Search

Copyright of HMD: Praxis der Wirtschaftsinformatik is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Here, we show the conversion of unactivated alkenes into α‐branched enones via regioselective chloroacylation with acyl chlorides. The method relies upon the initial in situ generation of chlorine radicals directly from the acyl chloride precursor under cooperative nickel/photoredox catalysis. Subsequent HCl elimination provides enones and α,β‐unsaturated esters that are not accessible via the conventional acylation approaches that provide the other, linear constitutional isomer. [ABSTRACT FROM AUTHOR]

Here, we show the conversion of unactivated alkenes into α‐branched enones via regioselective chloroacylation with acyl chlorides. The method relies upon the initial in situ generation of chlorine radicals directly from the acyl chloride precursor under cooperative nickel/photoredox catalysis. Subsequent HCl elimination provides enones and α,β‐unsaturated esters that are not accessible via the conventional acylation approaches that provide the other, linear constitutional isomer. [ABSTRACT FROM AUTHOR]

The article discusses the "2020 Quick Fixes" introduced in European Union (EU) tax law, specifically focusing on their application to intra-community movements of goods. It addresses the issue of whether a valid Value-added tax identification number (USt-IdNr) of the recipient is required at the time of the movement for it to be considered an intra-community transfer. It highlights the lack of legal provisions for correcting such situations and argues for a compliant interpretation of EU law.

To date, very little research has been conducted regarding visitor satisfaction with operations at mega events and mass gatherings. We examine the user satisfaction of passengers of the Makkah Metro in Saudi Arabia during Hajj. Hajj is one of the largest mass gatherings in the world. Our aim is to compare the sensitivities towards waiting time of different user groups in order to identify user groups that are particularly sensitive to waiting time. Those user groups might then be scheduled preferably to the Hajj rituals in such a way that their expected waiting time is minimized. For this reason, we are interested in the interactions between the passengers' person-specific attributes and their perceived waiting time at the stations. We apply an ordered logit model to unique survey data. Our results reveal that women are much more sensitive to waiting time than men. In addition to gender, a pilgrim's country of origin also seems to play a significant role, which has operational implications on crowd management. [ABSTRACT FROM AUTHOR]

Spatially organized reaction dynamics between proto‐oncogenic epidermal growth factor receptor (EGFR) and protein tyrosine phosphatases determine EGFR phosphorylation dynamics in response to growth factors and thereby cellular behavior within developing tissues. We show that the reaction dynamics of mutual inhibition between RPTPγ phosphatase and autocatalytic ligandless EGFR phosphorylation enable highly sensitive promigratory EGFR signaling responses to subnanomolar EGF levels, when < 5% receptors are occupied by EGF. EGF thereby triggers an autocatalytic phospho‐EGFR reaction by the initial production of small amounts of phospho‐EGFR through transient, asymmetric EGF‐EGFR2 dimers. Single cell RPTPγ oxidation imaging revealed that phospho‐EGFR induces activation of NADPH oxidase, which in turn inhibits RPTPγ‐mediated dephosphorylation of EGFR, tilting the autocatalytic RPTPγ/EGFR toggle switch reaction towards ligandless phosphorylated EGFR. Reversibility of this reaction to EGF is maintained by the constitutive phosphatase activity of endoplasmic reticulum‐associated TCPTP. This RPTPγ/EGFR reaction at the plasma membrane causes promigratory signaling that is separated from proliferative signaling induced by accumulated, liganded, phosphorylated EGF‐EGFR in endosomes. Accordingly, loss of RPTPγ results in constitutive promigratory signaling from phosphorylated EGFR monomers. RPTPγ is thus a suppressor of promigratory oncogenic but not of proliferative EGFR signaling. Synopsis: Inhibition of RPTPγ‐catalyzed EGFR dephosphorylation is mediated by NADPH oxidase, and required for the phosphorylation of EGFR in response to growth factors. Here, the ROS‐mediated toggle‐switch coupling of RPTPγ to autocatalytic ligandless EGFR phosphorylation is shown to enable ultrasensitive EGFR activation and a promigratory response at the plasma membrane to physiological levels of EGF.EGF triggers an autocatalytic phosphorylation of ligandless EGFR by catalytic generation of small amounts of phospho‐EGFR through transient, asymmetric EGF‐EGFR2 dimers.The EGFR/RPTPγ (auto‐)catalytic toggle‐switch reaction is distinct from the canonical EGFR phosphorylation that occurs within stable EGF2‐EGFR2 dimers.RPTPγ/EGFR reaction dynamics are poised at the edge of bistability by endoplasmic reticulum‐associated TCPTP phosphatase activity, thus enabling cells to reversibly respond to low EGF stimuli while being robust to noise.RPTPγ is a suppressor of promigratory signaling from ligandless EGFR at the plasma membrane but not of proliferative signaling of liganded EGFR from endosomes. [ABSTRACT FROM AUTHOR]

