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Significance Diabetes mellitus type 1 is an autoimmune disease that results in irreversible destruction of insulin-producing beta cells. Substantial advances have been made in beta cell replacement therapies during the last decades. However, lack of eligible donor organs and the need for chronic immunosuppression to prevent rejection critically limit widespread application of these strategies. In this manuscript, we present an experimental study using a bioartificial pancreas device for the transplantation of xenogeneic islet without affecting the immune system in nonhuman primates. We could demonstrate stable graft function and adequate glucose-regulated insulin secretion without the need for immunosuppressive medication. This strategy opens up new avenues for more widespread and safe application of various cell-based therapies.

A theory of an optical breather of self-induced transparency for small area surface plasmon-polariton waves is constructed. The wave equation for an optical nonlinear electric field consisting of surface transverse magnetic modes, traveling along a two-dimensional layer of atomic systems (or semiconductor quantum dots), with a graphene monolayer (or graphene-like two-dimensional material), are shown to reduce to the nonlinear Schr\"odinger equation with damping. It is also shown that damped small intensity surface plasmon-polariton breathers can propagate in such a system and its characteristic parameters depends on the connected media, graphene conductivity, transition layer and transverse structures of the surface plasmon polariton. Explicit analytical expressions for the parameters of an optical surface breather are given. The breather and the soliton in graphene are compared with each other and the differences between their properties are contrasted.

E. multilocularis (Em) is the etiologic agent of alveolar echinococcosis (AE), a severe and potentially fatal disease, primarily affecting the liver of and occurring in aberrant intermediate hosts, e.g., humans and non-human primates. Due to increasing numbers of spontaneous cases of AE in the Old World monkey colonies of the German Primate Center, the question arose as to whether vaccination of non-human primates may represent a useful prophylactic approach. In this pilot study, the recombinant antigen Em14-3-3, which has provided a 97 % protection against E. multilocularis challenge infection in rodent models, was used for the first time to immunize rhesus macaques. In order to increase immunogenicity, the antigen was formulated with different adjuvants including Quil A®, aluminum hydroxide (alum), and muramyl dipeptide (MDP). Also, different vaccination regimens were tested. All vaccinated animals developed antigen-specific antibodies. While Quil A® induced a local adverse reaction, alum proved to be the most potent adjuvant in terms of induced antibody levels, longevity as well as tolerability. In conclusion, our pilot study demonstrated that recombinant Em14-3-3 is safe and immunogenic in rhesus monkeys. As a next step, efficacy of the vaccination remains to be explored.

The influence of the transverse and longitudinal magnetic relaxations on the propagation of an acoustic resonance soliton is considered. The dynamics of the changes of the width and frequency shift of acoustic pulse in both the Markovian and the non-Markovian cases are compared. It is shown that memory effects do cause a qualitatively change in the nature of the effects of transverse magnetic relaxations on an acoustic soliton, in comparison to that of the Markovian case. The pulse width in both the Markovian and the non-Markovian cases for experimentally realized parameters are presented.

The authors describe genital alterations and detailed histologic findings in baboons naturally infected with Treponema pallidum. The disease causes moderate to severe genital ulcerations in a population of olive baboons ( Papio hamadryas anubis) at Lake Manyara National Park in Tanzania. In a field survey in 2007, 63 individuals of all age classes, both sexes, and different grades of infection were chemically immobilized and sampled. Histology and molecular biological tests were used to detect and identify the organism responsible: a strain similar to T pallidum ssp pertenue, the cause of yaws in humans. Although treponemal infections are not a new phenomenon in nonhuman primates, the infection described here appears to be strictly associated with the anogenital region and results in tissue alterations matching those found in human syphilis infections (caused by T pallidum ssp pallidum), despite the causative pathogen’s greater genetic similarity to human yaws-causing strains.

Summary Shock was induced in 37 SPF-Han Wistar rats by intravenous injections of E. coli neurotoxin; 16 control animals received physiological saline solution. The main glomerular lesions were present in the mesangium and the visceral epithelial cells and were less pronounced than the interstitial alterations after neurotoxin shock. The mesangial lesions appear to be similar to those in chronic interstitial nephritis in dogs and the visceral epithelial cells show comparable alterations to those, for example, in acute renal failure in man and acute hog cholera in swine. Zusammenfassung Ultrastrukturelle glomerulare Veranderungen bei einem experimentell induzierten Neurotoxinschock an Ratten Ein Schock wurde bei 37 SPF-Han Wistar Ratten durch intravenose Injektionen von E. coli Neurotoxin induziert. 16 Kontrolltiere erhielten physiologische Kochsalzlosung. Die wichtigsten glomerularen Schadigungen zeigten sich im Mesangium und in den viszeralen Epithelzellen und waren weniger ausgepragt als die interstitiellen Veranderungen nach Neurotoxinschock. Die mesangialen Schadigungen schienen ahnlich denjenigen einer chronischen interstitiellen Nephritis bei Hunden, und die viszeralen Epithelzellen zeigten Veranderungen, wie beim akuten Nierenversagen des Menschen und akuter Schweinepest. Resume Lesions ultrastructurelles glomerulaires lors d'un choc neurotoxique induit experimentalement chez des rats Un choc a ete induit par des injections intraveineuses de neurotoxine de E. coli chez 37 rats SPF-Han Wistar. 16 animaux de controle ont recu une solution physiologique. Les principales lesions glomerulaires se sont manifestees dans le Mesangium et dans les cellules epitheliales viscerales et furent moins etendues que les lesions interstitielles apres un choc du a une nephrite interstitielle chronique chez des chiens et les cellules epitheliales viscerales presenterent des lesions comparables par exemple a celles rencontrees lors d'un blocage renal aigu chez l'etre humain et d'une peste porcine aigue. Resumen Alteraciones glomerulares ultraestructurales en choques neurotoxinicos inducidos experimentalmente en ratas Se indujo un choque en 37 ratas Wistar SPF-Han mediante inyecciones endovenosas de neurotoxina de E. coli. 16 animales testigos recibieron solucion salina fisiologica. Las lesiones glomerulares mas importantes se mostraron en el mesangio y en las celulas epiteliales viscerales y eran menos marcadas que las modificaciones intersticiales tras el choque neurotoxinico. Las lesions mesangiales se asemejaban a las de una nefritis intersticial cronica en perros, y las celulas epiteliales viscerales ostentaban modificaciones comparables, por ej. con la insuficiencia renal aguda en el ser humano y con la peste porcina aguda.

