Audio source location for a digital TV-Director

Three algorithms are presented for location of audio sources using standard workstations and a minimal amount of resources. The audio source location is based on time-delay estimation. The algorithms use general human speech properties and straightforward heuristics on human speaker behaviour to acquire accurate and efficient estimation of delays

Distance Measures for Embedded Graphs

We introduce new distance measures for comparing straight-line embedded graphs based on the Fr\'echet distance and the weak Fr\'echet distance. These graph distances are defined using continuous mappings and thus take the combinatorial structure as well as the geometric embeddings of the graphs into account. We present a general algorithmic approach for computing these graph distances. Although we show that deciding the distances is NP-hard for general embedded graphs, we prove that our approach yields polynomial time algorithms if the graphs are trees, and for the distance based on the weak Fr\'echet distance if the graphs are planar embedded. Moreover, we prove that deciding the distances based on the Fr\'echet distance remains NP-hard for planar embedded graphs and show how our general algorithmic approach yields an exponential time algorithm and a polynomial time approximation algorithm for this case.Comment: 27 pages, 14 Figure

PENYALAHGUNAAN ASET NEGARA DALAM BENTUK JARINGAN SATELIT UNTUK KEPENTINGAN KORPORASI DIHUBUNGKAN DENGAN UNDANGUNDANG NOMOR 36 TAHUN 1999 TENTANG TELEKOMUNIKASI JO UNDANGUNDANG NOMOR 20 TAHUN 2001 TENTANG TINDAK PIDANA KORUPSI

telekomunikasi sebagaimana dilakukan oleh IM2. IM2 telah menyalahgunakan pita frekuensi 2.1 Ghz, dan secara melawan hukum beroperasi pada jaringan tersebut sehingga menimbulkan kerugian negara. Berdasarkan hal tersebut maka penulis tertarik meneliti, bagaimana Undang-Undang Telekomunikasi jo Peraturan Menteri Komunikasi dan Informatika dan Undang-Undang Tindak Pidana Korupsi mengatur mekanisme pemanfaatan aset negara berupa jaringan satelit, mengapa aset negara berupa jaringan satelit kerap kali disalahgunakan didalam pemanfaatannya oleh korporasi, serta bagaimana upaya yang dapat dilakukan untuk melindungi aset negara dalam bentuk jaringan satelit terhadap penyalahgunaan yang dilakukan oleh korporasi. Penelitian ini menggunakan spesifikasi penelitian yang bersifat deskriftif analitis dengan pendekatan yuridis normatif dibantu yuridis empiris, data yang diperlukan dalam penelitian ini dikumpulkan melalui studi kepustakaan dan studi lapangan, kemudian dianalisis menggunakan teknik analisis data berupa yuridis kualitatif. Pemanfaatan aset negara berupa jaringan satelit melalui pita frekuensi merupakan salah satu hak yang dalam pemanfaatannya diatur oleh peraturan perundang-undangan agar tercipta keadilan, kepastian dan ketertiban, keamanan, keseimbangan, perlindungan dan pemeliharaan dalam pemanfataannya. Jaringan satelit yang merupakan jaringan satelit aset negara pemanfaatannya mensyaratkan izin dan pembayaran tarif tertentu, sehingga konsekuensinya ketika terjadi penyalahgunaan pemanfaatan jaringan satelit, negara akan mengalami kerugian. Aset negara berupa jaringan satelit kerap kali disalahgunakan didalam pemanfaatannya oleh korporasi disebabkan beberapa faktor diantaranya faktor hukum itu sendiri dalam hal ini peraturan perundang-undangannya, faktor penegak hukum, faktor sarana atau fasilitas yang mendukung pengawasan dan penegakan hukum itu sendiri, faktor masyarakat, yakni lingkungan dimana hukum tersebut berlaku atau diterapkan, dalam hal ini yaitu lingkungan korporasi, faktor kebudayaan yakni kurangnya kesadaran hukum korporasi dalam upaya pemanfaatan aset negara secara berkeadilan dan tertib sesuai peraturan perundang-undangan yang berlaku, dimana pemanfaatan yang tidak secara berkeadilan akan membawa negara menuju kepada kehancuran. Upaya yang dapat dilakukan untuk melindungi aset negara dalam bentuk jaringan satelit terhadap penyalahgunaan yang dilakukan oleh korporasi harus berangkat dari beberapa faktor yang menjadi penyebab penyalahgunaan pemanfaatan jaringan satelit diantaranya yaitu melalui upaya preventif berupa revisi perunang-undangan, pengawasan, sosialisasi sert upaya represif berupa penegakan hukum. Penegakan hukum harus dilaksanakan tanpa pandang bulu, sebagai bentuk keyakinan atas doktrin hukum, bahwa setiap orang mempunyai kedudukan yang sama di depan hukum. Kata Kunci: Penyalahgunaan Aset Negara, Jaringan Sateli

Brain imaging and human nutrition: which measures to use in intervention studies?

