Development and in-vitro evaluation of an optimized carvedilol transdermal therapeutic system using experimental design approach

The effect of formulation variables on in-vitro release and permeation properties of carvedilol from transdermal patch was studied by varying one factor at a time as preliminary study.Based on these results,design of experiments technique was applied followed by regression analysis and response surface methodology to optimize formulation variables.Central Composite IV model design was used with four formulation variables:drug loading,matrix thickness,adhesive layer thickness,and propylene glycol concentration.Nineteen formulations were prepared according to the design;and the effect of formulation variables was studied on in-vitro release and permeation profiles of these formulations.In all cases,the permeation profiles paralleled in-vitro release profiles.The drug released at 7 h and 24 h was used as release response parameters while permeation flux obtained was employed as permeation response parameter.All four formulation variables were found to be significant for release properties and three of these exhibited significant effect on permeation profile of carvedilol across artificial membrane.Constrained optimization,using 47.9%of cumulative carvedilol released at 7 h and 99.8%at 24 h as well as 25.7 mg/cm2/h of permeation flux,was applied to obtain desired release and permeation profiles.Experimentally,carvedilol was observed to release from the optimized formulation with 51.4%drug release at 7 h and 98.5%at 24 h with an observed flux value of 27.4 mg/cm2/h across artificial membrane,which showed an excellent agreement with the predicted values.The results of this investigation show that the quadratic mathematical model developed could be used to further predict formulations with desirable release and permeation properties.

Monthly gravity field solution from GRACE range measurements using modified short arc approach

In this paper we present a series of monthly gravity field solutions from Gravity Recovery and Climate Experiment（GRACE） range measurements using modified short arc approach,in which the ambiguity of range measurements is eliminated via differentiating two adjacent range measurements.The data used for developing our monthly gravity field model are same as Tongji-GRACEOl model except that the range measurements are used to replace the range rate measurements,and our model is truncated to degree and order 60,spanning Jan.2004 to Dec.2010 also same as Tongji-GRACE01 model.Based on the comparison results of the C_（2,0）,C_（2,1）,S_（2,1）,and C_（15,15）,S_（15,15）,time series and the global mass change signals as well as the mass change time series in Amazon area of our model with those of Tongji-GRACE01 model,we can conclude that our monthly gravity field model is comparable with Tongji-GRACE01 monthly model.

WHU-Grace01s:A new temporal gravity field model recovered from GRACE KBRR data alone

A new temporal gravity field model called WHU-Grace01s solely recovered from Gravity Recovery and Climate Experiment （GRACE） K-Band Range Rate （KBRR） data based on dynamic integral approach is presented in this paper. After meticulously preprocessing of the GRACE KBRR data, the root mean square of its post residuals is about 0.2 micrometers per second, and seventy-two monthly temporal solutions truncated to degree and order 60 are computed for the period from January 2003 to December 2008. After applying the combi- nation filter in WHU-Grace01s, the global temporal signals show obvious periodical change rules in the large-scale fiver basins. In terms of the degree variance, our solution is smaller at high degrees, and shows a good consistency at the rest of degrees with the Release 05 models from Center for Space Research （CSR）, GeoForschungsZentrum Potsdam （GFZ） and Jet Pro- pulsion Laboratory 0PL）. Compared with other published models in terms of equivalent water height distribution, our solution is consistent with those published by CSR, GFZ, JPL, Delft institute of Earth Observation and Space system （DEOS）, Tongji University （Tongji）, Institute of Theoretical Geodesy （ITG）, Astronomical Institute in University of Bern （AIUB） and Groupe de Recherche de Geodesie Spatiale （GRGS}, which indicates that the accuracy of WHU-Grace01s has a good consistency with the previously published GRACE solutions.

Monthly gravity field recovery from GRACE orbits and K-band measurements using variational equations approach

The Gravity Recovery and Climate Experiment（GRACE） mission can significantly improve our knowledge of the temporal variability of the Earth＇s gravity field.We obtained monthly gravity field solutions based on variational equations approach from GPS-derived positions of GRACE satellites and K-band range-rate measurements.The impact of different fixed data weighting ratios in temporal gravity field recovery while combining the two types of data was investigated for the purpose of deriving the best combined solution.The monthly gravity field solution obtained through above procedures was named as the Institute of Geodesy and Geophysics（IGG） temporal gravity field models.IGG temporal gravity field models were compared with GRACE Release05（RL05） products in following aspects：（i） the trend of the mass anomaly in China and its nearby regions within 2005-2010; （ii） the root mean squares of the global mass anomaly during 2005-2010; （iii） time-series changes in the mean water storage in the region of the Amazon Basin and the Sahara Desert between 2005 and 2010.The results showed that IGG solutions were almost consistent with GRACE RL05 products in above aspects（i）-（iii）.Changes in the annual amplitude of mean water storage in the Amazon Basin were 14.7 ± 1.2 cm for IGG,17.1 ± 1.3 cm for the Centre for Space Research（CSR）,16.4 ± 0.9 cm for the GeoForschungsZentrum（GFZ） and 16.9 ± 1.2 cm for the Jet Propulsion Laboratory（JPL） in terms of equivalent water height（EWH）,respectively.The root mean squares of the mean mass anomaly in Sahara were 1.2 cm,0.9 cm,0.9 cm and 1.2 cm for temporal gravity field models of IGG,CSR,GFZ and JPL,respectively.Comparison suggested that IGG temporal gravity field solutions were at the same accuracy level with the latest temporal gravity field solutions published by CSR,GFZ and JPL.

