bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating connectionism: A developmental perspective
Authors: O'Loughlin Claire F. , Karmiloff-Smith Annette
Published: April 2004

This commentary questions the applicability of the Newell Test for evaluating the utility of connectionism. Rather than being a specific theory of cognition (because connectionism can be used to model nativist, behaviorist, or constructivist theories), connectionism, we argue, offers researchers a collection of computational and conceptual tools that are particularly useful for investigating and rendering specific fundamental issues of human development. These benefits of connectionism are not well captured by evaluating it against Newell's criteria for a unified theory of cognition.
Time for Antarctic scientists to reach out
Authors: McClintock James B.
Published: April 2004

In the United States there has been a move afoot to try to stimulate federally funded investigators to explore meaningful ways of communicating their scientific activities through educational outreach programs. The goal is to help improve the quality of mathematics and science education in both early and secondary education. Dr Rita Colwell, the current Director of the US National Science Foundation (NSF), feels strongly that the time has come for higher education to do its part to help improve precollege science education, a persistent problem in the United States and many other industrialized countries. After all, institutions of higher education stand to benefit by seeing students enter college with sound fundamental science skills, and the taxpayers, who ultimately fund national science programs, benefit from an economy fuelled by both renewed and improved scientific talent.
Fish in the diet of the Antarctic shag at four colonies on the Danco Coast, Antarctic Peninsula
Authors: Casaux R. , Baroni A. , Barrera-Oro E.
Published: April 2004

The diet of breeding Antarctic shags (Phalacrocorax bransfieldensis) was investigated at four colonies on the Danco Coast, Antarctic Peninsula, by the analysis of 616 pellets (regurgitated casts) collected from December 1997 to February 1998. Overall, demersal-benthic fish were the most frequent and important prey at all the colonies, followed by octopods and gastropods. Amongst fish, Notothenia coriiceps was the main prey in all of the sampling sites, followed in similar importance by Gobionotothen gibberifrons at Cape Herschel, Primavera Island and Midas Island and in less importance by Harpagifer antarcticus at Py Point. There were marked differences among colonies in the size of the fish consumed. The largest and the smallest specimens were eaten by shags from Midas Island and Py Point respectively. This was mainly influenced by the number of specimens of the smallest fish species, H. antarcticus, consumed at Py Point. The differences in the diet composition may be related to the different foraging areas used by the shags. Results from this study differ from previous studies around the Antarctic Peninsula. The shags at the Danco Coast preyed markedly more intensively than those at the South Shetland Islands on G. gibberifrons. This finding reflects the low abundance of this fish species in inshore waters (< 100 m depth) at the South Shetland Islands and supports the use of the Antarctic shags to monitor trends in local populations of coastal fish species.
Pulling the plug
Authors: COHEN LEWIS M.
Published: April 2004

Each year, hundreds of thousands of Americans die following withholding
or withdrawal of life-support treatments. This dramatic change in the practice
of medicine has quietly taken place and been accompanied by minimal publicity
or discussion.
Zeit, Psyche und Demenz
Authors: Jost Annemarie
Published: April 2004

Zusammenfassung: Zeit nicht als objektiv vorhandenen Zeitpfeil, sondern als eine kulturell und individuell geformte Konstruktion zu betrachten, erscheint für den Umgang mit psychisch kranken Menschen hilfreich. Neuere neurowissenschaftliche Forschungen geben Aufschlüsse über Störungsmuster der zeitlichen Strukturierung bei einzelnen Erkrankungen, und darauf basierend sind interessante Therapieverfahren entwickelt worden. Auch im Umgang mit dementen Menschen ist die Beschäftigung mit Störungen der zeitlichen Organisation der Wahrnehmungen, der Handlungen und des Gedächtnisses weiterführend. Es gilt, Behandlungsmethoden zu entwickeln, die größten Wert auf Synchronisation legen. Bereits zum jetzigen Zeitpunkt können aus der Analyse der Zeitstörungen dementer Menschen wichtige Schlussfolgerungen für Pflege und Therapie gezogen werden.
Peripheral kappa‐opioid agonists for visceral pain
Authors: Rivière Pierre J‐M
Published: April 2004

Kappa (κ)‐ opioid receptor agonists are particularly effective analgesics in experimental models of visceral pain. Their analgesic effects are mediated in the periphery. The molecular targets involved include peripherally located κ‐receptors and possibly, at least for some nonpeptidic κ‐agonists, additional nonopioid molecular targets such as sodium channels located on primary sensory afferents.

Overall, these properties are expected to be of therapeutic interest in various visceral pain conditions, including abdominal surgery associated with postoperative pain and ileus, pancreatitis pain, dysmennorhea, labor pain and functional disorders such as irritable bowel syndrome or dyspepsia.

The first κ‐agonists to be developed were brain‐penetrating organic small molecules. Their development was eventually discontinued due to central side effects such as sedation and dysphoria attributed to κ‐receptors located behind the blood–brain barrier.

New drug discovery programs are now geared towards the design of peripherally‐selective κ‐agonists. So far, most of the organic molecule‐based peripheral κ‐agonists have achieved limited peripheral selectivity and a practically insufficient therapeutic window to justify full development.

