bluuebunny/crossref_metadata_2025 huggingface dataset:
Language, Articulation, Voice and Resonance Characteristics in 4 Children with Goldenhar Syndrome: A Pilot Study
Authors: van Lierde Kristiane M. , van Cauwenberge Paul , Stevens Ines , Dhooge Ingeborg
Published: April 2004

The purpose of this study was to describe the language, articulation, voice and resonance characteristics in children with Goldenhar syndrome. The 4 Dutch-speaking subjects were 2 boys (age 4.5 and 10.2 years) and 2 girls (aged 5.0 and 5.4 years) with normal cognitive functioning. Language testing showed a delay in the development of morphosyntactic abilities. Speech analysis showed that these four children were capable of producing all the sounds of their mother tongue. One type of distortion error, namely dentalization, was found in 2 children. Phonological process analysis revealed the persistence of processes such as final consonant deletion, unstressed syllable deletion and cluster reduction, which are normal in young children but are suppressed with maturation. Also the substitution process of devoicing was observed in these 4 children. It is not clear how the speech and language problems demonstrated in these 4 children are to be explained. It must be taken into consideration that the Goldenhar syndrome has a variable expression. It is possible that the presence of a mandibular defect, hearing impairment, the type and severity of palatal abnormality and decreased linguistic processing skills influence articulation in an individual child. The voices of 2 children were characterized by the presence of slight roughness, corresponding with a higher jitter percentage. How the occurrence of the hoarse voices is to be explained is not quite clear. Laryngoscopic evaluation of the vocal folds showed no organic or functional voice disorder. Regarding resonance, only the child with a cleft palate showed hypernasality and nasal emission. The ENT specialist and the speech-language pathologist must be aware of these communication disorders in order to start preventive and early ‘tailor-made’ speech and language intervention as soon as possible.
Der Einfluss der grossen Verbinder von zahnärztlichen Teilprothesen auf die Lautbildung
Authors: Hörschgen J. , Wisser W. , Berger R. , Lotzmann U.
Published: April 2004

In der zahnmedizinischen Teilprothetik zur Versorgung des Lückengebisses wird die Lautbildung durch viele Variablen beeinflusst, deren Auswirkungen im Einzelnen noch weitgehend unbekannt sind. Ziel dieser Untersuchung war es, den Einfluss von verschiedenen Konstruktionselementen von Ober- und Unterkieferteilprothesen auf die Bildung der Plosiv-, Nasal-, Lateral- und Frikativlaute zu untersuchen. Für jeden der 24 Probanden wurden 5 verschiedene Testprothesen hergestellt. Jeder Proband trug seine Testprothesen jeweils 6 h. Es erfolgten 6 digitale Sprachaufnahmen je Testprothese zu verschiedenen Zeitpunkten des Untersuchungszeitraumes von 24 h. Über eine rechnergestützte Frequenzanalyse nach dem Prinzip der schnellen Fouriertransformation (FFT) war es möglich, Unterschiede in der Lautbildung der untersuchten Konsonanten als Folge der jeweils getragenen Testprothese objektiv und reproduzierbar nachzuweisen. Ausserdem wurden während der Untersuchung Daten zum Tragekomfort und zur subjektiven Lautbildung der Testprothesen erhoben. Die Studie belegt unter anderem einen unerwartet grossen Einfluss des Sublingualbügels auf die Lautbildung. Der Sprecher versucht, gewohnte Artikulationsmuster trotz eingesetzter Testprothese zunächst aktiv beizubehalten. Eine Sprechprobe direkt nach der Eingliederung einer neu angefertigten zahnmedizinischen Teilprothese ist daher für die endgültige Beurteilung der Lautbildung vorsichtig zu interpretieren. Aufgrund der Ergebnisse können Empfehlungen für die zahnärztliche Therapie gegeben werden.
Voice Onset Time Production in Older and Younger Female Monozygotic Twins
Authors: Ryalls Jack , Shaw Heather , Simon Marni
Published: April 2004

A comparison of voice onset time (VOT) production in younger and older female monozygotic twins revealed greater similarity for the younger than the older female twin pairs. Based on findings from this study and a review of previous twin literature, it is hypothesized that ‘source’ characteristics of speech (voice properties) are under more constraints by genetics, while ‘filter’ characteristics of speech (VOT, formant frequencies) are freer to diverge due to environmental factors such as different linguistic environments. Since the older twins separated to two distinct linguistic areas of the United States at the age of 25 years, while the 2 younger twins continue to share domicile at 21 years, the findings of this study appear to support this preliminary hypothesis.
Sound Pressure Level of Running Speech: Percentile Level Statistics and Equivalent Continuous Sound Level
Authors: Corthals Paul
Published: April 2004

Sound pressure level estimates of running speech must accurately reflect everyday communication in an appropriate unit of measure. Several factors may influence the overall sound pressure level of speech under everyday circumstances, such as age of the listener and speaker, speaking distance, surrounding noise and room acoustics. It is very difficult to estimate how all these factors will combine to affect speech intensity in a given situation. Without that knowledge it is best to deal with measures that reflect running speech in a representative sample of talkers. As to measuring units, there is considerable variation in the way speech intensity is measured and quantified. Due to their fluctuating nature, sound pressure levels of running speech require some type of averaging over time. Equivalent continuous sound levels (Leq) and percentile levels (LN) by definition reflect temporal distribution of sound energy. The aim of this study was to collect time-weighted sound pressure level estimates of speech in order to obtain normative descriptive statistics. 400 volunteers between 7 and 95 years of age participated in the study, providing a sample representative of official local demographic data. Descriptive statistics of overall Leq and eleven LN measures are presented. Overall Leq is extrapolated to other speaker-listener distances and absorption coefficients. 3 × 2 ANOVA analyses are used to screen the data for significant differences among gender and age groups. Restrictions and advantages of time-weighting units for speech intensity level are discussed, as well as their relevance for audiometry and voice pathology.
Daily Variations in Skin Surface Properties Using Mixed Model Methodology
Authors: Latreille J. , Guinot C. , Robert-Granié C. , Le Fur I. , Tenenhaus M. , Foulley J.-L.
Published: April 2004

