bluuebunny/crossref_metadata_2025 huggingface dataset:
Virological and biochemical relapse according to YMDD motif mutant type during long‐term lamivudine monotherapy
Authors: Akuta Norio , Suzuki Fumitaka , Kobayashi Mariko , Matsuda Marie , Sato Junko , Takagi Kimiko , Tsubota Akihito , Suzuki Yoshiyuki , Hosaka Tetsuya , Someya Takashi , Kobayashi Masahiro , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: October 2003

Whether the type of lamivudine‐resistant virus in hepatitis B virus (HBV) influences the clinical outcome, it is not completely understood. We evaluated the serial changes in YMDD motif mutant in 60 Japanese genotype C–HBV patients who received long‐term lamivudine monotherapy. YIDD or YVDD alone tended to stop shifting to the mixed type (YVDD and YIDD) within 12 months after the detection of mutant virus. Hence, the characteristics, virological relapse (DNA breakthrough) and biochemical relapse (breakthrough hepatitis) of 49 patients, who could be classified into three types (continuous YVDD, continuous YIDD, and the mixed type), were investigated. YVDD and YIDD type tended to have the opposite background with regard to age, histology, and viral load. The mixed and YIDD types tended to have similar backgrounds, except for viral load. In the mixed type, both the HBeAg‐positive rate and viral load as risk factors for emergence of the mutant tended to be high. Mutant virus, DNA breakthrough and breakthrough hepatitis emerged significantly earlier in the mixed type than the two other types. The incidence of severe breakthrough hepatitis accompanied by icteric flare‐up tended to be higher in the mixed type than the other types. Our results suggest that the YMDD motif mutant type might emerge from different backgrounds and modulate the virological and biochemical relapse after the emergence. Large‐scale studies of each mutant type should be conducted in the future to confirm these findings. J. Med. Virol. 71:504–510, 2003. © 2003 Wiley‐Liss, Inc.
Behavior of the dengue virus in solution
Authors: Sithisarn Patchima , Suksanpaisan Lukkana , Thepparit Chutima , Smith Duncan R.
Published: October 2003

The dengue virus consists of four antigenically related but distinct viruses, termed Dengue virus 1–4 (DEN 1–4). We have established that the dengue virus loses infectivity over time in solution in an exponentially declining manner. The four strains examined (one from each serotype) have half‐lives that range from 2.5 to 7.5 hr in defined medium. The half‐life is temperature and pH‐dependent and is affected by the nature of the host cell in which it is produced, but is not dependent upon the presence of either Mg2+ ions or chelating agents. Electron microscopy (EM) of solutions of the dengue virus show almost complete virus aggregation after 24 hr at room temperature, while RT‐PCR shows an intact RNA genome. These results show that the solution environment of the dengue virus is an important determinant of dengue virus infectivity. J. Med. Virol. 71:532–539, 2003. © 2003 Wiley‐Liss, Inc.
Broadly cross‐reactive mimotope of hypervariable region 1 of hepatitis C virus derived from DNA shuffling and screened by phage display library
Authors: Zhang Xin‐Xin , Deng Qiang , Zhang Shen‐Ying , Liu Jing , Cai Qian , Lu Zhi‐Meng , Wang Yuan
Published: October 2003

The hypervariable region 1 (HVR1) is the target of neutralizing antibodies but with isolate specificity. The aim of this study was to obtain immunogenic mimotopes of HVR1, which can react broadly with different HVR1 antibodies and could be one of the candidate immunogens in an effective vaccine against HCV. Thirty‐one HVR1 cDNA fragments were digested by DNase I into a pool of random fragments and reassembled by repeated cycles of annealing in the presence of DNA polymerase to their original size. The shuffled HVR1 was then inserted into the gene III phagemid vector pCANTAB‐5E and displayed on the surface of the phage. Eight individual phages were selected after four rounds of biopanning against anti‐HVR1. ELISA was carried out on immobilized purified phages, respectively, to detect their reactivity with a panel of sera. DNA sequences of the inserts were analyzed and compared with the consensus sequences defined by Puntoriero et al. [(1998) EMBO J 17:3521–3533]. The reactivity of the eight selected clones to the 30 sera were from 53.3 to 80%. Among these, phage 13 (ETYVSGGSAARNAYGLTSLFTVGPAQK, aa 384–410) reacted most broadly. None of the selected sequences encoded for peptides corresponded to known HVR1 from original viral isolates. The two high reactive phages had the similar amino acid sequences with the consensus, which might play a particular role in determining the frequency of reactivity. In conclusion, this study has used effectively DNA shuffling combined with phage display technology to identify broadly cross‐reactive mimotopes recognized by human polyclonal antibodies. Mimotope 13 and 23 appeared to be most reactive immunologically and could be candidate immunogens. Efforts are now underway to identify their neutralizing antibodies by immunization of animals. J. Med. Virol. 71:511–517, 2003. © 2003 Wiley‐Liss, Inc.
Mathematical model to simulate the cellular dynamics of infection with human herpesvirus‐6 in EBV‐negative infectious mononucleosis
Authors: Wang Guanyu , Krueger Gerhard R.F. , Buja L. Maximilian
Published: October 2003

