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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]

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]

Correction to Krohn, Ralf, Sven Müller, and Knut Haase. “Correction to: Preventive healthcare facility location planning with quality-conscious clients.” OR Spectrum (2024): 1-1. [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.

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]

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]

Background and Aim: In up to 3% of laparoscopic cholecystectomies, procedure-related complications occur. Routine postoperative ultrasound is one means of screening for these complications. The aim of this study was to determine the utility of this practice after laparoscopic cholecystectomy. Methods: A series of consecutive patients (n = 1,044) undergoing laparoscopic cholecystectomy from January 2007 to January 2011 was analysed. Primary endpoint was the detection of procedure-related complications by routine ultrasound. Results: Routine ultrasound within the first 48 h after laparoscopic cholecystectomy was performed in 967 of 1,044 patients. Overall, 25 (2.4%) of the 1,044 patients suffered from procedure-related complications, but only in 2 patients was the complication detected by routine ultrasound. Findings were false-positive in 103 patients. This corresponds to a sensitivity of 8% and a specificity of 89%. Hospital stay was prolonged in the false-positive group. Conclusion: Routine postoperative ultrasound has a low sensitivity for the detection of complications after laparoscopic cholecystectomy. In almost all cases, the diagnosis is initiated by clinical findings. Therefore, routine ultrasound is of limited value in screening for postoperative complications after cholecystectomy. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In a spatial context, flexible substitution patterns play an important role when modeling individual choice behavior. Issues of correlation may arise if two or more alternatives of a selected choice set share characteristics that cannot be observed by a modeler. Multivariate extreme value ( MEV) models provide the possibility to relax the property of constant substitution imposed by the multinomial logit ( MNL) model through its independence of irrelevant alternatives ( IIA) property. Existing approaches in school network planning often do not account for substitution patterns, nor do they take free school choice into consideration. In this article, we briefly operationalize a closed-form discrete choice model (generalized nested logit [ GNL] model) from utility maximization to account for spatial correlation. Moreover, we show that very simple and restrictive models are usually not adequate in a spatial choice context. In contrast, the GNL is still computationally convenient and obtains a very flexible structure of substitution patterns among choice alternatives. Roughly speaking, this flexibility is achieved by allocating alternatives that are located close to each other into nests. A given alternative may belong to several nests. Therefore, we specify a more general discrete choice model. Furthermore, the data and the model specification for the school choice problem are presented. The analysis of free school choice in the city of Dresden, Germany, confirms the influence of most of the exogenous variables reported in the literature. The estimation results generally indicate the applicability of MEV models in a spatial context and the importance of spatial correlation in school choice modeling. Therefore, we suggest the use of more flexible and complex models than standard logit models in particular. En un contexto espacial, los patrones sustitución flexible juegan un papel importante en el modelamiento del comportamiento de las decisiones individuales. Varios problemas de correlación pueden presentarse si dos o más alternativas de elección comparten características no observables por el modelador. Los modelos de valor extremo ( multivariate extreme value-MEV) ofrecen la posibilidad de relajar la propiedad de sustitución constante (constant substitution) presente en los modelos logit multinomiales ( multinomial logit-MNL), a través de su propiedad de independencia de alternativas irrelevantes ( Independence of irrelevant alternatives property -IIA). A menudo, los enfoques existentes en la planificación de redes escolares no toman en consideración los patrones de sustitución y de libre elección de escuela. En este artículo, los autores presentan brevemente el funcionamiento de un modelo de elección discreta (discrete choice model) para la maximización de utilidad o modelo logit anidado generalizado ( generalized nested logit model-GNL) para dar cuenta de la autocorrelación espacial. Los autores sostienen que modelos demasiado simples y restrictivos no suelen ser adecuados en un contexto de elección espacial. En contraste el modelo GNL es conveniente en términos de su computación y obtiene una estructura muy flexible de los patrones de sustitución entre las alternativas de elección. En términos generales, esta flexibilidad se logra mediante la asignación (o anidación) de las alternativas cercanas en el espacio (una alternativa puede pertenecer a varios nidos). Por lo tanto, los autores presentan un modelo de elección discreta más general. El estudio presenta además datos y la especificación del modelo para un caso de elección de escuela concreto: el análisis de libre elección de escuela en la ciudad de Dresden, Alemania. El análisis confirma la influencia de la mayoría de las variables exógenas presentes en la literatura. Los resultados de la estimación demuestran en términos generales la aplicabilidad de los modelos MEV en un contexto espacial y la importancia de la autocorrelación espacial en el modelado de elección de escuela. Los autores concluyen sugiriendo el uso de modelos más flexibles y complejos que los modelos utilizados habitualmente, en particular los modelos logit estándar. 从空间视角看，灵活的替代模式在个人行为选择建模中发挥着重要作用。当存在两个或两个以上备选方案集具有共性且无法被建模者观察到时，就可能出现相关性问题。多元极值模型（MEV）通过不相关的替代属性（IIA）实现了对多元logit模型（MNL）中常数限制的松弛替代。现有校园网络规划方法通常无法解释替代模式，而且没有考虑到自由择校因素。本文简要地建立一个封闭离散选择模型（广义嵌套（GNL）模型），从效用最大化角度来解释空间相关性。此外分析还表明，非常简单的约束模型通常不具有足够的空间选择情境。相比之下，GNL模型计算便捷，且可以在各选择方案中获得非常灵活的替代模式。大致而言，这种灵活性大体是通过与住处位置距离上彼此靠近的替代选择分配而获得，一个给定的选择可能属于不同的住处。因此，我们给出了一个更一般的离散选择模型。此外，还给出了针对择校问题的数据和模型设定。基于德国德累斯顿市自由择校分析，证实了已有研究中多数外生变量的影响。估计结果证实了MEV模型在空间分析中的适用性以及择校模型中空间相关的重要性，并建议使用更加灵活和复杂的模型而不是标准的logit模型。 [ABSTRACT FROM AUTHOR]

