bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Chloride Ions on the Mechanism of the Oxidative Addition of Cyclic Allylic Carbonates to Pd0 Complexes by Formation of Neutral[(η1‐allyl)PdClL2] Complexes
Authors: Cantat Thibault , Agenet Nicolas , Jutand Anny , Pleixats Roser , Moreno‐Mañas Marcial
Published: August 2005

The reversible oxidative addition of a cyclic allylic carbonate cis‐1 to palladium(0) complexes ligated by PPh3 is affected by chloride ions in DMF or chloroform. In the presence of chloride ions, the oxidative addition may become irreversible and the rate of isomerization of cis‐1 to trans‐1 is slowed down. This is a consequence of a slower isomerization of the cationic complex [(η3‐allyl)Pd(PPh3)2]+ (cis‐2+) to trans‐2+ due to the formation of neutral [(η1‐allyl)PdCl(PPh3)2] (cis‐3/trans‐3) complexes. Such complexes are formed instead of the cationic cis‐2+ and trans‐2+ whatever the source of chloride ions, i.e., whether voluntarily added to the cationic complexes cis‐2+ and trans‐2+, voluntarily added in the oxidative addition of cis‐1 with Pd0 complexes ligated to PPh3, or introduced in the dimeric complexes [(η3‐allyl)Pd(μ‐Cl)]2 (cis‐5/trans‐5). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
The Asymmetric Suzuki Coupling Route to Axially Chiral Biaryls
Authors: Baudoin Olivier
Published: August 2005

Axially chiral biaryls are ubiquitous structural motifs in biologically active natural products or ligands for homogeneous catalysis. Their properties relate to the particular spatial arrangement of the two aromatic residues and therefore the control of their absolute configuration constitutes an issue of major importance. The asymmetric Suzuki–Miyaura coupling has recently emerged as an attractive alternative to standard methods for the control of biaryl axial chirality. Recent diastereo‐ and enantioselective approaches, as well as some applications in target‐oriented synthesis, are commented on in this microreview. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis and Structure of Macrolactams of 3α‐Aminodeoxycholanic Acid
Authors: Feigel Martin , Ladberg Rüdiger , Winter Manuela , Bläser Dieter , Boese Roland
Published: August 2005

The macrolactams cyclo(3α‐aminodeoxycholic amide)2 (1) and cyclo(3α‐aminodeoxycholic amide)3 (2) were prepared in high yields (1: 32 %; 2: 41 %) from the pentafluorophenyl esters of the linear precursors. The solid‐state structures of both macrocycles were determined by X‐ray diffraction. Compound 1 forms a cleft of C2 symmetry which holds two methanol and two water molecules fixed by hydrogen bonds. The crystals of compound 2 contain two slightly different macrolactam rings of 7–8 Å diameter. The polar α‐surface of the deoxycholanic parts and the amide NH groups are oriented into the center of the rings. The cavity formed by the ring system and the void volume between the macrocycles is filled by disordered solvent molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A Highly Stereoselective Synthesis of the Indolo[2,3‐a]quinolizine Ring System and Application to Natural Product Synthesis
Authors: Allin Steven M. , Thomas Christopher I. , Allard James E. , Doyle Kevin , Elsegood Mark R. J.
Published: August 2005

We present a facile and highly stereoselective approach to the indolo[2,3‐a]quinolizine ring system from a readily available, non‐racemic chiral template. We demonstrate the potential for application of this methodology to natural product synthesis through conversion of the template to some representative indole alkaloids with high enantiomeric purity in both enantiomeric series. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Efficient Acetylation of Carbohydrates Promoted by Imidazole
Authors: Tiwari Pallavi , Kumar Rishi , Maulik Prakas R. , Misra Anup Kumar
Published: August 2005

An efficient per‐O‐acetylation of carbohydrate derivatives and unprotected reducing sugars promoted by imidazole is reported. The reaction conditions have been successfully employed to acetylate carbohydrate derivatives containing acid‐susceptible functional groups. In most of the cases the yields obtained were excellent. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Morphological effects of local scouring in step–pool streams
Authors: Comiti Francesco , Andreoli Andrea , Lenzi Mario A.
Published: August 2005

Step–pool morphology characterizes many high‐gradient streams in a variety of natural settings, but formative processes and evolutionary dynamics are still poorly understood. In this paper, natural step–pool geometry is compared with steep alluvial channels where grade‐control structures such as check‐dams and bed sills make the stream profile resemble a natural stepped stream. Along these channels, local scouring due to falling jets forms plunge pools under each structure, analogous to natural steps determining the formation of pools. In order to test the hypothesis that natural pools are analogous to pools formed below grade‐control works with respect to their dimensions, shape and formative dynamics, 37 natural pools and 73 artificial pools were surveyed in 10 mountain streams of the eastern Italian Alps. Pools below grade‐control works featured a transitional zone between the scour hole and the downstream sloping bed, marked by a depositional berm. When geometric parameters such as maximum pool depth, length and step–berm distances are normalized to the jet virtual energy, no statistically significant differences were detected between natural and artificial systems. These results lend support to an upstream‐forced cascade model for step–pool formation, where the energy of falling jets controls the geometry of the pools, and is therefore regarded as the most important scaling‐independent variable. Copyright © 2005 John Wiley & Sons, Ltd.
Homozygous germ line mutation in exon 27 of murine Brca2 disrupts the Fancd2–Brca2 pathway in the homologous recombination‐mediated DNA interstrand cross‐links' repair but does not affect meiosis
Authors: Atanassov Boyko S. , Barrett J. Carl , Davis Barbara J.
Published: August 2005