In order to explore the variations over the course of a day in certain skin biophysical properties, a study was conducted on 8 female volunteers. An assessment of several skin biophysical properties was carried out on the face and the volar forearm every 4 h over a period of 48 h. The biophysical parameters were assessed on the face for sebum secretion, skin surface pH, skin colour, transepidermal water loss, capacitance and skin surface temperature. The same parameters were measured on the volar forearm (excepted for sebum secretion). A statistical analysis based on mixed effect models was conducted. Four models, with different covariance structures, were successively tested. The analysis allowed us to identify a structure that repeated itself over time in the same way over each 24-hour period for capacitance on the forearm and for sebum secretion, skin surface pH and skin colour (L* and a* parameters) on the face. Mixed effect methodology is a powerful tool to analyse longitudinal data involving correlations among repeated measurements made on the same subject.
Pituitary Resistin Gene Expression: Effects of Age, Gender and Obesity
Authors: Morash Barbara A. , Ur Ehud , Wiesner Glen , Roy Jeremy , Wilkinson Michael
Published: April 2004

Resistin is a new adipocytokine which is expressed in rat, mouse and possibly human adipose tissue. Its putative role as a mediator of insulin resistance is controversial. We hypothesized that resistin, like leptin, would have multiple roles in non-adipose tissues and we reported that resistin is expressed in mouse brain and pituitary. Moreover, resistin expression in female mouse pituitary is developmentally regulated and maximal expression occurs peripubertally. Although the role of endogenous resistin in mouse brain and pituitary has not been determined, our data suggest that resistin could be important in the postnatal maturation of the hypothalamic-pituitary system. In the present study we compared the ontogeny of resistin gene expression in the pituitary of male and female mice using semi-quantitative RT-PCR analysis. We show that resistin expression is developmentally regulated in the pituitary of male and female CD1 mice. However, significant gender differences were evident (male > female at postnatal day 28 and 42) and this was not modified by neonatal treatment of female pups with testosterone. Since resistin expression in adipose tissue is also influenced by obesity, we evaluated resistin expression in fat, brain and pituitary of the obese ob/ob mouse. Resistin mRNA was significantly increased in both visceral and subcutaneous adipose depots in postnatal day 28 ob/ob mice compared to controls, but pituitary resistin expression was significantly reduced. In contrast to the prepubertal levels, and in agreement with other reports, adipose resistin expression was reduced in adult ob/ob mice. In a third set of experiments we examined the influence of food deprivation on pituitary and fat resistin mRNA. Resistin gene expression was severely down-regulated by a 24-hour fast in adipose and pituitary tissue but not in hypothalamus. In conclusion, pituitary resistin expression is age- and gender-dependent. In ob/ob mice, and in fasted mice, resistin is regulated in a tissue-specific manner. Thus in visceral fat obesity increases but starvation decreases resistin mRNA. In contrast, pituitary levels are decreased in the presence of both high (ob/ob) and low (fasting) adipose stores. Further studies are required to define the unexpected hormonal regulation of resistin gene expression in the pituitary.
Riboflavin Deficiency Induces Ocular Surface Damage
Authors: Takami Yumiko , Gong Huaqing , Amemiya Tsugio
Published: April 2004

Purpose: To examine the conjunctiva and cornea of riboflavin-deficient rats with scanning (SEM) and transmission (TEM) electron microscopes. Materials and Methods: Three-week-old Wistar Kyoto rats were fed a riboflavin-deficient diet (0.05 mg riboflavin/100 g) for 3 months. As a recovery experiment, rats which had been on a riboflavin-deficient diet for 3 months were given water with 1 mg riboflavin/300 ml for 2 months. The conjunctiva and the cornea were examined with SEM and TEM. Results: The serum riboflavin level was significantly lower in the riboflavin-deficient group than in the controls. In rats on a riboflavin-deficient diet for 3 months, SEM showed decreased microvilli and microplicae in the superficial epithelium of the conjunctiva and a decrease in the number of goblet cells. The cornea showed many dark cells and a marked decrease of microvilli and microplicae. In the riboflavin-deficient rats, TEM of the conjunctiva showed a decrease of microvilli and microplicae in the most superficial epithelial cells, a decrease in the layers of the epithelium and a marked decrease in the number of goblet cells, while the cornea had decreased microvilli and microplicae in the superficial epithelium, dark wing cells, loss of the basement membrane and hemidesmosomes of basal cells, cell debris and degenerative stroma cells and deposits of dense bodies in the subepithelial layer of the stroma. In rats recovered from riboflavin deficiency, the conjunctiva and cornea showed no abnormalities. Discussion: Riboflavin plays a role in the development and maintenance of the surface structures of epithelial cells. Riboflavin may also be necessary for the development and maintenance of goblet cells. Conclusion: Riboflavin is essential for maintaining the structure and function of the ocular surface.
Effect of Growth Factors on Bovine Retinal Pigment Epithelial Cell Migration and Proliferation
Authors: Spraul Christoph W. , Kaven Corinna , Lang Gerhard K. , Lang Gabriele E.
Published: April 2004

