281 research outputs found
Minimizing weighted total earliness, total tardiness and setup costs
The paper considers a (static) portfolio system that satisfies adding-up contraints and the gross substitution theorem. The paper shows the relationship of the two conditions to the weak dominant diagonal property of the matrix of interest rate elasticities. This enables to investigate the impact of simultaneous changes in interest rates on the asset demands.
Status report of the three phase 25 kA, 1.5 kW thermally switched superconducting rectifier, transformer and switches
A 25 kA, 1.5 kW superconducting rectifier system has been developed. This rectifier system working like an a.c.-d.c, converter with a primary current of 35 A at 0.1Hz, will energize a 25 kA coil with an average power of 5.4 MJ/hr and a proposed energy efficiency of at least 96%. Such a highly efficient device might work instead of a 'normal' rectifier and a pair of 25 kA current leads with its energy loss of at least 2 W/kA. The 25 kA current step-up transformer has been tested succesfully concerning its maximum current (26.4 kA) and a.c. losses (2 W at 25 kA and 0.1Hz). A conductor for the 25 kA switches has been manufactured and processed into the switching system. Their construction is described
A 25 kA, 2T, 78 kJ, 52 litre superconducting test coil. Strength calculations and construction
Within the scope of our research program for a 25 kA superconducting rectifier, we have built a 25 kA s.c. coil being a single layer solenoid with a bore of 0.45 meter and a volume of 52 litre. The starting point for the design was to avoid any metallic structural material. This unique coil consists of 26 turns of a Rutherford cable in one layer covered at the outside with 6 millimeter glassfibre reinforced epoxy, in order to lower the azimuthal and axial stresses in the conductor to acceptable values. The coil has been vacuum impregnated with a glassfilling factor of 0.529. The paper describes the strength calculations and the construction details. A theoretical analysis of the mechanical behaviour of the glassfibre-epoxy-conductor lamination is given
Liposomal amphotericin B (AmBisome) reduces dissemination of infection as compared with amphotericin B deoxycholate (Fungizone) in a rate model of pulmonary aspergillosis
The efficacy of AmBisome, a liposomal formulation of amphotericin B, was
compared with that of Fungizone (amphotericin B desoxycholate), in a rat
model of unilateral, pulmonary aspergillosis. Repeated administration of
cyclophosphamide resulted in persistent, severe granulocytopenia. The left
lung was inoculated with a conidial suspension of Aspergillus fumigatus,
thus establishing an unilateral infection. Antifungal treatment was
started 40 h after fungal inoculation, at which time mycelial disease was
confirmed by histological examination. Both Fungizone 1 mg/kg and AmBisome
10 mg/kg resulted in increased survival in terms of delayed as well as
reduced mortality. Quantitative cultures of lung tissue showed that only
AmBisome 10 mg/kg resulted in reduction of the number of fungal cfus in
the inoculated left lung. Compared with Fungizone, both AmBisome 1
mg/kg/day and AmBisome 10 mg/kg/day significantly prevented dissemination
from the infected left lung to the right lung. In addition, both AmBisome
regimens reduced hepatosplenic dissemination, and the 10 m/kg dosage fully
prevented this complication. In conclusion, when compared with Fungizone,
in this model AmBisome is more effective in reducing dissemination of
unilateral, pulmonary aspergillosis, even when given in relatively low
dosage. Such low dosages may have a place in prophylactic settings
In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime
Antimicrobial agents may interact synergistically. But to ensure synergy
in vivo, the drugs should both be present at the site of infection at
sufficiently high concentrations for an adequate period of time.
Coencapsulation of the drugs in a drug carrier may ensure parallel tissue
distributions. Since liposomes localize preferentially at sites of
infection, this mode of drug delivery could, in addition, increase drug
concentrations at the focus of infection. The therapeutic efficacy of
gentamicin and ceftazidime coencapsulated into liposomes was examined by
monitoring survival in a rat model of an acute unilateral pneumonia caused
by antibiotic-susceptible and antibiotic-resistant Klebsiella pneumoniae
strains. It is shown that administration of gentamicin in combination with
ceftazidime in the free form either as single dose or as 5-day treatment
resulted in an additive effect on rat survival in both models. In
contrast, targeted delivery of liposome-coencapsulated gentamicin and
ceftazidime resulted in a synergistic interaction of the antibiotics in
both models. Consequently, liposome coencapsulation of gentamicin and
ceftazidime allowed both a shorter course of treatment at lower cumulative
doses compared with administration of the antibiotics in the free form to
obtain complete survival of rats. Liposomal coencapsulation of synergistic
antibiotics may open new perspectives in the treatment of severe
infections
Addition of 17-(allylamino)-17-demethoxy-geldanamycin to a suboptimal caspofungin treatment regimen in neutropenic rats with invasive pulmonary aspergillosis delays the time to death but does not enhance the overall therapeutic efficacy