Background: Incisional hernia is a frequent complication following loop ileostomy reversal. Incisional hernias are associated with morbidity, loss of health-related quality of life and costs and warrant the investigation of prophylactic measures. Prophylactic mesh implantation at the time of surgical stoma reversal has shown to be a promising and safe method to prevent incisional hernias in this setting. However, the efficacy of this method has not yet been investigated in a large multicentre randomised-controlled trial (RCT) with adequate external validity. The P.E.L.I.O.N. trial will evaluate the efficacy of prophylactic mesh reinforcement after loop ileostomy closure in decreasing the rate of incisional hernia versus standard closure alone. Methods: P.E.L.I.O.N. is a multicentre, patient- and observer-blind RCT. Patients undergoing loop ileostomy closure will undergo intraoperative 1:1 randomisation into either abdominal wall closure with a continuous slowly absorbable suture in small-stitch technique without mesh reinforcement (control group) or abdominal wall closure with an additional reinforcement with a retromuscular non-absorbable, macro-pore (pore size ≥ 1000 μm or effective porosity >0%) light-weight monofilament or mixed structure mesh. A total of 304 patients (152 per group) will need to be randomised in the study. Based on inclusion and exclusion criteria, 1,014 patients are expected to be screened for eligibility in order to recruit the necessary number of patients. The primary endpoint will be the frequency of incision hernias within 24 months according to the European Hernia Society definition. Secondary endpoints will be the frequency of surgical site occurrences (including surgical site infections, wound seromas and hematomas, and enterocutaneous fistulas), postoperative pain, the number of revision surgeries and health-related quality of life. Safety will be assessed by measuring postoperative complications ≥ grade 3 according to the Dindo-Clavien classification. Discussion: Depending on the results of the P.E.L.I.O.N. trial, prophylactic mesh implantation could become the new standard for loop ileostomy reversal. Trial registration: DRKS00027921, U1111-1273-4657 [ABSTRACT FROM AUTHOR]

Pd-catalyzed alkenylations of metallocenes via C–H activation were developed using electronically tunable pyrazolonaphthyridine (PzNPy) ligands. Ferrocene was alkenylated using the most electron-deficient ligand in the series, whereas the less reactive ruthenocene needed balancing of the electrophilicity and stability of catalysts. Various alkenes were installed, allowing fine-tuning of redox potentials. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Preventive healthcare facility location planning with quality-conscious clients" published in OR Spectrum. The correction addresses missing constraints in the mathematical model presented in the article. The correction ensures that the results in Table 1 align with the model formulation. The correction notice also includes a statement from the publisher, Springer Nature, emphasizing their neutrality regarding jurisdictional claims and institutional affiliations. The authors of the article are Ralf Krohn, Sven Müller, and Knut Haase. [Extracted from the article]

A key challenge to advance the efficiency of bioprocesses is the uncoupling of biomass from product formation, as biomass represents a by-product that is in most cases difficult to recycle efficiently. Using the example of rhamnolipid biosurfactants, a temperature-sensitive heterologous production system under translation control of a fourU RNA thermometer from Salmonella was established to allow separating phases of preferred growth from product formation. Rhamnolipids as bulk chemicals represent a model system for future processes of industrial biotechnology and are therefore tied to the efficiency requirements in competition with the chemical industry. Experimental data confirms function of the RNA thermometer and suggests a major effect of temperature on specific rhamnolipid production rates with an increase of the average production rate by a factor of 11 between 25 and 38 °C, while the major part of this increase is attributable to the regulatory effect of the RNA thermometer rather than an unspecific overall increase in bacterial metabolism. The production capacity of the developed temperature sensitive-system was evaluated in a simple batch process driven by a temperature switch. Product formation was evaluated by efficiency parameters and yields, confirming increased product formation rates and product-per-biomass yields compared to a high titer heterologous rhamnolipid production process from literature. [ABSTRACT FROM AUTHOR]

