We present a number of alternative ways of handling transitive binary relations that commonly occur in first-order problems, in particular equivalence relations, total orders, and transitive relations in general. We show how such relations can be discovered syntactically in an input theory, and how they can be expressed in alternative ways. We experimentally evaluate different such ways on problems from the TPTP, using resolution-based reasoning tools as well as instance-based tools. Our conclusions are that (1) it is beneficial to consider different treatments of binary relations as a user, and that (2) reasoning tools could benefit from using a preprocessor or even built-in support for certain types of binary relations.
The lysosomal storage disease Niemann–Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sphingomyelin and glucosylceramide (GlcCer). Similar to Gaucher disease (GD), patients deficient in glucocerebrosidase (GCase) degrading GlcCer, NPC patients show an elevated glucosylsphingosine and glucosylated cholesterol. In livers of mice lacking the lysosomal cholesterol efflux transporter NPC1, we investigated the expression of established biomarkers of lipid-laden macrophages of GD patients, their GCase status, and content on the cytosol facing glucosylceramidase GBA2 and lysosomal integral membrane protein type B (LIMP2), a transporter of newly formed GCase to lysosomes. Livers of 80-week-old Npc1−/− mice showed a partially reduced GCase protein and enzymatic activity. In contrast, GBA2 levels tended to be reciprocally increased with the GCase deficiency. In Npc1−/− liver, increased expression of lysosomal enzymes (cathepsin D, acid ceramidase) was observed as well as increased markers of lipid-stressed macrophages (GPNMB and galectin-3). Immunohistochemistry showed that the latter markers are expressed by lipid laden Kupffer cells. Earlier reported increase of LIMP2 in Npc1−/− liver was confirmed. Unexpectedly, immunohistochemistry showed that LIMP2 is particularly overexpressed in the hepatocytes of the Npc1−/− liver. LIMP2 in these hepatocytes seems not to only localize to (endo)lysosomes. The recent recognition that LIMP2 harbors a cholesterol channel prompts the speculation that LIMP2 in Npc1−/− hepatocytes might mediate export of cholesterol into the bile and thus protects the hepatocytes. 相似文献
Multivariate data visualization is a classic topic, for which many solutions have been proposed, each with its own strengths and weaknesses. In standard solutions the structure of the visualization is fixed, we explore how to give the user more freedom to define visualizations. Our new approach is based on the usage of Flexible Linked Axes: The user is enabled to define a visualization by drawing and linking axes on a canvas. Each axis has an associated attribute and range, which can be adapted. Links between pairs of axes are used to show data in either scatter plot- or Parallel Coordinates Plot-style. Flexible Linked Axes enable users to define a wide variety of different visualizations. These include standard methods, such as scatter plot matrices, radar charts, and PCPs [11]; less well known approaches, such as Hyperboxes [1], TimeWheels [17], and many-to-many relational parallel coordinate displays [14]; and also custom visualizations, consisting of combinations of scatter plots and PCPs. Furthermore, our method allows users to define composite visualizations that automatically support brushing and linking. We have discussed our approach with ten prospective users, who found the concept easy to understand and highly promising. 相似文献
Satisfiability solving, the problem of deciding whether the variables of a propositional formula can be assigned in such a
way that the formula evaluates to true, is one of the classic problems in computer science. It is of theoretical interest
because it is the canonical NP-complete problem. It is of practical interest because modern SAT-solvers can be used to solve
many important and practical problems. In this tutorial paper, we show briefly how such SAT-solvers are implemented, and point
to some typical applications of them. Our aim is to provide sufficient information (much of it through the reference list)
to kick-start researchers from new fields wishing to apply SAT-solvers to their problems. Supervisory control theory originated
within the control community and is a framework for reasoning about a plant to be controlled and a specification that the
closed-loop system must fulfil. This paper aims to bridge the gap between the computer science community and the control community
by illustrating how SAT-based techniques can be used to solve some supervisory control related problems. 相似文献
