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This paper presents novel multicore fibers with broadband emission in the 1.4–2.1 μm range. Based on our previous work with barium gallo-germanate glasses and fibers, the 4 and 11-core fiber structures, each containing core glasses doped with Er3+ and Yb3+/Tm3+/Ho3+, were developed. Our efforts have resulted in flat emission in 3 dB and 10 dB bands, achievable under excitation at 796 nm, 808 nm, 940 nm, and 980 nm. The measured emission spectra of these fibers are described as a superposition of emission bands from each individual core, corresponding to the transitions of Er3+, Tm3+, and Ho3+ ions. Our method demonstrates the potential of emission profiling in multicore optical fibers as a new way to construct eye-safe broadband fiber sources. [ABSTRACT FROM AUTHOR]

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Multiple myeloma (MM) is a hematological malignancy whose curability is greatly challenged by recurrent patient relapses and therapy resistance. We have previously proposed the high expression of ADAM8, ADAM9 and ADAM15 (A Disintegrin And Metalloproteinase 8/9/15) as adverse prognostic markers in MM. This study focused on the so far scarcely researched role of ADAM8/9/15 in MM using two patient cohorts and seven human MM cell lines (HMCL). High ADAM8/9/15 expression was associated with high-risk cytogenetic abnormalities and extramedullary disease. Furthermore, ADAM8/15 expression increased with MM progression and in relapsed/refractory MM compared to untreated patient samples. RNA sequencing and gene set enrichment analysis comparing ADAM8/9/15high/low patient samples revealed an upregulation of proliferation markers and proliferation-associated gene sets in ADAM8/9/15high patient samples. High ADAM8/9/15 expression correlated with high Ki67 and high ADAM8/15 expression with high MYC protein expression in immunohistochemical stainings of patient tissue. Conversely, siRNA-mediated knockdown of ADAM8/9/15 in HMCL downregulated proliferation-related gene sets. Western blotting revealed that ADAM8 knockdown regulated IGF1R/AKT signaling and ADAM9 knockdown decreased mTOR activation. Lastly, high ADAM8/9/15 expression levels were verified as prognostic markers independent of Ki67/MYC expression and/or high-risk abnormalities. Overall, these findings suggest that ADAM8/9/15 play a role in MM progression and proliferation signaling. [ABSTRACT FROM AUTHOR]

Simple Summary: Overexpression and/or mutations of the receptor tyrosine kinase IGF1R are associated with an adverse prognosis in MM but do not appear to have any impact on treatment response, and their functional role in MM is so far unknown. In the current study, we aim to understand the impact of IGF1R mutations on MM cell survival signaling, viability/proliferation and treatment response. We show that IGF1R mutations can impact IGF1R activation and/or downstream signaling and that the combination of the pIGF1R/pINSR inhibitor linsitinib with the second-generation proteasome inhibitor carfilzomib shows promising anti-myeloma activity, regardless of the IGF1R mutation status. High expression of the receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R) and RTK mutations are associated with high-risk/worse prognosis in multiple myeloma (MM). Combining the pIGF1R/pINSR inhibitor linsitinib with the proteasome inhibitor (PI) bortezomib seemed promising in a clinical trial, but IGF1R expression was not associated with therapy response. Because the oncogenic impact of IGF1R mutations is so far unknown, we investigated the functional impact of IGF1R mutations on survival signaling, viability/proliferation and survival response to therapy. We transfected four human myeloma cell lines (HMCLs) with IGF1RWT, IGF1RD1146N and IGF1RN1129S (Sleeping Beauty), generated CRISPR-Cas9 IGF1R knockouts in the HMCLs U-266 (IGF1RWT) and L-363 (IGF1RD1146N) and tested the anti-MM activity of linsitinib alone and in combination with the second-generation PI carfilzomib in seven HMCLs. IGF1R knockout entailed reduced proliferation. Upon IGF1R overexpression, survival signaling was moderately increased in all HCMLs and slightly affected by IGF1RN1129S in one HMCL, whereby the viability remained unaffected. Expression of IGF1RD1146N reduced pIGF1R-Y1135, especially under serum reduction, but did not impact downstream signaling. Linsitinib and carfilzomib showed enhanced anti-myeloma activity in six out of seven HMCL irrespective of the IGF1R mutation status. In conclusion, IGF1R mutations can impact IGF1R activation and/or downstream signaling, and a combination of linsitinib with carfilzomib might be a suitable therapeutic approach for MM patients potentially responsive to IGF1R blockade. [ABSTRACT FROM AUTHOR]

