bluuebunny/crossref_metadata_2025 huggingface dataset:
Lost Causes
Authors: Hoover Kevin D.
Published: July 2004

Often papers begin with an idea. Once the paper is written, sometimes little sometimes much effort goes into finding a title. This lecture worked the other way round. It started with the title, which I passed on to Roy Weintraub, my successor as President of the Society, when I still had but the vaguest idea ol what I would write. When Roy heardmy title he pointed me to a passage from C. Vann Woodward, that he hadhimself quotedinStablizing Dynamics:

Lost causes, especially those that foster loyalties and nostalgic memories are among the most prolific breeders of historiography. If survivors deem the cause not wholly lost andperhaps in some measure retrievable, the search of the past becomes more frantic and the books about it more numerous. Blame must be fixed, villains found, heroes celebrated, old quarrels settled, old dreams restored, and motives vindicated. Amid the ruins controversy thrives and books proliferate (quoted by Weintraub 1991, p. 125, from Vann Woodward 1986).
The Culture of Quantification and the History of Public Reason
Authors: Porter Theodore M.
Published: July 2004

It is an unusual and memorable privilege to address so international a gathering here in North Carolina on the Fourth of July. American nationalism in recent times has not been very broad-minded, and I'm envious of a society that can attract so many participants from all over the world. But the issue of cosmopolitanism and parochialism pertains to academic discipline as well as to nationality. Historians and economists do not always understand one another very well, and while economists are able to bring in bigger incomes and to maintain a higher public profile, historians maintain a certain authority in regard to scholarly writing about the past. Practitioners of history of economics have often been upbraided for failing to write “real” history, and I have been known to write in this vein. At least I am among those who have tried to persuade members of this society of the merits of history, history of science, and science studies as models for writing history of economics. At the same time I have been seduced by the fascination of this field to devote much of my own research to it, and in these efforts I have come to admire and to draw inspiration from what is distinctive in historical writing on economics, as well as what seems most familiar from the standpoint of the historical discipline.
Signaling Pathways for Early Brain Injury after Subarachnoid Hemorrhage
Authors: Kusaka Gen , Ishikawa Mami , Nanda Anil , Granger D. Neil , Zhang John H.
Published: July 2004

Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood–brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.
Changes in TrkB–ERK1/2–CREB/Elk-1 Pathways in Hippocampal Mossy Fiber Organization after Traumatic Brain Injury
Authors: Hu Bingren , Liu Chunli , Bramlett Helen , Sick Thomas J. , Alonso Ofelia F. , Chen Shaoyi , Dietrich W. Dalton
Published: July 2004

Traumatic brain injury (TBI) leads to mossy fiber reorganization, which is considered to be a causative factor in the development of temporal lobe epilepsy. However, the underlying mechanism is not fully understood. Emerging evidence suggests that TrkB–ERK1/2–CREB/Elk-1 pathways are highly related to synaptic plasticity. This study used the rat fluid-percussion injury model to investigate activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways after TBI. Rats were subjected to 2.0-atm parasagittal TBI followed by 30 minutes, 4 hours, 24 hours, and 72 hours of recovery. After TBI, striking activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways in mossy fiber organization were observed with confocal microscopy and Western blot analysis. ERK1/2 was highly phosphorylated predominantly in hippocampal mossy fibers, whereas TrkB was phosphorylated both in the mossy fibers and the dentate gyrus region at 30 minutes and 4 hours of recovery after TBI. CREB was also activated at 30 minutes, peaked at 24 hours of recovery, and returned to the control level at 72 hours of recovery in dentate gyrus granule cells. Elk-1 phosphorylation was seen in CA3 neurons at 4 hours after TBI. The results suggest that the signaling pathways of TrkB–ERK1/2–CREB/Elk-1 are highly activated in mossy fiber organization, which may contribute to mossy fiber reorganization seen after TBI.
A comparison of the effects of oral inoculation with Rotashield and pentavalent reassortant rotavirus vaccine (WC3-PV) on suckling CB17scid mice
Authors: Qiao Haiping , Clark H. Fred , DiVietro Matthew , Riepenhoff-Talty Marie
Published: July 2004

The effects of oral inoculation into infant CB17scid mice of two reassortant rotavirus vaccines were compared. The vaccines were Rotashield and WC3-PV, a mixture of five reassortants (G1, G2, G3, G4 and P1; pentavalent reassortant vaccine). Control mice were inoculated with a placebo. At 6 days post-inoculation (p.i.), 8 of 13 (62 %; P<0·005) Rotashield-inoculated mice developed hepatitis and/or bile-duct obstruction compared with none of 11 mice given WC3-PV and none of 14 given placebo. In the Rotashield-inoculated mice, only serotype G3 rhesus rotavirus (RRV) was isolated from multiple sites, including intestine, liver, pancreas, spleen, blood and mesenteric lymph nodes. Recovery of RRV from Rotashield-inoculated mice followed a biphasic pattern. The two peaks of RRV recovery appeared to coincide firstly with replication in the intestine during days 1–3 p.i., and secondly with virus infection of the liver from days 10 to 15 p.i. WC3 reassortants of four different serotypes were detected only at day 1 p.i. in the intestine, liver, pancreas and blood cells from three WC3-PV-inoculated mouse pups. However, WC3-PV did not produce any hepatopathology. Rotashield and WC3-PV appeared to exhibit different biological activity in infant CB17scid mouse pups.
Total viral genome copies and virus–Ig complexes after infection with influenza virus in the nasal secretions of immunized mice
Authors: Yoshikawa Tomoki , Matsuo Keiko , Matsuo Kazutoshi , Suzuki Yujiro , Nomoto Akio , Tamura Shin-ichi , Kurata Takeshi , Sata Tetsutaro
Published: July 2004

