Polymer-drug conjugates: current status and future trends

Polymer conjugates are nano-sized, multicomponent constructs already in the clinic as anticancer compounds, both as single agents or as elements of combinations. They have the potential to improve pharmacological therapy of a variety of solid tumors. Polymer-drug conjugation promotes passive tumor targeting by the enhanced permeability and retention (EPR) effect and allows for lysosomotropic drug delivery following endocytic capture. In the first part of this review, we analyze the promising results arising from clinical trials of polymer-bound chemotherapy. The experience gained on these studies provides the basis for the development of a more sophisticated second-generation of polymer conjugates. However, many challenges still lay ahead providing scope to develop and refine this field. The "technology platform'' of polymer therapeutics allows the development of both new and exciting polymeric materials, the incorporation of novel bioactive agents and combinations thereof to address recent advances in drug therapy. The rational design of polymer drug conjugates is expected to realize the true potential of these "nanomedicines".

Performance and conformance results of the deterministic DVB-T equalizer

One of the enablers for new consumer electronics based products to be accepted in to the market is the availability of inexpensive, flexible and multi-standard chipsets and services. DVB-T, the principal standard for terrestrial broadcast of digital video in Europe, has been extremely successful in leading to governments reconsidering their targets for analogue television broadcast switch-off. To enable one further small step in creating increasingly cost effective chipsets, the ODFM deterministic equalizer has been presented before with its application to DVB-T. This paper discusses the test set-up of a DVB-T compliant baseband simulation that includes the deterministic equalizer and DVB-T standard propagation channels. This is then followed by a presentation of the found inner and outer Bit Error Rate (BER) results using various modulation levels, coding rates and propagation channels in order to ascertain the actual performance of the deterministic equalizer(1).

Deterministic equalization and results of a DVB-T multipath equalizer for both 16-QAM and 64-QAM operation

Recent developments in the UK concerning the reception of Digital Terrestrial Television (DTT) have indicated that, as it currently stands, DVB-T receivers may not be sufficient to maintain adequate quality of digital picture information to the consumer. There are many possible reasons why such large errors are being introduced into the system preventing reception failure. It has been suggested that one possibility is that the assumptions concerning the immunity to multipath that Coded Orthogonal Frequency Division Multiplex (COFDM) is expected to have, may not be entirely accurate. Previous research has shown that multipath can indeed have an impact on a DVB-T receiver performance. In the UK, proposals have been made to change the modulation from 64-QAM to 16-QAM to improve the immunity to multipath, but this paper demonstrates that the 16-QAM performance may again not be sufficient. To this end, this paper presents a deterministic approach to equalization such that a 64-QAM receiver with the simple equalizer presented in this paper has the same order of MPEG-2 BER performance as that to a 16-QAM receiver without equalization. Thus, alleviating the requirement in the broadcasters to migrate from 64-QAM to 16-QAM Of course, by adding the equalizer to a 16-QAM receiver then the BER is also further improved and thus creating one more step to satisfying the consumers(1).

Comparison of the computational cost of a Monte Carlo and deterministic algorithm for computing bilinear forms of matrix powers

In this paper we consider bilinear forms of matrix polynomials and show that these polynomials can be used to construct solutions for the problems of solving systems of linear algebraic equations, matrix inversion and finding extremal eigenvalues. An almost Optimal Monte Carlo (MAO) algorithm for computing bilinear forms of matrix polynomials is presented. Results for the computational costs of a balanced algorithm for computing the bilinear form of a matrix power is presented, i.e., an algorithm for which probability and systematic errors are of the same order, and this is compared with the computational cost for a corresponding deterministic method.

