bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust control from data via uncertainty model sets identification
Authors: Malan S. , Milanese M. , Regruto D. , Taragna M.
Published: April 2004

In this paper an integrated robust identification and control design procedure is proposed. The plant to be controlled is supposed to be linear, time invariant, stable, possibly infinite dimensional and a set of noise‐corrupted input–output measurements is supposed to be available. The emphasis is placed on the design of controllers guaranteeing robust stability and robust performances, and on the trade‐off between controller complexity and achievable robust performances. First, uncertainty models are identified, consisting of parametric models of different order and tight frequency bounds on the magnitude of the unmodelled dynamics. Second, Internal Model Controllers, guaranteeing robust closed‐loop stability and best approximating the ‘perfect control’ ideal target, are designed usingH∞/μ‐synthesis techniques. Then, the robust performances of the designed controllers are computed, allowing one to determine the level of model/controller complexity needed to guarantee desired closed‐loop performances. Copyright © 2004 John Wiley & Sons, Ltd.
Die Verbindung La5Br4Al4 und ihre topologische Verwandtschaft mit dem Ln3ClGa4‐Typ
Authors: Mattausch Hansjürgen , Oeckler Oliver , Zheng Chong , Simon Arndt
Published: April 2004

Aus La‐Metall, LaBr3 und Al‐Spänen (2:1:1) entsteht bei 950 °C die Verbindung La5Br4Al4 in 20 %‐iger Ausbeute. La5Br4Al4 kristallisiert tetragonal in I4/mcmmit a = b = 8.292(1)Å, c = 20.122(4)Å. In der Kristallstruktur liegen drei aufeinander folgende Schichten aus Br/La‐, La/Al‐ und La/Br‐Atomen vor, die längs [001] gestapelt und durch Br‐Atomschichten miteinander verknüpft sind. Die Al‐Atome bilden gewellte Netze aus kondensierten Al8‐ und Al4‐Ringen. Die La‐Atome sind tetragonal antiprismatisch angeordnet. Diese Einheiten sind durch kristallographisch unabhängige La‐Atome zentriert und zu Schichten verknüpft. In La3ClGa4 wird die identische 3fach‐Schichtfolge aus La‐, Ga‐ und Cl‐Atomen gefunden, die in La5Br4Al4 durch Br‐Atomebenen aufgetrennt ist.
Darstellung und Struktur einer Hochdruckmodifikation des Bariumthioplatinats(II), BaPt2S3
Authors: Huster J. , Bronger W.
Published: April 2004

Das über BaPt(CN)4·2H2O dargestellte BaPt2S3 geht bei 10 kbar und 600 °C in eine bisher unbekannte Hochdruckmodifikation über. Die Struktur konnte über Einkristalldaten bestimmt werden. (Raumgruppe P41212, Z = 12, a = 11, 058(1) Å, c = 13, 125(1) Å). Zwei planare [PtS4]‐Einheiten bilden über eine gemeinsame Seite verknüpfte [Pt2S6]‐Baueinheiten, die ein dreidimensionales Gerüst aufbauen. Die Bariumionen sind von sieben Schwefelionen koordiniert.
Stopping Warfarin Therapy is Unnecessary for Hand Surgery
Authors: WALLACE D. L. , LATIMER M. D. , BELCHER H. J. C. R.
Published: April 2004

Interruption of appropriate therapeutic warfarin therapy imposes a risk of morbidity and mortality on the patient. Strategies to reduce the risks of interruption impose relatively large costs in terms of prolonged hospital stay, medication and coagulation monitoring. We report a series of 47 consecutive surgical episodes on the hands of 39 patients without interruption of therapeutic warfarin anticoagulation and with an INR of between 1.3 and 2.9. There was no difficulty with intraoperative haemostasis. Two patients had minor bleeding-related complications with no long-term sequelae. The authors conclude that interruption to warfarin therapy is unnecessary if the INR is less than 3.0 and therefore inappropriate for therapeutically anticoagulated patients undergoing hand surgery.
Elective Hand Surgery in Patients Taking Warfarin
Authors: SMIT A. , HOOPER G.
Published: April 2004

We reviewed 22 patients who had undergone either carpal tunnel decompression or release of Dupuytren’s contractures while anticoagulated with warfarin. All patients continued with their usual anticoagulant regime over the period of operation, provided that the international normalized ratio (INR) was 3 or less. There was no abnormal intraoperative or postoperative bleeding in any patient.
“Machiavellian” Intelligence as a Basis for the Evolution of Cooperative Dispositions
Authors: ORBELL JOHN , MORIKAWA TOMONORI , HARTWIG JASON , HANLEY JAMES , ALLEN NICHOLAS
Published: April 2004

How to promote cooperative behavior is classically solved by incentives that lead self-interested individuals in socially desirable directions, but by now well-established laboratory results show that people often do act cooperatively, even at significant cost to themselves. These results suggest that cooperative dispositions might be an evolved part of human nature. Yet such dispositions appear inconsistent with the “Machiavellian intelligence” paradigm, which develops the idea that our brains have evolved, in substantial part, for capturing adaptive advantage from within-group competition. We use simulation to address the evolutionary relationship between basic Machiavellian capacities and cooperative dispositions. Results show that selection on such capacities can (1) permit the spread of cooperative dispositions even in cooperation-unfriendly worlds and (2) support transitions to populations with high mean cooperative dispositions. We distinguish between “rationality in action” and “rationality in design”—the adaptive fit between a design attribute of an animal and its environment. The combination of well-developed Machiavellian intelligence, modest mistrust, and high cooperative dispositions appears to be a rational design for the brains of highly political animals such as ourselves.
Between Eros and Will to Power: Rousseau and “The Desire to Extend Our Being”
Authors: COOPER LAURENCE D.
Published: April 2004