The kinetics of infectious virus (p.f.u.), total virus and virus–Ig complex formation following influenza A/PR8 (H1N1) viral infection was examined in the nasal secretions of naive mice and mice immunized with A/PR8, A/Yamagata (H1N1), A/Guizhou (H3N2) and B/Ibaraki influenza viruses. The total number of virus particles and the number within virus–Ig complexes, captured in advance using an anti-mouse Ig-coated plate, were determined on the basis of viral genome copy number using quantitative RT-PCR. The kinetics of infectious and total virus particle formation, the latter of which increased by 103–104-fold above infectious virus numbers, showed that virus elimination from the nasal area was earlier in A/PR8, A/Yamagata and A/Guizhou-X virus-immunized mice, in decreasing order, compared with naive mice. Early virus elimination correlated with the level of A/PR8 virus-reactive antibodies in immunized mice. Virus elimination coincided with the appearance of virus–Ig complexes shortly after infection. This result suggested that antibodies led to the formation of immune complexes in a dose-dependent manner together with a reduction in number of infectious virus particles. The fact that a large number of virus particles was observed in immune complexes for a wide range antibody levels made it difficult to detect slight differences in virus number within the immune complexes, depending on antibody level. These results suggested that the formation of virus–Ig complexes in virus-immunized mice shortly after infection is involved in early virus elimination, which is determined by the strength of protective immunity against challenge viruses.
Population structure and genetic variability within isolates of Grapevine fanleaf virus from a naturally infected vineyard in France: evidence for mixed infection and recombination
Authors: Vigne Emmanuelle , Bergdoll Marc , Guyader Sébastien , Fuchs Marc
Published: July 2004

The nematode-borne Grapevine fanleaf virus, from the genus Nepovirus in the family Comoviridae, causes severe degeneration of grapevines in most vineyards worldwide. We characterized 347 isolates from transgenic and conventional grapevines from two vineyard sites in the Champagne region of France for their molecular variant composition. The population structure and genetic diversity were examined in the coat protein gene by IC-RT-PCR-RFLP analysis with EcoRI and StyI, and nucleotide sequencing, respectively. RFLP data suggested that 55 % (191 of 347) of the isolates had a population structure consisting of one predominant variant. Sequencing data of 51 isolates representing the different restrictotypes confirmed the existence of mixed infection with a frequency of 33 % (17 of 51) and showed two major predominant haplotypes representing 71 % (60 of 85) of the sequence variants. Comparative nucleotide diversity among population subsets implied a lack of genetic differentiation according to host (transgenic vs conventional) or field site for most restrictotypes (17 of 18 and 13 of 18) and for haplotypes in most phylogenetic groups (seven of eight and six of eight), respectively. Interestingly, five of the 85 haplotypes sequenced had an intermediate divergence (0·036–0·066) between the lower (0·005–0·028) and upper range (0·083–0·138) of nucleotide variability, suggesting the occurrence of homologous RNA recombination. Sequence alignments clearly indicated a mosaic structure for four of these five variants, for which recombination sites were identified and parental lineages proposed. This is the first in-depth characterization of the population structure and genetic diversity in a nepovirus.
The adenovirus E1A and E1B19K genes provide a helper function for transfection-based adeno-associated virus vector production
Authors: Matsushita Takashi , Okada Takashi , Inaba Toshiya , Mizukami Hiroaki , Ozawa Keiya , Colosi Peter
Published: July 2004

Although the adenoviral E1, E2A, E4 and VA RNA regions are required for efficient adeno-associated virus (AAV) vector production, the role that the individual E1 genes (E1A, E1B19K, E1B55K and protein IX) play in AAV vector production has not been clearly determined. E1 mutants were analysed for their ability to mediate AAV vector production in HeLa or KB cells, when cotransfected with plasmids encoding all other packaging functions. Disruption of E1A and E1B19K genes resulted in vector yield reduction by up to 10- and 100-fold, respectively, relative to the wild-type E1. Interruption of the E1B55K and protein IX genes had a modest effect on vector production. Interestingly, expression of anti-apoptotic E1B19K cellular homologues such as Bcl-2 or Bcl-xL fully complemented E1B19K mutants for AAV vector production. These findings may be valuable for the future development of packaging cell lines for AAV vector production.
Active NF-κB signalling is a prerequisite for influenza virus infection
Authors: Nimmerjahn Falk , Dudziak Diana , Dirmeier Ulrike , Hobom Gerd , Riedel Alexander , Schlee Martin , Staudt Louis M. , Rosenwald Andreas , Behrends Uta , Bornkamm Georg W. , Mautner Josef
Published: July 2004

