bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the typological plausibility of Processability Theory: language development in Italian second language and Japanese second language
Authors: Di Biase Bruno , Kawaguchi Satomi 
Published: September 2002

This article aims to test the typological plausibility of Processability Theory (PT) (Pienemann, 1998). This is ‘a theory of processability of grammatical structures... [which] formally predicts which structures can be processed by the learner at a given level of development’ (p. xv). Up till now the theory has been tested mainly for Germanic languages, while here we propose to test it for two typologically different languages, namely Italian and Japanese. Language specific predictions for these two languages will be derived from PT, and the structures instantiating them will be described within a Lexical Functional Grammar (LFG) framework. The occurrence and distribution of relevant structures will then be analysed in empirical, naturalistic data produced by adult learners. To test whether PT is typologically plausible we will demonstrate the following points for Japanese and Italian: • The notion of ‘exchange of grammatical information’ is a productive concept for typologically different languages. • Predictions that can be derived from the general architecture of the theory for specific languages will be borne out by empirical observation. (Pienemann 1998: 166).
Induction in a modular learner
Authors: Carroll Susanne E. 
Published: September 2002

This paper presents a theory of inductive learning (i-learning), a form of induction which is neither concept learning nor hypothesis-formation, but rather which takes place within the autonomous and modular representational systems (levels of representation) of the language faculty. The theory is called accordingly the Autonomous Induction Theory. Second language acquisition (SLA) is conceptualized in this theory as:• learning linguistic categories from universal and potentially innate featural primitives;• learning configurations of linguistic units; and• learning correspondences of configurations across the autonomous levels.Here I concentrate on the problem of constraining learning theories and argue that the Autonomous Induction Theory is constrained enough to be taken seriously as a plausible approach to explaining second language acquisition.
Effects of two differently heparin-coated extracorporeal circuits on markers for brain and myocardial dysfunction
Authors: Flom-Halvorsen Hanne I , Øvrum E , Brosstad F , Tangen G , Ringdal M AL , Øystese R 
Published: September 2002

Objective: The two most commonly used heparin-coated systems for cardiopulmonary bypass (CPB) are the Carmeda Bio-Active Surface (CBAS) (Medtronic, Minneapolis, MN, USA) and the Duraflo II coating (Baxter Healthcare, Irvine, CA, USA). The two surfaces are technically unequal and previous experimental studies have demonstrated disparities in effects on the immune system and blood cells. However, little is known concerning the influence of the two surfaces on markers for brain and myocardial dysfunction. Methods: Forty patients undergoing elective, primary coronary bypass grafting with CPB were prospectively randomized to either the CBAS system or the Duraflo II circuit. During and after CPB, biological markers for brain dysfunction and myocardial injury were analysed. Results: Both markers for brain dysfunction S-100B and neuron-specific enolase (NSE) increased significantly during CPB ( p =0.01). The elevation during bypass correlated significantly with the duration of CPB ( r = 0.39 and r= 0.38, respectively, both p< 0.02). NSE was somewhat more elevated in the Duraflo II group at the end of CPB ( p =0.01) and 5 h after CPB ( p= 0.02); for S-100B, there were no intergroup differences. Also, the markers related to myocardial injury, myoglobin and creatine kinase (CK-MB) mass increased during CPB ( p= 0.01), while elevation of troponin-I occurred 5 h after CPB ( p= 0.01). There were no statistically significant intergroup differences. No significant correlation was seen between the release of cardiac markers and the duration of CPB. The clinical course was similar in both groups. Conclusions: Except for a slightly higher elevation of NSE at the end of CPB and 5 h after CPB in the Duraflo II group, there were no significant differences between the CBAS group and the Duraflo II group concerning markers for brain and myocardial dysfunction.
Do S100β protein level increases due to inflammation during cardiopulmonary bypass occur without any neurological deficit?
Authors: Özatik Mehmet Ali , Tarcan Onurcan , Kale Arzum , Aşkõn Göktan , Balcõ Mustafa , Ündar Akif , Küçükaksu Deniz Süha , Şener Erol , Taşdemir Oğuz 
Published: September 2002

