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In this work, we have subjected protonated nucleobases MH+(M = guanine, adenine, thymine, uracil and cytosine) to a range of experiments that involve high-energy (50 keV) collision-induced dissociation (CID) and electron capture-induced dissociation. In the latter case, both neutralisation reionisation and charge reversal were done. For the CID experiments, the ions interacted with O2. In neutral reionisation, caesium atoms were used as the target gas and the protonated nucleobases captured electrons to give neutrals. These were reionised to cations a microsecond later in collisions with O2. In choosing Cs as the target gas, we have ensured that the first electron transfer process is favourable (by about 0.1–0.8 eV depending on the base). In the case of protonated adenine, charge reversal experiments (two Cs collisions) were also carried out, with the results corroborating those from the neutralisation–reionisation experiments. We find that while collisional excitation of protonated nucleobases in O2may lead to hydrogen loss with limited probabilities, this channel becomes dominant for electron capture events. Indeed, when sampling reionised neutrals on a microsecond timescale, we see that the ratio between MH+and M+is 0.2–0.4 when one electron is captured from Cs. There are differences in these ratios between the bases but no obvious correlation with recombination energies was found.

In recent years, with important advances in molecular biology, experimental and measurement technologies, it has become possible to generate the quantitative data that are needed for building mathematical models of complex biochemical processes. Cartoon-like diagrams of biological pathways can be turned into dynamical models, allowing simulation and analysis to gain an insight into the underlying control mechanisms and the behaviour of the overall system. This kind of system-level understanding has not been reachable from the study of the components of pathways in isolation. However, mathematical modelling does not only integrate the available knowledge about a certain system with newly generated experimental results. During the process of modelling, questions need to be addressed that lead to an increased quantitative understanding of the system. Models can be used to optimize experimental approaches and protocols and to test different hypotheses about the underlying biological mechanisms. Finally, a validated mathematical model can be used to perform in silico experiments that might be hard or impossible to do in the laboratory. In this chapter we present a case study of a systematic modelling approach applied to the thiamine uptake system of the yeast Saccharomyces cerevisiae. This example is part of our broader effort to model the whole of thiamine metabolism in yeast, which involves several additional processes such as thiamine utilization, biosynthesis and gene regulation. Our main goal is to describe how systematic modelling has improved the knowledge about the system under study.

Information technology is an important part within the highly interdisciplinary scientific field of systems biology. In this paper we are presenting an overview over systems biology, focusing on the information technological aspects, current developments, and future challenges.

This paper presents a new haptic locomotion interface, which comprises two programmable foot platforms with permanent foot machine contact. It is designed as a scalable and modular system with unit-by-unit extensibility offering up to six plus one degrees of freedom (DOF) per foot. The basic setup comprises three DOF per foot in the sagittal plane.The machine is based on a rigid hybrid parallel-serial robot kinematics structure. It is equipped with electrical direct drive motors, enabling highly dynamic footplate motions. For contact force measurement, six DOF force/torque sensors are mounted under each foot platform. The system was developed for major application in gait rehabilitation, hence great importance was attached to the incorporation of maximum passive and active security measures for machine users and medical operating personnel.The simulator is able to perform walking trajectories with speeds of up to 5 km/h and 120 steps/min. The system is able to simulate not only slow and “smooth” trajectories like walking on an even floor, up/down staircases, but also foot motions like walking on rough ground or even stumbling or sliding, which require high system dynamics.The machine is controlled by a self-developed full-featured robot control whose soft and hardware is based on up-to-date industrial standards and interfaces. The robot control software is based on RTLinux and runs on an industrial PC. The real-time motion generator includes a newly developed Fourier-based algorithm for the interpolation of natural cyclic walking trajectories. For the implementation of asynchronous events (e.g., sliding, stumbling), the controller comprises especially developed algorithms for automatic motion override adaptation. Different modes of haptic behavior needed for gait rehabilitation, ranging from full foot support during swing phase to completely passive behavior, are currently under development.Intuitive and safe machine operation by nontechnical personnel such as clinicians and physiotherapists is achieved via a separate Windows-based graphical user interface software comprising different window areas for machine programming and operation, real-time off-line simulation and online data visualization in two and three dimensions has been developed as well.A working prototype of the system has been built and tested successfully, including all soft and hardware components. Although the machine has been designed and built for major application in gait rehabilitation, its range of applicability is not limited to this area. It could be integrated into any setup requiring a highly dynamic haptic foot interface and permanent foot machine contact if needed.