Most scholars, following Rousseau himself, have had little to say about what Rousseau calls “the desire to extend our being.” Yet the concept is foundational to his political philosophy. Though less compelling a formulation (and deliberately so) than Plato's “eros” or Nietzsche's “will to power,” “the desire to extend our being” is comparable to these in its strength and reach, and hence in its power to unlock the full meaning of Rousseau's thought. My purpose in this paper is to uncover Rousseau's view of the meaning and significance of this desire; its pervasive influence on moral and political life; and the means through which it can and cannot, and should and should not, be fulfilled.
The evolutionary origin of the mammalian isocortex: Towards an integrated developmental and functional approach
Authors: Aboitiz Francisco , Morales Daniver , Montiel Juan
Published: April 2004

The isocortex is a distinctive feature of mammalian brains, which has no clear counterpart in the cerebral hemispheres of other amniotes. This paper speculates on the evolutionary processes giving rise to the isocortex. As a first step, we intend to identify what structure may be ancestral to the isocortex in the reptilian brain. Then, it is necessary to account for the transformations (developmental, connectional, and functional) of this ancestral structure, which resulted in the origin of the isocortex. One long-held perspective argues that part of the isocortex derives from the ventral pallium of reptiles, whereas another view proposes that the isocortex originated mostly from the dorsal pallium. We consider that, at this point, evidence tends to favor correspondence of the isocortex with the dorsal cortex of reptiles. In any case, the isocortex may have originated partly as a consequence of an overall “dorsalizing” effect (that is, an expansion of the territories expressing dorsal-specific genes) during pallial development. Furthermore, expansion of the dorsal pallium may have been driven by selective pressures favoring the development of associative networks between the dorsal cortex, the olfactory cortex, and the hippocampus, which participated in spatial or episodic memory in the early mammals. In this context, sensory projections that in reptiles end in the ventral pallium, are observed to terminate in the isocortex (dorsal pallium) of mammals, perhaps owing to their participation in these associative networks.
Nonclassical connectionism should enter the decathlon
Authors: Calvo Garzón Francisco
Published: April 2004

In this commentary I explore nonclassical connectionism (NCC) as a coherent framework for evaluation in the spirit of the Newell Test. Focusing on knowledge integration, development, real-time performance, and flexible behavior, I argue that NCC's “within-theory rank ordering” would place subsymbolic modeling in a better position. Failure to adopt a symbolic level of thought cannot be interpreted as a weakness.
A complete theory of tests for a theory of mind must consider hierarchical complexity and stage
Authors: Commons Michael Lamport , Sturgeon White Myra
Published: April 2004

We distinguish traditional cognition theories from hierarchically complex stacked neural networks that meet many of Newell's criteria. The latter are flexible and can learn anything that a person can learn, by using their mistakes and successes the same way humans do. Shortcomings are due largely to limitations of current technology.
Diatoms as food source indicator for some Antarctic Cumacea and Tanaidacea (Crustacea)
Authors: Blazewicz-Paszkowycz Magdalena , Ligowski Ryszard
Published: April 2004

The gut contents of three species of cumaceans: Eudorella splendida, Vaunthompsonia inermis and Campylaspis maculata, and three species of tanaids: Nototanais antarcticus, N. dimorphus and Peraeospinosus pushkini from the shelf of Admiralty Bay and two cumaceans: Diastylis mawsoni and Ekleptostylis debroyeri from the deeper Antarctic shelf were studied. With the exception of Campylaspis maculata, which is a predator or scavenger, and Ekleptostylis debroyeri, whose gut was filled with mud only, detritus was an important diet component of all the species studied. On the basis of qualitative and quantitative components of diatom taxa it can be concluded that the food of Diastylis mawsoni comes from the pelagial, whereas the food of the other peracarids is of benthic origin. Species inhabiting the shallowest waters consume almost exclusively epipelic food, whilst those living below the euphotic zone feed mostly on particles sedimented from the pelagial; taxa occurring at intermediate depths feed on pelagic matter, but also of epiphytic and of epipelic origin.
An investigation of thermohaline circulation in Terra Nova Bay polynya
Authors: Buffoni G. , Cappelletti A. , Picco P.
Published: April 2004

This paper addresses the study of the thermohaline circulation and convective processes induced by the presence of a coastal polynya in Terra Nova Bay (Ross Sea, Antarctica). These processes are analysed by means of oceanographic observations and numerical simulations. Time series of hydrological parameters and currents show the High Salinity Shelf Water (HSSW) formation with the mixing of the water column down to great depths, and a seasonal cycle of kinetic energy. A two-dimensional time dependent model for the numerical simulation of the effects of polynya on the circulation has been implemented. This model allows estimation of the contribution of thermohaline forcing on the circulation pattern, the amount of ice production consistent with the observed salinity distribution and annual cycle of currents and the amount of HSSW exported. The thermohaline forcing due to the polynya is able to induce strong horizontal currents up to 40 cm s−1 near the polynya area, as well as vertical movements of the order of 1 cm s−1. An annual ice production, ranging from 45 m to 90 m, mixes the water column at great depths, up to 750 m, and increases the salinity of the surface incoming waters up to 34.82. The estimated net north-eastward transport of HSSW ranges from 0.34 Sv to 1.23 Sv, depending on ice production.
Can genital-tract human papillomavirus infection and cervical cancer be prevented with a vaccine?
Authors: Dillner Joakim , Brown Darron R.
Published: April 2004