Purpose: S100β protein level correlates with the duration of cardiopulmonary bypass (CPB) and aortic crossclamp times, but is different during pulsatile and nonpulsatile CPB. In this study, we investigated the time course of the release of S100β protein during and after pulsatile and nonpulsatile CPB. Patients and methods: This is a prospective study. Twenty patients had open-heart surgery with pulsatile flow and 20 with nonpulsatile flow. We compared complement proteins, interleukins, white blood cells and S100β protein before the initiation of CPB, immediately prior to aortic crossclamping, following unclamping, and at postoperative 1st and 24th hours. Results: In the pulsatile CPB group following aortic unclamping, S100β protein ( p= 0.028) and C3a ( p= 0.011) levels were significantly lower than those of the nonpulsatile group. In the pulsatile CPB group at postoperative first hour, C3a level ( p= 0.018) and absolute neutrophil count ( p= 0.034) were significantly lower than those of the nonpulsatile group. None of the patients developed a neurological deficit and all of the patients survived after the operation and were discharged from the hospital. Conclusion: During CPB, serum S100β protein level increases and this increase is higher in the nonpulsatile group. High serum level of S100β protein is associated with increased levels of serum inflammatory mediators and systemic inflammatory response.
Blood salvage with a continuous autotransfusion system compared with a haemofiltration system
Authors: Nitescu N , Bengtsson A , Bengtson J P 
Published: September 2002

Background: Red blood cells may be destroyed by autotransfusion processing during intraoperative salvage. The aim of the present study was to evaluate the blood component recovery rate of techniques built on either continuous centrifugation and washing, or haemofiltration (HF). Methods: Two different methods used in blood salvage - red cell salvage with continuous processing with centrifugation and saline washing (Continuous Auto Transfusion System, CATS) and whole blood recirculation through a 30000-Da filter, i.e., HF - were compared in a randomized laboratory study using donor whole blood activated by cobra venom factor. The recovery of red blood cells, haemoglobin, free haemoglobin, leucocytes, platelets, albumin, total protein and potassium was measured. Results: The recovery of red cells was 86% with CATS and 76% with HF. HF had a significantly higher recovery of leucocytes (CATS 20%, HF 63%), platelets (CATS 4%, HF 37%), albumin (CATS 0.2%, HF 70%), total protein (CATS 1.3%, HF 71%) and potassium (CATS 2%, HF 17%). Less than 1% haemolysis was obtained in processed blood from both groups. Conclusion: Both methods caused little destruction of the red blood cells during processing. There was a larger reinfusion of leucocytes, platelets, albumin, total protein and extracellular potassium when HF was used compared with the ‘CATS’ method.
On the ethical aspects of the testimony of statisticians in court
Authors: Gehan E A 
Published: September 2002

This article considers a legal case presented by the Gore campaign to the Florida Eleventh Circuit Court in December 2000 to contest the election results giving the 25 electoral votes from the State of Florida to George W Bush—basically awarding the presidency to Bush. Consideration is given to the ethical aspects of the testimony of two statisticians, one for Gore and one for Bush, who testified about whether the certified election results rejected a number of legal votes and included a number of illegal votes sufficient to place in doubt the results of the election. It is concluded that neither statistician violated accepted ethical standards of the statistical profession, though the Bush statistician’s testimony was at least borderline unethical on certain points. The main problem seems to be with the advocacy principle of the American legal system that leads to the prosecution witnesses testifying narrowly to the truths about the case, whereas the defense witnesses do the same from their viewpoint and also try to belittle the testimony of the prosecution witnesses. All of this makes it difficult to uncover the real truths in the case. The judge’s decision was to reject Gore’s case and this helped to clear the path to the election of Bush as President of the United States.
Stationary space-time Gaussian fields and their time autoregressive representation
Authors: Storvik Geir , Frigessi Arnoldo , Hirst David 
Published: September 2002