Background: To examine the effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and transforming growth factor beta 2 (TGFβ2) on bovine retinal pigment epithelial (RPE) cell migration and proliferation. Materials and Methods: Cultured bovine RPE cells were treated with 10 ng/ml PDGF, bFGF, aFGF, IGF-1, EGF, or TGFβ2. RPE cell migration studies were performed in multiwell plates confluently covered with RPE cells. After inhibition of proliferation and denudation of half of each well, cells were incubated with various growth factors. Migration was measured as the number of cells that had entered the denuded area after 20 h. RPE cell proliferation was determined by [3H]thymidine incorporation after growth factor stimulation for 24 h. Results: RPE cell migration was significantly enhanced after incubation with PDGF (stimulation of 213% compared to the negative control, p = 0.002), bFGF (206%, p = 0.003), aFGF (175%, p = 0.003), IGF-1 (150%, p = 0.003), and EGF (144%, p = 0.003). RPE cell proliferation was stimulated by bFGF (322% compared to the negative control, p < 0.005), PDGF (119%, p < 0.005), aFGF (121%, p < 0.005), and EGF (94%, p < 0.005). IGF-1 showed no significant effect on RPE cell proliferation; TGFβ2 displayed no effect on RPE cell migration nor on proliferation. Conclusions: The peptide growth factors PDGF, bFGF, aFGF, IGF-1, and EGF play an important role in initiating RPE cell migration. Basic FGF, PDGF, aFGF, and EGF stimulate RPE cell DNA synthesis.
Power Spectral Analysis of Heart Rate in Relation to Sleep Position
Authors: Jean-Louis Magali , Anwar Mujahid , Rosen Har’el , Craelius William , Hiatt Mark , Hegyi Thomas
Published: April 2004

We used spectral analysis of heart rate variability, as a measure of autonomic tone, to determine spectral power differences in infants sleeping supine and prone. We studied 29 infants with a birth weight of 1,915 ± 939 g, at the postconceptional age of 36 ± 2 weeks. We then calculated total power (TP), low-frequency power (LF, 0.03–0.15 Hz), and high-frequency power (HF, 0.5–1.0 Hz). TP corresponds to overall heart rate variability, LF to both sympathetic and parasympathetic activity, and HF to parasympathetic activity only. Median (25th, 75th percentile) TP (beats/min2) in the supine position was 32.60 (23.12, 59.90), which was significantly higher than the prone position of 25.87 (14.94, 35.57). Similarly, LF (beats/min2) in the supine position of 13.82 (8.63, 23.31) was significantly higher than the prone position of 9.79 (5.46, 14.33). No significant difference was seen in the HF. We conclude that the prone position is associated with decreased heart rate variability and probably decreased sympathetic tone, which imply decreased autonomic stability in this position.
Validation of the HIV Dementia Scale in an Elderly Cohort of Patients with Subcortical Cognitive Impairment Caused by Subcortical Ischaemic Vascular Disease or a Normal Pressure Hydrocephalus
Authors: van Harten Barbera , Courant Marise N.J. , Scheltens Philip , Weinstein Henry C.
Published: April 2004

Introduction: Most cognitive screening instruments are tailored to detect symptoms of cortical dysfunction in the elderly. Therefore, subcortical cognitive dysfunction may be missed using these tests. The aim of this study was to validate the Human Immunodeficiency Virus (HIV) Dementia Scale (HDS), a screening test developed to detect subcortical cognitive dysfunction in young HIV-infected patients, in a group of elderly patients with subcortical cognitive impairment (SCI) caused by subcortical ischaemic vascular disease (SIVD) or a normal pressure hydrocephalus (NPH). Materials and Methods:53patients with SCI caused by SIVD or an NPH and 54 age-matched control subjects without cognitive impairment were included. All subjects underwent the HDS and the Mini-Mental State Examination (MMSE). A neuropsychological examination was used as the best reference test for the diagnosis of SCI. Results: The mean HDS score (maximum 16) was 5.1 ± 3.5 in the SCI patients and 13.0 ± 2.4 in the controls (p < 0.0001). The mean MMSE score (maximum 30) was 26.5 ± 3.1 in the SCI group and 28.6 ± 1.4 in the controls (p < 0.0001). Among subjects who had an MMSE score of more than 26 points, SCI patients (n = 35) also scored significantly lower on the HDS than controls (n = 50), mean scores being 6.2 ± 3.4 and 13.0 ± 2.4, respectively (p < 0.0001). A receiver-operating characteristics curve was used to detect the optimal sensitivity and specificity of the HDS. A cut-off score of 9 yielded 91% sensitivity (95% CI: 79–97) and 96% specificity (95% CI: 87–99). With this cut-off score, the positive predictive value was 96% (95% CI: 86–99) and the negative predictive value was 91% (95% CI: 81–97). Conclusions: These results suggest that the HDS is able to detect SCI in an elderly population with SIVD or NPH and a normal MMSE score, and warrant its further development as a screening tool for SCI.
Fractal Analysis of Surface Growth Patterns in Endometrioid Endometrial Adenocarcinoma
Authors: Kikuchi Akihiko , Kozuma Shiro , Yasugi Toshiharu , Taketani Yuji
Published: April 2004

