bluuebunny/crossref_metadata_2025 huggingface dataset:
CTLA-4Ig Suppresses Liver Injury by Inhibiting Acquired Immune Responses in a Mouse Model of Fulminant Hepatitis *
Authors: Nakayama Yasuhiro , Shimizu Yukihiro , Hirano Katsuharu , Ebata Kazumi , Minemura Masami , Watanabe Akiharu , Sugiyama Toshiro
Published: September 2005

Expression of costimulatory molecules is significantly upregulated in various organs in an animal model of severe hepatitis induced by injection of

Propionibacterium acnes

(

P. acnes

) and lipopolysaccharide (LPS). In the present study, we examined whether blockade of costimulatory signals by CTLA-4Ig can suppress the liver injury in this model. We injected an adenovirus encoding CTLA-4Ig (AdCTLA-4Ig) into mice 7 days before, on the same day, or 3 days after

P. acnes

priming. The virus was found to infect the liver preferentially, and CTLA-4Ig was detected in the serum as early as 2 days after viral injection. After injection of LPS, liver injury and survival rates were examined. Most of the mice not injected with AdCTLA-4Ig died within 12 hours after injection of LPS. In contrast, all the AdCTLA-4Ig–injected mice survived when the virus was injected 7 days before or on the same day as

P. acnes

priming. Importantly, hemorrhagic liver injury and serum alanine aminotransferase levels were significantly reduced after LPS injection even when AdCTLA-4Ig was injected 3 days after

P. acnes

priming. Immunological analyses showed that CTLA-4Ig inhibited the activation and expansion of

P. acnes

–specific CD4+ T cells in the hepatic lymph nodes, leading to a reduction in the recruitment of the cells to the liver. The total amounts of interferon-γ, interleukin-12, and various chemokines in the liver were then decreased, resulting in inhibition of the secondary recruitment of not only T cells but also macrophages.
In conclusion
, CTLA-4Ig could be useful for treatment of severe liver injury.

Supplementary material for this article can be found on the Hepatology website (

http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html

).

(Hepatology 2005;42:915–924.)
Molecular Changes From Dysplastic Nodule to Hepatocellular Carcinoma Through Gene Expression Profiling *
Authors: Nam Suk Woo , Park Jik Young , Ramasamy Adaikalavan , Shevade Shirish , Islam Amirul , Long Philip M. , Park Cheol Keun , Park Soo Eun , Kim Su Young , Lee Sug Hyung , Park Won Sang , Yoo Nam Jin , Liu Edison T. , Miller Lance D. , Lee Jung Young
Published: September 2005

Progression of hepatocellular carcinoma (HCC) is a stepwise process that proceeds from pre-neoplastic lesions—including low-grade dysplastic nodules (LGDNs) and high-grade dysplastic nodules (HGDNs)—to advanced HCC. The molecular changes associated with this progression are unclear, however, and the morphological cues thought to distinguish pre-neoplastic lesions from well-differentiated HCC are not universally accepted. To understand the multistep process of hepato-carcinogenesis at the molecular level, we used oligo-nucleotide microarrays to investigate the transcription profiles of 50 hepatocellular nodular lesions ranging from LGDNs to primary HCC (Edmondson grades 1-3). We demonstrated that gene expression profiles can discriminate not only between dysplastic nodules and overt carcinoma but also between different histological grades of HCC via unsupervised hierarchical clustering with 10,376 genes. We identified 3,084 grade-associated genes, correlated with tumor progression, using one-way ANOVA and a one-versus-all unpooled

t

test. Functional assignment of these genes revealed discrete expression clusters representing grade-dependent biological properties of HCC. Using both diagonal linear discriminant analysis and support vector machines, we identified 240 genes that could accurately classify tumors according to histological grade, especially when attempting to discriminate LGDNs, HGDNs, and grade 1 HCC.
In conclusion
, a clear molecular demarcation between dysplastic nodules and overt HCC exists. The progression from grade 1 through grade 3 HCC is associated with changes in gene expression consistent with plausible functional consequences.

Supplementary material for this article can be found on the Hepatology website (

http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html

).

(Hepatology 2005;42:809–818.)
New Kinetic Models for the Hepatitis C Virus *
Authors: Perelson Alan S. , Herrmann Eva , Micol Florence , Zeuzem Stefan
Published: September 2005

Viral kinetic modeling has played an important role in the analysis of HCV RNA decay after the initiation of antiviral therapy. Models have provided a means of evaluating the antiviral effectiveness of therapy, of estimating parameters such as the rate of virion clearance and the rate of clearance of hepatitis C virus (HCV)–infected cells, and they have suggested mechanisms of action for both interferon and ribavirin. Nevertheless, the models that were originally formulated were unable to explain all of the observed HCV RNA profiles. We provide an update on the state of HCV kinetic modeling and discuss new models that have taken into consideration the different pharmacokinetics of standard and pegylated forms of interferon, allow for changes in drug effectiveness as drug concentrations fall between dosing intervals, and that have incorporated alanine aminotransferase kinetics and aspects of immune responses to provide a more comprehensive picture of the biology underlying changes in HCV RNA during therapy. (Hepatology 2005;42:749–754.)
Endocannabinoids Promote Hepatic Lipogenesis and Steatosis Through CB1 Receptors
Authors: Schwabe Robert F.
Published: September 2005