The present review describes brain imaging technologies that can be used to assess the effects of nutritional interventions in human subjects. Specifically, we summarise the biological relevance of their outcome measures, practical use and feasibility, and recommended use in short- and long-term nutritional studies. The brain imaging technologies described consist of MRI, including diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI, as well as electroencephalography/magnetoencephalography, near-IR spectroscopy, positron emission tomography and single-photon emission computerised tomography. In nutritional interventions and across the lifespan, brain imaging can detect macro- and microstructural, functional, electrophysiological and metabolic changes linked to broader functional outcomes, such as cognition. Imaging markers can be considered as specific for one or several brain processes and as surrogate instrumental endpoints that may provide sensitive measures of short- and long-term effects. For the majority of imaging measures, little information is available regarding their correlation with functional endpoints in healthy subjects; therefore, imaging markers generally cannot replace clinical endpoints that reflect the overall capacity of the brain to behaviourally respond to specific situations and stimuli. The principal added value of brain imaging measures for human nutritional intervention studies is their ability to provide unique in vivo information on the working mechanism of an intervention in hypothesis-driven research. Selection of brain imaging techniques and target markers within a given technique should mainly depend on the hypothesis regarding the mechanism of action of the intervention, level (structural, metabolic or functional) and anticipated timescale of the intervention's effects, target population, availability and costs of the technique

Advancing drug discovery through assay development: a survey of tool compounds within the human solute carrier superfamily

With over 450 genes, solute carriers (SLCs) constitute the largest transporter superfamily responsible for the uptake and efflux of nutrients, metabolites, and xenobiotics in human cells. SLCs are associated with a wide variety of human diseases, including cancer, diabetes, and metabolic and neurological disorders. They represent an important therapeutic target class that remains only partly exploited as therapeutics that target SLCs are scarce. Additionally, many small molecules reported in the literature to target SLCs are poorly characterized. Both features may be due to the difficulty of developing SLC transport assays that fulfill the quality criteria for high-throughput screening. Here, we report one of the main limitations hampering assay development within the RESOLUTE consortium: the lack of a resource providing high-quality information on SLC tool compounds. To address this, we provide a systematic annotation of tool compounds targeting SLCs. We first provide an overview on RESOLUTE assays. Next, we present a list of SLC-targeting compounds collected from the literature and public databases; we found that most data sources lacked specificity data. Finally, we report on experimental tests of 19 selected compounds against a panel of 13 SLCs from seven different families. Except for a few inhibitors, which were active on unrelated SLCs, the tested inhibitors demonstrated high selectivity for their reported targets. To make this knowledge easily accessible to the scientific community, we created an interactive dashboard displaying the collected data in the RESOLUTE web portal (https://re-solute.eu). We anticipate that our open-access resources on assays and compounds will support the development of future drug discovery campaigns for SLCs

Impedance-based phenotypic readout of transporter function: a case for glutamate transporters

Excitatory amino acid transporters (EAAT/SLC1) mediate Na+-dependent uptake of extracellular glutamate and are potential drug targets for neurological disorders. Conventional methods to assess glutamate transport in vitro are based on radiolabels, fluorescent dyes or electrophysiology, which potentially compromise the cell's physiology and are generally less suited for primary drug screens. Here, we describe a novel label-free method to assess human EAAT function in living cells, i.e., without the use of chemical modifications to the substrate or cellular environment. In adherent HEK293 cells overexpressing EAAT1, stimulation with glutamate or aspartate induced cell spreading, which was detected in real-time using an impedance-based biosensor. This change in cell morphology was prevented in the presence of the Na+/K+-ATPase inhibitor ouabain and EAAT inhibitors, which suggests the substrate-induced response was ion-dependent and transporter-specific. A mechanistic explanation for the phenotypic response was substantiated by actin cytoskeleton remodeling and changes in the intracellular levels of the osmolyte taurine, which suggests that the response involves cell swelling. In addition, substrate-induced cellular responses were observed for cells expressing other EAAT subtypes, as well as in a breast cancer cell line (MDA-MB-468) with endogenous EAAT1 expression. These findings allowed the development of a label-free high-throughput screening assay, which could be beneficial in early drug discovery for EAATs and holds potential for the study of other transport proteins that modulate cell shape.Medicinal Chemistr

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia

The majority of patients with advanced cancer are recognised by impaired immune competence influenced by several factors, including the type and stage of the tumour and the presence of cachexia. Recently, a specific nutritional combination containing fish oil, specific oligosaccharide mixture, high protein content and leucine has been developed aimed to support the immune system of cancer patients in order to reduce the frequency and severity of (infectious) complications. In a recently modified animal model cachexia is induced by inoculation of C26 tumour cells in mice. In a pre-cachectic state, no effect was observed on contact hypersensitivity, a validated in vivo method to measure Th1-mediated immune function, after adding the individual nutritional ingredients to the diet of tumour-bearing mice. However, the complete mixture resulted in significantly improved Th1 immunity. Moreover, in a cachectic state, the complete mixture reduced plasma levels of pro-inflammatory cytokines and beneficially affected ex vivo immune function. Accordingly, the combination of the nutritional ingredients is required to obtain a synergistic effect, leading to a reduced inflammatory state and improved immune competence. From this, it can be concluded that the specific nutritional combination has potential as immune-supporting nutritional intervention to reduce the risk of (infectious) complications in cancer patients

09 FERRY_04 LORD_c

Abstract: Interventions are crucial as they offer simple and inexpensive public health solutions that will be useful over the long term use. A Task Force on designing trials of nutritional interventions to slow cognitive decline in older adults was held in Toulouse in September 2012. The aim of the Task Force was to bring together leading experts from academia, the food industry and regulatory agencies to determine the best trial designs that would enable us to reach our goal of maintaining or improving cognitive function in apparently healthy aging people. An associated challenge for this Task Force was to determine the type of trials required by the Public Food Agencies for assessing the impact of nutritional compounds in comparison to well established requirements for drug trials. Although the required quality of the study design, rationale and statistical analysis remains the same, the studies designed to show reduction of cognitive decline require a long duration and the objectives of this task force was to determine best design for these trials. Two specific needs were identified to support trials of nutritional interventions: 1-Risk-reduction strategies are needed to tackle the growing burden of cognitive decline that may lead to dementia, 2-Innovative study designs are needed to improve the quality of these studies