Pursuing the overarching goal of saving both lives and healthcare costs, we introduce an approach to increase the expected participation in a preventive healthcare program, e.g., breast cancer screening. In contrast to sick people who need urgent medical attention, the clients in preventive healthcare decide whether to go to a specific facility (if this maximizes their utility) or not to take part in the program. We consider clients' utility functions to include decision variables denoting the waiting time for an appointment and the quality of care. Both variables are defined as functions of a facility's utilization. We employ a segmentation approach to formulate a mixed-integer linear program. Applying GAMS/CPLEX, we optimally solved instances with up to 400 demand nodes and 15 candidate locations based on both artificial data as well as in the context of a case study based on empirical data within one hour. We found that using a Benders decomposition of our problem decreases computational effort by more than 50%. We observe a nonlinear relationship between participation and the number of established facilities. The sensitivity analysis of the utility weights provides evidence on the optimal participation given a specific application (data set, empirical findings). [ABSTRACT FROM AUTHOR]

In Germany enrolment in majors is of considerable interest to academic departments, because their budget depends on the number of enrolled students. Besides observed factors, we presume that unobserved latent variables influence the major‐choice decision of students. Using stated preferences data from a discrete choice experiment among students pursuing a bachelor's degree in business administration at Hamburg Business School (HBS), we employ an integrated choice and latent variable model (ICLV). Thereby, we model the influence of a major‐specific latent variable, labeled image, on the major‐choice decision of the students. To identify the latent variables, we utilise ordered categorical indicators that we obtained from the assessment of major‐specific psychometric factors among students. Our findings reveal a significant impact of the latent variable image on the major‐choice decision. We further show the advantageous characteristic of an ICLV model by illustrating the cause‐and‐effect relationship compared to classic multinomial logit models. Based on our results, we examine practice‐oriented, requirements, research, and supervision to be the most relevant psychometric factors that lead to the identification of the latent variables and provide insights on how academic departments at HBS can raise their major's attractiveness from the student's perspective. Abstrakt: In Deutschland ist die Immatrikulation in den Studiengängen für die Fachbereiche von großem Interesse, da ihr Budget von der Anzahl der eingeschriebenen Studierenden abhängt. Neben den beobachteten Faktoren nehmen wir an, dass nicht beobachtete latente Variablen die Schwerpunktwahl der Studierenden beeinflussen. Auf der Grundlage von Präferenzdaten aus einem diskreten Auswahlexperiment unter den Studierenden des Bachelor‐Studiengangs der Betriebswirtschaftslehre an der Hamburg Business School (HBS) verwenden wir ein integriertes Wahl‐ und latente Variablenmodell (ICLV). Dabei modellieren wir den Einfluss einer Schwerpunkt‐spezifischen latenten Variable, die als Image bezeichnet wird, auf die Schwerpunktwahl der Studierenden. Um die latente Variable zu identifizieren, verwenden wir geordnete kategorische Indikatoren, die wir aus der Bewertung der Schwerpunkt‐spezifischen psychometrischen Faktoren erhalten haben. Unsere Ergebnisse zeigen einen signifikanten Einfluss der latenten Variable Image auf die Schwerpunktwahl. Wir zeigen ferner die vorteilhafte Eigenschaft eines ICLV‐Modells, indem wir die Ursache‐Wirkungs‐Beziehung im Vergleich zu klassischen multinomialen Logit‐Modellen veranschaulichen. Basierend auf unseren Ergebnissen untersuchen wir Praxisorientierung, Anforderung, Forschung und Betreuung als die relevantesten psychometrischen Faktoren, die zur Identifizierung der latenten Variable führen und Einblicke geben, wie die Schwerpunkte der HBS die Attraktivität ihres Studienfachs aus der Perspektive der Studierenden erhöhen können. [ABSTRACT FROM AUTHOR]

The article informs about mathematical planning for safety in major events that commemorate a variety of traditional rituals over a multi-day journey with Islamic pilgrimage to Mecca. Topics include transferred mathematical planning methods from operations research to the security planning of the socially highly relevant mega-event; and mass accidents of implementation of the approaches by Saudi Arabian authorities with major challenge for creativity of architects, logisticians and engineers.

