bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor‐α
Authors: Sriram Krishnan , Miller Diane B. , O'Callaghan James P. 
Published: January 2006

AbstractActivated microglia are implicated in the pathogenesis of disease‐, trauma‐ and toxicant‐induced damage to the CNS, and strategies to modulate microglial activation are gaining impetus. A novel action of the tetracycline derivative minocycline is the ability to inhibit inflammation and free radical formation, factors that influence microglial activation. Minocycline is therefore being tested as a neuroprotective agent to alleviate CNS damage, although findings so far have yielded mixed results. Here, we showed that administration of a single low dose of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) or methamphetamine (METH), a paradigm that causes selective degeneration of striatal dopaminergic nerve terminals without affecting the cell body in substantia nigra, increased the expression of mRNAs encoding microglia‐associated factors F4/80, interleukin (IL)‐1α, IL‐6, monocyte chemoattractant protein‐1 (MCP‐1, CCL2) and tumor necrosis factor (TNF)‐α. Minocycline treatment attenuated MPTP‐ or METH‐mediated microglial activation, but failed to afford neuroprotection. Lack of neuroprotection was shown to be due to the inability of minocycline to abolish the induction of TNF‐α and its receptors, thereby failing to modulate TNF signaling. Thus, TNF‐α appeared to be an obligatory component of dopaminergic neurotoxicity. To address this possibility, we examined the effects of MPTP or METH in mice lacking genes encoding IL‐6, CCL2 or TNF receptor (TNFR)1/2. Deficiency of either IL‐6 or CCL2 did not alter MPTP neurotoxicity. However, deficiency of both TNFRs protected against the dopaminergic neurotoxicity of MPTP. Taken together, our findings suggest that attenuation of microglial activation is insufficient to modulate neurotoxicity as transient activation of microglia may suffice to initiate neurodegeneration. These findings support the hypothesis that TNF‐α may play a role in the selective vulnerability of the nigrostriatal pathway associated with dopaminergic neurotoxicity and perhaps Parkinson's disease.
Presenilin clinical mutations can affect γ‐secretase activity by different mechanisms
Authors: Bentahir Mostafa , Nyabi Omar , Verhamme Jan , Tolia Alexandra , Horré Katrien , Wiltfang Jens , Esselmann Hermann , De Strooper Bart 
Published: January 2006

AbstractMutations in human presenilin (PS) genes cause aggressive forms of familial Alzheimer's disease. Presenilins are polytopic proteins that harbour the catalytic site of the γ‐secretase complex and cleave many type I transmembrane proteins including β‐amyloid precursor protein (APP), Notch and syndecan 3. Contradictory results have been published concerning whether PS mutations cause ‘abnormal’ gain or (partial) loss of function of γ‐secretase. To avoid the possibility that wild‐type PS confounds the interpretation of the results, we used presenilin‐deficient cells to analyse the effects of different clinical mutations on APP, Notch, syndecan 3 and N‐cadherin substrate processing, and on γ‐secretase complex formation. A loss in APP and Notch substrate processing at ɛ and S3 cleavage sites was observed with all presenilin mutants, whereas APP processing at the γ site was affected in variable ways. PS1‐Δ9 and PS1‐L166P mutations caused a reduction in β‐amyloid peptide (Aβ)40 production whereas PS1‐G384A mutant significantly increased Aβ42. Interestingly PS2, a close homologue of PS1, appeared to be a less efficient producer of Aβ than PS1. Finally, subtle differences in γ‐secretase complex assembly were observed. Overall, our results indicate that the different mutations in PS affect γ‐secretase structure or function in multiple ways.
O6‐methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells
Authors: Hermisson Mirjam , Klumpp Andrea , Wick Wolfgang , Wischhusen Jörg , Nagel Georg , Roos Wynand , Kaina Bernd , Weller Michael 
Published: January 2006