These compounds have been used in a small number of clinical pilot studies involving visceral pain. Although encouraging, the clinical data available so far with this class of compounds are too limited and fragmented to fully validate the therapeutic utility of κ‐agonists in visceral pain. Additional clinical studies with safer κ‐agonists (i.e. with higher peripheral selectivity) are still required.

The most suitable tools to address this question in the future appear to be the newly discovered class of tetrapeptide‐based κ‐agonists, which have shown unprecedented levels of peripheral selectivity.

British Journal of Pharmacology (2004) 141, 1331–1334. doi:10.1038/sj.bjp.0705763
Evidence for two distinct binding sites for tau on microtubules
Authors: Makrides Victoria , Massie Michelle R. , Feinstein Stuart C. , Lew John
Published: April 2004

The microtubule-associated protein tau regulates diverse and essential microtubule functions, from the nucleation and promotion of microtubule polymerization to the regulation of microtubule polarity and dynamics, as well as the spacing and bundling of axonal microtubules. Thermodynamic studies show that tau interacts with microtubules in the low- to mid-nanomolar range, implying moderate binding affinity. At the same time, it is well established that microtubule-bound tau does not undergo exchange with the bulk medium readily, suggesting that the tau-microtubule interaction is essentially irreversible. Given this dilemma, we investigated the mechanism of interaction between tau and microtubules in kinetic detail. Stopped-flow kinetic analysis reveals moderate binding affinity between tau and preassembled microtubules and rapid dissociation/association kinetics. In contrast, when microtubules are generated by copolymerization of tubulin and tau, a distinct population of microtubule-bound tau is observed, the binding of which seems irreversible. We propose that reversible binding occurs between tau and the surface of preassembled microtubules, whereas irreversible binding results when tau is coassembled with tubulin into a tau-microtubule copolymer. Because the latter is expected to be physiologically relevant, its characterization is of central importance.
A comparative study of feature selection and multiclass classification methods for tissue classification based on gene expression
Authors: Li Tao , Zhang Chengliang , Ogihara Mitsunori
Published: April 2004

Summary: This paper studies the problem of building multiclass classifiers for tissue classification based on gene expression. The recent development of microarray technologies has enabled biologists to quantify gene expression of tens of thousands of genes in a single experiment. Biologists have begun collecting gene expression for a large number of samples. One of the urgent issues in the use of microarray data is to develop methods for characterizing samples based on their gene expression. The most basic step in the research direction is binary sample classification, which has been studied extensively over the past few years. This paper investigates the next step—multiclass classification of samples based on gene expression. The characteristics of expression data (e.g. large number of genes with small sample size) makes the classification problem more challenging.

The process of building multiclass classifiers is divided into two components: (i) selection of the features (i.e. genes) to be used for training and testing and (ii) selection of the classification method. This paper compares various feature selection methods as well as various state-of-the-art classification methods on various multiclass gene expression datasets.

Our study indicates that multiclass classification problem is much more difficult than the binary one for the gene expression datasets. The difficulty lies in the fact that the data are of high dimensionality and that the sample size is small. The classification accuracy appears to degrade very rapidly as the number of classes increases. In particular, the accuracy was very low regardless of the choices of the methods for large-class datasets (e.g. NCI60 and GCM). While increasing the number of samples is a plausible solution to the problem of accuracy degradation, it is important to develop algorithms that are able to analyze effectively multiple-class expression data for these special datasets.
A System for Automated Bacterial (genome) Integrated Annotation—SABIA
Authors: Almeida Luiz G. P. , Paixão Roger , Souza Rangel C. , da Costa Gisele C. , Barrientos Frank J. A. , dos Santos M. Trindade , de Almeida Darcy F. , Vasconcelos Ana Tereza R.
Published: April 2004

Summary: A web-based software suite, SABIA (System for Automated Bacterial Integrated Annotation), is described that provides a comprehensive computational support for the assembly and annotation of whole bacterial genomes from the data derived from sequencing projects.

Availability: Both SABIA and supplementary materials are available at http://www.sabia.lncc.br

Supplementary information:  http:www.sabia.lncc.br/what.htm
Distinct conformational stability and functional activity of four highly homologous endonuclease colicins
Authors: van den Bremer Ewald T.J. , Keeble Anthony H. , Jiskoot Wim , Spelbrink Robin E.J. , Maier Claudia S. , Van Hoek Arie , Visser Antonie J.W.G. , James Richard , Moore Geoffrey R. , Kleanthous Colin , Heck Albert J.R.
Published: April 2004

The family of conserved colicin DNases E2, E7, E8, and E9 are microbial toxins that kill bacteria through random degradation of the chromosomal DNA. In the present work, we compare side by side the conformational stabilities of these four highly homologous colicin DNases. Our results indicate that the apo‐forms of these colicins are at room temperature and neutral pH in a dynamic conformational equilibrium between at least two quite distinct conformers. We show that the thermal stabilities of the apo‐proteins differ by up to 20°C. The observed differences correlate with the observed conformational behavior, that is, the tendency of the protein to form either an open, less stable or closed, more stable conformation in solution, as deduced by both tryptophan accessibility studies and electrospray ionization mass spectrometry. Given these surprising structural differences, we next probed the catalytic activity of the four DNases and also observed a significant variation in relative activities. However, no unequivocal link between the activity of the protein and its thermal and structural stability could easily be made. The observed differences in conformational and functional properties of the four colicin DNases are surprising given that they are a closely related (≥65% identity) family of enzymes containing a highly conserved (ββα‐Me) active site motif. The different behavior of the apo‐enzymes must therefore most likely depend on more subtle changes in amino acid sequences, most likely in the exosite region (residues 72–98) that is required for specific high‐affinity binding of the cognate immunity protein.
A homozygous HAMP mutation in a multiply consanguineous family with pseudo‐dominant juvenile hemochromatosis
Authors: Delatycki MB , Allen KJ , Gow P , MacFarlane J , Radomski C , Thompson J , Hayden MR , Goldberg YP , Samuels ME
Published: April 2004