Influenza virus still poses a major threat to human health. Despite widespread vaccination programmes and the development of drugs targeting essential viral proteins, the extremely high mutation rate of influenza virus still leads to the emergence of new pathogenic virus strains. Therefore, it has been suggested that cellular cofactors that are essential for influenza virus infection might be better targets for antiviral therapy. It has previously been reported that influenza virus efficiently infects Epstein–Barr virus-immortalized B cells, whereas Burkitt's lymphoma cells are virtually resistant to infection. Using this cellular system, it has been shown here that an active NF-κB signalling pathway is a general prerequisite for influenza virus infection of human cells. Cells with low NF-κB activity were resistant to influenza virus infection, but became susceptible upon activation of NF-κB. In addition, blocking of NF-κB activation severely impaired influenza virus infection of otherwise highly susceptible cells, including the human lung carcinoma cell lines A549 and U1752 and primary human cells. On the other hand, infection with vaccinia virus was not dependent on an active NF-κB signalling pathway, demonstrating the specificity of this pathway for influenza virus infection. These results might be of major importance for both the development of new antiviral therapies and the understanding of influenza virus biology.
Characterization of germline porcine endogenous retroviruses from Large White pig
Authors: Scobie Linda , Taylor Samantha , Logan Nicola A. , Meikle Sharon , Onions David , Patience Clive , Quinn Gary
Published: July 2004

Porcine endogenous retroviruses (PERV) are of concern when the microbiological safety aspects of xenotransplantation are considered. Four unique isolates of PERV B have been identified previously from a lambda library constructed from genomic DNA from a Large White pig. This study shows that none of these isolates are replication competent when transfected into permissive human or pig cells in vitro, and the removal of flanking genomic sequences does not confer a human tropic replication competent (HTRC) phenotype on these PERV proviruses. Analysis of the envelope sequences revealed that PERV B demonstrated high similarity to the envelope sequences derived from replication-competent PERV, indicating that lack of replication competence does not appear to be attributable to this region of the provirus. These data complement recent findings that HTRC PERV are recombinants between the PERV A and PERV C subgroups, and that these recombinants are not present in the germline of miniature swine. Together, these results indicate that these individual PERV B proviruses are unlikely to give rise to HTRC PERV.
CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals
Authors: Eriksson Kristina , Bellner Lars , Görander Staffan , Löwhagen Gun-Britt , Tunbäck Petra , Rydberg Kristina , Liljeqvist Jan-Åke
Published: July 2004

T-cell recognition of the secreted and membrane-bound portions of the herpes simplex virus type 2 (HSV-2) glycoprotein G (sgG-2 and mgG-2, respectively) was compared in symptomatic and asymptomatic HSV-2-infected individuals and in HSV-2-seronegative controls and the responses with HSV-1 glycoproteins C and E (gC-1 and gE-1) were compared. CD4+T cells from HSV-2-infected individuals specifically recognized both sgG-2 and mgG-2, whereas HSV-1-infected and HSV-seronegative controls did not respond to these glycoproteins. The responses to gC-1 and gE-1, on the other hand, were not type specific, as blood mononuclear cells from both HSV-1- and HSV-2-infected individuals respondedin vitro. There was an association between the status of the infection (symptomatic versus asymptomatic) and the CD4+T-cell responsiveness. Symptomatic HSV-2-seropositive individuals responded with significantly lower Th1 cytokine production to sgG-2 and mgG-2 than did asymptomatic HSV-2-infected carriers, especially within the HSV-1-negative cohort. No differences in T-cell proliferation were observed between asymptomatic and symptomatic individuals. The results have implications for studies of HSV-2-specific CD4+T-cell reactivity in general and for analysis of immunological differences between asymptomatic and symptomatic individuals in particular.
Complete nucleotide sequence of Kashmir bee virus and comparison with acute bee paralysis virus
Authors: de Miranda J. R. , Drebot M. , Tyler S. , Shen M. , Cameron C. E. , Stoltz D. B. , Camazine S. M.
Published: July 2004

The complete nucleotide sequence of a novel virus is presented here together with serological evidence that it belongs to Kashmir bee virus (KBV). Analysis reveals that KBV is a cricket paralysis-like virus (family Dicistroviridae: genus Cripavirus), with a non-structural polyprotein open reading frame in the 5′ portion of the genome separated by an intergenic region from a structural polyprotein open reading frame in the 3′ part of the genome. The genome also has a polyadenylated tail at the 3′ terminus. KBV is one of several related viruses that also includes acute bee paralysis virus (ABPV). Although KBV and ABPV are about 70 % identical over the entire genome, there are considerable differences between them in significant areas of the genome, such as the 5′ non-translated region (42 % nucleotide identity), between the helicase and 3C-protease domains of the non-structural polyprotein (57 % amino acid identity) and in a 90 aa stretch of the structural polyprotein (33 % amino acid identity). Phylogenetic analyses show that KBV and ABPV isolates fall into clearly separated clades with moderate evolutionary distance between them. Whether these genomic and evolutionary differences are sufficient to classify KBV and ABPV as separate species remains to be determined.
Phylogenetic evidence of widespread distribution of genotype 3 JC virus in Africa and identification of a type 7 isolate in an African AIDS patient
Authors: Venter Marietjie , Smit Sheilagh B. , Leman Patricia , Swanepoel Robert
Published: July 2004