AbstractTemozolomide (TMZ) is a methylating agent which prolongs survival when administered during and after radiotherapy in the first‐line treatment of glioblastoma and which also has significant activity in recurrent disease. O6‐methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme attributed a role in cancer cell resistance to O6‐alkylating agent‐based chemotherapy. Using a panel of 12 human glioma cell lines, we here defined the sensitivity to TMZ in acute cytotoxicity and clonogenic survival assays in relation to MGMT, mismatch repair and p53 status and its modulation by dexamethasone, irradiation and BCL‐XL. We found that the levels of MGMT expression were a major predictor of TMZ sensitivity in human glioma cells. MGMT activity and clonogenic survival after TMZ exposure are highly correlated (p < 0.0001,r2 = 0.92). In contrast, clonogenic survival after TMZ exposure does not correlate with the expression levels of the mismatch repair proteins mutS homologue 2, mutS homologue 6 or post‐meiotic segregation increased 2. The MGMT inhibitor O6‐benzylguanine sensitizes MGMT‐positive glioma cells to TMZ whereas MGMT gene transfer into MGMT‐negative cells confers protection. The antiapoptotic BCL‐XLprotein attenuates TMZ cytotoxicity in MGMT‐negative LNT‐229 but not in MGMT‐positive LN‐18 cells. Neither ionizing radiation (4 Gy) nor clinically relevant concentrations of dexamethasone modulate MGMT activity or TMZ sensitivity. Abrogation of p53 wild‐type function strongly attenuates TMZ cytotoxicity. Conversely, p53 mimetic agents designed to stabilize the wild‐type conformation of p53 sensitize glioma cells for TMZ cytotoxicity. Collectively, these results suggest that the determination of MGMT expression and p53 status will help to identify glioma patients who will or will not respond to TMZ.
Interleukin‐1 beta‐induced expression of the prostaglandin E2‐receptor subtype EP3 in U373 astrocytoma cells depends on protein kinase C and nuclear factor‐kappaB
Authors: Waschbisch Anne , Fiebich Bernd L. , Akundi Ravi Shankar , Schmitz M. Lienhard , Hoozemans Jeroen J. M. , Candelario‐Jalil Eduardo , Virtainen Nina , Veerhuis Robert , Slawik Helen , Yrjänheikki Juha , Hüll Michael 
Published: January 2006

AbstractBoth interleukin‐1β (IL‐1β) and prostaglandins (PGs) are important mediators of physiological and pathophysiological processes in the brain. PGE2 exerts its effects by binding to four different types of PGE2 receptors named EP1–EP4. EP3 has found to be expressed in neurons, whereas expression of EP3 in glial cells has not been reported in the brain yet. Here we describe IL‐1β‐induced EP3 receptor expression in human astrocytoma cells, primary astrocytes of rat and human origin and in rat brain. Using western blot, we found a marked up‐regulation of EP3 receptor synthesis in human and rat primary glial cells. Intracerebroventricular administration of IL‐1β stimulated EP3 receptor synthesis in rat hippocampus. The analysis of involved signal transduction pathways by pathway‐specific inhibitors revealed an essential role of protein kinase C and nuclear factor‐κB in astrocytic IL‐1β‐induced EP3 synthesis. Our data suggest that PGE2 signaling in the brain may be altered after IL‐1β release due to up‐regulation of EP3 receptors. This might play an important role in acute and chronic conditions such as cerebral ischemia, traumatic brain injury, HIV‐encephalitis, Alzheimer's disease and prion diseases in which a marked up‐regulation of IL‐1β is followed by a prolonged increase of PGE2 levels in the brain.
Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease
Authors: Colom Luis V. 
Published: January 2006

AbstractInformation processing and storing by brain networks requires a highly coordinated operation of multiple neuronal groups. The function of septal neurons is to modulate the activity of archicortical (e.g. hippocampal) and neocortical circuits. This modulation is necessary for the development and normal occurrence of rhythmical cortical activities that control the processing of sensory information and memory functions. Damage or degeneration of septal neurons results in abnormal information processing in cortical circuits and consequent brain dysfunction. Septal neurons not only provide the optimal levels of excitatory background to cortical structures, but they may also inhibit the occurrence of abnormal excitability states.
Computed Tomographic Evaluation of Canine Radioulnar Incongruence In Vivo
Authors: KRAMER ALON , HOLSWORTH IAN G. , WISNER ERIK R. , KASS PHILLIP H. , SCHULZ KURT S. 
Published: January 2006