Objective: A fractal is a shape made of parts similar to the whole in some way. The objective of this study was to determine whether surface growth patterns in endometrioid endometrial adenocarcinoma are fractal, and the mean fractal dimension differs according to histologic grades and depth of myometrial invasion. Methods: After the images of photographs of 120 resected uteri with endometrial cancers were digitized, the fractal dimensions of surface of tumors were measured using a fractal analysis software. Results: The mean fractal dimensions of surface growth patterns in G1, G2, and G3 adenocarcinoma were 2.318, 2.303, and 2.383, respectively. These values were significantly greater than the topological dimension of a surface (= 2). The value was significantly higher in G3 than in G2 (p = 0.03). And although not statistically significant, the value of G3 was greater than G1 (p = 0.10) and than (G1 and G2) group (p = 0.06). No significant difference nor tendency was found in the fractal dimension of the surface of the tumor according to depth of invasion. Conclusion: This study shows that the surface of endometrioid endometrial adenocarcinoma has a fractal structure, and the mean fractal dimension may differ according to histologic grades. Our report proposes a new way of looking at endometrial cancer pathology. We believe that fractal geometry gives insights into tumor morphology and becomes a useful tool for analyzing complex and irregular tumor growth patterns mathematically.
The Metabolism of Neuronal Iron and Its Pathogenic Role in Neurological Disease: Review
Authors: MOOS TORBEN , MORGAN EVAN H.
Published: April 2004

Abstract: Neurons need iron, which is reflected in their expression of the transferrin receptor. The concurrent expression of the ferrous iron transporter, divalent metal transporter I (DMT1), in neurons suggests that the internalization of transferrin is followed by detachment of iron within recycling endosomes and transport into the cytosol via DMT1. To enable DMT1‐mediated export of iron from the endosome to the cytosol, ferric iron must be reduced to its ferrous form, which could be mediated by a ferric reductase. The presence of nontransferrin‐bound iron in brain extracellular fluids suggests that neurons can also take up iron in a transferrin‐free form. Neurons are thought to be devoid of ferritin in many brain regions in which there is an association between iron accumulation and cellular damage, for example, neurons of the substantia nigra pars compacta. The general lack of ferritin together with the prevailing expression of the transferrin receptor indicates that iron acquired by activity of transferrin receptors is directed toward immediate use in relevant metabolic processes, is exported, or is incorporated into complexes other than ferritin. Iron has long been considered to play a significant role in exacerbating degradation processes in brain tissue subjected to acute damage and neurodegenerative disorders. In brain ischemia, the damaging role of iron may depend on the inhibition of detoxifying enzymes responsible for catalyzing the oxidation of ferrous iron. Brain ischemia may also lead to an increase in iron supply to neurons as transferrin receptor expression by brain capillary endothelial cells is increased. Pharmacological blockage of the transferrin receptor/DMT1‐mediated uptake could be a target to prevent further iron uptake. In chronic neurodegenerative settings, a deleterious role of iron is suggested since cases of Alzheimer's disease, Parkinson's disease, and Huntington's disease have a significantly higher accumulation of iron in affected regions. Dopaminergic neurons are rich in neuromelanin, shown to be more redox‐active in Parkinson's disease cases. Iron‐containing inflammatory cells may, however, account for the main portion of iron present in neurodegenerative disorders. More knowledge about iron metabolism in normal and diseased neurons is warranted as this may identify pharmaceutical targets to improve neuronal iron management.
Hematoma Removal, Heme, and Heme Oxygenase Following Hemorrhagic Stroke
Authors: WAGNER KENNETH R. , DWYER BARNEY E.
Published: April 2004

Abstract: The hemorrhagic strokes, intracerebral (ICH) and subarachnoid hemorrhage (SAH), often have poor outcomes. Indeed, the most common hemorrhagic stroke, ICH, has the highest mortality and morbidity rates of any stroke subtype. In this report, we discuss the evidence for the staging of red blood cell removal after ICH and the significance of control of this process. The protective effects of clinically relevant metalloporphyrin heme oxygenase inhibitors in experimental models of ICH and in superficial siderosis are also discussed. We also examine literature paradoxes related to both heme and heme oxygenase in various disorders of the central nervous system. Last, new data are presented that support the concept that heme, although primarily a pro‐oxidant, can also have antioxidant properties.
Hereditary Causes of Disturbed Iron Homeostasis in the Central Nervous System
Authors: PONKA PREM
Published: April 2004