Human papillomavirus (HPV) infection is the cause of squamous cell carcinoma of the uterine cervix. This causative relationship has provided the rationale and incentive for development of a prophylactic vaccine. Such a vaccine, if found to be effective, could reduce the need for cervical cancer screening and have a profound effect on the incidence of cervical and other anogenital cancers. This review begins by examining the basic biological and epidemiological principles relevant to the development of HPV preventative vaccines. It then summarises studies examining the use of vaccines to prevent HPV infection in animals and humans, and, finally, discusses some of the unanswered issues surrounding vaccine development against HPV infection and cervical cancer.
Confirmation of the “disability paradox” among hospice patients: Preservation of quality of life despite physical ailments and psychosocial concerns
Authors: KUTNER JEAN S. , NOWELS DAVID E. , KASSNER CORDT T. , HOUSER JANET , BRYANT, LUCINDA L. , MAIN DEBORAH S.
Published: April 2004

Objective:The purpose of this study was to describe quality of life (QOL) and psychosocial and spiritual issues among patients receiving hospice care.

Methods:A questionnaire addressing QOL, spirituality, optimism, loss, fears about the terminal process and death anxiety was administered to 66 adults receiving care from 14 hospices. The physical components of QOL (physical symptoms and physical well-being) were rated lower than the psychosocial and spiritual aspects (support, existential well-being, psychological symptoms).

Results:Respondents had a strong spiritual connection and a strong sense of hope. Although these individuals did not express anxiety or fear about death, there were concerns about the dying process itself. Also, although most felt at ease with their current situation, respondents were concerned about how their illness was affecting their family. Financial and legal issues did not concern most of these individuals.

Significance of results:There were few significant associations between patient characteristics and the QOL or other psychosocial or spiritual issues addressed. Among this older terminally ill population receiving hospice care, whose functional status was fair and for whom physical symptoms were troublesome, QOL persisted and a positive outlook prevailed.
Justification for information and knowledge: Perceptions of family members in palliative home care in Sweden
Authors: FRIEDRICHSEN MARIA J.
Published: April 2004

Objective: Several studies have concluded that family members in palliative home care want information about the patient's disease. The aim of this study was to describe family members' perceptions of their motivation for receiving information about the patient's disease.

Method:Semistructured tape-recorded interviews were performed with 20 family members of patients with incurable progressive cancer who were admitted to hospital-based home care in Sweden. Data were analyzed using a qualitative phenomenographic method.

Results:Family members justified their informational needs by emphasizing that they needed to understand and confirm what would happen when the disease progressed, to be mentally prepared for the future, to organize their daily life, to be a source of information to others, and that receiving information was a natural right.

Significance of results:This study has revealed some explanations as to why family members want information. In clinical practice, it is important that palliative care team members are aware of family members' level of knowledge and their need for information, as this mental preparation is important.
Caregiving near the end of life: Unmet needs and potential solutions
Authors: MANGAN, PATRICIA A. , TAYLOR KATHRYN L. , YABROFF K. ROBIN , FLEMING DAVID A. , INGHAM JANE M.
Published: April 2004

Objective:A key aspect of the role of clinicians caring for patients in the setting of advanced illness focuses on attending to the needs of informal caregivers during the end-of-life period. The purpose of this study was twofold: (1) to complement and enrich existing quantitative findings regarding caregiver burden near the end of life, and (2) to identify potential solutions to caregivers' unmet needs in an effort to assist clinicians in the development of clinical interventions.

Methods:This qualitative study, using focus groups and content analysis of transcripts, was conducted in a comprehensive cancer center in Washington, DC. Seven focus groups were held: three with recently bereaved caregivers and four with active caregivers of patients with metastatic cancer and an expected survival of 6 to 12 months.

Results:Data were stratified into two broad categories: (1) general problems and (2) behaviors/activities that were helpful/would have been helpful in alleviating these problems. Within each of these two categories, five subcategories emerged: medical care (including provision of information, coordination of care, bedside manner, satisfaction with care), quality of life (including well-being, role adjustments), help from others (including practical assistance, social support), positives of caregiving, and unsolicited themes (including job flexibility, impact of the disease on the family, informational needs, relationship with patient).