JC virus (JCV) is the cause of progressive multifocal leukoencephalophathy (PML) in immunocompromised patients. The paucity of reports from Africa has led to the hypothesis that PML is rare because of an absence of virus genotypes associated with the condition. Genotypes 3 and 6 have been identified in East and West Africa but the distribution of types across the rest of Africa is unknown. Full-length sequences of five JCV cerebrospinal fluid samples from PML patients in South Africa are reported here. Three isolates from African AIDS patients grouped with type 3A or 3B, and one with type 7, while one from a Caucasian leukaemia patient grouped with type 2D. Widespread distribution of type 3 on the continent may reflect migration patterns in antiquity, but this is the first report of type 7 in an African individual. Type 2D has only been isolated previously in South Asia, although transmission of this genotype to Europeans who later settled in South Africa is not unlikely.
Characterization of pathogenic and non-pathogenic African swine fever virus isolates from Ornithodoros erraticus inhabiting pig premises in Portugal
Authors: Boinas F. S. , Hutchings G. H. , Dixon L. K. , Wilkinson P. J.
Published: July 2004

Ten African swine fever virus isolates from the soft tick Ornithodoros erraticus collected on three farms in the province of Alentejo in Portugal were characterized by their ability to cause haemadsorption (HAD) of red blood cells to infected pig macrophages, using restriction enzyme site mapping of the virus genomes and by experimental infection of pigs. Six virus isolates induced haemadsorption and four were non-haemadsorbing (non-HAD) in pig macrophage cell cultures. The restriction enzyme site maps of two non-HAD viruses, when compared with a virulent HAD isolate, showed a deletion of 9·6 kbp in the fragment adjacent to the left terminal fragment and of 1·6 kbp in the right terminal fragment and an insertion of 0·2 kbp in the central region. The six HAD viruses isolated were pathogenic and produced typical acute African swine fever in pigs and the four non-HAD isolates were non-pathogenic. Pigs that were infected with non-HAD viruses were fully resistant or had a delay of up to 14 days in the onset of disease, after challenge with pathogenic Portuguese viruses. Non-HAD viruses could be transmitted by contact but with a lower efficiency (42–50 %) compared with HAD viruses (100 %). The clinical differences found between the virus isolates from the ticks could have implications for the long-term persistence of virus in the field because of the cross-protection produced by the non-pathogenic isolates. This may also explain the presence of seropositive pigs in herds in Alentejo where no clinical disease had been reported.
The p36 and p95 replicase proteins of Carnation Italian ringspot virus cooperate in stabilizing defective interfering RNA
Authors: Pantaleo Vitantonio , Rubino Luisa , Russo Marcello
Published: July 2004

The p36 and p95 proteins of Carnation Italian ringspot virus (CIRV), when expressed in Saccharomyces cerevisiae, supported the replication of defective interfering (DI) RNA. Double-label confocal immunofluorescence showed that both proteins localized to mitochondria, independently of each other. DI RNA progeny was localized by in situ hybridization both to mitochondria and to their proximity. Fractionation of cell extracts showed that replicase proteins associated with membranes with a consistent portion of DI RNA. DI RNA transcripts were stabilized more efficiently when co-expressed with both p36 and p95 than with either protein alone. By using the copper-inducible CUP1 promoter, p36 was shown to have an effect on DI RNA stability only above a threshold concentration, suggesting an ‘all-or-none’ behaviour. Conversely, the stabilizing activity of p95 was proportional to protein concentration in the range examined. Similarly, DI RNA replication level was proportional to p95 concentration and depended on a threshold concentration of p36.
Identification of the homotypic interaction domain of the core protein of dengue virus type 2
Authors: Wang Shao-Hung , Syu Wan-Jr , Hu Shiau-Ting
Published: July 2004

Dengue virus causes dengue haemorrhagic fever or dengue shock syndrome with a high mortality rate. The genome of dengue virus is a positive-sense, single-stranded RNA encoding three structural and seven non-structural proteins. The core protein is one of the three structural proteins and is the building block of the nucleocapsid of dengue virus. The core protein of dengue virus type 2 (DEN2) is composed of 100 aa with four α-helix domains. An internal hydrophobic domain located at aa 44–60 was identified. The DEN2 core protein was shown to form homodimers. Deletion of aa 1–36 or 73–100 decreased but did not completely abolish the core-to-core homotypic interaction, whereas deletion of a portion (aa 44–60) within aa 37–72 completely abolished the ability of the DEN2 core proteins to interact with each other. A recombinant DEN2 core protein corresponding to aa 37–72 was able to undergo homotypic interaction and bound to a native DEN2 core protein. The results of this study indicated that the homotypic interaction domain of the DEN2 core protein is located at aa 37–72 and that the internal hydrophobic domain located at aa 44–60 plays a pivotal role in core-to-core homotypic interaction.
Mutation of Phe50 to Ser50 in the 126/183-kDa proteins of Odontoglossum ringspot virus abolishes virus replication but can be complemented and restored by exact reversion
Authors: Wang Hai-He , Yu Hai-Hui , Wong Sek-Man
Published: July 2004