Comparison of three different CFD methods for dense fluidized beds and validation by a cold flow experiment

This work focuses on a comparison between three different numerical CFD methods, namely Euler-Euler, Euler-Lagrange-stochastic, and Euler-Lagrange-deterministic, to treat a dense spouted bed, A simple cold flow experiment was used to investigate the hydrodynamics of a gas-solid flow in a three dimensional lab-scale spouted bed, In this context, two different air mass flow rates, 0,005 and 0.006 kg/s, were applied during fluidization. The experimental bed behaviour was recorded with a high-speed camera to validate the numerical predictions in terms of bubble size, bed expansion rate, and particle velocities at different reactor heights. The numerical setup was kept similar between all three modelling approaches, At both gas mass flow rates all three approaches are able to capture the overall bed expansion. However, at higher gas mass flow rates, discrepancies between experiment and simulation increase for the Euler-Euler and Euler-Lagrange-stochastic models. The Euler-Lagrange deterministic model most accurately predicts the flow pattern at both mass flow rates. The main reasons for discrepancies between simulation and experiment result from modelling of the collision and friction forces.

A NEW EXPERIMENTAL AND CLINICAL APPROACH OF COMBINING USAGE OF HIGHLY ACTIVE TUMOR-INFILTRATING LYMPHOCYTES AND HIGHLY SENSITIVE ANTITUMOR DRUGS FOR THE ADVANCED MALIGNANT TUMOR

In recent years, tumor-nfiltrating lymphocytes (TILs) have been reported to be effective for tumors in experimental and clinical research. In order to increase the therapeutical effect, we modified some steps of Rosenberg's approach a. cold digestion with collagenase at 4C for 24 hours; b. sedimentation instead of centrifugation; c. elimination of tumor cells before the cultivation procedure. Compared with the original approach, the proliferation, activity and cytotoxicity of TILs obtained by the modified procedure were much improved. TILs' expansion-old was greater than that with the original approach. Cytotoxicity against rumor cells was more potent. Increased TILs' subsets were CD3 and CD8 cells. Meanwhile, we took tumor cells from tumor tissues to test their in vitro chemosensitivities to different drugs in order to select highly sensitive antitumor drugs for treatment of cases with advanced tumors. According to the design of using highly active TILs and highly sensitive drugs (H & H therapy), preliminary clinical results of 50 cases showed higher response rates than those in treatment with TIL / IL2, LAK / 1L2 and TIL+IL2+CTX. Less toxic side effects were observed in 14 patients.

Ground-based investigations on phase-moving phenomenon with space sublimation cooling for lunar exploration missions

The lunar surface is a typical vacuum environment,and its harsh heat rejection conditions bring great challenges to the thermal control technology of the exploration mission.In addition to the radiator,the sublimator is recommended as one of the promising options for heat rejection.The sublimator makes use of water to freeze and sublimate in a porous medium,rejecting heat to the vacuum environment.The complex heat and mass transfer process involves many physical phenomena such as the freezing and sublimation phase change of water in the porous medium and the movement of the phase-change interface.In this paper,the visualized ground-based experimental approaches of space sublimation cooling were presented to reveal the moving law of threephase point and the growth phenomenon of ice-peak and icicle in microchannels under vacuum conditions.The visualized experiments and results prove that the freezing ice is divided into the porous ice-peak and the transparent icicle.As the sublimation progresses,the phase-change interface moves downward steadily,the length of the ice-peak increases,but the icicle decreases.The visualized experiments of space sublimation cooling in the capillary have guiding significance to reveal the sublimation cooling mechanism of water in the sublimator for lunar exploration missions.

Seamless handover between unicast and multicast multimedia streams

With the deployment of heterogeneous networks, mobile users are expecting ubiquitous connectivity when using applications. For bandwidth-intensive applications such as Internet Protocol Television(IPTV), multimedia contents are typically transmitted using a multicast delivery method due to its bandwidth efficiency. However, not all networks support multicasting. Multicasting alone could lead to service disruption when the users move from a multicast-capable network to a non-multicast network. In this paper, we propose a handover scheme called application layer seamless switching(ALSS) to provide smooth real-time multimedia delivery across unicast and multicast networks. ALSS adopts a soft handover to achieve seamless playback during the handover period. A real-time streaming testbed is implemented to investigate the overall handover performance, especially the overlapping period where both network interfaces are receiving audio and video packets. Both the quality of service(QoS) and objective-mapped quality of experience(QoE) metrics are measured. Experimental results show that the overlapping period takes a minimum of 56 and 4 ms for multicast-to-unicast(M2U) and unicast-to-multicast(U2M) handover, respectively. The measured peak signal-to-noise ratio(PSNR) confirms that the frame-by-frame quality of the streamed video during the handover is at least 33 dB, which is categorized as good based on ITU-T recommendations. The estimated mean opinion score(MOS) in terms of video playback smoothness is also at a satisfactory level.