Summary The changes in the rat kidney described here following prolonged experimental shock over a period of 1 to 79 days demonstrate in an animal model the pathogenetic processes occurring in the shock kidney. Shock was induced in 130 Wistar rats by a single or several intravenous injections of Escherichia coli neurotoxin (up to 8 injections). The kidneys were examined with the light and electron microscopes. Changes in the kidneys depended on the duration of the shock as well as on the number of injections and were characterized by three morphological phases. Phase 1 (1 to 5 days post injectionem [p. i.] with one or two neurotoxin injections) is marked by extensive interstitial oedama. In Phase 2 (beginning on the 5th day p. i.) the first mononuclear cellular infiltrates are seen in the interstitial connective tissue within the oedematous regions and intensify with increasing numbers of toxin injections and continuing shock. The cellular infiltrates are recruited from migratory mononuclear blood cells as well as through local cell proliferation. In this phase an atrophy of renal tubules can be observed in areas with marked expansion of the interstice. In the beginning of Phase 3 (20 days p. i. and later) there is an increase of collagen fibrils and fibroblasts. After about 30 days p. i. extensive foci of fibrosis are visible in the interstitial tissue of the kidney. The causes of this intensive mesenchymal reaction in shock, also involving other organs such as liver, lung, gastrointestinal tract and adrenal glands, are discussed. Zusammenfassung Pathogenese der Nierenveranderung im experimentellen protrahierten Schock Die vorliegende Arbeit beschreibt die Veranderungen an der Niere und die dabei ablaufenden pathogenetischen Prozesse nach experimentellem protrahierten Schock der Ratte uber einen Zeitraum von 1 bis 79 Tagen. Bei 130 Wistar-Ratten erfolgte die Schockauslosung durch ein- und mehrmalige (max. 8) intravenose Injektionen des Neurotoxin von Escherichia coli-Bakterien des Serotypes O 139:K82 (B). Die licht- und elektronenmikroskopisch festgestellten Nierenveranderungen waren dabei sowohl von der Schockdauer als auch von der Anzahl der Injektionen abhangig und liesen sich in 3 Phasen einteilen. Die erste Phase (1 bis 5 Tage nach 1 oder 2 Neurotoxin-Injektionen) ist gekennzeichnet durch ausgedehnte interstitielle Odeme. In der zweiten Phase (ab dem 5. Tage p. i.) kommt es in den odematisierten Bezirken des Interstitiums zu ersten mononuklearen Zellinfiltrationen, die sich mit zunehmender Schockdauer und mehrmaliger Toxininjektion verstarken. Die interstitiellen Zellansammlungen sind neben einer lokalen Zellproliferation auf eine Emigration mononuklearer Zellen aus dem Blutstrom zuruckzufuhren. In dieser Phase sind in den Bereichen mit deutlich verbreitertem Interstitium Anzeichen einer Atrophie der Nierentubuli zu beobachten. In der dritten Phase (20 Tage p. i. und spater) kann zunachst eine Vermehrung von Kollagenfibrillen und Fibroblasten festgestellt werden. Nach etwa 30 Tagen treten herdformig ausgedehnte Fibrosen im Interstitium der Nieren auf. Die Grunde dieser mesenchymalen Reaktion nach Schock, die auch andere Organe wie Leber, Lunge, Magen-Darmtrakt und Nebenniere erfast, werden diskutiert. Resume Pathogenese des modifications renales dans un choc experimental prolonge Ce travail decrit les modifications renales et les processus pathogenetiques en decoulant apres un choc experimental prolonge chez des rats pendant une periode de 1 a 79 jours. Chez 130 rats Wistar, le declenchement du choc a ete provoque par une ou plusieurs (maximum 8) injections intraveineuses de neurotoxine d'E. coli du serotype O 139:K82 (B). Les lesions renales etablies au microscope optique et electronique dependaient aussi bien de la duree du choc que du nombre des injections et ont ete divisees en 3 phases. La premiere phase (1 a 5 jours apres 1 ou 2 injections de neurotoxine) se reconnait a un oedeme interstitiel etendu. Dans la deuxieme phase (des le 5e jour p. i.), on constate les premieres infiltrations de cellules mononucleees dans l'interstitium cellulaire locale, a une emigration de cellules mononucleees a partir de la circulation sanguine. Dans les regions d'un interstitium nettement elargi, on observe dans cette phase une atrophie des tubuli renaux. Dans la troisieme phase (20 jours p.i. et plus tard), on a etabli tout d'abord une multiplication des fibrilles collagenes et des fibroblastes. Des fibroses etendues en foyers sont apparues dans l'interstitium des reins apres environ 30 jours. On discute les bases de cette reaction mesenchymateuse apres un choc qui atteint egalement d'autres organes tels le foie, les poumons, le tube gastro-intestinal et les surrenales. Resumen La patogenia de las modificaciones renales en el choque experimental prolongado Describe el trabajo presente las modificaciones habidas en el rinon y los procesos patogenicos que discurren con ello tras el choque experimental prolongado en la rata a lo largo de un espacio de tiempo de 1 hasta 79 dias. En 130 ratas Wistar se desencadeno el choque mediante una inyeccion unica o reiterada (max. 8) intravenosa de neurotoxina bacteriana Escherichia coli de los serotipos O 139: K 82 (B). Las modificaciones renales comprobadas con el microscopio optico y en el electronico dependian de la duracion del choque y del numero de inyecciones, y se pudieron dividir en tres fases. La fase primera se halla caracterizada (1 hasta 5 dias tras 1 o 2 inyecciones de neurotoxina) por edemas intersticiales abundantes. En la fase segunda (a partir del dia 5° p. i.) se producen en las circunscripciones edematizadas del intersticio las primeras infiltraciones celulares mononucleares, las cuales se refuerzan al aumentar la duracion del choque y con las inyecciones reiteradas de toxina. Las acumulaciones celulares intersticiales se atribuyen, al lado de una proliferacion celular local, a la emigracion de celulas mononucleares del torrente sanguineo. En esta fase se observan en los contornos con intersticio ensanchado de manera evidente indicios de una atrofia de los tubulos renales. En la fase tercera (20 dias p. i. y mas tarde) se puede evidenciar al momento una multiplicacion de las fibrillas colagenas y fibroblastos. Al cabo de unos 30 dias aparecen fibrosis focales difusas en el intersticio de los rinones. Se discuten las razones de esta reaccion mesenquimatosa tras el choque, la cual afecta tambien otros organos, tales como el higado, pulmon, tracto gastro-intestinal y la glandulas anterrenales.