Endogenous cannabinoids acting at CB1 receptors stimulate appetite, and CB1 antagonists show promise in the treatment of obesity. CB1−/− mice are resistant to diet-induced obesity even though their caloric intake is similar to that of wild-type mice, suggesting that endocannabinoids also regulate fat metabolism. Here, we investigated the possible role of endocannabinoids in the regulation of hepatic lipogenesis. Activation of CB1 in mice increases the hepatic gene expression of the lipogenic transcription factor SREBP-1c and its targets acetyl-CoA carboxylase-1 and fatty acid synthase (FAS). Treatment with a CB1 agonist also increases de novo fatty acid synthesis in the liver or in isolated hepatocytes, which express CB1. High-fat diet increases hepatic levels of the endocannabinoid anandamide (arachidonoyl ethanolamide), CB1 density, and basal rates of fatty acid synthesis, and the latter is reduced by CB1 blockade. In the hypothalamus, where FAS inhibitors elicit anorexia, SREBP-1c and FAS expression are similarly affected by CB1 ligands. We conclude that anandamide acting at hepatic CB1 contributes to diet-induced obesity and that the FAS pathway may be a common molecular target for central appetitive and peripheral metabolic regulation.
NADPH Oxidase-Dependent Reactive Oxygen Species are Important to the Early Stage of CD95 Engagement in Hepatocytes *
Authors: Yin Xiao-Ming
Published: September 2005

CD95 ligand (CD95L) triggers a rapid formation of reactive oxygen species (ROS) as an upstream event of CD95 activation and apoptosis induction in rat hepatocytes. This ROS response was sensitive to inhibition by diphenyleneiodonium, apocynin, and neopterin, suggestive of an involvement of NADPH oxidases. In line with this, hepatocytes expressed mRNAs not only of the phagocyte gp91

phox

(Nox 2), but also of the homologs Nox 1 and 4 and Duox 1 and 2, as well as the regulatory subunit p47

phox

. gp91

phox

(Nox 2) and p47

phox

were also identified at the protein level in rat hepatocytes. CD95L induced within 1 min ceramide formation and serine phosphorylation of p47

phox

, which was sensitive to inhibitors of sphingomyelinase and protein kinase Cζ (PKCζ). These inhibitors and p47

phox

protein knockdown inhibited the early CD95L-induced ROS response, suggesting that ceramide and PKCζ are upstream events of the CD95Linduced Nox/Duox activation. CD95L also induced rapid activation of the Src family kinase Yes, being followed by activation of c-Src, Fyn, and c-Jun-N-terminal kinases (JNK). Only Yes and JNK activation were sensitive to

N

-acetylcysteine, inhibitors of NADPH oxidase, PKCζ, or sphingomyelinase, indicating that the CD95L-induced ROS response is upstream of Yes and JNK but not of Fyn and c-Src activation. Activated Yes rapidly associated with the epidermal growth factor receptor (EGFR), which became phosphorylated at Tyr845 and Tyr1173 but not at Tyr1045. Activated EGFR then triggered an AG1478-sensitive CD95-tyrosine phosphorylation, which was a signal for membrane targeting of the EGFR/CD95 complex, subsequent recruitment of Fas-associated death domain and caspase 8, and apoptosis induction. All of these events were significantly blunted by inhibitors of sphingomyelinase, PKCζ, NADPH oxidases, Yes, or EGFR-tyrosine kinase activity and after protein knockdown of either p47

phox

, Yes, or EGFR. The data suggest that CD95L-induced apoptosis involves a sphingomyelinase- and PKCζ-dependent activation of NADPH oxidase isoforms, which is required for Yes/EGFR/CD95 interactions as upstream events of CD95 activation. (Hepatology 2005;42:956–958.)
Comment on “Using quaternions to calculate RMSD” [J. Comp. Chem. 25, 1849 (2004)]
Authors: Kneller G. R.
Published: September 2005

Coutsias et al. have recently published a method to find the optimal rotational superposition of two molecular structures, which is based on a representation of rotations by quaternions (J. Comp. Chem. 25(15), 1849 (2004)). The method, which has been suggested by other authors before, is compared to the one by Kabsch, where the elements of the rotation matrix are directly used as variables of the optimization problem. The statement that the two methods are equivalent is misleading in the sense that the Kabsch method may yield an improper optimal rotation, which must be explicitly checked for, whereas the quaternion method does not mix proper and improper rotations. Nevertheless, both types of solutions can be considered by solving the same eigenvector problem. The relation between the two types of solutions is briefly discussed and bounds for the eigenvalues are given. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1660–1662, 2005
Effects of axotomy on telomere length, telomerase activity, and protein in activated microglia
Authors: Flanary Barry E. , Streit Wolfgang J.
Published: September 2005