Global pollinator declines: trends, impacts and drivers

Pollinators are a key component of global biodiversity, providing vital ecosystem services to crops and wild plants. There is clear evidence of recent declines in both wild and domesticated pollinators, and parallel declines in the plants that rely upon them. Here we describe the nature and extent of reported declines, and review the potential drivers of pollinator loss, including habitat loss and fragmentation, agrochemicals, pathogens, alien species, climate change and the interactions between them. Pollinator declines can result in loss of pollination services which have important negative ecological and economic impacts that could significantly affect themaintenance of wild plant diversity, wider ecosystemstability, crop production, food security and human welfare.

Tropospheric temperature trends: history of an ongoing controversy

Changes in atmospheric temperature have a particular importance in climate research because climate models consistently predict a distinctive vertical profile of trends. With increasing greenhouse gas concentrations, the surface and troposphere are consistently projected to warm, with an enhancement of that warming in the tropical upper troposphere. Hence, attempts to detect this distinct ‘fingerprint’ have been a focus for observational studies. The topic acquired heightened importance following the 1990 publication of an analysis of satellite data which challenged the reality of the projected tropospheric warming. This review documents the evolution over the last four decades of understanding of tropospheric temperature trends and their likely causes. Particular focus is given to the difficulty of producing homogenized datasets, with which to derive trends, from both radiosonde and satellite observing systems, because of the many systematic changes over time. The value of multiple independent analyses is demonstrated. Paralleling developments in observational datasets, increased computer power and improved understanding of climate forcing mechanisms have led to refined estimates of temperature trends from a wide range of climate models and a better understanding of internal variability. It is concluded that there is no reasonable evidence of a fundamental disagreement between tropospheric temperature trends from models and observations when uncertainties in both are treated comprehensively

Coupled chemistry climate model simulations of stratospheric temperatures and their trends for the recent past

Temperature results from multi-decadal simulations of coupled chemistry climate models for the recent past are analyzed using multi-linear regression including a trend, solar cycle, lower stratospheric tropical wind, and volcanic aerosol terms. The climatology of the models for recent years is in good agreement with observations for the troposphere but the model results diverge from each other and from observations in the stratosphere. Overall, the models agree better with observations than in previous assessments, primarily because of corrections in the observed temperatures. The annually averaged global and polar temperature trends simulated by the models are generally in agreement with revised satellite observations and radiosonde data over much of their altitude range. In the global average, the model trends underpredict the radiosonde data slightly at the top of the observed range. Over the Antarctic some models underpredict the temperature trend in the lower stratosphere, while others overpredict the trends

An update of observed stratospheric temperature trends

An updated analysis of observed stratospheric temperature variability and trends is presented on the basis of satellite, radiosonde, and lidar observations. Satellite data include measurements from the series of NOAA operational instruments, including the Microwave Sounding Unit covering 1979–2007 and the Stratospheric Sounding Unit (SSU) covering 1979–2005. Radiosonde results are compared for six different data sets, incorporating a variety of homogeneity adjustments to account for changes in instrumentation and observational practices. Temperature changes in the lower stratosphere show cooling of 0.5 K/decade over much of the globe for 1979–2007, with some differences in detail among the different radiosonde and satellite data sets. Substantially larger cooling trends are observed in the Antarctic lower stratosphere during spring and summer, in association with development of the Antarctic ozone hole. Trends in the lower stratosphere derived from radiosonde data are also analyzed for a longer record (back to 1958); trends for the presatellite era (1958–1978) have a large range among the different homogenized data sets, implying large trend uncertainties. Trends in the middle and upper stratosphere have been derived from updated SSU data, taking into account changes in the SSU weighting functions due to observed atmospheric CO2 increases. The results show mean cooling of 0.5–1.5 K/decade during 1979–2005, with the greatest cooling in the upper stratosphere near 40–50 km. Temperature anomalies throughout the stratosphere were relatively constant during the decade 1995–2005. Long records of lidar temperature measurements at a few locations show reasonable agreement with SSU trends, although sampling uncertainties are large in the localized lidar measurements. Updated estimates of the solar cycle influence on stratospheric temperatures show a statistically significant signal in the tropics (30N–S), with an amplitude (solar maximum minus solar minimum) of 0.5 K (lower stratosphere) to 1.0 K (upper stratosphere).

