Evaluation of polymeric nanomedicines targeted to PSMA: Effect of ligand on targeting efficiency

Targeted nanomedicines offer a strategy for greatly enhancing accumulation of a therapeutic within a specific tissue in animals. In this study, we report on the comparative targeting efficiency toward prostate-specific membrane antigen (PSMA) of a number of different ligands that are covalently attached by the same chemistry to a polymeric nanocarrier. The targeting ligands included a small molecule (glutamate urea), a peptide ligand, and a monoclonal antibody (J591). A hyperbranched polymer (HBP) was utilized as the nanocarrier and contained a fluorophore for tracking/analysis, whereas the pendant functional chain-ends provided a handle for ligand conjugation. Targeting efficiency of each ligand was assessed in vitro using flow cytometry and confocal microscopy to compare degree of binding and internalization of the HBPs by human prostate cancer (PCa) cell lines with different PSMA expression status (PC3-PIP (PSMA+) and PC3-FLU (PSMA−). The peptide ligand was further investigated in vivo, in which BALB/c nude mice bearing subcutaneous PC3-PIP and PC3-FLU PCa tumors were injected intravenously with the HBP-peptide conjugate and assessed by fluorescence imaging. Enhanced accumulation in the tumor tissue of PC3-PIP compared to PC3-FLU highlighted the applicability of this system as a future imaging and therapeutic delivery vehicle.

Communication: Evidence of dynamic heterogeneity in glassy polymer monolayers from interface microrheology measurements

We have developed a novel nanoparticle tracking based interface microrheology technique to perform in situ studies on confined complex fluids. To demonstrate the power of this technique, we show, for the first time, how in situ glass formation in polymers confined at air-water interface can be directly probed by monitoring variation of the mean square displacement of embedded nanoparticles as a function of surface density. We have further quantified the appearance of dynamic heterogeneity and hence vitrification in polymethyl methacrylate monolayers above a certain surface density, through the variation of non-Gaussian parameter of the probes. (C) 2010 American Institute of Physics. [doi:10.1063/1.3471584].

回声探测仪在我国内陆水体鱼类资源调查中的初步应用

介绍了2005—2008年在国内内陆水体鱼类资源调查中,EY60回声探测仪的使用及其效果。该探测仪利用分裂波束(Split-beam)技术,通过交叉过滤(Cross-filter)及轨迹跟踪分析(Tracking analysis),实现了对鱼类个体的自动判别及计数;另外对使用中噪声消减、渔获物调查数据的参考等进行了说明;强调回声探测仪自主品牌产品研发的必要性。