The adult central nervous system (CNS) is generally thought of as a postmitotic organ. However, DNA labeling studies have shown that one major population of nonneuronal cells, called microglia, retain significant mitotic potential. Microglial cell division is prominent during acute CNS injury involving neuronal damage or death. Prior work from this laboratory has shown that purified microglia maintained in vitro with continual mitogenic stimulation exhibit telomere shortening before entering senescence. In the current study, we sought to investigate whether telomere shortening occurs in dividing microglia in vivo. For this purpose, we used a nerve injury model that is known to trigger localized microglial proliferation in a well‐defined CNS region, the facial motor nucleus. Adult Sprague‐Dawley rats underwent facial nerve axotomy, and facial motor nuclei were microdissected after 1, 4, 7, and 10 days. Whole tissue samples were subjected to measurements of telomere length, telomerase activity, and telomerase protein. Results revealed a tendency for all of these parameters to be increased in lesioned samples. In addition, microglial cells isolated directly from axotomized facial nuclei with fluorescence‐activated cell sorting (FACS) showed increased telomerase activity relative to unoperated controls, suggesting that microglia are the primary cell type responsible for the increases observed in whole tissue samples. Overall, the results show that microglia activated by injury are capable of maintaining telomere length via telomerase during periods of high proliferation in vivo. We conclude that molecular mechanisms pertaining to telomere maintenance are active in the injured CNS. © 2005 Wiley‐Liss, Inc.
Developmental change and function of chondroitin sulfate deposited around cerebellar Purkinje cells
Authors: Shimazaki Yumiko , Nagata Isao , Ishii Maki , Tanaka Masahiko , Marunouchi Tohru , Hata Toshihiro , Maeda Nobuaki
Published: September 2005

Chondroitin sulfate is a long sulfated polysaccharide with enormous structural heterogeneity that binds with various proteins, such as growth factors, in a structure‐dependent manner. In this study, we analyzed the expression of chondroitin sulfate in the postnatally developing cerebellar cortex by using three monoclonal antibodies against chondroitin sulfate, MO‐225, 2H6, and CS‐56, which recognize different structural domains in this polysaccharide. During the first postnatal week, the patterns of immunohistochemical staining made by these antibodies were quite similar, and the molecular layer, the granule cell layer, and Bergmann glial fibers in the external granular layer were densely stained. After postnatal day 12 (P12), the expression of 2H6 epitopes was down‐regulated in the molecular layer, and the expression of CS‐56 epitopes in this layer was also reduced after P16. On the other hand, the strong expression of MO‐225 epitopes, GlcA(2S)β1–3GalNAc(6S) (D unit)‐containing structures, remained until adulthood. These chondroitin sulfate epitopes were observed around Purkinje cells, including cell soma and dendrites. Detailed immunohistochemical analysis suggested that chondroitin sulfate was deposited between Purkinje cell surfaces and the processes of Bergmann glia. Furthermore, the amount of pleiotrophin, a heparin‐binding growth factor, in the cultured cerebellar slices was remarkably diminished after treatment with chondroitinase ABC or D unit‐rich chondroitin sulfate. With the previous findings that pleiotrophin binds to D unit‐rich chondroitin sulfate, we suggest that the D‐type structure is important for the signaling of pleiotrophin, which plays roles in Purkinje cell–Bergmann glia interaction, and that the structural changes of chondroitin sulfate regulate this signaling pathway. © 2005 Wiley‐Liss, Inc.
Notch 1 interacts with the amyloid precursor protein in a Numb‐independent manner
Authors: Fassa Angeliki , Mehta Pankaj , Efthimiopoulos Spiros
Published: September 2005

We hypothesized that the physical interaction between the amyloid precursor protein (APP) and Notch 1 (N1) may be mediating the reported cross‐talk between the respective signaling pathways. Immunoprecipitation of mouse N1 (mN1) or extracellular domain truncated mN1 (mN1‐TM, mimics TACE‐produced membrane‐bound C‐terminal fragment) specifically coprecipitated APP751. Conversely, immunoprecipitation of APP751 specifically coprecipitated mN1, furin‐generated membrane‐bound mN1 C‐terminal fragment (f.mN1‐TM), or mN1‐TM. The London mutation of APP did not affect the APP751/mN1 interaction. Coexpression of APP751 and mN1 did not affect APP processing or production of mN1 intracellular domain (mNICD). The APP751/mN1 interaction was Numb‐independent, insofar as it was observed in HEK293 cells that lack detectable levels of Numb and was unaffected by the expression of exogenous Numb or deletion of the APP cytoplasmic domain, including the Numb‐binding YENPTY sequence. This interaction was unaffected even when the N‐terminal 647 amino acids of APP were replaced by a sequence of secreted alkaline phosphatase. These data combined with data showing interaction between mN1‐TM and APP751 suggest that their transmebrane domains and short sequences around them are sufficient for the interaction and that APP751 and mN1 interact in cis. Our results imply novel functions of APP and/or N1 that derive from their interaction. © 2005 Wiley‐Liss, Inc.
Functional significance of HCN2/3‐mediated Ih in striatal cells at early developmental stages
Authors: Bajorat Rika , Bräuer Anja U. , Wasner Ulrike , Rolfs Arndt , Strauss Ulf
Published: September 2005

