Modal Interface Automata

De Alfaro and Henzinger's Interface Automata (IA) and Nyman et al.'s recent combination IOMTS of IA and Larsen's Modal Transition Systems (MTS) are established frameworks for specifying interfaces of system components. However, neither IA nor IOMTS consider conjunction that is needed in practice when a component shall satisfy multiple interfaces, while Larsen's MTS-conjunction is not closed and Bene\v{s} et al.'s conjunction on disjunctive MTS does not treat internal transitions. In addition, IOMTS-parallel composition exhibits a compositionality defect. This article defines conjunction (and also disjunction) on IA and disjunctive MTS and proves the operators to be 'correct', i.e., the greatest lower bounds (least upper bounds) wrt. IA- and resp. MTS-refinement. As its main contribution, a novel interface theory called Modal Interface Automata (MIA) is introduced: MIA is a rich subset of IOMTS featuring explicit output-must-transitions while input-transitions are always allowed implicitly, is equipped with compositional parallel, conjunction and disjunction operators, and allows a simpler embedding of IA than Nyman's. Thus, it fixes the shortcomings of related work, without restricting designers to deterministic interfaces as Raclet et al.'s modal interface theory does.Comment: 28 page

Siddiqui, Negative refraction and focusing in hyperbolic transmission-line periodic grids

between an interface and the channel axes (cf. Ref. 3). This feature is counterintuitive to the conventional optical laws but it is totally consistent with the analysis based on the isofrequencies' for the channeled waves on anisotropic lattices discussed earlier. In the conventional isotropic periodic structures, a unit cell is representative of the respective finite arrangement when the edge cells are terminated into the matched loads. However, the feature of L-C mesh to funnel power from a point source into the narrow beam leads to the question whether load impedances of the edge cells nonadjacent to the beam axis affect the channel formation and properties of the propagating waves. To explore this effect, the load impedances outside the vicinities of the source and the channel output cells were varied. A comprehensive analysis of finite BM simulated in ADS has shown that only the first three edge nodes at the channel axis contribute to the beam formation. These observations led us to the conclusion that the channels arising on the anisotropic L-C mesh are well confined and guide waves along their axes as predicted by isofrequencies. To further elucidate the mechanism of wave channeling, the lattice portions were progressively removed to retain the mesh only around the channel axis. These alterations of the mesh arrangement incurred no visible changes of the beam shape and intensity on the truncated grids. Thus, the simulation results have proved that the propagation channel formed on the L-C mesh is truly confined to a few cells at the channel axis. This property of the L-C mesh suggests that a number of independent channels with their own impedances and axis orientations could be formed on the grid. Since the channel directions vary with frequency and the unit cell parameters, the L-C mesh can act as a spatial frequency discriminator CONCLUSIONS It has been shown that 2D periodic meshes composed of L-C circuits collimate waves from a point source into beams. The beam directions are prescribed by the lattice symmetry and the admittance ratio (Y 2 /Y 1 ) Ͻ 0. The basic properties of the channeled waves, determined by the isofrequencies, are invariant to the physical arrangements of the unit cells as long as the ratio (Y 2 /Y 1 ) remains constant. Effect of the unit cell structure on the channeled wave propagation has been explored for the unit cell configurations composed of double series (SSM), double parallel (PPM), and mixed parallel-series (PSM) L-C circuits. Analysis of these meshes has shown that the type (forward or backward) of channeled wave can be altered in the designed frequency band by varying only capacitance in the mesh arms. These findings are of particular significance for implementation of tunable meshes used in beam steering and phase compensation applications. Analysis of the channeled wave scattering at interfaces of dual L-C meshes showed that, in general, the "refracted" beams propagate only along the channel axes whose directions depend on the lattice parameters but not the angle of incidence onto interface. HIGH DIRECTIVITY IN LOW-PERMITTIVITY METAMATERIAL SLABS: RAY-OPTIC VS. LEAKY-WAVE MODEL

Robustness of a bisimulation-type faster-than preorder

TACS is an extension of CCS where upper time bounds for delays can be specified. Luettgen and Vogler defined three variants of bismulation-type faster-than relations and showed that they all three lead to the same preorder, demonstrating the robustness of their approach. In the present paper, the operational semantics of TACS is extended; it is shown that two of the variants still give the same preorder as before, underlining robustness. An explanation is given why this result fails for the third variant. It is also shown that another variant, which mixes old and new operational semantics, can lead to smaller relations that prove the same preorder.Comment: Express Worksho

On the Unification of Process Semantics: Logical Semantics

We continue with the task of obtaining a unifying view of process semantics by considering in this case the logical characterization of the semantics. We start by considering the classic linear time-branching time spectrum developed by R.J. van Glabbeek. He provided a logical characterization of most of the semantics in his spectrum but, without following a unique pattern. In this paper, we present a uniform logical characterization of all the semantics in the enlarged spectrum. The common structure of the formulas that constitute all the corresponding logics gives us a much clearer picture of the spectrum, clarifying the relations between the different semantics, and allows us to develop generic proofs of some general properties of the semantics.Comment: In Proceedings SOS 2011, arXiv:1108.279

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

New Bisimulation Semantics for Distributed Systems

Bisimulation semantics are a very pleasant way to define the semantics of systems, mainly because the simplicity of their definitions and their nice coalgebraic properties. However, they also have some disadvantages: they are based on a sequential operational semantics defined by means of an ordinary transition system, and in order to be bisimilar two systems have to be “too similar”. In this work we will present several natural proposals to define weaker bisimulation semantics that we think properly capture the desired behaviour of distributed systems. The main virtue of all these semantics is that they are real bisimulation semantics, thus inheriting most of the good properties of bisimulation semantics. This is so because they can be defined as particular instances of Jacobs and Hughes’ categorical definition of simulation, which they have already proved to satisfy all those properties