Juvenile hemochromatosis (JH) is an autosomal recessive condition that leads to significant morbidity due to early onset systemic iron overload. The majority of families with JH link to chromosome 1q and were recently found to have mutations in the HFE2 gene encoding hemojuvelin; however, several JH families have been reported to have mutations in the HAMP gene encoding hepcidin. Here, we report a multiply consanguineous family with a father and daughter showing iron overload consistent with JH. Sequence analysis of HAMP revealed homozygosity for amino acid substitution C78T due to a c.233G > A mutation. This mutation disrupts one of eight highly conserved cysteines that are believed to be critical for the function of the active enzyme. This finding adds support to the importance of the role of these conserved cysteines in the activity of hepcidin.
Equilibrium Price Dispersion in a Matching Model with Divisible Money*
Authors: Kamiya Kazuya , Sato Takashi
Published: April 2004

The main purpose of this article is to show that, for any given parameter value, an equilibrium with dispersed prices (two‐price equilibrium) exists in Green and Zhou's matching model with divisible money. The welfare effect of price dispersion is also analyzed.
Psychoneuroimmunological Outcomes in Dementia Caregiver Intervention Studies: An Idea Whose Time Has Come?
Authors: Farran Carol J. , Loukissa Dimitra , Hauser Penny M. , McCann Judith J. , Swanson Barbara , Zeller Janice M.
Published: April 2004

Purpose

(1) Mounting evidence indicates that the chronic stress of family caregiving has physiological effects and that caregiver stress may be associated with changes in the caregiver's physical health. Existing caregiver behavioral intervention studies have focused on caregiver stress and psychological distress outcomes. To date, no known caregiver intervention studies have included psychoneuroimmunological (PNI) outcome measures. Two bodies of literature were reviewed to determine if the current state‐of‐the‐science supports the development of caregiver intervention studies that examine PNI outcomes–first, dementia caregiver PNI studies; and second, cognitive behavioral PNI intervention studies conducted with other clinical populations.

Conclusions

(2) If this line of research is pursued, the following issues need to be addressed: a) sampling strategies and study designs; b) measurement issues; and c) the need for multidisciplinary collaborative research teams.

Implications

(3) Nurses' preparation in the biomedical and behavioral sciences establishes a knowledge base that enables nurses to apply a PNI model in clinical situations. Their preparation and access to family caregivers put them in a unique position to design and implement improved caregiver interventions that focus on caregiver psychological, physiological, and physical health outcomes.
Use of florfenicol in non‐human primates
Authors: Cook Anthony L. , St Claire Marisa , Sams Richard
Published: April 2004

Abstract:  Studies were undertaken to determine if florfenicol, an antimicrobial agent structurally similar to chloramphenicol, could be used as an effective broad spectrum antibiotic for the treatment of bacterial infections in primates. Florfenicol was developed as an injectable antibiotic for use in cattle on an every other day dosing schedule. Its broad spectrum activity, long duration of action following i.m. administration, and its safety as compared with chloramphenicol made it an attractive antibiotic for use in non‐human primates. Previous studies had shown that florfenicol is effective against common primate pathogens such as Salmonella, Klebsiella, Escherichia coli, Bordetella bronchiseptica, Streptococcus pneumoniae, Staphylococcus spp., and Yersinia pseudotuberculosis. We performed experiments on a total of 15 macaques. The animals were given florfenicol at 50 mg/kg i.m. and blood samples taken at various time points. Serum was evaluated for florfenicol absorption. Necropsies were also performed to determine if major organs were affected and to determine the effects of i.m. injection of florfenicol. We determined that florfenicol given every 48 hours in rhesus macaques results in blood levels that were acceptable for therapeutic use. The effect on muscle tissue of i.m. injection was similar to ketamine and normal saline. There were no gross lesions observed and no changes with tissues submitted for histology. Our work shows that with further studies, florfenicol may be useful when injectable antibiotic therapy is required in non‐human primates.
The Role of the Nonfamily Administrator in Family Foundations
Authors: Lossberg Ann von
Published: April 2004

The role of the nonfamily administrator in a family foundation is a challenging one and is often the key to the foundation's ability to accomplish its goals. This article explores the decision to hire nonfamily staff, the impact of family dynamics on administrators, and the factors that influence their effectiveness and job satisfaction. Special mention is made of gender factors in the relationship between trustees and staff.
Taxation and Statutory Considerations in the Formation of Family Foundations
Authors: Hayes John T. , Adams Roy M.
Published: April 2004