Hyperpolarization‐activated cAMP‐gated cation currents (Ih) were recently linked to pre‐ and postnatal developmental processes in several brain regions, including the ventral telencephalon. To evaluate the role of Ih in striatal development, we used short‐term cultured cells from the lateral ganglionic eminence at embryonic day 14 (E14) and postnatal days 1–3 (P1–3) as well as the embryonic striatal progenitor cell line ST14A. Western blot analysis of the Ih underlying subunit proteins HCN1–4 revealed strong HCN2 expression in proliferating ST14A cells and weak expression in postmitotic ST14A cells and in cells from the developing brain. We also found HCN3 expression only in ST14A cells at both proliferative and nonproliferative stages but not in short‐term cultured striatal cells. In all cases, HCN1 and HCN4 transcripts were below the detection level. Despite the selective protein expression, RT‐PCR analysis showed stable expression of HCN2–4 but not HCN1 mRNA in all short‐term‐cultured striatal cells and in the ST14A cell line. Consistent with the strong protein expression, an Ih was recorded with features of an HCN2‐mediated current in ST14A cells at the proliferative stage and in short‐term‐cultured E14 cells. Of particular importance is that we detected no currents upon hyperpolarization in the ST14A cells at the nonproliferative stage when only HCN3 protein was present. These results suggest the potential importance of ST14A cells in defining the molecular mechanisms regulating Ih expression and function. © 2005 Wiley‐Liss, Inc.
Differential effects of ethanol on glial signal transduction initiated by lipopolysaccharide and interferon‐γ
Authors: Choi Dong‐Kug , Lee Heasuk , Jeong Jaeyoon , Lim Beongou , Suk Kyoungho
Published: September 2005

Although the pathogenic effects of alcohol abuse on brain are well established, its specific effects on the intracellular signal transduction pathways of glial cells in the central nervous system (CNS) are poorly understood. In this study, we evaluated how ethanol affects the glial signal transduction associated with inflammatory activation. Lipopolysaccharide (LPS), gangliosides, and interferon (IFN)‐γ induced the inflammatory activation of glia, which was differentially influenced by ethanol: 1) ethanol inhibited LPS‐ or gangliosides‐induced, but not IFNγ‐induced, glial activation as demonstrated by the production of nitric oxide and the expression of inflammatory genes such as interleukin‐1β, tumor necrosis factor‐α, IP‐10, and CD86; 2) nuclear factor (NF)‐κB or JAK/STAT1 pathway was necessary for LPS‐ or IFNγ‐induced glial activation, respectively; 3) ethanol inhibited LPS‐induced NF‐κB activation; and 4) ethanol did not significantly affect IFNγ‐induced STAT1/IRF‐1 activation. Based on these results, ethanol seems to inhibit selectively some parts of the glial signal transduction pathways that are associated with inflammatory activation, which may lead to the deregulation of CNS inflammatory responses. © 2005 Wiley‐Liss, Inc.
“I still like Google”: University student perceptions of searching OPACs and the web
Authors: Fast Karl V. , Campbell D. Grant
Published: September 2005

This paper reports on an exploratory study of how university students perceive and interact with Web search engines compared to Web‐based OPACs. A qualitative study was conducted involving sixteen students, eight of whom were first‐year undergraduates and eight of whom were graduate students in Library and Information Science. The participants performed searches on Google and on a university OPAC. The interviews and think‐afters revealed that while students were aware of the problems inherent in Web searching and of the many ways in which OPACS are more organized, they generally preferred Web searching. The coding of the data suggests that the reason for this preference lies in psychological factors associated with the comparative ease with which search engines can be used, and system and interface factors which made searching the Web much easier and less confusing. As a result of these factors, students were able to approach even the drawbacks of the Web—its clutter of irrelevant pages and the dubious authority of the results—in an enthusiastic and proactive manner, very different from the passive and ineffectual admiration they expressed for the OPAC. The findings suggest that requirements of good OPAC interface design must be aggressively redefined in the face of new, Web‐based standards of usability.
Evaluation of periodic leg movements and associated transcranial magnetic stimulation parameters in restless legs syndrome
Authors: Kutukcu Yasar , Dogruer Erhan , Yetki̇n Si̇nan , Ozgen Fuat , Vural Okay , Aydi̇n Hamdullah
Published: September 2005

Restless legs syndrome (RLS), a sensorimotor disorder characterized by unpleasant sensations commonly localized in the legs, is frequently associated with periodic limb movements (PLMs) during sleep. We investigated the role of transcranial magnetic stimulation (TMS) and cortical silent period (CSP) duration as diagnostic and monitoring tools in 20 patients with primary RLS before and after 1 month of treatment and also studied 15 normal age‐ and gender‐matched subjects. Polysomnographic assessment was undertaken and the PLM index determined in 17 of the 20 patients. We also studied the correlation between sleep efficiency index and CSP duration because of the increasing severity of the sleep disturbance and PLMs in patients with RLS. Our results demonstrate that the duration of the CSP was reduced in patients with RLS, and that dopaminergic treatment normalized this duration. There was no correlation between the PLM index and CSP duration. It may be speculated that PLMs and the CSP are due to different inhibitory mechanisms and they may be used separately as diagnostic and monitoring tools in patients with primary RLS. Muscle Nerve, 2005
Thermal analysis of the multiple melting behavior of poly(butylene succinate‐co‐adipate)
Authors: Wang Yaming , Bhattacharya Mrinal , Mano João F.
Published: September 2005

The melting behavior of poly(butylene succinate‐co‐adipate) (PBSA) isothermally crystallized from the melt was investigated by differential scanning calorimetry. Triple, double, or single melting endotherms were observed in subsequent heating scan for the samples isothermally crystallized at different temperatures. These endothermic peaks were labeled as I, II, and III for low‐, middle‐, and high‐temperature melting endotherms, respectively. The independence of endotherm III to the crystallization temperature, the existence of an exothermic crystallization peak just below the endotherm III, and the heating rate dependence of endotherm III indicated that endotherm III was due to the remelting of recrystallized lamellar during a heating scan. The influence of crystallization time on the melting behavior of PBSA showed that endotherms II and III developed prior to endotherm I; endotherm III developed rather simultaneously with endotherm II. Further investigation showed that the peak temperature of endotherm I increased linearly with the logarithm of the crystallization time. It suggested that endotherm II was attributed to the melting of the primary lamellae, while endotherm I was due to the melting of secondary lamellae. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3077–3082, 2005
Self‐organization of functional gradient structure in the biodegradable chitosan/poly(vinyl alcohol) blend film
Authors: Hexig B. , Alata H. , Inoue Y.
Published: September 2005

