Knowledge acquisition from text in a complex domain

Complex real world domains can be characterized by a large amount of data, their interactions and that the knowledge must often be related to concrete problems. Therefore, the available descriptions of real world domains do not easily lend themselves to an adequate representation. The knowledge which is relevant for solving a given problem must be extracted from such descriptions with the help of the knowledge acquisition process. Such a process must adequately relate the acquired knowledge to the given problem. An integrated knowledge acquisition framework is developed to relate the acquired knowledge to real world problems. The interactive knowledge acquisition tool COKAM+ is one of three acquisition tools within this integrated framework. It extracts the knowledge from text, provides a documentation of the knowledge and structures it with respect to problems. All these preparations can serve to represent the obtained knowledge adequately

Clamping, COKAM, KADS, and OMOS : the construction and operationalization of a KADS conceptual model

For a simplified version of the clamping tool selection problem in mechanical engineering, the knowledge acquisition tool COKAM is applied to obtain an informal knowledge base and explanation structures from technical documents and previously solved cases. The output of COKAM is used to construct a three layered KADS conceptual model, which is then transformed into an operational model in the language OMOS. The OMOS formalization allows to verify the informal KADS conceptual model and to check the completeness of the domain knowledge. The results of this analysis are utilized in the next knowledge elicitation session with COKAM

Integrated knowledge acquisition from text, previously solved cases, and expert memories

Within the model-based knowledge engineering framework, an integrated knowledge acquisition method was developed for a complex real-world domain with different traces of expertise. By having an expert constructively explain the previously solved cases with more general information from other traces of expertise (text, expert memories) a model-centered knowledge base is constructed. The proposed method allows for an early knowledge verification where the relevance, sufficiency, redundancy, and consistency of knowledge are already assessed at an informal level. The early knowledge verification efficiently prepares the consecutive knowledge formalization. Through a cognitively adequate model of expertise and the explanation-oriented knowledge elicitation procedures, user friendly second generation expert systems may be developed

Identifizierung potentieller Zielgene des Transkriptionsfaktors Sp3 in vitro und in vivo

Der ubiquitär vorkommende Transkriptionsfaktor Sp3 (Specificity protein) sowie Sp1, Sp2 und Sp4 gehören zu einer Protein-Familie, die an Sequenzen auf der DNA wie die GC-Box oder die GT-Box binden. Die Proteine dieser Familie besitzen große strukturelle Gemeinsamkeiten. Ihre DNA-Bindungsdomänen am C-Terminus sind hoch konserviert und bestehen aus drei Zinkfingern von Cys2/His2-Typ. N-terminal befinden sich je zwei -bei Sp2 nur eine- glutaminreiche Regionen, die als Aktivierungsdomänen dienen. Für Sp3 existiert darüber hinaus eine weitere funktionelle Domäne zwischen den glutaminreichen Regionen und den Zinkfingern. Dieser Abschnitt wirkt als inhibitorische Domäne und ist in der Lage die Transaktivierung durch die glutaminreichen Aktivierungsdomänen zu reprimieren. Die Sp3-defizienten Tiere sterben unmittelbar nach der Geburt. Sie sind in der Embryonalentwicklung gegenüber den Wildtyp-Tieren zurückgeblieben und deutlich kleiner. Es gibt Hinweise auf eine Retardierung einzelner Organe. In histologischen Schnitten konnte gezeigt werden, daß die Zahnentwicklung in Sp3-defizienten Mäusen nicht so weit fortgeschritten ist wie bei den vergleichbaren Wildtyp-Tieren. Bei neugeborenen Mäusen konnte eine Atembewegung festgestellt werden, die jedoch nicht dazu führte, daß Luft in die Lungen der Tiere gelangte. Bei histologischen Untersuchungen konnte in der Lunge von Wildtyp-Mäusen ein weites Alveolarlumen beobachtet werden, während das Lumen in Lungen von Sp3-defizienten Mäusen eng war und das Septum zwischen den Alveolen verdickt zu sein schien. Ziel der Arbeit war es, die Expression verschiedener Gene in Sp3-defizienten und Wildtyp-Mäusen zu untersuchen, um potentielle Zielgene des Transkriptionsfaktors beschreiben zu können. Der Phänotyp der Sp3-defizienten Mäuse deutet auf Veränderungen in der Lunge hin. Auf Grund dieser Beobachtung sollte die Expression von Lungenproteinen in vivo in Sp3(-/-)-Mäusen mit der in Sp3(+/+)-Mäusen verglichen werden, um mögliche Erklärungen für den beschriebenen Phänotyp zu erhalten. In einem Versuch mit Sp3-defizienten und Wildtyp-embryonalen Maus-Stammzellen konnte ein potentielles Zielgen von Sp3 identifiziert werden: Preadipozytenfaktor-1 (Pref-1). Im Rahmen dieser Arbeit sollte überprüft werden, ob die Expression der Pref-1 mRNA in einem anderen Zellkultursystem, in Maus-Fibroblastenzellen, auch von der Anwesenheit des Transkriptionsfaktors Sp3 abhängig ist. Pref-1 spielt eine Rolle bei der Adipozytendifferenzierung. Es sollte deshalb getestet werden, ob sich Sp3-defiziente und Wildtyp-Fibroblastenzellen gleichermaßen zu Adipozyten differenzieren lassen