The successful motor rehabilitation of stroke, traumatic brain-injured and spinal cord-injured patients requires an intensive and task-specific therapy approach. Budget constraints limit a hand-to-hand therapy approach, so that intelligent machines may offer a solution to promote motor recovery and obtain a better understanding of motor control. This new field of automated or robot-assisted motor rehabilitation has emerged since the 1990s.

Background and introduction:Damage to the AV conduction system is a frequent complication of percutaneous septal ablation (PTSMA) that needs early and reliable identification of those patients (pts.) at risk for complete heart block (CHB) and subsequent pacemaker implantation. Methods and results:In the first 39 pts. who underwent PTSMA in 1996, AV conduction recovery needed up to 11 days. One pt. suffered from unexpected CHB after 9 days. Seven pts. who needed a DDD pacemaker (DDD-PM) were compared to those without conduction disturbances. A score was established which identified all DDD-PM candidates retrospectively if they presented with >12 score points. In the following 137 consecutive pts. treated in 1997 and 1998, this score was applied prospectively, and again correctly identified all candidates for a DDD-PM. In addition, a low risk group was identified with <8 score points. From 1999 on, the score was applied in routine clinical decision-making in 120 consecutive pts. with respect to DDD-PM implantation. All low risk pts. (<8 points) remained free from bradycardias, while 2/54 pts. (4%) of the intermediate risk group, and 20/23 pts. (87%) of the high risk group had to undergo DDD-PM implantation. Pts. with a first-degree AV block or those with a right bundle branch block at baseline had no excess risk, while 50% of the pts. with a left bundle branch block (LBBB) needed a DDD-PM. Conclusions:Based on pre-interventional data and careful monitoring of the first 48 hours after PTSMA, identification of pts. at risk for CHB and subsequent DDD-PM implantation seems to be possible. Pts. with a score <8 seem to be at low, those with >12 points at high risk. In the remaining cases watchful waiting with prolonged monitoring may allow AV conduction to recover, thus, reducing the number of unnecessary DDD-PM implantations. In cases with LBBB at baseline, however, implantation of a DDD-PM should be considered first-line therapy. Einleitung:Höhergradige AV-Überleitungsstörungen (AVB) stellen eine häufige Komplikation der perkutanen Septumablation (PTSMA) dar und erfordern eine frühzeitige und verlässliche Identifikation derjenigen Patienten (Pat.), die einen permanenten DDD-Schrittmacher (DDD-SM) benötigen. Methoden und Ergebnisse:Wir beobachteten den Spontanverlauf des AVB bei den ersten 39 im Jahr 1996 mittels PTSMA behandelten Pat., ausgenommen 6 Pat. mit bereits implantiertem DDD-SM bzw. vorbestehenden Erregungsleitungsstörungen, wobei die stabile Erholung einer gestörten Überleitung maximal 11 Tage benötigte. Sieben der verbleibenden 33 Pat. erhielten einen DDD-SM. Der Vergleich dieser Pat. mit denen ohne AVB resultierte in einem Scoresystem, welches mit >12 Punkten retrospektiv alle DDD-SM-Kandidaten identifizierte. Bei den 137 nachfolgenden Pat. der Jahrgänge 1997 und 1998 wurde dieser Score prospektiv angewendet und klassifizierte ebenfalls alle weiteren DDD-SM-Kandidaten korrekt. Darüber hinaus konnte eine Gruppe niedrigen Risikos mit <8 Score-Punkten ermittelt werden. Ab dem Jahr 1999 an erfolgte die Anwendung des Score-Systems bei 120 konsekutiven Pat. in der klinischen Routine. In der Niedrig-Risikogruppe (<8 Punkte) blieben sämtliche Pat. ereignisfrei. Ein DDD-SM war bei 2/52 (4%) der Gruppe mit mittlerem Risiko, und bei 20/23 (87%) der Hochrisikogruppe erforderlich. Ein AV-Block Grad I oder ein Rechtsschenkelblock im Ausgangs-EKG vor PTSMA erhöhte die Wahrscheinlichkeit einer DDD-SM-Implantation nicht, während Pat. mit Linksschenkelblock (LSB) eine Schrittmacher-Quote von 50% aufwiesen. Schlussfolgerung:Basierend auf der Kombination präinterventioneller Daten mit einer sorgfältigen Überwachung der ersten 48 h nach PTSMA erscheint die zuverlässige Identifikation von DDD-SM-Kandidaten möglich. Patienten mit <8 Punkten des vorgestellten Score haben ein äußerst geringes, solche mit >12 Punkten ein sehr hohes Risiko für einen permanenten AVB. In den verbleibenden Fällen kann unter prolongiertem Monitoring die Erholung der AV-Überleitung abgewartet und so die Zahl langfristig unnötiger DDD-SM-Implantationen verringert werden. Bei Pat. mit LSB erscheint die primäre Versorgung mit einem DDD-SM sinnvoll.