Biologically inspired optimal structures combining the bioresorbable and bioactive properties are expected for the next generation of biomaterials. A compositional gradient structure was found to be spontaneously formed in the film of biodegradable chitosan/poly(vinyl alcohol) blend by casting aqueous solution on an aluminum dish. The formation of compositional gradient structure was confirmed by FTIR mapping measurement, DMTA measurement, and SEM observation on the freeze‐fractured cross section. In DMTA measurement, a broadening of the α‐relaxation curve corresponding to the glass transition was observed for the compositional gradient film, while a composition‐dependent single glass transition was observed for the homogeneous blend films. The resulted film with stable self‐organized compositional gradient exhibits novel physical properties inaccessible for the film of homogeneous blends obtained by casting from the same solution on a Teflon dish. The compositional gradient films present a unique combination of stronger stress and higher yield strain when compared with those of the homogeneous films at both dry and wet states. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3069–3076, 2005
Course of psychological distress and its predictors in advanced non‐small cell lung cancer patients
Authors: Akechi Tatsuo , Okuyama Toru , Akizuki Nobuya , Azuma Hideki , Sagawa Ryuichi , Furukawa Toshiaki A. , Uchitomi Yosuke
Published: September 2005

This study investigated longitudinal changes and predictive factors for psychological distress among 85 newly diagnosed advanced non‐small cell lung cancer (NSCLC) patients. Whereas tension‐anxiety after diagnosis (T1) was significantly reduced at two months (T2) and six months (T3) after diagnosis and depression‐dejection at T1 was significantly reduced at T2, other forms of psychological distress, including anger–hostility, vigor, fatigue, and confusion, did not show significant changes. Total mood disturbance did not show significant change. Only a higher total mood disturbance at T1 was a significant predictor of total mood disturbance at T3. These findings demonstrate that most types of psychological distress experienced by advanced NSCLC patients is likely to persist during the subsequent clinical course. The findings also suggest that initial psychological distress itself after cancer diagnosis is the most important predictor for subsequent psychological distress and that early intervention beginning immediately after the disclosure of a diagnosis of cancer is one way to prevent and/or reduce subsequent psychological distress in advanced NSCLC patients. Copyright © 2005 John Wiley & Sons, Ltd.
Role of the liver in the pathogenesis of cerebral disorders in phenylketonuria
Authors: Barashnev Y. I. , Korneichuk V. V. , Klembovsky A. I. , Klyushina L. A.
Published: September 2005

Comprehensive studies on structure and function of the liver (biochemical profiles, light and electron microscopy, determination of phenylalanine hydroxylase activity) were performed in children with phenylketonuria (PKU). It was established that the liver is always involved in the pathological process. Comparison of results obtained with peculiarities of neuropsychiatric disorders revealed a dependence of the initial manifestations and the severity of PKU on the extent of enzyme deficiency. Amino acid disorders and abnormal lipid metabolism both contribute to the genesis of cerebral lesions.
Aminoacidopathies in andhra pradesh; report of a screening programme
Authors: Uma S. M. , Jyothy A. , Reddy P. P. , Reddi O. S.
Published: September 2005

A systematic and selective screening programme to detect disorders of amino acid metabolism was undertaken to gain insight into the incidence and prevalence of such disorders in the southern part of India. This region was selected due to the high incidence of consanguineous marriages. No earlier data were available. We based our study on mentally retarded children. We have attempted dietary therapy in two patients with phenylketonuria; the biochemical response in both cases was satisfactory. The highlight of this survey was the detection of a new metabolic defect, threoninaemia.
Glycogen storage disease type 1b due to a defect of glucose‐6‐phosphate translocase
Authors: Narisawa K. , Otomo H. , Igarashi Y. , Arai N. , Otake M. , Tada K. , Kuzuya T.
Published: September 2005

Abstracts

Patients with glycogen storage disease (GSD) type 1b have shown normal activity of glucose‐6‐phosphatase (EC 3.1.3.9) as assayed in frozen liver, though their clinical and biochemical findings were similar to those of patients with GSD 1a (McKusick 23220) (Senior and Loridan, 1968). In 1978, we suggested that a basic defect of GSD 1b exists in the glucose‐6‐phosphate (G6P) transport system (Narisawa et al., 1978; Igarashiet al., 1979). Since then, there have been reports confirming our observation (Beaudetet al., 1980; Langeet al., 1980; Corbeelet al., 1981; Schaubet al., 1981). Recently, it was postulated that the G6Pase system contains a phosphate translocase which mediates the efflux of phosphate, in addition to a G6P translocase and a non‐specific phosphohydrolase (Arionet al., 1980). Therefore, it is possible that GSD 1b is caused by a defect of phosphate translocase. In this paper, the basic defect in GSD type 1b was investigated in two patients; one with severe, the other with mild, clinical symptoms.
Hepatic tyrosine aminotransferase in tyrosinaemia type II
Authors: Kida K. , Takahashi M. , Fujisawa Y. , Matsuda H. , Machino H. , Miki Y.
Published: September 2005

Tyrosinaemia type II (Richner‐Hanhart's syndrome), first reported by Wadmanet al. (1968), is characterized by a highly elevated level of tyrosine in blood and corneal ulcer, dermal hyperkeratosis and mental retardation. Fellmanet al. (1969) showed that this disease was caused by the defect of the cytosolic tyrosine aminotransferase of the liver. We now report a case of this disease with enzymological studies of the biopsied liver.
Structures of a peptide fragment of β2‐microglobulin studied by replica‐exchange molecular dynamics simulations – Towards the understanding of the mechanism of amyloid formation
Authors: Nishino Masamichi , Sugita Yuji , Yoda Takao , Okamoto Yuko
Published: September 2005

We investigate in detail the structural properties of the monomeric peptide fragment that corresponds to residues 21–31 of β2‐microglobulin. As a first step towards the understanding of the mechanism of the amyloid formation, we have performed a replica‐exchange molecular dynamics simulation of this peptide with explicit water molecules. We analyze various structural properties as functions of temperature. Although the corresponding part of the native protein is a fully extended β‐strand, our results show that β‐hairpin structures are formed with high frequency around 310 K. We conjecture that this β‐hairpin formation is closely related to the amyloid fibrillogenesis.
Integrating service design principles and information technology to improve delivery and productivity in public sector operations: The case of the South Carolina DMV
Authors: Karwan Kirk R. , Markland Robert E.
Published: September 2005

One relatively unanswered question regarding operational efficiency and effectiveness is whether and how public sector or government operations can employ service strategy and design concepts to deal with the conflicting objectives of minimizing expenditures while providing for an increasing number of “causes” [Haywood‐Farmer, J., Nollet, J., 1991. Service Plus: Effective Service Management, G. Morin Publisher, Quebec]. In this paper, we argue that the mechanism that permits or enables simultaneous success on these dimensions in public sector operations is information technology applied in conjunction with a unified set of service operations concepts. To demonstrate this contention, we employ an adaptation of the Goldstein et al. [Goldstein, S.M., Johnston, R., Duffy, J., Rao, J., 2002. The service concept: the missing link in service design research? Journal of Operations Management 20 (2), 121–134] service planning design framework, taking issue with some interpretative aspects of their strategic model. The modified planning framework was applied to an initiative in South Carolina state government to improve operations and technology deployment at the Department of Motor Vehicles (DMV). The detailed and ongoing case study illustrates the utility of a broad service‐based, IT‐enabled approach to designing a government service, while simultaneously demonstrating that operational service alignment is the key to avoiding results that have long been labeled a dilemma in the public sector.
RETRACTED: Advance of the outlet glaciers during regional warming as inferred from Late Holocene massive diamicton in the King George Island fjords, the South Shetland Islands, West Antarctica
Authors: Yoo Kyu-Cheul , Il Yoon Ho , Park Byong-Kwon , Kim Yeadong
Published: September 2005

This article has been retracted at the request of the Editor-in-Chief. Please see http://www.elsevier.com/locate/withdrawalpolicy.Reason: Following publication of this article, the Editor-in-Chief has realized that much of the included information had been previously published in the paper Yoon, H.I., Yoo, K.-C., Park, B.-K., Kim, Y., Khim, B.-K., and Kang, C.-Y., 2004. The origin of massive diamicton in Marian and Potter coves, King George Island, West Antarctica. Geosciences Journal 8, 1–10. As a result, the later manuscript is being retracted; readers interested in this topic should refer to the earlier paper.
Genetic improvement of forage crops – past, present and future
Authors: HUMPHREYS M. O.
Published: September 2005

Grass is a complex crop and its value for agriculture must be assessed in terms of the quantity and quality of downstream livestock products (milk, meat and wool). In addition to being a natural low-cost feed for ruminants, grassland protects soil and water resources and enhances the landscape. Temperate grasslands support a major share of the world's milk and beef production but now there is increasing emphasis on sustainability in livestock farming systems rather than maximizing outputs. The economic sustainability of livestock producers in many developed temperate regions is increasingly linked to production from fewer animals giving a higher quality product. A key element in the efficiency of all grassland systems is to optimize the protein/energy balance of forage and value it in a similar way to other livestock feeds. Grasses are rich in energy comprising structural and non-structural carbohydrates while forage legumes are rich in protein. The main forage legumes used in Europe are white and red clover, and lucerne, which form an essential part of sustainable farming systems because of their high nutritive value and ability to fix nitrogen. The productivity of grasslands containing legumes generally reflects the amount of N fixation, which is 65–280 kg/ha/year in W. Europe. Animal production from white clover-based pastures in Europe can be 0·8 that obtained from grass pastures fertilized with 400 kg N/ha/year, and that from lucerne and red clover can be equivalent to animal production from such pastures.
Solar wind control of Jovian auroral emissions
Authors: Galopeau Patrick H. M. , Boudjada Mohammed Y.
Published: September 2005

