bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in the X region and core promoter are rare and have little impact on response to interferon therapy for chronic hepatitis B
Authors: Hannoun Charles , Horal Peter , Krogsgaard Kim , Lindh Magnus ,   and the INTERPRED Study Group
Published: August 2002

Therapy for chronic hepatitis B with interferon‐α (IFN) may result in viral clearance and hepatitis B e seroconversion in 30–40% of patients. It is still unclear whether viral genetic variability influences response rates. However, certain core promoter mutations were recently associated with a better response to IFN. In the present study, the entire X region, including the core promoter, of hepatitis B virus (HBV) from 26 HBeAg‐positive patients treated with IFN for 12 weeks, was sequenced. Serum samples pre‐treatment, at end‐of‐treatment, and at follow‐up of 18 sustained and 8 nonsustained responders were analyzed. Most patients were of European origin and had moderate aminotransferase elevation (mean 2.4 × upper limit of normal) and genotype A infection. Before treatment, 16 patients had an X region identical to a consensus sequence of the corresponding genotype; in the remaining 10 patients, a median of 1.5 mutations were found. After treatment, 1–4 new mutations (mean 1.8) had emerged in 5 patients. There was no association between specific mutations, or the number of mutations, and response to IFN. The low frequency of mutations indicates that analysis of this region is of limited clinical value and that emerging mutations in this region are not major determinants of response to treatment with IFN‐α. J. Med. Virol. 66:171–178, 2002. © 2002 Wiley‐Liss, Inc.
Enterovirus infection can induce immune responses that cross‐react with β‐cell autoantigen tyrosine phosphatase IA‐2/IAR
Authors: Härkönen T. , Lankinen H. , Davydova B. , Hovi T. , Roivainen M.
Published: August 2002

Insulin‐dependent (type 1) diabetes is characterized by progressive destruction of insulin‐producing β cells probably by autoreactive T lymphocytes. Viral infections, especially those caused by coxsackieviruses, are postulated to play a role in the pathogenesis of the disease in humans. One mechanism by which viral infections could initiate or accelerate diabetogenic processes is “molecular mimicry,” induction of antiviral immune responses cross‐reacting with epitopes in the β‐cell autoantigens. Tyrosine phosphatases (IA‐2, IAR) represent a major target autoantigen in type 1 diabetes. Both humoral and cellular immune responses are directed to the carboxy‐terminal (C‐terminal) part of the protein. This region has a 5‐amino acid sequence identity, followed by five amino acid similarity with the conservative motif in the VP1‐protein of enteroviruses (PALTAVETGA/HT), which is a highly immunogenic B‐ and T‐cell epitope in enterovirus infection‐induced immune responses. This observation prompted us to investigate potential humoral cross‐reactions between immune responses induced by tyrosine phosphatases and enteroviruses. The reactivities of various peptide‐ and virus‐induced rabbit antisera clearly demonstrated that cross‐reactions do exist, and in both directions. Using epitope mapping, we were able to show that several diabetes‐linked epitopes in IA‐2 were also recognized by CBV‐4‐induced antisera. Immunization of female NOD‐mice with formalin‐inactivated purified strain of coxsackievirus B4 (CBV‐4‐E2) induced an immune response that recognized the IA‐2/IAR diabetogenic peptide. The results obtained with human paired sera, collected during enterovirus infection, indicated that enterovirus infection in humans may also occasionally induce a humoral response that cross‐reacts with IA‐2/IAR. J. Med. Virol. 66:340‐350, 2002. © 2002 Wiley‐Liss, Inc.
Evolution of viral quasispecies in four dominant HlA‐A2 restricted T cell epitopes is not a major reason for viral persistence in interferon‐treated patients with chronic hepatitis C
Authors: Pingel Sabine , Weyer Sandra , Galle Peter R. , Löhr Hanns F.
Published: August 2002

In most patients, chronic hepatitis C virus (HCV) infection persists despite antiviral treatment with interferon‐alpha (IFN‐α) and ribavirin. The aim of the study was to determine whether HCV could evade cellular immune responses through mutations within T cell epitopes. Viral sequences flanking four major CTL epitopes within the HCV core and envelope regions were analyzed by PCR amplification, cloning and sequencing in seven HLA‐A2 positive HCV patients before, during and after antiviral therapy. In addition, cytotoxic T lymphocyte precursor (CTLp) frequencies specific to these epitopes were quantitated by ELISPOT. A total of 13 coding mutations were observed among 650 cloned and sequenced PCR products under or post IFN treatment but no clear selection of viral variants. In detail, the diversity of quasispecies in the two core epitopes remained fairly stable over time despite variable CTLp induction in some individuals. The overall mutation rate in the two envelope epitopes was higher but there was no correlation with specific CTLp frequencies. In conclusion, although evolution of the viral quasispecies during and after antiviral therapy was demonstrated, immune evasion by epitope specific mutations seemed to be not common in interferon nonresponders because the viral complexity did not increase. J. Med. Virol. 66:472–480, 2002. © 2002 Wiley‐Liss, Inc.
Case report: Human herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell transplant recipient
Authors: Chan Paul K.S. , Chik Ki‐Wai , To Ka‐Fai , Li Chi‐Kong , Shing Matthew M.K. , Ng King‐Cheung , Yuen Patrick M.P. , Cheng Augustine F.
Published: August 2002