Titanium sheets were irradiated by free electron laser radiation in cw mode in pure nitrogen. Due to the interaction, nitrogen diffusion occurs and titanium nitride was synthesized in the tracks. Overlapping tracks have been utilized to create coatings in order to improve the tribological properties of the sheets. Caused by the local heating and the spatial dimension of the melt pool, convection effects were observed and related to the track properties. Stress, hardness, and nitrogen content were investigated with x-ray diffraction, nanoindention, and resonant nuclear reaction analysis. The measured results were correlated with the scan parameters, especially to the lateral track shift. Cross section micrographs were prepared and investigated by means of scanning electron microscopy. They show the solidification behavior, phase formation, and the nitrogen distribution. The experiments give an insight into the possibilities of materials processing using such a unique heat source. [ABSTRACT FROM AUTHOR]

With micro-Raman spectroscopy and x-ray diffraction (XRD), we studied ZnO crystals implanted with Mn, Fe, Co, and Ni, respectively, with implantation concentrations from 4 up to 16 at. %. Using thermal treatments in air up to 700 °C, we analyzed the annealing effect on the ZnO crystal lattice as well as the onset of secondary phases and their microstructure on the sample surface. While the 500 °C treatment induces a considerable annealing, secondary phases are observed for transition metal (TM) concentrations ≥8 at. % after the treatment at 700 °C. Their microstructure strongly depends on the TM species. Various stoichiometric and nonstoichiometric TM oxide precipitates as well as elemental TM clusters are identified by their Raman and XRD signatures and their possible magnetic impact is discussed. [ABSTRACT FROM AUTHOR]

Pulsed laser deposited ZnO films were implanted with vanadium ions using ion energies between 30 and 250 keV with different fluences yielding vanadium concentrations in the range between 0.8 and 5 at. %. After annealing under oxygen ambient at 800 °C, a broad luminescence band observed by photoluminescence covers nearly the total visible spectral region. This luminescence is a superposition of different bands triggered by the incorporated V and remaining implantation defects. The visual impression of the bright whitish emission of the implanted ZnO has been quantified using the color space map of the Commission internationale de l’Éclairage. Furthermore, the intensity of the white emission strongly increases with increasing V concentration, whereas Ar-implanted reference sample shows only weak white emission. [ABSTRACT FROM AUTHOR]

By Islam's principle, each adult Muslim who is physically and financially capable is obligated to perform Hajj—Pilgrimage to Mecca—once in his lifetime. With millions of faithful pilgrims, the Hajj is one the largest annual pedestrian events in the world. It is also a stress test to the authority's ability to protect pilgrims' safety throughout the multiday rituals. In "A Pilgrim Scheduling Approach to Increase Safety during the Hajj," K. Haase, M. Kasper, M. Koch, and S. Müller describe the combined optimization and simulation approach used in the years 2007–2014 and 2016–2017 to plan safe pilgrim flows between the ritual sites and pilgrim camps. The Hajj—the great pilgrimage to Mecca, Saudi Arabia—is one of the five pillars of Islam. Up to four million pilgrims perform the Hajj rituals every year. This makes it one of the largest pedestrian problems in the world. Ramy al-Jamarat—the symbolic stoning of the devil—is known to be a particularly crowded ritual. Up until 2006, it was repeatedly overshadowed by severe crowd disasters. To avoid such disasters, Saudi authorities initiated a comprehensive crowd management program. A novel contribution to these efforts was the development of an optimized schedule for the pilgrims performing the stoning ritual. A pilgrim schedule prescribes specific routes and time slots for all registered pilgrim groups. Together, the assigned routes strictly enforce one-way flows toward and from the ritual site. In this paper, we introduce a model and a solution approach to the Pilgrim Scheduling Problem. Our multistage procedure first spatially smooths the utilization of infrastructure capacity to avoid dangerous pedestrian densities in the network. In the next optimization step, it minimizes overall dissatisfaction with the scheduled time slots. We solve the Pilgrim Scheduling Problem by a fix-and-optimize heuristic, and subsequently simulate the results to identify necessary modifications of the scheduling constraints. Our numerical study shows that the approach solves instances with more than 2.3 million variables in less than 10 minutes on average. At the same time, the gap between optimal solution and upper bound never exceeds 0.28%. The scheduling approach was an integral part of the Hajj planning process in 2007–2014 and 2016–2017. No crowd disaster occurred in these years. Our approach was not applied in 2015, when a severe crowd crush happened close to the ritual site. We briefly discuss possible causes and consequences of this accident. [ABSTRACT FROM AUTHOR]