Significance of results:Results suggest caregivers may benefit from more information about patient prognosis and hospice, attention to quality-of-life issues, and enhanced, direct communication with clinicians. Although information of this nature is likely to be known to palliative care clinicians, the specific details and verbal insights provided by caregivers give an important voice to existing quantitative data and may provide more detailed information to assist palliative care clinicians seeking to develop interventions to meet caregiver needs during the period near the end of life.
Determination of platinum in protein-bound CDDP and DBP by inductively coupled plasma optical emission spectrometry and electrothermal atomic absorption spectrometry
Authors: Einhäuser Thorsten J. , Galanski Mathea S. , Keppler Bernhard K.
Published: April 2004

The plasma protein binding ability of cis-diammine-{[bis(phosphonatomethyl)amino]acetato(2–)-O1, N1}platinum(II)(DBP), a tumour-inhibiting platinum phosphonato compound with osteotropic properties, was compared with that of the well established anticancer drug cisplatin (CDDP). The separation of the plasma protein-platinum adducts was performed by a fractionated ultrafiltration experiment. The platinum levels in the protein fraction and the ultrafiltrate of the blood plasma were detected with an échelle-based ICP-OES system with an ultrasonic nebulizer (USN) and by ETAAS with Zeeman-effect background correction. The over-all performance of ETAAS was better than that of ICP-OES. Owing to strong, protein-induced matrix effects in the USN, the ICP-OES measurements resulted in lower platinum levels in the protein fraction of blood. In the determination of platinum in the ultrafiltrate, both systems showed good performance. In comparison with CDDP, DBP shows a significant tendency to bind to plasma proteins of lower molecular mass.
Corazonin receptor signaling in ecdysis initiation
Authors: Kim Young-Joon , Spalovská-Valachová Ivana , Cho Kook-Ho , Zitnanova Inka , Park Yoonseong , Adams Michael E. , Žitňan Dušan
Published: April 2004

Corazonin is a highly conserved neuropeptide hormone of wide-spread occurrence in insects yet is associated with no universally recognized function. After discovery of the corazonin receptor in
Drosophila
, we identified its ortholog in the moth,
Manduca sexta
, as a prelude to physiological studies. The corazonin receptor cDNA in
M. sexta
encodes a protein of 436 amino acids with seven putative transmembrane domains and shares common ancestry with its
Drosophila
counterpart. The receptor exhibits high sensitivity and selectivity for corazonin when expressed in
Xenopus
oocytes (EC
50
≈ 200 pM) or Chinese hamster ovary cells (EC
50
≈ 75 pM). Northern blot analysis locates the receptor in peripheral endocrine Inka cells, the source of preecdysis- and ecdysis-triggering hormones. Injection of corazonin into pharate larvae elicits release of these peptides from Inka cells, which induce precocious preecdysis and ecdysis behaviors.
In vitro
exposure of isolated Inka cells to corazonin (25-100 pM) induces preecdysis- and ecdysis-triggering hormone secretion. Using corazonin receptor as a biosensor, we show that corazonin concentrations in the hemolymph 20 min before natural preecdysis onset range from 20 to 80 pM and then decline over the next 30-40 min. These findings support the role of corazonin signaling in initiation of the ecdysis behavioral sequence. We propose a model for peptide-mediated interactions between Inka cells and the CNS underlying this process in insect development.
Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: Implications for a common fertility disorder
Authors: Sullivan Shannon D. , Moenter Suzanne M.
Published: April 2004

Polycystic ovary syndrome, a fertility disorder affecting ≈7% of women, is characterized by elevated androgens, disrupted reproductive cycles, and high luteinizing hormone, the latter reflecting increased gonadotropin-releasing hormone (GnRH) release. In animal models, a similar reproductive endocrine phenotype occurs after prenatal androgen exposure. To study the effects of
in utero
androgen exposure directly on GnRH neurons, the central regulators of fertility, we prenatally androgenized (PNA) transgenic mice that express GFP in these cells. Pregnant females were injected with dihydrotestosterone, and their female offspring were studied as adults. PNA mice had irregular estrous cycles and elevated testosterone and luteinizing hormone levels, suggesting altered hypothalamo–pituitary–gonadal axis function. GnRH neurons receive a major input from γ-aminobutyric acid (GABA)ergic neurons, and GABA type A receptor activation may play a role in their regulation by steroids. We tested whether PNA alters GABAergic drive to GnRH neurons by comparing frequency and size of GABAergic postsynaptic currents in GnRH neurons from PNA and control females. Both postsynaptic current frequency and size were increased in PNA mice; these effects were reversed by
in vivo
treatment with the androgen receptor antagonist flutamide, suggesting that androgens mediated these effects. Changes in postsynaptic current frequency and size were action potential-independent, suggesting the possibility that PNA increased connectivity between GABAergic and GnRH neurons. The ability of prenatal steroid exposure to initiate changes that alter functional inputs to GnRH neurons in adults has important implications for understanding the regulation of normal reproduction as well as the hypothalamic abnormalities of fertility disorders.
Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site
Authors: Liu Hua , Ren Jian-Guo , Cooper William L. , Hawkins Charles E. , Cowan Mitra R. , Tong Patrick Y.
Published: April 2004

Vascular permeability plays a key role in a wide array of life-threatening and sight-threatening diseases. Vascular endothelial growth factor can increase vascular permeability. Using a model system for nonproliferative diabetic retinopathy, we found that pigment epithelium-derived factor (PEDF) effectively abated vascular endothelial growth factor-induced vascular permeability. A 44-amino acid region of PEDF was sufficient to confer the antivasopermeability activity. Additionally, we identified four amino acids (glutamate-101, isoleucine-103, leucine-112, and serine-115) critical for this activity. PEDF, or a derivative, could potentially abate or restore vision loss from diabetic macular edema. Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability.
Histamine modulates thalamocortical activity by activating a chloride conductance in ferret perigeniculate neurons
Authors: Lee Kendall H. , Broberger Christian , Kim Uhnoh , McCormick David A.
Published: April 2004