Optical fiber with YPO4:Pr3+ nanocrystals (NCs) is presented for the first time using the glass powder—NCs doping method. The method's advantage is separate preparation of NCs and glass to preserve luminescent and optical properties of NCs once they are incorporated into optical fiber. The YPO4:Pr3+ nanocrystals were synthesized by the co-precipitation and hydrothermal methods, optimized for size (< 100 nm), shape, Pr3+ ions concentration (0.2 mol%), and emission lifetime. The core glass was selected from the non-silica P2O5-containing system with refractive index (n = 1.788) close to the NCs (no = 1.657, ne = 1.838). Optical fiber was drawn by modified powder-in-tube method after pre-sintering of glass powder—YPO4:Pr3+ (wt 3%) mixture to form optical fiber preform. Luminescent properties of YPO4:Pr3+ and optical fiber showed their excellent agreement, including sharp Pr3+ emission at 600 nm (1D2–3H4) and 1D2 level lifetime (τ = 156 ± 5 µs) under 488 nm excitation. The distribution of the YPO4:Pr3+ NCs in optical fiber were analyzed by TEM-EDS in the core region (FIB-SEM-prepared). The successful usage of glass powder—NCs doping method was discussed in the aspect of promising properties of the first YPO4:Pr3+ doped optical fiber as a new way to develop active materials for lasing applications, among others. [ABSTRACT FROM AUTHOR]

The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/– interferon). [ABSTRACT FROM AUTHOR]

Mutations were detected at similar frequencies in both cohorts: 58.1% of patients from our cohort had a mutation in at least one of the ECM gene families (ECM SP mut sp ) (56.5% in the MMRF cohort). PFS was also significantly shorter in patients with a high GE of 10/26 integrins, 11/44 collagens, 4/12 laminins, 7/20 ADAMs and 6/19 ADAMTS genes. 1C) which revealed significantly more SNVs per protein length in ECM genes compared to non-ECM genes ( I p i = 0.000002), suggesting that ECM mutations might be potential cancer driver mutations. Having analyzed the role of ECM gene mutations, we subsequently assessed ECM gene expression (GE) using the MMRF RNA-sequencing dataset (estimates calculated using Salmon 0.7.2). [Extracted from the article]

Ride‐hailing services have the potential to play a major role within future transport systems. While the operation as well as environmental, social and economic consequences are research subjects, the focus in the literature lies on system efficiency and profitability. In this study, vehicle relocation strategies are investigated with respect to service provision equity using an agent‐based simulation approach. The aim is to identify ways of operation that support social fairness while maintaining the profitability and effectiveness of the service. The results show that a typical demand‐anticipatory relocation strategy leads to an imbalance in the spatial distribution of mean wait times for the use case of Berlin. This can be significantly improved by applying different relocation strategies. As a consequence, the overall demand for the system rises while the ratio of empty vehicle kilometres increases slightly. [ABSTRACT FROM AUTHOR]

Electric current‐assisted sintering (ECAS) technologies are highly promising for processing of NdFeB magnets. Due to the combination of direct Joule heating and application of external load, even powders, whose particle size distribution and morphology are not optimum for conventional powder processing like melt‐spun powders or magnet scrap, can be easily sintered to high densities. A systematic study is done to demonstrate the potential of field‐assisted sintering technique/spark plasma sintering (FAST/SPS) and flash spark plasma sintering (flash SPS) for sintering of NdFeB powders. Melt‐spun, commercial NdFeB powder (Magnequench MQU‐F) is used as starting material. Its platelet‐like shape makes this powder extremely difficult to sinter by conventional methods. This study clearly reveals that especially in the case of flash SPS application of external pressure in combination with short cycle times enables to achieve well‐pronounced anisotropic magnetic properties without the need of subsequent upset forging. Optimized flash SPS parameters are applied to NdFeB magnet scrap with broad particle size distribution, demonstrating the general potential of ECAS technologies for recycling of waste magnet materials. Finally, the results are benchmarked with respect to established NdFeB processing technologies and electrodischarge sintering (EDS), another promising ECAS technology with very short cycling time. [ABSTRACT FROM AUTHOR]

