The authors work closely with academia and governmental organizations in the UK and abroad to develop new, innovative schemes for social impact investing. Such schemes include considerations for ...public-private collaborations, legislative actions, and especially in this case, for the leveraged use of public and philanthropic funds in Crowdfunding (CF). The relatively new phenomenon of CF can not only provide necessary funds for the social enterprises, it may also lead to a higher legitimacy of these through early societal interaction and participation. This legitimacy can be understood as a strong positive signal for further investors. Governmental tax-reliefs and guarantees from venture-philanthropic funds provide additional incentives for investment and endorse future scaling by leveraging additional debt-finance from specialized social banks. This case study identifies idiosyncratic hurdles to why an efficient social finance market has yet to be created and examines a schema as a case of how individual players' strengths and weaknesses can be balanced out by a concerted action. The paper discusses the necessary actions, benefits and implications for the involved actors from the public, private and third sector.
•Vehicle subsystem dynamics can be characterized in the frequency domain by mechanical four-poles.•Four-pole coefficients are suitable to derive requirements to subsystem dynamics.•Subsystem ...identification is feasible in practice either experimentally or virtually.•The method is applicable to problems with limited knowledge about desirable subsystem and system dynamics.•The method is applicable to nonlinear systems whose dynamics depends on the input force level.
In a recent companion publication, we developed the basic theory for deriving requirements for the dynamic properties of vehicle components. These requirements correspond to targets at vehicle level, but they address stand-alone subsystems being developed simultaneously by different parties. For this purpose, the vehicle, i.e., the coupled system, is divided into subsystems such as the steering and the front axle. The substructuring method used for this was based on the four-pole theory, where frequency-dependent transfer matrices are needed. Thereby, the relevant transfer coefficients of each subsystem were assumed to be linear.
In this work, the method is extended to cope with nonlinear behavior of the subsystems. The basic idea is to characterize the nonlinear systems in the frequency domain by their mono-harmonic responses depending on the force level acting at their input. Both virtual and experimental methods can be used to identify the target-relevant four-pole model of the steering and the front axle. To consider nonlinearities in terms of amplitude-dependent behavior, each subsystem is investigated at multiple amplitude levels. As a main difference to the companion publication, the results are not limit curves, but rather limit surfaces in terms of the dynamics of each subsystem over frequency and force amplitude, which serve as envelope to subsystem design. Iterative algorithms are proposed to make the linear four-pole method still applicable to problems with this kind of nonlinearity where higher harmonics resulting from the nonlinearities can be neglected.
White mould (Sclerotinia sclerotiorum) is a destructive disease of soybean worldwide. However, little is known of its impact on soybean production in Brazil. A meta‐analytic approach was used to ...assess the relationship between disease incidence and soybean yield (35 trials) and between incidence and sclerotia production (29 trials) in experiments conducted in 14 locations across four seasons. Region, site elevation and season included as moderators in random‐effects and random‐coefficients models did not significantly explain the variability in the slopes of the incidence–yield relationship. The Pearson's r, obtained from back‐transforming the Fisher's Z estimated by an overall random‐effects model, showed that incidence of white mould was moderately and negatively correlated with yield (r = −0.76, P < 0.0001). A random‐coefficients model estimated a slope of −17.2 kg ha−1%−1, for a mean attainable yield of 3455 kg ha−1, indicating that a 10% increase in white mould incidence would result in a mean yield reduction of 172 kg ha−1. White mould incidence and production of sclerotia were strongly and positively correlated (r = 0.85, P < 0.0001). For every 10% increase in white mould incidence, 1 kg ha−1 of sclerotia was produced. The relationship between disease incidence and production of sclerotia was stronger in southern regions and at higher elevation. In the absence of management, economic losses associated with white mould epidemics, assuming 43% incidence in 22% of the soybean area, were estimated at approximately US $1.47 billion annually within Brazil.
•Mechanical four-pole coefficients are useful to identify vehicle subsystem dynamics.•Four-pole coefficients are suitable to represent requirements to subsystem dynamics.•Subsystem identification is ...feasible in practice either experimentally or virtually.•Compared to other substructuring methods, fewer coefficients have to be identified.•A new virtual roller test rig (MBS model) for the front axle subsystem is presented.
Vehicle design with respect to steering feel and steering vibration is challenging for many reasons. One of them is that several subsystems need to be considered simultaneously, which are developed separately by different departments or external suppliers. Therefore, the requirements, which are usually imposed on the vehicle level, i.e. the coupled system, have to be reformulated on the level of subsystems. In this work, objective requirements on the steering subsystem are derived using mechanical four-poles. For this purpose, the vehicle system is divided into steering and front axle subsystems. Basic equations are derived in order to determine the relevant four-pole coefficients and to derive requirements to the subsystems by disassembling them from given vehicle system dynamics. Both virtual and experimental methods can be used to determine the relevant four-pole coefficients of the steering and the front axle during the design and verification stages. Vehicle targets are introduced, depending on vehicle speed or excitation frequency. Then, requirements in terms of necessary, sufficient and phase-exact limit values to selected subsystem dynamics are calculated. By assembling actual and permissible dynamics of the subsystems, the performance at vehicle level becomes predictable. It is shown that target mismatch can be detected already at subsystem level during the design phase, where corrective measures are still feasible. Reversely, vehicle targets are met if the subsystems fulfill their respective requirements.