Acute infection with human herpesvirus‐6 induces physiological cell proliferation in persons without major immune deficiency. It thus can serve as a parameter to validate a mathematical model designed to simulate cell proliferation under physiological and pathological conditions. Such a mathematical model is presented to simulate various cell changes of the T‐cell immune system during the course of HHV‐6 infection. Model development follows several steps, beginning with a basic model containing physiological T‐cell pools to the introduction of infectious stimuli in the final model. A search algorithm designed to optimize the system parameters, as well as initial variables of the model, is presented. The results of simulation runs for acute HHV‐6 infection of the final computational model correspond well to the data, as documented in human patients; they suggest that the computational model presented for the simulation of T‐cell levels in a given viral infection may well serve as a tool for similar studies of other viral infections, including those that lead to cellular aplasia or neoplasia. J. Med. Virol. 71:569–577, 2003. © 2003 Wiley‐Liss, Inc.
Evaluation of antibody‐based and nucleic acid‐based assays for diagnosis of hepatitis E virus infection in a rhesus monkey model
Authors: Zhang Jun , Ge Sheng X. , Huang Guo Y. , Li Shao W. , He Zhi Q. , Wang Ying B. , Zheng Ying J. , Gu Ying , Ng Mun H. , Xia Ning S.
Published: October 2003

We have evaluated four hepatitis E virus (HEV) specific antibody assays, using sequential samples taken from 86 rhesus monkeys at intervals for up to 86 weeks after they had been infected with different doses of HEV. The animals are a common experimental model of hepatitis E. The large collection of sequential samples used avoids uncertainties encountered in previous studies regarding the precise infection status of study subjects and minimizes bias due to the individuality of response to infection. One assay (YES IgG) was produced with synthetic peptides; the others (E2 IgM, E2 IgG, and GL IgG) were produced with recombinant antigens. The results were compared with the viral RNA contents of the serum and stool samples and the occurrence of these virological and immunological markers in the course of the infection was temporally related to the development of hepatitis. Diagnostic utility of the markers was assessed according to their response rates and prevalence at different times in the course of infection. All the animals produced E2 IgG and developed viremia and all but one also produced E2 IgM and excreted the virus in stool, whereas response rates for the other antibodies were lower and decreased with virus dose. Hepatitis occurred over a period of 4 weeks between 3 and 7 weeks after infection. Virological activity occurred mainly during the incubation period and the prevalence of viral markers declined rapidly after the onset of hepatitis. Production of the E2 antibodies immediately preceded the onset of hepatitis, and this was followed about one week later by production of the other antibodies. Seroprevalence E2 IgM reached a peak value 3 weeks after the onset of hepatitis, whereas seroprevalence of GL IgG and YES IgG peaked after the disease had subsided. E2 IgG persisted in all animals for the entire duration of the experiment of up to 86 weeks and possibly beyond and, thus, can serve as a useful epidemiological marker of HEV infection. J. Med. Virol. 71:518–526, 2003. © 2003 Wiley‐Liss, Inc.
Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression
Authors: Keoshkerian Elizabeth , Ashton Lesley J. , Smith Danielle G. , Ziegler John B. , Kaldor John M. , Cooper David A. , Stewart Graeme J. , Ffrench Rosemary A.
Published: October 2003

Ex vivo effector cytotoxic T‐lymphocyte (CTL) activity was assessed in 27 members of the Australian Long‐Term Nonprogressor cohort and correlated with genetic, virological, and immunological markers. The 27 individuals were antiretroviral naive with CD4+ T‐cell counts of >500 cells/μl for more than 8 years after human immunodeficiency virus type 1 (HIV‐1) infection. Effector CTL activity was determined using a standard ex vivo chromium release assay. Individuals with CTL activity (HIV‐1 envIIIB or pol or gag) were then compared to those without CTL activity in relation to plasma HIV‐1 RNA, ICD p24 antigen, β2‐microglobulin, CD4 and CD8 T‐cell counts, CCR5 and CCR2b genotypes, and progression to CD4 <500 cells/μl or commencement of antiretroviral treatment. Of the 27 individuals examined, 19 had no detectable effector CTL activity. The eight individuals with detectable CTL activity had significantly higher plasma levels of HIV‐1 RNA (P = 0.014), immune complex dissociated p24 antigen (P = 0.006), and β2‐microglobulin (P = 0.009). There was increased risk of progression within 4 years of study entry in individuals with detectable effector CTL activity, higher plasma levels of HIV‐1 RNA, higher β2‐microglobulin levels, and higher immune complex dissociated p24 antigen levels at enrollment (P = 0.017, P = 0.004, P = 0.027, P = 0.008 respectively). Multivariate analysis demonstrated viral load remained the strongest predictor of disease progression within this group (P = 0.017). There were no significant associations between CTL response and chemokine receptor genotype. These findings demonstrate the importance of HIV replication in generating an effector CTL response and show that effector CTL activity may be an early predictor of progression in people with long‐term asymptomatic HIV infection. J. Med. Virol. 71:483–491, 2003. © 2003 Wiley‐Liss, Inc.
Moderate variation of the oncogenic potential among high‐risk human papillomavirus types in gynecologic patients with cervical abnormalities
Authors: Szőke Krisztina , Sápy Tamás , Krasznai Zoárd , Hernádi Zoltán , Szládek Györgyi , Veress György , Dillner Joakim , Gergely Lajos , Kónya József
Published: October 2003