Caspofungin (CAS) which is used as salvage therapy in patients with invasive pulmonary aspergillosis (IPA) inhibits the 1,3-β-D-glucan synthesis in Aspergillus fumigatus. Inhibiting 1,3-β-D-glucan synthesis induces a stress response and in an invertebrate model it was demonstrated that inhibiting this response with geldamycin enhanced the therapeutic efficacy of CAS. Since geldamycin itself is toxic to mammalians, the therapeutic efficacy of combining geldamycin with CAS was not studied in rodent models. Therefore in this study we investigated if the geldamycin derivate 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) was able to enhance the therapeutic efficacy of CAS in vitro and in our IPA model in transiently neutropenic rats. In vitro we confirmed the earlier demonstrated synergy between 17-AAG and CAS in ten A. fumigatus isolates. In vivo we treated A. fumigatus infected neutropenic rats with a sub-optimal dose of 0.75 mg/kg/day CAS and 1 mg/kg/day 17-AAG for ten days. Survival was monitored for 21 days after fungal inoculation. It appeared that the addition 17-AAG delayed death but did not improve overall survival of rats with IPA. Incre
Evidence Supporting a Role for Mammalian Chitinases in Efficacy of Caspofungin against Experimental Aspergillosis in Immunocompromised Rats
Objectives:Caspofungin, currently used as salvage therapy for invasive pulmonary aspergillosis (IPA), strangely only causes morphological changes in fungal growth in vitro but does not inhibit the growth. In vivo it has good efficacy. Therefore the question arises how this in vivo activity is reached. Caspofungin is known to increase the amount of chitin in the fungal cell wall. Mammals produce two chitinases, chitotriosidase and AMCase, which can hydrolyse chitin. We hypothesized that the mammalian chitinases play a role in the in vivo efficacy of caspofungin.Methods:In order to determine the role of chitotriosidase and AMCase in IPA, both chitinases were measured in rats which did or did not receive caspofungin treatment. In order to understand the role of each chitinase in the breakdown of the caspofungin-exposed cells, we also exposed caspofungin treated fungi to recombinant enzymes in vitro.Results:IPA in immunocompromised rats caused a dramatic increase in chitinase activity. This increase in chitinase activity was still noted when rats were treated with caspofungin. In vitro, it was demonstrated that the action of both chitinases were needed to lyse the f
Distinctive Cytokines as Biomarkers Predicting Fatal Outcome of Severe Staphylococcus aureus Bacteremia in Mice
Invasive Staphylococcus aureus infections are frequently associated with bacteraemia. To support clinical decisions on antibiotic therapy, there is an urgent need for reliable markers as predictors of infection outcome. In the present study in mice, bacteraemia was established by intravenous inoculation of a clinical S. aureus isolate at the LD50 inoculum. As potential biomarkers for fatal outcome, blood culture (qualitative and quantitative), serum levels of C-reactive protein (CRP), as well as 31 selected cytokines and chemokines were assessed during the first three days of infection. A positive S. aureus blood culture, the quantitative blood culture, CRP levels, and levels of eight cytokines were indicative for the presence of S. aureus bacteraemia. However, only tumor necrosis factor (TNF) α, interleukin (IL) 1α, and keratinocyte chemoattractant (KC; a functional homologue of human IL-8) were each significantly elevated in eventually non-surviving infected mice versus eventually surviving infected mice. In severe S. aureus bacteraemia in mice, TNF-α, IL-1α, and KC are biomarkers predicting fatal outcome of infection. KC was a biomarker elevated irrespective the progression of infection, which is very interesting regarding clinical application in view of the heterogeneity of patients experiencing bacteraemia in this respect
Value of cyclin A immunohistochemistry for cancer risk stratification in Barrett esophagus surveillance A multicenter case-control study
The value of endoscopic Barrett esophagus (BE) surveillance based on histological diagnosis of low-grade dysplasia (LGD) remains
debated given the lack of adequate risk stratification. The aim of this study was to evaluate the predictive value of cyclin A expression
and to combine these results with our previously reported immunohistochemical p53, AMACR, and SOX2 data, to identify a panel of
biomarkers predicting neoplastic progression in BE.
We conducted a case–control study within a prospective cohort of 720 BE patients. BE patients who progressed to high-grade
dysplasia (HGD, n=37) or esophageal adenocarcinoma (EAC, n=13), defined as neoplastic progression, were classified as cases
and patients without neoplastic progression were classified as controls (n=575). Cyclin A expression was determined by
immunohistochemistry in all 625 patients; these results were combined with the histological diagnosis and our previous p53,
AMACR, and SOX2 data in loglinear regression models. Differences in discriminatory ability were quantified as changes in area under
the ROC curve (AUC) for predicting neoplastic progression.
Cyclin A surface positivity significantly increased throughout the metaplasia–dysplasia–carcinoma sequences and was seen in 10%
(107/1050) of biopsy series without dysplasia, 33% (109/335) in LGD, and 69% (34/50) in HGD/EAC. Positive cyclin A expression was
associated with an increased risk of neoplastic progression (adjusted relative risk (RRa) 2.4; 95% CI: 1.7–3.4). Increases in AUC were
substantial for P53 (+0.05), smaller for SOX2 (+0.014), minor for cyclin A (+0.003), and none for AMARC (0.00).
Cyclin A immunopositivity was associated with an increased progression risk in BE patients. However, compared to p53 and SOX2,
the incremental value of cyclin A was limited. The use of biomarkers has the potential to significantly improve risk stratification in BE
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