Previous studies have suggested a neuroinvasive and neuropersistent potential of human herpesvirus 7 (HHV‐7). In this report, a case of fatal encephalitis is described and its association with HHV‐7 infection is discussed. An 8‐year‐old girl received a peripheral blood stem cell transplant for relapsed acute lymphoblastic leukaemia. The post‐transplant period was uneventful and a course of intrathecal chemotherapy was given on Day‐30. On Day‐41, she developed acute encephalopathy with diplopia and nystagmus. She ran a rapid downhill course and succumbed despite antiviral treatment. The only positive pathological finding was the multiple microscopic foci of haemorrhage associated with neuronal degeneration detected in the brain stem. All microbiological investigations were negative, except for the presence of HHV‐7 DNA in cerebrospinal fluid and brain stem tissue samples. J. Med. Virol. 66:493–496, 2002. © 2002 Wiley‐Liss, Inc.
Population‐based type‐specific prevalence of high‐risk human papillomavirus infection in middle‐aged Swedish Women
Authors: Forslund Ola , Antonsson Annika , Edlund Karin , van den Brule Adrian J.C. , Hansson Bengt‐Göran , Meijer Chris. J.L.M. , Ryd Walter , Rylander Eva , Strand Anders , Wadell Göran , Dillner Joakim , Johansson Bo
Published: August 2002

Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost‐effectiveness of HPV screening is dependent on the type‐specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high‐risk HPV types found in a large real‐life population‐based HPV screening trial undertaken entirely within the cervical screening program offered to middle‐aged Swedish women. Cervical brush samples from 6,123 women aged 32–38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction‐enzyme immunoassay (PCR‐EIA) combined with reverse dot‐blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2–7.5) (417/6,123) were confirmed as high‐risk HPV positive. Infections with 13 different high‐risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR‐EIA as a screening test and reverse dot‐blot hybridization as a confirmatory test, was found to be readily applicable to a real‐life population‐based cervical screening. The type‐specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy. J. Med. Virol. 66:535–541, 2002. © 2002 Wiley‐Liss, Inc.
3‐Ureidopropionate contributes to the neuropathology of 3‐ureidopropionase deficiency and severe propionic aciduria: A hypothesis
Authors: Kölker Stefan , Okun Jürgen G. , Hörster Friederike , Assmann Birgit , Ahlemeyer Barbara , Kohlmüller Dirk , Exner‐Camps Sonja , Mayatepek Ertan , Krieglstein Josef , Hoffmann Georg F.
Published: August 2002

3‐Ureidopropionate (3‐UPA) is a physiologic metabolite in pyrimidine degradation. Pathological accumulation of 3‐UPA in body fluids is found in 3‐ureidopropionase deficiency and severe forms of propionic aciduria. Both diseases clinically present with a severe neuropathology involving gray and white matter as well as with a dystonic dyskinetic movement disorder. To date nothing is known about the toxic nature of this metabolite. The aim of the present study was to elucidate whether 3‐UPA may act as endogenous neurotoxin. Exposure of cultured chick neurons to 3‐UPA induced a concentration‐ and time‐dependent neurodegeneration. Neuronal damage was reduced by the antioxidant α‐tocopherol and the N‐methyl‐D‐aspartate (NMDA) receptor antagonist MK‐801. In contrast, the non‐NMDA receptor antagonist CNQX, the metabotropic glutamate receptor antagonist L‐AP3, and succinate showed no protective effect. Furthermore, 3‐UPA elicited an increased production of reactive oxygen species followed by a delayed increase in intracellular calcium concentrations. Activity measurement of single respiratory chain complexes I‐V revealed an inhibition of complex V activity, but not of the electron‐transferring complexes I‐IV by 3‐UPA. In contrast, 3‐UPA did not affect the mitochondrial β‐oxidation of fatty acids. In conclusion, our results provide strong evidence that 3‐UPA acts as endogenous neurotoxin via inhibition of mitochondrial energy metabolism, resulting in the initiation of secondary, energy‐dependent excitotoxic mechanisms. J. Neurosci. Res. 66:666–673, 2001. © 2001 Wiley‐Liss, Inc.
Initiation and development of experimental autoimmune neuritis in Lewis rats is independent of the cytotoxic capacity of NKR‐P1A+ cells
Authors: Yu Shuo , Zhu Yu , Chen Zhiguo , Alheim Mats , Ljungberg Anna , Zhu Jie
Published: August 2002

Natural killer (NK) cells are implicated in T cell‐mediated autoimmune diseases. Experimental autoimmune neuritis (EAN) is a CD4+ T cell‐mediated animal model of the Guillain‐Barré syndrome in human. The role of NK cells in the initiation and development of EAN remains unclear. In the present study, we demonstrate that anti‐NKR‐P1A monoclonal antibody (mAb) treatment in vivo did not affect the initiation and development of clinical EAN in Lewis rats induced by immunization with peripheral nerve myelin P0 protein peptide 180–199 and Freund's complete adjuvant, as well as the proportion of NKR‐P1A+ cells (including NK cells and NKT cells) in the spleen. Furthermore, inflammatory cell infiltrations and demyelination in the peripheral nervous system (PNS) and in vitro P0 peptide 180–199‐specific splenocyte proliferation were not different in anti‐NKR‐P1A mAb‐treated rats compared to the control antibody‐treated rats. The cytotoxic activity of NKR‐P1A+ cells, determined by NK cell‐sensitive K562 cells as target cells, decreased markedly in anti‐NKR‐P1A mAb‐treated rats, suggesting that decrease of the cytotoxic activities of NKR‐P1A+ cells is not sufficient to alter clinical EAN, although NKR‐P1A+ cells may participate in the pathogenesis of T cell‐mediated autoimmune diseases, such as EAN, by the mechanisms that involve the release of cytokines. © 2002 Wiley‐Liss, Inc.
Adenosine triphosphate and diadenosine pentaphosphate induce [Ca2+]i increase in rat basal ganglia aminergic terminals
Authors: Giraldez Lisandro , Díaz‐Hernández Miguel , Gómez‐Villafuertes Rosa , Pintor Jesus , Castro Enrique , Miras‐Portugal M. Teresa
Published: August 2002