Zusammenfassung Aus funf Einsendungen von Wellensittich-Nestlingen (Melopsittacus undulatus), die von einer mit Hepatitis und Befiederungsstorungen einhergehenden Krankheit betroffen waren, konnte in Huhnerembryofibroblasten-Kulturen ein zytopathisches Agens isoliert werden. Dies erwies sich als Chloroform-stabil und empfindlich gegenuber Joddeoxi-Uridin. Elektronenmikroskopisch konnten in Ultradunnschnitten infizierter Zellen intranuklear gelagerte Viruspartikel nachgewiesen werden. Nach Negativkontrastierung zeigten sich spharische Partikel mit einem Durchmesser von 35 bis 45 nm und deutlichen Kapsomeren. Summary Studies on viral aetiology of a disease of budgerigar fledglings (Melopsittacus undulatus) with hepatitis and feather disturbance From five samples of material from budgerigar nestlings with a disease characterized by hepatitis and feather disturbance a cytopathogenic agent was isolated in chick embryo fibroblast culture. The isolate was chloroform-stable and susceptible to iodo-deoxyuridine. Electronmicroscopically, in ultrathin sections of infected cells, intranuclear virus particles were found. Using negative contrast, spherical particles with a diameter of 35–45 nm and clearly visible capsomeres were seen. Resume Recherches sur une etiologie virale d'une maladie avec hepatite et troubles du plumage apparue chez des oisillons de perruche ondulee (Melopsittacus undulatus) Un agent cytopathique a ete isole dans des cultures de fibroblastes d'embryons de poulet a partir de cinq envois d'oisillons de perruche ondulee (Melopsittacus undulatus) atteints d'une hepatite et de troubles du plumage. Cet agent etait stable au chloroforme et sensible a la jod-deoxi-uridine. Des particles virales intranucleaires ont pu etre mises en evidence au microscope electronique dans des ultra-coupes de cellules infectees. Des particules spheriques d'un diametre de 35 a 45 nm et des capsomeres distinctes sont apparues apres un contraste negatif. Resumen Estudios acerca de la etiologia virosica de una enfermedad en periquitos (Melopsittacus undulatus) pequenos en el nido acompanada de hepatitis y trastornos en la plumazon De cinco envios de periquitos (Melopsittacus undulatus) de nido, afectados por una enfermedad combinada con hepatitis y trastornos en el plumaje, se pudo aislar un agente citopatico en cultivos de fibroblastos de embrion de pollo. El mismo se mostro como estable frente al cloroformo y sensible frente a yododeoxi-uridina. Con el microscopio electronico se pudieron poner en evidencia particulas virosicas intranucleares en cortes ultradelgados por celulas infectadas. Tras contrastacion negativa se manifestaron particulas esfericas con un diametro de 35 hasta 45 nm y capsomeros evidentes.

Zusammenfassung Aus einem extensiv gehaltenem Wassergeflugelbestand konnte ein Virus isoliert werden, das sich aufgrund seiner physikalisch-chemischen Eigenschaften sowie seiner Morphologie als aviares Herpesvirus erwies. Die Ergebnisse der Kreuzneutralisationsteste belegen eine serologische Verwandtschaft mit einem bekannten Entenpestvirus, nicht aber mit anderen aviaren Herpesviren. Ein Ubertragungsversuch auf Flugenten ergab, das es sich um virulentes Virus handelt. Summary Duck plague among water birds From an extensively maintained water bird premises a virus was isolated which on the basis of its physico-chemical properties and its morphology was found to be an avian herpes virus. The results of cross-neutralization tests indicated a serological relationship with a known duck plague virus but not with other avian herpes viruses. A transmission attempt with ducks showed that the virus was virulent. Resume Peste du canard dans un elevage d'oiseaux aquatiques On a isole un virus dans une exploitation extensive d'oiseaux aquatiques. Ce virus s'est revele etre un virus Herpes aviaire sur la base de ses proprietes physico-chimiques et sa morphologie. Les resultats des tests de neutralisation croisee ont correspondu a une parente serologique avec un virus connu de la peste du canard, mais pas avec d'autres virus Herpes aviaires. Un essai de transmission sur des canards a revele qu'il s'agissait d'un virus virulent. Resumen Peste de los anades en un efectivo de palmipedas De un efectivo de aves acuaticas, criadas en regimen extensivo, se logro aislar un virus, el cual se revelo como un virus herpetico aviar a la vista de sus propiedades fisicoquimicas y de sus rasgos morfologicos. Los resultados de las pruebas de neutralizacion cruzada documentan el parentesco serologico con un virus peste de pato, conocido, mas no con otros virus herpeticos aviares. Un ensayo de transmision a patos voladores tuvo como resultado el que se trata de un virus virulento.