The oncogenic potential of human papillomavirus (HPV) infection was assessed by following the disease course in 455 patients who had had a routine diagnostic Hybrid Capture HPV test due to squamous cell abnormalities of the uterine cervix as detected by cytology and/or colposcopy. At entry, 308 patients had cytologic atypia classified as P3 by the Papanicolau classification, 168 had a positive high‐risk HPV test, and 23 were infected only with low‐risk HPV. The patients were followed‐up using the patient registry until the endpoint of histologically diagnosed cervical intraepithelial neoplasia (CIN). High‐grade CIN was diagnosed in 75 surgical biopsies. High‐risk HPV infection (relative risk: 76.8 CI95: 23.7–249.5), cytologic atypia (RR: 16.2 CI95: 3.9–66.6), and age above 35 (RR: 1.99 CI95: 1.26–3.16) were independent risk factors for high‐grade CIN, while the viral load did not predict oncogenic progression (P = 0.47). After PCR–RFLP typing, the high‐risk types were classified into groups as follows: (1) types 16 and 18, (2) types 45, 52, and 56, (3) types 31, 33, 35, 51, and 58. The relative risks of high‐grade CIN were 119.1 (CI95: 36.2–390.9) for group 1, 44.4 (CI95: 9.8–201) for group 2, and 39.7 (CI95: 10.9–144.8) for group 3, respectively. The risk ratios between the groups of high‐risk types were found to differ at most by a factor of 2.98 (corrected P value: 0.007) indicating that the oncogenic potential varies moderately within the high‐risk group of HPVs. J. Med. Virol. 71:585–592, 2003. © 2003 Wiley‐Liss, Inc.
Modifications and substitutions of the RNA extraction module in the ViroSeq™ HIV‐1 genotyping system version 2: Effects on sensitivity and complexity of the assay
Authors: Stürmer Martin , Berger Annemarie , Doerr Hans‐Wilhelm
Published: October 2003

Genotypic testing for HIV‐1 resistance to anti‐retroviral drugs has become accepted widely as a routine method to guide anti‐retroviral therapy. However, implementation into routine high‐throughput laboratory diagnosis is difficult due to the complexity of the assay. A commercially available assay is the ViroSeq™ HIV‐1 Genotyping System (Applied Biosystems, Weiterstadt, Germany). We modified and substituted the RNA extraction module to optimize the proportion of samples amplified successfully as follows: 1 ml plasma was concentrated by ultracentrifugation and extracted according to the manufacturer's instructions (Kit), by substituting the lysis buffer (Roche, Roche Diagnostics GmbH, Mannheim, Germany), and by using the QIAamp Viral RNA Kit (Qiagen GmbH, Hilden, Germany) with elution volumes of 60 (Q60) or 50 μl (Q50). Overall Q50 showed a higher success rate (97%) than the other extraction modules used (range 88–91%). In samples with a viral load range of 1,000–4,999 copies/ml, Q50 was superior (95 vs. 65% to 83%), while in samples with a viral load range of 5,000–9,999 copies/ml or those with 10,000 or more copies/ml, the success rate of the extraction procedures showed no significant differences. In 18 samples, which were negative using the Kit or Roche extraction, Q60 resulted in 7/18 positive results; in addition the Q50 was successful in amplifying 7/10 of the Q60 negative samples. When investigating samples with a measurable viral load of less than 1,000 copies/ml or lower, Q50 had the highest success rate with 80% compared to the other procedures (33–63%). A statistically significant new cut‐off could be defined for Q50 at a value of 250 copies/ml. The results showed clearly that the ViroSeq System is suitable for analyzing the HIV‐1 genotype over a wide range of viral loads but could be improved significantly when substituting the RNA extraction module with Q50 without using a nested PCR protocol. This is of great importance as it avoids further time‐ and cost‐intensive steps. J. Med. Virol. 71:475–479, 2003. © 2003 Wiley‐Liss, Inc.
Buccal exposure to human papillomavirus type 16 is a common yet transitory event of childhood
Authors: Mant Christine , Kell Barbara , Rice Philip , Best Jennifer M. , Bible Jon M. , Cason John
Published: October 2003

High‐risk human papillomaviruses, such as type 16 (HPV‐16), are established etiological agents for cervical carcinoma. In most cases, this virus is transmitted sexually, though can also be spread from mother to infant at delivery. We have demonstrated previously a high prevalence (∼52%) of HPV‐16 DNA in the mouths of prepubertal children, albeit with low levels of transcription [Rice et al., 2000]. We investigated whether childhood buccal infections with HPV‐16 are persistent or transient and whether children became infected through contact with their immediate family members. Two groups of children were selected: one group were all initially HPV‐16 E5 DNA‐positive in sensitive polymerase chain reaction tests of swabs from their buccal mucosa (n = 20), and the other group consisted of children who were all HPV‐16 E5‐negative (n = 19). Thirty months later, a second oral swab was collected from each child and tested for HPV DNA. At this second visit, 40% of the HPV‐16‐positive group had no detectable HPV‐16 DNA; conversely, 63% of children who were originally HPV‐16‐negative had now acquired the virus. Three months later, a third sample was collected from eight children and their immediate families (seven were HPV‐16 E5 DNA‐positive at the second visit). Amongst the family samples tested, in two families a single previously untested child was HPV‐16 DNA‐positive. It is concluded that HPV‐16 DNA in the oral cavities of children is a transient event and is most probably acquired from their peers. J. Med. Virol. 71:593–598, 2003. © 2003 Wiley‐Liss, Inc.
Molecular epidemiology of Kaposi's sarcoma‐associated herpesvirus/human herpesvirus 8 strains from Russian patients with classic, posttransplant, and AIDS‐associated Kaposi's sarcoma
Authors: Kadyrova Elena , Lacoste Vincent , Duprez Renan , Pozharissky Kazimir , Molochkov Vladimir , Huerre Michel , Gurtsevitch Vladimir , Gessain Antoine
Published: October 2003