The combination of Galileo/PWS and Wind/WAVES observations allows the study of the flux density variation of the Jovian hectometric emissions (HOM) observed from 31 August 1996 until 24 October 1996. It is found that the HOM emission presents periodic features; each one is called a “HOM event.” Such episodic emissions were concurrently observed by both experiments with similar spectral characteristics. The fluctuations of the Jovian hectometric emissions and the solar wind parameters are found to exhibit quasi‐similar variations when a time lag of about 153 days is taken into consideration. Also, “HOM enhancements,” like the “injection events” first reported by Mauk et al. (1997), are found to occur at some specific longitudes. The occurrence of these magnetospheric events increases at two “active longitudes,” i.e., 45° CML and 180° CML. The solar wind seems to be at the origin of both phenomena. Solar particles go through the polar regions where they interact with the Jovian magnetic field and give rise in the auroral and equatorial regions to an increase of Jovian hectometric emissions and/or injection events.
Turbulent diffusion and transport from a CO2 lake in the deep ocean
Authors: Haugan Peter M. , Alendal Guttorm
Published: September 2005

If liquid CO2 is stored as a dense “lake” on the deep ocean floor, it is expected to dissolve in seawater. Ocean currents and turbulence can increase the net rate of CO2 release by several orders of magnitude compared to molecular diffusion. However, density stratification in the seawater created by dissolved CO2 will tend to reduce vertical mixing. A two‐dimensional numerical study with a high‐resolution advection‐diffusion model, coupled with a general turbulence model, reveals significant modifications of the boundary layer structure above a generic CO2 lake taken to be 500 m in length and placed in a 10 km domain that is subject to specified far‐field currents in the range of 0.05–0.20 m s−1. Dissolution rates of order 0.07 μmol cm−2 s−1, reaching approximately 0.5 μmol cm−2 s−1 during a benthic storm, are predicted. The friction velocity is reduced above the CO2 lake, and CO2 concentrations corresponding to excess water densities of up to 0.5 kg m−3 occur in the lower 10 m of the water column. The persistency of this low‐pH, CO2‐enriched water layer in weakly stratified and neutral background conditions in the model suggests that gravity current dynamics are important over considerable distances and should be considered in future larger‐scale models and impact studies.
Atmospheric‐driven state transfer of shore‐fast ice in the northeastern Kara Sea
Authors: Divine Dmitry V. , Korsnes Reinert , Makshtas Alexander P. , Godtliebsen Fred , Svendsen Harald
Published: September 2005

Frequencies of observed occurrences of shore‐fast ice in the northeastern Kara Sea for each month during 1953–1990 reveal a multimodality of shore‐fast ice extent in late winter and spring. The fast ice extent exhibits mainly three different configurations (modes) associated with the regional topography of coasts and islands. These modes show fast ice areas equal to approximately 98 ± 6, 122 ± 6, and 136 ± 8 1000 km2. Analysis of the time series of fast ice extent shows that favorable conditions for expansion of fast ice seaward in winter and spring are met if the atmospheric circulation over the northeastern Kara Sea is controlled by the Arctic high, resulting in offshore winds and a significant (up to 6°C) decrease of the monthly mean surface air temperature. In contrast, the penetration of the Icelandic low into the Kara Sea, accompanied by Arctic cyclones coming from the west, is responsible for the partial breakup and decrease of fast ice extent in winter or spring.
Kelvin waves and ozone Kelvin waves in the quasi‐biennial oscillation and semiannual oscillation: A simulation by a high‐resolution chemistry‐coupled general circulation model
Authors: Watanabe Shingo , Takahashi Masaaki
Published: September 2005

Equatorial Kelvin waves and ozone Kelvin waves were simulated by a T63L250 chemistry‐coupled general circulation model with a high vertical resolution (300 m). The model produces a realistic quasi‐biennial oscillation (QBO) and a semiannual oscillation (SAO) in the equatorial stratosphere. The QBO has a period slightly longer than 2 years, and the SAO shows rapid reversals from westerly to easterly regimes and gradual descents of westerlies. Results for the zonal wave number 1 slow and fast Kelvin waves are discussed. Structure of the waves and phase relationships between temperature and ozone perturbations coincide well with satellite observations made by LIMS, CLAES, and MLS. They are generally in phase (antiphase) in the lower (upper) stratosphere as theoretically expected. The fast Kelvin waves in the temperature and ozone are dominant in the upper stratosphere because the slow Kelvin waves are effectively filtered by the QBO westerly. In this simulation, the fast Kelvin waves encounter their critical levels in the upper stratosphere when zonal asymmetry of the SAO westerly is enhanced by an intrusion of the extratropical planetary waves. In addition to the critical level filtering effect, modulations of wave properties by background winds are evident near easterly and westerly shears associated with the QBO and SAO. Enhancement of wave amplitude in the QBO westerly shear is well coincident with radiosonde observations. Increase/decrease of vertical wavelength in the QBO easterly/westerly is obvious in this simulation, which is consistent with the linear wave theory. Shortening of wave period due to the descending QBO westerly shear zone is demonstrated for the first time. Moreover, dominant periods during the QBO westerly phase are longer than those during the QBO easterly phase for both the slow and fast Kelvin waves.
Aggravation of radio interference effects on a dual polarized Earth‐space link by two adjacent interfering satellites under rain fades
Authors: Panagopoulos A. D. , Kritikos T. D. , Kanellopoulos J. D.
Published: September 2005