Synaptosomal preparations from rat midbrain exhibit specific responses to both ATP and Ap5A, which stimulate a [Ca2+]i increase in the presynaptic terminals via specific ionotropic receptors, termed P2X, and diadenosine polyphosphate receptors. Aminergic terminals from rat brain basal ganglia were characterized by immunocolocalization of synaptophysin and the vesicular monoamine transporter VMAT2 and represent 29% of the total. These aminergic terminals respond to ATP and/or Ap5A with an increase in the intrasynaptosomal calcium concentration as measured by a microfluorimetric technique. This technique, which allows single synaptic terminals to be studied, showed that roughly 8.2% ± 1.6% of the aminergic terminals respond to ATP, 16.9% ± 1.3% respond to Ap5A, 32.6% ± 0.8% to both, and 42.3% ± 1.5% of them have no response. Immunological studies performed with antibodies against ionotropic ATP receptor subunits showed positive labelling with anti‐P2X3 antibodies in 39% of the terminals. However, colocalization studies of VMAT and P2X3 receptor subunit indicate that only 25% of the aminergic terminals also contain this receptor subtype. These results demonstrate that the aminergic terminals from the rat brain basal ganglia are to a large extent under the modulation of presynaptic nucleotide and dinucleotide receptors. J. Neurosci. Res. 64:174–182, 2001. © 2001 Wiley‐Liss, Inc.
Activated microglia in the human glaucomatous optic nerve head
Authors: Yuan Liya , Neufeld Arthur H.
Published: August 2002

To investigate the distribution and potential participation of microglia, the resident defense cells of the central nervous system, in the optic nerve head (ONH) in glaucoma, histological paraffin sections of optic nerves from normal and glaucoma patients with mild to advanced nerve damage were studied using double labeling immunohistofluorescence. A monoclonal antibody for HLA‐DR, indicating activated microglia, was colocalized with antibodies for functional proteins. In normal ONHs, microglia do not contain TGF‐β2, COX‐2, or TNF‐α and are not positive for PCNA; however, in glaucomatous ONHs, microglia contain abundant TGF‐β2, TNF‐α, and PCNA. In glaucomatous eyes, a few microglia are usually positive for COX‐2. In normal ONHs, there are rarely microglia containing TGF‐β1, NOS‐2, TSP, TIMP‐2, and CD68, but, in glaucomatous tissue, a few microglia are positive from the prelaminar to the postlaminar regions. MMP‐1, MMP‐2, MMP‐3, and MMP‐14 are constitutively present in the perivascular microglia in normal ONHs and appear to be more abundant in glaucomatous tissue. COX‐1, TNF‐R1, TIMP‐1, and c‐fms are constitutively present in normal tissues and appear to be increased in microglia in the glaucomatous ONHs. HSP27 is not present in microglia. In glaucomatous ONHs, microglia become activated and phagocytic and produce cytokines, mediators, and enzymes that can alter the extracellular matrix. Our findings suggest that activated microglia may participate in stabilizing the tissue early in the disease process, but, as the severity of the glaucomatous damage increases, the activities of microglia may have detrimental consequences for the pathological course of glaucomatous optic neuropathy. J. Neurosci. Res. 64:523–532, 2001. © 2001 Wiley‐Liss, Inc.
Histochemical study of acute and chronic intraperitoneal nicotine effects on several glycolytic and Krebs cycle dehydrogenase activities in the frontoparietal cortex and subcortical nuclei of the rat brain
Authors: Turégano L. , Martínez‐Rodríguez R. , Álvarez M.I. , Gragera R.R. , Gómez de Segura A. , De Miguel E. , Toledano A.
Published: August 2002

The effects of nicotine on the activity of different dehydrogenases in frontoparietal regions and subcortical nuclei of the rat brain have been studied using histochemical methods. Nicotine sulphate was intraperitoneally administered in acute (4 mg/kg/day × 3 days) or chronic (ALZET osmotic pump providing 2 mg/kg/day × 15 days) doses. The enzymes analyzed were glyceraldehyde‐3‐phosphate, lactate, malate and succinate dehydrogenases (gly3PDH, LDH, MDH, and SDH, respectively). The results demonstrate that chronic as well as acute administration of nicotine produced strong increases in all these enzymatic activities in the superior layers (I, II and III) of the frontoparietal cortex (cingulate, motor and somatosensory regions); but high increases were not seen in the deeper layers of the cortex or in the subcortical nuclei (substantia nigra, caudate‐putamen, nucleus accumbens or nucleus basalis magnocellularis). These hyperactivities were produced in brain regions with normally low enzymatic activity (cortex), but not in those with great intensity (subcortical nuclei). The results are in rough agreement with previous reports on nicotine‐induced increases in glucose utilization, gly3PDH genic expression and neuronal hyperactivity in the brain cortex; but significant discrepancies between the cortical enzymatic maps and those obtained both in these studies and others on nicotine(N)‐receptor localization have been appreciated. The results support the hypothesis that nicotinic cholinergic drugs can have metabolic, long‐lasting stimulant effects on cortical neurons at specific points (probably layer III pyramidal cells and structures with α7‐N‐receptors) of the cortical circuits that could be of great interest in improving altered cognitive functions that are present in Alzheimer disease, as well as in other less severe mental disturbances. Mitochondrial hyperfunction should also be evaluated as a possible side‐effect (as an oxidative stress inductor) of these kinds of drugs. J. Neurosci. Res. 64:626–635, 2001. © 2001 Wiley‐Liss, Inc.
Disturbed oligodendrocyte development and recovery from hypomyelination in a c‐myc transgenic mouse mutant
Authors: Orian Jacqueline M. , Ahern Alan J. , Ayers Margaret M. , Levine Joel M. , Tapp Luke D. , Reynolds Richard
Published: August 2002