We report the molecular characterization of 38 new Kaposi's sarcoma‐associated herpesvirus (KSHV) strains from Russian patients with either classic (25 cases), epidemic/AIDS‐associated (7 cases), or posttransplant/immunosuppressed patients (6 cases), or Kaposi's sarcoma (KS). While a complete sequence of the K1 gene (870 bp) was obtained from 30 strains, only partial sequences of the hypervariable regions VR1 (372 bp) and/or VR2 (381 bp) of the K1 gene were obtained from eight strains of KS paraffin blocks. Sequence comparison and phylogenetic studies indicate that the novel KSHV strains belong to either the A subtype (28 cases) or the C subtype (10 cases). Within the 28 strains of A subtype, 24 (86%) belong to the large A′ subgroup, mostly A1 and A1′ clades, and 4 belong to the A″ subgroup, mostly A3 clade. Within the 10 strains of subtype C, 4 were of C′ subgroup, and 6 of the C″. Some molecular variants of subtype A′ were observed, with 3 strains exhibiting an insertion of a single amino acid at the position 65 and 2 strains (both from AIDS‐KS) with an unique deletion of 17 amino acids in the VR2 region. Polymerase chain reaction‐based subtyping of the K14.1 genomic region indicated that most (23/32) of the novel strains belonged to the P subtype. The results indicate that despite a wide genetic diversity of A and C K1 subtypes of KSHV strains present in Russia, most are closely related and belong to the A1 or A1′ molecular clades suggesting a common origin. This study also expands the data regarding the absence of any correlation between a K1 molecular subtype and a specific KS type (classic, epidemic, or posttransplant), as well as between the K1 and K14.1 molecular subtypes. J. Med. Virol. 71:548–556, 2003. © 2003 Wiley‐Liss, Inc.
Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects
Authors: Douche‐Aourik Fatima , Berlier Willy , Féasson Léonard , Bourlet Thomas , Harrath Rafik , Omar Shabir , Grattard Florence , Denis Christian , Pozzetto Bruno
Published: October 2003

Enterovirus RNA has been found previously in specimens of muscle biopsy from patients with idiopathic dilated cardiomyopathy, chronic inflammatory muscle diseases, and fibromyalgia or chronic fatigue syndrome (fibromyalgia/chronic fatigue syndrome). These results suggest that skeletal muscle may host enteroviral persistent infection. To test this hypothesis, we investigated by reverse transcription‐polymerase chain reaction (RT‐PCR) assay the presence of enterovirus in skeletal muscle of patients with chronic inflammatory muscle diseases or fibromyalgia/chronic fatigue syndrome, and also of healthy subjects. Three of 15 (20%) patients with chronic inflammatory muscle diseases, 4 of 30 (13%) patients with fibromyalgia/chronic fatigue syndrome, and none of 29 healthy subjects was found positive. The presence of VP‐1 enteroviral capsid protein was assessed by an immunostaining technique using the 5‐D8/1 monoclonal antibody; no biopsy muscle from any patient or healthy subject was found positive. The presence of viral RNA in some muscle biopsies from patients exhibiting muscle disease, together with the absence of VP‐1 protein, is in favor of a persistent infection involving defective viral replication. J. Med. Virol. 71:540–547, 2003. © 2003 Wiley‐Liss, Inc.
Frequency of human cytomegalovirus‐specific T cells during pregnancy determined by intracellular cytokine staining
Authors: Fujikawa Tomoko , Numazaki Kei , Asanuma Hideomi , Kudo Ryuichi , Tsutsumi Hiroyuki
Published: October 2003

The characteristics of cytomegalovirus (CMV)‐specific T‐cell immunity was investigated in pregnant women with primary, latent, or reactivated CMV infection, and in a comparative group of non‐pregnant women. Forty‐six pregnant and 8 non‐pregnant women were examined based on the presence of serum antibody activity against CMV and viral excretion in urine. The frequency of CMV‐specific CD4+ T cells in peripheral blood lymphocytes was determined by staining for intracellular cytokines, interferon (IFN)‐γ, and tumor necrosis factor (TNF)‐α. There was no change in the frequencies of CMV‐specific CD4+ T cells in CMV‐seropositive normal non‐pregnant and pregnant women at any gestation. However, the frequency of CMV‐specific CD4+ T cells in pregnant women associated with CMV reactivation or reinfection was significantly higher than in CMV‐seropositive normal pregnant and non‐pregnant women. There were no CMV transmissions to the infants of all these women. These CMV‐specific T cells responses in pregnant women may contribute some to block the intrauterine CMV infection in their infants. J. Med. Virol. 71:527–531, 2003. © 2003 Wiley‐Liss, Inc.
The central Andean west‐slope rainshadow and its potential contribution to the origin of hyper‐aridity in the Atacama Desert
Authors: Houston John , Hartley Adrian J.
Published: October 2003