The role of the region encoded by exon 27 of the Brca2 gene in DNA repair was studied in cells and tissues from Brca2Δ27/Δ27 mice. The COOH‐terminal truncated Brca2 localized to the nucleus in primary mouse embryo fibroblasts from Brca2Δ27/Δ27 mice. Fluorescence‐activated cell sorting (FACS) analysis demonstrated that these fibroblasts were hypersensitive to mitomycin C‐induced cross‐links, but not to double‐strand breaks (DSBs) induced by irradiation. The γH2AX appearance kinetics and comet assay showed that DSBs were repaired through non‐homologous end joining pathways, while interstrand cross‐links were not repaired due to deficient homologous recombination pathways. Immunoprecipitation experiments showed that Fancd2 did not coprecipitate with the mutated Brca2. There were also no detectable Rad51‐positive foci formed in these cells after damage. On the other hand, we did not find any difference during gametogenesis in mice harboring exon 27 truncating mutation of the Brca2 gene and control mice, and in both cases, Rad51 localized to the recombination foci. Our results suggest that exon 27 of murine Brca2 is crucial for the interaction of Brca2 and Fancd2 in Rad51‐mediated recombination in response to DNA damage, but that this interaction is not taking place in the homologous recombination during meiosis. Published 2005 Wiley‐Liss, Inc.
Estimating the price elasticity of expenditure for prescription drugs in the presence of non‐linear price schedules: an illustration from Quebec, Canada
Authors: Contoyannis Paul , Hurley Jeremiah , Grootendorst Paul , Jeon Sung‐Hee , Tamblyn Robyn
Published: August 2005

The price elasticity of demand for prescription drugs is a crucial parameter of interest in designing pharmaceutical benefit plans. Estimating the elasticity using micro‐data, however, is challenging because insurance coverage that includes deductibles, co‐insurance provisions and maximum expenditure limits create a non‐linear price schedule, making price endogenous (a function of drug consumption). In this paper we exploit an exogenous change in cost‐sharing within the Quebec (Canada) public Pharmacare program to estimate the price elasticity of expenditure for drugs using IV methods. This approach corrects for the endogeneity of price and incorporates the concept of a ‘rational’ consumer who factors into consumption decisions the price they expect to face at the margin given their expected needs. The IV method is adapted from an approach developed in the public finance literature used to estimate income responses to changes in tax schedules. The instrument is based on the price an individual would face under the new cost‐sharing policy if their consumption remained at the pre‐policy level. Our preferred specification leads to expenditure elasticities that are in the low range of previous estimates (between −0.12 and −0.16). Naïve OLS estimates are between 1 and 4 times these magnitudes. Copyright © 2005 John Wiley & Sons, Ltd.
Waiting lists, waiting times and admissions: an empirical analysis at hospital and general practice level
Authors: Windmeijer Frank , Gravelle Hugh , Hoonhout Pierre
Published: August 2005

We report an empirical analysis of the responses of the supply and demand for secondary care to waiting list size and waiting times. Whereas previous empirical analyses have used data aggregated to area level, our analysis focuses on the supply responses of a single hospital and the demand responses of the GP practices it serves, and distinguishes between first outpatient visits, inpatient admissions, day‐case treatment and emergency admissions. The results are plausible and in line with the theoretical model. For example: the demand from practices for first outpatient visits is negatively affected by waiting times and distance to the hospital. Increases in waiting times and waiting lists lead to increases in supply; the supply of elective inpatient admissions is affected negatively by current emergency admissions and positively by lagged waiting list and waiting time. We use the empirical results to investigate the dynamic responses to one off policy measures to reduce waiting times and lists by increasing supply. Copyright © 2005 John Wiley & Sons, Ltd.
Road injuries and long‐run effects on income and employment
Authors: Dano Anne Moller
Published: August 2005

This paper investigates whether unexpected shocks in terms of road injuries ‘cause’ a permanent change in disposable income, earnings, employment, and public transfer income. We use ‘propensity score matching’ and apply a difference‐in‐difference matching method to estimate the counterfactual of what the disposable income, earnings, employment, and the amount of public transfer income would have been of a particular group of persons injured by road accidents if they had not in fact been injured. We find that road injuries have important consequences. Older injured persons and injured persons in the lower part of the income distribution have significantly lower disposable incomes than older and low‐income non‐injured persons. In both the short and the long run the employment rates for the injured men are significantly lower than for non‐injured persons. No effects on the employment rate are found for women. Besides, earnings are reduced in the long run for men where significant effects are only found for older women. The analysis shows that both injured men and women are compensated in terms of a significant increase in public transfer incomes in both the short and the long run. Copyright © 2005 John Wiley & Sons, Ltd.
Glutathione Depletion Renders Rat Hepatocytes Sensitive to Nitric Oxide Donor–Mediated Toxicity *
Authors: Chen Tracy , Pearce Linda L. , Peterson Jim , Stoyanovsky Detcho , Billiar Timothy R.
Published: August 2005