We compare two different modelling strategies for continuous space discrete time data. The first strategy is in the spirit of Gaussian kriging. The model is a general stationary space-time Gaussian field where the key point is the choice of a parametric form for the covariance function. In the main, covariance functions that are used are separable in space and time. Nonseparable covariance functions are useful in many applications, but construction of these is not easy. The second strategy is to model the time evolution of the process more directly. We consider models of the autoregressive type where the process at time t is obtained by convolving the process at time t − 1 and adding spatially correlated noise. Under specific conditions, the two strategies describe two different formulations of the same stochastic process. We show how the two representations look in different cases. Furthermore, by transforming time-dynamic convolution models to Gaussian fields we can obtain new covariance functions and by writing a Gaussian field as a time-dynamic convolution model, interesting properties are discovered. The computational aspects of the two strategies are discussed through experiments on a dataset of daily UK temperatures. Although algorithms for performing estimation, simulation, and so on are easy to do for the first strategy, more computer-efficient algorithms based on the second strategy can be constructed.
RNA-acting antibiotics: in-vitro selection of RNA aptamers for the design of new bioactive molecules less susceptible to bacterial resistance
Authors: Maurel M-C , Biard B , Moulinier C , Braz D , Nugier J , Chaumas I , Reboud-Ravaux M , Décout J-L 
Published: September 2002

Abstract
During the last few years, antibiotic multiresistance has been increasing, not only in hospitals, but also, more worryingly, in general medicine. Different ways are being explored to bypass this problem. RNA-acting antibiotics such as aminosides (aminoglycosides) bind to bacterial RNA causing premature termination of proteins and mistranslation in bacteria. It is now possible to study the interactions of such antibiotics with their target by in-vitro selection of RNA molecules that recognize these antibiotics (RNA aptamers, SELEX method). The knowledge of the antibiotic-RNA interactions represents a promising way for the rational design of new bioactive compounds less susceptible to bacterial resistance.
Excipient crystallinity and its protein-structure-stabilizing effect during freeze-drying
Authors: Izutsu Ken-ichi , Kojima Shigeo 
Published: September 2002

Abstract
The relationship between mannitol crystallization during freeze-drying and its effects on stabilizing protein structures was studied using lysozyme, bovine serum albumin, ovalbumin, β-lactoglobulin and lactate dehydrogenase as model proteins. FT-IR analysis of the protein secondary structure indicated perturbation of both α-helix and β-sheet regions in freeze-drying without cosolutes, whereas the proteins retained most of their native structure in co-lyophilization with sucrose. Mannitol protected the protein structure to different degrees depending on the crystallinity. The combination of mannitol with potassium phosphate buffer reduced the mannitol crystallinity and the structural changes occurring during freeze-drying, whereas mannitol by itself showed little stabilizing effect. Heat-treatment of the frozen solutions at −10°C resulted in a higher mannitol crystallinity and a smaller stabilizing effect in freeze-drying. The secondary structure perturbation was mostly reversible in rehydrated solutions. The varied structure-stabilizing effects of mannitol paralleled its effects on maintaining lower concentrations of enzyme activity during freeze-drying. These results confirm the contribution of molecular interactions between amorphous excipients and proteins (e.g. hydrogen bonding) to structure stabilization during freeze-drying.
Solvent change co-precipitation with hydroxypropyl methylcellulose phthalate to improve dissolution characteristics of a poorly water-soluble drug
Authors: Sertsou Gabriel , Butler James , Hempenstall John , Rades Thomas 
Published: September 2002

Abstract
Research compound GWX belongs to biopharmaceutical classification system type II, and hence shows dissolution-rate-limited absorption. To improve its dissolution performance, GWX was formulated as a co-precipitate with hydroxypropyl methylcellulose phthalate (HPMCP). Co-precipitates with various drug-HPMCP ratios were prepared and characterised using modulated differential scanning calorimetry (MDSC), X-ray powder diffraction, HPLC and dissolution testing. Co-precipitates with 1: 9 and2: 8 drug-HPMCP ratios showed the highest extent of dissolution after both 5 and 90 min, followed by 3: 7, 4: 6, and 5: 5 drug-HPMCP co-precipitates, in respective order. Co-precipitates with drug-HPMCP ratios of 6: 4 and greater showed no significant improvement in dissolution over crystalline drug alone. The amounts of crystalline and amorphous drug in co-precipitates, as determined by MDSC, and HPLC quantification of the total amount of drug in co-precipitates were used to determine the amount of drug incorporated into solid solution. It was found that dissolution rate and extent was correlated to the amount of drug incorporated into amorphous solid solution for the 1:9 to 5: 5 drug-HPMCP ratio co-precipitates. Amorphous drug alone and physical mixtures of drug and HPMCP showed very little and no significant improvement in dissolution rate or extent, respectively, above crystalline drug alone. Amorphous drug alone re-crystallized to a large extent within 1 min of contact with the dissolution medium, whereas 4: 6 drug-HPMCP co-precipitate showed a lower degree of re-crystallization and 2: 8 drug-HPMCP co-precipitate showed very little re-crystallization. It was concluded that the likely mechanisms of improved dissolution of low drug-HPMCP ratio co-precipitates were improved wetting or increased surface area for mass transfer, thermodynamically enhanced dissolution of a higher energy amorphous form and inhibition of re-crystallization, when drug was incorporated into solid solution.
Enhanced oral absorption of halofantrine enantiomers after encapsulation in a proliposomal formulation
Authors: Brocks Dion R , Betageri Guru V 
Published: September 2002