The west slope of the central Andes exhibits a pronounced rainshadow effect. Precipitation between 15° and 27 °S is dominated by summer convective activity from Amazonia, and data analysis shows that the increase in precipitation with elevation due to the rainshadow effect best fits an exponential correlation. Coupling with limited data from high elevations suggests that the correlation is accurate to 4500 m above sea level (m a.s.l.) and perhaps to 5500 m a.s.l., suggesting that increased precipitation goes unrecorded over the peaks of the western Cordillera. South of 27 °S the precipitation is dominated by winter frontal sources and shows no well‐defined relationship with elevation. The core zone of hyper‐aridity in the Atacama Desert extends from 15 to 30 °S at elevations from sea level to 3500 m a.s.l. Although the Atacama Desert has existed since at least 90 Ma, it is considered that the initial onset of hyper‐aridity was most likely to have developed progressively with the uplift of the Andes as they reached elevations between 1000 to 2000 m a.s.l. coupled with the intensification of a cold, upwelling Peruvian Current between 15 and 10 Ma. Also apparent in the palaeogeographic record are subsequent fluctuations between (semi‐) arid to hyper‐arid conditions that were probably largely controlled by changes in orbital and oceanic forcing. Copyright © 2003 Royal Meteorological Society
Were southern Swedish summer temperatures before 1860 as warm as measured?
Authors: Moberg Anders , Alexandersson Hans , Bergström Hans , Jones Philip D.
Published: October 2003

Temperature series from Stockholm and Uppsala in southern Sweden indicate that summers from the mid‐18th century until around 1860 were, on average, warmer than the 1961–90 mean. The station histories suggest that the early observations could have been positively biased, for example because of insufficient radiation protection. We investigate if independent support for warm summers in the early period can be obtained from other climate variables. Using stepwise multiple regression analysis we investigate nine potential predictor variables: six air circulation indices, precipitation, air pressure and cloud amount. Three of these variables—cloud amount (the most important one), meridional geostrophic wind, and air pressure—together explain 65% of the June–August temperature variance in the calibration period 1873–2000. Application of the regression relationship back to 1780 shows that the model is equally successful in predicting year‐to‐year temperature variability before 1873 as it is in the calibration period, whereas the low‐frequency component is poorly reconstructed in the early period. This reduced skill is primarily due to poorer data quality of the predictor variables in the early period, in particular the cloud amount series. The observed decadal mean temperatures during 1780–1860 are found to be above the upper limit of a 95% confidence interval that accounts for uncertainties both in the regression relationship and in the cloud amount series. We conclude that the observed temperatures before around 1860 are, therefore, most likely positively biased. The size of this bias cannot be accurately determined from the evidence used here, but seems to be about 0.7–0.8°C for both stations. A comparison with long instrumental temperature series from central Europe suggests a slightly smaller bias (0.5–0.6°C). For more accurate assessment of the Stockholm and Uppsala temperatures, we recommend that extensive homogeneity testing of other long northern European temperature series are undertaken. Copyright © 2003 Royal Meteorological Society
A composite monthly temperature record from Tornedalen in northern Sweden, 1802–2002
Authors: Klingbjer Per , Moberg Anders
Published: October 2003

Previously unexplored observational temperature data for the period 1802–62 from Övertorneå and Kalix in the Tornedalen area in subarctic Sweden (∼66 °N), have been analysed. These early data have been combined with the temperature series from the synoptic weather station in Haparanda, beginning in August 1859, to develop a continuous Tornedalen temperature series with monthly means 1802–2002. The temperature data between 1802 and 1859 have been adjusted to correspond to Haparanda temperatures using information from time periods with overlapping observations, both in the early period and in recently made observations at the original sites. Additional information for homogenizing the series was obtained from temperature series for Vardø, Oulu, and Helsinki. Our judgement is that the reconstructed Tornedalen temperature record is reliable back to November 1832. Before this, the summer (June–August) temperatures in particular are less reliable, whereas data for the other seasons seem to be realistic, at least on decadal time scales. The annual mean temperatures are judged as realistic back to the start of the record.

Between 1802 and 2000 there has been a warming trend in Tornedalen at an average rate of 0.099 °C decade−1 or 1.97 °C in total. The total warming explained by linear trends was greatest in winter (2.83 °C) followed by spring (2.17 °C), autumn (1.87 °C) and summer (0.88 °C). The annual warming trend during 1802–1900 was slightly greater than that for 1901–2000. Warming in winter contributed most to the rise in annual temperatures during the 19th century, whereas spring contributed most in the 20th century. The warmest decade was the 1930s, after which a strong cooling trend occurred until the 1970s (−0.325 °C decade−1, 1941–70). Warming then set in again to the end of the series (0.227 °C decade−1, 1971–2002). Copyright © 2003 Royal Meteorological Society
Statistical correction of central Southwest Asia winter precipitation simulations
Authors: Tippett Michael K. , Barlow Mathew , Lyon Bradfield
Published: October 2003