Nitric oxide (NO) can be either cytoprotective or cytotoxic in hepatocytes, depending on conditions within the cell. We hypothesized that redox status is a determinant of NO effects on cell viability. To cause the disturbance of redox homeostasis in the hepatocytes, cells were treated with the following glutathione (GSH) depleting agents: (1) chronic depletion by 18 hours pretreatment with buthionine sulfoximine (BSO), which depletes GSH by blocking its biosynthesis; and (2) acute depletion by 1 hour pretreatment with diethyl maleate (DEM), which conjugates GSH by the GSH-S-transferase catalyzed reaction.

s

-nitroso-
N

-acetyl-d,l-penicillamine (SNAP), a NO donor, was added after removal of GSH-depleting agents. Individual treatment with either SNAP or GSH depletion did not appreciably affect viability. A significant increase of cytotoxicity in hepatocytes was observed with the combination of a concentration and time course regimen of SNAP and GSH depletion. SNAP treatment of GSH-depleted hepatocytes led to an increase in LDH release and oxidative stress, disruption of mitochondrial membrane potential, the presence of nitrotyrosine (an indicator of peroxynitrite (ONOO−) generation), and a decrease in adenosine triphosphate (ATP) content. The interference of mitochondrial respiratory enzymes, especially with the combination treatments, indicated different levels of disturbance of electron transfer, superoxide generation, and ATP production. Other commonly used NO donors were found to exhibit lower and slower toxicity in the setting of GSH depletion than that evident with SNAP.
In conclusion
, the disruption of cellular redox homeostasis by GSH depletion leads hepatocytes to be more susceptible to NO (especially

S

-nitrosothiols) and subsequent necrotic cell death. (Hepatology 2005;42:598–607.)
Modeling the Current and Future Disease Burden of Hepatitis C Among Injection Drug Users in Scotland *
Authors: Hutchinson Sharon J. , Bird Sheila M. , Goldberg David J.
Published: August 2005

Quantitative estimates of the current and future burden of hepatitis C virus (HCV) disease are required to plan a public health response to the HCV epidemic with regard to both prevention and treatment. A forward projection model was used to estimate the numbers of both current and former injecting drug users (IDUs) who acquired HCV and progressed to moderate and severe disease in Glasgow and Scotland during 1960-2030. The model was designed to synthesize information on the incidence and cessation of injecting drug use, the incidence of HCV infection among IDUs, the rate of HCV disease progression, and the annual number of IDUs developing HCV-related decompensated cirrhosis. During 2003, a total of 17,400 and 42,900 HCV-infected IDUs were estimated in Glasgow and Scotland, respectively; this compares with approximately 5,000 and 13,900 diagnosed, respectively, and 13,200 and 32,200 with chronic HCV, respectively. The number of IDUs developing HCV-related decompensated cirrhosis in Scotland is estimated to double between 2000 and 2020. As many as 16% and 27% of former IDUs in 2005 aged 30-39 and 40-49 years, respectively, were estimated to have moderate disease, which highlights the potential benefit of targeting HCV testing at former IDUs who belong to these age groups.
In conclusion
, the identification and treatment of a larger proportion of former IDUs with HCV disease and education about the importance of minimal alcohol consumption are needed to help achieve a greater impact on the future morbidity and mortality of this disease. (Hepatology 2005;42:711–723.)
Isatoribine, an Agonist of TLR7, Reduces Plasma Virus Concentration in Chronic Hepatitis C Infection *
Authors: Horsmans Yves , Berg Thomas , Desager Jean-Pierre , Mueller Tobias , Schott Eckart , Fletcher Simon P. , Steffy Kevin R. , Bauman Lisa A. , Kerr Bradley M. , Averett Devron R.
Published: August 2005

Immune-based therapy is the mainstay treatment for chronic hepatitis C virus (HCV) infection but causes multiple side effects and achieves durable viral clearance in only approximately 50% of patients. Most new investigational anti-HCV compounds are direct-acting antivirals for which durability of response and risk of viral mutations and resistance are not yet known. Therefore, continuing discovery and development of new immune-based treatments is desirable. Toll-like receptors (TLRs) are pathogen recognition receptors that initiate the innate immune response. The responsiveness of HCV or other ongoing chronic systemic infections to treatment with a selective TLR agonist has not been reported. Isatoribine is a selective agonist of TLR7. In a proof-of-concept study, we found that once-daily 7-day treatment with intravenous isatoribine 800 mg caused a significant (

P

= .001) reduction of plasma HCV RNA (mean, −0.76; range, −2.85 to +0.21 log10 units) in otherwise untreated patients (n = 12) who were chronically infected with HCV. Viral load reduction occurred in patients infected with genotype 1 as well as non-genotype 1 HCV. The reduction of viral load was correlated with induction of markers of a heightened immune antiviral state, including 2′-, 5′- oligoadenylate synthetase levels in whole blood. This treatment was well tolerated, with a low frequency of mild to moderate adverse events.
In conclusion,
systemic administration of the selective TLR7 agonist isatoribine resulted in dose-dependent changes in immunologic biomarkers and a statistically significant antiviral effect with relatively few and mild side effects. (Hepatology 2005;42:724–731.)
Telomere Shortening Correlates With Increasing Aneuploidy of Chromosome 8 in Human Hepatocellular Carcinoma *
Authors: Plentz Ruben R. , Schlegelberger Brigitte , Flemming Peer , Gebel Michael , Kreipe Hans , Manns Michael P. , Rudolph Lenhard K. , Wilkens Ludwig
Published: August 2005