Sequence comparison of a non-biologically active full-length cDNA clone of Odontoglossum ringspot virus (ORSV) pOT1 with a biologically active ORSV cDNA clone pOT2 revealed a single nucleotide change of T→C at position 211. This resulted in the change of Phe50 in OT2 to Ser50 in OT1. It was not the nucleotide but the amino acid change of Phe50 that was responsible for the inability of OT1 to replicate. Time-course experiments showed that no minus-strand RNA synthesis was detected in mutants with a Phe50 substitution. Corresponding mutants in Tobacco mosaic virus (TMV) showed identical results, suggesting that Phe50 may play an important role in replication in all tobamoviruses. Complementation of a full-length mutant OT1 was demonstrated in a co-infected local-lesion host, a systemic host and protoplasts by replication-competent mutants tORSV.GFP or tORSV.GFPm, and further confirmed by co-inoculation using tOT1.GFP+tORSV (TTC), suggesting that ORSV contains no RNA sequence inhibitory to replication in trans. Surprisingly, a small number of exact revertants were detected in plants inoculated with tOT1+tORSV.GFPm or tOT1.GFP+tORSV (TTC). No recombination was detected after screening of silent markers in virus progeny extracted from total RNA or viral RNA from inoculated and upper non-inoculated leaves as well as from transfected protoplasts. Exact reversion from TCT (OT1) to TTT (OT2), rather than recombination, restored its replication function in co-inoculated leaves of Nicotiana benthamiana.
Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice
Authors: Kocisko David A. , Morrey John D. , Race Richard E. , Chen Jiancao , Caughey Byron
Published: July 2004

In vitro inhibitors of the accumulation of abnormal (protease-resistant) prion protein (PrP-res) can sometimes prolong the lives of scrapie-infected rodents. Here, transgenic mice were used to test the in vivo anti-scrapie activities of new PrP-res inhibitors, which, because they are approved drugs or edible natural products, might be considered for clinical trials in humans or livestock with transmissible spongiform encephalopathies (TSEs). These inhibitors were amodiaquine, thioridazine, thiothixene, trifluoperazine, tetrandrine, tannic acid and polyphenolic extracts of tea, grape seed and pine bark. Test compounds were administered for several weeks beginning 1–2 weeks prior to, or 2 weeks after, intracerebral or intraperitoneal 263K scrapie challenge. Tannic acid was also tested by direct preincubation with inoculum. None of the compounds significantly prolonged the scrapie incubation periods. These results highlight the need to assess TSE inhibitors active in cell culture against TSE infections in vivo prior to testing these compounds in humans and livestock.
Expansion of host-cell tropism of foot-and-mouth disease virus despite replication in a constant environment
Authors: Ruiz-Jarabo Carmen M. , Pariente Nonia , Baranowski Eric , Dávila Mercedes , Gómez-Mariano Gema , Domingo Esteban
Published: July 2004

Foot-and-mouth disease virus (FMDV) variants adapted to BHK-21 cells showed an expanded host-cell tropism that extended to primate and human cell lines. Virus replication in human HeLa and Jurkat cells has been documented by titration of virus infectivity, quantification of virus RNA, expression of a virus-specific non-structural antigen, and serial passage of virus in the cells. Parallel serial infections of human Jurkat cells with the same variant FMDVs indicates a strong stochastic component in the progression of infection. Chimeric viruses identified the capsid as a genomic region involved in tropism expansion. These results indicate that, contrary to theoretical predictions, replication of an RNA virus in a constant cellular environment may lead to expansion of cellular tropism, rather than to a more specialized infection of the cellular type to which the virus has been adapted.
CIF applications. XVI.CIF2CRY: for CIF input into theCRYSTALSprogram
Authors: Cooper Richard Ian , Foxman Bruce M. , Yang Lin
Published: July 2004

CIF2CRYis a program for converting structural data and reflection data contained in a CIF into instructions to be read by theCRYSTALSprogram [Betteridge, Carruthers, Cooper, Prout & Watkin (2003).J. Appl. Cryst.36, 1487]. The program can be used, for example, to read in CIFs that are archived by crystallographic journals, allowing users to study and re-refine published structures. Multiple data blocks in one CIF can be converted into a continuous file ofCRYSTALSinstructions, including an instruction for running user-specified calculations after each structure has been input. The program uses the CIFtbx Fortran library.
CRYSTALSenhancements: refinement of atoms continuously disordered along a line, on a ring or on the surface of a sphere
Authors: Schröder Ludger , Watkin David John , Cousson Alain , Cooper Richard Ian , Paulus Werner
Published: July 2004

The programCRYSTALS[Betteridge, Carruthers, Cooper, Prout & Watkin (2003).J. Appl. Cryst.36, 1487] has been extended to include an option for the refinement of a continuous electron density distribution lying along a line, a ring or on the surface of a sphere. These additional non-atomic electron distributions can be refined in any combination with traditional anisotropically distributed spherical atoms, including the refinement of `partial' atoms overlapping with the special electron distributions.
X-ray absorption by macromolecular crystals: the effects of wavelength and crystal composition on absorbed dose
Authors: Murray James W. , Garman Elspeth F. , Ravelli Raimond B. G.
Published: July 2004