We briefly review the Ablowitz-Kaup-Newell-Segur (AKNS) formalism for 1D+1D integrable systems starting with the Lax pair and continuing into integrable perturbation theory and squared eigenfunctions. We emphasize the common features of the inverse scattering transform across a wide range of known 1D+1D systems. We tailor the various steps to be the same as in treating higher-order systems. We briefly review both the direct and inverse scattering problems and then consider perturbations of the potentials and the scattering data. For the latter topic, we reformulate the original treatment of perturbations of the AKNS system such that it aligns with the common features of 1D+1D systems. We use a recent approach to derive the perturbations of the potentials due to perturbations of the scattering data in the absence of solitons. Finally, we show that recent results where the squared eigenfunctions and their adjoints were found as sums of products (not simply products) of Jost functions are determined by symmetries imposed on the potential matrix.

Zusammenfassung Gegenstand und Ziel: Die Leberfibrose als Konsequenz chronischer Hepatopathien kann derzeit beim Hund nur mittels Biopsie diagnostiziert werden. Beim Menschen zeigt die TGF-β1-Plasmakonzentration, ein Zytokin der Fibrosierungskaskade, eine signifikante Korrelation zum Grad der Leberfibrose. In der vorliegenden Studie sollte die Plasmakonzentration von TGF-β1 bei Hunden mit Leberfibrose gemessen werden, um den Nutzen dieses Markers für den Hund zu überprüfen. Material und Methoden: In die Studie wurden 31 Hunde mit entzündlichen oder neoplastischen Lebererkrankungen aufgenommen. Die Diagnose-stellung erfolgte mittels Untersuchung von Leberbioptaten. Gleichzeitig wurde der Fibrosegrad bestimmt. Die Untersuchung von TGF-β1 im Plasma der Hunde wurde mittels ELISA durchgeführt. Als Vergleichsgruppe dienten 29 gesunde Hunde. Ergebnisse: Bei gesunden Hunden lag die TGF-β1-Plasmakonzentration zwischen 193 und 598 pg/ml (Median = 352), bei Hunden mit leichter Leberfibrose zwischen 126 und 475 pg/ml (Median = 390) und bei Hunden mit deutlicher Leberfibrose zwischen 417 und 1396 pg/ml (Median = 774). Der statistische Vergleich zwischen den Gruppen ergab einen signifikanten Unterschied in der Plasmakonzentration von TGF-β1 zwischen Hunden mit deutlichen Veränderungen und solchen mit leichten Veränderungen oder gesunden Hunden (p < 0,001). Der Vergleich zwischen Hunden mit leichten Veränderungen und gesunden Hunden war nicht signifikant (p > 0,05). Schlussfolgerung und klinische Relevanz: Die Ergebnisse der Studie zeigen, dass mit TGF-β1 ein Blutparameter zur Bestimmung der Leberfibrose beim Hund vorhanden ist, dessen Konzentration mit dem Grad der Fibrosierung steigt. Damit steht ein Parameter für die Diagnose höhergradiger Fibrosen bei Lebererkrankungen des Hundes zur Verfügung. Weitere Untersuchungen müssen zeigen, ob sich TGF-β1 als prognostischer Faktor und zur Kontrolle des Krankheitsverlaufs eignet.

Zusammenfassung Gegenstand und Ziel: In einem niederbayerischen Ferkelerzeugerbetrieb traten in den Monaten August und September 2006 bei 1–3 Wochen alten Saugferkeln aus zwei Würfen von Jungsauen sechs Fälle von proliferativer Dermatitis auf. Material und Methoden: Diagnose und Differenzialdiagnose wurden durch klinisch-dermatologische Untersuchung, kulturellen Erregernachweis, Elektronenmikroskopie, ELISA und PCR-Techniken gestellt. Ergebnisse: Die klinische Symptomatik bestand jeweils in multifokalen kreisförmig erhabenen, teils fluktuierenden Hautveränderungen und erregte den Verdacht auf eine Pockenvirusinfektion. Die klinische Verdachtsdiagnose wurde transmissionselektronenmikroskopisch durch den Nachweis typischer Pockenviruspartikel abgesichert. Die Identifizierung der Pockenviren als Suipoxvirus erfolgte mittels Polymerasekettenreaktion (PCR). Eine Beteiligung von Orthopockenviren am Krankheitsgeschehen konnte durch PCR, einen Differenzierungs-ELISA und das Replikationsverhalten der Virusisolate in Zell - kulturen ausgeschlossen werden. Schlussfolgerung und klinische Relevanz: Schweinepockenvirus-Infektionen werden sporadisch diagnostiziert, der Erreger ist endemisch in der Umwelt verbreitet. Durch neue molekularbiologische Untersuchungsverfahren lassen sich die Viren auch bei Vorliegen von bakteriellen Parallel- und Sekundärinfektionen schnell und sicher identifizieren.