Objective—To compare radioulnar incongruence (RUI) of normal canine elbows and elbows with arthroscopically confirmed medial compartment disease in vivo using systematic computed tomography (CT) measurements.Study Design—Prospective comparison of RUI measurements in normal and dysplastic canine elbows.Sample Population—Right elbows of 25 medium–large breed, adult dogs with medial compartment disease and 9 medium–large breed, adult dogs with no elbow disease.Methods—Transverse CT images of proximal radioulnar articulation were reformatted to dorsal and sagittal planes. RUI in 3 locations of the forelimb's medial coronoid was measured. Arthroscopy confirmed diagnosis of medial compartment disease in the diseased group. RUI measurements of the diseased and normal elbows were compared.Results—Cumulative statistical analysis of RUI in all planes revealed no significant difference between the normal and abnormal elbows (P=.61). The abnormal elbows had negative mean RUI at the mid (P=.56) and cranial (P=.24) coronoid regions that were not significantly different from normal elbows and mean positive RUI at the base coronoid that was significantly greater than in normal elbows (P=.00082).Conclusion—Canine elbows with established medial compartment disease do not have significant RUI at the medial coronoid region at the time of diagnosis when compared with normal elbows.Clinical Relevance—If RUI is a significant factor in the pathophysiology of medial compartment elbow disease in the dog, it does not appear to be present at the time of diagnosis of disease. Ulnar or radial osteotomies do not appear to be indicated for restoration of normal radioulnar articular surface alignment.
In Vitro Comparison of Two Techniques for Suture Prosthesis Placement in the Muscular Process of the Equine Arytenoid Cartilage
Authors: ROSSIGNOL FABRICE , PERRIN ROLAND , DESBROSSE FRANCIS , ELIE CAROLINE 
Published: January 2006

Objective—To compare in vitro the load necessary for a partial and complete rupture of the muscular process arytenoid cartilage when a suture prosthesis is positioned by a bone trocar versus a trocar point needle and to compare failure mode.Study Design—Experimental using cadaver specimens.Sample Population—Larynges from 18 Thoroughbred race horses, aged 2–20 years.Methods—Arytenoid cartilages were separated randomly into 2 groups: group 1—suture prosthesis inserted directly through the muscular process using a curved trocar point needle and group 2—suture passed through a hole predrilled with a 3 mm bone trocar. Distracting force (constant rate, 1 mm/s) was applied to the suture until failure of the muscular process. Partial failure load, maximum load at complete failure, and force–time curve were recorded. Each arytenoid cartilage was examined, radiographed, and classified as having a linear or curved failure plane.Results—No significant differences in mechanical test variables were detected. Failure mode followed the fissures occurring at the beginning of failure and then followed the tension axis. Significantly more linear failures occurred in group 2 (trocar) and more curved failures occurred in group 1 (needle).Conclusion—Use of a bone trocar for tunneling through the muscular process may reduce fissure formation.Clinical Relevance—Use of bone trocar to create a hole in the muscular process of the arytenoid cartilage for suture passage in laryngoplasty may reduce fissure formation and decrease the risk of cartilage failure from suture pullout.
Prosthetic treatment of maxillary lateral incisor agenesis with osseointegrated implants: a 24–39‐month prospective clinical study
Authors: Zarone Fernando , Sorrentino Roberto , Vaccaro Francesco , Russo Simona 
Published: January 2006

AbstractObjectives: The present study aimed at evaluating the marginal bone resorption and the peri‐implant tissue conditions around Narrow‐Neck ITI implants in the implant–prosthetic treatment of the agenesis of maxillary lateral incisors.Material and methods: Thirty patients affected by monolateral or bilateral agenesis of the maxillary lateral incisors were selected. Thirty‐four ITI‐SLA Narrow Neck implants were inserted and loaded about 4 months after the surgical procedure. The final restorations were realized using Aureo Galvan Crowns veneered with feldspathic ceramics. The follow‐up period ranged from 24 to 39 months. Both marginal bone resorption and soft tissue quality were evaluated. The data were statistically analysed using analysis of variance (ANOVA) for repeated measures, one‐way ANOVA and Tukey's post hoc test (P=0.05).Results: During the 24–39‐month follow‐up period, no implant showed either pain and sensitivity or mobility. After 39 months of functional loading, a cumulative survival rate of 97.06% and a cumulative success rate of 94.12% were calculated.Conclusions: In case of maxillary lateral incisor agenesis, the implant–prosthetic approach has proved to be a reliable and predictable treatment for both re‐establishment of function and aesthetics. Satisfactory values of marginal bone resorption over time and optimal conditions of peri‐implant tissue around Narrow‐Neck ITI implants were found.
The Nested Superblock Approach for Regional‐Scale Analytic Element Models
Authors: Craig James R. , Janković Igor , Barnes Randal 
Published: January 2006