Active vitamin D (1,25(OH)2D3) is known to exert direct anti-cancer actions on various malignant tissues through binding to the vitamin D receptor (VDR). These effects have been demonstrated in breast, prostate, renal and thyroid cancers, which all have a high propensity to metastasise to bone. In addition, there is evidence that vitamin D catabolism via 24-hydroxylase (CYP24A1) is altered in tumour cells, thus, reducing local active vitamin D levels in cancer cells. The aim of this study was to assess VDR and CYP24A1 expression in various types of bone metastases by using immunohistochemistry. Overall, a high total VDR protein expression was detected in 59% of cases (39/66). There was a non-significant trend of high-grade tumours towards the low nuclear VDR expression (p = 0.07). Notably, patients with further distant metastases had a reduced nuclear VDR expression (p = 0.03). Furthermore, a high CYP24A1 expression was detected in 59% (39/66) of bone metastases. There was a significant positive correlation between nuclear VDR and CYP24A1 expression (p = 0.001). Collectively, the VDR and CYP24A1 were widely expressed in a multitude of bone metastases, pointing to a potential role of vitamin D signalling in cancer progression. This is of high clinical relevance, as vitamin D deficiency is frequent in patients with bone metastases. [ABSTRACT FROM AUTHOR]

Roundabouts are well-known for their ability to improve upon traffic safety, especially for motorized traffic. An in-depth analysis on this topic is known from previous work. It was found that different types of roundabouts have different levels of safety. The work at hand is a replication study for a previous study in this regard. It uses a mix of traditional and a Machine Learning (ML)-based approach, expands on the previous results and replicates some of the previous findings. This was possible especially by using a factor of 10 more roundabouts in the analysis, with considerably less manual intervention. Furthermore, this study could also draw some additional conclusions regarding the safety of bicyclists, which were not included in the original study. Finally, by using cross-validation techniques, a kind of minimal model could be established that needs fewer factors and achieves better prediction quality than straightforward glm models. [ABSTRACT FROM AUTHOR]

Background/Aim: Multiple myeloma (MM) is characterized by accumulation of a malignant clone of plasma cells in the bone marrow. Curative treatments are not yet available. Therefore, we undertook a drug repurposing approach to identify possible candidates from a chemical library of 1,230 FDA-approved drugs by virtual drug screening. As a target, we have chosen the non-receptor Bruton's tyrosine kinase (BTK) which is one of the main regulators of the MM biomarker CD38. Materials and Methods: In silico virtual screening was performed by using PyRx. Flow cytometry was applied for cell cycle and apoptosis analysis. Furthermore, protein and gene expression was determined by western blotting and microarray hybridization. Lipid raft staining was observed by confocal microscopy. Results: The in silico identified lipid-lowering lomitapide presented with the strongest cytotoxicity among the top 10 drug candidates. This drug arrested the cell cycle in the G2/M phase and induced apoptosis in MM cells. Western blot analyses revealed that treatment with lomitapide induced cleavage of the apoptosis regulator PARP and reduced the expression of CD38, an integral part of lipid rafts. Using confocal microscopy, we further observed that lipid raft microdomain formation in MM cells was inhibited by lomitapide. In four MM cell lines (KMS-12-BM, NCI-H929, RPMI-8226, and MOLP-8) treated with lomitapide, microarray analyses showed not only that the expression of CD38 and BTK was down-regulated, but also that the tumor suppressor gene TP53 and the oncogene c-MYC were among the top deregulated genes. Further analysis of these data by Ingenuity pathway analysis (IPA) suggested that lomitapide interferes with the cross-talk of CD38 and BTK and apoptosis-regulating genes via TP53 and c-MYC. Conclusion: Lomitapide treatment led to disruption of lipid raft domains and induction of proapoptotic factors and might, therefore, be considered as a potential therapeutic agent in MM. [ABSTRACT FROM AUTHOR]

We report uniform Type-II GaInAsSb/InP UTC-PDs, and compare their performance to devices fabricated with GaAsSb uniform and graded (composition and doping) absorbers of the same thickness. The quaternary UTC-PDs show a transit limited bandwidth of 274 GHz in contrast to 107 and 185 GHz for uniform and graded GaAsSb absorber UTC-PDs. Because the uniform quaternary and ternary UTC-PDs only differ in their absorber material, the findings conclusively demonstrate enhanced transport in GaInAsSb. Performance comparison to GaInAs-based devices from the literature suggest that GaInAsSb is a superior absorber material for λ = 1.55 μm high-speed photodetectors. Additionally, the external responsivity of the GaInAsSb UTC-PDs (0.094 A/W) is ∼34% higher than the GaAsSb PDs (0.070 A/W). This is the first demonstration of a quaternary GaInAsSb absorber in UTC-PDs. [ABSTRACT FROM AUTHOR]