Variational problems have long been used to mathematically model physical systems. Their advantage has been the simplicity of the model as well as the ability to deduce information concerning the functional dependence of the system on various parameters embedded in the variational trial functions. However, the only method in use for estimating the error in a variational approximation has been to compare the variational result to the exact solution. In this Letter, we demonstrate that one can computationally obtain estimates of the errors in a one-dimensional variational approximation, without any a priori knowledge of the exact solution. Additionally, this analysis can be done by using only linear techniques. The extension of this method to multidimensional problems is clearly possible, although one could expect that additional difficulties could arise.

We consider the Camassa-Holm equation for general initial data, particularly when the potential in the scattering problem of the Lax pair, m + K, becomes negative over a finite region. We show that the direct scattering problem of the eigenvalue problem of the Lax pair for this equation may be solved by dividing the spatial infinite interval into a union of separate intervals. Inside each of these intervals, the initial potential is uniformly either positive or negative. Due to this, one can define Jost functions inside each interval, each of which will have a uniform asymptotic form. We then demonstrate that one can obtain the t-evolution of the scattering coefficients of the scattering matrix of each interval. In the process, we also demonstrate that the evolution of the zeros of m + K can be given entirely in terms of limits of the scattering coefficients at singular points.

The analytical modeling of the initialization stage of a relativistic magnetron of the A6 cylindrical design is presented, where only two dominant modes are used: a direct current (dc) background mode and a radio frequency (rf) pump mode. These two modes interaction nonlinearly, with the dc background being driven by the dc electromagnetic forces and the ponderomotive forces of the rf mode, while the rf mode is the most unstable linear eigenmode on this dc background. In cylindrical geometry, the diocotron resonance is found to occur over a broader region than in planar models. In fact, in certain parameter regimes, the resonance can appear twice, once near the Brillouin edge, and second, just below the anode. In these parameter regimes, the oscillating electrons can be accelerated twice. Numerical results for the initiation stage agree quite well with the known experimental results on the A6. Results for 350 kV are emphasized, and similar results have also been obtained for voltages between 300 and 500 kV. Numerical data are presented that indicate a possible source for a nonlinear instability, which could give rise to pulse shortening, in the later operating stage, where the device should be smoothly delivering power.

Prion diseases of animals and man are neurological diseases with amyloidal deposition of the respective proteins. As to prion disease, the cellular prion protein is in its abnormal isoform(s) an essential component of prion protein aggregates found in affected tissue. In contrast to all neurodegenerative diseases like Morbus Alzheimer or Huntington's disease, prion diseases are transmissible. Therefore, prion diseases were designated Transmissible Spongiform Encephalopathies (TSE). The diseases have been well known for decades. Scrapie was first described around 1750, a BSE case was reported in the 1850-ties most likely a misdiagnosis, and in 1920/1930 the human Creutzfeldt-Jakob disease (CJD) had been described. Transmission of CJD i. e. Kuru had been suspected in the early 1950 s and was erroneously classified as slow virus disease. The CJD transmission posed a problem to humans when transplants from CJD cases were used for treatment. Fortunately, these iatrogenic transmissions remained limited. But with the advent of BSE and appearance of variant CJD cases in the UK and some places in Europe scientists suspected that transmission from cattle to man could have happened. From animal models we know of successful transmission via several routes. Species barriers do not completely prevent transmission. Rather, transmission barriers might exist controlling individual susceptibility against prions. Modes of transmission, susceptibility to transmission, identification of receptor molecules as well as molecular mechanisms of the transmission process are being investigated with great intensity. Current knowledge leads us to assume that inapparent stages of prion infection wrongly suggest a (non-existent) species barrier. This inapparent infection precedes overt disease, and, hence, most research focuses on the development of highly sensitive assay systems for detection of minute amounts of pathological prion protein in suspected cases. Inapparence also should warn us to underestimate BSE or human vCJD cases; at present, approx. 145 cases occurred in Europe and one probable case in Hong Kong (June 2003). Whether BSE had spread to other parts of the world by animal nutrition components or meat can neither be excluded nor confirmed at this time. New data on transmission and consequences of BSE for the human population are summarised in this review.

To prevent sudden cardiac death of patients who are at risk from long standing tachyarrhythmia the implantable cardioverter defibrillator (ICD) is the first choice therapy. ICDs use a range of electrostimuli up to defibrillation, which is a non synchronous high energy shock, whereas cardioversion is synchronous with the ECG. In order to know when and how to react, a detection algorithm, which analyses an intracardial electrocardiogram (ECG) and classifies the heart rhythm, is implemented in every ICD. All detection algorithms use the heart rate to classify the different heart rhythms roughly. If a tachycardia is detected, it is important to discriminate between a ventricular tachycardia, which is life threatening and a supraventricular tachycardia, which is much less threatening. To be able to make this distinction the detection algorithms analyse the behaviour of the heart cycle intervals, the ECG-morphology or in addition to the ventricular ECG, an atrial ECG. In this paper morphological algorithms will be evaluated and newly developed algorithms will be presented. Recent algorithms use the mathematical wavelet theory. The evaluation shows that these get better results than all but one of the simpler classical morphological algorithms. A new wavelet based algorithm, developed by the authors, exhibits the best detection results.

A theory of dispersive soliton of the self-induced transparency in a medium consisting of atoms or semiconductor quantum dots of two types is considered. A two-component medium is modeled by a set of two-level atoms of two types embedded into a conductive host material. These types of atoms correspond to passive atoms (attenuator atoms) and active atoms (amplifier atoms) with inverse population of the energetic levels. The complete solution is given of the Maxwell\char21{}Bloch equations for ensembles of two-type atoms with different parameters and different initial conditions by inverse scattering transform. The solutions of the Maxwell\char21{}Bloch equations for many-component atomic systems by inverse scattering transform are also discussed. The influence of the difference between dipole moments of atoms, the longitudinal and transverse relaxation times, pumping, and conductivity on the soliton is taken into account by means of perturbation theory. The memory effects are described in terms of generalized non-Markovian optical Bloch equations. The condition of a balance between the energy supplied and lost is obtained.

