bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Large‐Scale Structure of Semantic Networks: Statistical Analyses and a Model of Semantic Growth
Authors: Steyvers Mark , Tenenbaum Joshua B. 
Published: January 2005

AbstractWe present statistical analyses of the large‐scale structure of 3 types of semantic networks: word associations, WordNet, and Roget's Thesaurus. We show that they have a small‐world structure, characterized by sparse connectivity, short average path lengths between words, and strong local clustering. In addition, the distributions of the number of connections follow power laws that indicate a scale‐free pattern of connectivity, with most nodes having relatively few connections joined together through a small number of hubs with many connections. These regularities have also been found in certain other complex natural networks, such as the World Wide Web, but they are not consistent with many conventional models of semantic organization, based on inheritance hierarchies, arbitrarily structured networks, or high‐dimensional vector spaces. We propose that these structures reflect the mechanisms by which semantic networks grow. We describe a simple model for semantic growth, in which each new word or concept is connected to an existing network by differentiating the connectivity pattern of an existing node. This model generates appropriate small‐world statistics and power‐law connectivity distributions, and it also suggests one possible mechanistic basis for the effects of learning history variables (age of acquisition, usage frequency) on behavioral performance in semantic processing tasks.
Sketches from a Design Process: Creative Cognition Inferred From Intermediate Products
Authors: Jaarsveld Saskia , van Leeuwen Cees 
Published: January 2005

AbstractNovice designers produced a sequence of sketches while inventing a logo for a novel brand of soft drink. The sketches were scored for the presence of specific objects, their local features and global composition. Self‐assessment scores for each sketch and art critics' scores for the end products were collected. It was investigated whether the design evolves in an essentially random fashion or according to an overall heuristic. The results indicated a macrostructure in the evolution of the design, characterized by two stages. For the majority of participants, the first stage is marked by the introduction and modification of novel objects and their local and global aspects; the second stage is characterized by changes in their global composition. The minority that showed the better designs has a different strategy, in which most global changes were made in the beginning. Although participants did not consciously apply these strategies, their self‐assessment scores reflect the stages of the process.
Perception as Abduction: Turning Sensor Data Into Meaningful Representation
Authors: Shanahan Murray 
Published: January 2005

AbstractThis article presents a formal theory of robot perception as a form of abduction. The theory pins down the process whereby low‐level sensor data is transformed into a symbolic representation of the external world, drawing together aspects such as incompleteness, top‐down information flow, active perception, attention, and sensor fusion in a unifying framework. In addition, a number of themes are identified that are common to both the engineer concerned with developing a rigorous theory of perception, such as the one on offer here, and the philosopher of mind who is exercised by questions relating to mental representation and intentionality.
Does the World Leak Into the Mind? Active Externalism, “Internalism” and Epistemology
Authors: Dartnall Terry 
Published: January 2005

AbstractOne of the arguments for active externalism (also known as the extended mind thesis) is that if a process counts as cognitive when it is performed in the head, it should also count as cognitive when it is performed in the world. Consequently, mind extends into the world. I argue for a corollary: We sometimes perform actions in our heads that we usually perform in the world, so that the world leaks into the mind. I call this internalism. Internalism has epistemological implications: If a process gives us an empirical discovery when it is performed in the world, it will also give us an empirical discovery when it is performed in the head. I look at a simple example that highlights this implication. I then explore the relation between internalism and active externalism in more detail and conclude by comparing internalism with mental modeling.
α1- and β1-Adrenoceptor Signaling Fully Compensates for β3-Adrenoceptor Deficiency in Brown Adipocyte Norepinephrine-Stimulated Glucose Uptake
Authors: Chernogubova Ekaterina , Hutchinson Dana S. , Nedergaard Jan , Bengtsson Tore 
Published: January 2005

