Efficient Engineering and Production Concepts for Products in Regulated Environments – Dream or Nightmare?

Manufacturing of chemical‐pharmaceutical products is moving increasingly fast on a global scale. Therefore, developing and starting up production facilities fast, with high quality, and at reasonable costs has become extremely challenging. Engineering concepts like modularization, standardization and simultaneous/parallel engineering are discussed as methods for speeding up process design and filing for regulatory approval. Transfer from batch to continuous operation mode of production is pointed out as the key‐issue in such strategies.     

Increasing Role of Targeted Immunotherapies in the Treatment of AML

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The standard of care in medically and physically fit patients is intensive induction therapy. The majority of these intensively treated patients achieve a complete remission. However, a high number of these patients will experience relapse. In patients older than 60 years, the results are even worse. Therefore, new therapeutic approaches are desperately needed. One promising approach in high-risk leukemia to prevent relapse is the induction of the immune system simultaneously or after reduction of the initial tumor burden. Different immunotherapeutic approaches such as allogenic stem cell transplantation or donor lymphocyte infusions are already standard therapies, but other options for AML treatment are in the pipeline. Moreover, the therapeutic landscape in AML is rapidly changing, and in the last years, a number of immunogenic targets structures eligible for specific therapy, risk assessment or evaluation of disease course were determined. For example, leukemia-associated antigens (LAA) showed to be critical as biomarkers of disease state and survival, as well as markers of minimal residual disease (MRD). Yet many mechanisms and properties are still insufficiently understood, which also represents a great potential for this form of therapy. Therefore, targeted therapy as immunotherapy could turn into an efficient tool to clear residual disease, improve the outcome of AML patients and reduce the relapse risk. In this review, established but also emerging immunotherapeutic approaches for AML patients will be discussed.     

Fault diagnosis of nonlinear systems using structured augmented state models

This paper presents an internal model approach for modeling and diagnostic functionality design for nonlinear systems operating subject to single- and multiple-faults. We therefore provide the framework of structured augmented state models. Fault characteristics are considered to be generated by dynamical exosystems that are switched via equality constraints to overcome the augmented state observability limiting the number of diagnosable faults. Based on the proposed model, the fault diagnosis problem is specified as an optimal hybrid augmented state estimation problem. Sub-optimal solutions are motivated and exemplified for the fault diagnosis of the well-known three-tank benchmark. As the considered class of fault diagnosis problems is large, the suggested approach is not only of theoretical interest but also of high practical relevance.     

Didesoxy-Ribonucleoside durch Schmelzkondensation

Dideoxy Ribonucleosides by Fusion Method The dideoxy nucleosides 2 , 4 and 6 are synthesized from the 1-O-acetyl-2,3-dideoxyribose derivatives 1 , 3 and 5 by fusion with chlorinated purines and other nitrogen heterocycles at 110–120°C without added catalyst. The ¹H-NMR and ¹³C-NMR spectra of the compounds are given.     

Diazoverbindungen. 72. (Diazoalkyl)phosphane – Synthese durch elektrophile Diazoalkansubstitution und oxidative Additionsreaktionen am Phosphor

Diazo Compounds. 72. Diazoalkylphosphanes – Synthesis by Electrophilic Diazoalkane Substitution and Oxidative Addition Reactions at Phosphorus Electrophilic diazoalkane substitution of the diazomethyl compounds 1a,b with the chloro phosphanes 2a-o in the presence of lithium diethylamide yields the diazoalkyl phosphanes 3a-z . Oxidative addition of oxygen, sulfur and selenium at phosphorus leads into the series of oxo, thioxo and selenoxo phosphanes having diazoalkyl substituents ( 4a-d, 5a-m and 7a-d ). The silyl group of 5n,o is cleaved by chromatography on aluminium oxide to yield the (diazomethyl)phosphane sulfides 6a,b .     

Shigella Outer Membrane Vesicles as Promising Targets for Vaccination

The clinical symptoms of shigellosis, a gastrointestinal infection caused by Shigella spp. range from watery diarrhea to fulminant dysentery. Endemic infections, particularly among children in developing countries, represent the majority of clinical cases. The situation is aggravated due to the high mortality rate of shigellosis, the rapid dissemination of multi-resistant Shigella strains and the induction of only serotype-specific immunity. Thus, infection prevention due to vaccination, encompassing as many of the circulating serotypes as possible, has become a topic of interest. However, vaccines have turned out to be ineffective so far. Outer membrane vesicles (OMVs) are promising novel targets for vaccination. OMVs are constitutively secreted by Gram-negative bacteria including Shigella during growth. They are composed of soluble luminal portions and an insoluble membrane and can contain toxins, bioactive periplasmic and cytoplasmic (lipo-) proteins, (phospho-) lipids, nucleic acids and/or lipopolysaccharides. Thus, OMVs play an important role in bacterial cell–cell communication, growth, survival and pathogenesis. Furthermore, they modulate the secretion and transport of biomolecules, the stress response, antibiotic resistance and immune responses of the host. Thus, OMVs serve as novel secretion machinery. Here, we discuss the current literature and highlight the properties of OMVs as potent vaccine candidates because of their immunomodulatory, antigenic and adjuvant properties.     

Stir bar sorptive extraction and trace analysis of selected endocrine disruptors in water, biosolids and sludge samples by thermal desorption with gas chromatography-mass spectrometry

Stir bar sorptive extraction (SBSE) in combination with thermal desorption coupled to gas chromatography-mass spectrometry (GC-MS) was successfully applied to analyze a range of endocrine disrupting compounds (EDCs) in wastewater, solids and sludge. The targeted EDCs include sex steroid hormones, phthalates, alkylphenols and tamoxifen. Recovery for the EDCs using this analytical technique ranged from 44% to 128%. Limit of detection (LOD) of the compounds was 2.0 ng/L for water samples and 0.02 ng/g for solid samples, whereas the limit of quantitation (LOQ) was 5.0 ng/L for water samples and 0.06 ng/g for solid samples. When this analytical technique was applied to measure EDC concentration in a biological nutrient removal (BNR) wastewater treatment plant located in South East Queensland, Australia, the results showed that there were high amounts of phthalates, alkylphenols and female hormones present in the raw influent wastewater and solids. These concentrations were dramatically reduced after passing through the various treatment zones of the bioreactor (anaerobic, aerobic and anoxic).     

Energy-aware resource sharing with mobile devices

Ad hoc sharing of resources by offering remote services through an appropriate infrastructure enables new applications for mobile devices. However, the willingness of device owners to contribute resources to such applications remains low as long as they cannot control the amount of energy spent in sharing. In this paper, we present a framework for energy-aware resource sharing among mobile devices of various kinds that comprises (1) energy-aware strategies for selecting remote service providers and (2) a generic energy estimator for forecasting and accounting the energy consumption of a remote service call. To illustrate the benefit of (1), we show by simulation that the battery lifetime of devices running the framework can be extended up to 40% by service selection strategies that take into account the energy cost of a requested service compared to energy-unaware (random) service selection. For providing the energy-related input for service selection, we present (2) a generic estimator that can be customized easily for different hardware-platforms by solving a linear equation system with coefficients derived from benchmark measurements. We present a prototype-based case study for three different platforms, the Nokia N810, the HTC Touch Cruise and the Samsung Galaxy S showing that for all of them the estimation error is below 10% for 90% of the service calls. Furthermore, measurements conducted with a prototype implementation of the resource sharing framework show that battery lifetime can in fact be extended by energy-aware service selection strategies.