The Institute of Space Systems at Technische Universität Braunschweig has long-term experience in the field of space debris modeling. This article reviews the current state of ongoing research in this area. Extensive activities are currently underway to update the European space debris model MASTER. In addition to updating the historical population, the future evolution of the space debris environment is also being investigated. The competencies developed within these activities are used to address current problems with regard to the possibility of an increasing number of catastrophic collisions. Related research areas include, for example, research in the field of orbit determination and the simulation of sensor systems for the acquisition and cataloging of orbital objects. In particular, the ability to provide simulated measurement data for object populations in almost all size ranges is an important prerequisite for these investigations. Some selected results on the distribution of space debris on Earth orbit are presented in terms of spatial density. Furthermore, specific fragmentation events will be discussed. [ABSTRACT FROM AUTHOR]

Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been associated with poor prognosis and resistance towards chemotherapy in several cancer forms. In a previous study we found an association between a low TIMP-1 tumor immunoreactivity and increased survival for glioblastoma patients, when compared to moderate and high TIMP-1 tumor immunoreactivity. The aim of the present study was to further evaluate TIMP-1 as a biomarker in gliomas by studying TIMP-1 gene copy numbers by fluorescence in situ hybridization (FISH) on 33 glioblastoma biopsies and by measuring levels of TIMP-1 in plasma obtained pre-operatively from 43 patients (31 gliomas including 21 glioblastomas) by enzyme-linked immunosorbent assay (ELISA). The results showed TIMP-1 gene copy numbers per cell ranging from 1 to 5 and the TIMP-1/CEN-X ratio ranging between 0.7 and 1.09, suggesting neither amplification nor loss of the TIMP-1 gene. The TIMP-1 protein levels measured in plasma were not significantly higher than TIMP-1 levels measured in healthy subjects. No correlation was identified between TIMP-1 tumor cell immunoreactivities and the TIMP-1 gene copy numbers or the plasma TIMP-1 levels. In conclusion, high immunohistochemical TIMP-1 protein levels in glioblastomas were not caused by TIMP-1 gene amplification and TIMP-1 in plasma was low and not directly related to tumor TIMP-1 immunoreactivity. The study suggests that TIMP-1 immunohistochemistry is the method of choice for future clinical studies evaluating TIMP-1 as a biomarker in glioblastomas. [ABSTRACT FROM AUTHOR]

The Hajj, the annual Muslim pilgrimage to Makkah in Saudi Arabia, is one of the largest pedestrian events in the world. Each year, up to four million pilgrims approach the holy sites in the region of Makkah to perform their religious duty. The key ritual, the stoning-of-the-devil, is particularly crowded. Until 2006, several crowd-related disasters led to thousands of casualties. In the aftermath of such a disaster in early 2006, the Ministry of Municipal and Rural Affairs of the Kingdom of Saudi Arabia (MOMRA) launched many projects to prevent future crowd-related accidents. In particular, MOMRA began the development of an operations research (OR)-based decision support system (ORDSS) for crowd management. ORDSS employs a range of tools from OR, analytics, and crowd dynamics. At its core, it implements a scheduling tool and a real-time video tracking system. The video tracking system measures infrastructure utilization, and an integrated series of mixed-integer programs and quadratic programs balance capacity utilization by considering preferred stoning times and infrastructure capacities. The ORDSS provides MOMRA with solutions that enable uncongested and smooth pilgrim flows and extensive real-time reporting. From 2007 to 2014, OR helped stop the tragic loss of human life that resulted from these crowd-related accidents. Unfortunately, a crowd-related disaster, which resulted in hundreds of casualties, occurred during Hajj season 2015; however, for this Hajj season, the authors and MOMRA were no longer in charge of the scheduling and routing recommendations for the stoning-of-the-devil ritual during the Hajj. [ABSTRACT FROM AUTHOR]

