To evaluate safety and pharmacokinetics (PK), and determine the recommended dose for efficacy studies, of L-377202, a novel peptide conjugate of doxorubicin (Dox) that releases the active metabolites ...leucine-doxorubicin (Leu-Dox) and Dox on cleavage by membrane-bound prostate-specific antigen (PSA).
Nineteen patients with advanced hormone-refractory prostate cancer were treated intravenously with 71 cycles of L-377202 at escalating dose levels of 20 (n = 1), 40 (n = 3), 80 (n = 4), 160 (n = 3), 225 (n = 6), and 315 mg/m(2) (n = 2) once every 3 weeks. Toxicity, response, and PK of L-377202 were assessed.
L-377202 was well tolerated. Dose-limiting grade 4 neutropenia was noted in two of two patients administered 315 mg/m(2) (both patients were able to resume therapy at 225 mg/m(2)). The recommended dose for efficacy studies was 225 mg/m(2), which induced grade 4 neutropenia in one of six patients. PK studies demonstrated that L-377202 was metabolized to Leu-Dox and Dox. PK were linear; after administration of single doses of 225 mg/m(2), the mean area under the concentration-time profiles of L-377202, Leu-Dox, and Dox were 6 micromol x L/h, 4 micromol x L/h, and 1 micromol x L/h, and peak concentrations were 14 micromol/L, 5 micromol/L, and 120 nmol/L, respectively. At 225 and 315 mg/m(2), five patients completed at least three cycles of therapy; two patients had a greater than 75% decrease in PSA, and one patient had a stabilized PSA. No response was noted at dose levels less than 225 mg/m(2).
This is the first study of selective drug delivery in humans using a novel PSA-activated agent. L-377202 was cleaved to produce detectable levels of the active metabolites Leu-Dox and Dox. L-377202 was well tolerated and established a safe dose level for further study.
For breakthrough development in solid oxide fuel cells, novel cell architectures integrating better performing materials and cost-effective manufacturing processes with potential for mass production ...must be realised. The present work addresses this on the basis of the recent discovery of acceptor doped rare-earth ortho-niobate proton conductors and the development of a versatile fabrication process. La sub(0.995Sr) sub(0).005NbO sub(4-delta/NiO anodes are produced by tape-casting and co-lamination of green layers. Their porosity is finely tuned by using a pyrolyzable pore former. La) sub(0).995Sr sub(0.005NbO) sub(4)-delta electrolytes are spin-coated using ceramic-based suspensions. Fully dense electrolytes with thickness ranging from 9 microm to 26 microm are obtained after sintering in air at 1350 degC. The cathode layers are then screen-printed. To match thermal expansion and to avoid chemical reaction between the functional layers, special attention is paid to the design of cathode architectures. CaTi sub(0.9Fe) sub(0).1O sub(3-delta, La) sub(2)NiO sub(4+delta and La) sub(4)Ni sub(3O) sub(1)0 mixed oxygen ion and electron conducting oxides are investigated as either monophase or La sub(0.995Sr) sub(0).005NbO sub(4-delta-based composite electrodes. The latter gives the whole cell an innovative "semi-monolithic" concept, which can take advantage of the chemical and mechanical stability of La) sub(0).995Sr sub(0.005NbO) sub(4)-delta, as well as of inherent material integration. Most promising cell architectures are finally selected based on thermo-mechanical and chemical compatibility of all functional layers.
The adhesion forces holding micron-sized particles to solid surfaces can be studied through the detachment forces developed by the transit of an air-liquid interface in a capillary. Two key variables ...affect the direction and magnitude of the capillary detachment force: (i) the thickness of the liquid film between the bubble and the capillary walls, and (ii) the effective angle of the triple phase contact between the particles and the interface. Variations in film thickness were calculated using a two-phase flow model. Film thickness was used to determine the time-variation of the capillary force during transit of the bubble. The curve for particle detachment was predicted from the calculated force. This curve proved to be non-linear and gave in situ information on the effective contact angle developing at the particle-bubble interface during detachment. This approach allowed an accurate determination of the detachment force. This theoretical approach was validated using latex particles 2km in diameter.
Brion Abel, Fontaine M., Fontaine M. P., Le François-Chabas D., Bennejan G., Meurier G. Sur les propriétés immunisantes d’une nouvelle souche de virus de la maladie de Newcastle. In: Bulletin de ...l'Académie Vétérinaire de France tome 119 n°5, 1966. pp. 165-171.
