participants took part in our survey. Of these, 1637 were students, 83.7% (N = 1370) of which were medical students and 16.3% (N = 267) other students. As expected, medical students reached a higher knowledge score regarding organ donation compared with other students (knowledge score 4.13 vs. 3.38; p < 0.001). They also demonstrated more confidence in organ donation, resulting in a higher confidence score (3.94 vs. 3.33; p < 0.001) and expressed less fear towards organ donation as indicated by the lower fear score (1.76 vs. 2.04; p < 0.01). Medical students declared their written willingness to donate organs more often than did other students (78.2% vs. 55.2%; p < 0.001). Entries on organ donation cards did not differ significantly between medical students and other students. Medical students possessing an organ donor card showed a higher knowledge and a higher trust score than did medical students without an organ donor card. In contrast, other students possessing an organ donor card showed a higher trust score but did not show a higher knowledge score. CONCLUSIONS: The higher level of knowledge and trust demonstrated by the medical students was associated with a higher rate of written decisions to donate organs. In contrast, the lower level of knowledge and trust observed in the non-medical students was associated with a lower rate of organ donor cards. Interestingly, in the group of non-medical students, the decision regarding organ donation was associated with a higher level of trust, but not with a higher level of knowledge. It would appear that knowledge, trust, and the decision to donate organs are closely related. In cases of a low level of knowledge, confidence is even more important. Therefore, organ donation campaigns should focus on increasing knowledge and fostering trust.

Benefit of an implanted solid barrier for the feasibility of a sequence of three different hepato-biliary operations in a small animal model.

BACKGROUND: Current liver surgery includes complex multi-stage procedures such as portal vein ligation (PVL) followed by extended liver resection, especially in patients with Klatskin tumours. The risk for severe adhesions increases with every procedure. Finally, this complex sequence could fail because of malignant adhesions. Therefore, we proved the hypothesis of reducing malignant adhesions and increasing feasibility of a sequence with three hepato-biliary operations by implantation of a solid barrier. MATERIALS AND METHODS: We operated in male rats (n=40). Our sequence included as 1st operation bile duct ligation mimicking Klatskin III° or IV°, the 2nd operation was a selective portal vein ligation (sPVL) and 3rd procedure was a 70% liver resection. The mechanical barrier (part of a sterile glove) was implanted at the end of the first operation between the upper (median lobe+left lateral lobe [ML+LLL]) and lower (right lobe+caudate lobe [RL+CL]) rat liver lobes. We assessed the degree of adhesions and the feasibility of the 2nd and 3rd operation by using an established adhesion score (Zühlke) and a feasibility score. The severity of the adhesions and the pro-inflammatory cellular response were further evaluated by morphometry of thickness (HE) of the adhesion layer and quantification of infiltrating neutrophils (ASDCL) in the adhesion layer on the liver surface. RESULTS: The planned liver resection as the third procedure was only feasible when a mechanical barrier was placed. Extent of cholestasis or time interval between the operations had no significant impact on adhesions score or feasibility of the whole sequence. CONCLUSION: A sequence of three hepato-biliary operations in a small animal model (rat) is feasible. It should be considered to implant a mechanical barrier in a sequence of more than two surgical interventions in an experimental model in order to assure the feasibility of the final operation.

Modulation of hepatic perfusion did not improve recovery from hepatic outflow obstruction.

BACKGROUND: Focal hepatic venous outflow obstruction frequently occurs after extended liver resection and leads to a portal hypertension, arterial hypoperfusion and parenchymal necrosis. In this study, we investigated the pharmacological modulation of liver perfusion and hepatic damage in a surgical model of hepatic outflow obstruction after extended liver resection by administration of 5 different drugs in comparison to an operative intervention, splenectomy. METHODS: Male inbred Lewis rats (Lew/Crl) were subjected to right median hepatic vein ligation + 70% partial hepatectomy. Treatment consisted of a splenectomy or the application of saline, carvedilol or isosorbide-5-mononitrate (ISMN) (5 mg · kg-1 respectively 7,2 mg · kg-1 per gavage 12 h-1). The splenectomy was performed during operation. The effect of the treatments on hepatic hemodynamics were measured in non-operated animals, immediately after operation (n = 4/group) and 24 h after operation (n = 5/group). Assessment of hepatic damage (liver enzymes, histology) and liver cell proliferation (BrdU-immunohistochemistry) was performed 24 h after operation. Furthermore sildenafil (10 µg · kg-1 i.p. 12h-1), terlipressin (0.05 mg · kg-1 i.v. 12 h-1) and octreotide (10 µg · kg-1 s.c. 12 h-1) were investigated regarding their effect on hepatic hemodynamics and hepatic damage 24 h after operation (n = 4/group). RESULTS: Carvedilol and ISMN significantly decreased the portal pressure in normal non-operated rats from 11,1 ± 1,1 mmHg (normal rats) to 8,4 ± 0,3 mmHg (carvedilol) respectively 7,4 ± 1,8 mmHg (ISMN). ISMN substantially reduced surgery-induced portal hypertension from 15,4 ± 4,4 mmHg to 9,6 ± 2,3 mmHg. Only splenectomy reduced the portal flow immediately after operation by approximately 25%. No treatment had an immediate effect on the hepatic arterial perfusion. In all treatment groups, portal flow increased by approximately 3-fold within 24 h after operation, whereas hepatic arterial flow decreased substantially. Neither treatment reduced hepatic damage as assessed 24 h after operation. The distribution of proliferating cells appeared very similar in all drug treated groups and the splenectomy group. CONCLUSION: Transient relative reduction of portal pressure did not result in a reduction of hepatic damage. This might be explained by the development of portal hyperperfusion which was accompanied by arterial hypoperfusion.