Abstract: Iron is essential for oxidation‐reduction catalysis and bioenergetics; however, unless appropriately shielded, this metal plays a crucial role in the formation of toxic oxygen radicals that can attack all biological molecules. Organisms are equipped with specific proteins designed for iron acquisition, export and transport, and storage, as well as with sophisticated mechanisms that maintain the intracellular labile iron pool at an appropriate level. Despite these homeostatic mechanisms, organisms often face the threat of either iron deficiency or iron overload. This review describes several hereditary iron‐overloading conditions that are confined to the brain. Recently, a mutation in the L‐subunit of ferritin has been described that causes the formation of aberrant L‐ferritin with an altered C‐terminus. Individuals with this mutation in one allele of L‐ferritin have abnormal aggregates of ferritin and iron in the brain, primarily in the globus pallidus. Patients with this dominantly inherited late‐onset disease present with symptoms of extrapyramidal dysfunction. Mice with a targeted disruption of a gene for iron regulatory protein 2 (IRP2), a translational repressor of ferritin, misregulate iron metabolism in the intestinal mucosa and the central nervous system. Significant amounts of ferritin and iron accumulate in white matter tracts and nuclei, and adult IRP2‐deficient mice develop a movement disorder consisting of ataxia, bradykinesia, and tremor. Mutations in the frataxin gene are responsible for Friedreich's ataxia, the most common of the inherited ataxias. Frataxin appears to regulate mitochondrial iron‐sulfur cluster formation, and the neurologic and cardiac manifestations of Friedreich's ataxia are due to iron‐mediated mitochondrial toxicity. Patients with Hallervorden‐Spatz syndrome, an autosomal recessive, progressive neurodegenerative disorder, have mutations in a novel pantothenate kinase gene (PANK2). The cardinal feature of this extrapyramidal disease is pathologic iron accumulation in the globus pallidus. The defect in PANK2 is predicted to cause the accumulation of cysteine, which binds iron and causes oxidative stress in the iron‐rich globus pallidus. Finally, aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by loss‐of‐function mutations in ceruloplasmin gene that leads to misregulation of both systemic and central nervous system iron trafficking. Affected individuals suffer from extrapyramidal signs, cerebellar ataxia, progressive neurodegeneration of retina, and diabetes mellitus. Excessive iron depositions are found in the brain, liver, pancreas, and other parenchymal cells, but plasma iron concentrations are decreased. These conditions are not common, but awareness about them is important for differential diagnosis of various neurodegenerative disorders.
Ironing Iron Out in Parkinson's Disease and Other Neurodegenerative Diseases with Iron Chelators: A Lesson from 6‐Hydroxydopamine and Iron Chelators, Desferal and VK‐28
Authors: YOUDIM MOUSSA B. H. , STEPHENSON GALIA , SHACHAR DORIT BEN
Published: April 2004

Abstract:In Parkinson's disease (PD) and its neurotoxin‐induced models, 6‐hydroxydopamine (6‐OHDA) andN‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), significant accumulation of iron occurs in the substantia nigra pars compacta. The iron is thought to be in a labile pool, unbound to ferritin, and is thought to have a pivotal role to induce oxidative stress‐dependent neurodegeneration of dopamine neurons via Fenton chemistry. The consequence of this is its interaction with H2O2to generate the most reactive radical oxygen species, the hydroxyl radical. This scenario is supported by studies in both human and neurotoxin‐induced parkinsonism showing that disposition of H2O2is compromised via depletion of glutathione (GSH), the rate‐limiting cofactor of glutathione peroxide, the major enzyme source to dispose H2O2as water in the brain. Further, radical scavengers have been shown to prevent the neurotoxic action of the above neurotoxins and depletion of GSH. However, our group was the first to demonstrate that the prototype iron chelator, desferal, is a potent neuroprotective agent in the 6‐OHDA model. We have extended these studies and examined the neuroprotective effect of intracerebraventricular (ICV) pretreatment with the prototype iron chelator, desferal (1.3, 13, 134 mg), on ICV induced 6‐OHDA (250 μg) lesion of striatal dopamine neurons. Desferal alone at the doses studied did not affect striatal tyrosine hydroxylase (TH) activity or dopamine (DA) metabolism. All three pretreatment (30 min) doses of desferal prevented the fall in striatal and frontal cortex DA, dihydroxyphenylacetic acid, and homovalinic acid, as well as the left and right striatum TH activity and DA turnover resulting from 6‐OHDA lesion of dopaminergic neurons. A concentration bell‐shaped neuroprotective effect of desferal was observed in the striatum, with 13 μg being the most effective. Neither desferal nor 6‐OHDA affected striatal serotonin, 5‐hydroxyindole acetic acid, or noradrenaline. Desferal also protected against 6‐OHDA‐induced deficit in locomotor activity, rearing, and exploratory behavior (sniffing) in a novel environment. Since the lowest neuroprotective dose (1.3 μg) of desferal was 200 times less than 6‐OHDA, its neuroprotective activity may not be attributed to interference with the neurotoxin activity, but rather iron chelation. These studies led us to develop novel brain‐permeable iron chelators, the VK‐28 series, with iron chelating and neuroprotective activity similar to desferal for ironing iron out from PD and other neurodegenerative diseases, such as Alzheimer's disease, Friedreich's ataxia, and Huntington's disease.
Redox Neurology: Visions of an Emerging Subspecialty
Authors: SCHIPPER HYMAN M.
Published: April 2004

Abstract:Recent years have witnessed a dramatic increase in publications implicating free radicals and oxidative stress in virtually every aspect of biology and medicine. Redox Neurology may be defined as the study of the roles of free radicals, transition metals, oxidative stress, and antioxidant defenses in diseases of the nervous system. In this position paper, an argument is presented for recognition of this field as an emerging subspecialty within medical neurology. A program for postresidency fellowship training in Redox Neurology that integrates laboratory experience with specialized clinical practice is proposed. Opportunities for research and teaching careers in the redox neurosciences are outlined. The paper concludes with a forecast of several research themes likely to preoccupy this nascent discipline in the days ahead.
Fast fibres in a large animal: fibre types, contractile properties and myosin expression in pig skeletal muscles
Authors: Toniolo Luana , Patruno Marco , Maccatrozzo Lisa , Pellegrino Maria A. , Canepari Monica , Rossi Rosetta , D'Antona Giuseppe , Bottinelli Roberto , Reggiani Carlo , Mascarello Francesco
Published: April 2004

Little is known about the influence of Myosin Heavy Chain (MHC) isoforms on the contractile properties of single muscle fibres in large animals. We have studied MHC isoform composition and contractile properties of single muscle fibres from the pig. Masseter, diaphragm, longissimus, semitendinosus,rectractor bulbi and rectus lateralis were sampled in female pigs (aged 6 months, mass 160 kg). RT-PCR, histochemistry, immunohistochemistry and gel electrophoresis were combined to identify and separate four MHC isoforms:MHC-slow and three fast MHC (2A, 2X, 2B).