The complexity of interactions underlying the elaboration of myelin has been extensively demonstrated. We provide evidence that signals promoting myelination are not confined to the normal developmental time window for myelination and persist well into adult life. The 2‐50 mutant, described previously, carries a c‐myc transgene regulated by a myelin basic protein promoter. This mutant is characterised by severe hypomyelination and abnormal oligodendrocytes in early life, followed by loss of the phenotype and normal longevity. We show that c‐myc expression in early oligodendrocyte development results in a substantial reduction of cells of this lineage. However, apparent complete recovery, associated with loss of c‐myc expression, axonal survival, and gradual myelin accumulation, is observed by 4 months of age. Thus, stimulation of myelination continues during adult life until normal myelin levels are established. We propose that this mutant may contribute to the characterisation of oligodendrocyte responses to myelinating signals. J. Neurosci. Res. 66:46–58, 2001. © 2001 Wiley‐Liss, Inc.
Glutamate transporter EAAC1 is expressed on Müller cells of lower vertebrate retinas
Authors: Zhao Jing‐Wei , Yang Xiong‐Li
Published: August 2002

The expression of glutamate transporter EAAC1 was investigated in carp and bullfrog retinas using Western blotting, immunofluorescence double labeling and confocal laser scanning microscopic techniques. In addition to a variety of retinal neurons, radially oriented elements spanning the whole neural retinas of carp and bullfrog were also EAAC1‐immunoreactive, and EAAC1 was found to be predominantly on the cell membrane. Virtually all EAAC1‐labeled radial elements were immunopositive to glial fibrillary acidic protein (GFAP), a specific marker for retinal Müller cells of carp and bullfrog, indicating that they were Müller cells. This finding suggests that EAAC1, which has been thought to be an exclusively neuronal type, may be a glial transporter as well. EAAC1 of Müller cells may play an important modulatory role in the retina by making contributions to glutamate homeostasis. J. Neurosci. Res. 66:89–95, 2001. © 2001 Wiley‐Liss, Inc.
Evidence for a ligand‐specific signaling through GFRα‐1, but not GFRα‐2, in the absence of Ret
Authors: Pezeshki Gita , Franke Barbara , Engele Jürgen
Published: August 2002

Glial cell line‐derived neurotrophic factor (GDNF) and neurturin (NTN) are two homologeous proteins that have been recognized as potent survival factors for distinct neuronal populations. GDNF and NTN act through a two‐component receptor system consisting of the ligand‐specific binding subunits GDNF family receptor (GFR)α‐1 and GFRα‐2 and the common transducing subunit c‐Ret. In addition, it has been demonstrated that GDNF can signal through GFRα‐1 in the absence of c‐Ret. In the present study, we sought to determine whether a similar c‐Ret‐independent signaling applies for GFRα‐2. In addition, we have characterized the ligand specificity of the c‐Ret‐independent action of GFRαs. To establish an assay system for these studies, several neural cell lines were screened for the presence of GDNF and NTN receptor subunits by RT‐PCR and immunoblot analysis. c‐Ret expression was detectable only in Neuro2A cells, which did not express GFRα‐1 or GFRα‐2. The neuronal cell line LS expressed GFRα‐2, and the glial cell line Mes42 expressed GFRα‐1, whereas the neuronal cell line B104 expressed both GFRα‐1 and GFRα‐2. Stimulation of B104 and Mes42 cells with GDNF, but not with NTN, for 10 min resulted in CREB phosphorylation. In apparent contrast, neither NTN nor GDNF promoted CREB activation in LS and Neuro2A cells. Moreover, exposure of LS cells to NTN or GDNF also failed to activate AKT and ERK. Together these findings provide evidence that, in contrast to GFRα‐1, GFRα‐2 fails to signal in the absence of c‐Ret. In addition, these observations reveal that c‐Ret‐independent signaling of GFRα‐1 is ligand‐ specific and occurs only with GDNF. J. Neurosci. Res. 66:390–395, 2001. © 2001 Wiley‐Liss, Inc.
FFT analysis on NDVI annual cycle and climatic regionality in Northeast Brazil
Authors: I. Negrón Juárez Robinson , T. Liu William
Published: August 2002

By considering that the climate of Northeast Brazil (NEB) has distinct wet and dry seasons, the mixed radix fast Fourier transform (mrFFT) algorithm, developed at the National Aerospace Centre of the Netherlands, was applied to a monthly Normalized Difference Vegetation Index (NDVI) time series from July 1981 to June 1993, to generate phase, amplitude and mean NDVI data using a 1‐year frequency in order to improve the analysis of its spatial variation.

The NDVI mean values varied from >0.7, which occurred in northwest and southeast regions, to <0.3 in the northeast and 0.4 in the southwest regions of the NEB. The 90° phase month at its maximum amplitude occurred in August and was observed in both southeastern and northwestern coasts, located at 10.5°S–37.5°W and 4°S–46°W, respectively. It changed rapidly from August, June to May, moved inland and changed gradually from May through to April and from March to February, then moved towards the centre Dry Polygon area. Then it changed gradually from February to January and ended up in December, and moved further southwards. The annual cycle amplitude varied from <0.075 in northwest and southeast regions to >0.25 in the northeast region. By using spatial variations of phase, amplitude and mean NDVI values, 15 climate types were delineated for the NEB.