AbstractA new approach is presented for improving the computational efficiency of regional‐scale ground water models based on the analytic element method (AEM). The algorithm is an extension of the existing “superblock” algorithm, which combines the effects of multiple analytic elements into Laurent series and Taylor series (superblock expansions). With the new “nested superblock” formulation, Laurent series are nested in a hierarchical (quad‐tree) data structure with direct mathematical relationships between parent and child superblock coefficients. Nested superblocks significantly accelerate the evaluation of the complex potential and discharge function in models that contain a large number of analytic elements at multiple scales. This evaluation process, the primary computational cost of AEM models, is required to determine the element coefficients, generate contour plots, and trace pathlines. The performance of the nested superblocks is demonstrated with a simplified model based on the Lake Ontario watershed geometry comprising thousands of hydrogeologic features at multiple geographic scales.
Ground Water Modeling Applications Using the Analytic Element Method
Authors: Hunt Randall J. 
Published: January 2006

AbstractThough powerful and easy to use, applications of the analytic element method are not as widespread as finite‐difference or finite‐element models due in part to their relative youth. Although reviews that focus primarily on the mathematical development of the method have appeared in the literature, a systematic review of applications of the method is not available. An overview of the general types of applications of analytic elements in ground water modeling is provided in this paper. While not fully encompassing, the applications described here cover areas where the method has been historically applied (regional, two‐dimensional steady‐state models, analyses of ground water–surface water interaction, quick analyses and screening models, wellhead protection studies) as well as more recent applications (grid sensitivity analyses, estimating effective conductivity and dispersion in highly heterogeneous systems). The review of applications also illustrates areas where more method development is needed (three‐dimensional and transient simulations).
The Synergistic Powers of AEM and GIS Geodatabase Models in Water Resources Studies
Authors: Steward David R. , Bernard Eric A. 
Published: January 2006

AbstractComprehensive studies of water resources systems require integration of modeling tools and data associated with individual processes. An object‐oriented approach is presented here that associates ground water models based upon the analytic element method (AEM) with geographic information system (GIS) geodatabase features using an AEM Model Interface. Each aquifer object contains a prescribed geometry, a mathematical representation in the AEM, and GIS hydrogeologic data. The synergistic understanding inherent in such an approach is illustrated by a study linking local AEM model predictions of water elevation with ground water geodatabase objects. This AEM Model Interface provides a key component in establishing a common object‐oriented geodatabase modeling approach linking ground water to a variety of natural and social processes.
A preliminary nonlinear analysis of the earth′s chandler wobble
Authors: Frede V. , Mazzega P. 
Published: January 2006

The Chandler wobble (CW) is a resonant response of the Earth rotational pole wandering around its figure axis whose excitation mechanism is still uncertain. It appears as polar motion oscillations with an average period of about 433 days and a slowly varying amplitude in the range (0–300) milliarcsec (mas). We here perform a nonlinear analysis of the CW via a time‐delay coordinate embedding of its measured X and Y components and show that the CW can be interpreted as a low dimensional unstable deterministic process.In a first step the trend, annual wobble and CW are separated from the raw polar motion data time series spanning the period 1846–1997. The optimal delays as deduced from the average mutual information function are 105 and 115 days for the X and Y components respectively. Then from the global statistics of the false neighbours, the embedding dimension DE = 4 is estimated for both series. The local dimension DL can also be extracted from the time series by testing the predictive skill of local mappings fitted to the embedded data vectors. The result DL = 3 is quite robust and corroborate the idea that the CW behaves like a dissipative oscillator driven by a deterministic process. Indeed the orbit reconstructions in pseudo‐phase space both draw the figure of a perturbated 1‐torus.The computation of the Lyapunov spectra further shows that this torus‐like figure is an attractor with a 1D unstable manifold. The theoretical horizons of prediction deduced from the (positive) principal exponents are about 367 and 276 days for the X and Y Chandler components respectively. Moreover the local Lyapunov exponents exhibit significant variations with maxima (and corresponding losses of predictibility) in the decades 1860–1870 and 1940–1950.
Monitoring the complexity of ventricular response in atrial fibrillation
Authors: Käsmacher H. , Wiese S. , Lahl M. 
Published: January 2006

