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Character encodings such as Unicode [15] make a strong difference between characters abstract linguistic entities ; and glyphs the rendition of characters ; and so ignore the "types" effectively used when composing books. Typical examples are ligatures such as " " ; , abbreviations or vanished characters such as the old French "c e n" ; This absence makes it difficult to standardize OCR outputs and quite impossible to get genuine plain text from electronic editions of old books especially Renaissance or even 18th century ones ; . Strangely, far more complicated texts, such as medieval manuscripts, are now electronically editable thanks to encoding projects. We first show how encodings have been applied to medieval manuscripts, then describe the equivalent, and not favorable, situation for old books. We follow with a presentation of the Cassetin project: its aims are to inventory all of the European types, to name them and to propose this list as a Unicode candidate.
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Iodothyronines and is therefore not suitable for measuring small amounts of several different iodothyronines from the same brain regions. To simplify the methodological procedure and to permit the measurement of several different iodothyronines from the same brain areas, we developed a method for purifying and separating the different iodothyronines by HPLC. In the course of the study, we detected small but clearly measurable amounts of 3, 5-T2 and 3, -T2 in some brain areas. We thus further investigated whether the concentrations of these hormones were particularly enhanced in mitochondrial fractions of the respective brain regions, as suggested by previous reports e.g. Ref. 21 ; . As nothing is known about the metabolic pathways leading to the production of 3, 5-T2, we investigated whether T3 is a substrate for outer-ring deiodination in regions of the rat brain under differing experimental conditions. Moreover, we previously reported diurnal variations in tissue concentrations of T3 in regions of the rat brain and liver 22 ; . We therefore investigated whether the concentrations of 3, 5-T2, which is claimed to have physiological functions see above ; , also exhibit circadian variations in different brain areas and the liver.
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5-Fluorouracil FU ; is widely used in the treatment of a range of cancers, particularly colorectal cancer but also cancers of the breast, head-and-neck, and aerodigestive tract 1 ; . After four decades in clinical use, FU or an oral prodrug 2 ; is presently used in the treatment of some two million individuals a year 3 ; . The fluorine-substituted uracil analogue is an antimetabolite that was designed to inhibit DNA synthesis in an early example of the rational development of a cytotoxic drug 4 ; . Inhibition of thymidylate synthase TS ; by FdUMP prevents the conversion of dUMP to the sole de novo source of dTMP Fig. 1 ; , depleting the cell of dTTP for use in DNA replication and repair. This leads to deoxynucleoside triphosphate precursor pool imbalances and increased levels of dUTP. In a frequently proposed model, FU-mediated cell death is attributed to the use of dUTP in place of dTTP during DNA synthesis, and subsequent DNA fragmentation due to extensive uracil excision in newly synthesized DNA or repeated futile repair attempts in the presence of a high dUTP dTTP ratio reviewed in ref. 1 ; . TS status has been correlated with and methocarbamol.
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A.flavus: uni- or biserrate, conidiophore length 400-850? m, rough-walled, hyphae colourless, vesicle elongate, becoming subspherical to spherical, conidial head radiate, becoming columnar with age, conidia spherical, echinulate, 3-6 ? m; colonies yellow to yellowish-green; produces aflatoxin B potent hepatocarcinogen ; , cyclopiazonic acid nuts, oilseeds, spices, stored commodities; worldwide causes aspergillosis, endocarditis, otitis externa, 1% of peritonitis in continuous ambulatory peritoneal dialysis, pneumonia especially in leukemia ; , chroni c sinusitis, thyroiditis, systemic infections in abnormal host; treatment: amphotericin B ? flucytosine or rifampicin, itraconazole A.fumigatus: uniseriate, conidiophores length up to 320 ? m, smooth-walled, greenish coloured hyphae, vesicle