Integrated knowledge acquisition for lathe production planning : a picture gallery

Diese Bildergalerie veranschaulicht den Einsatz der im ARC-TEC Projekt entwickelten integrativen Wissensakquisitionsmethode. Geleitet durch ein Modell der Expertise, wird das Wissen zur Fertigungsplanung für Drehteile aus Texten, Fallsammlungen und Expertenurteilen akquiriert. Drei aufeinander abgestimmte Tools unterstützen die Erhebung, Dokumentation, Überprüfung und Formalisierung des relevanten Wissens.This picture gallery illustrates the application of the integrated knowledge acquisition procedure which was developed in the ARC-TEC project. Guided by a model of expertise, the knowledge for lathe production planning is acquired from texts, previously solved cases, and expert memories. Three coordinated tools support the elicitation, documentation, verification and formalization of the relevant knowledge

Engineering NK Cells for CAR Therapy—Recent Advances in Gene Transfer Methodology

The development of chimeric antigen receptor (CAR) T cell therapy has introduced a new and effective strategy to guide and promote the immune response against tumors in the clinic. More recently, in an attempt to enhance its utility, this method has been expanded to novel cell types. One of the more successful variants has proven to be the expression of CARs in Natural Killer (NK) cells (CAR-NK). Gene engineering NK cells to express an exogenous CAR receptor allows the innate anti-tumor ability of NK cells to be harnessed and directed against a target tumor antigen. In addition, the biology of NK cells allows the development of an allogeneic cell therapeutic product useable with most or all patient haplotypes. NK cells cause little or no graft versus host disease (GvHD) and are therefore suitable for development of an "off the shelf" therapeutic product. Initial trials have also shown that CAR-NK cells rarely cause cytokine release syndrome. However, despite their potential NK cells have proven to be difficult to engineer, with high sensitivity to apoptosis and low levels of gene expression. The creation of optimized methods to introduce genes into NK cells will promote the widespread application of CAR-NK in research laboratories and the clinics

Using integrated knowledge acquisition to prepare sophisticated expert plans for their re-use in novel situations

Plans which were constructed by human experts and have been repeatedly executed to the complete satisfaction of some customer in a complex real world domain contain very valuable planning knowledge. In order to make this compiled knowledge re-usable for novel situations, a specific integrated knowledge acquisition method has been developed: First, a domain theory is established from documentation materials or texts, which is then used as the foundation for explaining how the plan achieves the planning goal. Secondly, hierarchically structured problem class definitions are obtained from the practitioners\u27 highlevel problem conceptualizations. The descriptions of these problem classes also provide operationality criteria for the various levels in the hierarchy. A skeletal plan is then constructed for each problem class with an explanation-based learning procedure. These skeletal plans consist of a sequence of general plan elements, so that each plan element can be independently refined. The skeletal plan thus accounts for the interactions between the various concrete operations of the plan at a general level. The complexity of the planning problem is thereby factored in a domain-specific way and the compiled knowledge of sophisticated expert plans can be re-used in novel situations