Fluctuation of the cytokine expression in the liver during the chronic woodchuck hepatitis virus (WHV) infection is not related to viral load.

The woodchuck together with the woodchuck hepatitis virus (WHV) is an excellent model to study the pathogenesis of hepadnaviral infections. Chronic WHV infection causes severe liver disease and hepatocellular carcinoma in woodchucks. The mechanism of viral clearance is not fully understood, interferons seem to play a major role in down-regulating viral replication prior to elimination of infected hepatocytes. We investigated on the pattern of cytokine and T-cell-marker expression in livers of woodchucks chronically infected with WHV. RNase-protection-assay (RPA) was used to determine mRNA of woodchuck specific genes (TNF-alpha, IFN-gamma, IL-15, CD3, CD4, CD8). Serial liver biopsies were performed daily or weekly in eight chronic WHV-carrier woodchucks. Cytokine/T-cell-marker expression differed significantly between the time points up to +/-50% within each woodchuck. The different expression patterns of cytokines or T-cell-markers did not correlate to the (weak) fluctuations in the viremia but may explain the observed fluctuations in the WHV/HBV-load in chronically infected individuals. Furthermore, we observed associations between cytokine and T-cell-marker expression. The marginal fluctuations in viremia during the chronic infection may indicate, that, once the chronic hepadnaviral infection is established, cytokines/interferons expressed endogenously (i.e. not vector-borne or injected) play only a minor role.

The "territorial belonging" of the middle hepatic vein: a troublesome dilemma in adult live donor liver transplantation--anatomical evidence based on virtual 3-dimensional-computed tomography-imaging reconstructions.

BACKGROUND: The venous drainage of the liver plays an essential role in securing viability of both graft and remnant in live donor liver transplantation (LDLT). There is still controversy on whether the middle hepatic vein (MHV) should be routinely included as part of the graft or retained with the remnant liver. The purpose of this study was to analyze hepatic venous drainage patterns based on information obtained by 3-dimensional CT-imaging reconstructions. METHODOLOGY: Fifty five potential live liver donors were evaluated between January 2003 and May 2004 at our Institution. We analyzed two anatomical definitions of liver dominance: total liver dominance (TLD) and hemiliver dominance (HLD). The following concepts were addressed: 1) Hepatic vein territories, 2) Hepatic vein dominance relationship, 3) Territorial belonging- patterns of the MHV to the right and left hemilivers, additionally an analysis of venous outflow in the central liver sectors was performed. RESULTS: Our results showed that: 1) The definitions of dominance: TLD vs. HLD overlap, displaying the MHV belonging, by taking into account the individual right hepatic vein (RHV) variability; 2) A dominant RHV for the whole liver indicates that the RHV is also dominant in the right hemiliver; 3) The MHV belongs predominantly to the left hemiliver (LHL); 4) The left hepatic vein (LHV) is dominant in the LHL. CONCLUSION: Both dominance definitions provide independent mappings of the liver and offer helpful insight into venous dominance relationship.

[Liver engineering as a new source of donor organs : A systematic review]. / "Liver engineering" als neue Quelle von Spenderorganen : Eine systematische Übersichtsarbeit.

BACKGROUND: Organ engineering is a new strategy to cope with the shortage of donor organs. A functional scaffold from explanted organs is prepared by removing all cellular components (decellularization) and the reseeding (repopulation) of the organ scaffold to generate a functional organ in vitro for transplantation. This technique was also applied to the liver (liver engineering). OBJECTIVES: Outline of the current state of the art and resulting approaches for future research strategies. MATERIAL AND METHODS: Systematic review according to the PRISMA guidelines: a PubMed-based literature search (search terms liver, decellularization), selection of relevant articles based on predetermined criteria for relevance (e.g. decellularization, repopulation and transplantation), extraction and critical appraisal of data and results concerning the conditions for decellularization, repopulation and transplantation. RESULTS: Decellularization was successfully performed in small and large animal models. Hepatocytes as well as stem cells and hepatic cell lines were applied for repopulation and 7 publications could show the successful transplantation of acellular and repopulated organ scaffolds. The current scientific need for further studies concerning the source of donor organs, optimization of the decellularization process, the cell type for the reseeding process and the establishment of the optimal conditions for the repopulation of the scaffold is still tremendous. For successful recellularization of the liver three goals need to be achieved: (1) reseeding of the organ scaffold with a sufficient amount of parenchymal cells, (2) endothelialization of the vascular tree to ensure the supply of oxygen and nutrients to parenchymal cells and (3) an appropriate epithelialization of the biliary tree. In order to progress to clinical trials a suitable transplantation model to verify the function of the organ constructs must be established. CONCLUSION: Liver engineering using biological cell-free organ scaffolds represents a scientific and ethical challenge. The existing results emphasize the potential of this new and promising strategy to create organs for transplantation in the future.

Analysis of grain boundary dynamics using event detection and cumulative averaging.

To analyze extended time series of high resolution images, we have employed automated frame-by-frame comparisons that are able to detect dynamic changes in the structure of a grain boundary in Au. Using cumulative averaging of images between events allowed high resolution measurements of the atomic relaxation in the interface with sufficient accuracy for comparison with atomistic models. Cumulative averaging was also used to observe the structural rearrangement of atomic columns at a moving step in the grain boundary. The technique of analyzing changing features in high resolution images by averaging between incidents can be used to deconvolute stochastic events that occur at random intervals and on time scales well beyond that accessible to single-shot imaging.