The spatial distribution of climate types in the NEB delineated by the NDVI FFT analysis agreed mostly with the climatic types presented by Hargreaves (Precipitation dependability and potentials for agricultural production in Northeast Brazil. Empresa Brasileira de Pesquisa Agropecuária‐EMBRAPA, Brazil, 1974), except regions with higher spatial variability and limited surface meteorological data. Among the three components: phase, amplitude and mean NDVI, the phase image, informing the initiation and duration of rainy season, was the most important component for climate‐type delineation. Nevertheless, while the extreme values of amplitude, inferring a high wet–dry rainfall regime contrast, and mean NDVI, inferring annual rainfall total, occurred in the same phase area, amplitude and mean NDVI images were used for further delineation. It is concluded that the application of the mrFFT algorithm to NDVI time series analysis is an effective method for identifying vegetation phenology and hence to delineate the transit spatial change of climate types. Our further study is to construct and validate the alternative El Niño–Southern Oscillation (ENSO) drought onset model for each of the 15 climate types delineated for the NEB. Copyright © 2001 Royal Meteorological Society
Reconstruction of the North Atlantic Oscillation, 1429–1983
Authors: Glueck Mary F. , Stockton Charles W.
Published: August 2002

The North Atlantic Oscillation (NAO) is considered to be the dominant mode of winter atmospheric variability in the Northern Hemisphere (Barnston AG, Livezey RE. 1987. Classification, seasonality and persistence of low frequency atmospheric circulation patterns. Monthly Weather Review 115: 1083–1126), especially in the North Atlantic region. A better understanding of its recent variability in the context of pre‐instrumental period variations is critical for prediction purposes. A 555‐year (1429–1983) multi‐proxy reconstruction of the cool season NAO, calibrated against the Lisbon–Iceland (LISJHI) NAO, is presented. Predictor variables include tree‐ring chronologies from Morocco and Finland, GISP2 δ18O annual series, and a GISP2 snow accumulation record. Although the reconstructed values are generally lower than the instrumental values during the calibration period (1863–1983), the final reconstruction does capture the low frequency of the instrumental NAO. The reconstruction compares favourably with existing shorter NAO reconstructions and with the instrumental NAO. The variability in the reconstructed NAO is also discussed within the context of lengthy regional climate records. Results suggest that the occurrence and length of the recent persistently high phase of the NAO are not unusual over the 555‐year period of time, but that the magnitude of some of the instrumental values may, in fact, be unique. Copyright © 2001 Royal Meteorological Society
Metal complexes with tetrapyrrole ligands: Part LXXVII. New osmium complexes of the 5,10,15,20-tetrakis-(4-carboxyphenyl) porphyrin
Authors: BUCHLER JOHANN W. , SIMON JOACHIM R.
Published: August 2002

The synthesis and characterization of new alkali-soluble osmium tetraphenylporphyrinates, complexes of the 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin Os ( tH 4 cpp ) L 2 and Os ( tH 4 cpp ) LL ' (2a–j), is described. 2a–j are obtained from the corresponding new osmium porphyrinates Os ( tmecpp ) L 2 and Os ( tmecpp ) LL '(1a–k) by alkaline saponification and precipitation with hydrochloric acid. In fact, the osmium(II) porphyrinates 2c–f as well as 2i–j are oxidized to the osmium(III) porphyrinates Os ( tH 3 cpp ) L 2(3c–f) and Os ( tH 3 cpp ) LL '(3i–j) in the presence of air, as confirmed by UV-vis spectroscopy.
A computational study on heterodimerization of charged porphyrins
Authors: SAǦ ERDEM SAFİYE
Published: August 2002

The structures of the charged porphyrins and their dimers have been investigated with computational methods. Dimers have been formed based on electrostatic attraction of the opposite charges on two different porphyrin monomers, tetra ammonium porphyrin (TAP) and tetra carboxy porphyrin (TCP). Semi-empirical quantum mechanical calculations have been employed to explore the most stable ground-state structures of TCP, TAP and their hetero-dimers. Dimeric structures analyzed are all in face-to-face fashion indicating the strong electrostatic attraction between the two porphyrin rings. Calculations have also predicted that the protons transfer from [Formula: see text]; groups to -COO- groups when the interplanar separation is shorter than 3.7 Å.
Dinoflagellate cyst assemblages as tracers of sea‐surface conditions in the northern North Atlantic, Arctic and sub‐Arctic seas: the new ‘n = 677’ data base and its application for quantitative palaeoceanographic reconstruction
Authors: Vernal Anne de , Henry Maryse , Matthiessen Jens , Mudie Peta J. , Rochon André , Boessenkool Karin P. , Eynaud Frédérique , GrØsfjeld Kari , Guiot Joël , Hamel Dominique , Harland Rex , Head Martin J. , Kunz‐Pirrung Martina , Levac Elisabeth , Loucheur Virginie , Peyron Odile , Pospelova Vera , Radi Taoufik , Turon Jean‐Louis , Voronina Elena
Published: August 2002

