bluuebunny/crossref_metadata_2025 huggingface dataset:
Early bone formation adjacent to rough and turned endosseous implant surfaces
Authors: Abrahamsson Ingemar , Berglundh Tord , Linder Elena , Lang Niklaus P. , Lindhe Jan
Published: July 2004

Objective: To validate a proposed model (Berglundh et al. 2003) and to evaluate the rate and degree of osseointegration at turned (T) and sand blasted and acid etched (SLA) implant surfaces during early phases of healing.

Material and methods: The devices used for the study of early healing had a geometry that corresponded to that of a solid screw implant with either a SLA or a T surface configuration. A circumferential trough had been prepared within the thread region (intra‐osseous portion) that established a geometrically well‐defined wound chamber. Twenty Labrador dogs received totally 160 experimental devices to allow the evaluation of healing between 2 h and 12 weeks. Both ground and decalcified sections were prepared from mesial/distal and buccal/lingual device sites. Histometric and morphometric analyses of the ground sections and morphometric analysis of the tissue components in decalcified sections were performed.

Results: The ground sections provided an overview of the various phases of tissue formation, while the decalcified, thin sections enabled a more detailed study of events involved in bone tissue modeling and remodeling for both SLA and T surfaces. The initially empty wound chamber became occupied with a coagulum and a granulation tissue that was replaced by a provisional matrix. The process of bone formation started already during the first week. The newly formed bone present at the lateral border of the cut bony bed appeared to be continuous with the parent bone, but on the SLA surface woven bone was also found at a distance from the parent bone. Parallel‐fibered and/or lamellar bone as well as bone marrow replaced this primary bone after 4 weeks. In the SLA chambers, more bone‐to‐device contact, more initial woven bone and earlier lamellar bone formation was found than in the T chambers.

Conclusion: Osseointegration represents a dynamic process both during its establishment and its maintenance. While healing showed similar characteristics with resorptive and appositional events for both SLA and T surfaces, the rate and degree of osseointegration were superior for the SLA compared with the T chambers.
Large‐vessel arteritis and myelodysplastic syndrome: report of two cases
Authors: Steurer M. , Fritsche G. , Tzankov A. , Gotwald T. , Sturm W. , Konwalinka G. , Gruber J.
Published: July 2004

Abstract: Myelodysplastic syndrome (MDS) is frequently associated with autoimmune diseases such as polymyalgia, arthritis, and rarely, with systemic vasculitis. The pathogenesis of these autoimmune complications remains unknown, but there is increasing evidence of profound immune dysregulation in MDS. In the few cases reported so far, vasculitides associated with MDS affected mainly cutaneous vessels. Here we describe two cases of acute large‐vessel vasculitis in association with MDS. The first patient is a 67‐yr‐old male presenting with a massive large‐vessel arteritis as primary manifestation of refractory anemia with excess of blasts type 1 (RAEB‐1). The second patient is a 60‐yr‐old male, who presented with acute thoracic aortitis after a 2‐yr history of refractory anemia with ringed sideroblasts (RARS). Both patients received immunosuppressive treatment with steroids, leading to rapid improvement of systemic inflammatory symptoms, vessel wall injury and peripheral blood counts. Whereas the first patient displayed sustained favorable hematologic responses under long‐term steroid therapy, there was a rapid transformation into secondary acute myeloid leukemia in the second patient. We conclude that large‐vessel vasculitis should be added to the list of potential autoimmune complications in MDS. In this clinical setting, steroid therapy may alleviate inflammatory symptoms and result in beneficial hematologic responses.
Favourable outcome for patients with myeloid disorders treated with fludarabine–melphalan reduced‐intensity conditioning and allogeneic bone marrow stem cell transplantation without the use of T‐lymphocyte‐depleting antibodies
Authors: Malladi R. K. , Peniket A. J. , Norton A. E. , Campbell A. J. , Collins G. P. , Samol J. , Eagleton H. , Miller E. , Morgenstern G. , Jones J. , Keen‐Mcguire A. , Barnardo M. , Littlewood T. J.
Published: July 2004

Abstract:  We report the use of reduced‐intensity conditioning (RIC)‐matched sibling allogeneic bone marrow stem cell transplantation as a method of establishing a graft‐vs.‐leukaemia (GvL) effect against myeloid disorders using a fludarabine–melphalan protocol without the use of T‐lymphocyte‐depleting antibodies. The 16 patients in this group had predominantly poor‐risk acute myeloid leukaemia (AML) (n = 10), AML/myelodysplasia (MDS) (n = 2) and MDS (n = 4). All but one patient achieved full haematopoietic engraftment. Thirteen of 16 patients are alive and in continued complete remission on completion of this study with a median follow‐up of 426 d (range 83–1524). The actuarial 4 yr disease‐free and overall survival is 79% for both. Only one patient relapsed following transplant, giving a relapse rate of 6% during the study period. The treatment‐related mortality was 13% (n = 2). Overall, acute graft‐vs.‐host disease (GvHD) occurred in 53% (8/15), with acute GvHD grade II or above occurring in 47% (7/15). In the 13 evaluable patients, chronic GvHD occurred in 46% (6/13), with this being extensive in three patients. These results suggest that a GvL effect can be delivered against poor‐risk myeloid disorders with a low non‐relapse mortality using this fludarabine–melphalan RIC protocol.
Perioperative venous thromboembolism prophylaxis in Israel: a survey of academic surgical departments
Authors: Ellis Martin H. , Elis Avishay
Published: July 2004

Abstract:  Objective: Postoperative venous thromboembolism (VTE) represents a serious threat to patients undergoing surgical procedures. Without thromboprophylaxis, deep vein thrombosis occurs in up to 60% of patients undergoing major orthopedic surgery and 15% of patients undergoing major abdominal surgery. Although, many studies have shown the efficacy of pharmacologic and mechanical means of VTE prophylaxis, practice variations in this area abound worldwide. The purpose of this study was to determine the attitudes and practice of VTE prophylaxis of academic surgical department heads in Israel. Methods: A questionnaire covering various aspects of VTE prophylaxis was mailed to all surgical department heads of university teaching hospitals in Israel. Three months later, the same questionnaire was sent to department heads who had not yet replied. Data retrieved from the returned questionnaires were analyzed. Results: A total of 250 departments in 23 hospitals affiliated to the four medical schools in Israel were identified; 130 department heads (52%) returned the questionnaires. The current study analyzes results obtained from the general surgical, orthopedic, urological, vascular and gynecological departments only. The total number of responses from these departments was 90 (69% response rate). Sixty‐seven percent of the departments considered VTE to be a clinical problem. Ninety‐four percent of departments have a policy for VTE prophylaxis. The most frequently used modalities for VTE prophylaxis (more than one option possible) were low‐molecular‐weight heparin (LMWH) (59%), unfractionated heparin (43%) and an intermittent pneumatic compression device (20%). VTE prophylaxis is begun 12 h preoperatively by 33% of departments, 2–4 h preoperatively by 20% of departments and with premedication by 8% of departments. VTE prophylaxis was continued during the postoperative period by all departments, with 52% stopping prophylaxis upon patient mobilization. Bleeding complications have been noted by 55% of departments, of these 9% were considered major. In general surgical, orthopedic and gynecologic departments, VTE prophylaxis was widely used for those procedures for which published guidelines exist, while considerable variation in VTE prophylaxis administration was demonstrated in a number of commonly encountered clinical situations for which there are no published recommendations. Conclusions: This study confirms that academic surgical departments in Israel conform to standard VTE prophylaxis guidelines. However, considerable variations in practice exist regarding the means of prophylaxis, onset of prophylaxis and its duration. These areas should be the focus of ongoing educational efforts including the development of uniform practice guidelines to improve the quality of care regarding VTE prophylaxis. Furthermore, attention should be given to methods for decreasing hemorrhage caused by LMWH and unfractionated heparin usage.
Defective long‐term repopulating ability in hematopoietic stem cells lacking the Polycomb‐group gene rae28
Authors: Kim Ji Yoo , Sawada Akihisa , Tokimasa Sadao , Endo Hiroko , Ozono Keiichi , Hara Junichi , Takihara Yoshihiro
Published: July 2004

Abstract:  The rae28 gene (rae28) is a member of a Polycomb‐group (PcG) complex 1, which is known to help maintain transcription states once these have been initiated, by generating heritable higher‐order chromatin structures. In this study, we examined the capacity of rae28‐deficient (rae28−/−) hematopoietic stem cells (HSCs) to generate long‐term marrow reconstitution. rae28−/− fetal liver cells containing 20 competitive repopulation units (CRUs) were able to support the survival of lethally irradiated congenic mice for as long as 6 months. The marrow reconstituted with the rae28−/− cells, however, could not increase HSCs efficiently. This was evidenced by its inability to reconstitute marrow in serial transplantation experiments, as well as by the reduction in HSC‐enriched Lin− c‐kit+ Sca‐1high+ subpopulation in the bone marrow cells. Moreover, the reconstituted marrow produced less than half of the peripheral blood cells in each of the lineages examined. We also monitored the mean stem cell activity (MAS). MAS of rae28−/− CRUs was progressively reduced after transplantation, and after 12 months it was reduced to one‐tenth of that of the wild‐type. These in vivo results clearly indicate that rae28 is indispensable for the long‐term repopulating ability of HSCs. We further referred to the plausible mechanisms underlying defective long‐term repopulating ability of rae28‐deficient HSCs and argued for its involvement in maintenance of cell proliferation capability as well as that in self‐renewal ability.
Periodic fever, mild arthralgias, and reversible moderate and severe organ inflammation associated with the V198M mutation in the CIAS1 gene in three German patients – expanding phenotype of CIAS1 related autoinflammatory syndrome
Authors: Pörksen Gönke , Lohse Peter , Rösen‐Wolff Angela , Heyden Stefan , Förster Theresa , Wendisch Jörg , Heubner Georg , von Bernuth Horst , Sallmann Svea , Gahr Manfred , Roesler Joachim
Published: July 2004

Abstract:  Dominant mutations in the CIAS1 gene cause a spectrum of autoinflammatory diseases such as familial cold autoinflammatory syndrome, FCAS, which is characterized by episodes of urticaria, arthralgia, fever and conjunctivitis after generalized exposure to cold. We here describe patients of two German families with the 592G→A, V198M mutation, which has been described to induce FCAS before. However, in our patients the clinical phenotype was very different from this disease. They never had urticaria, cold induced fever or conjunctivitis; instead the following symptoms occurred: Very regular periodic fever, irregular severe febrile episodes, relatively mild arthralgia, dry cough, cardiomyopathy, nephropathy and euthyroid thyroiditis all being reversible. We conclude that the clinical phenotype associated with mutations in the CIAS1 gene is much broader than assumed before.
Clinical, haematological and histomorphological profile of adult myelodysplastic syndrome. Study of 96 cases in a single institute
Authors: Chatterjee T. , Dixit A. , Mohapatra M. , Tyagi S. , Gupta P. K. , Mishra P. , Bhattacharya M. , Karan A. S. , Pati H. P. , Saxena R. , Choudhry V. P.
Published: July 2004

Abstract:  Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders characterised by ineffective and dyspoietic haematopoiesis. The natural history of these disorders is variable and ranges from a chronic to a rapid course towards leukaemic progression. Certain shortcomings have been encountered in the French–American–British (FAB) classification over the years, and therefore there is a need for an alternative method of classification. In 1999, the WHO published a revised classification of MDS. In the present study, we have analysed the clinical, haematological and histomorphological features in 96 cases of primary MDS seen in the department of haematology at the All India Institute of Medical Sciences (AIIMS) over a 6‐yr period (1996–2001). Both FAB and WHO classifications have been incorporated and the Bournemouth scoring system applied in each case at presentation. The Bournemouth scoring system, in the absence of a cytogenetic study, offers a good prognostication and long‐term survival estimate.
Thalidomide alone or in combination with dexamethasone in patients with advanced, relapsed or refractory multiple myeloma and renal failure
Authors: Tosi Patrizia , Zamagni Elena , Cellini Claudia , Cangini Delia , Tacchetti Paola , Tura Sante , Baccarani Michele , Cavo Michele
Published: July 2004

Abstract:  Salvage therapy of patients with advanced, relapsed and refractory multiple myeloma (MM) is often limited by poor marrow reserve and multi‐organ impairment. In particular, renal failure occurs in up to 50% of such patients, and this further limits the use of conventional chemotherapy. Thalidomide, both alone and in combination with dexamethasone, has been demonstrated to be useful in patients with advanced MM, as responses could be achieved in 30–60% of the cases. From May 2000 to November 2003, 20 consecutive MM patients (15 males, five females, median age 66.5 yr) with stage III relapsed/refractory MM and renal failure, defined as serum creatinine >130 mmol/L, gave their informed consent to be enrolled in a clinical trial aimed at evaluating the efficacy and the toxic effects of thalidomide. Three patients were undergoing chronic haemodialysis during the time of entry in the study. Eight patients have been treated with thalidomide as a single agent, at a starting dose of 100 mg/d, that was to be increased to 400 mg/d in case of good tolerance. Twelve patients have been treated with thalidomide at the maimum dose of 200 mg/d plus dexamethasone 40 mg/d for four consecutive days every 4 wk. A >50% decrease in serum or urine M component was observed in nine patients (45%), seven of whom have been treated with thalidomide + dexamethasone and three with thalidomide alone. Six additional patients achieved a minor response (>25% paraprotein decrease); the total response rate was thus 75%. Median response duration was 7 months (range 2–24 months). Four patients were refractory to treatment. Recovery of a normal renal function was observed in 12 of 15 responsive patients, two additional patients, in chronic haemodialysis, showed a reduction of serum creatinine. Toxicity profile of thalidomide with or without dexamethasone was comparable with that observed in patients with a normal renal function. In conclusion, our data show that thalidomide can be safely administered in patients with advanced MM and renal failure.
A rare case of interstitial pneumonitis after tandem high‐dose melphalan conditioning and autologous stem cell transplantation in multiple myeloma
Authors: Buxhofer‐Ausch Veronika , Ruckser Reinhard , Kier Peter , Habertheuer Karl Heinz , Zelenka Peter , Tatzreiter Georg , Ausch Christoph , Schmid Isabel , Hruby Walter , Reiner‐Concin Angelika , Sebesta Christian , Ogris Emil , Hinterberger‐Fischer Margareta , Hinterberger Wolfgang
Published: July 2004

Abstract:  A 57‐yr‐old woman with multiple myeloma received an autologous tandem transplant at a 4‐month interval. She was conditioned twice with 225 mg/m2 melphalan. After the second transplant, interstitial pneumonitis (IP) ensued. The clinical course was life threatening and mechanical ventilation was required for 32 d. All attempts to identify an infectious agent failed. A presumptive diagnosis of idiopathic IP, possibly related to melphalan toxicity, was made. High‐dose methylprednisolone administration led to rapid and durable improvement. Melphalan was employed for conditioning in the tandem setting with an interval of only 3–4 months between two courses or a dose elevation to 225 instead of 200 mg/m2, may have induced IP which responded favorably to methylprednisolone.
Management of a complex dentoalveolar trauma with multiple avulsions: a case report
Authors: Sheroan Marianne Mills , Roberts Michael W.
Published: July 2004

Abstract –  Treatment of permanent tooth avulsions in an adolescent poses significant difficulties for the dental clinician. This case report gives details about the treatment of a complex dentoalveolar trauma involving multiple avulsions of primary molars, permanent incisors, permanent molars, and premolar toothbuds. Immediate treatment of the injury and short‐term esthetic replacement of the dentition is described. A brief review of current research relative to the treatment of permanent tooth avulsions is provided.
Successful treatment of a radicular groove by intentional replantation and Emdogain® therapy
Authors: Al‐Hezaimi Khalid , Naghshbandi Jafar , Simon James H. S. , Oglesby Samuel , Rotstein Ilan
Published: July 2004

Abstract –  Radicular groove is an anatomical malformation often predisposing to a severe periodontal defect. Treatment of such an anomaly presents a clinical challenge to the operator. Presented is a case of successful treatment of a radicular groove associated with a maxillary lateral incisor in a 15‐year‐old girl. A combination of endodontic, intentional replantation and Emdogain® therapy was used. At 1‐year follow‐up, the patient was comfortable and active healing was evident.
Re‐eruption of traumatically intruded mature permanent incisor: case report
Authors: Faria Gisele , Silva Raquel Assed Bezerra , Júnior Marco Fiori , Nelson‐Filho Paulo
Published: July 2004

Abstract –  This case report describes a case of intrusion of the right mature permanent central incisor. After gingivectomy and endodontic treatment with changes of the intracanal dressing (calcium hydroxide paste) every 30 days, spontaneous re‐eruption was observed. We conclude that waiting for spontaneous re‐eruption associated with gingivectomy and endodontic treatment is an alternative treatment for severe intrusive luxations in mature permanent teeth.
The biomechanical properties of the healing periodontium of replanted rat mandibular incisors
Authors: Shinohara Josuke , Shibata Tatsuya , Shimada Akemi , Komatsu Koichiro
Published: July 2004

Abstract –  One of the most important aspects in tooth replantation seems to be restoration of the tooth support function of the healing periodontal ligament (PDL). We examined the support function, as measured by the mechanical properties, of the healing PDL at 7, 14, and 21 days after replantation of the left mandibular incisor in rats. From each dissected left mandible, a transverse section(650 µm in thickness) of the incisor was cut through an axis near the labial alveolar crest. Each section was intrusively loaded at a rate of 5 mm min−1, and the shear stress–strain curve for the PDL was analyzed. Mechanical measures of the healing PDL showed gradual improvement after replantation. By 21 days, the mechanical strength returned to 53% of the control value; the extensibility, to 85%; the stiffness, to 61%; and the toughness, to 52%. The healing PDL exhibited reattachment of fibers in the middle region of the PDL, and the birefringent collagen fibers appeared to have regained the functional orientation by 14 days. The ratios occupied by the birefringent collagen fibers in the tooth‐related, middle, and bone‐related areas of the healing PDL gradually improved and returned to 78, 51, and 48% of the respective control values by 21 days. These results suggest that the support function of the healing PDL is gradually restored and that the biomechanical restoration is closely related to the reorganization and reorientation of collagen fiber bundles in replanted rat incisors.
Screening for novel ENU‐induced rhythm, entrainment and activity mutants
Authors: Bacon Y. , Ooi A. , Kerr S. , Shaw‐Andrews L. , Winchester L. , Breeds S. , Tymoska‐Lalanne Z. , Clay J. , Greenfield A. G. , Nolan P. M.
Published: July 2004

Chemical mutagenesis has provided an opportunity to develop and expand the repertoire of behavioural mutants for gene function studies. With this in mind, we have established a screen in mice for mutations affecting circadian rhythms, entrainment to light and other wheel‐running parameters. The screen consists of an assessment of mouse wheel‐running activity in a 12:12 h light/dark cycle for 7–10 days followed by assessment in constant darkness for up to 20 days. Responses to light are assessed using two protocols; a 15 minute light pulse given at circadian time 16 on the tenth day in constant darkness and an additional 12 h of light upon transition from light/dark conditions to constant darkness. To date, approximately 1300 progeny of chemically mutagenised mice have been screened. Computer‐aided assessment of wheel‐running parameters has helped in identifying abnormal phenotypes in approximately 5% of all animals screened. Inheritance testing of mice with abnormal phenotypes has confirmed the number of robustly inherited mutant phenotypes to be 1% of the total screened. Confirmed mutants including those affecting free‐running period, light‐responsiveness and wheel‐running endurance have been identified. Thus far, low‐resolution map positions have been established for four mutants by completing genome scans in backcross progeny. Mutant loci do not correspond with those previously associated with wheel‐running behaviour. This result confirms that phenotype‐driven approaches such as this should continue to provide material for mammalian gene function studies.
Behavioural profiles of inbred mouse strains used as transgenic backgrounds. I: motor tests
Authors: Brooks S. P. , Pask T. , Jones L. , Dunnett S. B.
Published: July 2004

One of the characteristic manifestations in several neurodegenarative diseases is the loss of voluntary motor control and the development of involuntary movements. In order to determine the suitability of six mouse strains as transgenic background strains we investigated performance on a variety of tasks designed to identify subtle changes in motor control. On both the accelerating and the staggered speed rotarod all six mouse strains performed well. However, latency to fall from the rod was sensitive to both rotarod speed and repeated exposure to the apparatus. Performance of the DBA/2 mouse strain was highly variable across the time points used. On the acoustic startle test CBA mice showed the greatest degree of reactivity to the acoustic startle stimuli with both the C57 and DBA showing the least. Complex strain differences were also identified on measures of habituation to the startle stimuli and variations in the prepulse noise level, and prepulse/startle delay. Gait analysis using the footprint test did not reveal strain differences on measures of base width, overlap or stride length but the 129S2/Sv strain took significantly longer to traverse the runway than the other mouse strains. Finally, the swim tank test detected complex strain differences in swim speed, and the number of fore‐ and hindpaw paddles required to swim the length of the tank. These data taken together suggest that choice of background strain is a crucial consideration for the repeated behavioural assessment of motor deficits in transgenic mouse models of disease.
A note on the effect of within‐strain sample sizes on QTL mapping in recombinant inbred strain studies
Authors: Crusio W. E.
Published: July 2004

This note explores the effect of within‐strain sample sizes on the correlations between a phenotype and a molecular‐genetic marker in a battery of inbred strains. It is shown that the maximum correlation possible between a molecular marker and a behavioral or neuronal phenotype equals the additive‐genetic correlation. How close the strain correlation will approach the additive‐genetic correlation depends only on heritability and within‐strain sample sizes. The equations derived can be used to optimize designs of studies attempting to localize Quantitative Trait Loci utilizing Recombinant Inbred Strains, provided information about the heritability of the character under study is available.
The impact of genetic background on neurodegeneration and behavior in seizured mice
Authors: Mohajeri M. H. , Madani R. , Saini K. , Lipp H.‐P. , Nitsch R. M. , Wolfer D. P.
Published: July 2004

We used pilocarpine‐induced seizures in mice to determine the impact of genetic background on the vulnerability of hippocampal neurons and associated changes of behavioral performance. The susceptibility of hippocampal neurons to seizure‐induced cell death paralleled the severity of the seizures and depended on genetic background. Hippocampal neurons in C57BL/6 mice were most resistant to cell death, whereas they were highly vulnerable in FVB/N mice. The degree of neuronal degeneration in F1 hybrid mice obtained by crossing the two strains was at an intermediate level between the parent strains. Two weeks after the severe seizures, performance in a water‐maze place navigation task showed a bimodal distribution. Seventeen of 19 (90%) F1 mice were completely unable to learn while the other two learned reasonably well. Of 28 C57BL/6 mice with similarly severe seizures, six were as strongly impaired as their F1 counterparts (22%). The remaining 22 performed normally, indicating a much lower probability of C57BL/6 mice to be affected. Treated mice showed a deficit of open‐field exploration which was strongly correlated with the impairment in the place navigation task and was again more severe in F1 mice. Our results show that the vulnerability of hippocampal neurons to pilocarpine‐induced seizures, as well as the associated behavioral changes, depended on genetic background. Furthermore, they confirm and extend our earlier finding that a relatively modest reduction of hippocampal cell death can be associated with dramatic changes of behavioral performance and emphasize the importance of tightly‐controlled genetic backgrounds in biological studies.
MAO‐B knockout mice exhibit deficient habituation of locomotor activity but normal nicotine intake
Authors: Lee M. , Chen K. , Shih J. C. , Hiroi N.
Published: July 2004

Low levels of monoamine oxidase‐B (MAO‐B) activity, such as those observed in smokers, are also associated with behavioral traits such as a heightened responsiveness to novelty. However, the exact mechanism by which low MAO‐B activity influences smoking and heightened responsiveness to novelty is still poorly understood. We used MAO‐B knockout (KO) mice to test the hypothesis that MAO‐B concomitantly affects locomotor responses in a novel inescapable open field and nicotine intake. Male wild‐type (WT) and MAO‐B KO mice were placed in an inescapable open field and their horizontal locomotor activity was measured for 30 min per day for 5 days. MAO‐B KO mice exhibited impaired within‐session habituation of locomotor activity, as compared to WT mice. Separate groups of male WT and MAO‐B KO mice were individually housed in their home cages with two water bottles. One of the bottles contained tap water and the other contained nicotine (0, 3.125, 6.25, 12.5, 25, 50 or 100 µg/ml). The total amount of water and nicotine solution consumed was measured every three days for 16 days. MAO‐B KO mice and WT mice consumed equal amounts of nicotine and exhibited comparable concentration‐dependent nicotine preference and aversion over a period of 16 days. The data suggest that the absence of MAO‐B impairs the ability of mice to habituate in the inescapable environment, but does not alter their nicotine intake.
Postural and locomotor control in normal and vestibularly deficient mice
Authors: Vidal P.‐P. , Degallaix L. , Josset P. , Gasc J.‐P. , Cullen K. E.
Published: July 2004

We investigated how vestibular information is used to maintain posture and control movement by studying vestibularly deficient mice (IsK−/− mutant). In these mutants, microscopy showed degeneration of the cristae of the semicircular canals and of the maculae of the utriculi and sacculi, while behavioural and vestibulo‐ocular reflex testing showed that vestibular function was completely absent. However, the histology of Scarpa's ganglia and the vestibular nerves was normal in mutant mice, indicating the presence of intact central pathways. Using X‐ray and high‐speed cineradiography, we compared resting postures and locomotion patterns between these vestibularly deficient mice and vestibularly normal mice (wild‐type and IsK+/−). The absence of vestibular function did not affect resting posture but had profound effects on locomotion. At rest, the S‐shaped, sagittal posture of the vertebral column was the same for wild‐type and mutant mice. Both held the head with the atlanto‐occipital joint fully flexed, the cervico‐thoracic junction fully flexed, and the cervical column upright. Wild‐type mice extended the head and vertebral column and could walk in a straight line. In marked contrast, locomotion in vestibularly deficient mice was characterized by circling episodes, during which the vertebral column maintained an S‐shaped posture. Thus, vestibular information is not required to control resting posture but is mandatory for normal locomotion. We propose that vestibular inputs are required to signal the completion of a planned trajectory because mutant mice continued rotating after changing heading direction. Our findings support the hypothesis that vertebrates limit the number of degrees of freedom to be controlled by adopting just a few of the possible skeletal configurations.
A quantitative analysis of cell volume and resting potential determination and regulation in excitable cells
Authors: Fraser James A. , Huang Christopher L.‐H.
Published: July 2004

This paper quantifies recent experimental results through a general physical description of the mechanisms that might control two fundamental cellular parameters, resting potential (Em) and cell volume (Vc), thereby clarifying the complex relationships between them. Em was determined directly from a charge difference (CD) equation involving total intracellular ionic charge and membrane capacitance (Cm). This avoided the equilibrium condition dEm/dt= 0 required in determinations of Em by previous work based on the Goldman‐Hodgkin‐Katz equation and its derivatives and thus permitted precise calculation of Em even under non‐equilibrium conditions. It could accurately model the influence upon Em of changes in Cm or Vc and of membrane transport processes such as the Na+–K+‐ATPase and ion cotransport. Given a stable and adequate membrane Na+–K+‐ATPase density (N), Vc and Em both converged to unique steady‐state values even from sharply divergent initial intracellular ionic concentrations. For any constant set of transmembrane ion permeabilities, this set point of Vc was then determined by the intracellular membrane‐impermeant solute content (X−i) and its mean charge valency (zX), while in contrast, the set point of Em was determined solely by zX. Independent changes in membrane Na+ (PNa) or K+ permeabilities (PK) or activation of cation–chloride cotransporters could perturb Vc and Em but subsequent reversal of such changes permitted full recovery of both Vc and Em to the original set points. Proportionate changes in PNa, PK and N, or changes in Cl− permeability (PCl) instead conserved steady‐state Vc and Em but altered their rates of relaxation following any discrete perturbation. PCl additionally determined the relative effect of cotransporter activity on Vc and Em, in agreement with recent experimental results. In contrast, changes in Xi− produced by introduction of a finite permeability term to X− (PX) that did not alter zX caused sustained changes in Vc that were independent of Em and that persisted when PX returned to zero. Where such fluxes also altered the effective zX they additionally altered the steady state Em. This offers a basis for the suggested roles of amino acid fluxes in long‐term volume regulatory processes in a variety of excitable tissues.
Postsynaptic production of nitric oxide implicated in long‐term depression at the mature amphibian (Bufo marinus) neuromuscular junction
Authors: Etherington Sarah J. , Everett Alan W.
Published: July 2004

We report here evidence for endogenous NO signalling in long‐term (> 1 h) synaptic depression at the neuromuscular junction induced by 20 min of 1 Hz nerve stimulation. Synaptic depression was characterized by a 46% reduction in the end‐plate potential (EPP) amplitude and a 21% decrease in miniature EPP (MEPP) frequency, but no change to MEPP amplitude, indicating a reduction in evoked quantal release. Both the membrane‐impermeant NO scavenger cPTIO and the NOS inhibitor+ release from the sarcoplasmic reticulum and muscle contraction were blocked with dantrolene. These data suggest that the depression depends on transmission, but not muscle contraction. The calcineurin inhibitors cyclosporin A and FK506, as well as ODQ, an inhibitor of NO‐sensitive soluble guanylyl cyclase, Rp‐8‐pCPT‐cGMPS, an inhibitor of cGMP‐dependent protein kinase, and the calmodulin antagonist phenoxybenzamine also blocked depression. We propose that low frequency synaptic transmission leads to production of NO at the synapse and depression of transmitter release via a cGMP‐dependent mechanism. The NO could be generated either directly from the muscle, or possibly from the Schwann cell in response to an unidentified muscle‐derived messenger. We showed that the long‐lasting depression of transmitter release was due to sustained activity of the NO signalling pathway, and suggest dephosphorylation of NOS by calcineurin as the basis for continued NO production.
Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes
Authors: Bassani Rosana A. , Altamirano Julio , Puglisi José L. , Bers Donald M.
Published: July 2004

After sarcoplasmic reticulum (SR) Ca2+ depletion in intact ventricular myocytes, electrical activity promotes SR Ca2+ reloading and recovery of twitch amplitude. In ferret, recovery of twitch and caffeine‐induced contracture required fewer twitches than in rabbit or rat. In rat, there was no difference in action potential duration at 90% repolarization (APD90) at steady state (SS) versus at the first post‐depletion (PD) twitch. The SS APD90 was similar in ferret and rabbit (but longer than in rat). However, compared to SS, the PD APD90 was lengthened in ferret, but shortened in rabbit. When rabbit myocytes were subjected to AP‐clamp patterns during SR Ca2+ reloading (ferret‐ or rabbit‐type APs), reloading was much faster using the ferret AP templates. We conclude that the faster SR Ca2+ refilling in ferret is due to the increased Ca2+ influx during the longer PD AP. The PD versus SS APD90 difference was suppressed by thapsigargin in ferret (indicating Ca2+ dependence). In rabbit, the PD AP shortening depended on the preceding diastolic interval (rather than Ca2+), because rest produced the same AP shortening, and SS APD90 increased as a function of frequency (in contrast to ferret). Transient outward current (Ito) was larger and recovered from inactivation much faster in ferret than in rabbit. Moreover, slow Ito recovery (τ∼ 3 s) in rabbit was a much larger fraction of Ito. Our data and a computational model (including two Ito components) suggest that in rabbit the slowly recovering Ito is responsible for short post‐rest and PD APs, for the unusual frequency dependence of  APD90, and ultimately for the slower post‐depletion SR Ca2+ reloading.
Nerve growth factor favours long‐term depression over long‐term potentiation in layer II–III neurones of rat visual cortex
Authors: Brancucci Alfredo , Kuczewski Nicola , Covaceuszach Sonia , Cattaneo Antonino , Domenici Luciano
Published: July 2004

Nerve growth factor (NGF) has been shown to regulate plasticity in the visual cortex of monocularly deprived animals. However, to date, few attempts have been made to investigate the role of NGF in synaptic plasticity at the cellular level. In the study reported here we looked at the effects of exogenously applied NGF on synaptic plasticity of layer II–III regular spiking (RS) neurones in visual cortex of 16‐ to 18‐day‐old rats. We found that local application of NGF converted high frequency stimulation (HFS)‐induced long‐term potentiation (LTP) into long‐term depression (LTD). We showed that this shift of synaptic plasticity was also obtained with bath application of NGF during HFS. Application of NGF subsequent to HFS left LTP unaffected, conferring temporal constraints on NGF efficacy. NGF effects on LTP were mediated by TrkA receptors. Indeed, blockade of TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS. Low frequency stimulation (LFS) elicited LTD in RS cells. We found that NGF or blockade of NGF signalling by anti‐TrkA antibody did not change the amplitude of the LTD induced by LFS. Thus, the NGF effect is selective for synaptic modifications induced by HFS in RS cells. The present results indicate that NGF may modulate the sign of long‐term changes of synaptic efficacy in response to high frequency inputs.
Integrase Inhibitors and Cellular Immunity Suppress Retroviral Replication in Rhesus Macaques
Authors: Hazuda Daria J. , Young Steven D. , Guare James P. , Anthony Neville J. , Gomez Robert P. , Wai John S. , Vacca Joseph P. , Handt Larry , Motzel Sherri L. , Klein Hilton J. , Dornadula Geethanjali , Danovich Robert M. , Witmer Marc V. , Wilson Keith A. A. , Tussey Lynda , Schleif William A. , Gabryelski Lori S. , Jin Lixia , Miller Michael D. , Casimiro Danilo R. , Emini Emilio A. , Shiver John W.
Published: July 2004

We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.
Compression, expansion, or dynamic equilibrium? The evolution of health expectancy in New Zealand
Authors: Graham Patrick , Blakely Tony , Davis Peter , Sporle Andrew , Pearce Neil
Published: July 2004

Study objective:To evaluate the New Zealand evidence for three theories of population health change: compression of morbidity, expansion of morbidity, and dynamic equilibrium.

Design:Using the Sullivan method, repeated cross sectional survey information on functional limitation prevalence was combined with population mortality data and census information on the utilisation of institutional care to produce health expectancy indices for 1981 and 1996.

Setting:The adult population of New Zealand in 1981 and 1996.

Participants:6891 respondents to the 1981 social indicators survey; 8262 respondents to the 1996 household disability survey.

Main results:As a proportion of overall life expectancy at age 15 the expectation of non-institutionalised mobility limitations increased from 3.5% to 6% for men, and from 4.5% to 8% for women; the expectation of agility limitation increased from 3% to 7.5% for men and from 4.5% to 8.5% for women, and the expectation of self care limitations increased from 2.0% to 4.5% for men and from 3.0% to 6.0% for women. These changes were primarily attributable to increases in the expectation of moderate functional limitation.

Conclusion:The dynamic equilibrium scenario provides the best fit to current New Zealand evidence on changes in population health. Although an aging population is likely to lead to an increase in demand for disability support services, the fiscal impact of this increase may be partially offset by a shift from major to moderate limitations, with a consequential reduction in the average levels of support required.
THE RELATIONS BETWEEN GENERALIZED FIELDS AND SUPERFIELDS FORMALISMS OF THE BATALIN–VILKOVISKY METHOD OF QUANTIZATION
Authors: DAYI ÖMER F.
Published: July 2004

A general solution of the Batalin–Vilkovisky master equation was formulated in terms of generalized fields. Recently, a superfields approach of obtaining solutions of the Batalin–Vilkovisky master equation is also established. Superfields formalism is usually applied to topological quantum field theories. However, generalized fields method is suitable to find solutions of the Batalin–Vilkovisky master equation either for topological quantum field theories or the usual gauge theories like Yang–Mills theory. We show that by truncating some components of superfields with appropriate actions, generalized fields formalism of the usual gauge theories result. We demonstrate that for some topological quantum field theories and the relativistic particle both of the methods possess the same field contents and yield similar results. Inspired by the observed relations, we give the solution of the BV master equation for on-shell N=1 supersymmetric Yang–Mills theory utilizing superfields.
SUPER HEAVY DARK MATTER ANISOTROPIES FROM D-PARTICLES IN THE EARLY UNIVERSE
Authors: MAVROMATOS N. E. , PAPAVASSILIOU J.
Published: July 2004

We discuss a way of producing anisotropies in the spectrum of superheavy dark matter, which are due to the distortion of the inflationary space–time induced by the recoil of D-particles upon their scattering with ordinary string matter in the early universe. We calculate such distortions by world-sheet Liouville string theory (perturbative) methods. The resulting anisotropies are found to be proportional to the average recoil velocity and density of the D-particles. In our analysis we employ a regulated version of de Sitter space, allowing for graceful exit from inflation. This guarantees the asymptotic flatness of the space–time, as required for a consistent interpretation, within an effective field theory context, of the associated Bogolubov coefficients as particle number densities. The latter are computed by standard WKB methods.
AGEING, DYNAMICAL SCALING AND CONFORMAL INVARIANCE
Authors: HENKEL MALTE
Published: July 2004

Building on an analogy with conformal invariance, local scale transformations consistent with dynamical scaling are constructed. Two types of local scale invariance are found which act as dynamical space–time symmetries of certain nonlocal free field theories. The scaling form of two-point functions is completely fixed by the requirement of local scale invariance. These predictions are confirmed through tests in the 3D ANNNI model at its Lifshitz point and in ageing phenomena of simple ferromagnets, here studied through the kinetic Ising model with Glauber dynamics.
TWISTED OPEN STRINGS FROM CLOSED STRINGS: THE WZW ORIENTATION ORBIFOLDS
Authors: HALPERN M. B. , HELFGOTT C.
Published: July 2004

Including world-sheet orientation-reversing automorphismsĥσ∈H-in the orbifold program, we construct the operator algebras and twisted KZ systems of the general WZW orientation orbifoldAg(H-)/H-. We find that the orientation-orbifold sectors corresponding to each ĥσ∈H-are twisted open WZW strings, whose properties are quite distinct from conventional open-string orientifold sectors. As simple illustrations, we also discuss the classical (high-level) limit of our construction and free-boson examples on Abelian g.
ON THE USE OF PARTIALLY LINEAR MODEL IN IDENTIFICATION OF ARCING-FAULT LOCATION ON OVERHEAD HIGH-VOLTAGE TRANSMISSION LINES
Authors: ŽIVANOVIĆ RASTKO
Published: July 2004

The task of locating an arcing-fault on overhead line using sampled measurements obtained at a single line terminal could be classified as a practical nonlinear system identification problem. The practical reasons impose the requirement that the solution should be with maximum possible precision. Dynamic behavior of an arc in open air is influenced by the environmental conditions that are changing randomly, and therefore the useful practically application of parametric modeling is out of question. The requirement to identify only one parameter is yet another specific of this problem. The parameter we need is the one that linearly correlates the voltage samples with the current derivative samples (inductance). The correlation between the voltage samples and the current samples depends on the unpredictable arc dynamic behavior. Therefore this correlation is reconstructed using nonparametric regression. A partially linear model combines both, parametric and nonparametric parts in one model. The fit of this model is noniterative, and provides an efficient way to identify (pull out) a single linear correlation from the nonlinear time series.
PHASE SPACE RECONSTRUCTION AND NONLINEAR PREDICTIONS FOR STATIONARY AND NONSTATIONARY MARKOVIAN PROCESSES
Authors: KANTZ HOLGER , RAGWITZ MARIO
Published: July 2004

We analyze prediction schemes for stochastic time series data. We propose that under certain conditions a scalar time series, obtained from a vector-valued Markov process, can be modeled as a finite memory Markov process in the observable. The transition rules of the process are easily computed using simple nonlinear time series predictors originally proposed for deterministic chaotic signals. The optimal time lag entering the embedding procedure is shown to be significantly smaller than in the deterministic case. The same concept can be extended to nonstationary stochastic processes, where an increase of the embedding dimension can help to identify instantaneous dynamical properties, and where redundant information in the past is exploited in an optimal way.
SCALE-DEPENDENCE OF SPATIOTEMPORAL FILTERS INSPIRED BY CELLULAR AUTOMATA
Authors: BUSCH HAUKE , HÜTT MARC-THORSTEN
Published: July 2004

We discuss analysis tools of spatiotemporal patterns. These tools are based on nearest-neighbor considerations similar to cellular automata. Application of these methods to a spatiotemporal data set means selecting certain scales in space and in time. Focusing on spatial length we show that the dependence of the results on this scale can be used to quantify separately the contribution to the dynamics of measurement noise and of dynamical (internal) noise, respectively. In particular, we test the spatiotemporal filters using sample data generated with a network of coupled Sel'kov oscillators. Possible application of our results to biological systems are briefly discussed.
TRAFFIC FORECAST IN LARGE SCALE FREEWAY NETWORKS
Authors: CHROBOK ROLAND , POTTMEIER ANDREAS , HAFSTEIN SIGURDUR F. , SCHRECKENBERG MICHAEL
Published: July 2004

Traffic flow in large and complex freeway networks is a highly nonlinear phenomenon, which makes traffic forecast a difficult task. In this article an approach to traffic forecast is presented, which uses a micro-simulator for traffic flow combined with current and historical traffic data. The micro-simulator and locally measured current traffic data are used to reconstruct the current network-wide traffic state. Then, this state is combined with historical traffic data to forecast the traffic development. This framework is applied to the freeway network of the German state North Rhine-Westphalia. The micro-simulator uses an advanced cellular-automaton model for traffic flow, and the data are supplied from more than 4,000 locally installed loop-detectors, which deliver information on the (local) traffic state online minute by minute.