The aim of this article is to establish the extent to which the history of music can offer new perspectives on the modern period. We need a change of perspective, moving away from the aesthetic debates on music to an investigation of actual experiences and practices of participants. Audience behaviour provides a link between musical production and society. In order to make opera houses and concert halls visible as social spheres, this article draws on examples from the musical life of Berlin and London in the 1800s. Music should no longer be regarded as a peripheral phenomenon, but instead as a potential historical question. The analysis of musical performances prompts at least one: music matters. [ABSTRACT FROM AUTHOR]

A key component of task preparation may be to anticipate the consequences of task-appropriate actions. This task switching study examined whether such type of 'intentional' preparatory control relies on the presentation of explicit action effects. Preparatory BOLD activation in a condition with task-specific motion effect feedback was compared to identical task conditions with accuracy feedback only. Switch-related activation was found selectively in the effect feedback condition in the middle mid-frontal gyrus and in the anterior intraparietal sulcus. Consistent with research on attentional control, the posterior superior parietal lobule exhibited switch-related preparatory activation irrespective of feedback type. To conclude, preparatory control can occur via complementary attentional and intentional neural mechanisms depending on whether meaningful task-specific action effects lead to the formation of explicit effect representations. [ABSTRACT FROM AUTHOR]

Abstract: Copy number changes in TOP2A have frequently been linked to ERBB2 (HER2) amplified breast cancers. To study this relationship, copy number changes of ERBB2 and TOP2A were investigated by fluorescence in situ hybridization (FISH) in two cell lines; one characterized by having amplification of both genes and the other by having amplification of ERBB2 and deletion of TOP2A. The characteristics are compared to findings on paired ERBB2 and TOP2A data from 649 patients with invasive breast cancer from a previously published biomarker study. The physical localization of FISH signals in metaphase spreads from cell lines showed that simultaneous amplification is not a simple co-amplification of a whole amplicon containing both genes. Most gene signals are translocated to abnormal marker chromosomes. ERBB2 genes but not TOP2A genes are present in tandem amplicons, leading to a higher ERBB2 ratio. This observation was confirmed by patient FISH data: among 276 (43% of all patients) abnormal tumors, 67% had different ERBB2 and TOP2A status. ERBB2 amplification with normal TOP2A status was found in 36% of the abnormal tumors (15% of all patients). Simultaneous amplification of both genes was found in 28% of the abnormal tumors (12% of all patients) while TOP2A deletion and ERBB2 amplification was observed in 16% of the abnormal cases (8% of all patients). A small number of tumors had TOP2A amplification (4%) or deletion (6%) without simultaneous changes of the ERBB2 gene. ERBB2 deletion was also observed (5%) but only in tumors with simultaneous TOP2A deletion. The average gene/reference ratio was significantly different: 5.0 for TOP2A but 7.2 for ERBB2 in the amplified tumors (P <0.01). Amplification of the two genes may be caused by different mechanisms, leading to higher level of amplification for ERBB2 compared to TOP2A. In the majority of breast cancer patients, simultaneous aberration of ERBB2 and TOP2A is not explained by simple co-amplification. [Copyright &y& Elsevier]