A model Goursat problem for second harmonic generation is treated by a formerly developed inverse scattering method on a finite or semi-infinite interval. For small or moderate values of the scaled characteristic coordinates χ, τ, the approximate solution is given in terms of N -pole formulae, and it is demonstrated that it becomes more accurate with increasing N . In another limit, this same problem is studied in the asymptotic region for large τ . For our particular boundary values it is shown that the asymptotic solution is a stationary wave solution (one for which there is no exchange of energy) modified by a boundary layer.

Captive callitrichids are prone to developing intestinal problems. Their captive and natural diets differ enormously, and diet has been suggested to play a major role in wasting marmoset syndrome. Proteins in wheat, soy and milk are included in callitrichid diets of most colonies and have been linked to an immune reaction in Saguinus oedipus and Callithrix jacchus. In the present study of 23 males and females of the two species, wheat protein was tested but soy and milk products were excluded. One group had wheat and the other had rice in their diet. Blood samples and biopsies from the colon were taken. Results showed changes in the colon and an immune reaction to gliadin, a wheat protein related to coeliac disease in humans. A further immune reaction was also observed. Suggestions for further study and exclusion of cereal in the diet of these small, New World primates are discussed.

The modeling of crossed-field electron vacuum devices, such as magnetrons and crossed-field amplifiers with a dc background mode and an rf pump mode is discussed. The dominant interaction in these devices is the wave-particle interaction (diocotron). This interaction drives the classical Brillouin flow nonlinearly unstable through a Rayleigh-type instability in a shear flow. This linear instability triggers the nonlinear instability, which is a second-order nonlinear diffusion process. This diffusion process is driven by the density gradient at the edge of the sheath, which causes the electron density to evolve into a new density profile, one which will be in equilibrium with the nonlinear diffusion process. The general physics of the various processes contained in this model is discussed, including a possible explanation for the ultra-low noise phenomena.

Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV-specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus-1 (HIV-1)-infected patients without PML (HIV), 4 HIV-1-negative patients with PML (PML), and 8 HIV-1-positive patients with PML (HIV/PML). As antigens, recombinant virus-like particles of the major structural protein VP1 (VP1-VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1-VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon-γ (IFN-γ) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin-10 (IL-10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1-VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1-type T-helper cell function of cell-mediated immunity.

During the course of simian immunodeficiency virus (SIV) infection, nearly 15% of rhesus macaques (Macaca mulatta) and up to 40% of cynomolgus macaques (Macaca fascicularis) developed SIV-associated non-Hodgkin's lymphomas. Most of these malignant lymphomas harbored lymphocryptoviruses, which are closely related to the human Epstein-Barr virus (EBV; Herpesvirus M. mulatta and Herpesvirus M. fascicularis). To characterize the oncogenic role of simian EBV infection for lymphomagenesis during SIV infection, expression of the EBV-encoded latent membrane protein-1 (LMP-1) was analyzed in malignant lymphomas of SIV-infected rhesus macaques. Nine seropositive rhesus macaques suffering from B-cell lymphomas during the late phase of SIV infection were euthanized. Latency stages of EBV infection within malignant lymphomas and simian EBV-infected lymphoblastoid cell lines (LCL8664, H50) were characterized by analyzing expression of the EBV-encoded nuclear antigens EBNA-1, EBNA-2, and small RNAs EBER1/2. In parallel, the presence of viral LMP-1 transcripts was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Results were compared with findings in AIDS-associated malignant lymphomas in two patients infected with human immunodeficiency virus (HIV)-1. Rhesus macaques developed high-grade B-cell lymphomas of the centroblastic (five of nine), immunoblastic (two of nine), centroblastic-centrocytic (one of nine), and Burkitt-like (one of nine) subtypes within 18-29 months postinfection with SIV(mac)251/32H. The presence of Herpesvirus M. mulatta was detected in eight of nine cases. Transcription of the viral oncogene LMP-1 could be demonstrated within the simian EBV-infected cell lines as well as in four of nine SIV-associated malignant lymphomas. These four cases and both of the HIV-1-related non-Hodgkin's lymphomas expressed the full spectrum of latent EBV gene products (LMP-1, EBER1/2, EBNA-1, EBNA-2) and were thus classified as latency type III stages of EBV infection. Simian EBV infection was demonstrated in 90% of lymphomas in SIV-infected rhesus macaques. Analysis of LMP-1 expression suggests an important role for this viral oncogene in the pathogenesis of both SIV and HIV-1-associated malignant lymphomas.

The purpose of this work is to understand theoretically what are the possible noise levels in a magnetron or a crossed-field amplifier (CFA), due to parametric three-wave interactions in the electron plasma, at various operating parameters. Our approach is to use the cold-fluid equations and their Fourier decomposition into a background (DC) mode, a pump (RF) mode, and two other noise (RF) modes. The two RF noise modes are assumed to interact parametrically with the large RF pump mode, and to satisfy the standard resonance conditions for the sum of the wave vectors and sum of the frequencies. We use our previous results to determine the background mode and the RF pump mode. Any strong RF electric field propagating in a crossed-field electron vacuum device can drive a Brillouin sheath unstable by means of a Rayleigh instability, whenever a wave–particle resonance can be found inside the sheath. What happens physically is that, at the resonance, the laminar flow of the electrons is strongly disturbed, and a diffusion process ensues, whereby the electrons diffuse away from the resonance region. This upsets the balance in the Brillouin flow, causing the electrons to redistribute into a new average DC density profile – which may be far from the original Brillouin profile, but is a stationary solution of a nonlinear diffusion equation. Using these stationary density profiles, we can then study the propagation of small RF signals on such a DC background, as well as their parametric interactions with the RF pump wave, at various DC voltages and magnetic fields. In addition to being able to predict the operating regime and the DC current flow, these studies demonstrate that parametric interactions probably limit the operating voltage range of a typical magnetron or crossed-field amplifier to about 20% above the Hartree voltage.