AbstractTo assess the relative roles and potential contribution of adrenergic receptor subtypes other than the β3-adrenergic receptor in norepinephrine-mediated glucose uptake in brown adipocytes, we have here analyzed adrenergic activation of glucose uptake in primary cultures of brown adipocytes from wild-type and β3-adrenergic receptor knockout (KO) mice. In control cells in addition to high levels of β3-adrenergic receptor mRNA, there were relatively low α1A-, α1D-, and moderate β1-adrenergic receptor mRNA levels with no apparent expression of other adrenergic receptors. The levels of α1A-, α1D-, and β1-adrenergic receptor mRNA were not changed in the β3-KO brown adipocytes, indicating that the β3-adrenergic receptor ablation does not influence adrenergic gene expression in brown adipocytes in culture. As expected, the β3-adrenergic receptor agonists BRL-37344 and CL-316 243 did not induce 2-deoxy-d-glucose uptake in β3-KO brown adipocytes. Surprisingly, the endogenous adrenergic neurotransmitter norepinephrine induced the same concentration-dependent 2-deoxy-d-glucose uptake in wild-type and β3-KO brown adipocytes. This study demonstrates that β1-adrenergic receptors, and to a smaller degree α1-adrenergic receptors, functionally compensate for the lack of β3-adrenergic receptors in glucose uptake. β1-Adrenergic receptors activate glucose uptake through a cAMP/protein kinase A/phosphatidylinositol 3-kinase pathway, stimulating conventional and novel protein kinase Cs. The α1-adrenergic receptor component (that is not evident in wild-type cells) stimulates glucose uptake through a phosphatidylinositol 3-kinase and protein kinase C pathway in the β3-KO cells.
Drug-induced block of cardiac HERG potassium channels and development of torsade de pointes arrhythmias: the case of antipsychotics
Authors: Calderone Vincenzo , Testai Lara , Martinotti Enrica , Del Tacca Mario , Breschi Maria Cristina 
Published: January 2005

Abstract
The prolongation of the cardiac repolarization process, a result of the blocking of the Human Ether-a-go-go Related Gene potassium channel, is an undesired accessory property shared by many pharmacological classes of non-cardiovascular drugs. Often the delayed cardiac repolarization process can be identified by a prolongation of the QT interval of the electrocardiograph. In these conditions, premature action potentials can trigger a dangerous polymorphic ventricular tachyarrhythmia, known as torsade de pointes, which occasionally can result in lethal ventricular fibrillation. In this work, brief descriptions of the electrophysiological basis of torsade de pointes and of the several pharmacological classes of torsadogenic drugs are given. Attention is focused on antipsychotics, with a deeper overview on the experimental and clinical reports about their torsadogenic properties.
Effects of glucose, fructose and 5-hydroxymethyl-2-furaldehyde on the presystemic metabolism and absorption of glycyrrhizin in rabbits
Authors: Hou Y C , Ching H , Chao P D L , Tsai S Y , Wen K C , Hsieh P H , Hsiu S L 
Published: January 2005

Abstract
Our previous study reported that co-administration of honey significantly increased the serum levels of glycyrrhetic acid (GA) after oral administration of glycyrrhizin (GZ) in rabbits. The components of honey are sucrose, glucose, fructose and 5-hydroxymethyl-furaldehyde (HMF). To clarify the causative component(s) in honey that altered the metabolic pharmacokinetics of GZ, rabbits were given GZ (150 mg kg−1) with and without glucose (5g/rabbit), fructose (5 g/rabbit) and HMF (1 mg kg−1), respectively, in crossover designs. An HPLC method was used to determine concentrations of GZ and GA in serum as well as GA and 3-dehydroglycyrrhetic acid (3-dehydroGA) in faeces suspension. A noncompartment model was used to calculate the pharmacokinetic parameters and analysis of variance was used for statistical comparison. Our results indicated that the area under curve (AUC) of GA was significantly increased by 29% when HMF was coadministered, whereas the pharmacokinetics of GZ and GA were not significantly altered by coadministration of glucose or fructose. An in-vitro study, using faeces to incubate GZ and GA individually, indicated that HMF significantly inhibited the oxidation of GA to 3-dehydroGA and this may explain the enhanced GA absorption in-vivo. It was concluded that HMF is the causative component in honey that affects the presystemic metabolism and pharmacokinetics of GZ in-vivo.
Fadolmidine-induced ocular hypotension in normotensive rabbits
Authors: Savolainen Jouko , Niemi Riku , Mäntylä Antti , Huuskonen Juhani , Järvinen Tomi 
Published: January 2005