We have cloned and sequenced the Schizosaccharomyces pombe ade10gene encoding 5‐phosphoribosyl‐4‐carboxamide 5‐aminoimidazole transformylase inosine monophosphate cyclohydrolase. The sequence has an uninterrupted open reading frame of 1755 nucleotides corresponding to 585 amino acid residues. The deduced amino acid sequence shows a high degree of similarity to the purH gene product of many species, including Saccharomyces cerevisiae, human, chicken and Escherichia coli.Moreover our data indicate that intrachromosomal recombination in Schiz. pombeis enhanced if the ade10gene product is defective. The sequence has been submitted to the EMBL data library under Accession Number Y16419. © 1998 John Wiley & Sons, Ltd.

The products of 11 switching (swi) genes are required for efficient mating-type (MT) switching in homothallic (h90) strains of Schizosaccharomyces pombe. The MT region of h90 comprises three cassette genes: the expression site mat1: 1 and two silent loci, mat2: 2 and mat3: 3. Besides reducing MT switching, the swi6 mutation leads to deletions in the MT region caused by intrachromosomal cross-overs between two paired cassettes. These deletions only arise if DNA double-strand breaks are present at mat1: 1, which initiate MT switching. Furthermore, swi6 allows meiotic recombination in the K region, a region of 16 kb between mat2: 2 and mat3: 3; in wild-type strains no recombination occurs in K. swi6 also allows the simultaneous expression of two different cassettes in the same haploid cell. Thus swi6 may have an influence on the general chromatin structure in the MT region.

Zusammenfassung: □ Fallbeschreibung: Eine 26jährige Patientin wurde in der 18. Schwangerschaftswoche ihrer dritten Schwangerschaft in einem auswärtigen Krankenhaus mit den Zeichen der Lungenstauung und zunehmenden Rechtsherzversagens auf der dortigen Intensivstation aufgenommen. Nach Diagnosestellung einer rheumatischen Mitralklappenstenose als Ursache für die pulmonale Stauung konnte unter konservativ-medikamentöser Therapie primär eine Rekompensation erreicht werden. Als in der 23. Schwangerschaftswoche erneut eine zunehmende kardiale Dekompensation mit Pleuraergüssen auftrat, wurde die Patientin in unsere Abteilung verlegt. Nach nichtinvasiver Voruntersuchung wurde die notfallmäßige perkutane Mitralvalvulotomie mit dem Inoue-Ballon durchgeführt. Unter maximaler Beachtung des Strahlenschutzes für Mutter und Feten wurde eine Verdopplung der Mitralklappenöffnungsfläche von 0,6 cm2 auf 1,3 cm2 erreicht. Mit diesem funktionell guten Ergebnis konnte die gravide Patientin am Folgetage in das Heimatkrankenhaus zurückverlegt werden. Die pleuralen Restergüsse entwickelten sich kurzfristig komplett zurück. Die Patientin war subjektiv vollständig beschwerdefrei und konnte am Termin von einem gesunden Kind entbunden werden.

Abstract: The Schizosaccharomyces pombe rhp51 + , rad22 + and rhp54 + genes are homologous to RAD51, RAD52 and RAD54 respectively, which are indispensable in the recombinational repair of double-strand breaks (DSBs) in Saccharomyces cerevisiae. The rhp51Δ and rhp54Δ strains are extremely sensitive to ionizing radiation; the rad22Δ mutant turned out to be much less sensitive. Homologous recombination in these mutants was studied by targeted integration at the leu1-32 locus. These experiments revealed that rhp51Δ and rhp54Δ are equally impaired in the integration of plasmid molecules (15-fold reduction), while integration in the rad22Δ mutant is only reduced by a factor of two. Blot-analysis demonstrated that the majority of the leu+ transformants of the wild-type and rad22Δ strains have integrated one or more copies of the vector. Gene conversion events were observed in less than 10% of the transformants. Interestingly, the relative contribution of gene conversion events is much higher in a rhp51Δ and a rhp54Δ background. Meiotic recombination is hardly affected in the rad22Δ mutant. The rhp51Δ and rhp54Δ strains also show minor deficiencies in this type of recombination. The viability of spores is 46% in the rad22Δ strain and 27% in the rhp54Δ strain, as compared with wild-type cells. However, in the rhp51Δ mutant the spore viability is only 1.7%, suggesting an essential role for Rhp51 in meiosis. The function of Rhp51 and Rhp54 in damage repair and recombination resembles the role of Rad51 and Rad54 in S. cerevisiae. Compared with Rad52 from S. cerevisiae, Rad22 has a much less prominent role in the recombinational repair pathway in S. pombe.