In the mammalian central nervous system only γ-aminobutyric acid (GABA) and glycine have been firmly linked to inhibition of neuronal activity through increases in membrane Cl
-
conductance, and these responses are mediated by ionotropic receptors. Iontophoretic application of histamine can also cause inhibitory responses
in vivo
, although the mechanisms of this inhibition are unknown and may involve pre- or postsynaptic factors. Here, we report that application of histamine to the GABAergic neurons of the thalamic perigeniculate nucleus (PGN), which is innervated by histaminergic fibers from the tuberomammillary nucleus of the hypothalamus, causes a slow membrane hyperpolarization toward a reversal potential of -73 mV through a relatively small increase in membrane conductance to Cl
-
. This histaminergic action appears to be mediated by the H
2
subclass of histaminergic receptors and inhibits the single-spike activity of these PGN GABAergic neurons. Application of histamine to the PGN could halt the generation of spindle waves, indicating that increased activity in the tuberomammillary histaminergic system may play a functional role in dampening thalamic oscillations in the transition from sleep to arousal.
Bistable UV pigment in the lamprey pineal
Authors: Koyanagi Mitsumasa , Kawano Emi , Kinugawa Yoshimi , Oishi Tadashi , Shichida Yoshinori , Tamotsu Satoshi , Terakita Akihisa
Published: April 2004

Lower vertebrates can detect UV light with the pineal complex independently of eyes. Electrophysiological studies, together with chromophore extraction analysis, have suggested that the underlying pigment in the lamprey pineal exhibits a bistable nature, that is, reversible photoreaction by UV and visible light, which is never achieved by known UV pigments. Here we addressed the molecular identification of the pineal UV receptor. Our results showed that the long-hypothesized pigment is a lamprey homologue of parapinopsin, which exhibits an absorption maximum at 370 nm, in the UV region. UV light causes
cis
-
trans
isomerization of its retinal
2
chromophore, forming a stable photoproduct having an absorption maximum at 515 nm, in the green region. The photoproduct reverts to the original pigment upon visible light absorption, showing photoregeneration of the pigment.
In situ
hybridization showed that parapinopsin is selectively expressed in the cells located in the dorsal region of the pineal organ. We successfully obtained the hyperpolarizing responses with a maximum sensitivity of ≈380 nm from the photoreceptor cells at the dorsal region, in which the outer segment was clearly stained with anti-parapinopsin antibody. These results demonstrated that parapinopsin is the pineal UV pigment having photointerconvertible two stable states. The bistable nature of the parapinopsin can account for the photorecovery of the pineal UV sensitivity by background green light in the lamprey. Furthermore, we isolated the parapinopsin homologues from fish and frog pineal complexes that exhibit UV sensitivity, suggesting that parapinopsin is a common molecular basis for pineal UV reception in the vertebrate.
Improving vision in adult amblyopia by perceptual learning
Authors: Polat Uri , Ma-Naim Tova , Belkin Michael , Sagi Dov
Published: April 2004

Practicing certain visual tasks leads, as a result of a process termed “perceptual learning,” to a significant improvement in performance. Learning is specific for basic stimulus features such as local orientation, retinal location, and eye of presentation, suggesting modification of neuronal processes at the primary visual cortex in adults. It is not known, however, whether such low-level learning affects higher-level visual tasks such as recognition. By systematic low-level training of an adult visual system malfunctioning as a result of abnormal development (leading to amblyopia) of the primary visual cortex during the “critical period,” we show here that induction of low-level changes might yield significant perceptual benefits that transfer to higher visual tasks. The training procedure resulted in a 2-fold improvement in contrast sensitivity and in letter-recognition tasks. These findings demonstrate that perceptual learning can improve basic representations within an adult visual system that did not develop during the critical period.
A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl-channel
Authors: Shimizu Takahiro , Numata Tomohiro , Okada Yasunobu
Published: April 2004

Apoptotic volume decrease is a pivotal event triggering a cell to undergo apoptosis and is induced by ionic effluxes resulting mainly from increased K+and Cl-conductances. Here, we demonstrate that in human epithelia HeLa cells both mitochondrion- and death receptor-mediated apoptosis inducers [staurosporine and Fas ligand or tumor necrosis factor (TNF)-α] rapidly activate Cl-currents that show properties phenotypical of volume-sensitive outwardly rectifying Cl-channel currents, including outward rectification, voltage-dependent inactivation gating at large positive potentials, inhibition by osmotic shrinkage, sensitivity to classic Cl-channel blockers, and dependence on cytosolic ATP. Staurosporine, but not Fas ligand or TNF-α, rapidly (within 30 min) increased the intracellular level of reactive oxygen species (ROS). A ROS scavenger and an NAD(P)H oxidase inhibitor blocked the current activation by staurosporine but not by Fas ligand or TNF-α. A ROS scavenger also inhibited apoptotic volume decrease, caspase-3 activation, and apoptotic cell death induced by staurosporine. Thus, it is concluded that an apoptosis-triggering anion conductance is carried by the volume-sensitive outwardly rectifying Cl-channel and that the channel activation on apoptotic stimulation with staurosporine, but not with Fas ligand or TNF-α, is mediated by ROS.
Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver
Authors: Dobrzyn Pawel , Dobrzyn Agnieszka , Miyazaki Makoto , Cohen Paul , Asilmaz Esra , Hardie D. Grahame , Friedman Jeffrey M. , Ntambi James M.
Published: April 2004

Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the biosynthesis of monounsaturated fatty acids. Mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased energy expenditure, and up-regulated expression of several genes encoding enzymes of fatty acid β-oxidation in liver. The mechanisms by which SCD deficiency leads to these metabolic changes are presently unknown. Here we show that the phosphorylation and activity of AMP-activated protein kinase (AMPK), a metabolic sensor that regulates lipid metabolism during increased energy expenditure is significantly increased (≈40%,
P
< 0.01) in liver of SCD1 knockout mice (SCD1-/-). In parallel with the activation of AMPK, the phosphorylation of acetyl-CoA carboxylase at Ser-79 was increased and enzymatic activity was decreased (≈35%,
P
< 0.001), resulting in decreased intracellular levels of malonyl-CoA (≈47%,
P
< 0.001). An SCD1 mutation also increased AMPK phosphorylation and activity and increased acetyl-CoA carboxylase phosphorylation in leptin-deficient ob/ob mice. Lower malonyl-CoA concentrations are known to derepress carnitine palmitoyltransferase 1 (CPT1). In SCD1-/- mice, CPT1 and CPT2 activities were significantly increased (in both cases ≈60%,
P
< 0.001) thereby stimulating the oxidation of mitochondrial palmitoyl-CoA. Our results identify AMPK as a mediator of increased fatty acid oxidation in liver of SCD1-deficient mice.
Soi3p/Rav1p Functions at the Early Endosome to Regulate Endocytic Trafficking to the Vacuole and Localization ofTrans-Golgi Network Transmembrane Proteins
Authors: Sipos György , Brickner Jason H. , Brace E.J. , Chen Linyi , Rambourg Alain , Kepes Francois , Fuller Robert S.
Published: April 2004

SOI3 was identified by a mutation, soi3-1, that suppressed a mutant trans-Golgi network (TGN) localization signal in the Kex2p cytosolic tail. SOI3, identical to RAV1, encodes a protein important for regulated assembly of vacuolar ATPase. Here, we show that Soi3/Rav1p is required for transport between the early endosome and the late endosome/prevacuolar compartment (PVC). By electron microscopy, soi3-1 mutants massively accumulated structures that resembled early endosomes. soi3Δ mutants exhibited a kinetic delay in transfer of the endocytic tracer dye FM4-64, from the 14°C endocytic intermediate to the vacuole. The soi3Δ mutation delayed vacuolar degradation but not internalization of the a-factor receptor Ste3p. By density gradient fractionation, Soi3/Rav1p associated as a peripheral protein with membranes of a density characteristic of early endosomes. The soi3 null mutation markedly reduced the rate of Kex2p transport from the TGN to the PVC but had no effect on vacuolar protein sorting or cycling of Vps10p. These results suggest that assembly of vacuolar ATPase at the early endosome is required for transport of both Ste3p and Kex2p from the early endosome to the PVC and support a model in which cycling through the early endosome is part of the normal itinerary of Kex2p and other TGN-resident proteins.
APSES Proteins Regulate Morphogenesis and Metabolism inCandida albicans
Authors: Doedt Thomas , Krishnamurthy Shankarling , Bockmühl Dirk P. , Tebarth Bernd , Stempel Christian , Russell Claire L. , Brown Alistair J.P. , Ernst Joachim F.
Published: April 2004

Fungal APSES proteins regulate morphogenetic processes, including filamentation and differentiation. The human fungal pathogen Candida albicans contains two APSES proteins: the regulator Efg1p and its homologue Efh1p, described here. Overexpression of EFG1 or EFH1 led to similar phenotypes, including pseudohypha formation and opaque-white switching. An efh1 deletion generated no phenotype under most conditions but caused hyperfilamentation in an efg1 background under embedded or hypoxic conditions. This suggests cooperation of these APSES proteins in the suppression of an alternative morphogenetic signaling pathway. Genome-wide transcriptional profiling revealed that EFG1 and EFH1 regulate partially overlapping sets of genes associated with filament formation. Unexpectedly, Efg1p not only regulates genes involved in morphogenesis but also strongly influences the expression of metabolic genes, inducing glycolytic genes and repressing genes essential for oxidative metabolism. Using one- and two-hybrid assays, we further demonstrate that Efg1p is a repressor, whereas Efh1p is an activator of gene expression. Overall, the results suggest that Efh1p supports the regulatory functions of the primary regulator, Efg1p, and indicate a dual role for these APSES proteins in the regulation of fungal morphogenesis and metabolism.
SAD—a normalized structural alignment database: improving sequence–structure alignments
Authors: Marsden Brian , Abagyan Ruben
Published: April 2004

Motivation: We present a structural alignment database that is specifically targeted for use in derivation and optimization of sequence–structure alignment algorithms for homology modeling. We have paid attention to ensure that fold-space is properly sampled, that the structures involved in alignments are of significant resolution (better than 2.5 Å) and the alignments are accurate and reliable.

Results: Alignments have been taken from the HOMSTRAD, BAliBASE and SCOP-based Gerstein databases along with alignments generated by a global structural alignment method described here. In order to discriminate between equivalent alignments from these different sources, we have developed a novel scoring function, Contact Alignment Quality score, which evaluates trial alignments by their statistical significance combined with their ability to reproduce conserved three-dimensional residue contacts. The resulting non-redundant, unbiased database contains 1927 alignments from across fold-space with high-resolution structures and a wide range of sequence identities.