Severe drought is a notable feature of the hydrology of central Southwest (CSW) Asia. Although studies have linked the region's interannual precipitation variability to remote forcings that include East Asia jet stream variability and western Pacific tropical convection, atmospheric general circulation models (GCMs) forced by observed sea‐surface temperatures demonstrate little skill in simulating interannual precipitation variability in this region. Here, statistical methods of correcting systematic errors in GCM simulations of CSW Asia precipitation are investigated. Canonical correlation analysis is used to identify model fields related to observed precipitation anomaly patterns. These relationships are then used to predict observed precipitation anomalies. This approach is applied to the ECHAM 4.5 GCM using regional precipitation, upper‐level winds and western Pacific tropical precipitation as predictors of observed CSW Asia precipitation anomalies. The statistical corrections improve the GCM precipitation simulations, resulting in modest, but statistically significant, cross‐validated skill in simulating CSW Asia precipitation anomalies. Applying the procedure to hindcasts with persisted sea‐surface temperatures gives lower, but statistically significant, precipitation correlations in the region along the Hindu Kush mountain range. Copyright © 2003 Royal Meteorological Society
Interannual variations of storm tracks in the Southern Hemisphere and their connections with the Antarctic oscillation
Authors: Brahmananda Rao V. , do Carmo Alexandre M. C. , Franchito Sergio H.
Published: October 2003

Interannual variations of storm tracks in the Southern Hemisphere (SH) are studied. Large interannual variations are found in the enveloping function of meridional wind ve and these suggest some dominant periodicities. Some of these periodicities are a quasi‐biennial oscillation in the subtropical branch of the winter storm track and the midlatitude spring storm track, a 3 year period and a long period of 8 years. The Antarctic oscillation (AAO) seems to be connected to the interannual variation of storm tracks in the SH. A significant negative correlation between ve and the AAO index in the high latitudes, a positive correlation in the midlatitudes and again a negative correlation in the subtropics are found throughout the year. During the high index phase of the AAO, the low‐level zonal wind shear increases in the region of midlatitude storm tracks and the static stability decreases, increasing the growth rate of baroclinic eddies, i.e. increase of ve (the opposite occurs during the negative phase). This explains the positive correlation in the midlatitudes between ve and the AAO index. In the region of the subtropical storm track during the high index phase the wind shear decreases and the static stability increases, decreasing the growth rates, thus explaining the negative correlation between ve and the AAO index. Copyright © 2003 Royal Meteorological Society
Identification of three dominant rainfall regions within Indonesia and their relationship to sea surface temperature
Authors: Aldrian Edvin , Dwi Susanto R.
Published: October 2003

The characteristics of climatic rainfall variability in Indonesia are investigated using a double correlation method. The results are compared with empirical orthogonal function (EOF) and rotated EOF methods. In addition, local and remote responses to sea‐surface temperature (SST) are discussed. The results suggest three climatic regions in Indonesia with their distinct characteristics. Region A is located in southern Indonesia from south Sumatera to Timor island, southern Kalimantan, Sulawesi and part of Irian Jaya. Region B is located in northwest Indonesia from northern Sumatra to northwestern Kalimantan. Region C encompasses Maluku and northern Sulawesi. All three regions show both strong annual and, except Region A, semi‐annual variability. Region C shows the strongest El Niño–southern oscillation (ENSO) influence, followed by Region A. In Region B, the ENSO‐related signal is suppressed. Except for Region B, there are significant correlations between SST and the rainfall variabilities, indicating a strong possibility for seasonal climate predictions. March to May is the most difficult season to predict the rainfall variability. From June to November, there are significant responses of the rainfall pattern to ENSO in Regions A and C. A strong ENSO influence during this normally dry season (June to September) is hazardous in El Niño years, because the negative response means that higher SST in the NIÑO3 of the Pacific region will lower the rainfall amount over the Indonesian region. Analyses of Indonesian rainfall variability reveal some sensitivities to SST variabilities in adjacent parts of the Indian and Pacific Oceans. Copyright © 2003 Royal Meteorological Society
The influence of wind and topography on precipitation distribution in Sweden: statistical analysis and modelling
Authors: Johansson Barbro , Chen Deliang
Published: October 2003

To estimate daily catchment precipitation from point observations there is a need to understand the spatial pattern, particularly in mountainous regions. One of the most important processes occurring there is orographic enhancement, which is affected by, among other things, wind speed and wind direction. The objective of this paper was to investigate whether the relationship between precipitation, airflow and topography could be described by statistical relationships using data easily available in an operational environment. The purpose was to establish a statistical model to describe basic patterns of precipitation distribution. This model, if successful, can be used to account for the topographical influence in precipitation interpolation schemes. A statistical analysis was carried out to define the most relevant variables, and, based on that analysis, a regression model was established through stepwise regression. Some 15 years of precipitation data from 370 stations in Sweden were used for the analysis. The geostrophic wind, computed from pressure observations, was assumed to represent the airflow at the relevant altitude. Precipitation data for each station were divided into 48 classes representing different wind directions and wind speeds. Among the variables selected, the single most important one was found to be the location of a station with respect to a mountain range. On the upwind side, precipitation increased with increasing wind speed. On the leeward side there was less variation in precipitation, and wind speed did not affect the precipitation amounts to the same degree. For ascending air, slope multiplied by wind speed was another important factor. The effect of slope was enhanced close to the coast, and reduced for mountain valleys with upwind barriers. The stepwise procedure led to a regression model that also included the meridional and zonal wind components. Their inclusion might indicate the importance of air mass characteristics not explicitly accounted for. Copyright © 2003 Royal Meteorological Society
Recalibration of general circulation model output to austral summer rainfall over southern Africa
Authors: Bartman A. G. , Landman W. A. , Rautenbach C. J. DE W.
Published: October 2003

