Route Planning in Transportation Networks

We survey recent advances in algorithms for route planning in transportation networks. For road networks, we show that one can compute driving directions in milliseconds or less even at continental scale. A variety of techniques provide different trade-offs between preprocessing effort, space requirements, and query time. Some algorithms can answer queries in a fraction of a microsecond, while others can deal efficiently with real-time traffic. Journey planning on public transportation systems, although conceptually similar, is a significantly harder problem due to its inherent time-dependent and multicriteria nature. Although exact algorithms are fast enough for interactive queries on metropolitan transit systems, dealing with continent-sized instances requires simplifications or heavy preprocessing. The multimodal route planning problem, which seeks journeys combining schedule-based transportation (buses, trains) with unrestricted modes (walking, driving), is even harder, relying on approximate solutions even for metropolitan inputs.Comment: This is an updated version of the technical report MSR-TR-2014-4, previously published by Microsoft Research. This work was mostly done while the authors Daniel Delling, Andrew Goldberg, and Renato F. Werneck were at Microsoft Research Silicon Valle

The absence of a dense potential core in supercritical Injection: A thermal break-up mechanism

Certain experiments in quasi-isobaric supercritical injection remain unexplained by the current state of theory: Without developing a constant value potential core as expected from the mechanical view of break-up, density is observed to drop immediately upon entering the chamber. Furthermore, this phenomenon has never been captured in computational fluid dynamics (CFD) despite having become a de facto standard case for real fluid CFD validation. In this paper, we present strong evidence for a thermal jet disintegration mechanism (in addition to classical mechanical break-up) which resolves both the theoretical and the computational discrepancies. A new interpretation of supercritical jet disintegration is introduced, based on pseudo-boiling, a nonlinear supercritical transition from gas-like to liquid-like states. We show that thermal disintegration may dominate classical mechanical break-up when heat transfer takes place in the injector and when the fluid state is sufficiently close to the pseudo-boiling point. A procedure which allows to capture subsided cores with standard CFD is provided and demonstrated

Neurodynamic evaluation of hearing aid features using EEG correlates of listening effort

In this study, we propose a novel estimate of listening effort using electroencephalographic data. This method is a translation of our past findings, gained from the evoked electroencephalographic activity, to the oscillatory EEG activity. To test this technique, electroencephalographic data from experienced hearing aid users with moderate hearing loss were recorded, wearing hearing aids. The investigated hearing aid settings were: a directional microphone combined with a noise reduction algorithm in a medium and a strong setting, the noise reduction setting turned off, and a setting using omnidirectional microphones without any noise reduction. The results suggest that the electroencephalographic estimate of listening effort seems to be a useful tool to map the exerted effort of the participants. In addition, the results indicate that a directional processing mode can reduce the listening effort in multitalker listening situations

Vestigial auriculomotor activity indicates the direction of auditory attention in humans

Unlike dogs and cats, people do not point their ears as they focus attention on novel, salient, or task-relevant stimuli. Our species may nevertheless have retained a vestigial pinna-orienting system that has persisted as a 'neural fossil’ within in the brain for about 25 million years. Consistent with this hypothesis, we demonstrate that the direction of auditory attention is reflected in sustained electrical activity of muscles within the vestigial auriculomotor system. Surface electromyograms (EMGs) were taken from muscles that either move the pinna or alter its shape. To assess reflexive, stimulus-driven attention we presented novel sounds from speakers at four different lateral locations while the participants silently read a boring text in front of them. To test voluntary, goal-directed attention we instructed participants to listen to a short story coming from one of these speakers, while ignoring a competing story from the corresponding speaker on the opposite side. In both experiments, EMG recordings showed larger activity at the ear on the side of the attended stimulus, but with slightly different patterns. Upward movement (perking) differed according to the lateral focus of attention only during voluntary orienting; rearward folding of the pinna’s upper-lateral edge exhibited such differences only during reflexive orienting. The existence of a pinna-orienting system in humans, one that is experimentally accessible, offers opportunities for basic as well as applied science

Resource-aware Research on Universe and Matter: Call-to-Action in Digital Transformation

Given the urgency to reduce fossil fuel energy production to make climate tipping points less likely, we call for resource-aware knowledge gain in the research areas on Universe and Matter with emphasis on the digital transformation. A portfolio of measures is described in detail and then summarized according to the timescales required for their implementation. The measures will both contribute to sustainable research and accelerate scientific progress through increased awareness of resource usage. This work is based on a three-days workshop on sustainability in digital transformation held in May 2023.Comment: 20 pages, 2 figures, publication following workshop 'Sustainability in the Digital Transformation of Basic Research on Universe & Matter', 30 May to 2 June 2023, Meinerzhagen, Germany, https://indico.desy.de/event/3748

An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus

DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear γH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, γH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of γH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses

COordination of Standards in MetabOlomicS (COSMOS): facilitating integrated metabolomics data access

Metabolomics has become a crucial phenotyping technique in a range of research fields including medicine, the life sciences, biotechnology and the environmental sciences. This necessitates the transfer of experimental information between research groups, as well as potentially to publishers and funders. After the initial efforts of the metabolomics standards initiative, minimum reporting standards were proposed which included the concepts for metabolomics databases. Built by the community, standards and infrastructure for metabolomics are still needed to allow storage, exchange, comparison and re-utilization of metabolomics data. The Framework Programme 7 EU Initiative ‘coordination of standards in metabolomics’ (COSMOS) is developing a robust data infrastructure and exchange standards for metabolomics data and metadata. This is to support workflows for a broad range of metabolomics applications within the European metabolomics community and the wider metabolomics and biomedical communities’ participation. Here we announce our concepts and efforts asking for re-engagement of the metabolomics community, academics and industry, journal publishers, software and hardware vendors, as well as those interested in standardisation worldwide (addressing missing metabolomics ontologies, complex-metadata capturing and XML based open source data exchange format), to join and work towards updating and implementing metabolomics standards

Microenvironmental Influences that Drive Progression from Benign Breast Disease to Invasive Breast Cancer

Invasive breast cancer represents the endpoint of a developmental process that originates in the terminal duct lobular units and is believed to progress through stages of increasing proliferation, atypical hyperplasia, and carcinoma in situ before the cancer acquires invasive and metastatic capabilities. By comparison with invasive breast cancer, which has been studied extensively, the preceding stages of benign breast disease are more poorly understood. Much less is known about the molecular changes underlying benign breast disease development and progression, as well as the transition from in situ into invasive disease. Even less focus has been given to the specific role of stroma in this progression. The reasons for lack of knowledge about these lesions often come from their small size and limited sample availability. More challenges are posed by limitations of the models used to investigate the lesions preceding invasive breast cancer. However, recent studies have identified alterations in stromal cell function that may be critical for disease progression from benign disease to invasive cancer: key functions of myoepithelial cells that maintain tissue structure are lost, while tissue fibroblasts become activated to produce proteases that degrade the extracellular matrix and trigger the invasive cellular phenotype. Gene expression profiling of stromal alterations associated with disease progression has also identified key transcriptional changes that occur early in disease development. In this review, we will summarize recent studies showing how stromal factors can facilitate progression of ductal carcinoma in situ to invasive disease. We also suggest approaches to identify processes that control earlier stages of disease progression