Availability: The database can be interactively queried either over the web at http://abagyan.scripps.edu/lab/web/sad/show.cgi or by using MySQL, and is also available to download over the web.
How independent are the appearances of n-mers in different genomes?
Authors: Fofanov Yuriy , Luo Yi , Katili Charles , Wang Jim , Belosludtsev Yuri , Powdrill Thomas , Belapurkar Chetan , Fofanov Viacheslav , Li Tong-Bin , Chumakov Sergey , Pettitt B. Montgomery
Published: April 2004

Motivation: Analysis of statistical properties of DNA sequences is important for evolutional biology as well as for DNA probe and PCR technologies. These technologies, in turn, can be used for organism identification, which implies applications in the diagnosis of infectious diseases, environmental studies, etc.

Results: We present results of the correlation analysis of distributions of the presence/absence of short nucleotide subsequences of different length (‘n-mers’, n = 5 – 20) in more than 1500 microbial and virus genomes, together with five genomes of multicellular organisms (including human). We calculate whether a given n-mer is present or absent (frequency of presence) in a given genome, which is not the usually calculated number of appearances of n-mers in one or more genomes (frequency of appearance). For organisms that are not close relatives of each other, the presence/absence of different 7–20mers in their genomes are not correlated. For close biological relatives, some correlation of the presence of n-mers in this range appears, but is not as strong as expected. Suppressed correlations among the n-mers present in different genomes leads to the possibility of using random sets of n-mers (with appropriately chosen n) to discriminate genomes of different organisms and possibly individual genomes of the same species including human with a low probability of error.

Supplementary information: Supplementary data is available at http://www.bioinfo.uh.edu/publications/independence_genomes/.
Transient formation of nano‐crystalline structures during fibrillation of an Aβ‐like peptide
Authors: Otzen Daniel E. , Oliveberg Mikael
Published: April 2004

During the first few minutes of fibrillation of a 14‐residue peptide homologous to the hydrophobic C‐terminal part of the Aβ‐peptide, EM micrographs reveal small crystalline areas (100 to 150 nm, repeating unit 47 Å) scattered in more amorphous material. On a longer time scale, these crystalline areas disappear and are replaced by tangled clusters resembling protofilaments (hours), and eventually by more regular amyloid fibrils of 60 Å to 120 Å diameter (days). The transient population of the crystalline areas indicates the presence of ordered substructures in the early fibrillation process, the diameter of which matches the length of the 14‐mer peptide in an extended β‐strand conformation.
Texas physicians' perceptions of genomic medicine as an innovation
Authors: Suther SG , Goodson P
Published: April 2004

Primary care providers (PCPs) are believed to be the professionals who, in the near future, will be responsible for incorporating genomic medicine (GM) into primary care. Given the dearth of empirical data describing PCPs' beliefs about GM and the relationship between beliefs and the incorporation of GM into practice, this study assessed whether (and to what extent) PCPs' perceptions of GM as an innovation influence their likelihood of adopting this innovation into primary care. The study utilized diffusion of innovations theory as a framework. A state‐wide representative sample of PCPs practicing in Texas responded to a mailed survey. The survey measured PCPs' perceptions of five characteristics of GM as an innovation. Findings suggest that among the five characteristics examined GM's relative advantage, compatibility with current practice, its complexity, and observability were the strongest predictors of likelihood to adopt GM tasks into primary care practice.
Cis/trans conformational equilibrium across the N‐methylphenylalanine2‐ N‐methylphenylalanine3 peptide bond of arginine vasopressin analogs
Authors: Trzepałka E. , Kowalczyk W. , Lammek B.
Published: April 2004

Abstract:  Two cyclic analogs of vasopressin, ‐Pro‐Arg‐Gly‐NH2 (1) and ‐Pro‐Arg‐Gly‐NH2 (2) were synthesized by the solid phase method. Their structure was determined in aqueous solution by two‐dimensional NMR techniques and simulated annealing algorithm from an extended template in X‐PLOR. The total chemical shift correlation spectroscopy and rotating‐frame Overhauser enhancement spectroscopy of the peptides displayed four distinct sets of residual proton resonances. This suggests that both analogs adopt four families of conformations in H2O/D2O (9 : 1) (one major and three minor species). In further analysis only signals of major species (M) and of one minor species (m1) were considered. The major species of both peptides include a trans peptide bond between the first and second residue, and a cis form between the second and third residue. In the minor species, all peptide bonds were found to exist in trans geometry.
Liver regeneration in FGF‐2‐deficient mice: VEGF acts as potential functional substitute for FGF‐2
Authors: Sturm Jörg , Keese Michael , Zhang Honyue , Bönninghoff Roderich , Magdeburg Richard , Vajkoczy Peter , Dono Rosanna , Zeller Rolf , Gretz Norbert
Published: April 2004

Background/Aims: The angiogenic properties, its role in mesoderm differentiation and cell culture studies implicate an important role of fibroblast growth factor (FGF‐2) in liver regeneration. The aim of the study was to evaluate this role in a FGF‐2 knockout mouse model.

Methods: Liver regeneration after left hemihepatectomy (partial hepatectomy, PH) was evaluated in homozygous FGF‐2 deficient (−/−) mice (male C57BL/6J) and their FGF‐2 competent (+/+) littermates (controls) (day 0–10).