domeshaped, conidial head compact and columnar, conidia spherical to subspherical, echinulate, 2.5-3 ? m diameter; colonies whitish green to grey-green; produces exotoxin, proteinases, oxidoreductases; causes 75% of aspergillosis, endocarditis, otitis externa including rare malignant ; , 1% of peritonitis in continuous ambulatory peritoneal dialysis, pneumonia especially in leukemia ; , thyroiditis, systemic infections in abnormal host; susceptible to interferon -? and tissue necrosis factor-stimulated macrophages; treatment: amphotericin B ? flucytosine or rifampicin, itraconazole A.glaucus Group: contains several species; causes aspergillosis, systemic infections in abnormal host A.nidulans: causes mycetoma A.niger: biserrate; conidiophore length 1.5-3 mm, smooth-walled, colourless or brownish, vesicle spherical, conidial head radiate, conidia spherical, brown black, roughened, 4-5 ? m; colonies white yellow, developing a black mat of conidia; causes otitis externa; some isolates produce ochratoxin sun -dried fruit, peanuts ; A.ochraceuous: produces ochratoxin in coffee beans A.parasiticus: produces aflatoxins B and G in peanuts, corn and cottonseed less widely distributed than A.fumigatus ; A.terreus: biserrate, conidiophore length 100-250 ? m, smooth-walled, colourless, vesicl e hemispherical or dome shaped, conidial head long columnar, conidia spherical to elliptical, smooth-walled, 2-2.5 ? m; causes aspergillosis A tus: primary cutaneous aspergillosis following reduced intensity stem cell transplantation Neosartorya: resembles Aspergillus fumigatus in conidial state but colonies may remain white N.fischeri: 2 cases of systemic infection in transplant patients, single case of mixed pulmonary infection in patient with myeloma N.hiratsukae: reticulated ascospores growing restrictedly on Czapek agar; isolated from air, pasteurised aloe juice and cerebral infection; resistant to amphotericin B, flucytosine; susceptible to itraconazole N.pseudofischeri: ascospore walls ornamented with raised flaps of tissue resembling triangular projections or long ridge lines; causes localised and invasive infections Penicillium: causes bagassosis and farmer' lung, pneumonia in cancer patients, systemic infections in abnormal host; s diagnosis: Grocott methenamine silver, PAS and Wright' stain and culture; treatment: amphotericin B, itraconazole, s flucytosine, ketoconazole P.citreum: causes urinary infections P.citrinum: most widespread species in tropics; most common species in flour; produces citrinin mycoto xin ; P mune: produces cyclopiazonic acid mycotoxin ; in cheese P.crustosum: produces penitrem A mycotoxin ; in wide range of processed foods P.expansum: produces patulin and citrinin mycotoxins ; in pome fruits, grapes, tomatoes, refrigerated foods P.marneffei: causes infections in T helper lymphocyte deficiency, penicilliosis in AIDS in S E Asia P.verrucosum: produces ochratoxin A in processed meats and stored grains Micropolyspora faeni Thermosporapolyspora vulgaris ; : causes bagassosis and farmer' lung s Paecilomyces lilacinus: causes chronic sinusitis in immunocompromised Trichoderma: resistant to most antifungal agents T.longibrachiatum: causes peritonitis in continuous ambulatory peritoneal dialysis, invasive infections in immunocompromised patients T.viride: causes peritonitis in continuous ambulatory peritoneal dialysis Fonsecaea: causes chromoblastomycosis; diagnosis: micro and culture, co mplement fixation test; treatment: surgery, flucytosine + thiabendazole or amphotericin B, ketoconazole ? flucytosine, itraconazole F pacta: causes chromoblastomycosis Far East ; F rosoi: causes brain and epidural abscess, chromoblastomycosis Far East ; Alternaria: causes chronic eye infections, chronic sinusitis in immunocompromised, keratitis and iritis, local and generalised sepsis, mucosal and visceral infections; treatment: itraconazole, natamycin A.alternata: causes phaeohyphomycosis; produces tenuazonic acid, alternanol and alternanolmonomethyl ether mycotoxins ; in tomatoes, capsicums, eggplants, sorghum, wheat and related grains Cladophiolophora bantiana: causes brain and epidural abscess, phaeohyphomycosis, systemic infections in abnormal host; susceptible to clotrimazole MIC 0.4 mg L ; C rrionii: causes chromoblastomycosis Australia, S Africa, Venezuela ; C.cladosporiodes: causes systemic infections in abnormal host and methotrexate.