Empirical techniques are developed to adjust dynamic model forecasts on the seasonal time scale for southern African summer rainfall. The techniques, perfect prognosis and model output statistics (MOS), are utilized to ‘recalibrate’ the CSIRO 9 general circulation model (GCM) large‐scale fields statistically to three equi‐probable rainfall categories for December to February. The recalibration is applied to a GCM experiment where simultaneously observed sea‐surface temperature fields serve as the lower boundary forcing. An optimal canonical correlation analysis model is designed for MOS and perfect prognosis and the 700 hPa geopotential height field is selected as the single predictor field in the two sets of statistical equations that are subsequently used to produce recalibrated rainfall simulations over a 10 year independent test period. MOS produced the higher forecast skill for southern Africa over the independent test period. Copyright © 2003 Royal Meteorological Society
Inter‐specific variability in organic nitrogen uptake of three temperate grassland species
Authors: Weigelt Alexandra , King Rosalind , Bol Roland , Bardgett Richard D.
Published: October 2003

We tested the inter‐specific variability in the ability of three dominant grasses of temperate grasslands to take up organic nitrogen (N) in the form of amino acids in soils of differing fertility. Amino acid uptake was determined by injecting dual labeled glycine‐2‐13C‐15N into the soil, and then measuring the enrichment of both 13C and 15N in plant tissue after 50 hours. We found enrichment of both 13C and 15N in root and shoot material of all species in both soils, providing first evidence for direct uptake of glycine. We show that there was considerable inter‐specific variability in amino acid uptake in the low fertility soil. Here, direct uptake of amino acid was greater in the grass Agrostis capillaris, which typically dominates low fertility grassland, than Lolium perenne, which inhabits more fertile sites. Direct uptake of amino acid for Holcus lanatus. was intermediate between the above two species. Unlike in the low fertility soil, there was no difference in uptake of either 13C or 15N by grasses in the high fertility soil, where uptake of mineral N is thought to be the major mechanism of N uptake of these grasses. Overall, our findings may contribute to our understanding of differences in competitive interactions between grasses in soils of different fertility status.
Preparing a soil carbon inventory of Saxony‐Anhalt, Central Germany using GIS and the state soil data base SABO_P
Authors: Grabe Matthias , Kleber Markus , Hartmann Klaus‐Jörg , Jahn Reinhold
Published: October 2003

To obtain information on regional soil carbon (C) stocks, we prepared a soil C inventory for the central German State Saxony‐Anhalt. We used the State Soil Database SABO_P (Sachsen‐Anhalt Boden_Profildatenbank), which contains data from 3,600 soil profiles with 16,300 individual soil horizons and combined it with a geographic information system (GIS ArcView). Soil C stocks down to a depth of 100 cm were compiled for the three major soil regions of Saxony‐Anhalt (soil region 2: river valleys and floodplains; soil region 4: pre‐Weichselian moraines, and soil region 6: loess‐covered areas), which represent 83 % of the total state territory. The three major soil regions in Saxony‐Anhalt comprise on average 12.7 (soil region 2), 8.9 (soil region 4), and 12.8 kg C m–2 (soil region 6). Total C content of the area investigated was 191 tg. The typical soils of the region, Haplic Chernozems, contain on average 13.9 kg C m–2. With few exceptions, soil C did not vary significantly within identical taxonomic groups among different soil subregions. However, Chernozems of soil subregion 3 (Wanzlebener Löß‐Plateau; 19.8 kg C m–2) contain significantly more C than the Chernozems of soil subregions 9 (Pollebener, Gerbstedter and Lettewitzer Löß‐Plateau; 12.1 kg C m–2) and 15 (Barnstädter Löß‐Plateau 12.2 kg C m–2). The spatial distribution of C stocks in Saxony‐Anhalt was represented in a map which suggests the existence of a strong link between the geomorphologic position of a given soil and its capacity to store organic C. Within the same taxonomic unit, finer textured soils stored more carbon than coarse‐textured ones.
Skin/bulk nanostructure and corrosion of SiC‐based fibres: a surface Rayleigh and Raman study
Authors: Havel M. , Colomban Ph.
Published: October 2003

SiC‐based fibres are complex systems of nanophases. Raman imaging of polished Tyranno SA3 fibre (UBE Industry) sections indicated that carbon species have different concentrations, natures and short‐range order on the fibre core and surface, which results from the production process. The monitoring of the fibre's skin/bulk nanostructure, composition and geometry was performed on sections by Raman and Rayleigh microspectrometry. Owing to the weak light penetration in these materials, Rayleigh diffusion can map the surface geometry. The spatial correlation model applied to the LO SiC Raman mode at ca 969 cm−1 allowed us to estimate the size variation of the small SiC crystallites across the fibre. A model based on the ID/IG Raman peak ratio was used to calculate and map the size distribution of the carbon moieties. The position of the D′ Raman peak at ca 1620 cm−1, which is correlated with the graphite in‐plane lattice contraction or expansion, allowed us to identify the intercalant ions. The fibre's core, which contains non‐aromatic carbon moieties, is corroded much faster than the periphery under an alkaline and oxidative environment (modelled by molten NaNO3 and LiNO3). This is considered to be linked to the nature of these carbon moieties and to their location (at triple points and grain boundaries), which constitutes a direct diffusion pathway. Copyright © 2003 John Wiley & Sons, Ltd.
Towards a philosophy of strategy: reassessing five critical dilemmas in strategy formulation and change
Authors: Parnell John A. , Lester Donald L.
Published: October 2003

Although there has been a considerable amount of prescriptive research in the strategic management field, top executives are still faced with a number of somewhat philosophical ‘judgment calls’ when formulating strategies for their companies.

