The relationship among development skills, design quality, and centrality in open source projects

The paradigm of the Internet of Services envisions trade on a global service-enabled internet. Companies, which participate in this new world of services, face the challenges of changing market conditions, new competitive threats, and new legal regulations. Service-oriented Architectures (SOA) provide a promising way to address some of these challenges at the level of the company’s IT infrastructure. In order to guideline an enterprise’s organization and IT and ensure smooth operations, governance frameworks have been established. More specifically, IT Governance and recently SOA Governance have been introduced. The basic structure of IT Governance frameworks is applicable to an SOA. However, they lack functionality or applicability concerning SOA-specific challenges. Current approaches, which focus on mere SOA Governance, lack framework scope and are mostly driven by individual companies. This issue aggravates taking into account the shift to an Internet of Services. We identify key issues and provide initial insights on building blocks for a Service Governance Framework which enables operations for companies in a moderated service network. We discuss service life cycle phases, stakeholder roles, and management processes taking into consideration existing frameworks such as ITIL and CObIT as well as industry-specific approaches from companies such as SAP, Oracle, and HP

Granger Causality Mapping during Joint Actions Reveals Evidence for Forward Models That Could Overcome Sensory-Motor Delays

Studies investigating joint actions have suggested a central role for the putative mirror neuron system (pMNS) because of the close link between perception and action provided by these brain regions [1], [2], [3]. In contrast, our previous functional magnetic resonance imaging (fMRI) experiment demonstrated that the BOLD response of the pMNS does not suggest that it directly integrates observed and executed actions during joint actions [4]. To test whether the pMNS might contribute indirectly to the integration process by sending information to brain areas responsible for this integration (integration network), here we used Granger causality mapping (GCM) [5]. We explored the directional information flow between the anterior sites of the pMNS and previously identified integrative brain regions. We found that the left BA44 sent more information than it received to both the integration network (left thalamus, right middle occipital gyrus and cerebellum) and more posterior nodes of the pMNS (BA2). Thus, during joint actions, two anatomically separate networks therefore seem effectively connected and the information flow is predominantly from anterior to posterior areas of the brain. These findings suggest that the pMNS is involved indirectly in joint actions by transforming observed and executed actions into a common code and is part of a generative model that could predict the future somatosensory and visual consequences of observed and executed actions in order to overcome otherwise inevitable neural delays

Orbital redistribution in molecular nanostructures mediated by metal-organic bonds

Dicyanovinyl-quinquethiophene (DCV5T-Me) is a prototype conjugated oligomer for highly efficient organic solar cells. This class of oligothiophenes are built up by an electron-rich donor (D) backbone and terminal electron-deficient acceptor (A) moieties. Here, we investigated its structural and electronic properties when it is adsorbed on a Au(111) surface using low temperature scanning tunneling microscopy/spectroscopy (STM/STS) and atomic force microscopy (AFM). We find that DCV5T-Me self-assembles in extended chains, stabilized by intercalated Au atoms. The effect of metal-ligand hybridization with Au adatoms causes an energetic downshift of the DCV5T-Me lowest unoccupied molecular orbital (LUMO) with respect to the uncoordinated molecules on the surface. The asymmetric coordination of a gold atom to only one molecular end group leads to an asymmetric localization of the LUMO and LUMO+1 states at opposite sides. Using model density functional theory (DFT) calculations, we explain such orbital reshaping as a consequence of linear combinations of the original LUMO and LUMO+1 orbitals, mixed by the attachment of a bridging Au adatom. Our study shows that the alignment of molecular orbitals and their distribution within individual molecules can be modified by contacting them to metal atoms in specific sites

Efficient Coding and Statistically Optimal Weighting of Covariance among Acoustic Attributes in Novel Sounds

To the extent that sensorineural systems are efficient, redundancy should be extracted to optimize transmission of information, but perceptual evidence for this has been limited. Stilp and colleagues recently reported efficient coding of robust correlation (r = .97) among complex acoustic attributes (attack/decay, spectral shape) in novel sounds. Discrimination of sounds orthogonal to the correlation was initially inferior but later comparable to that of sounds obeying the correlation. These effects were attenuated for less-correlated stimuli (r = .54) for reasons that are unclear. Here, statistical properties of correlation among acoustic attributes essential for perceptual organization are investigated. Overall, simple strength of the principal correlation is inadequate to predict listener performance. Initial superiority of discrimination for statistically consistent sound pairs was relatively insensitive to decreased physical acoustic/psychoacoustic range of evidence supporting the correlation, and to more frequent presentations of the same orthogonal test pairs. However, increased range supporting an orthogonal dimension has substantial effects upon perceptual organization. Connectionist simulations and Eigenvalues from closed-form calculations of principal components analysis (PCA) reveal that perceptual organization is near-optimally weighted to shared versus unshared covariance in experienced sound distributions. Implications of reduced perceptual dimensionality for speech perception and plausible neural substrates are discussed

Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial

Abstract Early results of the randomized placebo-controlled SORAML trial showed that, in patients with newly diagnosed acute myeloid leukaemia (AML), sorafenib led to a significant improvement in event-free (EFS) and relapse-free survival (RFS). In order to describe second-line treatments and their implications on overall survival (OS), we performed a study after a median follow-up time of 78 months. Newly diagnosed fit AML patients aged ≤60 years received sorafenib (n = 134) or placebo (n = 133) in addition to standard chemotherapy and as maintenance treatment. The 5-year EFS was 41 versus 27% (HR 0.68; p = 0.011) and 5-year RFS was 53 versus 36% (HR 0.64; p = 0.035). Allogeneic stem cell transplantation (allo SCT) was performed in 88% of the relapsed patients. Four years after salvage allo SCT, the cumulative incidence of relapse was 54 versus 35%, and OS was 32 versus 50%. The 5-year OS from randomization in all study patients was 61 versus 53% (HR 0.82; p = 0.282). In conclusion, the addition of sorafenib to chemotherapy led to a significant prolongation of EFS and RFS. Although the OS benefit did not reach statistical significance, these results confirm the antileukaemic activity of sorafenib

Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Analyse und Implementierung von Shopfloor Management in der Produktion

Die Abschlussarbeit beinhaltete nicht nur die Implementierung des Shopfloor Management sondern auch die sorgfältige Analyse davon und den dazugehörigen Lean Methoden. Shopfloor Management bedeutet führen, kommunizieren und steuern am Ort der Wertschöpfung. Jeder Prozess besteht aus Wertschöpfung und Verschwendung und mittels der Lean Prinzipien die auch im Shopfloor Management angewandt werden, soll die Verschwendung vermieden werden. Durch eine transparente Visualisierung der aktuellen und wichtigen Kennzahlen direkt am Ort wird eine Akzeptanz bei den Mitarbeitern geschaffen. Diese neue Unternehmensführung sieht vor, eine offene Fehlerkultur zu entwickeln und die Fehler nachhaltig zu vermeiden. Es wurde die Wichtigkeit einer regelmäßigen Kommunikation erläutert, in denen die Themen und Probleme angesprochen werden. In dieser Arbeit wurden die Lean Prinzipien herausgearbeitet und ein Shopfloor Board entwickelt mit dem gestartet wurde. Zudem wurden die Mitarbeiter auf die Einführung vorbereitet und geschult. Die Mitarbeiter sollen durch das Shopfloor Management gezielt in den Verbesserungsprozess einbezogen werden und eine Eigenverantwortlichkeit entwickeln. Der optimale Zustand sieht vor, dass durch dieses System jeder Mitarbeiter die Ziele des Unternehmens kennt und durch die tägliche Revision der Kennzahlen, nachhaltige Poblemlösungsmethoden angewandt werden um die Ziele zu erreichen

In search of an Orthodox way: The development of biblical studies in late imperial Russia.

In search of an Orthodox way: The development of biblical studies in late imperial Russia

Towards a service governance framework for the internet of services

The paradigm of the Internet of Services envisions trade on a global service-enabled internet. Companies, which participate in this new world of services, face the challenges of changing market conditions, new competitive threats, and new legal regulations. Service-oriented Architectures (SOA) provide a promising way to address some of these challenges at the level of the company’s IT infrastructure. In order to guideline an enterprise’s organization and IT and ensure smooth operations, governance frameworks have been established. More specifically, IT Governance and recently SOA Governance have been introduced. The basic structure of IT Governance frameworks is applicable to an SOA. However, they lack functionality or applicability concerning SOA-specific challenges. Current approaches, which focus on mere SOA Governance, lack framework scope and are mostly driven by individual companies. This issue aggravates taking into account the shift to an Internet of Services. We identify key issues and provide initial insights on building blocks for a Service Governance Framework which enables operations for companies in a moderated service network. We discuss service life cycle phases, stakeholder roles, and management processes taking into consideration existing frameworks such as ITIL and CObIT as well as industry-specific approaches from companies such as SAP, Oracle, and HP