Because of strict and complex federal regulations and costly penalties, individuals who are contemplating establishing a family foundation need expert legal and financial advice. However, all family and family business leaders who want to engage in philanthropy can dramatically increase their range of options if they are familiar with the basics of taxation law. This article discusses the benefits and drawbacks of various charitable alternatives and offers suggestions for reducing the cost of charitable giving.
Evaluation of Auditors' Going-Concern Risk in Family Businesses
Authors: Schaefer Michael A. , Frishkoff Patricia A.
Published: April 2004

This article discusses recently altered mandates for auditors considering an entity's ability to continue as a going concern. The authors evaluate the appropriateness of these standards in engagements involving family firms and conclude that existing procedures are inadequate to assess the risks unique to family businesses. A detailed checklist of questions is proposed as warning signals in family businesses about problems affecting the going-concern status.
Federal Estate and Gift Taxes: Are They Worth the Cost?
Authors: Soldano Pat
Published: April 2004

Everyone is aware of the federal income tax. What many do not realize is that federal estate tax may have a bigger impact than the income tax. While the income tax decreases take-home pay, the estate tax threatens job creation, business growth, and family harmony. This article examines the impact of the federal estate taxes and reviews several studies which indicate that the estate tax has a deleterious impact on capital accumulation, business growth, job creation, and federal tax revenues.
A Conversation with Henry Mintzberg
Authors: Pervin Aron
Published: April 2004

Henry Mintzberg is both Cleghorn Professor of Management Studies at McGill University in Montreal, Canada, and professor of organization at INSEAD in Fontainebleau, France. His research deals with issues of general management and organizations; his current focus is on the nature and styles of managerial work, as well as forms of organizing and on the strategy formation process. He also heads up a team of people from five universities around the world, a group working to establish what they hope will be “next generation management education”—specifically, a master's program aimed at the “development in context” of practicing managers. His own teaching activities focus on ad hoc seminars for experienced managers and work with doctoral students. Over the years, he has worked with a number of substantial family firms and contributed to a film about a patriarchal Canadian grocery family enterprise, Steinberg's.

Mintzberg received his doctorate and master of science degrees from MIT's Sloan School of Management and his mechanical engineering degree from McGill. Mintzberg is the author of the Nature of Managerial Work (1973), The Structuring of Organizations (1983), The Strategy Process (a textbook with James Brian Quinn, now in its third edition), Mintzberg on Management (1989), The Rise and Fall of Strategic Planning (1994), and the Canadian Condition: Reflections of a “Pure Cotton ” (1995). He has written about a hundred articles, including two Harvard Business Review McKinsey prize winners, “The Manager's Job: Folklore and Fact” and “Crafting Strategy.”

FBR talked to Mintzberg about planning, collaboration, boards, governance and his new management program.
Palmitate increases L‐type Ca2+ currents and the size of the readily releasable granule pool in mouse pancreatic β‐cells
Authors: Olofsson Charlotta S. , Salehi Albert , Holm Cecilia , Rorsman Patrik
Published: April 2004

We have investigated the in vitro effects of the saturated free fatty acid palmitate on mouse pancreatic β‐cells by a combination of electrophysiological recordings, intracellular Ca2+ ([Ca2+]i) microfluorimetry and insulin release measurements. Addition of palmitate (1 mm, bound to fatty acid‐free albumin) to intact islets exposed to 15 mm glucose increased the [Ca2+]i by ∼30% and insulin secretion 2‐fold. Palmitate remained capable of increasing [Ca2+]i and insulin release in the presence of tolbutamide and in islets depolarized by high K+ in combination with diazoxide, indicating that the stimulation occurs independently of closure of ATP‐regulated K+ channels (KATP channels). Palmitate (0.5 mm) augmented exocytosis (measured as an increase in cell capacitance) in single β‐cells and increased the size of the readily releasable pool (RRP) of granules 2‐fold. Whole‐cell peak Ca2+ currents rose by ∼25% following addition of 0.5 mm palmitate, an effect that was abolished in the presence of 10 μm isradipine indicating that the free fatty acid specifically acts on L‐type Ca2+ channels. The actions of palmitate on exocytosis and Ca2+ currents were not mimicked by intracellular application of palmitoyl‐CoA. We conclude that palmitate increases insulin secretion by a KATP channel‐independent mechanism exerted at the level of exocytosis and that involves both augmentation of L‐type Ca2+ currents and an increased size of the RRP.
A NOTE ON A FUZZY TIME SERIES MODEL OF FUZZY NUMBER OBSERVATIONS
Authors: HONG DUG HUN
Published: April 2004

Song et al.[3] proposed a new fuzzy time series model by means of defining some new operations on fuzzy numbers. They presented the new model in the form of two theorems, which indicate that the value of F(t) at t+1 can be related to its previous ones by means of forward and backward linguistic difference, as a necessary condition for the homogeneous fuzzy time series. In this note, we prove that it is also a sufficient condition for the homogeneous fuzzy time series.
Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose metabolism in humans
Authors: Clore John N. , Stillman Julie S. , Li Jing , O'Keefe Stephen J. D. , Levy James R.
Published: April 2004