Long-lived halocarbon trends and budgets from atmospheric chemistry modelling constrained with measurements in polar firn

The budgets of seven halogenated gases (CFC-11, CFC-12, CFC-113, CFC-114, CFC-115, CCl4 and SF6) are studied by comparing measurements in polar firn air from two Arctic and three Antarctic sites, and simulation results of two numerical models: a 2-D atmospheric chemistry model and a 1-D firn diffusion model. The first one is used to calculate atmospheric concentrations from emission trends based on industrial inventories; the calculated concentration trends are used by the second one to produce depth concentration profiles in the firn. The 2-D atmospheric model is validated in the boundary layer by comparison with atmospheric station measurements, and vertically for CFC-12 by comparison with balloon and FTIR measurements. Firn air measurements provide constraints on historical atmospheric concentrations over the last century. Age distributions in the firn are discussed using a Green function approach. Finally, our results are used as input to a radiative model in order to evaluate the radiative forcing of our target gases. Multi-species and multi-site firn air studies allow to better constrain atmospheric trends. The low concentrations of all studied gases at the bottom of the firn, and their consistency with our model results confirm that their natural sources are small. Our results indicate that the emissions, sinks and trends of CFC-11, CFC-12, CFC-113, CFC-115 and SF6 are well constrained, whereas it is not the case for CFC-114 and CCl4. Significant emission-dependent changes in the lifetimes of halocarbons destroyed in the stratosphere were obtained. Those result from the time needed for their transport from the surface where they are emitted to the stratosphere where they are destroyed. Efforts should be made to update and reduce the large uncertainties on CFC lifetimes.

Intestinal microflora of human infants and current trends for its nutritional modulation

Diet, among other environmental and genetic factors, is currently recognised to have an important role in health and disease. There is increasing evidence that the human colonic microbiota can contribute positively towards host nutrition and health. As such, dietary modulation has been proposed as important for improved gut health, especially during the highly sensitive stage of infancy. Differences in gut microflora composition and incidence of infection occur between breast- and formula-fed infants. Human milk components that cannot be duplicated in infant formulae could possibly account for these differences. However, various functional food ingredients such as oligosaccharides, prebiotics, proteins and probiotics could effect a beneficial modification in the composition and activities of gut microflora of infants. The aim of the present review is to describe existing knowledge on the composition and metabolic activities of the gastrointestinal microflora of human infants and discuss various possibilities and opportunities for its nutritional modulation.

Deterministic IIR video deghoster for all ghost carrier phases

It is known that certain video deghoster systems cannot fully process the induced signal derived from the quadrature carrier forming nature of the VSB filter under a multipath condition. A new deterministic IIR deghoster filter structure is given which is capable of deghosting terrestrial video for any relative ghost carrier phase.

Trends in the start of the wet season over Africa

A quarter of a century of daily rainfall data from the Global Telecommunications System are used to define the temporal and spatial variability of the start of the wet season over Africa and surrounding extreme south of Europe and parts of the Middle East. From 1978 to 2002, the start of the wet season arrived later in the year for the majority of the region, as time progressed. In some parts of the continent, there was an annual increase in the start date of up to 4 days per year. On average, the start of the wet season arrived 9–21 days later from 1978 to 2002, depending on the threshold used to define the start of the rains (varying from 10–30 mm over 2 days, with no dry period in the following 10 days). It is noted that the inter-annual variability of the start of the wet season is high with the range of start dates varying on average from 116 to 142 days dependent on the threshold used to determine the start date. These results may have important implications for agriculturists on all levels (from the individual farmer to those responsible for regional food supply), as knowledge of potential future climate changes starts to play an increasingly important role in the agricultural decision-making process, such as sowing and harvesting times.