The distribution of dinoflagellate cyst (dinocyst) assemblages in surface sediment samples from 677 sites of the northern North Atlantic, Arctic and sub‐Arctic seas is discussed with emphasis on the relationships with sea‐surface parameters, including sea‐ice cover, salinity and temperature of the coldest and warmest months. Difficulties in developing a circum‐Arctic data base include the morphological variation within taxa (e.g. Operculodinium centrocarpum, Islandinium? cezare and Polykrikos sp.), which probably relate to phenotypic adaptations to cold and/or low salinity environments. Sparse hydrographical data, together with large interannual variations of temperature and salinity in surface waters of Arctic seas constitute additional limitations. Nevertheless, the use of the best‐analogue technique with this new dinocyst data base including 677 samples permits quantitative reconstruction of sea‐surface conditions at the scale of the northern North Atlantic and the Arctic domain. The error of prediction calculated from modern assemblages is ±1.3 °C and ±1.8 °C for the temperature of February and August, respectively, ±1.8 for the salinity, and ±1.5 months yr−1 for the sea‐ice cover. Application to late Quaternary sequences from the western and eastern subpolar North Atlantic (Labrador Sea and Barents Sea) provide reconstructions compatible with those obtained using the previous dinocyst data base (n = 371), which mainly included modern data from the northern North Atlantic. Copyright © 2001 John Wiley & Sons, Ltd.
Infrared and Raman spectra of Hg2MoO4 and Hg2WO4
Authors: Baran Enrique J. , Mormann Thomas J. , Göcke Hans‐J. , Jeitschko Wolfgang
Published: August 2002

The Fourier transform infrared and Raman spectra of the low‐temperature form of mercury(I) molybdate and the corresponding tungstate were recorded and are discussed on the basis of their structural characteristics, with the aid of factor group analysis. Copyright © 2001 John Wiley & Sons, Ltd.
A review on linear and non‐linear resonance Raman spectroscopy of the conjugated system polydiacetylene
Authors: Materny A. , Chen T. , Vierheilig A. , Kiefer W.
Published: August 2002

We review resonance Raman investigations of the linear conjugated π‐electron system of polydiacetylenes embedded in single‐crystalline monomer matrices. Absorption, luminescence, resonance Raman and resonance CARS spectroscopy were used to investigate vibronic properties of the polymers. As an example, we discuss the theoretical model applied for the simulation of the resonance Raman line and excitation profiles obtained from the polymer chains in FBS, TS/FBS and TS6 diacetylene single crystals. The theory is based on a Franck– Condon model, which considers a chain length dependence. The electronic transition energies and matrix elements were calculated by means of an LCAO MO (linear combination of atomic orbitals molecular orbital) calculation in the Hückel approach. An interaction between ensemble and intramolecular properties due to defects can be shown. Besides the well known polymer absorption, the partially polymerized single crystals of the diacetylenes under investigation show blue‐shifted absorption bands in sharply separated crystal areas. The spectroscopic investigations of this chromism revealed that most probably growth defects in {111} crystal growth sectors influence the side‐group geometry of the polymer chains. Using femtosecond time‐resolved CARS spectroscopy, the dynamics of the vibrational excitation in the electronic ground and excited states can be investigated. Here, we report the controlled selective excitation of the polymers. We used a CARS scheme where the difference of pump and Stokes laser wavelengths is chosen to achieve resonance with several chain modes of the polydiacetylenes. By varying the timing and the phases of the femtosecond laser pulses, the timing and the intensity of these modes can be strongly influenced. Copyright © 2001 John Wiley & Sons, Ltd.
Study of the segregation process in GaAs/AlAs superlattices using Raman spectroscopy
Authors: Zanelato G. , Pusep Yu. A. , Galzerani J. C. , Lubyshev D. I. , González‐Borrero P. P.
Published: August 2002

A Raman scattering study of cation segregation in GaAs/AlAs ultrathin‐layer superlattices grown with different temperatures and As pressures is reported. The optical confined modes of the samples were measured. The kinetic segregation model was modified in order to allow the calculation of the compositional profiles of the samples. After utilizing the Raman wavenumbers as references to adjust the calculated values by the next‐nearest‐neighbor linear chain model, it was possible to determine the parameters characterizing the segregation. It is shown that an increase in the pressure of As results in a more abrupt compositional profile, equivalent to the decrease in the growth temperature. Copyright © 2001 John Wiley & Sons, Ltd.
Trypsin inhibitor activity in vegetative tissue of sweet potato plants and its response to heat treatment
Authors: Zhang Zhitian , Corke Harold
Published: August 2002

Trypsin inhibitor activity (TIA) and crude protein content of seven genotypes of sweet potato were investigated. There was considerable genotypic variation in TIA, with a four‐ to fivefold range in roots and a threefold range in stems. The mean TIA in stems at harvest time was 36% of that in roots, whilst the mean TIA in leaves was only 17% of that in roots. The TIA level in roots was correlated with that in stems (r  = 0.83, p  = 0.02) and leaves (r  = 0.70, p  = 0.08). In most genotypes the TIA level in vine‐tips was low during the early growth stage, increased from day 30 to day 110 after transplanting, then remained constant in subsequent growth stages. However, in genotype Guang 70‐9, vine‐tips had a high level of TIA at all growth stages. Sweet potato green tissue contained three‐ to fivefold more crude protein than roots. No correlation between TIA and crude protein in sweet potato roots was found across genotypes, but TIA was significantly correlated with crude protein content (r  = 0.73, p  = 0.06) in sweet potato vine‐tips. Moist heat treatment (MHT) was found to be effective in eliminating TIA in sweet potato. Most TIA in sweet potato green tissue and roots was eliminated by MHT at ≥80 °C, but heat stability was dependent on genotype. Guang 70‐9 had relatively highly heat‐stable trypsin inhibitor. The results suggested that screening for genotypes with high protein content and low TIA and use of an appropriate processing method could improve the utilisation of sweet potato for both human food and animal feed.