开发早期油藏动态地质模型与油藏工程优化研究——以埕岛油田馆上段油藏为例

In order to developing reservoir of Upper of Ng at high-speed and high-efficient in Chengdao oilfield which is located in the bally shallow sea, the paper builds up a series of theory and means predicting and descripting reservoir in earlier period of oilfield development. There are some conclusions as follows. 1. It is the first time to form a series of technique of fine geological modeling of the channel-sandy reservoir by means of mainly seismic methods. These technique include the logging restriction seismic inversion, the whole three dimension seismic interpretation, seismic properties analysis and so on which are used to the 3-dimension distributing prediction of sandy body, structure and properties of the channel reservoir by a lot of the seismic information and a small quantity of the drilling and the logging information in the earlier stage of the oil-field development. It is the first time that these methods applied to production and the high-speed development of the shallow sea oilfield. The prediction sandy body was modified by the data of new drilling, the new reservoir prediction thinking of traced inversion is built. The applied effect of the technique was very well, according to approximately 200 wells belonging to 30 well groups in Chengdao oilfield, the drilling succeeded rate of the predicting sandy body reached 100%, the error total thickness only was 8%. 2. The author advanced the thinking and methods of the forecasting residual-oil prediction at the earlier stage of production. Based on well data and seismic data, correlation of sediment units was correlated by cycle-correlation and classification control methods, and the normalization and finely interpretation of the well logging and sedimentation micro-facies were acquired. On the region of poor well, using the logging restriction inversion technique and regarding finished drilling production well as the new restriction condition, the sand body distributing and its property were predicted again and derived 3-dimension pool geologic model including structure, reservoir, fluid, reservoir engineering parameter and producing dynamic etc. According to the reservoir geologic model, the reservoir engineering design was optimized, the tracking simulation of the reservoir numerical simulation was done by means of the dynamic data (pressure, yield and water content) of development well, the production rule and oil-water distributing rule was traced, the distributing of the remaining oil was predicted and controlled. The dynamic reservoir modeling method in metaphase of development was taken out. Based on the new drilling data, the static reservoir geologic model was momentarily modified, the research of the flow units was brought up including identifying flow units, evaluating flow units capability and establishing the fine flow units model; according to the dynamic data of production and well testing data, the dynamic tracing reservoir description was realized through the constant modification of the reservoir geologic model restricted these dynamic data by the theory of well testing and the reservoir numerical simulation. It was built the dynamic tracing reservoir model, which was used to track survey of the remaining oil on earlier period. The reservoir engineering tracking analysis technique on shallow sea oilfield was founded. After renewing the structure history since tertiary in Chengdao area by the balance section technique and estimating the activity character of the Chengbei fault by the sealing fault analysis technique, the meandering stream sediment pattern of the Upper of Ng was founded in which the meandering border was the uppermost reservoir unit. Based on the specialty of the lower rock component maturity and the structure maturity, the author founded 3 kinds of pore structure pattern in the Guanshang member of Chengdao oil-field in which the storing space mainly was primary (genetic) inter-granular pore, little was secondary solution pore and the inter-crystal pore tiny pore, and the type of throat mainly distributed as the slice shape and the contract neck shape. The positive rhythmic was briefly type included the simple positive rhythm, the complex positive rhythm and the compound rhythm. Interbed mainly is mudstone widely, the physical properties and the calcite interbed distribute localized. 5. The author synthetically analyzed the influence action of the micro-heterogeneity, the macro-heterogeneity and the structure heterogeneity to the oilfield water flood development. The efficiency of water flood is well in tiny structure of convex type or even type at top and bottom in which the water breakthrough of oil well is soon at the high part of structure when inject at the low part of structure, and the efficiency of water flood is poor in tiny structure of concave type at top and bottom. The remaining oil was controlled by sedimentary facies; the water flooding efficiency is well in the border or channel bar and is bad in the floodplain or the levee. The separation and inter layer have a little influence to the non-obvious positive rhythm reservoir, in which the remaining oil commonly locate within the 1-3 meter of the lower part of the separation and inter layer with lower water flooding efficiency.

Assessment of PEG on Polymeric Particles Surface, a Key Step in Drug Carrier Translation

Injectable drug nanocarriers have greatly benefited in their clinical development from the addition of a superficial hydrophilic corona to improve their cargo pharmacokinetics. The most studied and used polymer for this purpose is poly(ethylene glycol), PEG. However, in spite of its wide use for over two decades now, there is no general consensus on the optimum PEG chain coverage-density and size required to escape from the mononuclear phagocyte system and to extend the circulation time. Moreover, cellular uptake and active targeting may have conflicting requirements in terms of surface properties of the nanocarriers which complicates even more the optimization process. These persistent issues can be largely attributed to the lack of straightforward characterization techniques to assess the coverage-density, the conformation or the thickness of a PEG layer grafted or adsorbed on a particulate drug carrier and is certainly one of the main reasons why so few clinical applications involving PEG coated particle-based drug delivery systems are under clinical trial so far. The objective of this review is to provide the reader with a brief description of the most relevant techniques used to assess qualitatively or quantitatively PEG chain coverage-density, conformation and layer thickness on polymeric nanoparticles. Emphasis has been made on polymeric particle (solid core) either made of copolymers containing PEG chains or modified after particle formation. Advantages and limitations of each technique are presented as well as methods to calculate PEG coverage-density and to investigate PEG chains conformation on the NP surface.