The subject of this paper is a new approach to multiperiod school location planning in urban areas. Most of the existing approaches in the field do not consider free school choice nor are they able to consider substitution effects between school locations. We minimize the location and transport costs with respect to students choosing the school with the highest utility. Since these school choice probabilities (determined by a mixed multinominal logit model) depend on the available schools, we have to consider two steps. First, we generate for each period a set of scenarios indicating which school is open and which is not. For each scenario we allocate the students to available schools according to capacity and utility. Second, we select for each period one scenario in order to minimize total costs. Problems with a long planning horizon and a large number of demand points are solvable. We apply this approach to schools of the City of Dresden, Germany. [ABSTRACT FROM AUTHOR]

Abstract: Because of declining enrollment and school closures in some German regions students have to choose a certain school location from a reduced set of schools. For the analysis of adverse effects of school closures on transport mode choice the patterns of school choice are specified first. It seems that proximity and the profile offered (languages as a core for example) are adequate factors. Second, the travel-to-school mode choice are modelled using a multinomial logit approach, since students might switch from low cost transport modes (cycling for instance) to modes with remarkably higher costs (public transport for instance). Here, the most influencing factors are distance, car availability and weather. Furthermore, these findings are incorporated into a case study to quantify the effects of a modal-shift (switch from one transport mode to another). For this analysis a comprehensive survey was undertaken and a method of data disaggregation and geocoding is presented. [Copyright &y& Elsevier]

Abstract: The use of Kobayashi vinylogous aldol reaction in the reaction with acetaldehyde led to anti-aldol product 11. After reductive removal of the chiral auxiliary, the primary alcohol was converted to the allyliodide 14. This compound could be engaged in an Evans alkylation reaction, leading eventually to hydroxy acid 19. Inclusion of a Mitsunobu inversion reaction on the sequence starting with ent-11 led to hydroxy ester 30, featuring a 6,7-syn-configuration. These hydroxy acids should help to elucidate the correct stereostructure of the chondramide depsipeptides. [Copyright &y& Elsevier]

Abstract: Piperidinones with a 2-bromobenzyl substituent in the 5-position were subjected to a Heck coupling reaction with ethyl acrylate resulting in the highly functionalized cinnamates 9a–d. A subsequent deprotonation of the piperidinones using NaN(SiM3)2 in THF induced an intramolecular Michael addition of the enolate to the cinnamate part. In this way, a range of novel 2,6-methano-4H-4-benzazonines 10–13 were obtained. In each case, a separable mixture of endo/exo-diastereomers was obtained. [Copyright &y& Elsevier]

The long 19th century was not only the era of the industrial and political revolutions -- it was the heyday of musical performances and musical representations as well. Opera-going was an integral part of the leisure time of the European aristocracy and the bourgeoisie in the 19th century. Opera-houses, therefore, mattered because they were not only musical but social spheres as well. Thus, in the framework of social conventions, the public appropriation and evaluation of music had a twofold function in the metropolitan societies during the 19th century: on the one hand, it confirmed social identity by a habitualized social practice; on the other hand, a taste for art practically displayed served as a means of distinction, in order to maintain and sustain borderlines and distances within society and in order to label oneself as an individual or a social group. The article concentrates on the social influence, cultural practice and political significance of opera-going in Berlin and London, and it intends to reveal the primarily social and habitual functions of musical entertainments by analysing the behaviour of audiences, rather than by looking at the music itself. Of particular importance was the development of a new behaviour of listening during the performances. The article demonstrates with the help of Norbert Elias categories, how a more or less inattentive audience increasingly disciplined itself and gradually turned into »listeners« in the second half of the 19th century as a part of a »process of civilization«. Moreover, the transfer of cultural norms between the two cities -- like, first and foremost, the habit of silent listening and the elevation of »absolute music« -- epitomizes the emergence of a common European culture of music. The point is to compare the development of common cultural practices and forms of public representation in Europe. The communication about music, therefore, can be understood as an integral part of an emerging European elite culture, which referred to common cultural institutions, ideals, and practices. [ABSTRACT FROM AUTHOR]