Prolonged infusions of lipid and heparin that achieve high physiological free fatty acid (FFA) concentrations inhibit hepatic (and peripheral) insulin sensitivity in humans. These infusions are composed largely of polyunsaturated fatty acids (PUFA; linoleic and linolenic). It is not known whether fatty acid composition per se affects hepatic glucose metabolism in humans. To address this issue, we examined the impact of enteral infusions of either palm oil (48% palmitic, 35% oleic, and 8% linoleic acids) or safflower oil (6% palmitic, 12% oleic, 74% linoleic acids) in 14 obese nondiabetic subjects.2H2O was administered to determine the contribution of gluconeogenesis to endogenous glucose production (EGP), and a primed continuous infusion of [6,6-2H]glucose was administered to assess glucose appearance. As a result of the lipid infusions, plasma FFA concentrations increased significantly in both the palm oil (507.5 ± 47.4 to 939.3 ± 61.3 μmol/l, P < 0.01) and safflower oil (588.2.0 ± 43.0 to 857.8 ± 68.7 μmol/l, P < 0.01) groups after 4 h. EGP was similar at baseline (12.4 ± 1.8 vs. 11.2 ± 1.0 μmol·kg FFM−1·min−1). During a somatostatin-insulin clamp, the glucose infusion rate was significantly lower (AUC glucose infusion rate 195.8 ± 50.7 vs. 377.8 ± 38.0 μmol/kg FFM, P < 0.01), and rates of EGP were significantly higher (10.7 ± 1.4 vs. 6.5 ± 1.5 μmol·kg FFM−1·min−1, P < 0.01) after palm oil compared with safflower oil, respectively. Baseline rates of gluconeogenesis and glycogenolysis were also similar. However, after lipid infusion, rates of glycogenolysis were suppressed by safflower oil but not by palm oil. Thus these studies demonstrate, for the first time in humans, a differential effect of saturated fatty acids and PUFA on hepatic glucose metabolism.
Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO
Authors: Green Christina L. , Ho Winnie , Sharkey Keith A. , McKay Derek M.
Published: April 2004

In normal colon, ACh elicits a luminally directed Cl−efflux from enterocytes via activation of muscarinic receptors. In contrast, in the murine model of dextran sodium sulfate (DSS)-induced colitis, an inhibitory cholinergic ion transport event due to nicotinic receptor activation has been identified. The absence of nicotinic receptors on enteric epithelia and the ability of nitric oxide (NO) to modulate ion transport led us to hypothesize that NO mediated the cholinergic nicotinic receptor-induced changes in ion transport. Midportions of colon from control and DSS-treated mice were examined for inducible NO synthase (iNOS) expression by RT-PCR and immunofluorescence or mounted in Ussing chambers for assessment of cholinergic-evoked changes in ion transport (i.e., short-circuit current) with or without pretreatment with pharmacological inhibitors of NO production. iNOS mRNA and protein levels were increased throughout the tissue from DSS-treated mice and, notably, in the myenteric plexus, where the majority of iNOS immunoreactivity colocalized with the enteric glial cell marker glial fibrillary acidic protein. The drop in short-circuit current evoked by the cholinomimetic carbachol in tissue from DSS-treated mice was prevented by selective inhibitors of iNOS activity { N6-(1-iminoethyl)-lysine HCl and N-[3-(aminomethyl)benzyl]acetamidine} or an NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] or by removal of the myenteric plexus. Thus, in this model of colitis, a “switch” occurs from muscarinic to nicotinic receptor-dominated control of cholinergic ion transport. The data indicate a novel pathway involving activation of nicotinic receptors on myenteric neurons, resulting in release of NO from neurons or enteric glia and, ultimately, a dampening of stimulated epithelial Cl−secretion that would reduce secretory diarrhea.
Comparison of resistance and conduit vessel nitric oxide-mediated vascular function in vivo: effects of exercise training
Authors: Green Daniel J. , Walsh Jennifer H. , Maiorana Andrew , Burke Valerie , Taylor Roger R. , O'Driscoll J. Gerard
Published: April 2004

Exercise training improves vascular function in subjects with cardiovascular disease and risk factors, but there is mounting evidence these vascular adaptations may be vessel bed specific. We have therefore examined the hypothesis that exercise-induced improvements in conduit vessel function are related to changes in resistance vessel function. Endothelium-dependent and -independent conduit vessel function were assessed by using wall-tracking of high-resolution brachial artery ultrasound images of the response to flow-mediated dilation (FMD) and nitroglycerine [glyceryl trinitrate (GTN)] administration. Resistance vessel endothelium-dependent and -independent function were assessed using intrabrachial administration of acetylcholine (ACh) and nitroprusside (SNP). Randomized crossover studies of 8-wk exercise training were undertaken in untreated hypercholesterolemic ( n = 10), treated hypercholesterolemic ( n = 10), coronary artery disease ( n = 8), and Type 2 diabetic subjects ( n = 15). Exercise training significantly enhanced responses to ACh ( P < 0.05) and FMD ( P < 0.0001). There were no significant changes in either SNP or GTN responses. The correlation between ACh and FMD responses at entry was not significant ( r = 0.186; P = 0.231), and training-induced changes in the ACh did not correlate with those in FMD ( r = −0.022; P = 0.890). Similarly, no correlation was evident between the SNP and GTN responses at entry ( r = −0.010; P = 0.951) or between changes in these variables with training ( r = −0.211; P = 0.191). We conclude that, although short-term exercise training improves endothelium-dependent nitric oxide-mediated vascular function in both conduit and resistance vessels, the magnitude of these improvements are unrelated.
Catheter Ablation of Ventricular Epicardial Tissue
Authors: d’Avila André , Houghtaling Christopher , Gutierrez Paulo , Vragovic Olivera , Ruskin Jeremy N. , Josephson Mark E. , Reddy Vivek Y.
Published: April 2004