Chromosomal instability (CIN) leads to an increase in aneuploidy and chromosomal aberrations in human hepatocellular carcinoma (HCC). Telomere shortening appears as one mechanism fostering the development of CIN. Whether telomere shortening correlates to specific genetic changes that characterize a certain type of cancer has yet to be established. In our recent study, we combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosome 8—one of the hallmark chromosomal alterations in hepatocellular carcinoma (HCC). We investigated 15 cytological fine-needle biopsies of aneuploid HCC and 5 touch prints of cadaver livers without cancer. Hepatocyte-specific TFI and the measurement of centromere-specific probe for chromosome 8 were both performed by quantitative fluorescence

in situ

hybridization (qFISH) or FISH. Combined analysis of both methods (coFISH) allowed measurement of telomere length and chromosome 8 copy number on a single cell level. We observed that telomere shortening correlates significantly with increasing copy number of chromosome 8 in HCC on the cellular level. Above the level of 5 copies of chromosome 8 per nucleus, no further shortening of telomeres was found, indicating that telomeres had reached a critically short length at this stage of aneuploidy.
In conclusion
, our study gives direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC. (Hepatology 2005;42:522–526.)
Function Follows Form: The Structure of the N-Terminal Domain of HCV NS5A *
Authors: Moradpour Darius , Brass Volker , Penin Francois
Published: August 2005

Hepatitis C virus (HCV) is a human pathogen affecting nearly 3% of the world's population. Chronic infections can lead to cirrhosis and liver cancer. The RNA replication machine of HCV is a multi-subunit membrane-associated complex. The nonstructural protein NS5A is an active component of HCV replicase, as well as a pivotal regulator of replication and a modulator of cellular processes ranging from innate immunity to dysregulated cell growth. NS5A is a large phosphoprotein (56-58 kd) with an amphipathic α-helix at its amino terminus that promotes membrane association. After this helix region, NS5A is organized into 3 domains. The N-terminal domain (domain I) coordinates a single zinc atom per protein molecule. Mutations disrupting either the membrane anchor or zinc binding of NS5A are lethal for RNA replication. However, probing the role of NS5A in replication has been hampered by a lack of structural information about this multifunctional protein. Here we report the structure of NS5A domain I at 2.5-Å resolution, which contains a novel fold, a new zinc-coordination motif, and a disulfide bond. We use molecular surface analysis to suggest the location of protein-, RNA-, and membrane-interaction sites.
A physically based distributed subsurface–surface flow dynamics model for forested mountainous catchments
Authors: Mulungu Deogratias M. M. , Ichikawa Yutaka , Shiiba Michiharu
Published: August 2005

This study was designed to develop a physically based hydrological model to describe the hydrological processes within forested mountainous river basins. The model describes the relationships between hydrological fluxes and catchment characteristics that are influenced by topography and land cover. Hydrological processes representative of temperate basins in steep terrain that are incorporated in the model include intercepted rainfall, evaporation, transpiration, infiltration into macropores, partitioning between preferential flow and soil matrix flow, percolation, capillary rise, surface flow (saturation‐excess and return flow), subsurface flow (preferential subsurface flow and baseflow) and spatial water‐table dynamics. The soil–vegetation–atmosphere transfer scheme used was the single‐layer Penman–Monteith model, although a two‐layer model was also provided. The catchment characteristics include topography (elevation, topographic indices), slope and contributing area, where a digital elevation model provided flow direction on the steepest gradient flow path. The hydrological fluxes and catchment characteristics are modelled based on the variable source‐area concept, which defines the dynamics of the watershed response. Flow generated on land for each sub‐basin is routed to the river channel by a kinematic wave model. In the river channel, the combined flows from sub‐basins are routed by the Muskingum–Cunge model to the river outlet; these comprise inputs to the river downstream. The model was applied to the Hikimi river basin in Japan. Spatial decadal values of the normalized difference vegetation index and leaf area index were used for the yearly simulations. Results were satisfactory, as indicated by model efficiency criteria, and analysis showed that the rainfall input is not representative of the orographic lifting induced rainfall in the mountainous Hikimi river basin. Also, a simple representation of the effects of preferential flow within the soil matrix flow has a slight significance for soil moisture status, but is insignificant for river flow estimations. Copyright © 2005 John Wiley & Sons, Ltd.
Soil moisture states, lateral flow, and streamflow generation in a semi‐arid, snowmelt‐driven catchment
Authors: McNamara James P. , Chandler David , Seyfried Mark , Achet Shiva
Published: August 2005

Hydraulic connectivity on hillslopes and the existence of preferred soil moisture states in a catchment have important controls on runoff generation. In this study we investigate the relationships between soil moisture patterns, lateral hillslope flow, and streamflow generation in a semi‐arid, snowmelt‐driven catchment. We identify five soil moisture conditions that occur during a year and present a conceptual model based on field studies and computer simulations of how streamflow is generated with respect to the soil moisture conditions. The five soil moisture conditions are (1) a summer dry period, (2) a transitional fall wetting period, (3) a winter wet, low‐flux period, (4) a spring wet, high‐flux period, and (5) a transitional late‐spring drying period. Transitions between the periods are driven by changes in the water balance between rain, snow, snowmelt and evapotranspiration. Low rates of water input to the soil during the winter allow dry soil regions to persist at the soil–bedrock interface, which act as barriers to lateral flow. Once the dry‐soil flow barriers are wetted, whole‐slope hydraulic connectivity is established, lateral flow can occur, and upland soils are in direct connection with the near‐stream soil moisture. This whole‐slope connectivity can alter near‐stream hydraulics and modify the delivery of water, pressure, and solutes to the stream. Copyright © 2005 John Wiley & Sons, Ltd.
The historical and palaeoflood record of Katherine river, northern Australia: evaluating the likelihood of extreme discharge events in the context of the 1998 flood
Authors: Sandercock Peter , Wyrwoll Karl‐Heinz
Published: August 2005

