A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

From information to probability: An axiomatic approach—Inference is information processing

We define the very rich language of composed conditionals on a three‐valued logic and use this language as the communication tool between man and machine. Communication takes place for three reasons: knowledge acquisition, query, and response. Learning, thinking, and answering questions are of a pure information theoretical nature. The pivot of this knowledge processing concept is the amount of information (bit) we receive if a conditional becomes true. We follow an axiomatic approach to information theory rather than the classical probabilistic approach of Shannon; information comes first, and then comes probability. In the light of this philosophy, query and response experience new interpretations. Both, acquisition and response are realized by maximizing entropy and minimizing relative entropy, respectively. The iterative solution of these mathematical optimization problems gives new insights into the adaptation of prior knowledge to new information. Our expert system shell SPIRIT supports this kind of knowledge processing, which will be established by suitable examples. © 2003 Wiley Periodicals, Inc.     

Wide-band symmetrical analog multiplier IC for coherentoptical-fiber receivers operating up to 10 Gb/s

A versatile analog four-quadrant multiplier IC with large bandwidth (DC to 6 GHz and 10 Gb/s) and large dynamic range is presented. It was mainly developed for differential-phase-shift-keying (DPSK) phase demodulator and polarization diversity receivers in coherent optical-fiber transmission systems. The circuit consumes 450 mW and only needs a single power supply of -5 V. The circuit principle used allows exact symmetry with respect to both linear inputs, which reduced multiplication errors. In the intended application, especially, the time jitter and the offset voltage of the output pulse patterns are reduced to negligible values. The IC was realized in a 1.25-μm double-polysilicon bipolar technology     

Presence of pressure ulcer prevention methods used among patients considered at risk versus those considered not at risk

PURPOSE: This study examined pressure ulcer-prevention strategies available for patients considered at risk versus those considered not at risk. DESIGN: The study used a prospective, longitudinal design. SETTING AND SUBJECTS: Six hundred ninety-four patients from units of five acute care hospitals, a rehabilitation facility, and two nurses' home care caseloads participated in the investigation. INSTRUMENTS: Data-collection instruments included the Braden Scale for risk assessment, demographic information, and the Pressure Ulcer-Prevention Strategies tool, which assessed for the presence of 16 pressure ulcer-prevention strategies. METHODS: All patients admitted to a participating unit during a 2-month period were followed up until discharge. Depending on the site, patients were assessed for the presence of pressure ulcer-prevention strategies one to three times per week. RESULTS: Patients in the at-risk group versus those in the not-at-risk group were more likely (p < 0.01) to have the head of the bed in a low position, a pressure-reducing bed surface, pressure ulcer prevention charted, a positioning wedge, incontinence cleanser and ointment, heel protection, a prevention care plan, a trapeze, and a posted turning schedule. The at-risk group had significantly (p < 0.01) more prevention strategies present than did the not-at-risk group. However, the percentage of patients placed on a pressure ulcer-prevention program was low for both groups. CONCLUSIONS: Pressure ulcer prevention was evident for the at-risk group, but at a low rate. Institutions must continue to explore this critical area affecting patient outcomes.     

Fast, large-scale model predictive control by partial enumeration

Partial enumeration (PE) is presented as a method for treating large, linear model predictive control applications that are out of reach with available MPC methods. PE uses both a table storage method and online optimization to achieve this goal. Versions of PE are shown to be closed-loop stable. PE is applied to an industrial example with more than 250 states, 32 inputs, and a 25-sample control horizon. The performance is less than 0.01% suboptimal, with average speedup factors in the range of 80-220, and worst-case speedups in the range of 4.9-39.2, compared to an existing MPC method. Small tables with only 25-200 entries were used to obtain this performance, while full enumeration is intractable for this example.     

Semiconductor laser amplifier as optical switching gate

The properties of a semiconductor laser amplifier as optical switching gate are investigated. Particular attention is paid to gain, contrast ratio, and switching time of the device. These properties are studied experimentally and theoretically with respect to the injection current, optical input power, and cavity resonances. The experimental arrangements and the theoretical method are described. As an example of the various applications of semiconductor laser amplifier gates, packet switching experiments with self-routing, employing cascaded switching gates, are reported. In a theoretical analysis the restrictions that the properties of semiconductor laser amplifier gates impose on a larger switching system consisting of many such gates are investigated     

Semantical investigations into nonmonotonic and probabilistic logics

Different forms of semantics have been proposed for conditionals of the form “Usually, if A then B”, ranging from quantitative probability distributions to qualitative approaches using plausibility orderings, possibility distributions, or conditional objects. Atomic-bound systems, also called big-stepped probabilities, allow qualitative reasoning with probabilities, aiming at bridging the gap between qualitative and quantitative argumentation and providing a model for the nonmonotonic reasoning system P. By using Goguen and Burstall’s notion of institutions for the formalization of logical systems, we elaborate precisely which formal connections exist among big-stepped probabilities, standard probabilities, and qualitative logics. Based on our investigations, we also develop two variants of conditional objects, one of them having a simpler semantics while still providing a model for system P.