Interference phenomena affecting the performance and availability of an Earth‐space system are of utmost importance for the reliable design of a satellite communication network. Commercial satellite networks operate or will operate at Ku, Ka, and V frequency bands, in which rain is the dominant fading mechanism. Nominal interference induced on an Earth‐space link by an adjacent satellite network operating at the same frequency is further aggravated because of the potential existing differential rain attenuation, as well as the rain and ice crystals depolarization valid for a frequency reuse system. In the present paper, an existing model, predicting the degradation of the total carrier‐to‐interference ratio under rain fade conditions, is properly modified considering interference effects by two adjacent satellites. The method is based on a convective rain cell model and the lognormal assumption for the point rain rate statistics. The obtained numerical results indicate the significant impact of the second interfering satellite on the aggravation of radio interference effects. Also presented are some simple mathematical formulas for the prediction of the carrier‐to‐interference ratio, based on the above theoretical results, appropriate for use by the system designer for back of the envelope computations.
Kinematics of flow within headcut scour holes on hillslopes
Authors: Bennett Sean J. , Alonso Carlos V.
Published: September 2005

The development and migration of headcuts in rills and gullies can adversely impact soil resources in agricultural areas and accelerate landscape degradation worldwide. Analytical treatments of this erosion process have been based on a turbulent impinging jet analogue, though partially validated by field and laboratory data. Experiments were conducted using fixed headcut models to define the mean flow structure within these erosional features and to assess the applicability of similarity arguments for jets to characterize this flow domain. These data show that (1) flow within headcut scour holes is analogous to plane turbulent reattached wall jets and (2) similarity arguments used to define the limits, length scales, and velocity distributions in classical free jets and wall jets are applicable within discrete regions of the headcut scour hole domain but are affected by the ventilation characteristics of the overfall. This study contributes new knowledge on the hydrodynamics within headcut scour holes, and it confirms the applicability of jet theory for analyzing such soil erosion processes.
Sedimentation problems and management strategies of Sanmenxia Reservoir, Yellow River, China
Authors: Wang Guangqian , Wu Baosheng , Wang Zhao‐Yin
Published: September 2005

Reservoir sedimentation management is of critical importance for the sustainable development of surface water resources. Sanmenxia Dam, located on the middle reach of the Yellow River, in China, is notorious for its severe sedimentation problems. Because of the alarming rate of loss of reservoir storage capacity and the unacceptable negative impact induced by the rapid upstream extension of sediment deposited in the river's backwater region, the dam has been reconstructed to provide high sediment releasing capacity, and the dam operation has been changed in order to achieve a balance between sediment inflow and outflow. As a result, the dam is still providing the basin with flood control, irrigation, and hydropower generation, even though some benefits are lower than the original design. Complex sedimentation processes in response to the dam reconstruction and changes of dam operation are discussed in this paper. The engineering experiences and management practices of Sanmenxia Dam are valuable assets to the sustainable use of reservoirs built on sediment‐laden rivers.
Multiscaling in earthquakes diffusion
Authors: Godano C. , Pingue F.
Published: September 2005

Earthquakes can be viewed as a relaxation process of the earth crust loaded with stresses mainly at the lithospheric plate boundaries. When an earthquake occurs the stress in the crust shall be redistributed generating new earthquakes where and when the stress assume again a value greater than the slipping threshold. This observation leads to study the earthquakes diffusion mechanism. Here we investigate the fluctuations of the average free walk between an earthquake and another, evaluating the scaling of the distance between earthquakes with the waiting time τ. We find scaling exponents varying with the order of the statistical moments and always less than 1. This implies strong anomalous diffusion that we interpret as due to different mechanisms of diffusion depending by the scale.
Lightning current waves measured at short instrumented towers: The influence of sensor position
Authors: Visacro Silvério , Silveira Fernando H.
Published: September 2005

The influence of the current sensor position along short‐instrumented towers on the contamination of measured lightning current waves was evaluated. The evaluation was performed by simulation, employing a hybrid electromagnetic model. Assuming certain simplifications, the dynamic behavior of lightning channel was considered, including core losses and corona sheath. The results showed that, for realistic front time values of negative downward strokes, the current wave measured at tower top and at its base is practically the same, for first and subsequent strokes. Therefore, for short towers, the wave amplitude is not dependent on the current sensor position.
Archival precipitation data set for the Mississippi River Basin: Evaluation
Authors: Nelson Brian R. , Krajewski Witold F. , Smith James A. , Habib Emad , Hoogenboom Gerrit
Published: September 2005

The goals of the Global Energy and Water Cycle Experiment Continental‐Scale International Project (GCIP) point to the need for high resolution data sets on all elements of the land surface and atmospheric hydrologic cycle. A high resolution precipitation data set has been derived from radar reflectivity observations taken from the National Weather Service WSR‐88D radars in the continental U.S. To evaluate the product the authors provide several case studies of radar‐rain gauge comparisons at locations throughout the Mississippi River Basin. They present bias, root mean square difference, fractional standard difference, and correlation coefficient statistics for radar‐rain gauge comparisons for the hourly, daily, monthly, yearly and warm season temporal scale. These point (gauge) and pixel (radar) comparisons show large discrepancies at the hourly scale, on the order of 600–800%. An evaluation of the differences associated with temporally integrated estimates shows marked reduction in these discrepancies. At the long‐term (warm season), these reduce to about 10%. An estimate of the difference in the comparison of the long term accumulation of gridded gauge based estimates and radar estimates at 0.25° × 0.25° shows values in the range of 20% but decrease to about 15% after applying filtering techniques in the basin‐wide comparisons.