Radiation damage restricts the useful lifetime for macromolecular crystals in the X-ray beam, even at cryotemperatures. With the development of structural genomics pipelines, it will be essential to incorporate projected crystal lifetime information into the automated data collection software routines. As a first step towards this goal, a computer program,RADDOSE, is presented which is designed for use by crystallographers in optimizing the amount of data that can be obtained from a particular cryo-cooled crystal at synchrotron beamlines. The program uses the composition of the crystal and buffer constituents, as well as the beam energy, flux and dimensions, to compute the absorption coefficients and hence the theoretical time taken to reach an absorbed dose of 2 × 10^7 Gy, the so-called `Henderson limit'. At this dose, the intensity of the diffraction pattern is predicted to be halved. A `diffraction–dose efficiency' quantity is introduced, for the convenient comparison of absorbed dose per diffracted photon for different crystals. Four example cases are considered, and the implications for anomalous data collection are discussed in the light of the results fromRADDOSE.
A `beam-selection' high-resolution X-ray diffractometer
Authors: Fewster Paul F.
Published: July 2004

A new diffractometer that can be described as a high-intensity low-background high-resolution diffractometer for analysing perfect, nearly perfect and highly imperfect materials on a routine basis is presented. The instrumentation is very simple and uncomplicated, yet the way in which it works is less obvious. The sample requires minimal sample alignment, the resolution can be adjusted to optimize the experiment and the wavelength dispersion can be controlled. This diffractometer can produce near perfect profiles from bent and imperfect samples. The illuminated area can easily be varied from greater than 3 mm down to 50 µm diameter, offering great opportunities in microdiffraction with high resolution. The instrument appears similar to a double-crystal diffractometer in reverse,i.e.the sample and collimating crystal of a conventional double-crystal diffractometer are reversed; however, the concept is quite different.
X-ray interferometric method for investigation of deformation fields caused in interferometer blocks by implanted ions
Authors: Drmeyan H. R.
Published: July 2004

Lateral deformations caused by argon ions with energy 180 keV implanted in silicon are investigated by the X-ray interferometric method. By means of interferometric topograms, relative deformations and integral stresses are determined depending on radiation dose. Maximum local stresses are assessed to be σx(max)= 8.4 × 107 N m−2and σy(max)= 6.7 × 107 N m−2.
SNAP-1D: a computer program for qualitative and quantitative powder diffraction pattern analysis using the full pattern profile
Authors: Barr Gordon , Gilmore Christopher J. , Paisley Jonathan
Published: July 2004

SNAP-1Dis a computer program for the qualitative and quantitative analysis of powder diffraction data using the full measured data set. As measures of similarity between patterns, non-parametric statistical tests based on Spearman's correlation coefficient and the Kolmogorov–Smirnov test are used. Traditional correlation coefficients based on the Pearson formalism are also employed. This combination, suitably weighted, gives a reliable measure of qualitative pattern similarity. The method can be extended to the quantitative analysis of mixtures by using the above methods in conjunction with singular value decomposition techniques. A full description of the theory with suitable examples has been published elsewhere [Gilmoreet al.(2004).J. Appl. Cryst.37, 231–242]; here the focus is on the computer software itself. The program is commercially available, and runs on PCs under the Windows 2000 and XP operating systems with modest hardware requirements. An easy to use graphical interface is supplied.
Modified Porod's law estimate of the transition-layer thickness between two phases: test of triangular smoothing function
Authors: Kim Man-Ho
Published: July 2004

An analytical method to estimate the thickness of the interface between two phases from small-angle scattering (SAS) data has been developed using Porod's law modified by a triangular smoothing function. The convolution with a `top-hat' function describing a sharp density profile results in a semi-sigmoidal density profile. This analytical method allows an interfacial layer thickness to be estimated from the negative slope of a Porod plot. The interfacial layer thickness (T) obtained from this model is related to similar models, namely a linear (E) and a sigmoidal density profile (σ) model, as follows:T= 21/2E= 2(61/2)σ, where σ is the standard deviation of the Gaussian function and does not represent the boundary thickness itself. The interfacial layer thickness obtained from any convolution method is a model-dependent parameter.
A laboratory furnace for obtaining crystals
Authors: Cabric B. , Janicijevic A.
Published: July 2004

A design for a modular device (`crystallization shelf') installed in a laboratory furnace is presented. The setup allows regulation and simultaneous crystallization tests of several substances at different temperature gradients, shapes of crystallization fronts and rate intervals, with the purpose of obtaining crystals.
Response to Lees' comments onNeutron diffraction studies of collagen in human cancellous bone
Authors: Aspden R. M. , Skakle J. M. S.
Published: July 2004

Some additional comments are made regarding neutron diffraction from bone.
How university students view online study: a PCP perspective
Authors: Wang Wei
Published: July 2004

With the ever‐increasing impact of information technology (IT) on society, universities are pushed to deliver the courses through the Internet by the format of Web course or online study. There are relatively few studies of how students construe this new mode of delivery and study. This study aimed to better understanding of how students construe the online learning with the framework of personal construct psychology. A total of 41 students participated in the study, generating more than 500 elements regarding the online versus traditional learning mode. The grid analysis results in terms of students’ construct are reported in this paper. The implications of understanding and facilitating the “match” between the institutional drive for online delivery and students’ constructs are discussed in the context of online learning.
Data‐mining algorithms in Oracle9i and Microsoft SQL Server
Authors: Hanna Margo
Published: July 2004

In today's competitive marketplace, it is crucial that companies manage their most valuable assets – customers and customers' information that is achieved via using data mining applications that sift through massive amounts of data and find hidden information – that help better understand customers and anticipate their behaviour. This paper aims at discussing data mining methods in Oracle, widely used for large corporate business, and Microsoft data mining applications, commonly used within SMEs. It discusses Oracle9i and Microsoft Data Mining algorithms which provides a powerful, scalable infrastructure for building applications that automate the extraction of business intelligence and its integration into other applications. It addresses the capabilities and limitations of data mining tools within Oracle9i and Microsoft, highlighting how the intelligent tools are beneficial for different scales and sectors of business and industry.
Oxygenation Prevents Sudden Death in Seizure‐prone Mice
Authors: Venit Elizabeth L. , Shepard Blythe D. , Seyfried Thomas N.
Published: July 2004

Summary:  Purpose: Sudden unexpected death in epilepsy (SUDEP) is a significant health problem for some with epilepsy, but no preventive therapy has been developed for high‐risk patients. Sudden death in mice, after sound‐induced (audiogenic) seizures, can model the seizure‐associated respiratory arrest that contributes to SUDEP in some humans and may be useful for evaluating potential SUDEP therapies. This study evaluated the effects of oxygenation on sudden fatal audiogenic seizures (AGSs) in three mouse strains, DBA/2J (D2), B6SAS, and primed C57BL/6J (B6) that differ in genetic background and seizure etiology (idiopathic or acquired).

Methods: The incidence of fatal AGSs was measured in (a) a normal air environment; (b), an oxygen‐rich environment; (c) a normal air environment 24 h after a nonfatal AGS; (d) an oxygen‐rich environment 24 h after a nonfatal AGS; and (e) a normal air environment 60 s after exposure to an oxygen‐rich environment.

Results: Sudden, fatal AGS occurred in 100%, 100%, and 58% of the D2, B6SAS, and primed‐B6 mice, respectively, in the air environment. Oxygenation completely prevented fatal AGSs in each strain, but had no effect on seizure incidence or severity. Furthermore, the protective effect of oxygenation against fatal seizures occurred only when the mice were in an oxygen‐rich environment.

Conclusions: These findings indicate that oxygenation prevents sudden death in seizure‐prone mice and suggest that oxygenation may protect some seizure‐prone humans at risk for SUDEP.
Preclinical Profile of Combinations of Some Second‐generation Antiepileptic Drugs: An Isobolographic Analysis
Authors: Luszczki Jarogniew J. , Czuczwar Stanislaw J.
Published: July 2004

Summary:  Purpose: The need for an efficacious treatment of patients with intractable seizures is urgent and pressing, because ∼30% of epilepsy patients worldwide are still inadequately medicated with current frontline antiepileptic drugs (AEDs). This study sought to determine the interactions among some newer AEDs [topiramate (TPM), felbamate (FBM), oxcarbazepine (OXC), and lamotrigine (LTG)] in the maximal electroshock‐induced seizures (MES) and chimney test (motor performance) in mice, by using the isobolographic analysis.

Methods: Evaluation of the anticonvulsant and acute adverse (neurotoxic) effects in mice produced by the AEDs in combinations at the fixed ratios of 1:3, 1:1, and 3:1 allowed the assessment of their preclinical profile and the determination of benefit indices (BIs) for all individual combinations.

Results: Combinations of TPM+FBM at the fixed ratios of 1:3, 1:1, and 3:1 offered supraadditive (synergistic) interactions against electroconvulsions and subadditivity (antagonism) in terms of acute neurotoxic effects in the chimney test (BIs ranged between 1.90 and 2.59, the best combinations from a preclinical point of view). The examined combinations of TPM+OXC also were advantageous due to synergistic interactions in the MES, and additivity in terms of acute neurotoxic effects produced by the AEDs (BIs ranged between 1.35 and 1.71). In contrast, OXC+FBM exerted subadditive (antagonistic) interactions in the MES test and additive interactions in terms of acute motor impairment of animals (BIs ranged between 0.53 and 0.71). The worst combination was observed for OXC+LTG, at the fixed ratio of 1:1, displaying subadditivity (antagonism) against electroconvulsions and supraadditivity (synergy) with respect to neurotoxicity (BIs, 0.43). The remaining combinations of OXC+LTG tested (i.e., 1:3 and 3:1) exerted additivity in the MES test and supraadditivity in the chimney test (BIs 0.54 and 0.49, respectively). None of the studied AEDs affected the brain concentrations of other AEDs, so the existence of any pharmacokinetic interactions to be responsible for the observed effects is improbable.