Feature models are a helpful means to document, manage, maintain, and configure the variability of a software system, and thus are a core artifact in software product-line engineering. Due to the various purposes of feature models, they can be a cross-cutting concern in an organization, integrating technical and business aspects. For this reason, various stakeholders (e.g., developers and consultants) may get involved into modeling the features of a software product line. Currently, collaboration in such a scenario can only be done with face-to-face meetings or by combining single-user feature-model editors with additional communication and version-control systems. While face-to-face meetings are often costly and impractical, using version-control systems can cause merge conflicts and inconsistency within a model, due to the different intentions of the involved stakeholders. Advanced tools that solve these problems by enabling collaborative, real-time feature modeling, analogous to Google Docs or Overleaf for text editing, are missing. In this article, we build on a previous paper and describe (1) the extended formal foundations of collaborative, real-time feature modeling, (2) our conflict resolution algorithm in more detail, (3) proofs that our formalization converges and preserves causality as well as user intentions, (4) the implementation of our prototype, and (5) the results of an empirical evaluation to assess the prototype’s usability. Our contributions provide the basis for advancing existing feature-modeling tools and practices to support collaborative feature modeling. The results of our evaluation show that our prototype is considered helpful and valuable by 17 users, also indicating potential for extending our tool and opportunities for new research directions. [ABSTRACT FROM AUTHOR]

This work analyzes the relationship between crash frequency N (crashes per hour) and exposure Q (cars per hour) on the macroscopic level of a whole city. As exposure, the traffic flow is used here. Therefore, it analyzes a large crash database of the city of Berlin, Germany, together with a novel traffic flow database. Both data display a strong weekly pattern, and, if taken together, show that the relationship N(Q) is not a linear one. When Q is small, N grows like a secondorder polynomial, while at large Q there is a tendency towards saturation, leading to an S-shaped relationship. Although visible in all data from all crashes, the data for the severe crashes display a less prominent saturation. As a by-product, the analysis performed here also demonstrates that the crash frequencies follow a negative binomial distribution, where both parameters of the distribution depend on the hour of the week, and, presumably, on the traffic state in this hour. The work presented in this paper aims at giving the reader a better understanding on how crash rates depend on exposure. [ABSTRACT FROM AUTHOR]

This study investigates the compaction of nanocrystalline NdFeB magnet powder by electro-discharge sintering (EDS). On this account, process parameters, microstructure, and the associated magnetic properties of the EDS-densified nanocrystalline NdFeB specimens were investigated by varying the discharge energy EEDS and compression load pEDS. Although optimized process parameters could be evaluated, three different microstructures (fully densified zone, insufficiently densified zone, and melted zone) are present in the EDS-compacted specimens. Thereby, volume fractions of these formed three different microstructures determine the resulting mechanical and magnetic properties of the specimens. For all specimens, the intrinsic coercivity Hc,J deteriorates with increasing discharge energy, as the generated Joule heat leads to microstructural changes (grain growth, dissolution of magnetic phases), which reduces the magnetic properties. The compression load has less influence on the coercivity Hc,J, as it only affects the initial resistance of the pre-compacted powder loose. The residual induction Br deteriorates with increasing the discharge energy due to microstructural changes. An increase in the compression load pEDS results in an increase in the specimens' density and thus promotes the residual induction Br. [ABSTRACT FROM AUTHOR]

For graphene to achieve its full scientific and commercial potential, reliable mass production of the material on the multi‐tonne scale is essential. We have investigated five samples of graphene obtained from commercial sources that state they can supply the product on the tonne scale per annum. From electron microscopy at the micrometre to the nanometre scale, and neutron vibrational spectroscopy, we find that none of the materials examined were 100 % isolated graphene sheets. In all cases, there was a substantial content of graphite‐like material. The samples exhibited varying oxygen contents, this could be present as carboxylic acid (although other oxygenates, quinones, phenols may also be present) or water. We emphasise that INS spectroscopy is particularly useful for the investigation of inorganic materials that will be used commercially: it provides atomic scale information from macroscopic (10's of g) amounts of sample, thus ensuring that the results are truly representative. [ABSTRACT FROM AUTHOR]