Results: FGF‐2‐(−/−) mice displayed normal dynamics in liver regeneration. FGF‐2 protein was overexpressed 4 days post PH in controls. BrdU incorporation showed a biphasic pattern in FGF‐2‐(−/−) mice, whereas it decreased continuously after one peak (day 2) in controls. In FGF‐2‐(−/−) livers hepatic growth factor mRNA post PH was 1 day longer decreased and markedly less elevated thereafter compared with control. Vascular endothelial growth factor (VEGF) mRNA levels were clearly increased in FGF‐2‐(−/−) mice pre‐ and postoperatively in contrast to controls. VEGF protein levels in livers of FGF‐2‐(−/−) mice were elevated preoperatively, but similar in both groups after PH. With SU5416, a VEGF‐receptor inhibitor, liver regeneration in FGF‐2‐(−/−) mice was reduced significantly, whereas it remained unchanged in controls.

Conclusions: Liver regeneration dynamics in FGF‐2‐(−/−) mice were comparable with controls, potentially due to a functional substitution of FGF‐2 by VEGF.
Clinical and histopathological features of NASH in workers exposed to chemicals with or without associated metabolic conditions
Authors: Cotrim Helma P. , De Freitas Luiz AR , Freitas Carolina , Braga Luciana , Sousa Rodrigo , Carvalho Fernando , Paraná Raymundo , Santos‐Jesus Rogerio , Andrade Zilton
Published: April 2004

Background/Aims: Non‐alcoholic steatohepatitis (NASH) has been associated with exposure to chemicals among workers from an industrial complex in Brazil. We investigated the NASH profile of these individuals associated or not with metabolic conditions.

Methods: Eighty‐four patients with NASH were classified into three groups: G1, 31 patients exposed to chemicals (benzene, xylene, vinyl chloride and others); G2, 30 exposed patients who also presented with obesity, hyperlipidemia and diabetes; and G3, 23 non‐exposed patients who presented with metabolic conditions.

Results: G1 and G2 were similar in terms of gender (97% and 100% males) and age (37±5.4 and 39±6.5 years). In G3, 74% were males and the age was 48±3.4 years (P<0.05). In G2, obesity was present in 26.6%, hyperlipidemia in 66.6% and diabetes in 6.6%. In G3, obesity was observed in 43.4%, hyperlipidemia in 30.4% and diabetes in 26%. Macro‐ and microsteatosis were observed in 100% of cases. Perisinusoidal fibrosis was observed in 71% patients in G1, 80% in G2 and 52% in G3 (P<0.05). Histological evidence of cholestasis was present in 53% of cases in G1, 50% in G2 and 13% in G3 (P<0.05).

Conclusions: Exposure to chemicals appears to be an independent risk factor for NASH that presents a peculiar profile. It is more frequently seen in men younger than non‐exposed ones. Steatosis, fibrosis and cholestasis were frequent histological findings. Co‐existing metabolic factors did not seem to influence clinical or histopathological presentation.
Use of the molecular adsorbent recycling system in the treatment of postoperative hepatic failure and septic multiple organ dysfunction – preliminary results
Authors: Rittler Peter , Ketscher Christian , Inthorn Dietrich , Jauch Karl‐Walter , Hartl Wolfgang H.
Published: April 2004

Purpose of the study: Molecular adsorbent recycling system (MARS) has been applied successfully in patients with a variety of liver diseases. However, preliminary results in patients with multiple organ failure (MOF) and sepsis were disappointing, possibly because the number of applied MARS cycles was too low. To determine potential effects of prolonged MARS treatment in patients with postsurgical MOF we evaluated five postoperative patients with acute liver failure and septic multiple organ dysfunction in a retrospective observational study.

Methods:  MARS cycles (13.4±1.9) were applied during an average time period of 17.2±5.2 days. Fresh frozen plasma, thrombocyte units and blood units were transfused to maintain pre‐MARS Quick values and thrombocyte counts, and to keep the hemoglobin concentration above 8 g/dl.

Main findings:  Plasma bilirubin concentrations declined significantly during treatment. In contrast, ammonia concentration remained constant, and parameters of the clotting system (Quick value) did not get better or even worsened (partial thromboplastin time) despite significantly increasing the substitution frequency of coagulatory factors. Due to poor clotting, we observed significant bleeding complications during MARS therapy causing a simultaneous rise in the number of transfused blood units. All patients demonstrated persistent, severe abdominal infection during MARS therapy. After discontinuing MARS treatment because of insufficient efficiency, all patients died of progressive septic organ malfunction.

Conclusion:  Our preliminary findings do not support use of MARS in patients with postoperative hepatic failure and progressive septic multiple organ dysfunction, particularly if the septic focus cannot be eliminated. If MARS is still applied, special attention should be paid to simultaneous clotting disorders and bleeding complications.
A Program of Research Evaluating the Effects of a Collaborative Research Utilization Model
Authors: Dufault Marlene A.
Published: April 2004

(1) Advances in research are meaningless unless they reach clinicians at the point of care. This article describes a program of research in which a collaborative research utilization (CRU) model was developed and tested in four clinical studies in the context of pain management. The overall aim of the research program was to decrease the long lag time from when research innovations are developed to when they appear in clinicians' day‐to‐day caregiving activities. In the model, partnerships are formed between researchers, undergraduate and graduate students, and clinicians in academic and practice settings. The developmental process, structure, and steps of the model are described as well as outcomes that have been achieved in the student, scientist, clinician, nursing practice, and most importantly, the patient.