The discharge regimes of the large rivers of northern Australia are characterized by the occurrence of extreme flood events with far‐reaching environmental and societal impacts. In January 1998 the largest flood ever recorded on the Katherine River, northern Australia, resulted in widespread inundation and resultant damage to the town of Katherine. The occurrence of the flood emphasized the unreliability of the then available flood probability estimates and prompted a palaeoflood approach to estimate the recurrence interval of the event. The location of Katherine is ideal for such a study, as the town is located immediately downstream from Katherine Gorge, which provides the necessary bedrock‐confined channel required for such an approach. In addition, previous work in Katherine Gorge had demonstrated that the gorge sections hold suitable deposits for palaeoflood stage reconstruction. The results of the present study show that at least two flow events with discharges similar to the 1998 flood have occurred within the last 600 years, and that high‐magnitude floods are a general feature of the discharge record of the Katherine River over the last c. 2000 years. Furthermore, because the study was undertaken within a few months of the occurrence of the 1998 flood, it provided the opportunity to evaluate the previously obtained flood discharge estimates and draw attention to the general uncertainties associated with palaeoflood studies. Our results emphasize that palaeoflood stage estimates based on slackwater deposits need to be treated as conservative estimates only. More specifically, with respect to the 1998 event, our study demonstrates that the controls of flood peak were more complex than simply flood routing through the gorge sections. It is clear that the areas downstream from Katherine Gorge made an important contribution to the flood peak of the 1998 event. Copyright © 2005 John Wiley & Sons, Ltd.
The great Atacama flood of 2001 and its implications for Andean hydrology
Authors: Houston John
Published: August 2005

In February 2001, widespread flooding occurred throughout the Atacama Desert of northern Chile and southern Peru. It was particularly severe in the Río Loa basin, where roads and bridges were disrupted and the town of Calama inundated. The instantaneous peak flow in the Río Salado, a tributary of the Río Loa, reached 310 m3 s−1, an order of magnitude higher than any previously recorded event. The flood is estimated to have a return period of 100–200 years and is shown to have been caused by intense, long‐duration rainfall in the western Cordillera associated with La Niña. The surface water response is typical of arid areas and highly dependent on antecedent conditions, but is quite different in perennial and ephemeral catchments. Ephemeral flood flows suffer high transmission losses, recharging phreatic aquifers. Perennial rivers have lower runoff coefficients, but baseflow levels remained high after the event for several months due to bank storage rebound and interflow. Extremely high energies of ∼3000 W m−2 were generated by the floods in the Cordillera, becoming less in the Precordillera and downstream. Erosion and sediment transport were consequently highest in the upper and middle reaches of the rivers, with mixed erosion‐deposition in the lowest reach. The new insights gained from the interpretation and quantification of this event have important implications for palaeoenvironmental analysis, hazard management, water resource evaluation and the palaeohydrological evolution of the Andes. Copyright © 2005 John Wiley & Sons, Ltd.
Comparative anatomical study of the autonomic cardiac nervous system in macaque monkeys
Authors: Kawashima Tomokazu , Sato Kenji , Akita Keiichi , Sasaki Hiroshi
Published: August 2005

The main aim of this study was to clarify the general morphology of the autonomic cardiac nervous system in macaque monkeys. A submacroscopic comparative anatomical study of the autonomic cardiac nervous system was performed by examining 22 sides of 11 bodies of four species of macaque monkeys, including some previously unreported species (pig‐tailed and stump‐tailed monkeys), under a surgical stereomicroscope. The following results were obtained. 1) The basic arrangement of the autonomic cardiac nervous system is constant in all examined macaques. 2) A superior cardiac nerve originating from the superior cervical ganglion was not observed, whereas the thoracic cardiac nerve originating from the sympathetic trunk/ganglia under the cervicothoracic ganglion was rarely observed in all the examined macaques. 3) The main cardiac nerve is the middle cardiac nerve originating from the middle cervical ganglion, similar to the situation in humans. 4) Although the superior, inferior, and thoracic cardiac branches of the vagus nerve were consistently observed, the left thoracic cardiac branch is rarely absent because of its lower origin to the heart. 5) The cranial autonomic nerves tend to distribute into the heart medially (arterial porta), and the caudal autonomic nerves tend to distribute into the heart laterally (venous porta). To comprehend the comparative morphological and evolutionary changes more completely, these results were compared with our previous studies and some references. Consequently, differences in the sympathetic cardiac nerves of macaques and humans are recognized, in spite of the similar morphologies of the vagal cardiac branches. These differences include the composition of the cervicothoracic ganglion, the lower positions of the middle cervical and cervicothoracic ganglia, and the narrow range for the origin of the cardiac nerves in macaques compared to that in humans. J. Morphol. © 2005 Wiley‐Liss, Inc.
Structural characterization of chelator‐terminated dendrimers and their synthetic intermediates by mass spectrometry
Authors: Ch. Berndt Ursula E. , Zhou Tao , Hider Robert C. , Liu Zu D. , Neubert Hendrik
Published: August 2005