Zusammenfassung: Klinische Symptome und diagnostische Befunde bei Patienten mit Mitralstenose werden in der Regel vom Ausmaß der Stenose bestimmt. Bei einer normalen Mitralklappenöffnungsfläche von über 4 cm2 ist bei Patienten mit höhergradiger Mitralstenose die Mitralklappenöffnungsfläche meist auf < 1,5 cm2 reduziert. Bei älteren Patienten beeinflussen Begleiterkrankungen häufig die Symptomatik (zum Beispiel Vorhofflimmern, arterielle Hypertonie und Lungenerkrankungen). Wichtigster Bestandteil der Diagnostik neben Anamnese, Auskultation, EKG und Röntgenaufnahmen des Thorax ist die Echokardiographie, um nichtinvasiv zuverlässig Mitralklappengradienten, Mitralklappenöffnungsfläche und morphologische Veränderungen der Klappen sowie begleitende Vitien, Ventrikelfunktionen und eventuelle linksatriale Thromben zu erfassen. Neben den seit 50 Jahren bewährten chirurgischen Behandlungsverfahren bei Patienten mit hochgradiger Mitralstenose hat sich in den letzten Jahren die perkutane Ballonmitralvalvuloplastie etabliert. Zum gegenwärtigen Zeitpunkt scheint die Inoue-Technik die meisten Vorteile aufzuweisen. Nach transseptaler Punktion wird der Inoue-Ballon transvenös über einen speziellen Wechseldraht in den linken Vorhof und nachfolgend in den linken Ventrikel vorgebracht. Eine spezielle Entfaltungscharakteristik erlaubt eine sichere Plazierung im Bereich der Mitralklappe ohne Gefahr von Ventrikelrupturen durch den Ballon (Abbildung 1); spezielle im Ventrikel liegende steife Unterstützungsdrähte sind nicht erforderlich, so daß mit dieser Methode bisher keine Vetrikelrupturen Beschrieben wurden. Wie bei einer chirurgischen Kommissurotomie führt die Ballonvalvuloplastie zu einer Separation der verwachsenen Kommissuren. Es kommt zu einer deutlichen Reduktion des Mitralklappengradienten mit begleitender Zunahme der Mitralklappenöffnungsfläche (Abbildung 2). Die Ergebnisse und Erfolge der Ballonmitralvalvuloplastie werden stark von der Morphologie der Klappen und der Veränderungen des subvalvulären Apparates bestimmt. In randomisierten Studien waren die Ergebnisse der chirurgischen Kommissurotomie mit denen der Ballonmitralvalvulotomie vergleichbar. In unserer Klinik wurde bei 899 Patienten mit einem mittleren Alter von 56±3 Jahren eine Zunahme der Klappenöffnungsfläche von 1,0 auf 1,8 cm2 erzielt. Bei jüngeren Patienten mit weniger stark veränderten Klappen waren die Ergebnisse entsprechend günstiger als bei älteren Patienten (Abbildung 3); auch ein Rezidiv nach vorausgegangener chirurgischer Kommissurotomie stellt bei geeigneter Klappenmorphologie keine Kontraindikation für eine Ballonmitralvalvuloplastie dar. Die Komplikationsrate ist in geübter Hand sehr niedrig: Die Letalität liegt. unter 1%; mit dem Auftreten einer schweren Mitralinsuffizienz muß bei 3 bis 10% der Eingriffe gerechnet werden; in unserem Kollektiv haben wir eine höhergradige Mitralinsuffizienz bei 5% der Eingriffe beobachtet. Thromboembolische Komplikationen lassen sich mit Ausschluß von Vorhofthromben durch eine transösophagiale Echokardiographie verhindern. Das Auftreten eines hämodynamisch bedeutsamen Vorhofseptumdefekts ist eine Ausnahme. Die mittelfristigen Ergebnisse (fünf bis zehn Jahre) und die niedrige Restenosierungsrate nach Ballonmitralvalvuloplastie bei Patienten mit geeigneten Klappen sind denen der operativen Kommissurotomie vergleichbar. Bei älteren Patienten mit stark veränderten, verkalkten und fibrosierten Klappen ist mit einer Restenosierung innerhalb von ein bis fünf Jahren zu rechnen; bei diesen Patienten stellt die Ballonmitralvalvuloplastie nur einen palliativen Eingriff dar, um den Operationszeitpunkt hinauszuzögern, zum Beispiel bei Patienten mit einem begleitenden Aortenklappenvitium, das allein noch keine Operationsindikation darstellt. Besondere Indikationen ergeben sich bei jungen, noch wenig symptomatischen Patienten mit hochgradiger Mitralstenose, bei Schwangeren und in Notfallsituationen sowie bei Patienten mit Mitralstenose vom Schweregrad II mit intermittierendem Vorhofflimmern. Im Vergleich zur operativen Behandlung ist die Kathetertherapie sehr viel weniger invasiv; da die Letalität ausgesprochen niedrig ist, bleibt den Patienten auch im Fall eines Mißerfolgs die Möglichkeit der operativen Therapie. Dem ist gegenüberzustellen, daß Patienten mit morphologisch stärker veränderten Klappen bei der Operation in der Regel einen Klappenersatz erhalten, da durch eine mißlungene Rekonstruktion kurzfristig eine Zweitoperation erforderlich würde. Kontraindikationen der Ballonmitralvalvuloplastie sind Thromben im linken Vorhof, eine vorbestehende Mitralinsuffizienz > Grad II und ausgeprägte destruktive Veränderungen oder fortgeschrittene Verkalkungen der Klappen. Somit stellt die Ballonmitralvalvuloplastie eine bedeutsame Erweiterung des Spektrums perkutaner Behandlungsverfahren kardiologischer Krankheitsbilder dar.