Five of these key issues include: (1) approaching strategy as an art or as a science; (2) publicizing strategy content or maintaining its secrecy; (3) seeking strategic consistency over the long term or maintaining flexibility; (4) embracing or avoiding strategic risk; and (5) adopting a top‐down or a bottom‐up approach to strategic planning.

This paper examines the predispositions of managers concerning these challenges and integrates them into four comprehensive philosophical approaches to strategy formulation. Prospects for future research are also presented.

Copyright © 2003 John Wiley & Sons, Ltd.
Strategic positioning: a study of the Nordic paper and pulp industry
Authors: Kald Magnus
Published: October 2003

Few perspectives in research on strategy have had as great an impact as Porter's (1980, 1985) framework for strategic positioning. The concepts of cost leadership and differentiation have been used both by practitioners in strategic planning and by scholars as the starting point for empirical studies. This widespread use has probably contributed to the high level of interest in the possibilities and limitations of the perspective.

In this paper, certain central aspects of strategic positioning are examined empirically. The study covers seven business units in two segments of the paper and pulp industry in the Nordic region over a 10‐year period from 1991 to 2000.

Among the aspects discussed are the possibility of strategic change and the possibility of combining strategic position. Other aspects treated are the relationship of the intended strategic position, as declared in the annual reports, to the realized strategic position, as shown by the relative positions of the business units compared to their competitor.

The findings indicate that strategic positions are stable over time and that none of the business units was able to combine the positions of cost leadership and differentiation for a longer period of time. The results also suggest substantial congruence between the intended strategy and the realized strategy, at the units studied.

Copyright © 2003 John Wiley & Sons, Ltd.
Strategic implications for the development of on‐line banking in Spain
Authors: Arbussà Anna , Bernal Enrique
Published: October 2003

The development of on‐line banking has the potential to affect the Spanish banking industry, facilitating the entry of new competitors into the market.

New entrants may choose to specialize in standardized services, where on‐line technology has the potential to give them a competitive advantage and compete against existing players who have a universal banking business model. However, standardized services have low switching costs and therefore on‐line banks may not enjoy the market power that established players currently enjoy.

This paper examines the development of on‐line banking technology, focusing on the strategies developed by two on‐line banks in Spain that have recently entered the market, and documents the strategic responses of the incumbent players.

Copyright © 2003 John Wiley & Sons, Ltd.
Strategic management in the Japanese context: the East Japan Railway Company (JR East) 1987–2002
Authors: Smith Ian B.
Published: October 2003

This paper reviews the operation of the Japanese Railway (JR) Companies since the dissolution and privatization of the Japanese National Railways in 1987 and evaluates the changes in the strategic management approach of the JR Companies in the ensuing period. It focuses on JR East, which operates the largest passenger network in Japan and examines both the changes in the company's operating environment since privatization and its strategic management policy in relation to these developments.

The key strategic and business environment issues identified in the paper are primarily government regulation of railway operations, social change — particularly in terms of the demographic profile — and a changing competitive environment.

The reaction of the company's management to these events may be summarized as little discernible change in the strategic management approach in the first 10 years after privatization, for two principal reasons. During that period Japanese companies continued to observe the strategic targets of revenue growth and market share (rather than profitability) and there continued to be acceptance that the Japanese railway companies were obliged, for social reasons, to run unprofitable services, the closure of which would have boosted the company's profitability.

It appears, however, that the company's strategy over the past five years has become clarified and simplified, with a greater emphasis on profitability targets and shareholder value.

Copyright © 2003 John Wiley & Sons, Ltd.
Tramadol Release from a Delivery System Based on Alginate‐Chitosan Microcapsules
Authors: Acosta Niuris , Aranaz Inmaculada , Peniche Carlos , Heras Angeles
Published: October 2003

Alginate‐chitosan microcapsules to control the release of Tramadol‐HCl were prepared using two different methods. In the two‐stage procedure (Variant I) alginate was first pumped into a CaCl2/NaCl solution and then transferred into a chitosan solution. In the one‐stage procedure (Variant II) alginate was directly pumped into a chitosan/CaCl2 solution, and different behavior could be noted in each case. The microcapsules were spherical in both variants and they swelled to a greater extent in a basic medium as compared to an acid one. The drug release profile of Tramadol from microcapsules in simulated gastric fluid and simulated intestinal fluid was also studied. The maximum release of Tramadol at 24 h was 64% and 86% for Variant I and II, respectively, in simulated intestinal fluid. Release was adjusted using the power law of the semi‐empirical Peppas equation in order to gain information about the release mechanism. In both cases the values of the exponent were found to be between 0.53 and 0.84 for swellable microcapsules in simulated gastric and intestinal fluids, respectively, indicating anomalous drug transport for both variants. The good results obtained with alginate‐chitosan microcapsules are comparable to those of the best products so far described in the scientific bibliography and in addition, chitosan is useful in pharmacy.

Surface morphology of Tramadol‐loaded microcapsule.

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Surface morphology of Tramadol‐loaded microcapsule.