The role of pneumolysin and autolysin in the pathology of pneumonia and septicemia in mice infected with a type 2 pneumococcus

Mice were infected intranasally with a serotype 2 pneumococcus, a pneumolysin-negative derivative (PLN-A), or an autolysin-negative derivative (AL-2). Numbers of wild type pneumococci were seen in the lung from approximately 12 h after infection and were first detected in the blood around this time. Immunofluorescent staining of lung sections showed that pneumolysin was produced in vivo. Pneumococcal infection resulted in alteration of the composition of the blood but not the bone marrow. Some of the hematologic changes did not occur after PLN-A. PLN-A had a slower growth rate in the lung and bacteremia was delayed. AL-2 was rapidly cleared from the lungs and was not detected in the blood. These events paralleled the pattern of histology in the lung, with the severity of inflammation reduced with PLN-A and no inflammation or hematologic changes with AL-2.     

Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity

We here demonstrated the prophylactic effect of an extract (KM-110) from Viscum album coloratum, a Korean mistletoe, on tumor metastasis produced by highly metastatic tumor cells, colon 26-M3.1 carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, using experimental models in mice. Intravenous (i.v.) administration of KM-110 (100 microg/mouse) 2 days before tumor inoculation significantly inhibited lung metastasis of B16-BL6 and colon 26-M3.1 cells, and liver and spleen metastasis of L5178Y-ML25 cells. The prophylactic effect of KM-110 on tumor metastasis was evident with various administration routes, i.e. subcutaneous, oral, intranasal as well as i.v., and was dependent upon the dose of KM-110 administered. Furthermore, mice given KM-110 (100 microg) 2 days before tumor inoculation showed significantly prolonged survival rates compared with the untreated mice. In a time course analysis of NK activity, i.v. administration of KM-110 (100 microg) significantly augmented NK cytotoxicity to Yac-a tumor cells from 1 to 3 days after KM-110 treatment. Furthermore, depletion NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of KM-110 on lung metastasis of colon 26-M3.1 cells. These results suggest that KM-110 possesses immunopotentiating activity which enhances the host defense system against tumors, and that its prophylactic effect on tumor metastasis is mediated by NK cell activation.     

Studies on modeling and control of spouted bed reactors—II: Control

Control and operability characteristics of an adiabatic spouted bed reactor with a first order reaction are investigated. The reactor transient response to changing operating conditions is analyzed and the generic control problems are formulated. Reduced-order state space models suitable for process control studies are constructed by utilizing the methods of orthogonal collocation and singular perturbation.Based on modern control and estimation techniques a hierarchy of different control systems is systematically generated. The assessment of alternative d     

Solving job shop scheduling with setup times through constraint-based iterative sampling: an experimental analysis

This paper presents a heuristic algorithm for solving a job-shop scheduling problem with sequence dependent setup times and min/max separation constraints among the activities (SDST-JSSP/max). The algorithm relies on a core constraint-based search procedure, which generates consistent orderings of activities that require the same resource by incrementally imposing precedence constraints on a temporally feasible solution. Key to the effectiveness of the search procedure is a conflict sampling method biased toward selection of most critical conflicts and coupled with a non-deterministic choice heuristic to guide the base conflict resolution process. This constraint-based search is then embedded within a larger iterative-sampling search framework to broaden search space coverage and promote solution optimization. The efficacy of the overall heuristic algorithm is demonstrated empirically both on a set of previously studied job-shop scheduling benchmark problems with sequence dependent setup times and by introducing a new benchmark with setups and generalized precedence constraints.     

Incremental construction of minimal deterministic finite cover automata

We present a fast incremental algorithm for constructing minimal Deterministic Finite Cover Automata (DFCA) for a given language. Since it was shown that the minimal DFCA for a language L has less states than the minimal Deterministic Finite Automata (DFA) for the same language L, this technique seems to be the best choice for incrementally building the automaton for a large language, especially when the number of states in the DFCA is significantly less than the number of states in the corresponding minimal DFA. We have implemented the proposed algorithm and have tested it against the best-known DFCA minimization technique.     