Abstract
In this study, we evaluated the ability of a coated, encapsulated formulation to increase the oral bioavailability of (±)-halofantrine (HF) enantiomers, a drug with low and erratic oral bioavailability. After encapsulation of HF in distearoylphosphatidylcholine, the dried particles were coated with cellulose acetate phthalate. A suspension of the product was made using methylcellulose as a dispersion agent, and the product was administered to Sprague-Dawley rats to provide a HF dose of 7 mg kg−1 as the HCl salt. HF HCl powder in 1 % methylcellulose with or without liposomal product excipients was also administered to separate groups of rats, which served as control groups. Serial blood samples were obtained from the rats and plasma was assayed by stereospecific high-performance liquid chromatography. There were no significant differences in the area under the concentration-time curve (AUC) or maximum concentration (Cmax) between the two control groups. Plasma concentrations of both HF enantiomers were significantly higher in the rats given HF as an encapsulated proliposomal formulation compared with the control groups. Compared with methyl-cellulose control, the encapsulation product resulted in increases of 41 to 47% in the AUC of HF enantiomers, and 90 to 100% in Cmax. The ability of an encapsulated proliposomal product to significantly increase the oral absorption of HF was clearly demonstrated.
Contribution of P-glycoprotein to efflux of ramosetron, a 5-HT3 receptor antagonist, across the blood-brain barrier
Authors: Yamamoto Chika , Murakami Hideyasu , Koyabu Noriko , Takanaga Hitomi , Matsuo Hirotami , Uchiumi Takeshi , Kuwano Michihiko , Naito Mikihiko , Tsuruo Takashi , Ohtani Hisakazu , Sawada Yasufumi 
Published: September 2002

Abstract
In-situ rat and mouse brain perfusion data indicated that the brain distribution of ramosetron (R-ramosetron), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, was extremely low compared with that expected from its lipophilicity. We hypothesized the involvement of an efflux system(s) and investigated the contribution of P-glycoprotein to efflux transport of ramosetron across the blood-brain barrier by means of an in-vitro uptake study in cell lines that over-express P-glycoprotein. We examined the contributions of mdr1a, mdr1b and MDR1 P-glycoprotein by using LV500 cells, MBEC4 cells and LLC-GA5-COL300 cells, which over-express mdr1a P-glycoprotein, mdr1b P-glycoprotein and MDR1 P-glycoprotein, respectively. The uptake of [14C]ramosetron by LV500 cells and LLC-GA5-COL300 cells was significantly lower than that by the respective parental cells. Next, we studied the effects of P-glycoprotein inhibitors, verapamil and ciclosporin, on uptake of [14C] ramosetron by these cell lines. The uptake of [14C]ramosetron by LV500 cells and LLC-GA5-COL300 cells was significantly increased in the presence of verapamil or ciclosporin, while verapamil did not affect the uptake of [14C]ramosetron by MBEC4 cells. These results indicate that the efflux of [14C]ramosetron is partly mediated by mdr1a P-glycoprotein, but not by mdr1b P-glycoprotein, and that there is a difference in substrate specificity between mdr1a P-glycoprotein and mdr1b P-glycoprotein. Further, [14C]ramosetron was confirmed to be effluxed by human MDR1 P-glycoprotein. We conclude that the limited distribution of ramosetron to the brain is due, at least in part, to efflux mediated by the P-glycoprotein at the blood-brain barrier.
Lung surfactant phospholipids inhibit the uptake of respirable microspheres by the alveolar macrophage NR8383
Authors: Jones B G , Dickinson P A , Gumbleton M , Kellaway I W 
Published: September 2002