AbstractAccurate traffic state information is essential for both travelers and transportation agencies. In the past, traffic condition data were usually collected by a government agency using its own ...sensors. Recently, a number of private sector companies have started selling travel-time and speed data collected using probe vehicles, which provides a viable opportunity to outsource traffic data collection. Because these data sources and their related algorithms are proprietary, the reliability and accuracy of this private sector data is often an important issue for transportation agencies. Previous studies have examined the accuracy of private sector data on freeways, but arterials have not been examined extensively. Arterials represent a fundamentally more challenging environment for probe vehicle data given the larger variance in travel times created by traffic signals and other intermediate access points. In the research, the quality of private sector data on arterials is evaluated by utilizing Bluetooth travel-time data as the ground truth. The evaluation is conducted from two perspectives: the ability to track real-time conditions, and the ability to identify long-term traffic state changes. The study sites are three signalized arterials in the state of Virginia. The results indicate that the private sector data evaluated were not suitable for real-time applications, but could be used to measure long-term traffic state changes for performance measurement programs.
The impact of work zones on mean travel time and travel time reliability has gained attention as agencies focus on performance measurement. Travel time reliability in work zones often has been ...difficult for agencies to quantify because of the time and expense required to collect travel time data. Several private-sector companies have begun to sell travel time data; this availability has created an opportunity to examine cost-effectively work zone impacts on travel time reliability on a broader basis. The Virginia Department of Transportation recently acquired probe vehicle-based travel time data for 2010 from a private-sector data provider. These data were used to calculate measures of travel time reliability at 15 work zones and to examine factors that affected travel time reliability. Travel time reliability was quantified with 95th percentile travel time, a buffer index, and a planning time index. The work zones experienced a statistically significant degradation across all measures of travel time reliability as compared with baseline conditions. Work zone mean buffer index, planning time index, and 95th percentile travel time rates were higher by 48%, 18%, and 16%, respectively. Although lane closures occurred during off-peak periods, work zones that involved lane closures experienced increases in their mean buffer index, planning time index, and 95th percentile travel time with rates of 67%, 23%, and 22%, respectively. Annual average daily traffic per lane and the number of access points per mile were found to have the most obvious relationships with declines in reliability at work zones.
By the middle of the sixteenth century, the Italian Wars, economic disaster, social strife, and religious controversy upset any semblance of unity, peace, or order in Modena, a little city in ...north-central Italy. Just as chaos and crisis reached a peak, Edigio Foscarari arrived as Modena's first resident bishop in over fifty years. He immediately began to forge an alliance with the ruling elite. Together, the bishop and the elite addressed pressing issues involving Christian morality and social ethics by leading urban religious ritual, mediating social conflicts, and caring for poverty-stricken citizens. This essay on the crisis in Modena and the alliance between the bishop and the ruling elite in the public sphere casts new light on the nature of episcopal activity, the intersection of religion and politics, and the development of Catholic reform in Tridentine Italy.
For breakthrough development in solid oxide fuel cells, novel cell architectures integrating better performing materials and cost-effective manufacturing processes with potential for mass production ...must be realised. The present work addresses this on the basis of the recent discovery of acceptor doped rare-earth ortho-niobate proton conductors and the development of a versatile fabrication process. La
0.995Sr
0.005NbO
4−
δ
/NiO anodes are produced by tape-casting and co-lamination of green layers. Their porosity is finely tuned by using a pyrolyzable pore former. La
0.995Sr
0.005NbO
4−
δ
electrolytes are spin-coated using ceramic-based suspensions. Fully dense electrolytes with thickness ranging from 9
μm to 26
μm are obtained after sintering in air at 1350
°C. The cathode layers are then screen-printed. To match thermal expansion and to avoid chemical reaction between the functional layers, special attention is paid to the design of cathode architectures. CaTi
0.9Fe
0.1O
3−
δ
, La
2NiO
4+
δ
and La
4Ni
3O
10 mixed oxygen ion and electron conducting oxides are investigated as either monophase or La
0.995Sr
0.005NbO
4−
δ
-based composite electrodes. The latter gives the whole cell an innovative “semi-monolithic” concept, which can take advantage of the chemical and mechanical stability of La
0.995Sr
0.005NbO
4−
δ
, as well as of inherent material integration. Most promising cell architectures are finally selected based on thermo-mechanical and chemical compatibility of all functional layers.
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