A controlled study of supplementation with essential amino acids and α-keto acids in the conservative management of patients with chronic renal failure

Art und Zusammensetzung einer optimalen eiweißarmen Ernährung für Patienten mit Niereninsuffizienz sind weiterhin umstritten. Die orale medikamentöse Behandlung mit essentiellen Aminosäuren oder α-Ketosäuren wird häufig empfohlen. Unsere Untersuchungen vergleichen nacheinander bei 15 ambulanten Patienten mit chronischem Nierenversagen (mittlere Kreatinin-Clearance 10,8 ml/min) unter einer eiweißarmen Ernährung von 0,57 g/kg Körpergewicht (40 g/70 kg) die Wirkung einer Substitution mit essentiellen Aminosäuren, danach die Substitution mit α-Ketosäuren gegenüber Plazebo. Der nachgewiesene Proteingehalt in der Nahrung betrug 0,55 g/kg, die Energiezufuhr 27 kcal/kg Körpergewicht, wie mehrfach Ernährungsprotokolle über jeweils 7 Tage bei den Patienten zeigen ließen. Nach einer Vorperiode von 6 Wochen nur unter diätetischen Maßnahmen erhielten alle Patienten zusätzlich 0,112 g essentielle Aminosäuren/kg Körpergewicht über 6 Wochen, danach in einer Doppelblinduntersuchung 0,105 g α-Ketosäuren/kg Körpergewicht im Vergleich gegenüber Plazebo, ebenfalls jeweils über 6 Wochen. Nüchtern-Blutuntersuchungen wurden für ein Standard-Laborwertprogramm, insbesondere für 15 Proteinmangelparameter, alle 3 Wochen durchgeführt, ferner anthropometrische und klinische Kontrollen. Die Laborwerte erbrachten keine Hinweise auf einen manifesten Proteinmangel. Die Therapie mit α-Ketosäuren erniedrigte die Phosphatspiegel signifikant (p<0,05). Dagegen konnten weder unter essentiellen Aminosäuren oder α-Ketosäuren andere für den Patienten wesentliche Effekte nachgewiesen werden. Deshalb erscheint uns eine Substitution mit essentiellen Aminosäuren oder Ketosäuren überflüssig bei Patienten mit einer chronischen Niereninsuffizienz, die sich in einem stabilen Stoffwechselgleichgewicht befinden und mit einer Eiweißzufuhr von 0,55 g/kg Körpergewicht behandelt werden. Oral therapy with essential amino acids (EAA) or α-keto acids (α-KA) has been recommended in patients with renal failure, but quality and quantity of optimal protein intake are still controversial. This study compares sequentially the effect of supplementation with EAA, and with α-KA versus placebo in 15 ambulatory patients with chronic renal failure (average creatinine clearance 10.8 ml/min), maintained on a protein diet of 0.57 g/kg body weight (40 g for a 70-kg patient). The actual dietary intake averaged 0.55 g protein/kg and 27 kcal/kg according to repeated 7-day dietary recordings. After a 6-week baseline period on this diet, all patients received additionally 0.112 g EAA/kg for 6 weeks followed by a double-blind cross-over study of 0.105 g α-KA/kg versus placebo supplementation for 6 weeks each. Fasting blood samples for multiple parameters, including 15 indicators for protein deficiency, as well as anthropometric and clinical data were evaluated every 3 weeks. Laboratory data revealed no indications of protein deficiency. Therapy with α-KA diminished serum phosphate concentration (p<0.05), however no other significant beneficial effects could be demonstrated during supplementation with either EAA or α-KA. Therefore, such supplementation to a 0.55-g/kg-protein diet appears superfluous in stable ambulatory patients with renal insufficiency.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41743/1/394_2005_Article_BF02020747.pd

Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy

Background Nephronophthisis associated ciliopathies (NPHP-AC) comprise a group of autosomal recessive cystic kidney diseases that includes nephronophthisis (NPHP), Senior-Loken syndrome (SLS), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). To date, causative mutations in NPHP-AC have been described for 18 different genes, rendering mutation analysis tedious and expensive. To overcome the broad genetic locus heterogeneity, a strategy of DNA pooling with consecutive massively parallel resequencing (MPR) was devised.Methods In 120 patients with severe NPHP-AC phenotypes, five pools of genomic DNA with 24 patients each were prepared which were used as templates in order to PCR amplify all 376 exons of 18 NPHP-AC genes (NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, GLIS2, RPGRIP1L, NEK8, TMEM67, INPP5E, TMEM216, AHI1, ARL13B, CC2D2A, TTC21B, MKS1, and XPNPEP3). PCR products were then subjected to MPR on an Illumina Genome-Analyser and mutations were subsequently assigned to their respective mutation carrier via CEL I endonuclease based heteroduplex screening and confirmed by Sanger sequencing.Results For proof of principle, DNA from patients with known mutations was used and detection of 22 out of 24 different alleles (92% sensitivity) was demonstrated. MPR led to the molecular diagnosis in 30/120 patients (25%) and 54 pathogenic mutations (27 novel) were identified in seven different NPHP-AC genes. Additionally, in 24 patients only single heterozygous variants of unknown significance were found.Conclusions The combined approach of DNA pooling followed by MPR strongly facilitates mutation analysis in broadly heterogeneous single gene disorders. The lack of mutations in 75% of patients in this cohort indicates further extensive heterogeneity in NPHP-AC

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation