bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid ubiquitination of Syk following GPVI activation in platelets
Authors: Dangelmaier Carol A. , Quinter Patricia G. , Jin Jianguo , Tsygankov Alexander Y. , Kunapuli Satya P. , Daniel James L.
Published: February 2005

Spleen tyrosine kinase (Syk) activation is a key intermediate step in the activation of platelets by the physiologic agonist collagen. We have found that Syk is rapidly ubiquitinated upon activation of platelets by collagen, collagen-related peptide (CRP), and convulxin. The Src family kinase inhibitors prevented Syk phosphorylation and its ubiquitination, indicating that the process is downstream of Src kinases. The ubiquitination of Syk did not cause degradation of the protein as evidenced by the lack of effect of proteasomal and lysosomal inhibitors. We separated ubiquitinated Syk from its nonubiquitinated counterpart and used an in vitro kinase assay to compare their activities. We found that the ubiquitinated Syk appeared to be about 5-fold more active. Using a phosphospecific antibody to Syk (Tyr525/Tyr526) that measures activated Syk, we found that most (60%-75%) of the active Syk is in the ubiquitinated fraction. This result explains the apparent high specific activity of ubiquitinated Syk. In c-Cbl–deficient mice, Syk is not ubiquitinated, implicating c-Cbl as the E3 ligase involved in Syk ubiquitination. Furthermore, Syk is not dephosphorylated in these mice. We propose that c-Cbl plays a regulatory role in glycoprotein VI (GPVI)/Fc receptor γ (FcRγ)-chain–dependent platelet activation through its interaction with Syk.
Alternative fuels and their application to combustion engines
Authors: Kowalewicz A , Wojtyniak M
Published: February 2005

Alternative fuels for both spark ignition (SI) and compression ignition (CI) engines have become very important owing to increased environmental protection concern, the need to reduce dependency on petroleum and even socioeconomic aspects. In the paper a review of alternative fuels for combustion engines has been performed, including physicochemical properties of these fuels, their sources and technological aspects of production, as well as recent data on R&D work and application. Fuels that are most used at present are natural gas, liquefied petroleum gas (LPG) and biofuels, such as transesterified vegetable oils and alcohols (bioethanol). Some species cannot be directly applied as neat fuels, but may be used as additives, e.g. dimethyl ether (DME), alcohols and oxygenates.
Application of non-linear observers to on-line estimation of indicated torque in automotive engines
Authors: Wang Yunsong , Chu Fulei
Published: February 2005

Estimation of the indicated torque for automotive engines is profitable for evaluation of engine combustion conditions, optimization of engine performance, diagnosis of engine faults and control of automotive transmission. On the basis of the crankshaft-wheel system dynamics of the automotive multicylinder engine without including load torque, this paper describes mainly the application of three non-linear observers to the on-line estimation of indicated torque and analyses the similarities and differences between them. Of all the proposed observers the second-order sliding mode observers are most robust and exact. The classical sliding mode observers are slightly more accurate than the high gain observers, but have the undesired chattering effect. These observers require crank angle and crankshaft speed measurements. Experimental results strongly demonstrate that the on-line estimation techniques of the indicated torque based on non-linear observers are valid, not only for steady state operation but also under transients.
Multi-objective optimization of heavy duty diesel engines under stationary conditions
Authors: Desantes J M , Benajes J V , Molina S A , Herández L
Published: February 2005

New technological developments are helping to control contaminants in diesel engines but, as new degrees of freedom become available, the assessment of optimal values that combine to reduce different emissions has become a difficult task. This paper studies the feasibility of using artificial neural networks (ANNs) as models to be integrated in the optimization of diesel engine settings, with the objective of complying with the increasingly stringent emission regulations while also keeping, or even reducing, the fuel consumption. A large database of stationary engine tests covering a wide range of experimental conditions was used for the development of the ANN models. The optimization was developed within the frame of the European legislation for heavy duty diesel engines. Experimental validation of the optimized results was carried out and compared with the ANN predictions, showing a high level of accuracy, especially for fuel consumption and nitrogen oxides (NOx).
A study of the effect of rear suspension auxiliary roll damping on vehicle-handling dynamics
Authors: Uzunsoy E , Olatunbosun O A
Published: February 2005

The handling dynamics of a University of Birmingham Racing Formula Student racing car, incorporating a novel rear suspension load transfer system which provides auxiliary roll damping, is modelled using a simulation tool, HANDSIM, developed for vehicle-handling studies, and the effect of the system on the vehicle's handling performance is discussed by considering the results obtained from the simulation. The aim of implementing this suspension load transfer system is to improve the handling characteristics of the vehicle in severe cornering manoeuvres.
A GRASP for Parallel Machine Scheduling with Time Windows
Authors: Rojanasoonthon Siwate , Bard Jonathan
Published: February 2005

This paper presents a greedy randomized adaptive search procedure (GRASP) for scheduling n jobs on m nonhomogeneous parallel machines with time windows. An additional feature of the problem is that each job falls into one of ρ priority classes. The objective is to maximize the number of jobs scheduled, where a job in a higher priority class has infinitely more value than a job in a lower priority class. The GRASP consists of two phases. The first phase produces feasible solutions by ranking each job with a greedy function and then selecting one at random from a restricted candidate list. The process is repeated until no more jobs can be scheduled. The second phase seeks a local optimum by searching over a series of neighborhoods defined by job insertions and exchanges. The algorithm is compared to a dynamic-programming heuristic that sequentially schedules the jobs in each priority class. Extensive computational results are presented based on data drawn from an application involving the use of communications relay satellites.
A Local-Search-Based Heuristic for the Demand-Constrained Multidimensional Knapsack Problem
Authors: Cappanera Paola , Trubian Marco
Published: February 2005

We consider an extension of the 0–1 multidimensional knapsack problem in which there are greater-than-or-equal-to inequalities, called demand constraints, in addition to the standard less-than-or-equal-to constraints. Moreover, the objective function coefficients are not constrained in sign. This problem is worth considering because it is embedded in models of practical application, it has an intriguing combinatorial structure, and it appears to be a challenging problem for commercial ILP solvers. Our approach is based on a nested tabu-search algorithm in which neighborhoods with different structures are exploited. First, a tabu-search procedure is carried out in which mainly the infeasible region is explored. Once feasibility has been established, a second tabu-search procedure, which analyzes only feasible solutions, is applied. The algorithm has been tested on a wide set of instances. Computational results are discussed.
An Experimental Study of LP-Based Approximation Algorithms for Scheduling Problems
Authors: Savelsbergh Martin W. P. , Uma R. N. , Wein Joel
Published: February 2005

Recently there has been much progress on the design of approximation algorithms for a variety of scheduling problems in which the goal is to minimize the average weighted completion time of the jobs scheduled. Many of these approximation algorithms have been inspired by polyhedral formulations of the scheduling problems and their use in computing optimal solutions to small instances.

In this paper we demonstrate that the progress in the design and analysis of approximation algorithms for these problems also yields techniques with improved computational efficacy. Specifically, we give a comprehensive experimental study of a number of these approximation algorithms for 1|rj∑wjCj, the problem of scheduling jobs with release dates on one machine so as to minimize the average weighted completion time of the jobs scheduled. We study both the quality of lower bounds given for this problem by different linear-programming relaxations and combinatorial relaxations, and the quality of upper bounds delivered by a number of approximation algorithms based on them. The best algorithms, on almost all instances, come within a few percent of the optimal average weighted completion time. Furthermore, we show that this can usually be achieved with O(n log n) computation.

In addition we observe that on most kinds of synthetic data used in experimental studies a simple greedy heuristic, used in successful combinatorial branch-and-bound algorithms for the problem, outperforms (on average) all of the LP-based heuristics. We identify, however, other classes of problems on which the LP-based heuristics are superior and report on experiments that give a qualitative sense of the range of dominance of each. We consider the impact of local improvement on the solutions as well.

We also consider the performance of the algorithms for the average weighted flow-time criterion, which, although equivalent to average weighted completion time at optimality, is provably much harder to approximate. Nonetheless, we demonstrate that for most instances we consider that the algorithms give very good results for this criterion as well.

Finally, we extend the techniques to a rather different and more complex problem that arises from an actual manufacturing application: resource-constrained project scheduling. In this setting as well, the techniques yield algorithms with improved performance; we give the best-known solutions for a set of instances provided by BASF AG, Germany.
Suspected β-Antagonist—Induced Thrombocytopenia
Authors: Stamm Pamela L , Jenkins J Kimble , Vigrass Howard G
Published: February 2005

OBJECTIVE:

To report a case of possible β-antagonist—induced thrombocytopenia.

CASE SUMMARY:

A 44-year-old African American woman with systemic lupus erythematosus developed thrombocytopenia. Splenic sequestration was suspected, but the rise in platelets after splenectomy was temporary. Bacterial and viral etiologies were ruled out, since thrombocytopenia continued 6 months after splenectomy. Her medications acetaminophen, amitriptyline, amlodipine, β-antagonists, and diphenhydramine were suspected. Nadolol and labetalol were started immediately prior to splenectomy. Six months after splenectomy, the woman was hospitalized for pneumonia; the platelet count was 50 times 103/mm3. Nadolol was discontinued on day 2. Within 24 hours, the platelet count rose to 128 times 103/mm3 and exceeded 200 times 103/mm3 by day 7. Labetalol was discontinued on day 8, but no additional significant rise occurred. The patient developed thrombocytopenia one year later when placed on nadolol and famotidine during admission for a gastrointestinal bleed. The platelet count decreased during the admission. Both drugs were discontinued after the last platelet count (100 times 103/mm3). The platelet count had normalized by the follow-up visit 16 days later and remained normal until the patient's death almost a year later.

DISCUSSION:

Thrombocytopenia is not a common adverse effect of β-antagonist therapy. As of February 1, 2005, only 4 case reports of suspected β-antagonist—associated thrombocytopenia have been published in English, and the medications cited are unavailable within the US. After splenectomy, the thrombocytopenia might have resolved if the β-antagonists had not been present. Since thrombocytopenia resolved within 24 hours of discontinuation of nadolol, it is likely that the continued thrombocytopenia was β-antagonist induced. The likelihood that the β-antagonist caused the adverse event is possible according to the Naranjo probability scale.

CONCLUSIONS:

The temporal association between the discontinuation of nadolol and the rise in platelets suggests that the thrombocytopenia resulted from nadolol.
Treatment of Type 2 Diabetes in Primary Health Care: A Drug Utilization Study
Authors: Mino-León Dolores , Figueras Albert , Amato Dante , Laporte Joan-Ramon
Published: February 2005

BACKGROUND:

Metabolic control in type 2 diabetes depends on patient adherence to therapy. Quantitative consumption data do not supply information regarding the appropriate use of medicine. Drug utilization studies are useful to identify treatment adherence problems and, thus, design interventions to improve drug use.

OBJECTIVE:

To describe the treatment and outcome in terms of degree of metabolic control in these patients, assess the agreement between the doses of antidiabetic drugs reported by the patient and those written in the medical record, and describe the drug utilization characteristics in relation to the standards of care.

METHODS:

This drug utilization study was conducted in primary care centers in Barcelona, Spain. Consecutive patients with type 2 diabetes attending a follow-up visit were interviewed regarding lifestyle, diet, glycosylated hemoglobin level, and treatment. Concordance between the information obtained through medical records and patient interviews was analyzed.

RESULTS:

Metabolic control was deficient in 73 (40%), acceptable in 50 (28%), and good in 58 (32%) of the 181 patients with available information. For 38 (19%) patients, there was disagreement between the dose of the antidiabetic drug reported by the patient and that written in the medical record. For 83 (41%) patients, the treatment in the medical history was in agreement with published standards.

CONCLUSIONS:

Identification of disagreement between standards of care and clinical practice in type 2 diabetes management is the basis to improve drug utilization and achieve better metabolic control in these patients.
Pharmacokinetics and Pharmacodynamics of Linezolid in Obese Patients with Cellulitis
Authors: Stein Gary E , Schooley Sharon L , Peloquin Charles A , Kak Vivek , Havlichek Daniel H , Citron Diane M , Tyrrell Kerin L , Goldstein Ellie JC
Published: February 2005

BACKGROUND:

Linezolid is an oxazolidinone antimicrobial with excellent oral bioavailability and tissue penetration and is active against multidrug-resistant skin/soft tissue pathogens.

OBJECTIVE:

To study the pharmacokinetics and antibacterial activity of linezolid against selective skin/soft tissue pathogens in obese patients.

METHODS:

We obtained multiple serum samples from 7 obese patients (>50% over their calculated ideal body weight) receiving oral linezolid 600 mg every 12 hours for treatment of cellulitis. Following a minimum of 3 doses, serum concentrations of linezolid were measured in each subject prior to (trough) and 1 and 6 hours after a dose. These samples were then tested against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (linezolid minimum inhibitory concentrations [MICs] 1.0, 2.0, 4.0 μg/mL) and one strain each of vancomycin-resistant Enterococcus faecium (VRE) (MIC 2.0 μg/mL), Bacteroides fragilis (MIC 2.0 μg/mL), and Peptostreptococcus magnus (MIC 1.0 μg/mL). Serum inhibitory titers (SITs) and bactericidal titers (SBTs) were measured at each time point, and the median activity for these 7 patients was calculated.

RESULTS:

Mean linezolid serum concentrations were 4.2, 12.3, and 7.2 μg/mL at these respective time points. Median SITs for 12 hours (100% of the dosing interval) were observed against each organism with the exception of the least susceptible strain of MRSA (MIC 4.0 μg/mL); serum inhibitory activity was observed only at the one-hour time point against this isolate. Furthermore, prolonged (⩾6 h) median SBTs were observed against one isolate of MRSA (MIC 1.0 μg/mL) as well as the strain of VRE and P. magnus.

CONCLUSIONS:

Serum concentrations of oral linezolid in this patient population were diminished compared with those of healthy volunteers, but still provided prolonged serum inhibitory activity against common pathogens associated with skin/soft tissue infections. One treatment concern would be an obese patient receiving oral linezolid who was infected with a less susceptible (MIC ⩾4.0 μg/mL) strain of S. aureus. Bactericidal activity was also observed against selective pathogens.
Propranolol-Exacerbated Mesenteric Ischemia in a Patient with Hyperthyroidism
Authors: Köksal Aydin Şeref , Üsküdar Oğuz , Köklü Seyfettin , Yüksel Osman , Beyazit Yavuz , Şahin Burhan
Published: February 2005

OBJECTIVE:

To report a case of acute mesenteric ischemia associated with the use of oral propranolol.

CASE SUMMARY:

A 59-year-old white man was admitted to the hospital with chronic diarrhea and weight loss. The patient was diagnosed as having hyperthyroidism. Therapy with propylthiouracil 100 mg 3 times daily and propranolol 20 mg twice daily was initiated on an outpatient basis. The following day, the patient was readmitted to our hospital with increased abdominal pain and bloody diarrhea. Angiography revealed superior mesenteric artery occlusion. Antegrade aorta-mesenteric bypass surgery was performed for revascularization, and the patient was discharged 10 days after the surgery. The patient was well both clinically and endoscopically at a follow-up visit 8 months later.

DISCUSSION:

Although mesenteric ischemia is a devastating illness of varied causes, drug-associated mesenteric ischemia is rarely seen. By decreasing cardiac output and selective vasodilatory receptor inhibition in the splanchnic circulation, propranolol can cause a decline in splanchnic blood flow. An objective causality assessment indicated that propranolol was the possible cause of the arterial occlusion.

CONCLUSIONS:

Propranolol may rarely be associated with mesenteric ischemia. In cases of newly developed acute abdomen undergoing propranolol therapy, physicians should be aware of this rare and serious adverse reaction to this drug.
Myelinogenesis and Axonal Recognition by Oligodendrocytes in Brain Are Uncoupled inOlig1-Null Mice
Authors: Xin Mei , Yue Tao , Ma Zhenyi , Wu Fen-fen , Gow Alexander , Lu Q. Richard
Published: February 2005

Myelin-forming oligodendrocytes facilitate saltatory nerve conduction and support neuronal functions in the mammalian CNS. Although the processes of oligodendrogliogenesis and differentiation from neural progenitor cells have come to light in recent years, the molecular mechanisms underlying oligodendrocyte myelinogenesis are poorly defined. Herein, we demonstrate the pivotal role of the basic helix-loop-helix transcription factor, Olig1, in oligodendrocyte myelinogenesis in brain development. Mice lacking a functionalOlig1gene develop severe neurological deficits and die in the third postnatal week. In the brains of these mice, expression of myelin-specific genes is abolished, whereas the formation of oligodendrocyte progenitors is not affected. Furthermore, multilamellar wrapping of myelin membranes around axons does not occur, despite recognition and contact of axons by oligodendrocytes, andOlig1-null mice develop widespread progressive axonal degeneration and gliosis. In contrast, myelin sheaths are formed in the spinal cord, although the extent of myelination is severely reduced. At the molecular level, we find thatOlig1regulates transcription of the major myelin-specific genes,Mbp,Plp1, andMag, and suppresses expression of a major astrocyte-specific gene,Gfap. Together, our data indicate thatOlig1is a central regulator of oligodendrocyte myelinogenesis in brain and that axonal recognition and myelination by oligodendrocytes are separable processes.
Transgenic Expression of HumanConnexin32in Myelinating Schwann Cells Prevents Demyelination inConnexin32-Null Mice
Authors: Scherer Steven S. , Xu Yi-Tian , Messing Albee , Willecke Klaus , Fischbeck Kenneth H. , Jeng Linda Jo Bone
Published: February 2005

Mutations inGap Junctionβ1(GJB1), the gene encoding the gap junction protein connexin32 (Cx32), cause the X-linked form of Charcot-Marie-Tooth disease (CMT1X), an inherited demyelinating neuropathy. We investigated the possibility that the expression of mutant Cx32 in other cells besides myelinating Schwann cells contributes to the development of demyelination. Human Cx32 was expressed in transgenic mice using a ratmyelin protein zero(Mpz) promoter, which is exclusively expressed by myelinating Schwann cells. Male mice expressing the human transgene were crossed with femaleGjb1/cx32-null mice; the resulting male offspring were allcx32-null (on the X chromosome), and one-half were transgene positive. In these transgenic mice, all of the Cx32 was derived from the expression of the transgene and was found in the sciatic nerve but not in the spinal cord or the liver. Furthermore, the Cx32 protein was properly localized (within incisures and paranodes) in myelinating Schwann cells. Finally, the expression of human Cx32 protein “rescued” the phenotype ofcx32-null mice, because the transgenic mice have significantly fewer demyelinated or remyelinated axons than their nontransgenic littermates. These results indicate that the loss of Schwann-cell-autonomous expression of Cx32 is sufficient to account for demyelination in CMT1X.
Collaboration of PSD-Zip70 with Its Binding Partner, SPAR, in Dendritic Spine Maturity
Authors: Maruoka Hisato , Konno Daijiro , Hori Kei , Sobue Kenji
Published: February 2005

Recent studies have reported on the molecular mechanisms underlying dendritic spine (spine) dynamics. Because most of these studies investigated spine dynamics by overexpressing constitutively active or dominant-negative PSD (postsynaptic density) proteins in cultured mature neurons, the results represent the enlargement of mature spines or their return to an immature state. Here, we developed the technique ofin uteroelectroporation to investigate spine dynamics. Using this technique, we demonstrated the suppression of spine maturation by the C-terminal variants of PSD-Zip70in vitroandin vivo. Transient overexpression of the C terminus of PSD-Zip70 and knock-down of PSD-Zip70 also displayed the destabilization of mature spines. We further found the PSD-Zip70 and SPAR (spine-associated RapGAP) interaction via the short C-terminal region of PSD-Zip70 and the GK-binding domain of SPAR. In association with immature spines induced by overexpression of the PSD-Zip70 C terminus or knock-down of PSD-Zip70, SPAR lost its spine localization. Overexpression of the GK-binding domain of SPAR also induced to form immature spines without affecting the localization of PSD-Zip70 in the small heads of filopodial spines. Our results suggest that PSD-Zip70 in collaboration with SPAR is critically involved in spine maturity, especially in the mature spine formation and the maintenance of spine maturity.
Thalamic Neuronal Activity in Dopamine-Depleted Primates: Evidence for a Loss of Functional Segregation within Basal Ganglia Circuits
Authors: Pessiglione Mathias , Guehl Dominique , Rolland Anne-Sophie , François Chantal , Hirsch Etienne C. , Féger Jean , Tremblay Léon
Published: February 2005

Different analyses of neuronal activity in primate models of Parkinson's disease (PD) have resulted in two different views on the effects of dopamine depletion. The first is based on the higher firing rate and bursty firing pattern, and assumes that dopamine depletion results in a hyperactivity of basal ganglia (BG) output structures. The second is based on the less-specific responses to passive joint manipulation and the excessive correlations between neuronal discharges, and assumes that dopamine depletion results in a loss of functional segregation in cortico-BG circuits. The aim of the present study was to test out the predictions of these two different views on thalamic neuronal activity. Three male vervet monkeys (Cercopithecus aethiops) were progressively intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal activities were characterized using standard analyses (firing rates and patterns, receptive fields, and cross-correlations) and compared between the normal, asymptomatic (before the stabilization of motor symptoms), and parkinsonian (with persistent akinesia and rigidity) stages of MPTP intoxication. The pallidonigral thalamus (receiving projections from the BG) was characterized in both the asymptomatic and parkinsonian states by (1) an unchanged firing rate and pattern and (2) a proliferation of nonspecific neurons and correlated pairs. In contrast, the cerebellar thalamus (receiving projections from the cerebellum), was characterized by no change (asymptomatic state) or minor changes (symptomatic state). Thus the major dysfunction after dopamine depletion appeared to be the loss of functional segregation within cortico-BG circuits, which could also be at the heart of parkinsonian pathophysiology.
Peri-Infarct Depolarizations Reveal Penumbra-Like Conditions in Striatum
Authors: Umegaki Masao , Sanada Yasuhiro , Waerzeggers Yannic , Rosner Gerhard , Yoshimine Toshiki , Heiss Wolf-Dieter , Graf Rudolf
Published: February 2005

Spreading depression-like peri-infarct depolarizations not only characterize but also worsen penumbra conditions in cortical border zones of experimental focal ischemia. We intended to investigate the relevance of ischemic depolarization in subcortical regions of ischemic territories.

Calomel electrodes measured DC potentials simultaneously in the lateral and medial portions of the caudate nucleus (CN) of 11 anesthetized cats after permanent occlusion of the middle cerebral artery. Additionally, platinum electrodes measured cerebral blood flow (CBF) in the CN, and laser Doppler probes CBF in the cortex.

Depolarizations (negative DC shifts >10 mV) were obtained in 10 of 11 cats. Further differentiation revealed that short-lasting spreading depression-like depolarizations (SDs; 5 of 10 cats: 5.24 ± 1.22 min total duration; 23.3 ± 4.2 mV amplitude) were predominantly found in medial and longer depolarizations (LDs; 4 of 10 cats: 64.7 ± 47.5 min; 25.0 ± 11.3 mV) in the lateral CN. Terminal depolarizations (TDs; 6 of 10 cats; without repolarization) occurred immediately after occlusion or at later stages, being then accompanied by elevations of intracranial pressure presumably inducing secondary CBF reduction. CBF tended to be lower in regions with TDs (33.3 ± 29.9% of control) and LDs (37.3 ± 22.8%) than in regions with SDs (51.5 ± 48.0%).

We conclude that in focal ischemia, transient peri-infarct depolarizations emerge not only in cortical but also in striatal gray matter, thereby demonstrating the existence of subcortical zones of ischemic penumbra. The generation of these ischemic depolarizations is a multifocal process possibly linked to brain swelling and intracranial pressure rise in the later course of focal ischemia, and therefore a relevant correlate of progressively worsening conditions.
Octopamine and Experience-Dependent Modulation of Aggression in Crickets
Authors: Stevenson Paul A. , Dyakonova Varya , Rillich Jan , Schildberger Klaus
Published: February 2005

Intraspecific aggression is influenced in numerous animal groups by the previous behavioral experiences of the competitors. The underlying mechanisms are, however, mostly obscure. We present evidence that a form of experience-dependent plasticity of aggression in crickets is mediated by octopamine, the invertebrate counterpart of noradrenaline. In a forced-fight paradigm, the experience of flying maximized the aggressiveness of crickets at their first encounter and accelerated the subsequent recovery of aggressiveness of the normally submissive losers, without enhancing general excitability as evaluated from the animals' startle responses to wind stimulation. This effect is transitory and concurrent with the activation of the octopaminergic system that accompanies flight. Hemocoel injections of the octopamine agonist chlordimeform (CDM) had similar effects on aggression but also enhanced startle responses. Serotonin depletion, achieved using α-methyl-tryptophan, enhanced startle responses without influencing aggression, indicating that the effect of CDM on aggression is not attributable to increased general excitation. Contrasting this, aggressiveness was depressed, and the effect of flying was essentially abolished, in crickets depleted of octopamine and dopamine using α-methyl-p-tyrosine (AMT). CDM restored aggressiveness in AMT-treated crickets, indicating that their depressed aggressiveness is attributable to octopamine depletion rather than to dopamine depletion or nonspecific defects. Finally, the flight effect was blocked in crickets treated with the octopamine receptor antagonist epinastine, or with the α-adrenoceptor and octopamine receptor antagonist phentolamine, but not with the β-adrenoceptor antagonist propranolol. The idea that activity-specific induction of the octopaminergic system underlies other forms of experience-dependent plasticity of aggressive motivation in insects is discussed.
Amygdalar Inactivation Blocks Stress-Induced Impairments in Hippocampal Long-Term Potentiation and Spatial Memory
Authors: Kim Jeansok J. , Koo Ja Wook , Lee Hongjoo J. , Han Jung-Soo
Published: February 2005

Electrolytic lesions to the amygdala, a limbic structure implicated in stress-related behaviors and memory modulation, have been shown to prevent stress-induced impairments of hippocampal long-term potentiation (LTP) and spatial memory in rats. The present study investigated the role of intrinsic amygdalar neurons in mediating stress effects on the hippocampus by microinfusing the GABAAreceptor agonist muscimol into the amygdala and examining stress effects on Schaffer collateral/commissural-CA1 LTP and spatial memory. The critical period of the amygdalar contribution to stress effects on hippocampal functions was determined by applying muscimol either before stress or immediately after stress. Our results indicate that intra-amygdalar muscimol infusions before uncontrollable restraint-tailshock stress effectively blocked stress-induced physiological and behavioral effects. Specifically, hippocampal slices prepared from vehicle-infused stressed animals exhibited markedly impaired LTP, whereas slices obtained from muscimol-infused stressed animals demonstrated robust LTP comparable with that of unstressed animals. Correspondingly, vehicle-infused stressed animals displayed impaired spatial memory (on a hidden platform version of the Morris water maze task), whereas muscimol-infused stressed animals revealed unimpaired spatial memory. In contrast to prestress muscimol effects, however, immediate poststress infusions of muscimol into the amygdala failed to interfere with stress impairments of LTP and spatial memory. Together, these results suggest that the amygdalar neuronal activity during stress, but not shortly after stress, is essential for the emergence of stress-induced alterations in hippocampal LTP and memory.
Alveolar Ridge Augmentation: A Comparative Longitudinal Study Between Calvaria and Iliac Crest Bone Grafts
Authors: Carinci Francesco , Farina Antonio , Zanetti Umberto , Vinci Raffaele , Negrini Stefano , Calura Giorgio , Laino Gregorio , Piattelli Adriano
Published: February 2005

Insertion of endosseous implants is often difficult because of lack of supporting bone. In the case of severe atrophy of the jaws, a large volume of autogenous bone can be harvested from the iliac crest and calvaria. Both grafts undergo partial resorption with time, but the rate of bone loss has not been fully elucidated. The aim of this study was to evaluate the alveolar bone height gain (ABHG) obtained with iliac crest and calvaria bone grafts. Twenty-five patients had mandibular bone grafts, 32 had maxillary bone grafts, and 11 had both mandibular and maxillary bone grafts. Measures were made on preoperative, postoperative, and follow-up radiographs. A general linear model was used to evaluate the rate of ABHG plotted against months elapsed from the time of the operation to the time of follow-up. General linear model output showed a statistically significant effect for only the type of donor bone graft (P = .004), with a better ABHG for calvaria. The iliac crest bone grafts lost most of the ABHG in the first 6 months, whereas calvaria bone grafts lost ABHG over a greater interval of time. The type of bone graft is the strongest predictor of ABHG, and calvaria bone graft had a higher stability than did iliac bone graft. However, the gap in ABHG between the 2 grafts tended to decrease over time.
Bone Remodeling in Immediately Loaded and Unloaded Titanium Dental Implants: A Histologic and Histomorphometric Study in Humans
Authors: Degidi Marco , Scarano Antonio , Piattelli Maurizio , Perrotti Vittoria , Piattelli Adriano
Published: February 2005

Remodeling is thought to prevent microdamage accumulation caused by repetitive loading and to increase the fatigue life of bone. The bone remodeling rate (BRR) is the period of time needed for new bone to replace the existing bone and to allow for the adaptation of bone to its environment. BRR is expressed as a percentage or volume of new bone within a specific time period. The aim of the present study was to evaluate bone remodeling events on submerged and immediately loaded dental implants. Twelve patients with edentulous mandibles participated in this study. All patients were rehabilitated with fixed mandibular prostheses, with 10 dental implants per patient. An additional implant was inserted in the most distal posterior mandibular jaw region. In 6 patients, these additional implants were loaded with a fixed provisional prosthesis the same day of the implant surgery and loaded. In the other 6 patients, the additional implants were left submerged and not loaded. After 6 months, all the additional implants were retrieved with a trephine. The percentage of woven and lamellar bone, number of osteoclasts and osteoblasts, and percentage of bone labeled by tetracycline at 0.5 mm and 2 mm from the implant surface were evaluated. The percentage of lamellar bone, number of osteoblasts, and percentage of bone tetracycline labeling was significantly higher in the loaded implants than in the unloaded implants (P = .0001). Also in the loaded implants, the percentage of woven and lamellar bone, number of osteoclasts and osteoblasts, and percentage of bone tetracycline labeling was significantly higher at 0.5 mm than at 2 mm from the implant surface (P = .0001). No such differences were found in unloaded implants (P = .377). In conclusion, we found that (1) loading appeared to stimulate bone remodeling at the interface, (2) a higher percentage of lamellar bone was found in loaded implants, (3) the percentage of bone labeling was higher at the interface of loaded implants, (4) no differences were found in the BRRs between immediately loaded and unloaded implants, and (5) immediate loading had not interfered on the lamellar bone formation at the interface and had not produced formation of woven bone at the interface.
A 7-year Follow-up of 93 Immediately Loaded Titanium Dental Implants
Authors: Degidi Marco , Piattelli Adriano
Published: February 2005

Recently, several experimental and clinical investigations found that immediately loaded implants obtained satisfactory levels of osseointegration with high success percentages. Only a few long-term studies of immediately loaded implants have been reported in the literature. The aim of this study was a 7-year clinical and radiographic follow-up of 93 immediately loaded dental implants in human patients. Eleven patients were consecutively enrolled in this study. A total of 7 full and 9 partial edentulous arches were rehabilitated. Patients presented a completely edentulous mandible (n = 6), a completely edentulous maxilla (n = 1), mandibular posterior edentulous areas (n = 5), or a posterior maxillary edentulous area (n = 1). Patients were rehabilitated with a bar and an overdenture (n = 4), a provisional prosthesis of 3 to 12 elements (n = 11), or a metal-ceramic bridge of 10 elements (n = 1). A total of 93 implants were inserted and loaded within a 24-hour time frame. Six implants failed in the first year after loading. No more failures were observed in the following 6 years, and all the other implants were well integrated from a clinical and radiographic point of view. The cumulative success rate at 7 years was 93.5%, and the prostheses survival rate was 98.5%. The mean marginal bone loss was 0.6 mm after the first year and 1.1 mm at the 7-year evaluation. Primary stability is one of the most important parameters in immediately loaded implants because it avoids micromotion at the bone-implant interface. Four of the 6 failures in our patients occurred in partially edentulous patients; an excessive load applied to these small bridges could be the reason for the failure. Also, the bone quality is important, for 3 of our failed implants had been inserted in D3 bone. Our clinical and radiographic results have shown that these immediately loaded implants have remained osseointegrated for a long period. Our results point to the possibility of using the immediate loading technique in selected and well-informed cases.
Comparing faculty information seeking in teaching and research: Implications for the design of digital libraries
Authors: Borgman Christine L. , Smart Laura J. , Millwood Kelli A. , Finley Jason R. , Champeny Leslie , Gilliland Anne J. , Leazer Gregory H.
Published: February 2005

ADEPT is a 5‐year project whose goals are to develop, deploy, and evaluate inquiry learning capabilities for the Alexandria Digital Library, an extant digital library of primary sources in geography. We interviewed nine geography faculty members who teach undergraduate courses about their information seeking for research and teaching and their use of information resources in teaching. These data were supplemented by interviews with four faculty members from another ADEPT study about the nature of knowledge in geography. Among our key findings are that geography faculty are more likely to encounter useful teaching resources while seeking research resources than vice versa, although the influence goes in both directions. Their greatest information needs are for research data, maps, and images. They desire better searching by concept or theme, in addition to searching by location and place name. They make extensive use of their own research resources in their teaching. Among the implications for functionality and architecture of geographic digital libraries for educational use are that personal digital libraries are essential, because individual faculty members have personalized approaches to selecting, collecting, and organizing teaching resources. Digital library services for research and teaching should include the ability to import content from common office software and to store content in standard formats that can be exported to other applications. Digital library services can facilitate sharing among faculty but cannot overcome barriers such as intellectual property rights, access to proprietary research data, or the desire of individuals to maintain control over their own resources. Faculty use of primary and secondary resources needs to be better understood if we are to design successful digital libraries for research and teaching.
parva germina, a gene involved in germ cell maintenance during male and female Drosophila gametogenesis
Authors: Riparbelli Maria Giovanna , Inoue Yoshihiro , Glover David M. , Callaini Giuliano
Published: February 2005

We report the initial characterization of a gene, parva germina (pag), required for germ cell maintenance in both males and females. pag gonads contain a small number of germline stem cells at the onset of gametogenesis. In contrast, adult mutant gonads are either empty or have a very small number of germ cells that never develop in 16‐cell cysts. Ovarioles and testes, therefore, are rudimentary, and the very few germ cells they contain are unable to differentiate into eggs or sperm. Germline stem cells are progressively depleted over time. The average number of germ cells, therefore, decreases in pag mutant ovarioles with the age of the mother, whereas the proportion of agametic germaria goes up. These observations suggest that the pag gene product is involved in germ cell maintenance in both male and female gametogenesis. Developmental Dynamics 232:835–844, 2005. © 2005 Wiley‐Liss, Inc.
Interactions between the Notch, EGFR, and decapentaplegic signaling pathways regulate vein differentiation during Drosophila pupal wing development
Authors: Sotillos Sol , De Celis Jose F.
Published: February 2005

The formation of longitudinal veins in the Drosophila wing involves cell interactions mediated by the conserved signaling pathways Decapentaplegic (Dpp), Notch, and epidermal growth factor receptor (EGFR). Interactions between Notch and EGFR taking place in the wing disc divide each vein into a central domain, where EGFR is active, and two boundary domains where Notch is active. The expression of decapentaplegic (dpp) is activated in the veins during pupal development, and we have generated Gal4 drivers using the regulatory region that drives dpp expression at this stage. By using these drivers, we studied the relationships between the Notch, EGFR, and Dpp signaling pathways that occur during pupal development. Our results indicate that the interactions between EGFR and Notch initiated in the imaginal disc are maintained throughout pupal development and contribute to determine the places where dpp is expressed. Once dpp expression is initiated, Dpp and EGFR activities in the provein maintain each other and, in cooperation, determine vein cell differentiation. Developmental Dynamics 232:738–752, 2005. © 2005 Wiley‐Liss, Inc.
L1 augments cell migration and tumor growth but not β3 integrin expression in ovarian carcinomas
Authors: Gast Daniela , Riedle Svenja , Riedle Svenja , Schabath Heidi , Schlich Sabine , Schneider Annette , Issa Yasmin , Stoeck Alexander , Fogel Mina , Joumaa Safwan , Wenger Till , Herr Ingrid , Gutwein Paul , Altevogt Peter
Published: February 2005

L1 is a neural cell adhesion molecule involved in cell migration, axon growth and guidance. Recent data have shown that L1 is overexpressed in ovarian and endometrial tumors and is associated with bad prognosis. How L1 promotes tumor progression is presently unknown. Here we show that L1 expression is predominantly confined to the invasive front of ovarian carcinomas. Overexpression of L1 in carcinoma cell lines by adenovirus‐mediated gene transfer enhanced the haptotactic cell migration on extracellular matrix proteins. Expression of L1 augmented tumor growth of carcinomas xenografted in nonobese diabetic/severe combined immunodeficient mice (NOD/SCID). A recent report has demonstrated L1‐dependent upregulation of β3 integrin involving activation of the extracellular signal‐regulated kinase (erk) pathway. We find that L1 and β3 integrin are not coexpressed in ovarian carcinoma tissues. Overexpression of L1 did not upregulate β3 integrin in ovarian carcinoma cell lines but could do so in HEK293 cells. Our results suggest that L1 could drive progression by enhancing cell migration and tumor growth but that L1 dependent and erk‐regulated gene expression requires cell‐type specific elements. © 2005 Wiley‐Liss, Inc.
IL1RN polymorphic gene and cagA‐positive status independently increase the risk of noncardia gastric carcinoma
Authors: Rocha Gifone Aguiar , Guerra Juliana Becattini , Rocha Andreia Maria Camargos , Saraiva Ivan Euclides Borges , da Silva Deborah Alves , de Oliveira Celso Affonso , Queiroz Dulciene Maria Magalhães
Published: February 2005

Helicobacter pylori cagA‐positive strains and host cytokine proinflammatory polymorphisms have been associated with gastric carcinoma. However, the individual role of each factor has not been evaluated yet. Our aim was to evaluate whether IL‐1 gene cluster and tumor necrosis factor‐α (TNFA)‐307 polymorphisms, as well as cagA‐positive status, are associated with gastric carcinoma in a non‐Caucasian population by analyzing the data in logistic regression models. We evaluated 166 patients with noncardia gastric carcinoma and 541 blood donors. Among them, 702 were successfully genotyped for all cytokine studied: 166 with gastric carcinoma and 536 controls. The carcinoma patients were considered to be H. pylori‐positive if culture alone or 2 among preformed urease test, stained smear or histologic section, serology, polymerase chain reaction (PCR) for ureA and urea breath test were positive. In blood donors, H. pylori status was based on enzyme‐linked immunosorbent assay. The cagA status was determined by PCR or serology. IL1B‐511/‐31, IL1RN (interleukin‐1 receptor antagonist) and TNFA‐307 polymorphisms were genotyped by PCR, PCR with restriction fragment length polymorphism, or PCR with confronting 2‐pair primers. We found that the IL1RN2 polymorphic allele (OR = 1.93) was associated with noncardia gastric carcinoma, even after inclusion of age, gender and cagA status in the logistic models. However, the cagA‐positive status was the strongest independent factor associated with gastric carcinoma (OR = 11.89). The other polymorphisms were not significantly associated with the disease when they were evaluated in logistic models. This study provides evidence supporting the independent associations of cagA‐positive H. pylori status and IL1RN polymorphisms with noncardia gastric carcinoma. © 2005 Wiley‐Liss, Inc.
Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas
Authors: Körner Meike , Waser Beatrice , Reubi Jean Claude
Published: February 2005

Numerous peptide receptors are overexpressed in human cancer, permitting in vivo tumor targeting. Among such receptors, those for the neurotransmitter neuropeptide Y (NPY) are overexpressed in various tumors. Since NPY can play a role in the kidney, NPY receptor expression and/or endogenous production of peptides of the NPY family (NPY, PYY, PP) were evaluated in 40 renal cell carcinomas (RCCs) and 18 nephroblastomas. NPY receptor protein expression was investigated by in vitro autoradiography using 125I‐labeled PYY in competition with NPY receptor subtype‐selective analogs. NPY, PYY and PP production was assessed immunohistochemically. Fifty‐six percent of RCCs expressed the Y1 receptor subtype in moderate density, and 80% of nephroblastomas expressed Y1 and Y2 subtypes in moderate to high density. Y1 was also highly expressed in intratumoral blood vessels. In selected cases, NPY was observed in nerve fibers in close association with intratumoral blood vessels and in the vicinity of tumor cells, while no PYY or PP was detected immunohistochemically in these sites. NPY receptors on renal tumor cells and tumor blood vessels may therefore be the molecular targets of endogenous NPY released by intratumoral nerve fibers. With regard to clinical applications, NPY receptors may act as in vivo targets for receptor‐directed therapy of RCCs and nephroblastomas for which alternative therapeutic approaches are still required. © 2005 Wiley‐Liss, Inc.
D. Liu and X. Zhu, Erratum to: “Fractional chromatic number and circular chromatic number for distance graphs with large clique size”. Journal of Graph Theory47(2) 2004, 129–146
Authors: Liu Daphne Der‐Fen , Zhu Xuding
Published: February 2005

The original article to which this Erratum refers was published in Journal of Graph Theory 47:129–146,2004.