Background—

Transthoracic epicardial catheter ablation is an emerging catheter ablation strategy being used clinically at increasing frequency. However, the efficacy of standard RF ablation on the epicardial surface of the heart is hindered by (1) the lack of convective cooling of the ablation electrode and (2) the varying presence of epicardial adipose tissue interposed between the ablation electrode and the target site. This experimental animal study examines the biophysical characteristics of radiofrequency (RF) ablation lesions generated by either standard or cooled-tip ablation of the ventricular epicardium.

Methods and Results—

Nonsurgical subxyphoid pericardial access was achieved in 10 normal goats and 7 pigs with healed myocardial infarctions. A 4-mm cooled-tip RF ablation catheter (continuous 0.9% saline circulation at 0.6 mL/s; goal temperature, 40°C; 60 seconds) was used to deliver epicardial ventricular lesions: 47 in normal tissue and 22 in infarcted tissue. Standard RF ablation lesions (n=33) using a 4-mm top catheter (goal temperature, 70°C; 60 seconds) were also placed on normal epicardial tissue. Lesions created with standard and cooled-tip RF ablation were 3.7±1.3 mm (25±16.8 W) and 6.7±1.7 mm (44.8±6.8 W) in depth, respectively. On scar tissue, lesions made with the cooled-tip catheter measured 14.6±2.7 mm in length, 11.8±2.9 mm in width, and 5.6±1.2 mm in depth (35.6±7.1 W). In areas covered by epicardial fat (3.1±1.2 mm thick), standard RF energy did not generate any appreciable lesions, but cooled-tip RF lesions were 4.1±2 mm in depth (45±4.4 W).

Conclusions—

Cooled-tip RF ablation can generate epicardial lesions more effectively than standard RF ablation and appears to be of particular benefit in ablating areas with overlying epicardial fat.
Temporal Profile of Matrix Metalloproteinases and Their Inhibitors After Spontaneous Intracerebral Hemorrhage
Authors: Alvarez-Sabín José , Delgado Pilar , Abilleira Sònia , Molina Carlos A. , Arenillas Juan , Ribó Marc , Santamarina Esteban , Quintana Manolo , Monasterio Jasone , Montaner Joan
Published: April 2004

Background and Purpose—

Matrix metalloproteinases (MMPs) are related to blood–brain barrier disruption, and some members of this family have been recently involved in brain bleedings. We aimed to investigate the temporal profile of MMPs and their natural inhibitors (TIMPs) after acute intracerebral hemorrhage (ICH) and to study its influence on neuroimaging and clinical outcome.

Methods—

MMP-2, MMP-9, and MMP-3, as well as TIMP-1 and TIMP-2, were serially determined by enzyme-linked immunosorbent assay on admission (<12 hours), and at 24 hours, 48 hours, 7 days, and 3 months in 21 ICH patients. ICH and perihematomal edema (PE) volumes were serially measured on baseline and follow-up computed tomography (48 hours, 7 days, and 3 months), just at the time of neurological assessment.

Results—

Deep ICH was found in 62% patients. Baseline ICH volume did not influence MMP-TIMP level. Highest levels of MMP-2 and TIMP-2 were found at baseline, for MMP-9 and TIMP-1 at 24 hours, and for MMP-3 at 24 to 48 hours. Baseline MMP-9 was positively correlated to PE volume (r=0.67,
P
=0.004) and, conversely, its inhibitor TIMP-1 was negatively correlated to PE (r=−0.51,
P
=0.04). Mortality reached 35% and MMP-3 was the only MMP/TIMP related to mortality (7.5 versus 2.4 ng/mL;
P
=0.035) and its most powerful baseline predictor (odds ratio = 22, confidence interval: 1.5 to 314.2). Both MMP-9 and MMP-3 correlated to the residual scar volume at 3 months (r=0.68,
P
=0.01 for baseline MMP-9, and r=0.86,
P
<0.001 for 24-hour MMP-3).

Conclusions—

A characteristic temporal profile of MMP/TIMP release exists in ICH. Increased MMP-9 is associated with PE, and increased MMP-3 is associated with mortality. Both molecules are related to residual cavity volume.
Hypercholesterolemia, HMG-CoA Reductase Inhibitors, and Risk of Intracerebral Hemorrhage
Authors: Woo Daniel , Kissela Brett M. , Khoury Jane C. , Sauerbeck Laura R. , Haverbusch Mary A. , Szaflarski Jerzy P. , Gebel James M. , Pancioli Arthur M. , Jauch Edward C. , Schneider Alexander , Kleindorfer Dawn , Broderick Joseph P.
Published: April 2004

Background and Purpose—

Several studies have demonstrated an association between hypocholesterolemia and intracerebral hemorrhage (ICH). We tested the hypothesis that hypercholesterolemia or use of HMG-CoA reductase inhibitors (statin) agents, or both, are associated with ICH.