Herein, we report the structural analysis of a novel family of iron‐chelating dendrimers and their synthetic intermediates utilizing matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) and electrospray ionization ion trap (ESI IT) MS. These dendrimers share a benzene tricarbonyl core moiety attached to three tripodal branching units, each linking to three terminal groups, ranging from carboxyl, catechol and 3‐hydroxy‐6‐methyl‐pyran‐4‐one moieties and their protected analogs. In order to monitor the progression of dendrimer synthesis, all intermediates and final products were mass analyzed by conventional MALDI‐TOF MS with and without alkali metal spiking. For structural characterization, interpretable post‐source decay (PSD) and electrospray ionization ion trap MS/MS spectra were obtained from proton, sodium and potassium adducts of the dendrimers. One major route of dendrimer fragmentation was at or adjacent to the amide bonds either of the terminal chelating groups or near the core moiety. Fragmentation in the latter case was primarily at the N‐terminal side of the amide bond and was directed by the proximity of a tertiary carbon of the branching unit. Furthermore, it was found that terminal ester, ether and amide linkages to the protecting and chelating groups could be sequentially broken in a single MS/MS spectrum through multiple cleavages resulting in product ions of decreasing intensity. Moreover, such cleavages could also be induced in a stepwise manner in a multistage ion trap MSnexperiment. Copyright © 2005 John Wiley & Sons, Ltd.
Variable low‐mass filtering using an electrodynamic ion funnel
Authors: Page Jason S. , Tolmachev Aleksey V. , Tang Keqi , Smith Richard D.
Published: August 2005

An adjustable low‐mass filter has been developed for an electrospray ionization (ESI) source to block ions associated with unwanted background species from entering the mass spectrometer. The low‐mass filter is made by using an adjustable potential energy barrier from the conductance‐limiting plate of an electrodynamic ion funnel, which prohibits species with higher ion mobilities from exiting the ESI source. We show that this arrangement provides a linear voltage adjustment for low‐mass filtering from m/z 0 to 500. Mass filtering above m/z 500 is also performed; however, higher‐mass species are attenuated. The mass filter was tested with a liquid chromatography/mass spectrometry (LC/MS) analysis of a bovine serum albumin (BSA) tryptic digest and resulted in the ability to block low‐mass, background species, which accounted for 40–70% of the total ion current immediately behind the ESI source during peak elution and detection. Copyright © 2005 John Wiley & Sons, Ltd.
TRH‐like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain
Authors: Eugene Pekary A. , Faull Kym F. , Paulson Mark , Lloyd Robert L. , Sattin Albert
Published: August 2005

We have previously reported the occurrence of pGlu‐Glu‐Pro‐NH2(Glu‐TRH, EEP), Val‐TRH, Tyr‐TRH, Leu‐TRH, Phe‐TRH, and Trp‐TRH in rat brain using a combination of HPLC and radioimmunoassays with antibodies that cross‐react with the general structure pGlu‐X‐Pro‐NH2 where ‘X’ maybe any amino acid residue (Peptides 2004; 25 : 647). This new family of TRH‐like peptides, along with TRH (pGlu‐His‐Pro‐NH2), has neuroprotective, anticonvulsant, antidepressant, euphoric, anti‐amnesic, and analeptic effects. We now report that a combination of affinity chromatography using a rabbit antibody specific for Tyr‐TRH and Phe‐TRH, along with HPLC and tandem mass spectrometry operating in the multiple reaction monitoring (MRM) mode, provide conclusive evidence for the presence of Tyr‐TRH in rat brain. Furthermore, synthetic Tyr‐TRH is active in the Porsolt Swim Test suggesting that it is a fourth member of this family of in vivo neuroregulatory agents that have psychopharmacotherapeutic properties. Copyright © 2005 John Wiley & Sons, Ltd.
Novel Photobleachable Deep UV Resists Based on Single Component Nonchemically Amplified Resist System
Authors: Kim Jin‐Baek , Kim Kyoung‐Seon
Published: August 2005

Summary: Photobleachable deep UV resists were designed by introducing diazoketo groups in polymer side chains. The diazoketo groups undergo the Wolff rearrangement upon irradiation in the deep UV, affording ketenes that react with water to provide base‐soluble photoproducts. The polymers were synthesized by radical copolymerization of 2‐(2‐diazo‐3‐oxo‐butyryloxy)‐ethyl methacrylate, 2‐hydroxyethyl methacrylate, and γ‐butyrolacton‐2‐yl methacrylate. The single component resist showed 0.7 µm line and space patterns using a mercury‐xenon lamp in a contact printing mode.