A new perspective on Southern hemisphere storm-tracks.

A detailed view of Southern Hemisphere storm tracks is obtained based on the application of filtered variance and modern feature-tracking techniques to a wide range of 45-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) data. It has been checked that the conclusions drawn in this study are valid even if data from only the satellite era are used. The emphasis of the paper is on the winter season, but results for the four seasons are also discussed. Both upper- and lower-tropospheric fields are used. The tracking analysis focuses on systems that last longer than 2 days and are mobile (move more than 1000 km). Many of the results support previous ideas about the storm tracks, but some new insights are also obtained. In the summer there is a rather circular, strong, deep high-latitude storm track. In winter the high-latitude storm track is more asymmetric with a spiral from the Atlantic and Indian Oceans in toward Antarctica and a subtropical jet–related lower-latitude storm track over the Pacific, again tending to spiral poleward. At all times of the year, maximum storm activity in the higher-latitude storm track is in the Atlantic and Indian Ocean regions. In the winter upper troposphere, the relative importance of, and interplay between, the subtropical and subpolar storm tracks is discussed. The genesis, lysis, and growth rate of lower-tropospheric winter cyclones together lead to a vivid picture of their behavior that is summarized as a set of overlapping plates, each composed of cyclone life cycles. Systems in each plate appear to feed the genesis in the next plate through downstream development in the upper-troposphere spiral storm track. In the lee of the Andes in South America, there is cyclogenesis associated with the subtropical jet and also, poleward of this, cyclogenesis largely associated with system decay on the upslope and regeneration on the downslope. The genesis and lysis of cyclones and anticyclones have a definite spatial relationship with each other and with the Andes. At 500 hPa, their relative longitudinal positions are consistent with vortex-stretching ideas for simple flow over a large-scale mountain. Cyclonic systems near Antarctica have generally spiraled in from lower latitudes. However, cyclogenesis associated with mobile cyclones occurs around the Antarctic coast with an interesting genesis maximum over the sea ice near 150°E. The South Pacific storm track emerges clearly from the tracking as a coherent deep feature spiraling from Australia to southern South America. A feature of the summer season is the genesis of eastward-moving cyclonic systems near the tropic of Capricorn off Brazil, in the central Pacific and, to a lesser extent, off Madagascar, followed by movement along the southwest flanks of the subtropical anticyclones and contribution to the “convergence zone” cloud bands seen in these regions.

Sensitivity of large-scale atmospheric analyses to humidity observations and its impact on the global water cycle and tropical and extratropical weather systems in ERA40

Reanalysis data obtained from data assimilation are increasingly used for diagnostic studies of the general circulation of the atmosphere, for the validation of modelling experiments and for estimating energy and water fluxes between the Earth surface and the atmosphere. Because fluxes are not specifically observed, but determined by the data assimilation system, they are not only influenced by the utilized observations but also by model physics and dynamics and by the assimilation method. In order to better understand the relative importance of humidity observations for the determination of the hydrological cycle, in this paper we describe an assimilation experiment using the ERA40 reanalysis system where all humidity data have been excluded from the observational data base. The surprising result is that the model, driven by the time evolution of wind, temperature and surface pressure, is able to almost completely reconstitute the large-scale hydrological cycle of the control assimilation without the use of any humidity data. In addition, analysis of the individual weather systems in the extratropics and tropics using an objective feature tracking analysis indicates that the humidity data have very little impact on these systems. We include a discussion of these results and possible consequences for the way moisture information is assimilated, as well as the potential consequences for the design of observing systems for climate monitoring. It is further suggested, with support from a simple assimilation study with another model, that model physics and dynamics play a decisive role for the hydrological cycle, stressing the need to better understand these aspects of model parametrization. .