Abstract
Fluorescent poly(lactic-co-glycolic acid) microspheres of a respirable size were fabricated for use in a fluorescent activated cell sorting assay utilizing the continuous alveolar macrophage NR8383. This is a suitable model of alveolar phagocytosis, which permitted an investigation of the influence of phospholipid structure on the inhibition of phagocytosis of microspheres. Phospholipid inhibition was found to be independent of phosphatidylcholine alkyl chain length. Head group effects were investigated by studies employing phosphatidyl-choline,-serine, and -ethanolamine, and inhibition was shown to be independent of head group. Closer modelling of the lung environment by co-culturing NR8383 on A549 alveolar epithelium showed type II secretions to also down-regulate phagocytosis. In addition, pre-incubation with microspheres coated with dipalmitoylphosphatidylcholine reduced the uptake of a second microsphere (fluorescein isothiocyanate-labelled latex).
Synthesis and evaluation of a monoreactive DOTA derivative for indium-111-based residualizing label to estimate protein pharmacokinetics
Authors: Mukai Takahiro , Namba Shinji , Arano Yasushi , Ono Masahiro , Fujioka Yasushi , Uehara Tomoya , Ogawa Kazuma , Konishi Junji , Saji Hideo 
Published: September 2002

Abstract
The purpose of this study was to develop an indium-111 (111In)-based residualizing label for estimating the pharmacokinetics of proteins. 1,4,7,10-Tetraazacyclododecane-N,N′,N′,N″-tetraacetic acid (DOTA), which produced a highly stable and hydrophilic 111In chelate, was selected as the chelating site, and the monoreactive DOTA derivative with a tetrafluorophenyl group as the protein binding site (mDOTA) was designed to avoid cross-linkings of proteins. mDOTA was synthesized with an overall yield of 11%. The stability in murine plasma, the radioactivity retention in the catabolic sites of proteins and the radiochemical yields of 111In-labelled proteins via mDOTA were investigated using human serum albumin (HSA), galactosyl-neoglycoalbumin (NGA) and cytochrome c (cyt c) as model proteins. 111In-labelled HSA via mDOTA was highly stable for 5 days after incubation in murine plasma. Long retention of radioactivity in the catabolic sites was observed after injection of 111In-DOTA-NGA in mice, due to the slow elimination of the radiometabolite from the lysosome. At a chelator concentration of 42.2 μM, 111In-DOTA-cytc was produced with over 91 % radiochemical yield. On the other hand, 111In-DOTA-lysine and 111In-DOTA were obtained with high radiochemical yields at lower chelator concentrations. These findings indicated that mDOTA would be an appropriate 111In-labelling agent for estimating protein pharmacokinetics. These findings also suggested that the introduction of a protein binding site at a position distal from the unmodified DOTA structure would be preferable to preparing 111In-DOTA-labelled proteins with higher specific activity.
Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in-vitro and growth of murine B16 melanomas in-vivo
Authors: Liu Xing , Chen Dawei , Xie Liping , Zhang Rongqing 
Published: September 2002

Abstract
Bee venom has been reported to exhibit antitumour activity in-vitro and in-vivo. Apoptosis, necrosis and lysis of tumour cells were suggested as possible mechanisms by which bee venom inhibited tumour growth. The aim of this study was to investigate potential mechanisms by which bee venom inhibits K1735M2 mouse melanoma cells in-vitro and B16 melanoma, a transplantable solid melanoma in C57BL/6 mice, in-vivo. The proliferation of K1735M2 cells in-vitro was inhibited by bee venom in a concentration- and time-dependent manner. The inhibition was indicated by the arrest of the cell cycle at the G1 stage, as detected by flow cytometric measurements. The bee venom induced apoptosis-like cell death as identified by histological observations and by DNA fragmentation. In the in-vivo experiments, the bee venom (1.0, 3.0, 9.0 mg kg−1 of body weight, on days 1–12) was injected intraperitoneally into mice 24 h after the mice were inoculated with B16 cells. Inhibition of the solid tumour was observed. Apoptosis of the K1735M2 cells was suggested as the possible mechanism by which bee venom inhibited cell proliferation and induced K1735M2 cell differentiation in-vitro. The in-vivo experiment indicated that bee venom could be used as a chemotherapeutic agent against malignant tumours.