Advances in therapies of pediatric acute myeloid leukemia (AML) have been minimal in recent decades. Although 82% of patients will have an initial remission after intensive therapy, approximately 40% ...will relapse.
is the most common chromosomal translocation in AML and has a poor prognosis resulting in high relapse rates and low chemotherapy efficacy. Novel targeted approaches are needed to increase sensitivity to chemotherapy. Recent studies have shown how interactions within the bone marrow (BM) microenvironment help AML cells evade chemotherapy and contribute to relapse by promoting leukemic blast survival. This study investigates how DNA hypomethylating agent azacitidine and histone deacetylase inhibitor panobinostat synergistically overcome BM niche-induced chemoprotection modulated by stromal, endothelial, and mesenchymal stem cells and the extracellular matrix (ECM). We show that direct contact between AML cells and BM components mediates chemoprotection. We demonstrate that azacitidine and panobinostat synergistically sensitize MV4;11 cells and
rearranged pediatric patient-derived xenograft lines to cytarabine in multicell coculture. Treatment with the epigenetic drug combination reduced leukemic cell association with multicell monolayer and ECM in vitro and increased mobilization of leukemic cells from the BM in vivo. Finally, we show that pretreatment with the epigenetic drug combination improves the efficacy of chemotherapy in vivo.
Understanding the effect of radiation on the functional properties of epoxy resins is crucial for their application in future particle accelerators like the Future Circular Collider (FCC). We compare ...the irradiation induced aging rates of six epoxy resin systems that can be used for the vacuum impregnation of magnet coils. Aging is assessed based on Dynamical Mechanical Analysis (DMA), 3-point bending and outgassing tests. DMA storage and loss moduli evolutions reveal the effect of the competing influence of cross-linking and chain scission on the glass transition temperature ( T g ). The same proton and gamma irradiation dose has a similar effect on the thermomechanical epoxy resin properties. Aging rates differ strongly for the different resins, and the fastest aging is observed for the MY750 resin system, which T g decreases with a rate of about minus 9 °C/MGy.
Crowdfunding (CF) in a social entrepreneurship (SE) context is praised in media narrations for its multifaceted potential. From an academic point of view, little has been written about CF as a whole, ...and enquiries from the SE sphere are mostly concerned with donation-based CF. This paper first reviews extant literature on financing social ventures and CF. Based upon the findings, the author draws up a schema of CF's inner workings and subsequently discusses it in an SE context. From this model, a research agenda consisting of eight themes is derived: types and utility functions; corporate governance; investor relations, reporting and risk; opportunity recognition; networking; legitimacy; financial metrics and legal and regulatory hurdles.
The multi-levelled processes taking place in Crowdfunding (CF), when tapping a large heterogeneous crowd for resources, and the often fundamentally different intentions of individual crowd members in ...the case of highly desirable social ventures with little prospect for economic gains, may lead to a different logic and approach to how entrepreneurship develops. Using this under-institutionalized sphere as both, context and subject, the author seeks evidence and a new understanding of entrepreneurial routes by using the sociological perspectives of Bourdieus' four forms of capital as a lens on 36 cases of social ventures. In the cases, opportunity recognition, formation and exploitation could not be distinguished as separate processes. CF and sourcing help form the actual opportunity and disperse information at the same time. In addition, the 'nexus' of opportunity and entrepreneur is breached in CF of social causes through the constant exchange of ideas with the crowd, leading to norm-value pairs between the funders and the entrepreneurs. Issues of identification and control are thus not based upon any formal relationship but based on perceived legitimization and offered democratic participation leading to the transformation of social capital (SC) into economic capital (EC). Success is based upon the SC of the entrepreneurial teams, yet the actual resource exchange and transformation into EC is highly moderated by cultural and symbolic capital that is being built up through the process.
We explore the long-term evolution of a bias-free orbital representation of the cometary nuclei (with diameters above 2 km) of the Kuiper Belt, using the so-called L7 synthetic model from CFEPS, ...which consists of three dynamical subpopulations: the Classical, the Resonant, and the Scattering. The dynamical evolution of belt particles is studied under the gravitational influence of the Sun and the four giant planets, as well as of the 34 largest known trans-Neptunian objects (i.e., those with HV < 4). Here, we indistinctly call Dwarf Planets (DPs) to the full sample of 34 large TNOs. Over a 1 Gyr timescale, we analyze the secular influence of the DPs over Kuiper Belt disk particles and their contribution to the injection rate of new visible Jupiter Family Comets (JFCs). We find that DPs globally increase the number of JFCs by 12.6%, when compared with the comets produced by the giant planets alone. When considering each population separately, we find the increment produced by DPs to be 17%, 12%, and 3% for the Classical, Resonant, and Scattering populations, respectively. Given the rate of escapes from the Kuiper Belt, we find upper limits to the number of objects in each population required to maintain the JFCs in steady state; the results are 55.9 × 106, 78.5 × 106, and 274.3 × 106 for the Scattering, Resonant, and Classical populations, respectively. Finally, we find that the Plutinos are the most important source of comets that were originally in a resonant configuration, where the presence of Pluto alone enhances by 10% the number of JFCs.
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