Abstract: To examine whether the fission yeast Mam1 ABC transporter can be used for secretion of heterologous proteins, thereby bypassing the classical secretion pathway, we have analyzed chimeric forms of the M-factor precursor. It was demonstrated that GFP can be exported when fused to both the amino-terminal prosequence from mfm1 and a CaaX motif. This secretion was dependent on the Mam1 transporter and not the classical secretion pathway. The secretion efficiency of GFP, however, was relatively low and most of the reporter protein was trapped in the vacuolar membranes. Our findings suggest that the Mam1 ABC protein is a promiscuous peptide transporter that can accommodate globular proteins of a relatively large size. Furthermore, our results help in defining the sequences required for processing and secretion of natural M-factor. [Copyright &y& Elsevier]

The First World War polarised British society. The British 'nation' needed a definition of the external enemy to generate internal cohesion as much as the production of modern hostility presupposed the existence of nationalism. Apparently, hostility which is nationalistically motivated is of functional importance for the cohesion of a society in war. But the construction of the nation along the lines of the dialectic structure of exclusion and inclusion implies that even its founding act encourages national splits. The manner in which nationalism generates social cohesion by excluding non-members at the same time always turns it into the expression of and the reason for internal conflicts. First and foremost, however, it was the co-existence of a whole host of concepts of the nation competing with each other for supremacy which turned nationalism into a disintegrative power in society. The co-existing national concepts by and large reflected the political factions and camps in the belligerent society. This article tries to outline the various ways in which the borderlines between the internal and the external enemy, between the hostile part of one's own society and a hostile foreign society converged under the circumstances of the exceptional burden of the First World War. At the end the hostility which was motivated and legitimised nationalistically both split and integrated British society. [ABSTRACT FROM AUTHOR]

• New insights into trade-offs between energy expenditure and other variables. • Improved understanding on substitution between means of transport. • Analysis of elasticities of energy input and social welfare. • Economic model of planning policies for commute-to-school. Altering the network of public facilities like schools is likely to affect travel choices, in particular route and mode choice. Traveling to school is not only a major contributor to public transport demand in peak periods, but is in many instances also the trip purpose where young people are engaged in bicycling. However, in contrast to public transport, an active travel mode like bicycling needs (substantial) own physical activity as input into the 'production' of a trip. The objective of this paper is to improve our understanding of the substitution between bicycling and public transport in school travel focusing on an underrated determinant in the literature – the personal effort (e.g. energy input in terms of kcal) of students when traveling by bike (or walk). It is shown that a local government aiming at maximizing social welfare when making decisions on the density of public school facilities would be well advised to take this cross effect into account. We use a large unique data set of travel-to-school mode choice in the city of Dresden (Germany). We estimate a series of multivariate extreme value models and derive the elasticity of bike usage and the cross-elasticity of public transport demand with respect to the physical effort. The results reveal that effort elasticity of bike usage is significantly negative, whereas the effort cross-elasticity of public transport demand is significantly positive. In both cases, the responses are highest for school travel distances between 1 and 3 km, but relatively inelastic, meaning that a widespread adoption of pedelecs (or even e-bikes) in school travel could have only limited impacts on peak-period public transport demand. [ABSTRACT FROM AUTHOR]

This paper analyses the way students travel to school and examines the influence of environmental conditions on travel patterns. More specifically, it studies how topographic changes affect the likelihood of choosing cycling as a transport mode. We use mode choice data on students' home-to-school commuting trips from a previous study by Müller et al. (2008). The results show that models perform better when they account for the topographic conditions of the urban environment. We included this information in the model by introducing the "energy exerted" variable, which significantly improves the model and the results. The implications of this study are manifold; it guides the consolidation or expansion of school-based transportation network planning in Germany and prompts further analysis of active transportation systems, such as bike, pedelec and e-bike sharing systems. Overall, transportation policy should seek to foster active transportation, as it provides the greatest benefits for society and has a direct impact on people's well-being, while notably reducing the negative environmental and socioeconomic impacts of motorized transport. [ABSTRACT FROM AUTHOR]