The introduction of h-DAF transgenic porcine organs into pre-clinical pig-to-primate discordant xenotransplantation has led to complete and reliable abrogation of hyperacute xenograft rejection (HAR). Despite additional heavy immunosuppression however, most xenografts are still lost due to acute vascular rejection (AVR), with current treatment protocols being of only limited value. In a life-supporting model of pig-to-primate kidney transplantation, unmodified (n = 8) or h-DAF-transgenic (n = 9) porcine kidneys were transplanted into cynomolgus monkeys under cyclophosphamide (CyP), cyclosporine and low-dose steroid immunosuppression. Longest recipient survival was 11 days in the control group and 68 days in the h-DAF transgenic group. Stable initial graft function with recipient survival > 4 days was generated in eight animals (two controls and six transgenics). In these animals, plasma complement levels were analyzed during ongoing AVR. Compared with baseline levels, a two-fold increase in C3a levels and a four-fold increase in sC5b-9 levels were measured. In parallel to systemic complement activation, increased deposition of C3 and C5b-9 along with massive staining for recipient IgM immunoglobulins was detected in the xenografts on immunohistochemistry. We conclude that acute vascular xenograft rejection of porcine kidneys in cynomolgus monkeys is associated with classical pathway complement activation following binding of induced recipient anti-porcine antibodies. This complement activation can be observed despite membrane bound expression of human complement regulators in the porcine xenografts. Therefore, additional short-term fluid phase complement inhibition seems necessary for the future development of protocols designed for treatment of AVR in the pig-to-primate combination.

In this paper, we study the stability and evolution of solitary waves in perturbed generalized nonlinear Schrodinger (NLS) equations. Our method is based on the completeness of the bounded eigenstates of the associated linear operator in L2 space and a standard multiple-scale perturbation technique. Unlike the adiabatic perturbation method, our method details all instability mechanisms caused by perturbations of such equations and explicitly specifies when such instabilities will occur. In particular, our method uncovers the instability caused by bifurcation of nonzero discrete eigenvalues of the linearization operator. As an example, we consider the perturbed cubic-quintic NLS equation in detail and determine the stability regions of its solitary waves. In the instability region, we also specify where the solitary waves decay, collapse, develop movingfronts, or evolve into a stable spatially localized and temporally periodic state. The generalization of this method to other perturbed nonlinear wave systems is also discussed.

We present a new type of soliton, found in models characterized by opposing dispersions and competing nonlinearities at fundamental and second harmonics. They are isolated solitary waves, existing at discrete values of the propagation constant inside the system’s continuous spectrum. We show analytically, and verify by simulations, that the fundamental solitons are linearly stable. They can be nonlinearly stable or unstable, depending on the sign of the energy perturbation, which could make these pulses useful for switching applications. Higher-order solitons are found, too, but they are linearly unstable. We report a new type of soliton, in the form of an isolated (codimension-one) solitary-wave solution whose intrinsic frequency resides inside the continuous spectrum of the radiation modes. It is a special member of a family of delocalized solitons, which are solitary waves with nonvanishing oscillating tails. In terms of the dynamicalsystems theory, these are trajectories homoclinic to cycles, whereas ordinary solitons are homoclinic to fixed points. Delocalized solitons are known in various models of the hydrodynamic [1] and optical [2] origin. We demonstrate that the amplitudes of the oscillating tails can exactly vanish at a discrete set of frequencies, resulting in a delocalized soliton becoming truly localized, and with finite energy. We call these solutions embedded (in the continuous spectra) solitons (ES). Because the vanishing of the tail’s amplitude is an additional condition, these solitons (in contrast to familiar gap solitons [3]), never exist in continuous families, but only as isolated solutions. A physical model giving rise to ES describes an optical medium with quadratic (x 2 ) and cubic (x 3 ) nonlinearities. Various systems of this type have been recently considered [4]. We start with a general one, iuz 1 12utt 1 u y1g 1juj 2 1 2jyj 2 u 0, (1) iyz 2 12dytt 1 q y1 12u 2 1

A procedure with an effective S-matrix is developed to apply the inverse scattering transform method to a finite interval. Second harmonic generation and stimulated Raman scattering are treated as two examples to demonstrate the applicability of this method.

Background & Aims: Human immunodeficiency virus (HIV) infection leads to severe immunologic and functional disturbances in the intestinal tract in late stages of the disease. Information on mucosal pathology directly after infection is limited. We characterized this early phase in rhesus macaques infected with simian immunodeficiency virus (SIV). Methods: Eight rhesus macaques were infected with SIV. Upper endoscopy was performed at defined times before and after infection. Viral load, percentage of CD4 + T cells, villus height, crypt depth, and Ki-67–positive crypt cells were analyzed in duodenal biopsy specimens. Serum β-carotene and vitamin D levels were assessed. Results: A rapid increase of duodenal SIV core protein (p27) concentration and an almost complete loss of intestinal CD4 + T cells was found within 2 weeks after infection. A decrease of villus height was observed, and the percentage of Ki-67–positive (proliferating) crypt cells increased. Serum concentrations of vitamin D decreased in 6 of 8 animals, and β-carotene concentrations decreased in 3 of 8 animals after infection. Conclusions: Mucosal SIV replication and intestinal CD4 + T cell depletion are early events in SIV-infected rhesus macaques. The structural changes of the mucosa strongly support the concept of HIV/SIV–induced enteropathy. In contrast to late-stage human HIV infection, early small intestinal villous atrophy in SIV infection is associated with crypt hyperplasia. GASTROENTEROLOGY 1999;116:1115-1123

This paper applies three-wave interaction (TWI)-soliton theory to optical parametric amplification when the signal, idler, and pump wave can all contain TWI solitons. We use an analogy between two different velocity regimes to compare the theory with output from an experimental synchronously pumped optical parametric amplifier. The theory explains the observed inability to compress the intermediate group-velocity wave and 20-fold pulse compression in this experiment. The theory and supporting numerics show that one can effectively control the shape and energy of the optical pulses by shifting the TWI solitons in the pulses.