Determination of squeeze film damping in capacitance-based cantilever force probes

Capacitance-based techniques are increasingly being used as the sensing method for low-force probes. Because the gap between electrodes is generally very small, relative motion between two electrode surfaces results in squeeze film forces that can provide an effective damping action. Recent investigations of the effect of damping on the fidelity of stylus measurement indicates that optimal dynamic conditions correspond to a system critical damping ratio between 0.4 and 0.8. This paper presents a theoretical analysis of the squeeze film forces between a cantilever beam and adjacent solid surface during lateral vibration based on an assumed mode of deflection. Two mode shapes were computed, one using the static beam deflection curve and the other the fundamental mode shape of a continuous prismatic beam. Experiments were carried out on 11 samples, of which 3 were too heavily damped for a realistic estimate of damping ratio. Comparison with calculated results revealed an absolute worst-case error of 0.063 in the damping ratio, with a standard deviation of 0.0175, which is considered to be within experimental error.     

Tyrosine-dependent and -independent mechanisms of STAT3 activation by the human granulocyte colony-stimulating factor (G-CSF) receptor are differentially utilized depending on G-CSF concentration

The granulocyte colony-stimulating factor receptor (G-CSF-R) activates multiple STAT proteins. Although the membrane-proximal cytoplasmic region of the G-CSF-R is necessary and sufficient for activation of STAT1 and STAT5, activation of STAT3 requires the membrane distal region that contains four tyrosines. Although one of these (Y704) has previously been shown to be involved in STAT3 activation from a truncated G-CSF-R derived from a patient with severe chronic neutropenia (SCN), this tyrosine is not required for STAT3 activation by the full-length G-CSF-R. To investigate possible alternative mechanisms of STAT3 activation, we generated a series of Ba/F3 cell transfectants expressing the wild-type G-CSF-R or mutant receptors that either completely lack tyrosines or retain just one of the four cytoplasmic tyrosines of the G-CSF-R. We show that, at saturating G-CSF concentrations, STAT3 activation from the full-length G-CSF-R is efficiently mediated by the C-terminal domain in a manner independent of receptor tyrosines. In contrast, at low G-CSF concentrations, Y704 and Y744 of the G-CSF-R play a major role in STAT3 activation. Both tyrosine-dependent and -independent mechanisms of STAT3 activation are sensitive to the Jak2 inhibitor AG-490, follow similar kinetics, and lead to transactivation of a STAT3 reporter construct, indicating functional equivalence. STAT3 activation is also impaired, particularly at nonsaturating G-CSF concentrations, in bone marrow cells from mice expressing a truncated G-CSF-R (gcsfr-triangle up715). These findings suggest that G-CSF-induced STAT3 activation during basal granulopoiesis (low G-CSF) and "emergency" granulopoiesis (high G-CSF) are differentially controlled. In addition, the data establish the importance of the G-CSF-R C-terminus in STAT3 activation in primary cells, which has implications for understanding why truncated G-CSF-R derived from SCN patients are defective in maturation signaling.     

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study

Simultaneous extracellular recordings were performed in stratum radiatum and stratum pyramidale of hippocampal slices 7 days following unilateral intracerebroventricular injections of kainic acid. In this ex vivo experimental model of human temporal lobe epilepsy, stimulation of the surviving commissural fibres in stratum radiatum produced graded epileptiform activity in the CA1 area. The oxidizing reagent 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) acting at NMDA receptors redox sites decreases NMDA receptor-mediated responses by half and suppresses evoked epileptiform discharges. We have examined the effect of DTNB on NMDA-dependent bidirectional synaptic plasticity and EPSP/spike coupling. DTNB treatment did not prevent either long-term potentiation induced by tetanic stimulation or long-term depression induced by low frequency stimulation of field EPSPs. Application of DTNB alone did not induce EPSP/spike dissociation. However, both high and low frequency stimulations induced EPSP/spike potentiation indicating that neurons had a high probability to discharge in synchrony. These results suggest that oxidizing reagents may provide novel antiepileptic treatments since they decrease NMDA-dependent evoked epileptiform activity but do not interfere with either NMDA-dependent synaptic plasticity or the probability of synchronous discharge.