Abstract: We report on the effective reduction of AlN host lattice defect cathodoluminescence by high dose ion implantation of light elements such as fluorine as well as chlorine and neon with peak concentrations of 1at.%. In order to distinguish between luminescence suppression in the visible to luminescence quenching due to radiation damage, all samples were additionally implanted with europium at fluences of 1·1013 ions/cm2. After annealing the samples at 1373K under vacuum conditions cathodoluminescence spectra were recorded at room temperature (300K) and at cryogenic temperature (12K). These investigations reveal that different light ion species have different influences on the defect luminescence of the AlN host lattice which is likely due to selective passivation of these defects. The best ratio of defect luminescence suppression to radiation damage induced luminescence quenching is achieved in the case of fluorine co-doping. [Copyright &y& Elsevier]

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]

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]

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]

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]

Hybrid index structures support access to heterogeneous data types in multiple columns. Several experiments confirm the improved efficiency of these hybrid access structures. Yet, very little is known about the worst case time and space complexity of them. This paper aims to close this gap by introducing a theoretical framework supporting the analysis of hybrid index structures. This framework then is used to derive the constraints for an access structure which is both time and space efficient. An access structure based on a B+-Tree augmented with bit lists representing sets of terms from texts is the outcome of the analysis which is then validated experimentally together with a hybrid R-Tree variant to show a logarithmic search time complexity. [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]

Having new potential applications in forging processes in mind, composites of an ordered mesoporous carbon and luminescent metal phosphate nanocrystals were synthesized for the first time. Three kinds of CMK-3/CePO4:Tb nanocomposites were prepared by treating a mesoporous CMK-3 host with different lanthanide phosphate precursor solutions. Characterization of the obtained nanocomposites by small-angle X-ray scattering, wide-angle X-ray diffraction, transmission electron microscopy, thermogravimetry, and nitrogen physisorption analysis showed that in two cases, the nanocrystals (ca. 2–3 nm in size) were located inside the mesopores, whereas in the third case the nanocystals (ca. 6 nm in size) merely adhered to the outer surfaces of the carbon particles. The CMK-3 and the two nanocomposites had ordered hexagonal structures (space group p6mm); all the materials possessed amorphous carbon walls. After combustion of the nanocomposites, the residues upon excitation with UV light exhibited the typical green luminescence of Tb3+. A preliminary evaluation of the lubrication properties of the CMK-3 and one nanocomposite material was performed. The friction factors determined by means of ring upsetting tests revealed that the carbon materials were able to lower frictional forces although they were 3–4 times less efficient than a commercial graphite-based reference lubricant. [ABSTRACT FROM AUTHOR]

The microbial production of rhamnolipids has been in the focus of research for the last decades. Today, mainly heterologous production systems are targeted due to the advantage of non-pathogenic hosts as well as uncoupling from complex quorum sensing regulatory networks compared to their natural producer Pseudomonas aeruginosa. In the recent past, the presence and function of a ROSE-like RNA-thermometer located in the 5′UTR of the rhamnosyltransferase genes rhlAB has been reported in wild type P. aeruginosa. In this study, the temperature-induced regulation of this native RNA-thermometer for heterologous rhamnolipid production was evaluated and its potential application for process control is discussed. For this purpose, the non-pathogenic production host P. putida KT2440 containing the rhlAB genes with the native P. aeruginosa 5′-UTR region was used. The system was evaluated and characterized regarding the effect of temperature on growth and product formation, as represented by efficiency parameters and yields. Experimental data suggests a major effect of temperature on specific rhamnolipid production rates. With maximum values of 0.23 g/(g h) at 37 °C, this constitutes a more than 60% increase compared to the production rate of 0.14 g/(g h) at the growth optimum of 30 °C. Interestingly however, control experiments unveiled that besides the regulatory effect of the RNA-thermometer, multiple metabolic effects may contribute equally to the observed increase in production rate. As such, this work constitutes an important step towards the utilization of temperature-based process designs and enables the possibility for novel approaches for process control. [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]

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]

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]