Maximum shortening velocity (Vo) and isometric tension(Po) were measured in single muscle fibres with known MHC isoform composition. Six groups of fibres (pure: slow, 2A, 2X and 2B, and hybrid: 2A-2X and 2X-2B) with large differences in Vo and Po were identified. Slow fibres had mean Vo=0.17±0.01 length s-1 and Po=25.1±3.3 mN mm-2. For fast fibres 2A,2X and 2B, mean Vo values were 1.86±0.18,2.55±0.19 and 4.06±0.33 length s-1 and mean Po values 74.93±8.36, 66.85±7.58 and 32.96±7.47 mN mm-2, respectively. An in vitromotility assay confirmed that Vo strictly reflected the functional properties of the myosin isoforms.

We conclude that pig muscles express high proportions of fast MHC isoforms,including MHC-2B, and that Vo values are higher than expected on the basis of the scaling relationship between contractile parameters and body size.
Raman investigation of single oxidized carbon nanotubes
Authors: Mews Alf , Jiang Chaoyang , Schuessler Thomas , Philipp Guenther , Fan Y. , Burghard Marko
Published: April 2004

The oxidation process of single‐walled carbon nanotubes via nitric acid treatment was followed by IR‐, UV‐Vis‐NIR, and single bundle Raman spectroscopy. The introduction of functional, oxygen‐containing groups is revealed by an additional absorption band at 1725 cm−1, characteristic of carbonyl stretch vibrations. No significant shift of the optical absorption bands could be detected after oxidation. The combination of atomic force microscopy and confocal scanning resonance‐enhanced Raman microscopy was used to investigate thin bundles and, eventually, individual nanotubes in detail. These experiments enabled determination of the dependence of the Raman intensity of the G‐line (around 1590 cm−1) on the bundle height for both non‐oxidized and oxidized tubes. The Raman cross‐section of the oxidized tubes was found to be reduced by a factor of ˜4, compared to the pristine tubes. This observation is ascribed to all tubes within a bundle that are oxidized to the same degree.
Theoretical studies on high‐valent manganese porphyrins: Toward a deeper understanding of the energetics, electron distributions, and structural features of the reactive intermediates of enzymatic and synthetic manganese‐catalyzed oxidative processes
Authors: Ghosh Abhik , Gonzalez Emmanuel
Published: April 2004

We present here a relatively comprehensive theoretical study, based on nonlocal density functional theory calculations, of the energetics, electron distributions, and structural features of the low‐lying electronic states of various high‐valent intermediates of manganese porphyrins. Two classes of molecules have been examined: (a) compounds with the general formula [(P)MnX2]0 (P = porphyrin; X = F, Cl, PF6) and (b) high‐valent manganese‐oxo species. For [(P)Mn(PF6)2]0, the calculations reveal a number of nearly equienergetic quartet and sextet states as the lowest states, consistent with experimental results on a comparable species, [(TMP)Mn(ClO4)2]0 (TMP = tetramesitylporphyrin). In contrast, [(P)MnCl2]0 and [(P)MnF2]0 have a single well‐defined S = 3/2 Mn(IV) ground state, again in agreement with experiment, with the three unpaired spins largely concentrated (>90%) on the manganese atom. Manganese(IV)‐oxo porphyrins have an S = 3/2 ground state, with the three unpaired spins distributed approximately 2.3:0.7 between the manganese and oxygen atoms. The metal‐to‐oxygen spin delocalization, as measured by the oxygen spin population, for MnIV = O porphyrins is less than, but still qualitatively similar to, that in analogous iron(IV)‐oxo intermediates, indicating that the MnIV = O bond is significantly weaker than the FeIV = O bond in an analogous molecule. Thus, the optimized metal—oxygen bond distances are 1.654 and 1.674 Å for (P)FeIV(O)(Py) and (P)MnIV(O)(Py), respectively (Py = pyridine). This is consistent with the experimental observation that MnIV = O stretching frequencies are over 10% lower than FeIV = O stretching frequencies for analogous compounds. For [(P)Mn(O)(PF6)]0, [(P)Mn(O)(Py)]+, and [(P)Mn(O)(F)]0, the ground states clearly correspond to a (dxy)2 Mn(V) configuration and the short Mn–O distances of 1.541, 1.546, and 1.561 Å for the three compounds, respectively, reflect the formal triple bond character of the Mn–O interaction. Interestingly, the corresponding Mn(IV)‐oxo porphyrin cation radical states are calculated to be a few tenths of an electrovolt higher than the Mn(V) ground states, suggesting that the Mn(IV)‐oxo porphyrin cation radicals are not likely to exist as ground‐state species.
Deviation of Fiber Tracts in the Vicinity of Brain Lesions: Evaluation by Diffusion Tensor Imaging
Authors: Assaf Yaniv , Pianka Pazit , Rotshtein Pia , Sigal Michal , Hendler Talma
Published: April 2004