Abstract
Fadolmidine, a novel selective α-adrenoceptor agonist, was evaluated for its efficacy to lower intraocular pressure in normotensive rabbits (n = 5–6). The dose-response profile between 0.004 μg and 12.5 μg of fadolmidine was determined. The effect of pH on the partition of fadolmidine was studied in order to select an optimal pH for topical fadolmidine administration. After topical administration, fadolmidine significantly lowered the intraocular pressure in normotensive rabbits. The onset of action was immediate, with no initial increase in intraocular pressure. A significant decrease in intraocular pressure was already observed at 1 h after dosing. The maximum decrease in intraocular pressure was observed after a 2.5 μg dose of fadolmidine in both eyes at 2 h after dosing. The mean maximum decrease in the treated and untreated eye was 6.4 mmHg and 3.9 mmHg, respectively. In conclusion, fadolmidine is a potent intraocular pressure lowering agent. In addition, fadolmidine does not cause a significant initial increase in intraocular pressure. Because of the strong dependence of the distribution coefficient on pH, the pH of the administered solution is important, with physiological pH being optimal in this respect.
Polyphenols from plants used in traditional Indonesian medicine (Jamu): uptake and antioxidative effects in rat H4IIE hepatoma cells
Authors: Steffan Bärbel , Wätjen Wim , Michels Gudrun , Niering Petra , Wray Victor , Ebel Rainer , Edrada RuAngelie , Kahl Regine , Proksch Peter 
Published: January 2005

Abstract
Phytochemical investigation of plants used in traditional Indonesian medicine (Jamu) yielded lignans (pinoresinol, 9α-hydroxypinoresinol and salicifoliol), flavonoids (3-β-D-glucopyranosyl-(1→6)-β-d-glucopyranosylkaempferol, luteolin and apigenin) and coumarins (coumarin, 8-hydroxycoumarin and 5-hydroxycoumarin). The beneficial effects of the respective plants for human health are thought to be associated with antioxidative activity. In the present study, the antioxidative capacity of the isolated compounds was determined in an in-vitro assay. Luteolin and kaempferol (cleavage product of 3-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosylkaempferol, which is thought to be formed in the intestine) showed strong antioxidant activity; pinoresinol and 9α-hydroxypinoresinol showed only minor antioxidative effects. The coumarins, as well as apigenin and 3-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosylkaempferol were inactive. The antioxidative effects of luteolin, kaempferol and pinoresinol were further investigated in H4IIE rat hepatoma cells. A strong protective effect of kaempferol and luteolin was found against H2O2-mediated intracellular reactive oxygen species formation measured using the dichlorofluorescein assay and H2O2-mediated DNA strand breaks. Pinoresinol did not have a protective effect against H2O2-mediated DNA-damage, but in the dichlorofluorescein assay, an antioxidative effect was detectable. During studies with H4IIE cells, kaempferol, luteolin and pinoresinol were taken up by the cells within 60 min. The flavonoids were found to be relatively toxic at higher concentrations, while pinoresinol was less cytotoxic. In conclusion, kaempferol and luteolin, at low concentrations (≤ 50μm), protect H4IIE cells against oxidative stress but are cytotoxic at higher concentrations; the biological effects of pinoresinol are less prominent in comparison. These results are important for the identification of pharmacologically active substances from traditional Indonesian medicinal plants.
The changes in the endothelial expression of cell adhesion molecules and iNOS in the vessel wall after the short-term administration of simvastatin in rabbit model of atherosclerosis
Authors: Nachtigal Petr , Kopecky Martin , Solichova Dagmar , Zdansky Petr , Semecky Vladimir 
Published: January 2005

Abstract
Cell adhesion molecules P-selectin, VCAM-1 and ICAM-1 play an important role in the pathogenesis of atherosclerosis. High levels of nitric oxide (NO) produced by inducible NO synthase (iNOS) have been associated with atherosclerotic processes. Simvastatin is an HMG-CoA reductase inhibitor responsible for many clinical benefits. The aim of this study was to detect and quantify changes in endothelial expression of P-selectin, VCAM-1, ICAM-1 and iNOS in the vessel wall after the short-term administration of simvastatin in a rabbit model of atherosclerosis. Eighteen New Zealand White rabbits were randomly divided into three groups (n = 6). In the cholesterol group, rabbits consumed an atherogenic diet (0.4% cholesterol) for eight weeks. In the simvastatin group, rabbits consumed an atherogenic diet for six weeks and then consumed an atherogenic diet supplemented with simvastatin (10 mg kg−1) for two weeks. Biochemical analysis showed that administration of simvastatin led to an almost two-fold lowering of the total serum cholesterol, VLDL, LDL and HDL, but not triglycerides, compared with the cholesterol-fed rabbits only. Stereological analysis of the immuno-histochemical staining revealed that administration of simvastatin (10 mg kg−1 daily) in an atherogenic diet decreased the endothelial expression of P-selectin, ICAM-1 and iNOS in both aortic arch and carotid artery compared with the cholesterol fed-rabbits only. We conclude that simvastatin has beneficial effects on endothelial function by decreasing expression of P-selectin, ICAM-1 and iNOS in endothelial cells in the very early stages of atherogenesis.
In-vitro evaluation of khaya and albizia gums as compression coatings for drug targeting to the colon
Authors: Odeku Oluwatoyin A , Fell John T 
Published: January 2005