To handle massively parallel systems and make them usable, an adaptive, application-oriented operating system is required. The application orientedness is represented by the family concept of parallel operating systems. Incremental loading of operating system services supports the family character by automatically extending the system's active object structure when it is necessary. This way, also the switching between different operating system family members may be realized. A new active object will be incrementally loaded if its invocation fails because it does not yet exist. This is noticed during object binding while using the naming services. The use of the naming system is exploited and extended to get a flexible and configurable mechanism for triggering incremental loading. This mechanism is built by the freely definable naming strategies and exceptions that result again in a family, namely a family of naming services.

Abstract: A protein essential for pre-mRNA splicing, the U2 auxiliary factor (U2AF), is composed of a large and small subunit. Previously we cloned and characterized both subunits, spU2AF59 and spU2AF23, from fission yeast. We now report a novel U2AF-associated-protein, spUAP2, which interacts with both subunits. SpUAP2 contains a classical and a degenerate RNA recognition motif (RRM), both of which are required for interaction with spU2AF59. Interaction also requires the arginine/serine-rich region and the first RRM of spU2AF59. A null allele of the gene for spUAP2 is lethal.

In Schizosaccharomyces pombe11 different switching genes (swi1to swi10and rad22) are known which are involved in mating-type (MT) switching. Mutations in swi5, swi9, swi10and rad22also cause an increased radiation sensitivity. We tested whether the survival of these mutants after UV irradiation is influenced by caffeine. We included rad1and rad13mutants in our experiments which do not affect MT switching. Several double and triple mutants were constructed. We were able to assign the switching genes to different repair pathways: swi9and swi10are involved in excision repair, rad22has a function in recombination repair, while swi5appears to be involved in a hitherto unknown pathway. This ‘swi5pathway’ is stimulated (!) by caffeine. Previously it was found that the swi5mutation also reduces meiotic recombination. As to radgenes, we found a few inconsistencies with previous reports in the literature.

The swi1+ gene is necessary for effective mating-type (MT) switching in Schizosaccharomyces pombe. It was cloned on a 4.2 kb genomic DNA fragment. By site-directed integration into the genome and gene disruption experiments it was proved that the swi1+ gene itself and not a suppressor had been isolated. Disruption of the swi1+ gene causes a phenotype identical to that of the original swi1 mutant, i.e. the strain still shows some MT switching. The swi1 gene is unique in the genome and gives rise to a 3 kb mRNA.