Diffusion Tensor Imaging (DTI) is used to characterize the diffusion properties of deviated white matter caused by brain tumors. DTI was recently shown to be very helpful in delineating white matter both within brain lesions and surrounding them. Displacement of white matter fibers may be one of the consequences of tumor growth adjacent to white matter. The combination of white matter mapping with DTI and gray matter mapping using functional MRI, in some cases, facilitated assessment of the relation between the shifted cortical areas and the corresponding white matter tracts. We found that the fractional anisotropy extracted from DTI is increased by 38% in areas of non‐edematous shifted white matter fibers. By contrast, trace apparent diffusion coefficient (ADC) values in those areas were found to be similar to contralateral side and normal control values. Analysis of the three diffusion tensor eigenvalues revealed that the increase in the fractional anisotropy is a result of two processes. The first is the increase in the diffusion parallel to the fibers—λ1 (by 18%), and the second is the decrease in the diffusion perpendicular to fibers—λ3 (by 34%) as compared with the contralateral side. These opposing changes cause an increase in the diffusion anisotropy but no change in the trace ADC. It is suggested that the pressure caused by the tumor may lead to an increase in white matter fiber tension, thus causing an increase in λ1. On the other hand, the same pressure causes increased fiber density per unit area, leading to a higher degree of restricted diffusion in the extracellular space and, hence, a reduction in λ3.
Ab initio molecular dynamics: Propagating the density matrix with gaussian orbitals. IV. Formal analysis of the deviations from born‐oppenheimer dynamics
Authors: Iyengar Srinivasan S. , Schlegel H. Bernhard , Voth Gregory A. , Millam John M. , Scuseria Gustavo E. , Frisch Michael J.
Published: April 2004

In the context of the recently developed Atom‐centered Density Matrix Propagation (ADMP) approach to ab initio molecular dynamics, a formal analysis of the deviations from the Born—Oppenheimer surface is conducted. These deviations depend on the fictitious mass and on the magnitude of the commutator of the Fock and density matrices. These quantities are found to be closely interrelated and the choice of the fictitious mass provides a lower bound on the deviations from the Born—Oppenheimer surface. The relations are illustrated with an example calculation for the Cl−(H2O)25 cluster. We also show that there exists a direct one‐to‐one correspondence between approximate Born—Oppenheimer dynamics, where SCF convergence is restricted by a chosen threshold value for the commutator of the Fock and density matrices, and extended Lagrangian dynamics performed using a finite value for the fictitious mass. The analysis is extended to the nuclear forces used in the ADMP approximation. The forces are shown to be more general than those standardly used in Born—Oppenheimer dynamics, with the addition terms in the nuclear forces depending on the commutator mentioned above.
Quantum quadratic brownian oscillator model for absorption lineshapes
Authors: Barsegov Valeri , Chernyak Vladimir , Mukamel Shaul
Published: April 2004

The absorption lineshape of a two‐level chromophore coupled quadratically to a collective Gaussian solvation coordinate with an arbitrary Brownian oscillator spectral density is calculated exactly using a path‐integral representation of the dipole correlation function in Liouville space.
Current–voltage–temperature characteristics for 2D arrays of metallic quantum dots
Authors: Remacle F. , Levine R. D.
Published: April 2004

Computational results for the temperature‐dependent conductivity of compressed arrays of size‐selected Ag nanodots are discussed. Special attention is given to the role of phase transitions of the array as a function of external control variables: the applied voltage, the temperature, and the compression of the array. The computations are based on a scattering formalism that is presented in detail so that all the assumptions are explicitly spelled out. The results demonstrate the ability of low‐lying excited electronic states of 2D lattices to probe by temperature‐dependent conductivity measurements.
Structural models for the alkaline conformers of yeast iso‐1‐ferricytochrome c
Authors: Ness Steven R. , Lo Terence P. , Mauk A. Grant
Published: April 2004

Structural models for three alkaline conformers of yeast iso‐1‐ferricytochrome c have been calculated from the atomic coordinates of the native protein through the use of molecular dynamics simulation. In the three models produced by this work, the Met80 axial ligand to the heme iron has been replaced by either Lys72, Lys73, or Lys79, and the related changes in structure of the cyto‐chrome are described. The principal changes in cytochrome structure predicted to result from this pH‐linked change in axial ligation involve location of residues 70–80, a region of the protein sequence that is phylogenetically conserved. The remainder of the protein fold in each model is essentially unchanged from the structure of the native protein, which is consistent with available spectroscopic information. The observation that this highly conserved region is apparently integrally involved in this conformational change may be interpreted as indicating a possible physiological role for the pH‐linkage of ferricytochrome c structure.
Quantum monte carlo methods for electronic structure of nanosystems
Authors: Mitas Lubos
Published: April 2004

We provide a brief review of recent applications of quantum Monte Carlo (QMC) methods to the electronic structure of nanosystems. We report on calculations of carbon rings with second‐order Jahn‐Teller effect, energy ordering of silicon clusters, dissociation enthalpies of protonated hydrogen clusters, and other interesting challenges. We point out the QMC accuracy and outline a few ideas that characterize the current position of QMC among the electronic structure methods and its future development.
Atmospheric trace gas analysis with cavity ring‐down spectroscopy
Authors: Kleine Daniel , Mürtz Manfred , Lauterbach Jörg , Dahnke Hannes , Urban Wolfgang , Hering Peter , Kleinermanns Karl
Published: April 2004