© 2001 Society of Chemical Industry
Effect of the addition of calcium hydroxide on some characteristics of extruded products from blue maize (Zea mays L) using response surface methodology
Authors: Zazueta‐Morales José J , Martínez‐Bustos Fernando , Jacobo‐Valenzuela Noelia , Ordorica‐Falomir César , Paredes‐López Octavio
Published: August 2002

The aim of this research was to study the effects of calcium hydroxide (0–0.2%) and screw speed (100–180 rpm) on the expansion index (EI), bulk density (BD), penetration force (PF) and specific mechanical energy (SME) values of blue maize meal extrudates. Blue maize meal was extruded using a commercial extruder (Brabender 20DN/8‐235‐00) with a compression screw ratio of 3:1. A second‐order, central composite experimental design was used. It was found that the EI and SME values decreased and the BD and PF values increased when the calcium hydroxide concentration was increased. The screw speed had a significant effect only on the SME and PF values. Quadratic model fitness was shown for all responses, with values of R2 > 0.74, p of F (model) <0.01 and variability coefficient <13.3% (except for PF, 29.18%), and for almost all cases there was no lack of fit (p > 0.055). Calcium hydroxide concentration showed good correlation (p < 0.01) with EI (r  = −0.81), PF (r  = 0.60), SME (r  = −0.76) and BD (r  = 0.83). However, screw speed was marginally or not correlated (r < 0.36, p > 0.14) with the responses. The results suggest that it is possible to produce appropriate extruded products from blue maize fortified with calcium in an optimised calcium hydroxide concentration and screw speed range of 0.02–0.078% and 117–180 rpm respectively.

© 2001 Society of Chemical Industry
Activation of matrix metalloproteinase‐2 is correlated with invasiveness in thymic epithelial tumors
Authors: Kondo Kazuya , Kinoshita Hidetaka , Ishikura Hisashi , Miyoshi Takanori , Hirose Toshiyuki , Matsumori Yasumichi , Monden Yasumasa
Published: August 2002

Background and Objects

Matrix degradation, which is a critical event in the process of tumor invasion and metastasis, is considered to be caused by the action of proteolytic enzymes.

Methods

We examined the gelatinolytic activity of matrix metalloproteinase (MMP)‐9, and the activity of active and inactive forms of MMP‐2 in five thymi, five noninvasive thymomas, eight invasive thymomas, and five thymic carcinomas by quantitative gelatinolytic zymography.

Results

The gelatinolytic activity of active MMP‐2 in five thymi was zero. The mean gelatinolytic activity of active MMP‐2 was 0.020 ± 0.015 in noninvasive thymoma, 0.084 ± 0.098 in invasive thymoma and 0.246 ± 0.194 in thymic carcinoma. The gelatinolytic activity of active MMP‐2 correlated with the invasiveness of thymic epithelial tumors (Spearman rank correlation: r‐value = 0.532). The gelatinolytic activity of active MMP‐2 in three thymoma cases with microscopic capsular invasion was the same as that of noninvasive thymoma. When thymoma cases showing microscopic capsular invasion were classified into the “macroscopically noninvasive thymoma” group, the gelatinolytic activity of active MMP‐2 correlated with the invasiveness of thymic epithelial tumors (Spearman rank correlation: r‐value = 0.621).

Conclusions

The gelatinolytic activity of active MMP‐2 significantly correlated with the invasiveness in thymic epithelial tumors. J. Surg. Oncol. 2001;76:169–175. © 2001 Wiley‐Liss, Inc.
A new model to assist in planning for sustainable cultural heritage tourism
Authors: du Cros Hilary
Published: August 2002

A natural link exists between tourism and cultural heritage management, yet little discourse and debate occurs between them on the sustainability of heritage tourism. What also is missing is a process whereby elements of both areas can be included in the identification and actualisation of the tourism potential of cultural heritage places. This paper presents a new model that is in the process of development, but which has the potential to assist in planning for sustainable cultural heritage tourism. Future testing of the model is likely to make a significant contribution to the advancement of both disciplines and also should help break down barriers between the two. The model is a matrix into which heritage places can be classified as falling into nine general areas of suitability for tourism in terms of their market appeal and ability to withstand the impacts of visitation likely to be associated with that appeal. Copyright © 2001 John Wiley & Sons, Ltd.
Tourism and economic regeneration: the role of skills development
Authors: Thomas Rhodri , Long Jonathan
Published: August 2002

An increasing number of local economic development agencies in the UK are turning to tourism as a means of urban regeneration and employment creation. Although initiatives vary, there is a nationally inspired emphasis on the development of employee skills as a core element of many regeneration strategies. This paper reports the findings of a qualitative study of the demand for and utilisation of skills by tourism firms in East London, an area that is the recipient of substantial urban aid funding, a proportion of which has an overt focus on skills enhancement designed to develop the tourism sector. It then examines the processes of skills supply within the locality. The paper concludes by identifying the key issues likely to be important if regeneration programmes are to be effective. Copyright
© 2001 John Wiley & Sons, Ltd.
Joint ventures between communities and tourism investors: experience in southern Africa
Authors: Ashley Caroline , Jones Brian
Published: August 2002

Tourism joint ventures between communities and private investors are an emerging trend in southern Africa. In each country they take different forms. This paper reviews experience in Namibia, within the wider regional context, in order to identify some key principles and challenges. Several lessons can be learnt from the eight Namibian negotiations, and three operating ventures concerning the long process of establishing joint ventures, and about the positive and negative impacts it has for both parties, which cover a range of commercial and livelihood concerns. The analysis suggests several critical factors influence joint‐venture success including: committed individuals, company philosophy, facilitation, time and trust, local institutions, national policy context and tourism market trends. Regional comparison indicates that critical factors need to be present in some, but widely varying, form. Joint ventures should become easier to develop as lessons are shared. Although they will remain a niche market, owing to high transaction costs, further policy and practical support can help develop this promising potential. Copyright © 2001 John Wiley & Sons, Ltd.
A consensus view of the temperature dependence of the gas phase reaction: OH + HBr → H2O + Br
Authors: Jaramillo Veronica I. , Gougeon Samuel , Le Picard Sébastien D. , Canosa André , Smith Mark A. , Rowe Bertrand R.
Published: August 2002