In Schizosaccharomyces pombe, mutations in 10 swi genes are known which reduce but not abolish mating-type (MT) switching in homothallic (h90) strains. Three classes (Ia, Ib, and II) of swi genes are distinguished. Three swi1 alleles are nonsense mutations. In strains with mutations in two or three swi genes, a cumulative reduction of MT switching only occurs if the genes belong to different classes. The class 1a combinations swi1 swi7 and swi3 swi7 are lethal. Besides its influence on MT switching, swi5 also reduces the frequencies of meiotic intragenic recombination and gene conversion in the ade6 locus.

In Schizosaccharomyces pombe the frequency of mating-type (MT) switching is reduced by mutations in the swi genes. The ten hitherto known swi genes can be subdivided into three classes: Ia, Ib and II. Strains having swi5 (class Ib), swi9 (class II) and swi10 (class II) mutations do not only show reduced MT switching, but also exhibit an increased sensitivity to UV- and ?-rays. For that reason, 19 previously described rad genes were tested for their effect on MT switching. We found that swi9, “rad10”, “rad16” and “rad20” are allelic with each other indicating that the former allocation of these rad mutations to three different genes must have been erroneous. Among the remaining 16 rad genes examined, rad22 seems to be a new class II swi gene. The double mutants swi5 swi9 and swi5 swi10, but not swi9 swi10, are much more sensitive to radiation than the respective single mutants. Thus a cumulative increase in sensitivity occurs only if the mutants belong to different classes; previously the same correlation was found with regard to cumulative effects in MT switching.

The RAD52gene of Saccharomyces cerevisiaeis required for recombinational repair of double-strand breaks. Using degenerate oligonucleotides based on conserved amino acid sequences of RAD52 and rad22, its counterpart from Schizosaccharomyces pombe, RAD52homologs from man and mouse were cloned by the polymerase chain reaction. DNA sequence analysis revealed an open reading frame of 418 amino acids for the human RAD52 homolog and of 420 amino acid residues for the mouse counterpart. The identity between the two proteins is 69% and the overall similarity 80%. The homology of the mammalian proteins with their counterparts from yeast is primarily concentrated in the N-terminal region. Low amounts of RAD52RNA were observed in adult mouse tissues. A relatively high level of gene expression was observed in testis and thymus, suggesting that the mammalian RAD52 protein, like its homolog from yeast, plays a role in recombination. The mouse RAD52gene is located near the tip of chromosome 6 in region G3. The human equivalent maps to region p13.3 of chromosome 12. Until now, this human chromosome has not been implicated in any of the rodent mutants with a defect in the repair of double-strand breaks.

A clinical study was made of 29 cases of erythropoietic protoporphyria in 14 families. There were 14 female and 15 male patients. The disease set in during early infancy. In 51% of the cases, there were mild systemic symptoms. The clinical appearances were similar to those described by others, except that only four patients (14%) had vesicles and four (14%) had a petechial rash. Scarring was, in most cases, a prominent feature. Thirteen patients (45%) noticed abatement of the disease with advancing age. Five patients (17%) had a marked subsidence of symptoms during pregnancy, but there was no change in the protoporphyrin level. One patient had no lunulae and eight patients (28%) had acute nail changes during the skin attack.Protoporphyrin in the erythrocytes was elevated 10 to 100 times beyond the normal level. Results of liver function tests were normal in all patients, but liver biopsy, performed in one patient, disclosed a high content of porphyrin in the liver.

Meade and Gutz (1976) have described mat2:2 mutants of Schizosaccharomyces pombe having various defects in the Plus (P) function; four different classes were distinguished. Of special interest are the class II mutants in which none of the P mating-type functions is expressed. We made Southern analyses of 23 “class II” strains. In most of these, the P cassette and the K region are deleted as in h-s strains, however, some distinct differences were found as to the intensity of the bands in the blots (classes Ila, Ilb 1, and IIb2). The class Ilb mutants have strong bands characteristic of lethal deletions (h-L) and mat2:10 plasmids. Two “class II” mutants turned out to have a typical h90 mating-type region with an intact P cassette, but they seem to have a completely defective switching signal at matl:1 (new class V). Mutants of classes I, III, and IV yielded band patterns identical to those of an h90 strain; they obviously have point mutations in the P cassette.