Conclusions: Based on the current preclinical data, the pharmacological profile of combinations of TPM+FBM and TPM+OXC evaluated with isobolography was beneficial and might be worth recommendation to further clinical practice. In contrast, utmost caution is required during the use of OXC+FBM or OXC+LTG in clinical practice, because of the high risk of neurotoxic adverse effect appearance.
Chromosomal Mapping of Genetic Loci Controlling Absence Epilepsy Phenotypes in the WAG/Rij Rat
Authors: Gauguier Dominique , Luijtelaar Gilles van , Bihoreau Marie Thérèse , Wilder Steven P. , Godfrey Richard F. , Vossen Jo , Coenen Anton , Cox Roger D.
Published: July 2004

Summary:  Purpose: The WAG/Rij rat is among the most appropriate models for the study of spontaneous childhood absence epilepsy, without complex neurologic disorders that are associated with some mouse models for absence epilepsy. Previous studies have allowed the identification of distinct types of spike–wave discharges (SWDs) characterizing seizures in this strain. The purpose of this study was to investigate the genetic basis of electroencephalographic (EEG) properties of SWDs.

Methods: An intercross was derived from WAG/Rij and ACI inbred strains that are known to differ substantially in the number of SWDs. Phenotypic analyses based on 23‐h EEG recording in all progenies allowed the quantification of type I and type II SWD phenotypes. A genome‐wide scan was performed with 145 microsatellite markers, which were used to test for evidence of genetic linkage to SWD quantitative phenotypes.

Results: We were able to map quantitative trait loci independently, controlling type I and type II SWD variables to rat chromosomes 5 and 9. Strongest linkages were obtained for D5Mgh15 and total duration of type II SWD (lod, 3.64) and for D9Rat103 and the average duration of type I SWD (lod, 3.91). These loci were denoted T2swd/wag and T1swd/wag, respectively.

Conclusions: The independent genetic control of type I and type II SWDs underlines the complexity of the molecular mechanisms participating in SWDs. The identification of these genetic loci represents an important step in our fundamental knowledge of the architecture of SWDs and may provide new insights for resolving the genetic heterogeneity of absence epilepsy.
Lateralization of Temporal Lobe Epilepsy and Learning Disabilities, as Defined by Disability‐related Civil Rights Law
Authors: Butterbaugh Grant , Olejniczak Piotr , Roques Betsy , Costa Richard , Rose Marcy , Fisch Bruce , Carey Michael , Thomson Jessica , Skinner John
Published: July 2004

Summary:  Purpose: Epilepsy research has identified higher rates of learning disorders in patients with temporal lobe epilepsy (TLE). However, most studies have not adequately assessed complex functional adult learning skills, such as reading comprehension and written language. We designed this study to evaluate our predictions that higher rates of reading comprehension, written language, and calculation disabilities would be associated with left TLE versus right TLE.

Methods: Reading comprehension, written language, and calculation skills were assessed by using selected subtests from the Woodcock‐Johnson Psycho‐Educational Tests of Achievement–Revised in a consecutive series of 31 presurgical patients with TLE. Learning disabilities were defined by one essential criterion consistent with the Americans with Disabilities Act of 1990. Patients had left hemisphere language dominance based on Wada results, left or right TLE based on inpatient EEG monitoring, and negative magnetic resonance imaging (MRI), other than MRI correlates of mesial temporal sclerosis.

Results: Higher rates of reading comprehension, written language, and calculation disabilities were associated with left TLE, as compared with right TLE. Nearly 75% of patients with left TLE, whereas fewer than 10% of those with right TLE, had at least one learning disability.

Conclusions: Seizure onset in the language‐dominant hemisphere, as compared with the nondominant hemisphere, was associated with higher rates of specific learning disabilities and a history of poor literacy or career development or both. These results support the potential clinical benefits of using lateralization of seizure onset as a predictor of the risk of learning disabilities that, once evaluated, could be accommodated to increase the participation of patients with epilepsy in work and educational settings.
Perceived Impact of Childhood‐onset Epilepsy on Quality of Life as an Adult
Authors: Sillanpää Matti , Haataja Leena , Shinnar Shlomo
Published: July 2004

Summary:  Purpose: Childhood‐onset epilepsy is a common disorder. The long‐term impact of having childhood epilepsy on quality of life (QOL) as an adult, whether or not seizures are in remission, has not been systematically studied.

Methods: A population‐based cohort of 245 children younger than 16 years with active epilepsy between 1961 and 1964 residing in the catchment area of Turku University Hospital was followed up prospectively until 1997. Of the 99 surviving cases with uncomplicated epilepsy and 99 matched population controls, 91 subjects and controls completed questionnaires on QOL and psychosocial outcomes.

Results: Of the 91 subjects, 61 (67%) were in remission off medication, 13 (14%) in remission on medications, and 17 (19%) were not in remission. Subjects on medication, whether in remission or not, had worse scores on both general measures of QOL and epilepsy‐specific measures than did either controls or subjects in remission off medications. They also had significantly higher rates of unemployment (p < 0.001) and lower socioeconomic status. These differences could not be accounted for by differences in education or seizure frequency. Subjects in remission off medication had rates of employment and socioeconomic status similar to those of controls. All subjects, regardless of remission status, had lower rates of marriage and of having children than did controls (p < 0.001).

Conclusions: Childhood‐onset epilepsy has a persistent long‐term adverse impact on health‐related quality of life. The major impact is on those still on medications as adults, whether or not they are in remission. The impact on those in remission off medications is relatively modest.