Scanning electron micrograph of 0.7 µm line and space patterns printed with polymer B at a dose of 70 mJ · cm−2.

image

Scanning electron micrograph of 0.7 µm line and space patterns printed with polymer B at a dose of 70 mJ · cm−2.
Strength deficits in primary focal hand dystonia
Authors: Prodoehl Janey , MacKinnon Colum D. , Comella Cynthia L. , Corcos Daniel M.
Published: August 2005

Cortical activation is reduced when patients with focal dystonia perform movements that do not induce dystonic posturing. This finding suggests that the cortical drive to muscles may in some circumstances actually be reduced not increased, as suggested by basal ganglia models of dystonia as a hyperkinetic disorder. The purpose of this study was to examine flexor and extensor strength at the wrist (a clinically affected joint) and elbow (a nonclinically affected joint) in 18 patients with primary focal hand dystonia compared to matched control subjects. We measured peak torque from maximum voluntary contractions, and agonist and antagonist muscle activation by means of surface electromyograms. Patients were significantly weaker than controls at both the elbow and wrist joints and in both flexors and extensors compared to controls. Peak elbow flexion torque was, on average, 14.4% lower in the dystonic compared to the control group, elbow extensor peak torque was 28.6% lower, wrist flexor peak torque was 17.4% lower, and wrist extensor peak torque was 20.7% lower. Strength did not differ as a function of clinical severity. Reductions in peak torque were accompanied by reduced agonist activation, although this finding only reached statistical significance at the elbow. The amount of co‐contraction of antagonistic muscles was not significantly different between the two groups. These results are discussed in the context of dystonia as a disorder resulting from dysfunction of basal ganglia output. © 2005 Movement Disorder Society
Ambulatory motor assessment in Parkinson's disease
Authors: Keijsers Noël L.W. , Horstink Martin W.I.M. , Gielen Stan C.A.M.
Published: August 2005

We developed an algorithm that distinguishes between on and off states in patients with Parkinson's disease during daily life activities. Twenty‐three patients were monitored continuously in a home‐like situation for approximately 3 hours while they carried out normal daily‐life activities. Behavior and comments of patients during the experiment were used to determine the on and off periods by a trained observer. Behavior of the patients was measured using triaxial accelerometers, which were placed at six different positions on the body. Parameters related to hypokinesia (percentage movement), bradykinesia (mean velocity), and tremor (percentage peak frequencies above 4 Hz) were used to distinguish between on and off states. The on–off detection was evaluated using sensitivity and specificity. The performance for each patient was defined as the average of the sensitivity and specificity. The best performance to classify on and off states was obtained by analysis of movements in the frequency domain with a sensitivity of 0.97 and a specificity of 0.97. We conclude that our algorithm can distinguish between on and off states with a sensitivity and specificity near 0.97. This method, together with our previously published method to detect levodopa‐induced dyskinesia, can automatically assess the motor state of Parkinson's disease patients and can operate successfully in unsupervised ambulatory conditions. © 2005 Movement Disorder Society
Phosphodiesterase 4 inhibition reduces skeletal muscle atrophy
Authors: Hinkle Richard T. , Dolan Elizabeth , Cody David B. , Bauer Mary Beth , Isfort Robert J.
Published: August 2005

Several GTP‐binding protein (G‐protein)–coupled receptors that signal through Gαs (GTP‐binding protein α stimulatory) and the cyclic adenosine monophosphate (cAMP) pathway increase skeletal muscle mass. In order to further evaluate the role of the cAMP pathway in the regulation of skeletal muscle mass, we utilized inhibitors of phosphodiesterase 4 (PDE 4), the major cAMP‐modifying PDE found in skeletal muscle, to modulate skeletal muscle cAMP levels. We found that PDE 4 inhibitors reduced the loss of muscle mass and force resulting from denervation and casting in rats and mice. These studies indicate that PDE 4 inhibitors may have a role in the treatment of skeletal muscle–wasting diseases. Muscle Nerve, 2005
Late‐onset distal myopathy with rimmed vacuoles without mutation in the GNE or dysferlin genes
Authors: Suzuki Naoki , Aoki Masashi , Mizuno Hideki , Onodera Yoshiaki , Takahashi Toshiaki , Nagata Tetsuya , Tateyama Maki , Itoyama Yasuto
Published: August 2005

We report two brothers from a Japanese family with a late‐onset distal myopathy characterized by rimmed vacuoles and dysferlin deficiency with no inflammatory infiltration and dystrophic changes in muscle biopsy. Mutations in the GNE, dysferlin, caveolin 3, emerin, and lamin A/C genes were excluded. We speculate that dysferlin is involved in the pathogenesis of the myopathy in these patients, which may represent a new disease entity presenting as a distal myopathy. Muscle Nerve, 2005
Cold elbow syndrome: Spurious slowing of ulnar nerve conduction velocity
Authors: Landau Mark E. , Barner Kristen C. , Murray Evan D. , Campbell William W.
Published: August 2005

Low temperature decreases nerve conduction velocity (NCV). The across‐elbow segment of the ulnar nerve is superficial and may be particularly susceptible to decreased temperature. We evaluated patients without clinical ulnar neuropathy at the elbow (UNE) but with isolated slowing of the across‐elbow ulnar NCV (normal group), and patients with clinical and electrodiagnostic findings of UNE (UNE group). All subjects had ulnar motor nerve studies completed before and after warming. The mean across‐elbow NCV was 43.4 m/s and 48.6 m/s (P < 0.0001) in the normal group, and 37.4 m/s and 37.7 m/s (P = 0.90) in the UNE group, before and after warming, respectively. There was no change in the forearm segment NCV in either group. Seventeen of 32 subjects in the normal group had completely normal studies after warming. No patients with UNE developed normal across‐elbow NCV with warming. Low temperature slows across‐elbow ulnar NCV in normal subjects without impact on the forearm segment. Warming of the elbow improves across‐elbow ulnar NCV in normals, but does not reverse the abnormalities in patients with UNE. Elbow warming should become a routine part of ulnar nerve conduction studies, especially when there is isolated conduction slowing in the across‐elbow segment. Muscle Nerve, 2005
Flexibility of Steiner trees in uniform orientation metrics
Authors: Brazil M. , Winter P. , Zachariasen M.
Published: August 2005