The legacy created in pursuit of a mega-event, like the Olympic Games, FIFA World Cup, World’s Fair or the Hajj, can provide tremendous opportunities for the host to advance urban development. The challenge faced by cities is how to direct the public and private spending on desired legacies to support their pre-bid urban agendas. To provide guidance for scholars and event planners interested in using events to further urban development agendas, we present a framework for cataloguing the outcomes associated with mega-event planning. [ABSTRACT FROM PUBLISHER]

Purpose – This paper aims to consider spatial effects in the analysis of the relationship of revenue and service quality. When firms’ customers are located in spatially dispersed areas, it can be difficult to manage service quality on a geographically small scale because the relative importance of service quality might vary spatially. Moreover, standard approaches discussed so far in the marketing science literature usually neglect spatial effects, such as spatial dependencies (e.g. spatial autocorrelation) and spatial drift (spatial non-stationarity). Design/methodology/approach – The authors propose a comprehensive but intelligible approach based on spatial econometric methods that cover spatial dependencies and spatial drift simultaneously. In particular, they incorporate the spatial expansion method (spatial drift) into spatial econometric models (e.g. spatial lag model). Findings – Using real company data on seasonal ticket revenue (dependent variable) and service quality (independent variables) of a regional public transport service provider, the authors find that the elasticity for the length of the public transport network is between 0.2 and 0.5, whereas the elasticity for the headway is between −0.2 and 0.6, for example. The authors control for several socio-economic, socio-demographic and land-use variables. Practical implications – Based on the empirical findings, the authors show that addressing spatial effects of service data can improve management’s ability to implement programs aimed at enhancing seasonal ticket revenue. Therefore, they derive a spatial revenue response function that enables managers to identify small-scale areas that are most efficient in terms of increasing revenue by service improvement. Originality/value – The paper addresses the need to account for spatial effects in revenue response functions of public transport companies. [ABSTRACT FROM AUTHOR]

In this contribution we build on the approach proposed by Zhang et al. (OR Spectrum 34:349-370, ) to consider clients' choice in preventive health care facility location planning. The objective is to maximize the participation in a preventive health care program for early detection of breast cancer in women. In order to account for clients' choice behavior the multinomial logit model is employed. In this paper, we show that instances up to 20 potential locations and 400 demand points can be easily solved (to optimality or at least close to optimality) by a commercial solver in reasonable time if the problem is modeled by an alternative formulation. We present an intelligible approach to derive a lower bound to the problem. Our paper provides interesting insights into the trade-off between minimum workload requirement (to ensure quality of care) and participation (and thus early diagnosis of disease). We present a general definition of clients' utility (which allows for clients' characteristics, for example) and discuss some fundamental issues (and pitfalls) concerning the specification of utility functions. [ABSTRACT FROM AUTHOR]

In this contribution, we discuss a facility location model to maximize firms' patronage, while demand is determined by a multinomial logit model (MNL). We account for customer segmentation based on customer characteristics. Hence, we are able to reduce the bias to the objective, which is due to constant substitution patterns of the MNL. Numerical studies show that averaging customer characteristics yield a bias of more than 15 % of the objective function value compared to segmentation. Using GAMS/CPLEX, we are able to solve problem sets with 2 segments, 500 demand points and 10 potential locations to optimality in 1 h computation time. If we consider 50 potential locations, the gap reported by CPLEX is $$<$$ 8 % in 1 h. We present an illustrative case example of a furniture store company in Germany (data are available as electronic supplementary material to this article). The corresponding problem is solved to optimality in a few minutes. [ABSTRACT FROM AUTHOR]