Abstract
Khaya and albizia gums were evaluated as compression coatings for target drug delivery to the colon using indometacin (a water insoluble drug) and paracetamol (a water soluble drug) as model drugs. The core tablets were compression-coated with 300 and 400mg of 100% khaya gum, 100% albizia gum and a mixture of khaya and albizia gum (1:1). Drug release studies were carried out in 0.1M HCI (pH 1.2) for 2h, Sorensen's buffer (pH 7.4) for 3 h and then in phosphate-buffered saline (pH 6.8) or in simulated colonic fluid for the rest of the experiment to mimic the physiological conditions from the mouth to colon. The results indicated that khaya and albizia gums were capable of protecting the core tablet in the physiological environment of the stomach and small intestine, with albizia gum showing greater ability than khaya gum. The release from tablets coated with the mixture of khaya and albizia gums was midway between the two individual gums, indicating that there was no interaction between the gums. Studies carried out using rat caecal matter in phosphate-buffered saline at pH 6.8 (simulated colonic fluid) showed that the gums were susceptible to degradation by the colonic bacterial enzymes, leading to release of the drug. The results demonstrate that khaya gum and albizia gum have potential for drug targeting to the colon.
Synthesis of baicalein derivatives as potential anti-aggregatory and anti-inflammatory agents
Authors: Huang Wen-Hsin , Lee An-Rong , Chien Pei-Yu , Chou Tz-Chong 
Published: January 2005

Abstract
The direct acylation of trimethoxyphenol (1) with substituted cinnamoyl chlorides followed by Fries rearrangement and cyclization afforded a practical route for the synthesis of novel baicalein derivatives 4 functionalized on the B-ring in good overall yields. In the methylthiazoletetrazolium bromide (MTT) assay, none of the synthetic polyhydroxyflavonoids were cytotoxic at concentrations up to 200 μm on lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages over 24 h, while in the same cells they significantly inhibited NO production. Among the derivatives, 4d (IC50 = 46.1 ± 0.3 μm) was found to exhibit the most potent activity compared with N-nitro-L-arginine methyl ester (L-NAME, IC50 &gt; 300 μm). Compounds 4b, 4e, 4f, 4h and 4i remarkably inhibited platelet aggregation induced by arachidonic acid and collagen in rabbit washed platelets compared with aspirin. Analysis of their structure-activity relationships indicated that, in the structural modification on the B-ring of baicalein (4a), introduction of appropriate electro-withdrawing substituents such as 2-CI (4b), 4-CI (4d), and 4-phenyl (4i) notably increased the potency on the inhibition of LPS-activated NO production and arachidonic acid- and collagen-induced aggregation. Baicalein itself was equally effective in the inhibition of LPS-activated NO production and collagen-induced aggregation but less active against arachidonic acid-induced aggregation. Our in-vitro results suggested that by appropriate structural modification of baicalein it may be possible to develop novel therapeutic agents against platelet-aggregation and inflammation.
Pharmacokinetic advantage of intraperitoneal injection of docetaxel in the treatment for peritoneal dissemination of cancer in mice
Authors: Shimada Tsutomu , Nomura Masaaki , Yokogawa Koichi , Endo Yoshio , Sasaki Takuma , Miyamoto Ken-ichi , Yonemura Yutaka 
Published: January 2005