The temperature dependence of the rate coefficient for the reaction, OH + HBr has been reinvestigated at low temperatures (T = 48–224 K) by using uniform supersonic flow reactors with laser induced fluorescence detection. This paper presents two forms of global fits: k(T) = 1.11 × 10−11 (T/298)−0.91 cm3 s−1 and k(T) = 1.06 × 10−11 (T/298)−1.09 $\exp({-10.5 K\over T})$ cm3 s−1, both of which accurately describe the temperature dependence of the rate coefficient for the title reaction within the temperature range 20–350 K. These fits indicate that at temperatures below 200 K, the rate coefficient for this reaction shows inverse temperature dependence, while above 200 K the reaction shows insignificant temperature dependence. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 339–344, 2002
Trans ligand influence in cobalt(III) Schiff base complexes: Electronic and steric effects on the kinetics of hydrolysis
Authors: Amirnasr Mehdi , Vafazadeh Rasoul
Published: August 2002

Rate constants for the hydrolysis (kh) of six different amines in trans‐[Co((BA)2en)(amine)2]ClO4 complexes (amine = aniline 1a, para‐toluidine 1b, benzylamine 1c (primary amines), pyrrolidine 2a, piperidine 2b, morpholine 2c (secondary amines), and (BA)2en = Bisbenzoylacetoneethylenediiminato) in mixed methanol/water (1:1) solvent have been determined between 30 and 55°C. The hydrolysis product of 2c, trans‐[Co((BA)2en)(morpholine)(H2O)]ClO4, has been separately prepared and characterized by UV–vis and 1H NMR spectroscopy. Depending on the nature of the axial amine ligand the limiting first‐order rate constants for the amine hydrolysis at 40°C range from (3.42 ± 0.10) × 10−5 to (5.32 ± 0.13) × 10−5 s−1. At the first glance, a reasonable trend cannot be established between kh and the basicity or the inductive trans effect of the amine ligands. However, when the complexes are classified into two groups, based on the type of the amine (primary and secondary), the values of kh correlate well with the basicity or inductive effect of the amine in each group. The observed trend in kh values for the complexes with primary amines is 1a (5.32 ± 0.13) × 10−5 s−1 > 1b (3.51 ± 0.14) × 10−5 > 1c (1.72 ± 0.03) × 10−5 (40°C), which is opposite to the amine basicity strength. In the case of the complexes with secondary amines, the observed trend in kh values is in accord with amine basicity (or inductive trans effect), i.e. 2a (5.02 ± 0.22) × 10−5 > 2b (4.18 ± 0.10) × 10−5 > 2c (3.42 ± 0.10) × 10−5 s−1 (40°C). © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 387–393, 2002
An electrospray‐ionization—flow‐tube study of H/D exchange in protonated leucine‐enkephalin
Authors: Ustyuzhanin Pavel , Kogan Alexandra , Reuben Bryan G. , Lifshitz Chava
Published: August 2002

An electrospray ionization fast flow technique has been employed to study reactions with CH3OD and ND3, respectively, of the protonated pentapeptide leucine enkephalin, and of protonated tri‐ and tetrapeptides that make up its backbone structure. Deconvolution of the experimental mass spectral data follod by simulation of the kinetic data by solution of differential equations leads to sets of apparent and site‐specific rate constants. On a time scale of several milliseconds, leucine enkephalin undergoes with ND3 four fast H/D exchanges and one slow exchange. Three equivalent exchanges are observed that are ascribed to the protonated amine group at the N‐terminus. Contrary to leucine enkephalin, some of the smaller peptides that do not have tyrosine at the N‐terminus are reactive with CH3OD, but the reactions are more than two orders of magnitude slower than the ND3 reactions. These peptides do not sequester the ionizing proton at the N‐terminus. The present study demonstrates the capabilities of a fast flow technique in studying gas phase reactions of small biomolecules. It forms part of an effort to understand gas phase conformational changes in proteins through hydrogen‐exchange electrospray ionization mass spectrometry. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 707–714, 2001
From tacit knowledge to knowledge management: leveraging invisible assets
Authors: K. Kakabadse Nada , Kouzmin Alexander , Kakabadse Andrew
Published: August 2002

Within competitive advantage considerations, knowledge has emerged as one of the more strategic, although invisible, assets for organizations. This is notwithstanding a wider and specifically economistic and cognitive discounting of knowledge as a factor of production — largely ignoring the socially constructed and socially mediated nature of knowledge. Intellectual capabilities and knowledge/information transformations now have a central place within globalizing information economies.

Constructing, transforming and commodifying knowledge and information require new organizational understandings and newer cognitive capabilities of strategic management praxis. Part of this cognitive awareness is a deliberate organizational designing for the role of symbolic analysts. As well, there is an emerging need for the Chief Knowledge Officer function going well beyond the Chief Information Officer requirements posited by an information technology‐driven restructuring of routine processes, as compared with innovation creation capacities associated with critically non‐routine functions within organizations discovered by Cranfield research.

The paper considers neglected institutional and organizational dimensions to knowledge creation and knowledge conversion — it reviews the renewed importance of internal recruitment and socialization within institutions and details knowledge codification and application functions within knowledge‐creating organizations. Knowledge management, as praxis, inevitably raises concerns about cognitive failure in leadership theory and praxis. Copyright © 2001 John Wiley & Sons, Ltd.