Aims To check the usefulness of a standardized protocol of PTEN FISH in 31 endometrial carcinomas ( ECs) in comparison with SNP array ( SNPA), multiplex ligation-dependent probe amplification ( MLPA), and immunohistochemistry. Methods and results Fluorescence in-situ hybridization analysis showed two PTEN copies in 17 cases, three copies in nine cases, hemizygous deletion in two cases, and diverse cell populations with different PTEN copy number in three cases. A good correlation was seen between FISH and SNPA, particularly in cases with three copies. FISH identified two cases with entire deletion of chromosome 10, but did not identify a focal deletion of PTEN. Five cases with PTEN deletion and duplication of the second allele by SNPA were interpreted as normal by FISH. Concordance between FISH and MLPA was seen in 15 cases with two copies, and in two cases with PTEN deletion. Six cases were interpreted as amplified by MLPA, but showed polyploidy by FISH. FISH was superior to SNPA and MLPA in assessing the tumours with diverse cell populations with different PTEN copies. Conclusions The results show good concordance between FISH, SNPA and MLPA. SNPA was superior in tumours with deletion of one copy and duplication of the second allele. FISH was superior in assessing tumour heterogeneity. [ABSTRACT FROM AUTHOR]

Dieser Beitrag beschreibt die Herausforderungen einer kombinierten Simulation von Energie- und IKT-Systemen für die Untersuchung von Smart-Grid-Applikationen und ihrer Auswirkungen auf die Stabilität des elektrischen Energieübertragungssystems. Hierbei wird der Co-Simulator INSPIRE vorgestellt, der eine zeitsynchronisierte Simulation von Kommunikationsnetzwerk, Energiesystem, sowie Mess-, Schutz- und Regelungsapplikationen ermöglicht. This paper presents the challenges of a combined simulation of power and ICT systems for the analysis of smart grid applications and their impact on power system stability. Moreover, the INSPIRE co-simulation environment is outlined enabling a time-synchronized simulation of communication network, power system as well as monitoring, protection and control systems. [ABSTRACT FROM AUTHOR]

Low energy ion beam pattern formation on Si with simultaneous co-deposition of Ag, Pd, Pb, Ir, Fe or C impurities was investigated by in situ scanning tunneling microscopy as well as ex situ atomic force microscopy, scanning electron microscopy, transmission electron microscopy and Rutherford backscattering spectrometry. The impurities were supplied by sputter deposition. Additional insight into the mechanism of pattern formation was obtained by more controlled supply through e-beam evaporation. For the situations investigated, the ability of the impurity to react with Si, i.e. to form a silicide, appears to be a necessary, but not a sufficient condition for pattern formation. Comparing the effects of impurities with similar mass and nuclear charge, the collision kinetics is shown to be not of primary importance for pattern formation. To understand the observed phenomena, it is necessary to assume a bi-directional coupling of composition and height fluctuations. This coupling gives rise to a sensitive dependence of the final morphology on the conditions of impurity supply. Because of this history dependence, the final morphology cannot be uniquely characterized by a steady state impurity concentration. [ABSTRACT FROM AUTHOR]

Background: Platinum-based chemotherapy has long been used in the treatment of a variety of cancers and functions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and have previously been implicated in resistance to platinum compounds. The aim of the current investigation is to determine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations in colorectal cancer (CRC).Methods: Fluorescent in situ hybridization probes directed at ERCC1 and ERCC4 with relevant reference probes were constructed. Probes were tested in a CRC cell line panel and in tumor sections from 152 stage III CRC chemonaive patients. Relationships between biomarker status and clinical endpoints (overall survival, time to recurrence, and local recurrence in rectal cancer) were analyzed by survival statistics.Results: ERCC1-19q13 copy number alterations were observed in a single cell line metaphase (HT29). In patient material, ERCC1-19q13 copy number gains (ERCC1-19q13/CEN-2 ≥ 1.5) were detected in 27.0% of specimens, whereas ERCC1-19q13 deletions (ERCC1-19q13/CEN-2 < 0.8) were only detected in 1.3%. ERCC1-19q13 gain was significantly associated with longer survival (multivariate analysis, HR: 0.45, 95% CI: 0.20-1.00, p = 0.049) in patients with colon tumors, but not rectal tumors. No ERCC4 aberrations were detected and scoring was discontinued after 50 patients.Conclusions: ERCC1-19q13 copy number gains occur frequently in stage III CRC and influences survival in patients with colon tumors. Future studies will investigate the effect of ERCC1-19q13 aberrations in a platinum-treated patient population with the aim of developing a predictive biomarker profile for oxaliplatin sensitivity in CRC. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate factors that determine the adoption of photovoltaic (PV) systems. Our case study of the city of Wiesbaden, Germany, is based on a geocoded data set of the grid-connected PV systems set up through 2009. We aim to determine whether the decision to install can be explained by peer effects measured by preexisting installations in the vicinity, i.e. the installed base which is determined for each decision-maker individually. We employ a binary panel logit model and control for spatial variations in buying power and population density. Our analysis reveals a significantly positive influence of previously installed systems located nearby on the decision to install a PV system. [ABSTRACT FROM AUTHOR]

