From Cleanroom to Desktop: Emerging Micro-Nanofabrication Technology for Biomedical Applications

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities

Gene expression profiling based identifications of potential prognostic molecular markers in decitabine treated acute myeloid leukemia

Introduction: The hypomethylating agent decitabine (DAC) represents a therapeutic option for acute myeloid leukemia (AML) patients who are not eligible for an intensive treatment regime. However, there are no reliable biomarkers available yet that can predict patients who will likely benefit from this epigenetic therapy. Therefore, we executed a gene expression analysis prior to the treatment of patients with DAC in order to evaluate gene expression patterns associated with response to DAC that ultimately might be used to predict DAC outcome. Patients had been entered in a multicenter phase II trial of DAC as first-line treatment of older AML patients judged unfit for induction chemotherapy (NCT00866073). Material and Methods: Specimens: Blood or bone marrow AML samples were collected from elderly patient who had been entered in a multicenter phase II trial of DAC as first-line treatment of older AML patients judged unfit for induction chemotherapy (NCT00866073). Cytogenetic and molecular genetic analyses: Samples were studied centrally by the lab of the AMLSG at the University Hospital of Ulm by conventional cytogenetic analysis and reverse transcriptase polymerase chain reaction (RT-PCR) for the recurring gene fusions resulting from t(8;21)(q22;q22), inv16(p13q22)/t(16;16)(p13;q22), t(15;17)(q22;q12-21), and t(9;11)(p22;q23), and all diagnostic samples were screened for mutations in FLT3 (FMS like tyrosine kinase 3), NPM1 (nucleophosmin), CEBPA (enhancer binding protein alpha) and DNMT3a (DNA methyltranferase). Gene expression profiling: A gene expression profiling analysis in clinically well annotated specimens (n=36) was executed using Affymetrix microarrays (Human Genome U133 Plus 2.0 Arrays; 3`IVT Express Kit) according to the manufacturer’s recommendations (Affymetrix, Santa Clara, CA). Filtering the fluorescence ratios JustRMA algorithm was applied. We investigated significant different gene expression patterns between responders and no responders DAC treatment. qRT-PCR: For Validation of the gene expression profiling results, we performed a quantitative RT-PCR analysis of randomly picked genes using the TaqMan 7900HT. Statistical Analysis: Supervised analyses including gene and pathway class comparison were carried out using BRB-Array Tools Version 4.3.0 Beta_3, and further statistical calculations were performed using SPSS, version 19 and Graph Prad-Prism version 5. Results and conclusion: While the study cohort comprised a heterogeneous group of AML patients, a class comparison analysis nevertheless could reveal a DAC response associated gene pattern comprising 301 genes at a significance level of p<0.05. This signature was enriched for genes belonging to pathways that are essential in immune response and tumor suppressor function such as the Notch pathway. While genes associated with DAC response including: ASCL2, INPP5D, MSI2, SLC24A3, PRAME, TNSFS9, MLL and several homoebox genes might be used as novel biomarkers, along genes that were significantly higher expressed in patients who did not respond to DAC treatment, such as IFI27, IFI44L reflecting an insufficient immune system, several TSG like THBS1, FAS, MX1 or genes involved in the Notch pathway including TRPS1, RBPJ, NOTCH2. The clinical implementation of findings warrants additional studies. In the future integrative analysis also taking epigenetic changes into account might further improve the value of transcriptomic based predictors and lead the way to improved patient management

Is There a Speculative Bubble in the Price of Gold?

Motivated by the current gold price boom, we investigate whether the rapidly growing investment activities have triggered a new asset price bubble. We draw on the convenience yield model and use commodity dividends to derive gold's fundamental value. Based on the deviations of the actual gold price from its fundamental value, we apply a Markov regime-switching Augmented Dickey- Fuller test to detect ex post and identify ex ante speculative gold price bubbles. The empirical evidence is favorable for a fundamentally justified price level even during the current period of a drastically rising gold price

The gold price in times of crisis

Motivated by the recent gold price boom, this paper examines whether an asset bubble exists in the gold market. We approximate gold's fundamental value using several econometric models and apply a Markov regime-switching Augmented Dickey–Fuller (ADF) test which has substantial power for detecting explosive behavior. Although our results are sensitive to the specification of the fundamental value, we show that a model accounting for the current European sovereign debt crisis accurately tracks the gold price observed in the market. We also note that inflation in a general commodity price index and gold ETF demand have a potential to explain the price trajectory

Does Futures Speculation Destabilize Spot Prices? New Evidence for Commodity Markets

Motivated by repeated price spikes and crashes over the last decade, we investigate whether the growing market shares of futures speculators destabilize commodity spot prices. We approximate conditional volatility and analyze how it is affected by speculative open interest. In this context, we split our sample into two equally long subperiods and document whether the speculative impact on conditional volatility increases. With respect to six heavily traded agricultural and energy commodities, we do not find robust evidence that this is the case.We thus conclude that the financialization of raw material markets does not make them more volatile

New Targeted Agents in Acute Myeloid Leukemia: New Hope on the Rise

The therapeutic approach for acute myeloid leukemia (AML) remains challenging, since over the last four decades a stagnation in standard cytotoxic treatment has been observed. But within recent years, remarkable advances in the understanding of the molecular heterogeneity and complexity of this disease have led to the identification of novel therapeutic targets. In the last two years, seven new targeted agents (midostaurin, gilteritinib, enasidenib, ivosidenib, glasdegib, venetoclax and gemtuzumab ozogamicin) have received US Food and Drug Administration (FDA) approval for the treatment of AML. These drugs did not just prove to have a clinical benefit as single agents but have especially improved AML patient outcomes if they are combined with conventional therapy. In this review, we will focus on currently approved and promising upcoming agents and we will discuss controversial aspects and limitations of targeted treatment strategies

Die deutsche Wirtschafts- und Finanzpolitik nach der Vereinigung

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel W 49 (55) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Do Commodity Index Traders Destabilize Agricultural Futures Prices

Motivated by repeated price spikes and crashes over the last decade, we investigate whether the intensive investment activities of commodity index traders (CITs) have destabilized agricultural futures markets. Using a stochastic volatility model, we treat conditional volatility as an unobserved component, and analyze whether it has been affected by the expected and unexpected open interest of CITs. However, with respect to twelve increasingly financialized grain, livestock, and soft commodities, we do not find robust evidence that this is the case. We thus conclude that justifying a tighter regulation of CITs by blaming them for more volatile agricultural futures markets appears to be unwarranted. JEL Classification: G10, G18, Q1