In the present study, X-ray diffraction was applied to measure stacking fault energy of Cr–Ni austenitic steels containing different amounts of alloying elements. The results in austenitic steels show that the Ni content and Cr/Ni ratio have a strong effect on SFE. Cu, Si and N increase SFE, being the effect of nitrogen more pronounced; Mo has the opposite effect. In situ XRD experiments up to 300 °C were employed to determine experimentally the SFE and its temperature dependence in Ni and AISI 304. The microstructural parameters required to determine SFE, obtained by Rietveld refinement, made possible to determine experimentally an increase in the SFE with the temperature, related to a decrease in the accumulated deformation, a lower tendency to form stacking faults and a thermal expansion as the temperature increases. The accuracy was determined based on SFE measurements of Au, Cu and Ni pure metals, where the error of the applied method was carefully evaluated. [ABSTRACT FROM AUTHOR]

Objective: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Methods: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). Results: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). Conclusion: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection. [ABSTRACT FROM AUTHOR]

This paper demonstrates an approach that makes it easy to find patterns in traffic crash databases, and to specify their statistical significance. The detected patterns might help to prevent traffic crashes from happening, since they may be used to tailor campaigns to the community at hand. Unfortunately, the approach described here comes at a cost: it identifies a considerable amount of patterns, not all of them are being useful. The second disadvantage is that is needs a certain size of the data-base: here it has been applied to a data-base of the city of Berlin that contains about 1.6 Million (M) crashes from the years 2001 to 2016, of which about 0.9M had been used in the analysis. [ABSTRACT FROM AUTHOR]

Potassium silanide [KSiH3]∞ contains 4.2 wt % of hydrogen and has been intensely studied as hydrogen storage material. The macrocyclic ligand Me4TACD (1,4,7,10‐tetramethyl‐1,4,7,10‐tetraaminocyclododecane, L) stabilizes the full range of triphenylsilyl complexes [(L)MSiPh3]n (M=Li–Cs), which react with H2 or PhSiH3 to form molecular [(L)MSiH3]n that can be isolated in soluble form and fully characterized. [ABSTRACT FROM AUTHOR]

A systematic literature review (SLR) is an empirical method used to provide an overview of existing knowledge and to aggregate evidence within a domain. For computer science, several threats to the completeness of such reviews have been identified, leading to recommendations and guidelines on how to improve their quality. However, few studies address to what extent researchers can replicate an SLR. To conduct a replication, researchers have to first understand how the set of primary studies has been identified in the original study, and can ideally retrieve the same set when following the reported protocol. In this article, we focus on this initial step of a replication and report a two-fold empirical study: Initially, we performed a tertiary study using a sample of SLRs in computer science and identified what information that is needed to replicate the searches is reported. Based on the results, we conducted a descriptive, multi-case study on digital libraries to investigate to what extent these allow replications. The results reveal two threats to replications of SLRs: First, while researchers have improved the quality of their reports, relevant details are still missing—we refer to a reporting threat. Second, we found that some digital libraries are inconsistent in their query results—we refer to a searching threat. While researchers conducting a review can only overcome the first threat and the second may not be an issue for all kinds of replications, researchers should be aware of both threats when conducting, reviewing, and building on SLRs. [ABSTRACT FROM AUTHOR]

This paper focuses on three important Library of Congress staff members from the period 1941–2015 to describe the library's interaction with Russia and the Soviet Union and the buildup of the library's Russian and Soviet collections. [ABSTRACT FROM AUTHOR]

Maintaining a program is a time-consuming and expensive task in software engineering. Consequently, several approaches have been proposed to improve the comprehensibility of source code. One of such approaches are comments in the code that enable developers to explain the program with their own words or predefined tags. Some empirical studies indicate benefits of comments in certain situations, while others find no benefits at all. Thus, the real effect of comments on software development remains uncertain. In this article, we describe an experiment in which 277 participants, mainly professional software developers, performed small programming tasks on differently commented code. Based on quantitative and qualitative feedback, we i) partly replicate previous studies, ii) investigate performances of differently experienced participants when confronted with varying types of comments, and iii) discuss the opinions of developers on comments. Our results indicate that comments seem to be considered more important in previous studies and by our participants than they are for small programming tasks. While other mechanisms, such as proper identifiers, are considered more helpful by our participants, they also emphasize the necessity of comments in certain situations. [ABSTRACT FROM AUTHOR]

The article offers the different types of sewerless toilets or sewage disposal systems available in the market or under development. These disposal systems include incinerating toilets, composting toilets, biological toilets, oil-flushed toilets, and household collection systems. The adverse effects of the present sewage disposal systems are also discussed, which includes the risk of transmitting diseases, enormous expenditures for sewer lines and treatment plants, and increased eutrophication of lakes and estuaries.