In homothallic (h90) Schizosaccharomyces pombe strains mutants occur which exhibit reduced frequencies of mating-type switching. The colonies of such mutants show a mottled iodine reaction. The underlying mutations map either in a switching signal at matl or in switching (swi) genes which are not linked to the mating-type region. Forty-nine swi mutants were examined. They map in ten different swi genes, swi1 to swi10. Seven swi genes were assigned to chromosomes I and II, respectively. Two classes of swi genes can be distinguished: when plated, class I mutants yield only mottled colonies, whereas class Il mutants yield mottled and iodine-negative colonies (most of the latter are h1).

Objectives. We report the acute results and midterm clinical course after percutaneous transluminal septal myocardial ablation (PTSMA) in symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM).

• Granulomatous dermatitis with eosinophilia (Wells' syndrome) occurred in an 11-year-old boy. To our knowledge, eosinophilic cellulitis in a child in whom atrophic alopecia of the affected scalp later develops during the regression phase has not previously been reported. No notable effect of steroid therapy was observed. The cause of eosinophilic cellulitis is still unknown, but the presence of disseminated fibrinoid necrosis, vasculitis, eosinophilia, and a positive antinuclear factor test result might indicate an autoimmune or allergic disease.(Arch Dermatol 1981;117:427-429)

The switching gene swi5 has a function in mating-type switching. In addition, the swi5 mutation causes an increased radiation sensitivity and reduces meiotic recombination about ten-fold. Based on the latter property, an experimental protocol was developed for using swi5 in long-range mapping in S. pombe. It is suitable for a speedy mapping of any new gene which has not yet been cloned. The procedure was used to clarify the map positions of some genes.

Two cases of Aldrich's syndrome are reported. One is an eight-year-old boy who to our knowledge is older than any patient earlier reported with this syndrome.In both patients reported here, the diminished resistance to infections is constantly pronounced, mostly indicated by repeated otitis media attacks.Topical treatment of the skin with steroid ointments (partly under plastic occlusion) together with pure coal tar, has had a beneficial effect.In both patients the titer of isoagglutinins is significantly reduced.

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TO THE EDITOR.— W. L. Macaulay has stated (unpublished data) that 59 cases of lymphomatoid papulosis, or as he has named it, "Rhythmic Paradoxical Eruptions," have now been reported. How many of these patients with an apparently benign clinical course but histopathologic findings indicating malignancy eventually turn out to have malignancies is still a controversial question. Usually, lymphomatoid papulosis presents itself as a skin condition resembling Mucha-Habermann disease, and only a few cases have been mentioned in which lymphomatoid papulosis occurred with other dermatoses.1The following is a report of two additional cases of lymphomatoid papulosis occurring on top of erythro-derma and parapsoriasis en plaque. REPORT OF CASES.—CASE 1.— A 64-year-old man had erythroderma for seven years. The etiology had never been established, but because of an associated pigmentincontinens, a pigmented contact dermatitis was suspected. During six years, dull-red nodules about 1 cm in diameter have recurred on various parts of the trunk and proximal extremities with a life-cycle of

TO THE EDITOR.— In Danish prisons, tattoo colors and instruments are forbidden. However, some prisoners constructed tattooing instruments by mounting steel needles on electric shavers. Owing to the lack of standard pigments, the prisoners improvised, viz, they used a paint that is used for posters, for hobby crafts and for decoration.The poster paint is available in scarlet and dark green, and is used for hobby work in the prison. The scarlet paint contains color index (CI) pigments 3, 4, and 95, all of which are monoazopigments, whereas the dark green paint contains CI yellow 1, which is a monoazopigment, CI 7, and CI blue 15, both of which are phthalocyanine pigments. Both poster paints contain chalk, dolomite, and casein as binders, and the preservative 0.4% chlormetacresol.In 1973, seven prisoners were referred to the Department of Dermatology, Odense University Hospital, Odense, Denmark, for treatment of ulcerating, itching skin tumors

Summary: We present a Systems Biology Toolbox for the widely used general purpose mathematical software MATLAB. The toolbox offers systems biologists an open and extensible environment, in which to explore ideas, prototype and share new algorithms, and build applications for the analysis and simulation of biological and biochemical systems. Additionally it is well suited for educational purposes. The toolbox supports the Systems Biology Markup Language (SBML) by providing an interface for import and export of SBML models. In this way the toolbox connects nicely to other SBML-enabled modelling packages. Models are represented in an internal model format and can be described either by entering ordinary differential equations or, more intuitively, by entering biochemical reaction equations. The toolbox contains a large number of analysis methods, such as deterministic and stochastic simulation, parameter estimation, network identification, parameter sensitivity analysis and bifurcation analysis. Availability: The Systems Biology Toolbox for MATLAB is open source and freely available from http://www.sbtoolbox.org. The website also contains a tutorial, extensive documentation and examples. Contact: henning@fcc.chalmers.se