Methods—

This study was part of the preplanned midway analysis of an ongoing, population-based, case-control study of the genetic and environmental risk factors of hemorrhagic stroke. Conditional stepwise logistic regression modeling was used to determine if self-reported hypercholesterolemia or statin use, or both, were independent risk factors for ICH.

Results—

Between December 1, 1997, and June 30, 2000, 188 cases of ICH and 366 age-, race-, and gender-matched controls were enrolled. Hypercholesterolemia and statin use were less common among cases than controls: 25% versus 38% (
P
=0.003) and 9% versus 17% (
P
=0.03), respectively. Hypercholesterolemia with statin use was associated with less risk of ICH (OR=0.30;
P
=0.0008) in multivariable analysis after controlling for alcohol use, hypertension, previous stroke, first-degree relative with ICH, education level, and apolipoprotein E alleles.

Conclusion—

Hypercholesterolemia was associated with a lower risk of ICH. We have not found an increased risk of ICH with the widespread use of statins in our population. Given the lack of cholesterol levels in the current study, further studies are needed to determine if lower cholesterol levels secondary to statin use bear the same risk as low cholesterol levels for ICH.
Kinetic analysis of ribozyme–substrate complex formation in yeast
Authors: YADAVA RAMESH S. , MAHEN ELISABETH M. , FEDOR MARTHA J.
Published: April 2004

Many RNA-mediated reactions in transcription, translation, RNA processing, and transport require assembly of RNA complexes, yet assembly pathways remain poorly understood. Assembly mechanisms can be difficult to assess in a biological context because many components interact in complex pathways and individual steps are difficult to isolate experimentally. Our previous studies of self-cleaving hairpin ribozymes showed that kinetic and equilibrium parameters measured in yeast agree well with parameters measured in vitro under ionic conditions that mimic the intracellular environment. We now report studies of intermolecular reactions with ribozyme and target sequences expressed in yeast as separate chimeric U3 snoRNAs. In this system, intracellular cleavage rates reflect the kinetics of ribozyme-substrate complex formation through annealing of base-paired helices. Second-order rate constants increased with increasing helix length for in vitro reactions with 2 mM MgCl2 and 150 mM NaCl and in vivo but not in reactions with 10 mM MgCl2. Thus, efficient RNA complex formation required a larger extent of complementarity in vivo than in vitro under conditions with high concentrations of divalent cations. The most efficient intracellular cleavage reactions exhibited second-order rate constants that were 15- to 30-fold below rate constants for cleavage of oligonucleotides in vitro. Careful analysis of structural features that influence cleavage efficiency points to substrate binding as the rate-determining step in the intracellular cleavage pathway. Second-order rate constants for intermolecular cleavage agree well with diffusion coefficients reported for U3 snoRNPs in vivo suggesting that complex formation between chimeric ribozyme and substrate snoRNPs in yeast nuclei is diffusion limited.
Conserved but nonessential interaction of SRP RNA with translation factor EF-G
Authors: SAGAR MADI BIDYA , LUCAST LOUISE , DOUDNA JENNIFER A.
Published: April 2004

4.5S RNA is essential for viability of Escherichia coli, and forms a key component of the signal recognition particle (SRP), a ubiquitous ribonucleoprotein complex responsible for cotranslational targeting of secretory proteins. 4.5S RNA also binds independently to elongation factor G (EF-G), a five-domain GTPase that catalyzes the translocation step during protein biosynthesis on the ribosome. Point mutations in EF-G suppress deleterious effects of 4.5S RNA depletion, as do mutations in the EF-G binding site within ribosomal RNA, suggesting that 4.5S RNA might play a critical role in ribosome function in addition to its role in SRP. Here we show that 4.5S RNA and EF-G form a phylogenetically conserved, low-affinity but highly specific complex involving sequence elements required for 4.5S binding to its cognate SRP protein, Ffh. Mutational analysis indicates that the same molecular structure of 4.5S RNA is recognized in each case. Surprisingly, however, the suppressor mutant forms of EF-G bind very weakly or undetectably to 4.5S RNA, implying that cells can survive 4.5S RNA depletion by decreasing the affinity between 4.5S RNA and the translational machinery. These data suggest that SRP function is the essential role of 4.5S RNA in bacteria.
RelativisticAb InitioTheory using the Regular Approximation
Authors: Filatov Michael
Published: April 2004

An account of the theoretical methods for atomic and molecular calculations in anab initiorelativistic quantum‐mechanical framework, based on the regular approximation to the exact formalism, is presented. A brief introduction into the nature of relativistic effects and into the full four‐component relativistic quantum‐mechanical formalism is given. A classification of the quasirelativistic methods including the methods based on the Foldy–Wouthuysen transformation of the Dirac equation is presented. The concept of the regular approximation to the exact relativistic formalism is introduced. Theab initiomethods within the regular approximation ranging from the zeroth‐order regular approximation (ZORA) to the infinite‐order regular approximation (IORA) methods are described and details of their implementation are discussed. A brief survey of the results of theab initiocalculations on atomic and molecular systems concludes the account.
Reduced Scaling Electron Correlation Methods
Authors: Carter Emily A. , Walter Derek
Published: April 2004