The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrPC). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrPC. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrPC-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrPC signaling

Exploring the cardiovascular disease continuum: blood pressure and target organ damage

Introduction The objectives of this thesis are to: (1) examine how ambulatory blood pressure monitoring (ABPM) refines office blood pressure (BP) measurement; (2) determine if absolute ambulatory BP or dipping status is better associated with target organ damage (TOD); (3) explore the association of isolated nocturnal hypertension (INH) with TOD; and (4) investigate the association of night-time BP with ultrasound markers of cardiovascular damage. Methods Data from the Mitchelstown Cohort Study was analysed to deliver objectives 1 and 2. Objective 3 was addressed by a systematic review and analysis of data from the Mitchelstown Study. A sample of participants from the Mitchelstown Study underwent an echocardiogram for speckle tracking analysis and carotid ultrasound to achieve objective 4. Results ABPM reclassifies hypertension status in approximately a quarter of individuals, with white coat and masked hypertension prevalence rates of 11% and 13% respectively. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level. In multi-variable models the odds ratio (OR) for LVH was 1.4 (95% CI 1.1 -1.8) and for albumin:creatinine ratio ≥ 1.1 mg/mmol was 1.5 (95% CI 1.2 – 1.8) for each 10 mmHg rise in night-time systolic BP. The evidence for the association of INH with TOD is inconclusive. Night-time systolic BP is significantly associated with global longitudinal strain (GLS) (beta coefficient 0.85 for every 10 mmHg rise, 95% CI 0.3 – 1.4) and carotid plaques (OR 1.9 for every 10 mmHg rise, 95% CI 1.1 – 3.2) in univariable analysis. The findings persist for GLS in sex and age adjusted models but not in multivariable models. Discussion Hypertension cannot be effectively managed without using ABPM. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level, and therefore, may be a better therapeutic target in future studies.

Analysis of phasor measurement method in tracking the power frequency of distorted signals

This paper presents an analysis of phasor measurement method for tracking the fundamental power frequency to show if it has the performance necessary to cope with the requirements of power system protection and control. In this regard, several computer simulations presenting the conditions of a typical power system signal especially those highly distorted by harmonics, noise and offset, are provided to evaluate the response of the Phasor Measurement (PM) technique. A new method, which can shorten the delay of estimation, has also been proposed for the PM method to work for signals free of even-order harmonics.

Over time assessment data analysis tracking a school's on-going performance

In Australia, as in some other western nations, governments impose accountability measures on educational institutions (Earl, 2005). One such accountability measure is the National Assessment Program - Literacy and Numeracy (NAPLAN) from which high-stakes assessment data is generated. In this article, a practical method of data analysis known as the Over Time Assessment Data Analysis (OTADA) is offered as an analytical process by which schools can monitor their current and over time performances. This analysis developed by the author, is currently used extensively in schools throughout Queensland. By Analysing in this way, teachers, and in particular principals, can obtain a quick and insightful performance overview. For those seeking to track the achievements and progress of year level cohorts, the OTADA should be considered.

A multi-genome analysis approach enables tracking of the invasion of a single Russian wheat aphid (Diuraphis noxia) clone throughout the New World

This study investigated the population genetics, demographic history and pathway of invasion of the Russian wheat aphid (RWA) from its native range in Central Asia, the Middle East and Europe to South Africa and the Americas. We screened microsatellite markers, mitochondrial DNA and endosymbiont genes in 504 RWA clones from nineteen populations worldwide. Following pathway analyses of microsatellite and endosymbiont data, we postulate that Turkey and Syria were the most likely sources of invasion to Kenya and South Africa, respectively. Furthermore, we found that one clone transferred between South Africa and the Americas was most likely responsible for the New World invasion. Finally, endosymbiont DNA was found to be a high resolution population genetic marker, extremely useful for studies of invasion over a relatively short evolutionary history time frame. This study has provided valuable insights into the factors that may have facilitated the recent global invasion by this damaging pest.