We present some fundamental flexibility properties for minimum length networks (known as Steiner minimum trees) interconnecting a given set of points in an environment in which edge segments are restricted to λ uniformly oriented directions. These networks are referred to as λ‐SMTs. They promise to play an increasingly important role in the future of optimal wire routing in VLSI physical design, particularly for the next generation of VLSI circuits. In this article we develop the concept of a flexibility polygon for a λ‐SMT, which is a region representing the union of all λ‐SMTs with the same topology on a given set of points. We show that this polygon can be constructed, for a given point set and given topology, in linear time. We discuss some of the future applications of this polygon, which can be thought of as a geometric representation of the amount of flexibility inherent in a given λ‐SMT. © 2005 Wiley Periodicals, Inc. NETWORKS, Vol. 46(3), 142–153 2005
Dihydropyridine zur Behandlung der arteriellen Hypertonie: Therapieoptionen zur Blutdrucksenkung
Authors: Gasser Robert , Bareza Niksa , Gasser Sandra , Toferer Ernst , Scheer Elisabeth , Pruthi Dafina
Published: August 2005

Dihydropyridine sind zur Primärprävention der KHK gut geeignet. Amlodipin und Felodipin können auch trotz Herzinsuffizienz gegeben werden. Dihydropyridine sind in der Lage, einerseits Diabetesneuerkrankungen zu reduzieren, andererseits kardiovaskuläre, zerebrovaskuläre Ereignisse und die Gesamtmortalität bei diabetischen Hypertonikern zu senken. Vorteile gegenüber anderen Antihypertensiva bringt die Therapie mit Calcium‐Antagonisten in der Primärprävention von Hypertonikern in Bezug auf das Schlaganfallrisiko. Mögliche Nebenwirkungen können durch den Einsatz einer Kombinationstherapie verringert werden. Calcium‐Antagonisten sind eine bewährte und sichere Therapieoption zur Blutdrucksenkung. Es konnte deutlich gezeigt werden, dass sie die Prognose bei Hypertonikern verbessern können und dass sie sich sehr gut für eine Kombinationstherapie eignen.
Arzneizubereitungen mit Calciumkanal‐Blockern: Wie die Arzneiform zum Therapieerfolg beiträgt
Authors: Warnke André , Blume Henning
Published: August 2005

Für die Dauerbehandlung von Bluthochdruckpatienten ist eine konsistente antihypertensive Wirksamkeit über den gesamten Tag wünschenswert. Diese ist am besten mit Produkten zu erreichen, die zur einmal täglichen Applikation geeignet sind. Solche Zubereitungen stehen inzwischen für verschiedene Calciumkanal‐Blocker zur Verfügung. Allerdings sollten die betreffenden Arzneiformen auch in der Lage sein, die Resorption des Wirkstoffs in den Organismus unter verschiedenen Applikationsbedingungen (vor oder nach dem Essen) so gezielt zu steuern, dass die angestrebten konstanten Plasmakonzentrationen sicher erreicht werden. Das Beispiel verschiedener handelsüblicher Nifedipin‐Präparate zeigt nachdrücklich, dass diese Zielvorgabe nicht mit allen Produkten tatsächlich realisiert werden kann. Insofern sind die Befunde aus sachgerecht durchgeführten Studien zur Interaktion mit Mahlzeiten für die Therapieentscheidung unbedingt zu beachten. Voraussetzung ist jedoch, dass die Erkenntnisse aus den Untersuchungen den Fachkreisen auch bekannt gemacht werden.
L‐Typ‐Calciumkanäle in T‐Zellen
Authors: Winckler Thomas
Published: August 2005

Die Aktivierung des T‐Zellrezeptors initiiert einen raschen Einstrom von Calciumionen, der für die Funktionen der T‐Zellen von Bedeutung ist.
Therapeutic choices in the current millennium: Hemophilia workshop highlights
Authors: Mathew Prasad , Manno Catherine S. , Aledort Louis M.
Published: August 2005

Many issues affect hemophilia care providers when managing bleeding episodes in individuals with hemophilia. A diverse group of hemophilia providers from the United States met at two workshops to discuss the issues influencing treatment choices in the current millennium and to learn about current advances in treatment of hemophilia. This paper provides a summary of the discussions at these workshops. Despite the progress made in the management of patients with hemophilia, the workshop highlighted the fact that there were still many unanswered questions. Pediatr Blood Cancer 2005;45:611–615. © 2005 Wiley‐Liss, Inc.
Deep intracranial extension of squamous cell carcinoma of the scalp
Authors: Etlik Ömer , Bay Ali , İzmirli Mustafa , Uğraş Serdar , Yılmaz Nebi , Turan Arzu
Published: August 2005

We report a case of recurrent squamous cell carcinoma (SCC) of the scalp with deep cerebral invasion in a 15‐year‐old girl. Plain films and CT showed extensive, full thickness, and skull destruction at the vertex. Gadolinium‐enhanced MRI revealed neoplastic invasion of the meninges and both cerebral hemisphers down to the lateral ventricle. This case represents an example of (SCC) imitating a primary brain tumor by exhibiting intracranial extension. © 2005 Wiley‐Liss, Inc.