Only four prp (pre-mRNA processing) genes of the fission yeast Schizosaccharomyces pombe have been reported. We exploited yeast genetics and identified and isolated the prp4 gene. Sequence analysis revealed that the splicing factor encoded by this gene contains the signature sequences that define the serine/ threonine protein kinase family. This is the first kinase gene identified whose product is involved in pre-mRNA splicing. The prp4 gene contains one intron in the kinase domain. Gene replacement studies provided evidence that this gene is essential for growth and is located on chromosome III.

In human cells DNA damage caused by UV light is mainly repaired by the nucleotide excision repair pathway. This mechanism involves dual incisions on both sides of the damage catalyzed by two nucleases. In mammalian cells XPG cleaves 3′ of the DNA lesion while the ERCC1-XPF complex makes the 5′ incision. The amino acid sequence of the human excision repair protein ERCC1 is homologous with the fission yeast Swi10 protein. In order to test whether these proteins are functional homologues, we overexpressed the human gene in a Schizosaccharomyces pombe swi10 mutant. A swi10 mutation has a pleiotropic effect: it reduces the frequency of mating type switching (a mitotic transposition event from a silent cassette into the expression site) and causes increased UV sensitivity. We found that the full-length ERCC1 gene only complements the transposition defect of the fission yeast mutant, while a C-terminal truncated ERCC1 protein also restores the DNA repair capacity of the yeast cells. Using the two-hybrid system of Saccharomyces cerevisiae we show that only the truncated human ERCC1 protein is able to interact with the S.pombe Rad16 protein, which is the fission yeast homologue of human XPF. This is the first example yet known that a human gene can correct a yeast mutation in nucleotide excision repair.

The switching gene swi10+ has a function in matingtype switching as well as in the repair of radiation damages. We have cloned the genomic swi10+ gene by functional complementation of the switching defect of the swi10-154 mutant. The swi10+ gene is not essential for viability. The DNA sequence revealed an open reading frame of 759 nucleotides interrupted by three introns of 127, 52 and 60 bp, respectively. The positions of intron I as well as of intron III of swi10 are evolutionary conserved in comparison to the introns III and IV of the human ERCC1 gene. The analysis of cDNA clones isolated by PCR amplification confirmed the structure of the swi10 gene. The putative Swi10 protein has homologies to the human and mouse ERCC1 protein, to Rad10 of Saccharomyces cerevisiae and to parts of UvrA and UvrC of E.coli. All these proteins are essential components for excision repair of damaged DNA. The swi10 protein contains a putative DNA binding domain previously found in other proteins. Northern blot experiments and the analyses of cDNA clones indicate that intron I of the swi10 gene is not efficiently spliced.

Degenerate oligonucleotides encoding conserved regions of the Rad52 protein of S.cerevisiae and its homologue, the Rad22 protein of S.pombe, were used to clone a chicken RAD52 counterpart by the polymerase chain reaction. Sequence comparison of the chicken and yeast proteins reveals a strongly conserved region between positions 40 and 178 of the chicken Rad52 sequence indicating that this part of the protein is under strong evolutionary pressure. The first 39 amino acids and the 3' end of the chicken Rad52 homologue does not share significant similarity with the yeast proteins. High abundance of the mRNA in testis makes it likely that the chicken Rad52 protein plays a role in meiotic recombination.

The gene rad22 of the fission yeast Schizosaccharomycespombe has a function in DNA repair and matingtype switching. We have cloned the rad22 gene from a genomic gene bank by functional complementation of the switching defect. An open reading frame coding for a putative protein of 469 amino acids was found by sequence analyses. The rad22 gene contains no intron. A region of 126 amino acids in the N-terminal half of the Rad22 protein has significant homologies (56% identity and 36% similarity) to the Rad52 protein of Saccharomyces cerevisiae. A rad22 disruption strain was constructed which seems to be inviable in a homothallic background. Southern blot analyses have shown that the rad22-67 mutant frequently gives rise to deletions in the mating-type region. These data indicate that the Rad22 protein has a function in the repair of DNA double-strand breaks.