The assessment of the glycemic index (GI) seems to be an important parameter to take into account in order to better understand the physiologic effects of foods with high carbohydrate levels. Among cereals, which are major sources of carbohydrates, spelt (Triticum spelta L.) has been considered as particularly interesting from a nutritional point of view. The aim of this study was to evaluate in vivo the GI of white spelt bread in healthy subjects. The wheat (Triticum aestivum L.) white bread was used as reference food. To avoid differences in the production of both breads, spelt and wheat breads were baked under the same controlled conditions. Results showed that the glycemic profile of spelt white bread was not different from that of wheat white bread (GI of 93 ± 9). The area under the glycemic curve significantly and negatively correlated to fasting glycemia and carbohydrate intake during evening meals preceding the test. In conclusion, the glycemic response to spelt bread was similar to that of wheat bread. However, in order to avoid more inter-individual variability, our data supports the importance to propose standardised carbohydrate content for the last meal before evaluating the GI of food. 相似文献
Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options. 相似文献
The Mott transistor is a paradigm for a new class of electronic devices—often referred to by the term Mottronics—which are based on charge correlations between the electrons. Since correlation‐induced insulating phases of most oxide compounds are usually very robust, new methods have to be developed to push such materials right to the boundary to the metallic phase in order to enable the metal–insulator transition to be switched by electric gating. Here, it is demonstrated that thin films of the prototypical Mott insulator LaTiO3 grown by pulsed laser deposition under oxygen atmosphere are readily tuned by excess oxygen doping across the line of the band‐filling controlled Mott transition in the electronic phase diagram. The detected insulator to metal transition is characterized by a strong change in resistivity of several orders of magnitude. The use of suitable substrates and capping layers to inhibit oxygen diffusion facilitates full control of the oxygen content and renders the films stable against exposure to ambient conditions. These achievements represent a significant advancement in control and tuning of the electronic properties of LaTiO3+x thin films making it a promising channel material in future Mottronic devices. 相似文献
OBJECTIVE: To study the pharmacokinetic behaviour of quinine in Caucasians with and without malaria. METHOD: Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 patients with falciparum malaria. Plasma quinine concentrations were measured by high-performance liquid chromatography RESULTS: Quinine pharmacokinetics are time-dependent: the apparent elimination halftime is shorter in the accumulation phase than in the elimination phase; in malaria patients the maximal quinine concentration was reached in half the time calculated on the basis of the elimination phase after the last quinine infusion. Nevertheless a loading dose seemed advisable to reach adequate therapeutic levels quickly. In malaria patients the highest plasma concentrations during or at the end of the infusions were positively correlated with body weight. There was no correlation between body weight and the volume of distribution of quinine as calculated during the elimination phase. Hearing loss was audiometrically documented in 9 healthy subjects at a mean maximal plasma quinine concentration of only 2 mg/l. All malaria patients suffered serious cochlear hearing impairment. The ototoxic effects in both healthy subjects and patients appeared to be reversible. No electrographic changes were noted in the healthy subjects, whereas a clinically insignificant mean lengthening of the corrected QT interval was seen in the malaria patients. CONCLUSION: Intravenous quinine pharmacokinetics in healthy Caucasians were similar to those reported for Nigerian or Thai subjects. At effective doses quinine causes considerable but reversible cochlear hearing losses in both healthy persons and in patients. Our findings do support the need for a loading dose. The fact that in malaria patients there was no correlation between body weight and quinine VD as calculated during the elimination phase renders questionable the usefulness of dosing quinine according to body weight. 相似文献
Most enzyme studies are carried out in bulk aqueous solution, at the so-called ensemble level, but more recently studies have appeared in which enzyme activity is measured at the level of a single molecule, revealing previously unseen properties. To this end, enzymes have been chemically or physically anchored to a surface, which is often disadvantageous because it may lead to denaturation. In a natural environment, enzymes are present in a confined reaction space, which inspired us to develop a generic method to carry out single-enzyme experiments in the restricted spatial environment of a virus capsid. We report here the incorporation of individual horseradish peroxidase enzymes in the inner cavity of a virus, and describe single-molecule studies on their enzymatic behaviour. These show that the virus capsid is permeable for substrate and product and that this permeability can be altered by changing pH. 相似文献