Abstract
Intraperitoneal administration of docetaxel has been used to treat peritoneal dissemination of cancer, but its safety has not yet been confirmed. We have compared the pharmacokinetic behaviour of docetaxel after intravenous and intraperitoneal administration in CD-1-nu/nu mice bearing MKN-45P, a gastric cancer variant line producing peritoneal dissemination. Docetaxel (8mg kg−1) was intravenously or intraperitoneally injected into the mice and at designated times the drug concentration was measured in plasma, ascites fluid, and abdominal tissues (liver, kidney, intestine and spleen, solid cancer, and suspended free cancer). The pharmacokinetic behaviour of docetaxel was similar in control mice and cancer-bearing mice after administration via either route, except that the transfer of docetaxel from the abdominal cavity to systemic blood (plasma) was slower in cancer-bearing mice than in control mice. As expected, the intraperitoneal drug concentration was much higher (approximately 100-fold) and was maintained for a longer time in the intraperitoneal injection group than in the intravenous injection group. The drug concentrations in peritoneal solid cancer tissue and suspended free cancer cells were also significantly higher for a longer time in the intraperitoneal injection group than in the intravenous injection group. The values of the plasma area under concentration-time curves (AUC) were similar for both administration routes. The ratio of AUC ascite/AUC plasma after intraperitoneal administration was higher than after intravenous administration. The drug concentration in abdominal organs after intraperitoneal injection was lower during the first 2 h, then became similar to those after intravenous injection. These results indicated that the intraperitoneal administration of docetaxel for peritoneal dissemination was likely to be an effective treatment method, without causing any increase in systemic toxicity.
The anxiolytic-like effect of 5-HT1B receptor ligands in rats: a possible mechanism of action
Authors: Chojnacka-Wójcik Ewa , Kłodzińska Aleksandra , Tatarczyńska Ewa 
Published: January 2005

Abstract
We have examined the effect of lesions of 5-hydroxytryptamine (5-HT) neurons, produced by p-chloroamphetamine (p-CA; 2 times 10 mg kg−1), and the influence of flumazenil (Ro 15–1788, 10 mg kg−1), a benzodiazepine receptor antagonist, on the anxiolytic-like activity of CP 94253 (5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1-H-pyrrolo[3,2-b]pyridine), a 5-HT1B receptor agonist, SB 216641 (N-[3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1′-biphenyl]-4-carboxamide), a 5-HT1B receptor antagonist, and GR 127935 (N-[4-methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1, 1′-biphenyl-4-carboxamide), a 5-HT1B/1D receptor antagonist, in the Vogel conflict drinking test in rats. Diazepam was used as a reference compound. CP 94253 (2.5 mg kg−1), SB 216641 (2.5 mg kg−1), GR 127935 (10 mg kg−1) and diazepam (5 mg kg−1) significantly increased the number of shocks accepted during experimental sessions in the conflict drinking test in vehicle- and p-CA-pretreated rats. Flumazenil did not change the anxiolytic-like effect of CP 94253 (2.5 mg kg−1), but wholly blocked the anxiolytic-like effects of SB 216641 (2.5 mg kg−1), GR 127935 (10 mg kg−1) and diazepam (5 mg kg−1). p-CA and flumazenil alone were inactive in the conflict drinking test. The results suggested that the anxiolytic-like effect of the 5-HT1B receptor ligands CP 94253, SB 216641 and GR 127935 was possibly linked to the postsynaptic 5-HT1B receptors or/and 5-HT1B heteroreceptors. The results suggested also that benzodiazepine receptors were indirectly involved in the effects of SB 216641 and GR 127935 (but not of CP 94253), which might have been due to a possible interaction between the 5-HT and the GABA/benzodiazepine systems.
Oleanolic acid nanosuspensions: preparation, in-vitro characterization and enhanced hepatoprotective effect
Authors: Chen Yajun , Liu Jie , Yang Xiangliang , Zhao Xiaoling , Xu Huibi 
Published: January 2005

Abstract
Oleanolic acid is a naturally derived triterpene used clinically in the treatment of hepatitis in China, but its poor solubility often leads to poor bioavailability. In the present study, oleanolic acid nanosuspensions were prepared by the nanoprecipitation method and then systematically characterized. The average particle size of the obtained nanosuspensions was 284.9 nm, with a polydispersity index of 0.216. Transmission electron microscopy and atomic force microscopy showed that the drug existed as spherical or near-spherical nanoparticles in the nanosuspensions. Differential scanning calorimetry and X-ray diffraction studies indicated that oleanolic acid was present in an amorphous state in the lyophilized nanosuspensions. At 25°C, the saturation solubility of oleanolic acid was increased by about 6 times after nanoation (25.72 μg mL−1 vs 4.37 μg mL−1). In the in-vitro drug release experiments, the lyophilized nanosuspensions showed a faster drug dissolution rate than that of the coarse drug powder (approx. 90% vs 15% during the first 20 min), and nearly 95% of the oleanolic acid was released by 120 min. As evidenced by the lower serum alanine aminotransferase activity and liver malondiadehyde content, pre-treatment with oleanolic acid nanosuspensions significantly enhanced the hepatoprotective effect of oleanolic acid against carbon tetrachlorideinduced liver injury.