Atrial fibrillation does not present a uniform extent of variability of the ventricular response exemplifying periodicities and more complex fluctuations, due to varying number and shape of atrial wavelets and aberrant conduction in the AV‐junction. It was sought to categorise different degrees of complexity introducing an uncomplicated monitoring method for that
objective.The fluctuation of RR‐intervals was investigated in 66 patients presenting with atrial fibrillation at different times of the day using conventional statistical methods as well as methods derived from non‐linear dynamics. Specifically Poincaré‐plots were employed to analyse the data. One hundred and seventy data sets consisting of 5000–8000 intervals each were considered.Statistical methods were shown to describe the observed dynamics not adequately due to background noise in the acquired data as well as owing to intrinsic qualities of the data sets. Namely non‐uniformly distributed data and trends within the data sets constituted limitations of statistical methods.Poincaré‐plots were proven to be an inexpensive and effective method to categorise the complexity of the ventricular response in atrial fibrillation. Periodical variation of interval lengths could be clearly differentiated from continuous variation in the considered data sets. The latter could be shown to exemplify either stochastic fluctuation or complex non‐linear dynamics of RR‐interval variation. Thus, different degrees of complexity could be clearly distinguished.It could be shown exemplary that the observed dynamics remained nearly constant within the observation period.Poincaré‐plots, thus, provide a means to appreciate the fluctuation of RR‐intervals semiquantitatively and to distinguish different patterns of fluctuation dynamics of the ventricular response in atrial fibrillation without being affected by contaminated or inconsistent data.For a complete visualisation of the concerned dynamics relatively small data sets suffice. Thus, it is possible to observe the pattern of fluctuation essentially in real time which makes them ideally suited for future investigation.
Rationals, periodicity and chaos: A Pythagorean view and a conjecture into socio‐spatial dynamics
Authors: Dendrinos Dimitrios S. 
Published: January 2006

Deep in the fascinating world of numbers there still might lurk useful insights into the processes of the socio‐spatial world. A rich section of the world of numbers is of course Number Theory and its pantheon of findings, a part of which is revisited here.It is suggested in this note that a smooth sequence of seemingly random periodic cycles hides the absence of chaotic dynamics in the sequence. Put differently, a seemingly chaotic sequence of periodic cycles, no matter the bandwidth, implies absence of chaotic motion at any point in the sequence; and conversely, the presence of chaotic motion at any specific point in the sequence implies smooth sequence of periodic cycles at any point in the sequence prior to the onset of quasi periodic or chaotic motions.To make this conjecture, the paper draws material from the well known property of rational numbers in Number Theory, namely that the division of unity by any integer will always produce a sequence of decimals in some form of periodicity. The conjecture is taken in a liberally interpreted “Pythagorean type” context, whereby a general principle is suggested to be present in all natural or social systems dynamics. Thus, the paper′s subtitle.
Quasi‐discreted dynamics of a neural net: The lighthouse model
Authors: Haken Hermann 
Published: January 2006

This paper studies the features of a net of pulse‐coupled model neurons, taking into account the dynamics of dendrites and axons. The axonal pulses are modelled by δ‐functions. In the case of small damping of dendritic currents, the model can be treated exactly and explicitly. Because of the δ‐functions, the phase‐equations can be converted into algebraic equations at discrete times. We first exemplify our procedure by two neurons, and then present the results for N neurons. We admit a general dependence of input and coupling strengths on the
neuronal indices. In detail, the results are(1) exact solution of the phase‐locked state;(2) stability of phase‐locked state with respect to perturbations, such as phase jumps and
random fluctuations, the correlation functions of the phases are calculated;(3) phase shifts due to spontaneous opening of vesicles or due to failure of opening;(4) effect of different sensory inputs on axonal pulse frequencies of coupled neurons.