We give a detailed description of recent developments in reduced scaling
ab initio
methods for treating electron correlation in atoms and molecules. Since configuration interaction (CI) is the simplest electron correlation method, it is introduced first and used as a context to describe the familiar local correlation and pseudospectral approximations. The article then goes on to discuss the application of these approximations to Møller–Plesset perturbation theories. We use the context of Møller–Plesset perturbation theories to introduce the use of integral‐direct techniques in electron correlation. These techniques are of particular importance as they eliminate major storage bottlenecks and pave the way for the treatment of ever larger systems. As such, we give step‐by‐step descriptions of the simplest integral‐direct algorithms. We discuss the particular usefulness of integral‐direct methods when the local correlation approximation is employed and how the combination of these two approaches can yield linear scaling electron correlation methods. Additionally, we describe some newly developed Møller–Plesset approaches based upon the direct use of highly localized atomic orbitals (AO) that exploit the same physical concepts as in the canonical approaches. The article concludes with a description of coupled cluster (CC) methods that take advantage of the full range of techniques described in the discussions of configuration interaction and Møller–Plesset theories. To enhance the accessibility of the article, the underlying theories behind the various
ab initio
electron correlation methods are described briefly prior to describing the reduced scaling versions of the methods.
Stabilized Blue Emission from Polymer–Dielectric Nanolayer Nanocomposites
Authors: Park J. H. , Lim Y. T. , Park O O. , Kim J. K. , Yu J. W. , Kim Y. C.
Published: April 2004

Blue‐light‐emitting polymer (polyfluorene)/dielectric nanolayer nanocomposites were prepared by the solution intercalation method and employed in an electroluminescent (EL) device. Their photoluminescence (PL) and electroluminescence characteristics demonstrates that the interruption of interchain interaction in intercalated organic/inorganic hybrid systems reduces the low‐energy emission that results from keto‐defects. By reducing the probability that the excitons initially generated on the polyfluorenes will find keto‐defects, both the color purity and the luminescence stability were improved. Furthermore, the dielectric nanolayers have an aspect ratio of about five hundred, and therefore act as efficient exciton blocking layers and barriers to oxygen diffusion, producing a dramatic increase in the device stability. A nanocomposite device with a Li:Al alloy cathode gave a quantum efficiency of 1.0 %(ph/el), which corresponds to an approximate five times enhancement compared to the neat polymer device. The nanocomposite emitting layer is considered to have a pseudo‐multiple quantum well structure.
Statistics of multiple particle breakage accounting for particle shape
Authors: Hill Priscilla J.
Published: April 2004

A method is presented for developing multiple particle breakage distribution functions that include the shape factor, as well as the particle size. The technique is to first develop a joint probability distribution that accounts for the size and shape factor of each child particle. This is then reduced by successive integration to the marginal probability used in the breakage equation. This technique guarantees mass conservation and exchangeability of child particles while allowing the user to choose the number of child particles formed per breakage. It also allows the user to choose the functional form for the size distribution of particles as well as independently choosing the functional form for the shape factor distribution of particles. To solve the breakage equation, a discretization method is used that conserves particle mass during breakage and correctly predicts changes in the total number of particles. Simulation results show that the shape distribution functions may yield distinguishable shape factor profiles after crushing. Comparison with experimental data indicates that these theoretical functions can be used to model real systems. © 2004 American Institute of Chemical Engineers AIChE J, 50: 937–952, 2004
Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients with peritoneal carcinomatosis of colorectal origin
Authors: Glehen O , Cotte E , Schreiber V , Sayag-Beaujard A C , Vignal J , Gilly F N
Published: April 2004

Background

Colorectal cancer with peritoneal carcinomatosis is usually considered incurable. The purpose of this study was to evaluate the efficacy of intraperitoneal chemohyperthermia (IPCH) following cytoreductive surgery in patients with colorectal carcinomatosis.

Methods

Between January 1989 and August 2002, 53 patients (mean age 48·6 years) were treated by IPCH with mitomycin C. IPCH was performed in 34 patients following extensive cytoreductive surgery (more than two peritonectomy procedures). Five patients underwent two operations and one patient three operations.

Results

Operative morbidity and mortality rates were 23 and 4 per cent respectively. At a median follow-up of 59·5 months, the overall median survival was 12·8 months. The extent of carcinomatosis, completeness of cytoreduction and histological differentiation were significant prognostic indicators by univariate analysis. The median survival was 32·9 months for patients whose resection was classified as completeness of cancer resection (CCR) 0 (complete cytoreduction), 12·5 months for those whose operation was CCR-1 (diameter of residual nodules 5 mm or less) and 8·1 months for patients who had a CCR-2 resection (diameter of residual nodules more than 5 mm) (P < 0·001). Completeness of cytoreduction was the only significant independent predictor of survival by multivariate analysis.

Conclusion

IPCH combined with cytoreductive surgery seems to be an effective therapy for carefully selected patients with carcinomatosis from colorectal cancer. This strategy was most effective in patients with carcinomatosis of limited tumour volume or when cytoreductive surgery allowed sufficient downstaging (residual tumour nodules smaller than 5 mm).