Graphical representation of covariant-contravariant modal formulae

Covariant-contravariant simulation is a combination of standard (covariant) simulation, its contravariant counterpart and bisimulation. We have previously studied its logical characterization by means of the covariant-contravariant modal logic. Moreover, we have investigated the relationships between this model and that of modal transition systems, where two kinds of transitions (the so-called may and must transitions) were combined in order to obtain a simple framework to express a notion of refinement over state-transition models. In a classic paper, Boudol and Larsen established a precise connection between the graphical approach, by means of modal transition systems, and the logical approach, based on Hennessy-Milner logic without negation, to system specification. They obtained a (graphical) representation theorem proving that a formula can be represented by a term if, and only if, it is consistent and prime. We show in this paper that the formulae from the covariant-contravariant modal logic that admit a "graphical" representation by means of processes, modulo the covariant-contravariant simulation preorder, are also the consistent and prime ones. In order to obtain the desired graphical representation result, we first restrict ourselves to the case of covariant-contravariant systems without bivariant actions. Bivariant actions can be incorporated later by means of an encoding that splits each bivariant action into its covariant and its contravariant parts.Comment: In Proceedings EXPRESS 2011, arXiv:1108.407

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

Alfvén wave far field from steady-current tethers

We analyzed he Alfvén waves ignaturele ft behindi n the ionospherbe y orbiting insulatedt etherso peratinga s thrusterso r generatorws ith steadyc urrentsU. sing a recentd escription of tetherr adiationt o determineth e far field, we showt hat, at their leadinge dges,t heA lfv6n wingsh avea n Airy functionc rosswises tructureT. he field amplitudef alls off weakly as the inversec uber oot of the distancea longt he wavef ront.T he fronti tself, whichc arriesa negligible fractiono f the powerr adiateda sA lfven waves,b roadensp roportionallyto the cuber oot of that distanceW. e showt hatc ollisionadl ecayb ecomesim portanat t about1 03k m alongt he front.F or tethersl ongert han about2 km, the top andb ottoms tructures("wings")a re fully disjoint

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

Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors

BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles

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