Cavity ring‐down spectroscopy (CRDS) is a highly sensitive laser absorption method. It can be used for quantitative analysis of molecular species at the sub‐ppb level. The absorption cell (cavity) is sealed by two high‐reflective mirrors on each side, which results in an effective absorption path‐length of some kilometers. Our experiments for atmospheric gas analysis have been carried out so far with an Excimer pumped dye laser in the UV‐VIS and a CO overtone sideband laser in the wavelength region around 3 μm. Experiments with an all solid‐state difference frequency laser system will follow. In the UV‐VIS region, we measured trace gas molecules like SO2, NO2, and CH2O. In the mid‐infrared, around 3 μm, we measured hydrocarbons like CH4, C2H6, and C2H4 with a detection limit of less than 1 ppb. The noise equivalent absorption coefficients in the MIR are in the order of 1.7·10−9 cm−1. Due to the high data acquisition rate and the high sensitivity, CRDS enables real‐time detection of trace gases in ambient air.
Second‐order nonlinear optical response of thin films containing organic chromophores. Theoretical aspects
Authors: Di Bella Santo , Fragalà Ignazio , Marks Tobin J.
Published: April 2004

This paper discusses some theoretical aspects associated with the unusual second‐order nonlinear optical response of chromophoric self‐assembled stilbalzolium superlattices, and of (N,N‐dimethylamino)‐4‐nitrostilbene (DANS)‐doped glass polymers poled in an “in‐plane” configuration. It is found that the bulk nonlinearity of such materials strongly depends upon specific chromophore interactions. While for the stilbalzolium superlattices the supramolecular hyperpola‐rizability is strongly affected by the ion‐pair configuration, the formation of (formally) centrosymmetric charged chromophore aggregates is likely responsible for the observed anomalous strong nonlinearity in DANS‐doped in‐plane poled polymers. The simple “chromophore gas” model is thus inadequate to describe the non‐linearity of such materials.
Electron transfer in the ruthenated heme domain of cytochrome P450BM‐3
Authors: Sevrioukova Irina F. , Immoos Chad E. , Poulos Thomas L. , Farmer Patric
Published: April 2004

Two mutants of the heme domain of Bacillus megaterium cytochrome P450BM‐3 (BMP) have been modified by covalent attachment of a photoactive Ru(bpy)3 complex at the surface‐exposed cysteine residues, 62 and 387. The laser‐flash/quench technique was used to study Ru1+ → Fe3+ electron transfer (ET) within the Ru‐BMP complexes. There was no reduction of the ferric heme by Ru1+ in Ru‐62‐BMP. In Ru‐387‐BMP, ET from Ru1+ to Fe3+ occurred with the rate constant of 4.6 × 105 s−1 and 2.5 × 106 s−1 in the absence and presence of substrate, respectively. The study demonstrates the importance of through‐bond pathways for electron flow to the heme iron of P450 and that the Gln387–Cys400 peptide is a potential ET root in P450BM‐3.
Classical description of the level density and the relaxation behavior of multidimensional molecular curve‐crossing systems
Authors: Dilthey Stefan , Stock Gerhard
Published: April 2004

Based on the mapping formulation of nonadiabatic dynamics (Phys. Rev. Lett. 1997, 78, 578), explicit classical expressions for the total level density N(E) of a vibronically coupled molecular system as well as quantum corrections to it are derived. The analytical results for N(E) reveal the relative importance of the various molecular parameters of a curve‐crossing system, such as the electronic bias, the reorganization energy, and the topology of the potential‐energy surfaces. To study the accuracy of the approximate description, numerical studies employing various spin‐boson models as well as a two‐state, three‐mode model of the ultrafast S2 → S1 electronic relaxation in pyrazine are presented. Comparing exact quantum and approximate classical data, the connection between the level density of a vibronically coupled molecular system and its nonadiabatic relaxation behavior is discussed in some detail.
[4 + 3] Cycloaddition Reactions
Authors: Rigby* James H. , Pigge F. Christopher
Published: April 2004

Cycloaddition in its many manifestations represents one of the most powerful methods in organic chemistry for making cyclic structures. The high levels of convergency and stereoselectivity that frequently characterize these processes are particularly attractive from a preparative point of view. Five‐ and six‐membered rings are typically made by the well‐known 1, 3‐dipolar and Diels–Alder cycloaddition reactions, respectively, and so‐called higher‐order cycloaddition processes have emerged recently as useful methodology for the construction of medium‐sized carbocycles.

Seven‐membered ring systems, owing primarily to their broad occurrence as substructures in many classes of natural products, are particularly important targets for synthesis, but there are relatively few ways currently available for
de novo
synthesis of these ring systems. As a general solution to this problem, [4 + 3] cycloaddition between a 1, 3‐diene and an allyl, or more frequently an oxyallyl, cation offers rapid access to functionalized seven‐membered carbocycles with many of the attendant virtues of other cycloaddition processes. Considerable effort has been expended recently to exploit the synthetic utility of these reactions, and several informative reviews of the subject are currently available. Electronically, the process is quite similar to the Diels–Alder reaction and can be viewed as a [4π(4C) + 2π(3C)] combination in which the allyl cation participates as the reactive 2π component. Much of the developmental work associated with [4 + 3] cycloaddition has focused on approaches to the generation of the allyl or oxyallyl cation reaction partner, and a number of useful methods have emerged.

While a wide range of 1, 3‐diene partners have been employed in these reactions, π‐excessive heterocycles such as furan and pyrrole have been shown to be particularly useful participants and, recently, intramolecular versions of the [4 + 3] process have been effectively applied to natural product synthesis.

This chapter reviews the literature of [4 + 3] cycloadditions that involve allyl and oxyallyl cations and closely related 2π(3C) reactants to mid‐1996. Those [4 + 3] cycloadditions previously compiled by Noyori and Hayakawa in their 1983 review of reductive dehalogenations of polyhaloketones are also included in the current review so that all relevant examples are located in one document. Other 4 + 3 annulation processes that afford seven‐membered carbocycles but that employ other types of reactive intermediates are not covered in this survey.