We develop a perturbation theory for the Benjamin-Ono (BO) equation. This perturbation theory is based on the inverse scattering transform for the BO equation, which was originally developed by Fokas and Ablowitz and recently refined by Kaup and Matsuno. We find the expressions for the variations of the scattering data with respect to the potential, as well as the dual expression for the variation of the potential in terms of the variations of the scattering data. This allows us to introduce the squared eigenfunctions for the BO equation, whose completeness and orthogonality in both x- and-spaces we also establish. We consider the two most important applications of the developed machinery. First, we present an explicit first-order solution of the BO equation driven by a small perturbation. Second, we introduce the Poisson bracket and a set of the canonical action-angle variables for the BO equation, and thus demonstrate its complete integrability as a Hamiltonian dynamical system.

Recommendations of the Federation of European Laboratory Animal Science Associations (FELASA) Working Group on Non-Human Primate Health accepted by the FELASA Board of Management, 21 November 1998 FELASA Working Group on Non-Human Primate Health: H. Weber (Convenor), E. Berge, J. Finch, P. Heidt, F.-J. Kaup, G. Perretta, B. Verschuere & S. Wolfensohn

We represent a pulse in the strongly dispersion managed fiber as a linear superposition of Hermite-Gaussian harmonics, with the zeroth harmonic being a chirped Gaussian with periodically varying width. We obtain the same conditions for the stationary pulse propagation as were obtained earlier by the variational method. Moreover, we find a simple approximate formula for the pulse shape, which accounts for the numerically observed transition of that shape from a hyperbolic secant to the Gaussian. Finally, using the same approach, we systematically derive the equations for the evolution of a pulse under a general perturbation. This systematic derivation justifies the validity of similar equations obtained earlier from the conservation laws.

We extend the inverse scattering transform (IST) for the Benjamin–Ono (BO) equation, given by A. S. Fokas and M. J. Ablowitz (Stud. Appl. Math. 68:1, 1983), in two important ways. First, we restrict the IST to purely real potentials, in which case the scattering data and the inverse scattering equations simplify. Second, we extend the analysis of the asymptotics of the Jost functions and the scattering data to include the nongeneric classes of potentials, which include, but may not be limited to, all N-soliton solutions. In the process, we also study the adjoint equation of the eigenvalue problem for the BO equation, from which, for real potentials, we find a very simple relation between the two reflection coefficients (the functions β(λ) and f(λ)) introduced by Fokas and Ablowitz. Furthermore, we show that the reflection coefficient also defines a phase shift, which can be interpreted as the phase shift between the left Jost function and the right Jost function. This phase shift leads to an analogy of Levinson's theorem, as well as a condition on the number of possible bound states that can be contained in the initial data. For both generic and nongeneric potentials, we detail the asymptotics of the Jost functions and the scattering data. In particular, we are able to give improved asymptotics for nongeneric potentials in the limit of a vanishing spectral parameter. We also study the structure of the scattering data and the Jost functions for pure soliton solutions, which are examples of nongeneric potentials. We obtain remarkably simple solutions for these Jost functions, and they demonstrate the different asymptotics that nongeneric potentials possess. Last, we show how to obtain the infinity of conserved quantities from one of the Jost functions of the BO equation and how to obtain these conserved quantities in terms of the various moments of the scattering data.

Using inverse scattering transform theory, we obtain new analytical expressions describing the process of parametric amplification by ultrashort pulses. We show that the result of parametric amplification of a small signal pulse by an intense pump wave does not depend on the shape of the pump. The output is determined solely by the intensity of any TWI-solitons contained in the pump.

Using the complex Toda chain we model the asymptotic behavior of the N soliton pulse trains of the nonlinear Schrodinger equation. Stable asymptotic regimes are: (i) asymptotically free propagation of all N solitons; (ii) bound state regime where the N solitons may move quasi-equidistantly (QED); and (iii) various intermediate regimes. Our method allows one to determine analytically the set of initial soliton parameters corresponding to each regime. We list the soliton parameters, which ensure QED propagation of all N solitons since this is important for optical fiber communication.

Using the variational method, we obtain analytical conditions for stationary propagation of a Gaussian pulse in a fibre with strong dispersion management. We consider both the lossless fibre and the one with losses and periodic amplification. The analytical predictions have been checked against direct numerical simulations, and a good agreement between the two has been demonstrated. In particular, we find that in a certain region of parameters, the average dispersion necessary to support the stationary propagation is negative (normal). We also show that under a certain assumption, the variance of the Gordon-Haus timing jitter for the pulse in a strongly dispersion-managed system approximately equals that for the conventional soliton, reduced by an energy enhancement factor. Using our analytical conditions, we obtain an estimate for this factor. In particular, we show that in the presence of losses and periodic amplification, this jitter suppression factor can be made to be as large as that for the lossless case, by properly choosing the segment lengths in the dispersion map.