Background: Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III CRC and how these can be detected by fluorescent in situ hybridization (FISH). Methods: Nine CRC cell line metaphase spreads were analyzed by FISH with a TOP1 probe in combination with a reference probe covering either the centromeric region of chromosome 20 (CEN-20) or chromosome 2 (CEN-2). Tissue sections from 154 chemonaive stage III CRC patients, previously studied with TOP1/CEN-20, were analyzed with TOP1/CEN-2. Relationships between biomarker status and overall survival (OS), time to recurrence (TTR) in CRC and time to local recurrence (LR; rectal cancer only) were determined. Results: TOP1 aberrations were observed in four cell line metaphases. In all cell lines CEN-2 was found to reflect chromosomal ploidy levels and therefore the TOP1/CEN-2 probe combination was selected to identify TOP1 gene gains (TOP1/CEN-2≥1.5). One hundred and three patients (68.2%) had TOP1 gain, of which 15 patients (14.6%) harbored an amplification (TOP1/CEN-20≥2.0). TOP1 gene gain did not have any association with clinical endpoints, whereas TOP1 amplification showed a non-significant trend towards longer TTR (multivariate HR: 0.50, p = 0.08). Once amplified cases were segregated from other cases of gene gain, non-amplified gene increases (TOP1/CEN-2≥1.5 and TOP1/CEN-20<2.0) showed a trend towards shorter TTR (univariate HR: 1.57, p = 0.07). Conclusions: TOP1 gene copy number increase occurs frequently in stage III CRC in a mechanism that often includes CEN-20. Using CEN-2 as a measurement for tumor ploidy levels, we were able to discriminate between different mechanisms of gene gain, which appeared to differ in prognostic impact. TOP1 FISH guidelines have been updated. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: A Topoisomerase 1 (Top1) poison is frequently included in the treatment regimens for metastatic colorectal cancer (mCRC). However, no predictive biomarkers for Top1 poisons are available. We here report a study on the TOP1 gene copy number in CRC patients and its association with patient prognosis and tumor cell proliferation. Experimental design: The study included TOP1 and CEN-20 fluorescence in situ hybridization (FISH) analyses on formalin fixed paraffin embedded (FFPE) tissue sections from 154 stage III CRC chemonaïve patients. The frequencies of aberration in the TOP1 gene copy number, the CEN-20 copy number and the TOP1/CEN-20 ratio were analyzed and associated with overall survival (OS), time to recurrence (TTR) and in a subgroup analysis of rectal cancer patients only with time to local recurrence (LR in RC). Moreover, the TOP1 and CEN-20 copy numbers were correlated with the tumor Ki67 proliferation index. Results: 35.7% of the tumors had an increased TOP1 copy number above 4n gene copies per cell and 28.6% and 9.7% had a TOP1/CEN-20 ratio ≥1.5 or ≥2.0, respectively. The TOP1 copy number and the TOP1/CEN-20 ratios were separately added into multivariate analyses as continuous variables, in which also age, gender, primary tumor location and Ki67 status were added as covariates. In contrast to the TOP1/CEN-20 ratio, the TOP1 copy number was significantly associated with OS (HR: 0.62; 95% CI: 0.42–0.90; p = 0.01). Neither the TOP1 copy number nor the ratio was significantly associated with TTR and only the TOP1/CEN-20 ratio was significantly associated with LR in RC (HR: 0.25; 95% CI: 0.08–0.83; p = 0.02). No significant correlation was found between the TOP1 copy number and proliferation, while a weak and inverse correlation between the CEN-20 copy number and proliferation was observed. Conclusions: This study showed that increased TOP1 gene copy numbers are frequent findings in cancer cells in stage III CRC tumors but unrelated to the proliferative status of the tumors. The association with prognosis is important to consider when planning and analyzing future studies investigating TOP1 as a potential predictive biomarker for Top1 poisons. [Copyright &y& Elsevier]