Abstract: When light alkali metal amides [M(Me3TACD)]n (M=Li, Na, K; (Me3TACD)H=1,4,7‐trimethyl‐1,4,7,10‐tetraazacyclododecane) were treated with H2SiPh2 in THF, [M{(H2SiPh2)Me3TACD}(thf)x] containing a pendant hypervalent dihydridosilicate were formed and characterized by elemental analysis, NMR/IR spectroscopy, and single‐crystal X‐ray crystallography. The lithium complex catalyzed the hydrosilylation of styrene derivatives under mild conditions with anti‐Markovnikov regioselectivity. [ABSTRACT FROM AUTHOR]

Summary: Software product lines enable developers to derive similar products from a common code base. Existing implementation techniques can be categorized as composition‐based and annotation‐based approaches, with both approaches promising complementary benefits. However, annotation‐based approaches are commonly used in practice despite composition allowing physical separation of features and, thus, improving traceability and maintenance. A main hindrance to migrate annotated systems toward a composition‐based product line is the challenging and time‐consuming transformation task. For a company, it is difficult to predict the corresponding costs, and a successful outcome is uncertain. To overcome such problems, a solution proposed by the previous work is to use a hybrid approach, utilizing composition and annotation simultaneously. Based on this idea, we introduce a stepwise migration process from annotation‐based toward composition‐based approaches to lower the adoption barrier of composition. This process itself is independent of used implementation techniques and enables developers to incrementally migrate toward composition. We support our approach with detailed examples by partially migrating a real‐world system. In detail, we describe the following: (1) our migration process, (2) its application on a real‐world system, and (3) discuss practical challenges we face. We implemented the proposed approach and show that appropriate tool support helps to migrate toward composition‐based product lines. Based on the case study, we show that the hybrid product lines work correctly and can compete with the performance of the original annotated system. However, the results also illustrate open issues that have to be solved to apply such migrations in practice. [ABSTRACT FROM AUTHOR]

Summary: Predominantly diffuse t(14;18) negative follicular lymphoma (FL) with 1p36 deletion shows distinctive clinical, morphological and molecular features that distinguish it from classical FL. In order to investigate whether it possesses a unique mutation profile, we performed whole exome sequencing of six well‐characterised cases. Our analysis showed that the mutational landscape of this subtype is largely distinct from classical FL. It appears to harbour several recurrent mutations, affecting STAT6, CREBBP and basal membrane protein genes with high frequency. Our data support the view that this FL subtype should be considered a separate entity from classical FL. [ABSTRACT FROM AUTHOR]

This paper presents a preliminary study on behalf of the Bavarian Red Cross (BRK). Its focus is on the traffic safety impact of additional blue lights for ambulance vehicles of the Bavarian Red Cross (BRK). The study examines if and to what extent a traffic safety impact can be measured. The high crash risk particular during emergency drives has been reported in numerous studies. The BRK endeavors to decrease the crash frequency of their ambulance vehicles by improving their visibility especially at intersections and narrow gateways. Therefore, additional side flashing lights have been proposed. The purpose of this study is to evaluate the effectiveness of these flashing lights. In this context, emergency drives conducted with equipped and unequipped ambulance vehicles were compared. More precisely, the exit of a BRK station and the adjacent road segment was observed for 14 days by a video camera, which enables computer-vision aided analysis of the traffic. Within this time frame, 38 traffic situations of unequipped and 13 situations of equipped ambulance vehicles were observed. The trajectories of interacting road users in these situations were analyzed. Indicators for the adaption of road users to ambulance vehicles leaving the BRK station were used, like deceleration, position and time of braking as well as time of reaching walking speed. The indicators showed, that road users entered the observation area slower encountering equipped ambulance vehicles-probably due to prior braking- than was measured at emergency drives without additional flash lights. Furthermore, road users on average were breaking 3.5 meters earlier, less intensely and reached walking speed 4 meters earlier when ambulance vehicles were equipped with additional flash lights. The interpretation of these results is that earlier reaction implies earlier perception of the ambulance vehicle. [ABSTRACT FROM AUTHOR]