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Human Molecular Genetics, 1998, Vol. 7, No. 3 between quantifiable repeat length and age of onset and disease course, a genotypic assay based on SCA7 allele size cannot provide sufficient predictive value for clinical prognosis. Although the range of repeat expansions seen in affected individuals is similar to that seen in many of the aforementioned diseases, it is notable that the normal alleles show low polymorphism and are constrained to a narrow range. Furthermore, with 97% of the unexpanded alleles harboring between 10 and 13 CAG repeats, the normal range is centered around a shorter CAG repeat length relative to the normal ranges seen in all other polyglutamine tract diseases except for SCA6 25 ; . We data not shown ; and others 18 ; have noted that in normal SCA7 alleles, the CAG tract lacks interrupting trinucleotides. As such intervening sequence have the hypothesized role of stabilizing repeat length 26 ; , it is paradoxical that unexpanded alleles show such low heterogeneity. Despite a lack of interrupting trinucleotide within the CAG tract, low repeat length alleles could remain quite stable, explaining the limited polymorphism seen in unexpanded alleles in our sample. However, expansions beyond the low, narrow range seen in normal chromosomes would be expected to be highly unstable within populations. Indeed, this marked instability is seen in expanded alleles, and appears to be more dramatic than in other known polyglutamine tract diseases. As instability and subsequent repeat expansion contribute to age of onset and severity of disease, selective pressures might be expected to exist to keep repeat length below a threshold where the allele becomes prone to instability. An initiating gene conversion event causing duplication of the repeat sequence 27 ; , might precipitate the appearance of the expanded allele; it is interesting to note in this regard that the smallest expanded allele is exactly twice as large as the largest unexpanded allele both alleles occur in the same individual, who is currently asymptomatic at the age of 48 ; . Due to the highly unstable nature of the repeat, the subsequent morbidity and the autosomal dominant nature of the disease, this mutation would not be expected to be transmitted intact through many generations before becoming incompatible with further transmission; this is consistent with the fact that SCA7 has a lower prevalence than most of the type I diseases 1, 2, 14 ; . Unequal sister chromatid exchange, polymerase slippage or changes in cis- 28 ; or trans-acting elements [reviewed in 29 ; and 30 ; ] may also be responsible for initial and or subsequent events conferring instability on the normal CAG repeat; more intensive sequence analysis on this large patient sample may give insight into these possibilities. The paternal bias in transmission of expanded alleles is particularly noticeable, and extends the pattern seen in other type I dynamic mutations. What is appreciated in this large sample of SCA7 kindreds is the further observation that actual disease transmission shows a strong maternal bias. Although fathers, on average, transmit significantly larger alleles to their offspring, mothers appear to be more consistent in passing on expanded alleles and thus maintaining disease within kindreds. Although females comprise 57% of total SCA7 family members and make up 64% of individuals harboring expanded alleles, they are responsible for a statistically significant 75% of all expanded allele transmissions and 80% of disease transmissions determined by pedigree history. This pattern can also be seen in previously described SCA7 families 16, 3136 ; . In a review of 17 other described kindreds with an autosomal dominant degenerative cerebellar retinal phenotype where a geneology was shown, or data regarding sex of affecteds and transmitting parents and methylcellulose.
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Department of Internal Medicine L.J.H., J.v.d.H., P.M.v.K., W.W.d.H., M.W., D.S.-M., R.F., A.-J.v.d.L., S.W.J.L. ; , Section of Endocrinology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands; Research Transplantation C.B., G.W. ; , Novartis Pharma A.G., Basel, Switzerland CH-4002; Service d'Endocrinologie A.B. ; , Center Hospitalier Universitaire de Liege, Domaine Universitaire du Sart-Tilman, Liege, Belgium 4000.
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Ing a 4# -year period, 511 patients underwent attempted insertion of gastrostomy or gastrojejunostomy tubes. Patients' ages ranged from premature to 18.6 years mean age, 3.8 years ; , and weight range was 0.8-86.0 kg mean weight, 12 kg ; . The charts of 453 patients were reviewed and methysergide.
On July 15, 2002, the Company acquired all of the outstanding common stock of Immunex in a transaction accounted for as a business combination. Immunex was a leading biotechnology company dedicated to developing immune system science to protect human health. The Immunex acquisition is expected to further advance Amgen's role as a global biotechnology leader with the benefits of accelerated growth and increased size, product base, product pipeline, and employees. The acquisition is also intended to enhance Amgen's strategic position within the biotechnology industry by strengthening and diversifying its 1 ; product base and product pipeline in key therapeutic areas, and 2 ; discovery research capabilities in proteins and antibodies. The results of Immunex's operations have been included in the consolidated financial statements commencing July 16, 2002. Each share of Immunex common stock outstanding at July 15, 2002 was converted into 0.44 of a share of Amgen common stock and .50 in cash. As a result, Amgen issued approximately 244.6 million shares of common stock and paid approximately .5 billion in cash to former Immunex shareholders. Amgen also paid Wyeth million at the closing of the merger for the termination of certain Immunex product rights in favor of Wyeth, as specified in the agreement regarding governance and commercial matters. In addition, each employee stock option to purchase Immunex common stock outstanding at July 15, 2002 was assumed by Amgen and converted into an option to purchase Amgen common stock based on the terms specified in the merger agreement. As a result, approximately 22.4 million options to purchase Amgen common stock were assumed, on a converted basis. The acquisition was structured to qualify as a tax-free reorganization within the meaning of Section 368 a ; of the Internal Revenue Code. The purchase price of the acquisition was in millions and methenamine.
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